JMJ Ch

Marist Brother
Notre Dame of Kidapawan College
Kidapawan City
Department of Nursing

MC 3

Microbiology and Parasitology

Compilation of Articles on Bacteria

Submitted to:
Analiza Valencia

Submitted by:
Meriam Kaye K. Llorente
BSN- 1

Date Submitted: April 23, 2024

Article No. 1 ANTHRAX
Anthrax Pathogenesis and Infection
Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus
anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and (b) an
antiphagocytic polyglutamic capsule. These are encoded by two large plasmids, the
former by pXO1 and the latter by pXO2. The expression of both is controlled by the
bicarbonate-responsive transcriptional regulator, AtxA. The anthrax toxins are three
polypeptides—protective antigen (PA), lethal factor (LF), and edema factor (EF)—that
come together in binary combinations to form lethal toxin and edema toxin. PA binds to
cellular receptors to translocate LF (a protease) and EF (an adenylate cyclase) into
cells. The toxins alter cell signaling pathways in the host to interfere with innate immune
responses in early stages of infection and to induce vascular collapse at late stages.
This review focuses on the role of anthrax toxins in pathogenesis. Other virulence
determinants, as well as vaccines and therapeutics, are briefly discussed.
Bacillus anthracis infection is rare in developed countries. However, recent
outbreaks in the United States and Europe and the potential use of the bacteria for
bioterrorism have focused interest on it. Furthermore, although anthrax was known to
typically occur as one of three syndromes related to entry site of (i.e., cutaneous,
gastrointestinal, or inhalational), a fourth syndrome including severe soft tissue infection
in injectional drug users is emerging. Although shock has been described with
cutaneous anthrax, it appears much more common with gastrointestinal, inhalational (5
of 11 patients in the 2001 outbreak in the United States), and injectional anthrax. Based
in part on case series, the estimated mortalities of cutaneous, gastrointestinal,
inhalational, and injectional anthrax are 1%, 25 to 60%, 46%, and 33%, respectively.
Nonspecific early symptomatology makes initial identification of anthrax cases difficult.
Clues to anthrax infection include history of exposure to herbivore animal products,
heroin use, or clustering of patients with similar respiratory symptoms concerning for a
bioterrorist event. Once anthrax is suspected, the diagnosis can usually be made with
Gram stain and culture from blood or surgical specimens followed by confirmatory
testing (e.g., PCR or immunohistochemistry). Although antibiotic therapy (largely
quinolone-based) is the mainstay of anthrax treatment, the use of adjunctive therapies
such as anthrax toxin antagonists is a consideration.
Anthrax is a serious infectious disease caused by the bacterium Bacillus anthracis. It
primarily affects animals, but it can also occur in humans. Anthrax has been studied
extensively due to its potential use as a biological weapon.
Anthrax is a disease that can be transmitted to humans through contact with
infected animals or their products, inhalation from contaminated materials, or ingestion
from undercooked meat. Symptoms include a raised, itchy bump, ulcer, swelling, lymph
node involvement, fever, nausea, vomiting, abdominal pain, and bloody diarrhea.
Preventative measures include vaccination, proper hygiene, and avoiding contaminated
sources. Treatment involves antibiotics and supportive therapy in severe cases. Anthrax
can affect various body parts, with cutaneous anthrax affecting the skin, inhalation
affecting the respiratory system, and gastrointestinal anthrax affecting the digestive
system. The disease begins when spores enter the body, activate and release toxins,
leading to symptoms. In severe cases, the bacteria can spread throughout the body,
causing tissue damage and potentially fatal complications.
References
Moayeri, M., Leppla, S. H., Vrentas, C., Pomerantsev, A. P., & Liu, S. (2015). Anthrax pathogenesis. Annual review of
microbiology, 69, 185-208.
Sweeney, D. A., Hicks, C. W., Cui, X., Li, Y., & Eichacker, P. Q. (2011). Anthrax infection. American journal of respiratory and critical
care medicine, 184(12), 1333-1341.

Article No. 2 BRUCELLOSIS

Brucellosis: An Overview
Brucellosis remains a major zoonosis worldwide. Although many countries have
eradicated Brucella abortus from cattle, in some areas Brucella melitensis has emerged
as a cause of infection in this species as well as in sheep and goats. Despite
vaccination campaigns with the Rev 1 strain, B. melitensis remains the principal cause
of human brucellosis. Brucella suis is also emerging as an agent of infection in cattle,
thus extending its opportunities to infect humans. The recent isolation of distinctive
strains of Brucella from marine mammals has extended its ecologic range. Molecular
genetic studies have demonstrated phylogenetic affiliation to Agrobacterium,
Phyllobacterium, Ochrobactrum, and Rhizobium. Polymerase chain reaction and gene
probe development may provide more effective typing methods. Pathogenicity is related
to production of lipopolysaccharides containing a poly N-formyl perosamine O chain,
CuZn superoxide dismutase, erythrlose phosphate dehydrogenase, stress-induced
proteins related to intracellular survival, and adenine and guanine monophosphate
inhibitors of phagocyte functions. Protective immunity is conferred by antibody to
lipopolysaccharide and T-cell-mediated macrophage activation triggered by protein
antigens. Diagnosis still centers on isolation of the organism and serologic test results,
especially enzyme immunoassay, which is replacing other methods. Polymerase chain
reaction is also under evaluation. Therapy is based on tetracyclines with or without
rifampicin, aminoglycosides, or quinolones. No satisfactory vaccines against human
brucellosis are available, although attenuated purE mutants appear promising.
Brucellosis is a bacterial infection caused by various species of the genus
Brucella, also known as Malta fever, undulant fever, or Mediterranean fever. It primarily
affects animals but can also be transmitted to humans through direct contact with
infected animals or consumption of contaminated animal products. Symptoms include
recurring fever, sweating, weakness, malaise, joint and muscle pain, headaches, and
sometimes more severe complications affecting organs like the heart, liver, spleen, or
bones. Prevention involves avoiding contact with infected animals, practicing good
hygiene, and vaccinating livestock. Treatment typically involves a prolonged course of
antibiotics, with relapses possible. Brucellosis primarily affects the reproductive system
and can affect various organs in humans. Symptoms can persist for weeks to months
and may recur or become chronic if not adequately treated.
References
Corbel, M. J. (1997). Brucellosis: an overview. Emerging infectious diseases, 3(2), 213.

Article No. 3 BURULI ULCER

Buruli Ulcer
Buruli ulcer is an indolent necrotizing disease of the skin, subcutaneous tissue,
and bone that is caused by Mycobacterium ulcerans. Buruli ulcer is presently the third
most common mycobacterial disease of humans, after tuberculosis and leprosy, and the
least understood of the three. The disease remained largely ignored by many national
public health programs, but more recently, it has been recognized as an emerging
health problem, primarily due to its frequent disabling and stigmatizing complications.
The contribution discusses various aspects of Buruli ulcer, including its geographic
distribution, incidence, and prevalence; mode of transmission, pathogenesis, and
immunity; clinical manifestations; laboratory diagnosis; differential clinical diagnosis; and
treatment.
Buruli ulcer, also known as Mycobacterium ulcerans infection, is a debilitating
skin disease caused by the bacterium Mycobacterium ulcerans. This disease primarily
affects the skin and sometimes bone, causing severe skin ulcers and tissue destruction.
Here's a breakdown of key aspects:
1. Cause: Buruli ulcer is caused by the bacterium Mycobacterium ulcerans. This
bacterium produces a toxin called mycolactone, which damages skin tissue and
suppresses the immune response.
2. Symptoms: The disease typically starts as a painless swelling or nodule on the
skin, often resembling a mosquito bite or a small lump. Over time, the swelling may
progress to form an ulcer with undermined edges. The ulcer may be painless or
mildly painful and can vary in size from small lesions to large, deep ulcers. Without
treatment, the ulcers can lead to extensive tissue destruction and deformity.
3. Affected Body Parts: Buruli ulcer primarily affects the skin, but it can also involve
subcutaneous tissue, leading to significant destruction of skin and soft tissue. In
severe cases, it can extend to involve bones and joints.
4. Transmission: The exact mode of transmission of Mycobacterium ulcerans is not
entirely understood, but it is believed to occur through contact with contaminated
water or soil. The bacterium may enter the skin through cuts, abrasions, or insect
bites.
5. Prevention: Preventive measures include avoiding contact with potentially
contaminated water or soil, especially in areas where Buruli ulcer is endemic.
 Wearing protective clothing, using insect repellent, and promptly cleaning and
covering cuts or wounds can help reduce the risk of infection.
6. Treatment: The treatment of Buruli ulcer typically involves a combination of
antibiotics and wound care. Antibiotic therapy with drugs such as rifampicin and
clarithromycin is effective in treating the infection and preventing disease
progression. In some cases, surgical intervention may be necessary to remove dead
tissue and promote healing.
References
Portaels, F., Silva, M. T., & Meyers, W. M. (2009). Buruli ulcer. Clinics in dermatology, 27(3), 291-305.

Article No. 4 CAPNOCYTOPHAGA CANIMORSUS

Capnocytophaga Canimorsus
Capnocytophaga canimorsus is a commensal bacterium in the oral flora of dogs
and cats. The bacterium is a zoonotic agent and has been isolated from humans,
infected by dog or cat bites, scratches, licks or simply exposure to dogs or cats. Here
the infectious agent, its pathogenicity and potential virulence factors, infection in
animals and humans, diagnostic methods, prevalence, therapy and prevention are
described. Suggestions for future research are given.
Capnocytophaga canimorsus is a bacterium commonly found in the mouths of
dogs and cats. While it is typically harmless in most cases, it can cause severe
infections, particularly in individuals with weakened immune systems or those who have
had their spleens removed. Here's an overview of Capnocytophaga canimorsus:
Capnocytophaga canimorsus is a disease that can cause various infections in
humans, including septicemia, cellulitis, meningitis, and endocarditis. Prevention
involves proper wound care, avoidance of dogs and cats, and regular handwashing.
The disease is typically treated with antibiotics, with the specific antibiotic prescribed
depending on the severity and location of the infection. The bacteria enter the body
through skin breaks, multiply, and cause infection. In individuals with weakened immune
systems, the bacteria can spread more easily. Symptoms of Capnocytophaga
canimorsus infection include fever, chills, fatigue, muscle and joint pain, headache,
nausea, vomiting, redness, swelling, and warmth at the infection site, confusion or
altered mental status, and shortness of breath or chest pain. It is crucial to seek medical
attention if symptoms develop after being bitten or scratched by a dog or cat, especially
if the person has a weakened immune system or has had their spleen removed.
References
Gaastra, W., & Lipman, L. J. (2010). Capnocytophaga canimorsus. Veterinary microbiology, 140(3-4), 339-346.
Article No. 5 ELIZABETHKINGIA INFECTIONS
Elizabethkingia Infections in Humans: From Genomics To Clinics
The genus Elizabethkingia has recently emerged as a cause of life-threatening
infections in humans, particularly in immunocompromised patients. Several new species
in the genus Elizabethkingia have been proposed in the last decade. Numerous studies
have indicated that Elizabethkingia anophelis, rather than Elizabethkingia
meningoseptica, is the most prevalent pathogen in this genus. Matrix-assisted laser
desorption/ionization–time of flight mass spectrometry systems with an extended
spectrum database could reliably identify E. anophelis and E. meningoseptica, but they
are unable to distinguish the remaining species. Precise species identification relies on
molecular techniques, such as housekeeping gene sequencing and whole-genome
sequencing. These microorganisms are usually susceptible to minocycline but resistant
to most β-lactams, β-lactam/β-lactam inhibitors, carbapenems, and aminoglycosides.
They often exhibit variable susceptibility to piperacillin, piperacillin-tazobactam,
fluoroquinolones, and trimethoprim-sulfamethoxazole. Accordingly, treatment should be
guided by antimicrobial susceptibility testing. Target gene mutations are markedly
associated with fluoroquinolone resistance. Knowledge on the genomic characteristics
provides valuable insights into in these emerging pathogens.
Elizabethkingia infections are caused by bacteria of the genus Elizabethkingia,
with the most common species being Elizabethkingia anophelis. These infections
primarily affect vulnerable individuals with weakened immune systems, such as the
elderly or those with underlying health conditions.
The bacteria can cause a range of infections, including bloodstream infections,
pneumonia, and meningitis. Symptoms vary depending on the type and severity of
infection but may include fever, chills, difficulty breathing, confusion, and sepsis.
Prevention primarily involves standard infection control measures, such as
proper hand hygiene and disinfection of medical equipment. Treatment typically involves
antibiotics, although resistance to multiple antibiotics has been reported, making
treatment challenging in some cases.
Elizabethkingia infections can affect various parts of the body, most commonly
the bloodstream, lungs, and central nervous system. The bacteria work by invading the
body's tissues and causing infection, leading to inflammation and potential organ
damage if left untreated. Early detection and appropriate management are essential for
improving outcomes in affected individuals.
References
Lin, J. N., Lai, C. H., Yang, C. H., & Huang, Y. H. (2019). Elizabethkingia infections in humans: from genomics to clinics.
Microorganisms, 7(9), 295.
Article No. 6 GLANDERS (BURKHOLDERIA MALLEI)
Glanders: Off to The Races with Burkholderia Mallei
Burkholderia mallei, the etiologic agent of the disease known as glanders, is
primarily a disease affecting horses and is transmitted to humans by direct contact with
infected animals. The use of B. mallei as a biological weapon has been reported and
currently, there is no vaccine available for either humans or animals. Despite the history
and highly infective nature of B. mallei, as well as its potential use as a bioweapon, B.
mallei research to understand the pathogenesis and the host responses to infection
remains limited. Therefore, this minireview will focus on current efforts to elucidate B.
mallei virulence, the associated host immune responses elicited during infection and
discuss the feasibility of vaccine development.
Glanders is a contagious and potentially fatal disease caused by the bacterium
Burkholderia mallei. It primarily affects horses, donkeys, and mules but can also infect
other mammals, including humans. The disease is transmitted through direct contact
with infected animals or contaminated materials.
In humans, glanders can manifest as acute or chronic infections, depending on
the mode of transmission and the individual's immune response. The bacterium can
enter the body through breaks in the skin, inhalation of contaminated aerosols, or
ingestion of contaminated food or water. Once inside the body, B. mallei can cause
respiratory, cutaneous, or systemic infections.
Symptoms of glanders in humans may include fever, chills, muscle aches,
fatigue, cough, chest pain, skin lesions, and swollen lymph nodes. If left untreated,
glanders can progress to severe complications, including pneumonia, septicemia, and
abscess formation.
Prevention of glanders involves strict hygiene practices, such as proper
sanitation of animal facilities, quarantine measures, and avoiding contact with infected
animals or contaminated materials. There is no vaccine available for glanders in
humans, and treatment typically involves antibiotics, although strains resistant to
multiple antibiotics have been reported, posing a challenge for treatment.
Due to its potential for spreading rapidly and its significant impact on both animal
and human health, glanders is considered a significant public health concern. Early
detection, prompt treatment, and effective prevention measures are crucial in controlling
the spread of the disease.
References
Whitlock, G. C., Mark Estes, D., & Torres, A. G. (2007). Glanders: off to the races with Burkholderia mallei. FEMS microbiology
letters, 277(2), 115-122.
Article No. 7 HANSEN'S DISEASE (LEPROSY)
Leprosy In The 21st Century
Despite significant improvements in leprosy (Hansen's disease) treatment and
outlook for patients since the introduction of multidrug therapy (MDT) 3 decades ago,
the global incidence remains high, and patients often have long-term complications
associated with the disease. In this article, we discuss recent findings related to
genetics, susceptibility, and disease reservoirs and the implications of these findings for
Hansen's disease control and health outcomes for patients. We describe the continued
difficulties associated with treatment of inflammatory episodes known as “leprosy
reactions,” which cause much of the disability associated with the disease and can
affect people for many years after MDT is complete. We also discuss some of the
contemporary challenges for physicians and patients, including international and
internal migration of people affected by the disease. We suggest some important areas
of focus for future Hansen's disease research.
Hansen's Disease, commonly known as leprosy, is a chronic infectious disease
caused by the bacterium Mycobacterium leprae. It primarily affects the skin, peripheral
nerves, mucosal surfaces of the upper respiratory tract, and eyes.
Symptoms of leprosy can vary widely but often include skin lesions, nodules,
numbness, and muscle weakness. The disease progresses slowly, leading to
deformities and disabilities if left untreated.
Prevention of leprosy primarily involves early diagnosis and treatment, as well as
public health measures such as contact tracing and surveillance. Multidrug therapy
(MDT) is highly effective in curing leprosy and preventing its transmission.
The bacterium primarily spreads through respiratory droplets from infected
individuals, although the exact mode of transmission is not fully understood.
Early detection and treatment are crucial in preventing complications and
reducing transmission. Despite being curable, stigma and discrimination associated with
leprosy remain significant challenges in many parts of the world.
References
White, C., & Franco-Paredes, C. (2015). Leprosy in the 21st century. Clinical microbiology reviews, 28(1), 80-94.
Article No. 8 LEPTOSPIROSIS
Animal Leptospirosis
Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in
many tropical regions and causes large epidemics after heavy rainfall and flooding.
Infection results from direct or indirect exposure to infected reservoir host animals that
carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine.
Although many wild and domestic animals can serve as reservoir hosts, the brown rat
(Rattus norvegicus) is the most important source of human infections. Individuals living
in urban slum environments characterized by inadequate sanitation and poor housing
are at high risk of rat exposure and leptospirosis. The global burden of leptospirosis is
expected to rise with demographic shifts that favor increases in the number of urban
poor in tropical regions subject to worsening storms and urban flooding due to climate
change. Data emerging from prospective surveillance studies suggest that most human
leptospiral infections in endemic areas are mild or asymptomatic. Development of more
severe outcomes likely depends on three factors: epidemiological conditions, host
susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly
in patients older than 60 years of age. High levels of bacteremia are associated with
poor clinical outcomes and based on animal model and in vitro studies, are related in
part to poor recognition of leptospiral LPS by human TLR4. Patients with severe
leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-
alpha, and IL-10. Patients with the HLA DQ6 allele are at higher risk of disease,
suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis
typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia,
and headache and may be confused with other entities such as influenza and dengue
fever. Newer diagnostic methods facilitate early diagnosis and antibiotic treatment.
Patients progressing to multisystem organ failure have widespread hematogenous
dissemination of pathogens. Nonoliguric (high output) renal dysfunction should be
supported with fluids and electrolytes. When oliguric renal failure occurs, prompt
initiation of dialysis can be lifesaving. Elevated bilirubin levels are due to hepatocellular
damage and disruption of intercellular junctions between hepatocytes, resulting in
leaking of bilirubin out of bile caniliculi. Hemorrhagic complications are common and are
associated with coagulation abnormalities. Severe pulmonary hemorrhage syndrome
due to extensive alveolar hemorrhage has a fatality rate of >50 %. Readers are referred
to earlier, excellent summaries related to this subject (Adler and de la Peña-Moctezuma
2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et
al. 2005).
References
Ellis, W. A. (2015). Animal leptospirosis. Leptospira and leptospirosis, 99-137.
Article No. 9 RHINOVIRUS
Rhinovirus And the Lower Respiratory Tract
Human rhinoviruses (HRVs) are well-recognised causes of common colds and
associated upper respiratory tract complications such as sinusitis and otitis media. This
article reviews information linking HRV infection to illness in the lower respiratory tract.
HRVs are capable of efficient replication in vitro at temperatures present in the
tracheobronchial tree and have been shown to cause productive infection, elaboration
of cytokines and chemokines, and up-regulation of cell surface markers in human
bronchial epithelial cells. In situ hybridisation studies have proven that HRV infection
occurs in the tracheobronchial tree following experimental infection. Clinical studies
report that HRV infection is the second most frequently recognised agent associated
with pneumonia and bronchiolitis in infants and young children and commonly causes
exacerbations of pre-existing airways disease in those with asthma, chronic obstructive
pulmonary disease or cystic fibrosis. HRV infection is associated with one-third to one-
half of asthma exacerbations depending on age and is linked to asthma hospitalizations
in both adults and children. Limited information implicates HRV infection as a cause of
severe lower respiratory tract illness in older adults and in highly immunocompromised
hosts, particularly bone marrow transplant recipients. More information is needed about
the pathogenesis of HRV infection with regard to lower respiratory tract complications in
these diverse patient groups. Given the large unmet medical need associated with HRV
infections, safe and effective antiviral agents are needed for both prevention and
treatment of these infections.
Rhinovirus is a common viral pathogen responsible for causing the common cold,
a mild respiratory illness. It primarily affects the upper respiratory tract, including the
nose and throat. Rhinovirus spreads through respiratory droplets when an infected
person coughs or sneezes, or by touching contaminated surfaces and then touching the
nose or mouth.
Rhinovirus infections cause symptoms like nasal congestion, cough, and sore
throat. They usually resolve within a week. Prevention strategies include handwashing,
avoiding contact, and respiratory hygiene. Treatment involves over-the-counter
medications, rest, hydration, and a healthy diet. There is no specific cure for rhinovirus
infections, but they can be managed through good hygiene practices.
References
Hayden, F. G. (2004). Rhinovirus and the lower respiratory tract. Reviews in medical virology, 14(1), 17-31.
Article No. 10 VARICELLA ZOSTER
Varicella-zoster Virus
Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which
can be severe in immunocompromised individuals, infants, and adults. Primary infection
is followed by latency in ganglionic neurons. During this period, no virus particles are
produced, and no obvious neuronal damage occurs. Reactivation of the virus leads to
virus replication, which causes zoster (shingles) in tissues innervated by the involved
neurons, inflammation, and cell death — a process that can lead to persistent radicular
pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown
and it is difficult to treat. Furthermore, other zoster complications can develop, including
myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and
gastroenterological infections such as ulcers, pancreatitis, and hepatitis. VZV is the only
human herpesvirus for which highly effective vaccines are available. After varicella or
vaccination, both wild-type and vaccine-type VZV establish latency, and long-term
immunity to varicella develops. However, immunity does not protect against reactivation.
Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this
Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV
infections, with an emphasis on the molecular events that regulate these diseases.
Varicella zoster virus (VZV, also
known as human herpesvirus 3) is
a ubiquitous alphaherpesvirus with
a double-stranded DNA genome.
VZV only naturally infects humans,
with no animal reservoir; its main
targets are T lymphocytes,
epithelial cells and ganglia.
Primary infection causes varicella
(chickenpox), during which VZV
becomes latent in ganglionic
neurons. As cellular immunity to
VZV wanes with advancing age or in immunocompromised individuals, VZV reactivates
to cause zoster (shingles). Zoster can be complicated by chronic pain (postherpetic
neuralgia (PHN)) and other serious neurological and ocular disorders (for example,
meningoencephalitis, myelitis, cranial nerve palsies, vasculopathy, keratitis and
retinopathy), as well as multiple visceral and gastrointestinal disorders, including ulcers,
hepatitis and pancreatitis. Antiviral drugs and vaccines against both varicella and zoster
are available and are effective in treating and preventing VZV-induced disease.
Primary infection with varicella zoster virus (VZV) in susceptible individuals
causes varicella, which usually is harmless in healthy children whose immune system
controls the infection. VZV establishes latency in ganglionic neurons, and reactivation of
viral replication and spread of the virus to the skin innervated by these neurons causes
zoster. Increasing age and compromised immune function are risk factors for
complications of VZV infections. However, some of these complications, such as
postherpetic neuralgia, can also occur without these predisposing factors.
References
Arvin, A. M. (1996). Varicella-zoster virus. Clinical microbiology reviews, 9(3), 361-381.

Article No. 11 RUBELLA

Rubella
Rubella remains an important pathogen worldwide, with roughly 100 000 cases
of congenital rubella syndrome estimated to occur every year. Rubella-containing
vaccine is highly effective and safe and, as a result, endemic rubella transmission has
been interrupted in the Americas since 2009. Incomplete rubella vaccination
programmes result in continued disease transmission, as evidenced by recent large
outbreaks in Japan and elsewhere. In this Seminar, we provide present results
regarding rubella control, elimination, and eradication policies, and a brief review of new
laboratory diagnostics. Additionally, we provide novel information about rubella-
containing vaccine immunogenetics and review the emerging evidence of interindividual
variability in humoral and cell-mediated innate and adaptive immune responses to
rubella-containing vaccine and their association with haplotypes and single-nucleotide
polymorphisms across the human genome.
Rubella is a contagious viral infection caused by the rubella virus. It primarily
affects the respiratory system and is known for causing symptoms such as a rash, fever,
and swollen lymph nodes. The virus spreads through respiratory droplets from coughs
and sneezes of an infected person. Rubella can lead to serious complications,
especially in pregnant women, such as congenital rubella syndrome, which can cause
birth defects in the developing fetus.
Prevention of rubella primarily involves vaccination, typically administered as part
of the MMR (measles, mumps, and rubella) vaccine. Vaccination helps prevent the
spread of the virus and protects individuals from contracting the disease. There is no
specific cure for rubella, but supportive care such as rest, hydration, and over-the-
counter medications to alleviate symptoms can help manage the infection.
Symptoms of rubella typically include a mild fever, sore throat, runny or stuffy
nose, headache, red eyes, enlarged lymph nodes, and a distinctive red rash that starts
on the face and spreads to the rest of the body. Most people recover from rubella
without complications, but it can pose significant risks to unborn babies if contracted
during pregnancy.
References
Banatvala, J. E., & Brown, D. W. (2004). Rubella. The Lancet, 363(9415), 1127-1137.
Article No. 12 BORDETELLA PERTUSSIS
Bordetella Pertussis
Pertussis is a highly contagious acute respiratory illness classically known as
“whooping cough” because of its characteristic cough. The majority of cases are caused
by Bordetella pertussis, with some caused by B. parapertussis (1, 2). Pertussis is a
vaccine-preventable disease that was a major cause of childhood morbidity and
mortality during the first half of the 20th century. Following worldwide implementation of
pertussis vaccination, cases declined significantly (3) (Fig. 1). However, it was never
fully eliminated, and epidemic peaks continued on a cycle of every 2 or 3 to 5 years. In
the past several years, even countries with generally high immunization rates in early
childhood have experienced a rise in pertussis cases. In 2014, the World Health
Organization (WHO) reported 139,786 cases of pertussis in spite of an estimated global
86% diphtheria-tetanus-pertussis (DTP) vaccine coverage with three doses (4). In 2013
and 2014, there were 28,639 and 32,791, respectively yearly reported cases of
pertussis in the United States, which makes pertussis the most prominent emerging
vaccine-preventable disease in this country. Of those cases involving patients 6 months
to 6 years of age, 42% had a DTaP vaccination history of 3 or more doses, 6% had 1 or
2 doses, 8% had none, and 44% had an unknown vaccination status (5). In 2014, there
were more than 10,000 reported cases of pertussis in California alone. The greatest
morbidity and mortality associated with pertussis infection occur in young infants,
particularly those under 3 months of age, often requiring hospitalization in an intensive
care setting (6, 7). With this upsurge in pertussis, much more has been learned about
the organism, the vaccines available, and the variability of illness presentation. This
complex disease has promoted many public health actions aimed at reducing the
spread of Bordetella pertussis, specifically to the fragile neonate, at risk of much worse
disease than older age groups and of high mortality.
References
Nieves, D. J., & Heininger, U. (2016). Bordetella pertussis. Emerging Infections 10, 311-339.
Article No. 13 YERSINIA PESTIS
Yersinia Pestis--Etiologic Agent of Plague
Plague is a widespread zoonotic disease that is caused by Yersinia pestis and
has had devastating effects on the human population throughout history. Disappearance
of the disease is unlikely due to the wide range of mammalian hosts and their attendant
fleas. The flea/rodent life cycle of Y. pestis, a gram-negative obligate pathogen, exposes
it to very different environmental conditions and has resulted in some novel traits
facilitating transmission and infection. Studies characterizing virulence determinants of
Y. pestis have identified novel mechanisms for overcoming host defenses. Regulatory
systems controlling the expression of some of these virulence factors have proven quite
complex. These areas of research have provided new insights into the host-parasite
relationship. This review will update our present understanding of the history, etiology,
epidemiology, clinical aspects, and public health issues of plague.
Yersinia pestis is a bacterium responsible for causing the plague, a severe
infectious disease that has plagued humanity for centuries. The bacterium primarily
affects the lymphatic system, causing swollen and painful lymph nodes, known as
buboes. There are three main forms of plague: bubonic, septicemic, and pneumonic.
Bubonic plague is the most common form, characterized by fever, chills,
weakness, and the development of painful, swollen lymph nodes. If left untreated, the
bacteria can enter the bloodstream, leading to septicemic plague, which causes fever,
chills, abdominal pain, shock, and sometimes organ failure. Pneumonic plague occurs
when the bacteria infect the lungs, leading to severe respiratory symptoms such as
cough, chest pain, and difficulty breathing. It is the deadliest form of the plague and can
be transmitted through respiratory droplets from person to person.
Prevention of the plague involves controlling the rodent populations that carry the
bacterium, avoiding contact with sick or dead animals, and taking precautions in regions
where the plague is endemic. Antibiotics like streptomycin, gentamicin, or doxycycline
are effective in treating the plague if administered promptly after symptoms appear.
Additionally, vaccines are available for individuals at high risk of exposure, such as
laboratory workers and healthcare professionals.
In summary, Yersinia pestis is a bacterium that causes the plague, a highly
contagious and potentially deadly disease affecting the lymphatic system, bloodstream,
and lungs. Prevention involves controlling rodent populations and practicing proper
hygiene, while treatment relies on antibiotics and supportive care. Early recognition of
symptoms and prompt medical intervention are crucial for successful management of
the disease.
References
Perry, R. D., & Fetherston, J. D. (1997). Yersinia pestis--etiologic agent of plague. Clinical microbiology reviews, 10(1), 35-66.
Article No. 14 MYCOBACTERIUM TUBERCULOSIS
Mycobacterium Tuberculosis

In this infographic, the genetics, phylogeny, physiology, and pathogenesis

mechanisms of Mycobacterium tuberculosis are shown.
Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), the
leading cause of death due to a single infectious agent, claiming 1.7 million lives in
2016. Of the deaths attributable to TB in 2016, 22% occurred in people coinfected with
HIV, and close to 5% of the 10.4 million incident cases of this disease were resistant to
at least two of the first-line TB drugs. In this infographic, we describe the fundamental
features of the genetics, phylogeny, and physiology of this member of the phylum
Actinobacteria, which is associated increasingly with drug resistance mediated by
mutations and rearrangements in its single, circular chromosome. We also highlight the
key pathogenesis mechanisms employed by this slow-growing, facultative intracellular
bacterium, which include avoidance of host cell clearance by arrest of the normal
macrophage maturation process.
Mycobacterium tuberculosis causes tuberculosis (TB), a contagious disease
affecting the lungs and other parts of the body. TB can be latent or active, with
symptoms including coughing, chest pain, weakness, fatigue, weight loss, fever, night
sweats, and chills. Preventive measures include vaccination, avoiding close contact,
improving ventilation, and early detection and treatment. Treatment typically involves
antibiotics and Directly Observed Therapy. Prompt diagnosis and treatment are crucial
for TB prevention.
References
Koch, A., & Mizrahi, V. (2018). Mycobacterium tuberculosis. Trends in microbiology, 26(6), 555-556.
Article No. 15 PLASMODIUM FALCIPARUM
Plasmodium Falciparum
Plasmodium falciparum is
the etiological agent of
malaria tropica, the
leading cause of death
due to a vector-borne
infectious disease,
claiming 0.5 million lives
every year. The single-cell
eukaryote undergoes a
complex life cycle and is
an obligate intracellular
parasite of hepatocytes
(clinically silent) and
erythrocytes (disease
causing). An infection can
progress to a wide range of pathologies, including severe anemia and cerebral malaria,
which can lead to death. P. falciparum repeatedly replicates over the course of 48 h
inside erythrocytes, resulting in exponential growth and rapid disease progression. As
the single most important infectious disease afflicting children, no other pathogen has
exerted a higher selection pressure on the human genome. Over 20 polymorphisms,
including the sickle-cell trait, have been selected in human populations, despite severe
fitness costs, since they offer protection against fatal P. falciparum infections. No
effective vaccine exists, but several curative treatments are available.
Plasmodium falciparum is a protozoan parasite that causes severe malaria in
humans, primarily affecting red blood cells and the liver. The disease is transmitted
through the bite of infected Anopheles mosquitoes and can lead to severe complications
such as organ failure, coma, and death. Preventive measures include using insecticide-
treated bed nets, wearing protective clothing, applying insect repellent, and taking
prophylactic medication. Treatment typically involves antimalarial medications like
artemisinin-based combination therapies. However, resistance to antimalarial drugs is a
growing concern, emphasizing the need for further research and development.
Treatment relies on timely treatment to prevent life-threatening complications.
References
Maier, A. G., Matuschewski, K., Zhang, M., & Rug, M. (2019). Plasmodium falciparum. Trends in parasitology, 35(6), 481-482.
Article No. 16 TRICHOPHYTON RUBRUM
Clinical Trichophyton Rubrum Strain Exhibiting Primary Resistance to Terbinafine
The study analyzed the in vitro antifungal susceptibilities of six clinical
Trichophyton rubrum isolates from a single onychomycosis patient who failed oral
terbinafine therapy. The isolates had significantly reduced susceptibilities to terbinafine,
with minimum fungicidal concentrations (MFCs) of terbinafine for all six strains being
over 128 μg/ml. The baseline strain's MIC was 4,000-fold higher than normal,
suggesting primary resistance to terbinafine.
The isolates showed normal susceptibilities to clinically available antimycotics but
were fully cross-resistant to several other known squalene epoxidase inhibitors,
suggesting a target-specific mechanism of resistance. This is the first confirmed report
of terbinafine resistance in dermatophytes. Trichophyton rubrum is a major causative
agent for superficial dermatomycoses like onychomycosis and tinea pedis, accounting
for as many as 69.5% of all dermatophyte infections. Terbinafine is widely used in the
therapy of dermatophyte infections, with no reports of resistance against this allylamine
antifungal.
Infections due to T. rubrum are often associated with frequent relapses following
cessation of antifungal therapy, but these have not been related to resistance to the
antifungals. Routine antifungal susceptibility testing is not carried out in the case of
dermatophyte infections, suggesting that resistance occurs but is not detected. In one
patient, all isolates, including baseline isolates, were found to have greatly reduced
susceptibilities to terbinafine in vitro. The study identifies the first known series of T.
rubrum strains with intrinsic resistance to terbinafine and suggests that resistance to
squalene epoxidase inhibitors could be operative in T. rubrum strains.
Six T. rubrum isolates were cultured from a patient for onychomycosis treatment.
The isolates showed significantly reduced susceptibilities to terbinafine compared to the
reference strains. To understand drug resistance, they were tested against clinically
used oral antifungals like itraconazole and griseofulvin. All isolates showed normal
susceptibilities to these agents, and the MICs of all three agents remained constant.
The results suggest that the T. rubrum strains isolated are specifically resistant to
terbinafine.
References
Mukherjee, P. K., Leidich, S. D., Isham, N., Leitner, I., Ryder, N. S., & Ghannoum, M. A. (2003). Clinical Trichophyton rubrum strain
exhibiting primary resistance to terbinafine. Antimicrobial agents and Chemotherapy, 47(1), 82-86.
Article No. 17 TRICHOPHYTON MENTAGROPHYTES
Population Differentiation, Antifungal Susceptibility, And Host Range of
Trichophyton Mentagrophytes Isolates Causing Recalcitrant Infections In
Humans And Animals.
The major problems in determining the causative factors of the high prevalence
of dermatophytoses include the lack of a well-standardized antifungal susceptibility
testing method, the low consistency of in vitro and clinical minimal inhibitory
concentration values, the high genomic diversity of the population, and the unclear
mechanism of pathogenicity. These factors are of particular importance when the
disease is recalcitrant and relapses. Herein, we identified and characterized
Trichophyton mentagrophytes isolates obtained from therapy-resistant cases in humans
and animals. We used genomic diversity analysis of 17 human and 27 animal clinical
isolates with the MP-PCR technique, determined their phenotypic enzymatic activity and
host range, and performed antifungal susceptibility testing to currently available
antifungal drugs from various chemical groups. Genomic diversity values of 35.3% and
33.3% were obtained for clinical isolates from humans and animals, respectively, yet
without any relationship to the host species or antifungal drug to which resistance in
therapy was revealed. The highest activity of keratinase enzymes was recorded for fox,
guinea pig, and human hairs. These hosts can be considered as the main species in the
host range of these isolates. A phenyl morpholine derivative, i.e. amorolfine, exhibited
superior activity against strains obtained from both humans and animals with the lowest
MIC50. Interestingly, high compliance of terbinafine in vitro resistance with clinical
problems in the treatment with this substance was shown as well. The high resistance
of dermatophytes to drugs is the main cause of the recalcitrance of the infection,
whereas the other features of the fungus are less important.
Trichophyton mentagrophytes is a fungus that causes dermatophytosis or
ringworm infections in humans and animals, primarily affecting the skin, hair, and nails.
Symptoms include red, itchy, and scaly patches on the skin, particularly in areas like the
feet, groin, scalp, or body. In severe cases, it can lead to hair loss and secondary
bacterial infections. Prevention involves good hygiene, keeping the skin clean and dry,
avoiding sharing personal items, and wearing appropriate footwear in public places.
Treatment usually involves antifungal medications, depending on the severity and
location of the infection. The fungus invades and feeds on keratin, causing
inflammation, itching, and skin lesions.
References
Gnat, S., Łagowski, D., Nowakiewicz, A., Osińska, M., & Kopiński, Ł. (2020). Population differentiation, antifungal susceptibility, and
host range of Trichophyton mentagrophytes isolates causing recalcitrant infections in humans and animals. European
Journal of Clinical Microbiology & Infectious Diseases, 39, 2099-2113.
Article No. 18 ACQUIRED IMMUNODEFICIENCY DISEASE
“Human Immunodeficiency Virus/AIDS in the Era of Coronavirus Disease 2019: A
Juxtaposition of 2 Pandemics”
The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted
persons with human immunodeficiency virus (HIV), interfering with critical health
services for HIV prevention, treatment, and care. While there are multiple profiles of
persons living with HIV and the impact of COVID-19 may differ for each, the severity of
COVID-19 in persons with HIV is related strongly to the presence of comorbidities that
increase the risk of severe disease in COVID-19 patients in the absence of HIV. An
effective response to the juxtaposition of the HIV and COVID-19 pandemics requires a
novel coordinated and collaborative global effort of scientists, industry, and community
partners to accelerate basic and clinical research, as well as implementation science to
operationalize evidence-based interventions expeditiously in real-world settings.
Accelerated development and clinical evaluation of prevention and treatment
countermeasures are urgently needed to mitigate the juxtaposition of the HIV and
COVID-19 pandemics.
AIDS (acquired immunodeficiency syndrome) is a viral disease caused by the
Human Immunodeficiency Virus (HIV). HIV attacks the immune system, specifically
targeting CD4 cells (T cells), weakening the body's ability to fight off infections and
diseases. The virus primarily spreads through unprotected sexual contact, contaminated
blood transfusions, sharing needles, or from mother to child during childbirth or
breastfeeding.
Prevention strategies include practicing safe sex, using clean needles, screening
blood donations, and administering antiretroviral therapy (ART) to HIV-positive
individuals to suppress viral replication and reduce transmission risk. While there is no
cure for HIV/AIDS, ART can effectively manage the virus and allow individuals to lead
healthy lives.
AIDS affects various parts of the body, but primarily targets the immune system,
leading to opportunistic infections and cancers. Common symptoms of HIV/AIDS
include fever, fatigue, weight loss, swollen lymph nodes, and recurrent infections. Early
detection through testing and prompt treatment with ART are crucial in managing the
disease and preventing its progression to AIDS.
References

Eisinger, R. W., Lerner, A. M., & Fauci, A. S. (2021). Human immunodeficiency virus/AIDS in the era of coronavirus disease 2019: a
juxtaposition of 2 pandemics. The Journal of infectious diseases, 224(9), 1455-1461.
Article No. 19 MUCORMYCOSIS
Mucormycosis
Mucormycosis is a rare fungal infection caused by mucormycetes, which live in various
environments and can result from ingestion of contaminated food, inhalation of spores,
or inoculation into disrupted skin or wounds. It mainly affects people with health
problems or those taking medicines that lower the body's ability to fight germs and
sickness. In developed countries, mucormycosis occurs primarily in
immunocompromised hosts, while in developing countries, most cases occur in poorly
controlled diabetes mellitus or immunocompetent subjects following trauma.
Mucormycosis can invade blood vessels, leading to thrombosis, necrosis, and tissue
infarction. Mortality rates are high for invasive mucormycosis, with 90% associated with
disseminated disease. Diagnosis relies on histopathology and culture, with blood tests
having limited diagnostic value. Mucormycosis can be classified into six forms: rhino-
orbital-cerebral mucormycosis (ROCM), pulmonary, cutaneous, gastrointestinal,
disseminated, and mucormycosis of uncommon sites. Due to its rarity, randomized
controlled therapeutic trials have not been performed. Lipid formulations of amphotericin
B (LFAB) are the mainstay of therapy, but newer triazoles, posaconazole (POSA) and
isavuconazole (ISAV), may be effective in patient’s refractory to or intolerant of LFAB.
Early surgical debridement or excision is important adjunctive treatment.
Mucormycosis, also known as "black fungus," is a serious fungal infection
primarily affecting individuals with weakened immune systems, such as those with
diabetes, cancer, or organ transplant recipients. It enters the body through inhalation of
fungal spores or skin wounds and can invade blood vessels and spread to organs like
the sinuses, lungs, brain, and skin. Symptoms include facial pain, nasal congestion,
black lesions, fever, cough, chest pain, headache, blurred vision, and skin ulcers.
Preventative measures include controlling underlying medical conditions, maintaining
good hygiene, avoiding fungal spore-prone environments, and treating skin injuries
promptly. Treatment involves antifungal medications, surgical removal, and managing
underlying medical conditions.
References
Reid, G., Lynch III, J. P., Fishbein, M. C., & Clark, N. M. (2020, February). Mucormycosis. In Seminars in respiratory and critical care
medicine (Vol. 41, No. 01, pp. 099-114). Thieme Medical Publishers.
Article No. 20 ESCHERICHIA COLI (E. COLI)
Structure and genetics of Escherichia coli O antigens
Escherichia coli includes clonal groups of both commensal and pathogenic
strains, with some of the latter causing serious infectious diseases. O antigen variation
is current standard in defining strains for taxonomy and epidemiology, providing the
basis for many serotyping schemes for Gram-negative bacteria. This review covers the
diversity in E. coli O antigen structures and gene clusters, and the genetic basis for the
structural diversity. Of the 187 formally defined O antigens, six (O31, O47, O67, O72,
O94 and O122) have since been removed and three (O34, O89 and O144) strains do
not produce any O antigen. Therefore, structures are presented for 176 of the 181 E.
coli O antigens, some of which include subgroups. Most (93%) of these O antigens are
synthesized via the Wzx/Wzy pathway, 11 via the ABC transporter pathway, with O20,
O57 and O60 still uncharacterized due to failure to find their O antigen gene clusters.
Biosynthetic pathways are given for 38 of the 49 sugars found in E. coli O antigens, and
several pairs or groups of the E. coli antigens that have related structures show close
relationships of the O antigen gene clusters within clades, thereby highlighting the
genetic basis of the evolution of diversity.
Escherichia coli (E. coli) is a bacterium commonly found in the intestines of
humans and animals. While most strains of E. coli are harmless, some can cause
illness. One of the most well-known strains is E. coli O157:H7, which can cause severe
food poisoning. Diseases caused by E. coli typically involve the gastrointestinal tract,
leading to symptoms such as diarrhea (often bloody), abdominal pain, nausea, and
vomiting. In severe cases, it can lead to complications like hemolytic uremic syndrome
(HUS), which can cause kidney failure. Prevention of E. coli infection involves proper
hygiene practices, such as washing hands thoroughly, cooking food thoroughly
(especially meat), avoiding unpasteurized dairy products, and drinking clean water.
Treatment for E. coli infections usually involves supportive care, such as staying
hydrated and managing symptoms. In severe cases or those with complications like
HUS, medical intervention may be necessary, including antibiotics and sometimes
dialysis for kidney failure.
Overall, E. coli primarily affects the gastrointestinal system, causing symptoms
ranging from mild diarrhea to severe complications like kidney failure. Prevention
through hygiene and safe food practices is key to avoiding infection, and treatment
focuses on supportive care and, in severe cases, medical intervention.
References

Denamur, E., Clermont, O., Bonacorsi, S., & Gordon, D. (2021). The population genetics of pathogenic Escherichia coli. Nature
Reviews Microbiology, 19(1), 37-54.
Article No. 21 STAPHYLOCOCCUS AUREUS
Pathogenicity and virulence of Staphylococcus aureus
Staphylococcus aureus is one of the most frequent worldwide causes of
morbidity and mortality due to an infectious agent. This pathogen can cause a wide
variety of diseases, ranging from moderately severe skin infections to fatal pneumonia
and sepsis. Treatment of S. aureus infections is complicated by antibiotic resistance and
a working vaccine is not available. There has been ongoing and increasing interest in
the extraordinarily high number of toxins and other virulence determinants that S.
aureus produces and how they impact disease. In this review, we will give an overview
of how S. aureus initiates and maintains infection and discuss the main determinants
involved. A more in-depth understanding of the function and contribution of S. aureus
virulence determinants to S. aureus infection will enable us to develop anti-virulence
strategies to counteract the lack of an anti-S. aureus vaccine and the ever-increasing
shortage of working antibiotics against this important pathogen.
Staphylococcus aureus is a bacterium found on the skin and nose of healthy
individuals, which can cause skin infections, food poisoning, and toxic shock syndrome
(TSS). Prevention involves good hygiene practices like handwashing, wound care, and
avoiding sharing personal items. In healthcare settings, proper infection control
measures are crucial. Treatment usually involves antibiotics, but antibiotic-resistant
strains may limit options. In severe cases, drainage of abscesses or surgical
intervention may be necessary. Staphylococcus aureus affects the skin, respiratory
tract, bloodstream, and internal organs, depending on the infection type. Symptoms
include redness, swelling, pain, fever, and organ dysfunction. Early detection and
prompt treatment are essential to prevent complications associated with
Staphylococcus aureus infections.
References

Cheung, G. Y., Bae, J. S., & Otto, M. (2021). Pathogenicity and virulence of Staphylococcus aureus. Virulence, 12(1), 547-569.
Article No. 22 STREPTOCOCCUS PNEUMONIAE
Recent Advances in The Epidemiology and Prevention of Streptococcus
Pneumoniae Infections
The introduction of pneumococcal conjugate vaccines (PCVs) 7 and 13 into
national childhood immunization programs in the US in 2000 and 2010, respectively,
proved to be remarkably successful in reducing infant mortality due to invasive
pneumococcal disease (IPD), resulting in widespread uptake of these vaccines.
Secondary herd protection of non-vaccinated adults against IPD has proven to be an
additional public health benefit of childhood immunization with PCVs, particularly in the
case of the vulnerable elderly who are at increased risk due to immunosenescence and
underlying comorbidity. Despite these advances in pneumococcal immunization, the
global burden of pneumococcal disease, albeit of unequal geographic distribution,
remains high. Reasons for this include restricted access of children living in many
developing countries to PCVs, the emergence of infection due to non-vaccine serotypes
of the pneumococcus, and non-encapsulated strains of the pathogen. Emerging
concerns affecting the elderly include the realization that herd protection conferred by
the current generation of PCVs (PCV7, PCV10, and PCV13) has reached a ceiling in
many countries at a time of global population aging, compounded by uncertainty
surrounding those immunization strategies that induce optimum immunogenicity and
protection against IPD in the elderly. All of the aforementioned issues, together with a
consideration of pipeline and pending strategies to improve access to, and serotype
coverage of, PCVs, are the focus areas of this review.
Streptococcus pneumoniae is a bacterium that causes pneumonia,
meningitis, sinusitis, and otitis media, primarily affecting the respiratory system.
Vaccination is a key preventive measure, and antibiotics are commonly used to treat
infections. The bacteria enter the body through the respiratory tract and multiply and
produce toxins, damaging tissues. Symptoms vary depending on the type and severity
of the infection, with pneumonia causing cough, fever, chest pain, and difficulty
breathing, meningitis causing headache, sinusitis causing facial pain, and otitis media
causing difficulty hearing.

References
Feldman, C., & Anderson, R. (2020). Recent advances in the epidemiology and prevention of Streptococcus pneumoniae
infections. F1000Research, 9.
Article No. 23 SALMONELLA SPP.
Antibiotic Resistance in Salmonella Spp. Isolated from Poultry: A Global Overview
Salmonella enterica is the most important foodborne pathogen, and it is often
associated with the contamination of poultry products. Annually, Salmonella causes
around 93 million cases of gastroenteritis and 155,000 deaths worldwide. Antimicrobial
therapy is the first choice of treatment for this bacterial infection; however, antimicrobial
resistance has become a problem due to the misuse of antibiotics both in human
medicine and animal production. It has been predicted that by 2050, antibiotic-resistant
pathogens will cause around 10 million deaths worldwide, and the WHO has suggested
the need to usher in the post-antibiotic era. The purpose of this review is to discuss and
update the status of Salmonella antibiotic resistance, in particular, its prevalence,
serotypes, and antibiotic resistance patterns in response to critical antimicrobials used
in human medicine and the poultry industry. Based on our review, the median
prevalence values of Salmonella in broiler chickens, raw chicken meat, and in eggs and
egg-laying hens were 40.5% (interquartile range [IQR] 11.5-58.2%), 30% (IQR 20-
43.5%), and 40% (IQR 14.2-51.5%), respectively. The most common serotype was
Salmonella Enteritidis, followed by Salmonella Typhimurium. The highest antibiotic
resistance levels within the poultry production chain were found for nalidixic acid and
ampicillin. These findings highlight the need for government entities, poultry
researchers, and producers to find ways to reduce the impact of antibiotic use in poultry,
focusing especially on active surveillance and finding alternatives to antibiotics.
Salmonella spp. is a bacterium that causes various diseases in humans,
including Salmonellosis, a mild illness causing diarrhea, abdominal cramps, fever,
nausea, and vomiting, and Typhoid Fever, a severe form causing high fever, weakness,
stomach pains, headache, and loss of appetite. Prevention involves food safety, proper
hygiene, safe water, and vaccines. Treatment involves supportive care to manage
symptoms and may include antibiotics for severe cases. Salmonella can affect various
parts of the body, primarily the gastrointestinal tract, but can also affect other organs. It
is commonly found in contaminated food and water and can be transmitted through
ingestion or direct contact with infected animals or their feces. Symptoms typically
appear within 6 to 72 hours after exposure and can vary depending on the strain and
individual's immune system.
References

Popa, G. L., & Papa, M. I. (2021). Salmonella spp. infection-a continuous threat worldwide. Germs, 11(1), 88.
Article No. 24 CLOSTRIDIUM DIFFICILE
Clostridium difficile Infection: An Epidemiology Update
Clostridium (reclassified as “Clostridioides”) difficile infection (CDI) is a healthcare-
associated infection and significant source of potentially preventable morbidity,
recurrence, and death, particularly among hospitalized older adults. Additional risk
factors include antibiotic use and severe underlying illness. The increasing prevalence
of community-associated CDI is gaining recognition as a novel source of morbidity in
previously healthy patients. Even after recovery from initial infection, patients remain at
risk for recurrence or reinfection with a new strain. Some pharmaco-epidemiologic
studies have suggested an increased risk associated with proton pump inhibitors and
protective effect from statins, but these findings have not been uniformly reproduced in
all studies. Certain ribotypes of C. difficile, including the BI/NAP1/027, 106, and 018, are
associated with increased antibiotic resistance and potential for higher morbidity and
mortality. CDI remains a high-morbidity healthcare-associated infection, and better
understanding of ribotypes and medication risk factors could help to target treatment,
particularly for patients with high recurrence risk.
Clostridium difficile (C. difficile) is a bacterium that causes a range of diseases,
including antibiotic-associated diarrhea and colitis. It often occurs after antibiotics,
disrupting the gut microbiota and allowing C. difficile to flourish and produce toxins that
damage the intestinal lining. Prevention measures include proper hand hygiene,
antibiotic stewardship, and environmental cleaning. Treatment options include
antibiotics like metronidazole, vancomycin, and fidaxomicin, or fecal microbiota
transplantation (FMT) to restore gut bacteria balance.
C. difficile primarily affects the gastrointestinal tract, particularly the colon, and
produces toxins that damage the colon lining, leading to inflammation and diarrhea.
Transmission occurs through fecal-oral routes, ingested through contaminated surfaces
or objects, and through healthcare settings. Symptoms include watery diarrhea,
abdominal pain, fever, nausea, and loss of appetite. In severe cases, complications can
occur, potentially leading to life-threatening conditions. C. difficile infections are
generally treatable if diagnosed and managed promptly. Prevention measures, including
good hand hygiene and judicious antibiotic use, are crucial in reducing the risk of
infection.
References

De Roo, A. C., & Regenbogen, S. E. (2020). Clostridium difficile infection: an epidemiology update. Clinics in colon and rectal
surgery, 33(02), 049-057.
Article No. 25 HELICOBACTER PYLORI
Pathogenesis Of Helicobacter Pylori Infection
The original strategies developed by Helicobacter pylori to persistently colonise
its host and to deregulate its cellular functions make this bacterium an outstanding
model to study host-pathogen interaction and the mechanisms responsible for bacterial-
induced carcinogenesis. During the last year, significant results were obtained on the
role of bacterial factors essential for gastric colonisation such as spiral shape
maintenance, orientation through chemotaxis and the formation of bacteria clonal
population islands inside the gastric glands. Particularities of the H pylori cell surface, a
structure important for immune escape, were demonstrated. New insights in the
bacterial stress response revealed the importance of DNA methylation-mediated
regulation. Further findings were reported on H pylori components that mediate natural
transformation and mechanisms of bacterial DNA horizontal transfer which maintain a
high level of H pylori genetic variability. Within-host evolution was found to be niche-
specific and probably associated with physiological differences between the antral and
oxyntic gastric mucosa.
In addition, with the progress of CryoEM, high-resolution structures of the major
virulence factors, VacA and CagT4SS, were obtained. The use of gastric organoid
models fostered research revealing, preferential accumulation of bacteria at the site of
injury during infection. Several studies further characterised the role of CagA in the
oncogenic properties of H pylori, identifying the activation of novel CagA-dependent
pathways, leading to the promotion of genetic instabilities, epithelial-to-mesenchymal
transition and finally carcinogenesis. Recent studies also highlight that microRNA-
mediated regulation and epigenetic modifications, through DNA methylation, are key
events in the H pylori-induced tumorigenesis process.
Helicobacter pylori is a bacterium that infects the stomach lining, leading to
gastrointestinal diseases such as gastric cancer. It causes inflammation, ulcers, and
potentially gastric cancer. Prevention involves good hygiene, avoiding contaminated
food and water, and early detection and treatment. Treatment involves antibiotics,
proton pump inhibitors, and bismuth supplements. The loci effect refers to the impact of
specific genetic variations on an individual's susceptibility to H. pylori infection and its
associated diseases. The bacteria weaken the stomach's protective mucous coating,
allowing acid to enter the sensitive lining, leading to inflammation, ulcers, and potentially
stomach cancer. Transmission occurs through oral-oral or fecal-oral routes, with factors
like poor hygiene, contaminated food, and close contact facilitating transmission.
Symptoms include gastric pain, peptic ulcers, and gastric cancer. Early detection and
treatment are crucial for managing H. pylori-related conditions and preventing long-term
complications.
References
Denic, M., Touati, E., & De Reuse, H. (2020). Pathogenesis of Helicobacter pylori infection. Helicobacter, 25, e12736.
Article No. 26 NEISSERIA GONORRHOEAE
Multiresistant Neisseria Gonorrhoeae: A New Threat in Second Decade of The XXI
Century
Neisseria gonorrhoeae is an etiologic agent of gonorrhoea, one of the most common
sexually transmitted diseases caused by bacteria. For many years, infections caused by
N. gonorrhoeae were relatively easy to treat; however, resistance has emerged
successively to all therapeutic agents used in treatment of the disease, e.g., penicillin,
ciprofloxacin or azithromycin. Currently, the global problem is the emergence and a
threat of spread of N. gonorrhoeae strains resistant to extended-spectrum
cephalosporins (ESC), such as injectable ceftriaxone and oral-used cefixime.
Especially, dangerous are multi-resistant strains resistant simultaneously to ESC and
azithromycin. Three strains with high-level resistance to azithromycin and resistant to
ESC were first time isolated in 2018. Moreover, in 2018, the first ESBL was described in
N. gonorrhoeae and that makes the threat of appearing the ESBL mechanism of
resistance in N. gonorrhoeae more real, even though the strain was sensitive to
ceftriaxone. Molecular typing revealed that variants resistant to ESC occurred also
among strains belonging to epidemic clonal complex CC1 (genogroup G1407)
distinguished in NG-MAST typing system. The G1407 genogroup, in particular the
ST1407 sequence type, is currently dominant in most European countries. The
presence of different mechanisms of drug resistance significantly affects clinical practice
and force changes in treatment regimens and introduction of new drugs.
Neisseria gonorrhoeae is a bacterium responsible for sexually transmitted
infections (STIs), primarily affecting the reproductive tract in both men and women. It
can also infect the throat, eyes, mouth, and rectum. Prevention involves abstinence,
consistent use of condoms, and regular testing for STIs. Gonorrhea can be cured with
antibiotics, but antibiotic resistance is a growing concern. Treatment usually involves a
combination of antibiotics, and it is important to complete the full course of antibiotics
prescribed by a healthcare provider.
The locus effect refers to genetic variations or mutations within the bacterial
genome that affect its virulence, antibiotic resistance, or other characteristics. Neisseria
gonorrhoeae primarily affects the genital tract, leading to infections such as urethritis in
men and cervicitis in women. It can also affect other mucous membranes, leading to
inflammation and discharge.
The disease is primarily transmitted through sexual contact, including vaginal,
anal, and oral sex. Symptoms include painful urination, unusual discharge, genital
itching or soreness, bleeding between menstrual periods, pain or swelling in the
testicles, sore throat, and redness, swelling, or discharge from the eyes. Early detection
and treatment can help prevent complications and reduce the risk of transmission to
others.
References
Młynarczyk-Bonikowska, B., Majewska, A., Malejczyk, M., Młynarczyk, G., & Majewski, S. (2020). Multiresistant Neisseria
gonorrhoeae: a new threat in second decade of the XXI century. Medical microbiology and immunology, 209, 95-108.
Article No. 27 CHLAMYDIA TRACHOMATIS
Chlamydia Trachomatis: Cell Biology, Immunology and Vaccination
Chlamydia trachomatis is the causative agent of a highly prevalent sexually
transmitted bacterial disease and is associated with a number of severe disease
complications. Current therapy options are successful at treating disease, but patients
are left without protective immunity and do not benefit the majority asymptomatic
patients who do not seek treatment. As such, there is a clear need for a broad acting,
protective vaccine that can prevent transmission and protect against symptomatic
disease presentation. There are three key elements that underlie successful vaccine
development: 1) Chlamydia biology and immune-evasion adaptations, 2) the correlates
of protection that prevent disease in natural and experimental infection, 3) reflection
upon the evidence provided by previous vaccine attempts. In this review, we give an
overview of the unique intra-cellular biology of C. trachomatis and give insight into the
dynamic combination of adaptations that allow Chlamydia to subvert host immunity and
survive within the cell. We explore the current understanding of chlamydial immunity in
animal models and in humans and characterise the key immune correlates of protection
against infection. We discuss in detail the specific immune interactions involved in
protection, with relevance placed on the CD4+ T lymphocyte and B lymphocyte
responses that are key to pathogen clearance. Finally, we provide a timeline of C.
trachomatis vaccine research to date and evaluate the successes and failures in
development so far. With insight from these three key elements of research, we suggest
potential solutions for chlamydial vaccine development and promising avenues for
further exploration.
Chlamydia trachomatis is a bacterium responsible for both sexually transmitted
infections (STIs) and non-sexually transmitted diseases. It primarily causes genital
infections, including urethritis in men and cervicitis in women, and can also infect the
rectum, throat, and eyes through sexual contact. It is also responsible for trachoma, a
leading cause of infectious blindness in developing countries.
Prevention strategies include using condoms correctly during sexual activity,
regular testing, and limiting sexual partners. Chlamydia infections are typically treated
with antibiotics, such as azithromycin or doxycycline. It can cause localized
inflammation and tissue damage in affected areas, such as the genital tract, rectum,
throat, and eyes.
Chlamydia infections can cause inflammation, pain, and discharge in the genital
tract, leading to complications like pelvic inflammatory disease (PID) and trachoma in
the eyes. The bacterium infects host cells, primarily epithelial cells, by entering them
and replicating within a specialized compartment called an inclusion. It is primarily
transmitted through sexual contact, including vaginal, anal, or oral sex, and can also be
transmitted from an infected mother to her newborn during childbirth.
Symptoms of chlamydia infection may include genital discharge, burning
sensation during urination, abdominal pain, painful intercourse, and in some cases,
rectal or throat symptoms.
References

Murray, S. M., & McKay, P. F. (2021). Chlamydia trachomatis: Cell biology, immunology and vaccination. Vaccine, 39(22), 2965-
2975.

Article No. 28 BORRELIA BURGDORFERI

The Lyme Disease Spirochete, Borrelia Burgdorferi, as a Model Vector-Borne
Pathogen: Insights on Regulation of Gene and Protein Expression
The Lyme disease spirochete persists in nature through cycles between ticks and
vertebrates. Although the spirochete interacts with numerous, distinct tissues and
environmental conditions during its infectious cycle, Borrelia burgdorferi appears to
possess a limited ability to sense its external environment. This apparent paradox is
being resolved through detailed investigations of the molecular mechanisms through
which B. burgdorferi controls production of virulence-associated factors such as the Erp
outer surface proteins. The results have led to development of a model for how B.
burgdorferi controls expression of its diverse proteins, wherein physiological and
metabolic states that are unique to specific points in the infectious cycle trigger changes
in gene and protein expression levels.
Borrelia burgdorferi is a bacterium responsible for Lyme disease, a multisystemic
illness that affects various parts of the body. The primary disease caused by Borrelia
burgdorferi is Lyme disease, which can lead to symptoms affecting the skin, joints,
heart, and nervous system.
Preventive measures include avoiding tick bites, wearing protective clothing,
using insect repellent, and avoiding areas with high tick populations. Regular tick
checks are also essential, especially after spending time outdoors in wooded or grassy
areas. Tick control involves reducing the tick population in residential areas by
maintaining lawns and using pesticides if necessary.
Vaccination is not widely available for humans, but there are dogs-specific
vaccines for Lyme disease. Lyme disease is typically treated with antibiotics, with the
specific antibiotic and duration depending on the stage and severity of the disease.
Early detection and treatment are crucial for preventing the progression of Lyme
disease to more severe stages.
 The loci effect refers to the impact of genetic variations at specific locations in an
organism's genome, and in the context of Lyme disease, genetic factors may influence
an individual's susceptibility to the infection and their response to treatment. The
bacterium infects the body primarily through the bite of infected ticks, which can spread
through the bloodstream and lymphatic system, leading to inflammation and various
symptoms.
Borrelia burgdorferi is primarily transmitted to humans through the bite of infected
black-legged ticks (deer ticks in North America) belonging to the Ixodes genus.
Symptoms of Lyme disease can vary depending on the stage of infection and may
include early-stage symptoms such as erythema migrans, fever, fatigue, headaches,
muscle and joint aches, later stages like severe headaches, arthritis, neurological
symptoms, and heart palpitations or irregularities.
References
Stevenson, B. (2023). The Lyme disease spirochete, Borrelia burgdorferi, as a model vector-borne pathogen: insights on regulation
of gene and protein expression. Current Opinion in Microbiology, 74, 102332.

Article No. 29 INFLUENZA VIRUS

The Ecology and Evolution of Influenza Viruses
The patterns and processes of influenza virus evolution are of fundamental
importance, underpinning such traits as the propensity to emerge in new host species
and the ability to rapidly generate antigenic variation. Herein, we review key aspects of
the ecology and evolution of influenza viruses. We begin with an exploration of the
origins of influenza viruses within the orthomyxoviruses, showing how our perception of
the evolutionary history of these viruses has been transformed with metagenomic
sequencing. We then outline the diversity of virus subtypes in different species and the
processes by which these viruses have emerged in new hosts, with a particular focus
on the role played by segment reassortment. We then turn our attention to documenting
the spread and phylodynamic of seasonal influenza A and B viruses in human
populations, including the drivers of antigenic evolution, and finish with a discussion of
virus diversity and evolution at the scale of individual hosts.
Transcription and replication of the influenza virus RNA genome is catalyzed by
the viral heterotrimeric RNA-dependent RNA polymerase in the context of viral
ribonucleoprotein (vRNP) complexes. Atomic resolution structures of the viral RNA
synthesis machinery have offered insights into the initiation mechanisms of viral
transcription and genome replication, and the interaction of the viral RNA polymerase
with host RNA polymerase II, which is required for the initiation of viral transcription.
Replication of the viral RNA genome by the viral RNA polymerase depends on host
ANP32A, and host-specific sequence differences in ANP32A underlie the poor activity of
avian influenza virus polymerases in mammalian cells. A failure to faithfully copy the
viral genome segments can lead to the production of aberrant viral RNA products, such
as defective interfering (DI) RNAs and mini viral RNAs (mvRNAs). Both aberrant RNA
types have been implicated in innate immune responses against influenza virus
infection. This review discusses recent insights into the structure–function relationship
of the viral RNA polymerase and its role in determining host range and virulence.
Influenza, also known as the flu, is a highly contagious viral infection caused by
three types: A, B, and C. It causes seasonal flu and pandemic flu, which are often
caused by new influenza A viruses. Prevention involves vaccination, hygiene practices,
and antiviral medications. Treatment involves antiviral medications, symptomatic
treatments, and rest. Influenza primarily affects the respiratory system, including the
nose, throat, and lungs, but can also have systemic effects. The virus infects respiratory
epithelial cells, replicating within them, causing cell damage and triggering an immune
response. The virus enters the body through the respiratory tract, usually through
inhalation of respiratory droplets from an infected person. It then attaches to host cells,
releasing new virus particles that spread to neighboring cells and can be expelled into
the environment through coughing and sneezing. Influenza has a zoonotic origin,
primarily circulating among animals but occasionally infecting humans. Symptoms
typically appear 1 to 4 days after exposure and can range from mild to severe, with
complications more likely in certain populations.
References
Wille, M., & Holmes, E. C. (2020). The ecology and evolution of influenza viruses. Cold Spring Harbor perspectives in
medicine, 10(7), a038489.
Article No. 30 HEPATITIS VIRUSES (A, B, C, D, E)
From Hepatitis A To E: A Critical Review of Viral Hepatitis
Viral infections affecting the liver have had an important impact on humanity, as
they have led to significant morbidity and mortality in patients with acute and chronic
infections. Once an unknown etiology, the discovery of the viral agents triggered interest
of the scientific community to establish the pathogenesis and diagnostic modalities to
identify the affected population. With the rapid scientific and technological advances in
the last centuries, controlling and even curing the infections became a possibility, with a
large focus on preventive medicine through vaccination. Hence, a comprehensive
understanding of hepatitis A, B, C, D and E is required by primary care physicians and
gastroenterologists to provide care to these patients. The review article describes the
epidemiology, pathogenesis, clinical presentation, diagnostic tools and current
medication regimens, with a focus on upcoming treatment options and the role of liver
transplantation.
Hepatitis is a liver inflammation caused by several viruses, including Hepatitis A,
B, C, D, and E. Each virus has its own symptoms, transmission methods, prevention,
treatment, and effects on the body. Hepatitis A (HAV) causes acute liver inflammation,
while HBV can cause acute or chronic liver inflammation, leading to liver cirrhosis or
liver cancer. Prevention involves vaccination, good hygiene practices, safe water and
food, and supportive care.
HCV causes chronic liver inflammation, leading to liver damage, cirrhosis, or liver
cancer. Prevention involves vaccination, safe sex practices, and antiviral medications.
Mode of transmission is blood or bodily fluids, sexual contact, sharing needles or
personal items, and mother-to-child transmission.
HDV causes severe liver inflammation, usually in those already infected with
HBV. Preventing HDV reduces the risk of HDV, and controlling HBV infection can help.
Treatment is usually non-specific, but controlling HBV infection can help.
HEV causes acute liver inflammation, similar to HAV, and can be prevented
through improved sanitation and safe water practices. Symptoms can vary depending
on the virus type and whether the infection is acute or chronic. Early diagnosis and
appropriate medical management are essential to prevent severe liver damage and
complications.
References
Castaneda, D., Gonzalez, A. J., Alomari, M., Tandon, K., & Zervos, X. B. (2021). From hepatitis A to E: A critical review of viral
hepatitis. World journal of gastroenterology, 27(16), 1691.
Article No. 31 HERPES SIMPLEX VIRUS (HSV)
Herpes Simplex Virus: Global Infection Prevalence and Incidence Estimates, 2016
Herpes simplex virus (HSV) is a common human virus that causes two types:
HSV-1 and HSV-2. Both types cause similar diseases, but they are associated with
different parts of the body. HSV-1 is primarily associated with oral herpes, causing cold
sores or fever blisters around the mouth and on the lips, and can also cause genital
herpes through oral-genital contact. HSV-2 is mainly responsible for genital herpes,
characterized by painful sores in the genital area.
Prevention involves avoiding direct contact with lesions or secretions from an
infected person, practicing safe sex, and avoiding sharing personal items with infected
individuals. There is no cure for HSV, but antiviral medications can help reduce the
severity and frequency of outbreaks. The loci effect refers to the tendency of HSV to
establish latency in sensory nerve ganglia after the initial infection, leading to recurrent
outbreaks of symptoms.
HSV is primarily transmitted through direct contact with infected lesions or
secretions, such as saliva, genital fluids, or skin-to-skin contact during sexual activity. It
can also be transmitted from mother to child during childbirth if the mother is
experiencing an active genital herpes outbreak.
Symptoms vary depending on the type of HSV and the site of infection. Early
diagnosis and appropriate management can help alleviate symptoms and reduce the
risk of transmission to others.
Herpes simplex virus (HSV) infections are a global health concern, with type 1
being primarily transmitted through oral-to-oral contact and commonly causing cold
sores. Type 2 is almost entirely sexually transmitted, causing genital herpes. Neonates
can also acquire HSV infection from genitally infected mothers during birth and from oral
contact with caregivers postnatally. Neonatal infection has a high fatality and disability
rate in surviving infants.
The World Health Organization (WHO) has produced global and regional
estimates of HSV type 2 infection prevalence and incidence, but these estimates are not
directly comparable to WHO estimates due to their age, assay performance, and
regional groupings. The Global Burden of Disease (GBD) study does not produce any
estimates for HSV type 1, an increasingly important cause of genital infection.
Estimates of HSV infection across geographical regions, age, sex, HSV type, and
infection site are needed for advocacy and resource planning. In 2016, an estimated
491.5 million people were living with HSV type 2 infection, equivalent to 13.2% of the
world's population aged 15-49 years. An estimated 3752.0 million people had HSV type
1 infection at any site, equivalent to a global prevalence of 66.6% in 0–49-year-olds.
 An estimated half a billion people had genital infection with HSV type 2 or type 1,
and several billion had oral HSV type 1 infection. Millions of people may also be at
higher risk of acquiring human immunodeficiency virus (HIV), particularly women in the
WHO African Region who have the highest HSV type 2 prevalence and exposure to
HIV.
References
James, C., Harfouche, M., Welton, N. J., Turner, K. M., Abu-Raddad, L. J., Gottlieb, S. L., & Looker, K. J. (2020). Herpes simplex
virus: global infection prevalence and incidence estimates, 2016. Bulletin of the World Health Organization, 98(5), 315.

Article No. 32 HUMAN PAPILLOMAVIRUS (HPV)

Human Papillomaviruses: Diversity, Infection and Host Interactions
HPV is a group of viruses that can cause various diseases in humans, including
genital warts and various cancers. The most common cancers associated with HPV
include cervical cancer, anal cancer, vulvar cancer, vaginal cancer, penile cancer, and
oropharyngeal cancer. HPV vaccines are highly effective in preventing infection with
targeted HPV types, and regular screenings can help detect precancerous changes in
the cervix. There is no cure for HPV, but many of the diseases it causes can be treated.
Treatment options include topical treatments, surgical removal of warts or lesions, or
treatments for cancer such as surgery, chemotherapy, or radiation therapy. HPV
infections can affect various parts of the body, with different strains associated with
different diseases. The virus infects the skin or mucous membranes, infecting epithelial
cells and leading to abnormal proliferation, warts, or cancerous tumors. It is primarily
transmitted through direct skin-to-skin contact, sexual activity, or mother-to-baby contact
during childbirth. Symptoms of HPV include genital warts, abnormal changes in cervix
cells, and symptoms associated with cancers such as persistent pain, bleeding, or
changes in bowel or urinary habits. It is crucial for individuals to be aware of HPV and
take preventive measures, such as vaccination and safe sex practices, to reduce the
risk of infection and associated diseases.
Human papillomaviruses (HPVs) are an ancient and highly successful group of
viruses that have co-evolved with their host to replicate in specific anatomical niches of
the stratified epithelia. They replicate persistently in dividing cells, hijack key host
cellular processes to manipulate the cellular environment and escape immune detection
and produce virions in terminally differentiated cells that are shed from the host. Some
HPVs cause benign, proliferative lesions on the skin and mucosa, and others are
associated with the development of cancer. However, most HPVs cause infections that
are asymptomatic and inapparent unless the immune system becomes compromised.
To date, the genomes of almost 450 distinct HPV types have been isolated and
sequenced. In this Review, I explore the diversity, evolution, infectious cycle, host
interactions and disease association of HPVs.
References
McBride, A. A. (2022). Human papillomaviruses: diversity, infection and host interactions. Nature Reviews Microbiology, 20(2), 95-
108.
Article No. 33 MEASLES VIRUS
Measles Virus in Cancer Therapy
The measles virus, also known as rubeola, is a highly contagious virus that
primarily affects the respiratory system. It is the most common disease, causing
symptoms such as high fever, cough, runny nose, sore throat, red eyes, and a
characteristic rash. To prevent measles, the measles, mumps, and rubella (MMR)
vaccine is the most effective method. High vaccination rates within a population help
establish herd immunity, reducing the virus's spread and protecting vulnerable
individuals. Treatment for measles typically focuses on alleviating symptoms and
providing supportive care, such as rest, hydration, and fever-reducing medications. In
areas with vitamin A deficiency, supplementation with vitamin A may be recommended
to reduce the risk of complications and improve outcomes.
The loci effect refers to the specific locations within the body where the virus
establishes infection, such as the respiratory tract, lymph nodes, and various organs.
Measles can affect other organs and systems, including the skin, lymphatic system, and
central nervous system. The virus spreads through respiratory droplets and can also
survive on surfaces for a short period, allowing indirect transmission through contact
with contaminated objects. The measles virus is believed to have originated from a virus
that infects cattle and likely evolved to infect humans through close contact between
humans and infected animals.
Over the last years, the development of viruses to treat cancer patients has re-
gained considerable attention. A genetically modified herpesvirus, Talimogene
laherparepvec, has already been authorized for the treatment of melanoma patients.
Also recombinant measles virus (MeV) is developed as an oncolytic virus. Because of
its high genetic flexibility, a number of different MeV strains have been the basis for the
generation of targeted, armed, or shielded viruses that are highly specific for a given
tumor target, more effective, or protected against serum neutralization. Such MeV have
been extensively tested in vitro and in vivo, whereby remarkable oncolytic potency is
accompanied by safety also in non-human primates. Therefore, MeV has been
introduced into 19 different clinical trials and has reached phase II against two different
tumor entities, multiple myeloma and ovarian carcinoma. Remarkably, one patient with
advanced stage myeloma experienced long-term remission after treatment, visualizing
the potency of this approach.
References
Muehlebach, M. D. (2020). Measles virus in cancer therapy. Current Opinion in Virology, 41, 85-97.
Article No. 34 ROTAVIRUS
Rotavirus Cell Entry: Not So Simple After All
Rotavirus is a highly contagious virus that primarily affects infants and young
children, causing gastroenteritis, inflammation of the stomach and intestines. Symptoms
include severe diarrhea, vomiting, fever, abdominal pain, and dehydration. Prevention
measures include vaccination, hand hygiene, environmental hygiene, and isolation.
Treatment focuses on managing symptoms and preventing dehydration, which may
include rehydration or medication to alleviate fever and discomfort.
The loci effect, a term not commonly associated with rotavirus, may be referring
to the genetic variability of rotavirus strains, which can impact the severity of the
disease and the effectiveness of vaccines. Rotavirus infects cells lining the small
intestine, leading to cell damage and loss of absorptive surface area, leading to
malabsorption of nutrients and fluid, leading to diarrhea and dehydration. The virus is
highly contagious and can spread easily through the fecal-oral route, primarily through
contact with contaminated objects, surfaces, food, or water.
Rotavirus is primarily transmitted through the fecal-oral route, meaning it spreads
when a person ingests the virus through contact with contaminated objects, surfaces,
food, or water. Symptoms of rotavirus infection include severe watery diarrhea,
vomiting, fever, abdominal pain, and dehydration, particularly in infants and young
children. Prevention through vaccination, hand hygiene, and environmental sanitation is
crucial in controlling the spread of the virus, while treatment focuses on managing
symptoms and preventing dehydration.
Rotaviruses are important agents of severe gastroenteritis in young children, and
show a very selective cell and tissue tropism, as well as significant age and host
restriction. In the last few years, these properties have been associated with the initial
interaction of the virus with histo-blood group antigens on the cell surface, although
post-attachment interactions have also been found to define the susceptibility to
infection of human enteroids. These initial interactions seem also to determine the virus
entry pathway, as well as the induction of signaling cascades that influence the virus
intracellular vesicular traffic and escape from endosomes. Here we review the current
knowledge of the different stages of the virus entry journey.
References

Arias, C. F., & López, S. (2021). Rotavirus cell entry: not so simple after all. Current opinion in virology, 48, 42-48.
Article No. 35 EBOLA VIRUS
Ebola Virus Disease: An Emerging and Re-Emerging Viral Threat
Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever (EHF), is
a severe and often fatal illness in humans caused by the Ebola virus. Symptoms
typically begin suddenly and include fever, headache, muscle pain, weakness, diarrhea,
vomiting, abdominal pain, and unexplained bleeding or bruising. In severe cases, it can
lead to multi-organ failure and death.
Prevention measures include avoiding contact with infected individuals,
practicing good hand hygiene, wearing appropriate personal protective equipment,
avoiding bushmeat consumption, and implementing infection control measures in
healthcare settings. There is currently no specific cure for Ebola virus disease, but
supportive care is primarily used to manage symptoms and complications. Experimental
treatments such as monoclonal antibodies and antiviral drugs have been used in some
cases, but their efficacy is still under investigation.
The loci effect refers to genetic factors that influence an individual's susceptibility
to infectious diseases, including Ebola virus disease. Genetic variations in host factors
can affect the severity of the disease and the likelihood of survival. Ebola virus primarily
targets the immune system and endothelial cells, infecting multiple organs, leading to
widespread tissue damage and organ failure. It enters the body through mucosal
surfaces or breaks in the skin, infecting immune cells, replicating within them, and
spreading to other tissues via the bloodstream.
Ebola virus is transmitted through direct contact with infected individuals,
contaminated surfaces, and healthcare workers. Symptoms typically begin suddenly
and can progress to shock, multi-organ failure, and death.
The genus Ebolavirus from the family Filoviridae is composed of five species
including Sudan ebolavirus, Reston ebolavirus, Bundibugyo ebolavirus, Taï Forest
ebolavirus, and Ebola virus (previously known as Zaire ebolavirus). These viruses have
a large non-segmented, negative-strand RNA of approximately 19 kb that encodes for
glycoproteins (i.e., GP, sGP, ssGP), nucleoproteins, virion proteins (i.e., VP 24, 30,40)
and an RNA dependent RNA polymerase. These viruses have become a global health
concern because of mortality, their rapid dissemination, new outbreaks in West-Africa,
and the emergence of a new condition known as “Post-Ebola virus disease syndrome”
that resembles inflammatory and autoimmune conditions such as rheumatoid arthritis,
systemic lupus erythematosus and spondyloarthritis with uveitis. However, there are
many gaps in the understanding of the mechanisms that may induce the development
of such autoimmune-like syndromes. Some of these mechanisms may include a high
formation of neutrophil extracellular traps, an uncontrolled “cytokine storm”, and the
possible formation of auto-antibodies. The likely appearance of autoimmune
phenomena in Ebola survivors suppose a new challenge in the management and
control of this disease and opens a new field of research in a special subgroup of
patients. Herein, the molecular biology, pathogenesis, clinical manifestations, and
treatment of Ebola virus disease are reviewed and some strategies for control of
disease are discussed.
References

Rojas, M., Monsalve, D. M., Pacheco, Y., Acosta-Ampudia, Y., Ramírez-Santana, C., Ansari, A. A., ... & Anaya, J. M. (2020). Ebola
virus disease: An emerging and re-emerging viral threat. Journal of autoimmunity, 106, 102375

Article No. 36 PLASMODIUM VIVAX

The Immunology of Plasmodium Vivax Malaria
Plasmodium vivax is a protozoan parasite that causes malaria, a disease
characterized by recurring fevers, chills, and flu-like symptoms. It primarily affects
humans and can be prevented through mosquito control and chemoprophylaxis.
Treatment usually involves antimalarial medications like chloroquine, primaquine, and
atovaquone-proguanil. The loci effect refers to genetic loci associated with susceptibility
or resistance to malaria.
P. vivax infects red blood cells in the human body and travels to the liver, where it
undergoes replication and infects red blood cells, causing them to rupture. This cycle of
invasion, replication, and rupture is responsible for malaria symptoms. The parasite's
life cycle involves both human and mosquito hosts, with sporozoites in the mosquito's
salivary glands and blood-stage parasites in the mosquito.
P. vivax is prevalent in tropical and subtropical regions, particularly in Asia, Latin
America, Africa, and the Middle East. It is transmitted through the bite of infected female
Anopheles mosquitoes, blood transfusions, organ transplants, or from mother to unborn
child during pregnancy.
Plasmodium vivax infection, the predominant cause of malaria in Asia and Latin
America, affects ~14 million individuals annually, with considerable adverse effects on
wellbeing and socioeconomic development. A clinical hallmark of Plasmodium infection,
the paroxysm, is driven by pyrogenic cytokines produced during the immune response.
Here, we review studies on the role of specific immune cell types, cognate innate
immune receptors, and inflammatory cytokines on parasite control and disease
symptoms. This review also summarizes studies on recurrent infections in individuals
living in endemic regions as well as asymptomatic infections, a serious barrier to
eliminating this disease. We propose potential mechanisms behind these repeated and
subclinical infections, such as poor induction of immunological memory cells and
inefficient T effector cells. We address the role of antibody-mediated resistance to P.
vivax infection and discuss current progress in vaccine development. Finally, we review
immunoregulatory mechanisms, such as inhibitory receptors, T regulatory cells, and the
anti-inflammatory cytokine, IL-10, that antagonizes both innate and acquired immune
responses, interfering with the development of protective immunity and parasite
clearance. These studies provide new insights for the clinical management of
symptomatic as well as asymptomatic individuals and the development of an efficacious
vaccine for vivax malaria.
References
Antonelli, L. R., Junqueira, C., Vinetz, J. M., Golenbock, D. T., Ferreira, M. U., & Gazzinelli, R. T. (2020). The immunology of
Plasmodium vivax malaria. Immunological reviews, 293(1), 163-189.

Article No. 37 GIARDIA LAMBLIA

Giardia lamblia: Laboratory Maintenance, Lifecycle Induction, and Infection of
Murine Models
Giardia lamblia is a microscopic parasite that causes giardiasis, an infection
affecting the intestines. It causes symptoms such as diarrhea, abdominal cramps,
bloating, nausea, and weight loss. Prevention involves ensuring water and food safety,
proper cooking, and good hygiene practices. Treatment involves medication like
metronidazole or tinidazole, and fluid replacement in cases of dehydration.
The locus effect refers to the specific location where the parasite establishes
itself and causes infection. Giardia lamblia primarily affects the small intestine, causing
inflammation and interfering with nutrient absorption. The parasite has two forms: a cyst
form and a trophozoite form. The cyst form is ingested via contaminated food or water,
and the trophozoite form attaches to the intestinal lining and reproduces, leading to
giardiasis symptoms.
Giardia lamblia is found worldwide and can be transmitted through waterborne
transmission, foodborne transmission, and person-to-person transmission. Symptoms
include diarrhea, abdominal cramps, bloating, flatulence, nausea, fatigue, and weight
loss. In some cases, individuals may be asymptomatic carriers. Seeking medical
attention is crucial for proper diagnosis and treatment to alleviate symptoms and
prevent the spread of the infection.
Giardia lamblia is a protozoan parasite that is found ubiquitously throughout the
world and is a major contributor to diarrheal disease. Giardia exhibits a biphasic lifestyle
existing as either a dormant cyst or a vegetative trophozoite. Infections are typically
initiated through the consumption of cyst-contaminated water or food. Giardia was first
axenized in the 1970s and can be readily maintained in a laboratory setting.
Additionally, Giardia is one of the few protozoans that can be induced to complete its
complete lifecycle using laboratory methods. In this article, we outline protocols to
maintain Giardia and induce passage through its lifecycle. We also provide protocols for
infecting and quantifying parasites in an animal infection model.
References
Fink, M. Y., Shapiro, D., & Singer, S. M. (2020). Giardia lamblia: Laboratory maintenance, lifecycle induction, and infection of murine
models. Current protocols in microbiology, 57(1), e102.
Article No. 38 ENTAMOEBA HISTOLYTICA
Pathogenicity And Virulence of Entamoeba Histolytica, The Agent of Amoebiasis
Entamoeba histolytica is a protozoan parasite that causes amoebiasis, a disease
affecting the intestines. It causes amoebic dysentery, characterized by severe diarrhea
with blood and mucus, and amoebic liver abscess, where the parasite can migrate to
the liver, forming life-threatening abscesses if not treated promptly. Prevention involves
proper hygiene, safe water and food sources, and sanitation. Treatment involves
medication like metronidazole or tinidazole, symptomatic relief, and liver abscess
drainage.
Entamoeba histolytica invades the intestinal lining, causing tissue damage,
inflammation, and ulcers. In severe cases, it can penetrate the intestinal wall and
migrate to the liver, where it forms abscesses. Transmission occurs through fecal-oral
routes and direct contact with infected individuals. Symptoms include abdominal pain,
diarrhea, fever, and fatigue, as well as liver abscess pain, fever, chills, and jaundice.
Entamoeba histolytica can be acquired through ingesting contaminated food or water,
especially in areas with poor sanitation and hygiene practices. Understanding these
aspects is crucial for preventing, diagnosing, and treating infections effectively. Prompt
medical attention is necessary, especially in cases of severe diarrhea or suspected liver
abscesses.
The amoeba parasite Entamoeba histolytica is the causative agent of human
amebiasis, an enteropathic disease affecting millions of people worldwide. This ancient
protozoan is an elementary example of how parasites evolve with humans, e.g. taking
advantage of multiple mechanisms to evade immune responses, interacting with
microbiota for nutritional and protective needs, utilizing host resources for growth,
division, and encystation. These skills of E. histolytica perpetuate the species and
incidence of infection. However, in 10% of infected cases, the parasite turns into a
pathogen; the host-parasite equilibrium is then disorganized, and the simple lifecycle
based on two cell forms, trophozoites and cysts, becomes unbalanced. Trophozoites
acquire a virulent phenotype which, when non-controlled, leads to intestinal invasion
with the onset of amoebiasis symptoms. Virulent E. histolytica must cross mucus,
epithelium, connective tissue and possibly blood. This highly mobile parasite faces
various stresses and a powerful host immune response, with oxidative stress being a
challenge for its survival. New emerging research avenues and omics technologies
target gene regulation to determine human or parasitic factors activated upon infection,
their role in virulence activation, and in pathogenesis; this research bears in mind that E.
histolytica is a resident of the complex intestinal ecosystem. The goal is to eradicate
amoebiasis from the planet, but the parasitic life of E. histolytica is ancient and complex
and will likely continue to evolve with humans.
References
Guillén, N. (2023). Pathogenicity and virulence of Entamoeba histolytica, the agent of amoebiasis. Virulence, 14(1), 2158656.
Article No. 39 TOXOPLASMA GONDII
Toxoplasma Gondii Infection and its Implications within the Central Nervous
System
Toxoplasma gondii is a single-celled parasite that can infect humans and other
warm-blooded animals. It causes a range of symptoms, from flu-like symptoms to
severe illness, especially in immunocompromised individuals. Prevention strategies
include cooking meat thoroughly, washing fruits and vegetables, avoiding untreated
water, wearing gloves, and practicing good hygiene. Treatment typically involves
antibiotics like pyrimethamine and sulfadiazine, which help suppress the infection.
Toxoplasma gondii can affect various parts of the body, including the brain, eyes,
and muscles. In immunocompromised individuals, it can lead to severe complications
such as encephalitis and retinochoroiditis. The parasite primarily affects the central
nervous system but can also affect other organs. Toxoplasma gondii enters the body
through ingestion of contaminated food or water, or by handling contaminated soil or cat
feces. Once ingested, the parasite reproduces in the intestines and spreads throughout
the body, forming cysts in various tissues. Toxoplasma gondii is found worldwide and
can infect a wide range of warm-blooded animals, including humans. The most common
mode of transmission is through ingestion of contaminated food or water, eating
undercooked or raw meat from infected animals, or handling contaminated soil or cat
litter.
Toxoplasma gondii is a parasite that infects a wide range of animals and causes
zoonotic infections in humans. Although it normally only results in mild illness in healthy
individuals, toxoplasmosis is a common opportunistic infection with high mortality in
individuals who are immunocompromised, most commonly due to reactivation of
infection in the central nervous system. In the acute phase of infection, interferon-
dependent immune responses control rapid parasite expansion and mitigate acute
disease symptoms. However, after dissemination the parasite differentiates into semi-
dormant cysts that form within muscle cells and neurons, where they persist for life in
the infected host. Control of infection in the central nervous system, a compartment of
immune privilege, relies on modified immune responses that aim to balance infection
control while limiting potential damage due to inflammation. In response to the activation
of interferon-mediated pathways, the parasite deploys an array of effector proteins to
escape immune clearance and ensure latent survival. Although these pathways are best
studied in the laboratory mouse, emerging evidence points to unique mechanisms of
control in human toxoplasmosis. In this Review, we explore some of these recent
findings that extend our understanding for proliferation, establishment, and control of
toxoplasmosis in humans.
References
Matta, S. K., Rinkenberger, N., Dunay, I. R., & Sibley, L. D. (2021). Toxoplasma gondii infection and its implications within the central
nervous system. Nature Reviews Microbiology, 19(7), 467-480.
Article No. 40 TRYPANOSOMA
Basic Biology of Trypanosoma
Trypanosoma is a genus of parasitic protozoans that cause diseases in humans
and animals. The two main species are Trypanosoma brucei and Trypanosoma cruzi,
which cause African trypanosomiasis and Chagas disease respectively. Prevention
strategies involve controlling vectors, avoiding contact with vectors, and using
insecticide-treated bed nets. For Chagas disease, prevention through blood transfusion,
organ transplantation, and vertical transmission from mother to child is important.
Treatment typically involves medications to kill the parasites. For African
trypanosomiasis, pentamidine and suramin are used for the early stage, while
eflornithine and melarsoprol are used for the late stage. For Chagas disease,
benznidazole and nifurtimox are used.
Trypanosoma parasites can affect various parts of the body, with brucei affecting
the central nervous system and cruzi affecting the heart and digestive system. They
enter the body through the bite of an infected insect vector or contaminated food or
drink, multiply and spread through the bloodstream, lymphatic system, and tissues,
causing damage to various organs. Transmission occurs through the bite of infected
vectors, blood transfusion, organ transplantation, congenital transmission from mother
to child, and rarely through contaminated food or drink.
The present review addresses basic aspects of the biology of the pathogenic
protozoa Trypanosoma cruzi and some comparative information of Trypanosoma brucei.
Like eukaryotic cells, their cellular organization is similar to that of mammalian hosts.
However, these parasites present structural particularities. That is why the following
topics are emphasized in this paper: developmental stages of the life cycle in the
vertebrate and invertebrate hosts; the cytoskeleton of the protozoa, especially the sub-
pellicular microtubules; the flagellum and its attachment to the protozoan body through
specialized junctions; the kinetoplast-mitochondrion complex, including its structural
organization and DNA replication; glycosome and its role in the metabolism of the cell;
acidocalcisome, describing its morphology, biochemistry, and functional role; cytostome
and the endocytic pathway; the organization of the endoplasmic reticulum and Golgi
complex; the nucleus, describing its structural organization during interphase and
division; and the process of interaction of the parasite with host cells. The unique
characteristics of these structures also make them interesting chemotherapeutic targets.
Therefore, further understanding of cell biology aspects contributes to the development
of drugs for chemotherapy.
References
Zuma, A. A., dos Santos Barrias, E., & de Souza, W. (2021). Basic biology of Trypanosoma cruzi. Current pharmaceutical
design, 27(14), 1671-1732.
Article No. 41 LEISHMANIA
A Review of Leishmaniasis: Current Knowledge and Future Directions
Leishmaniasis is a genus of parasitic protozoa that causes a range of diseases,
including cutaneous, mucocutaneous, and visceral forms. The most common form is
cutaneous leishmaniasis, which causes skin sores. Mucocutaneous leishmaniasis
affects both skin and mucous membranes, leading to ulcers in the nose, mouth, and
throat. Visceral leishmaniasis, also known as kala-azar, affects internal organs such as
the spleen, liver, and bone marrow and can be fatal if left untreated.
Prevention involves avoiding sandfly bites in endemic regions, using insect
repellents, wearing protective clothing, and sleeping under insecticide-treated bed nets.
Control measures include spraying insecticides to reduce sandfly populations and
reducing contact with reservoir hosts of the parasite. Treatment typically involves
antiparasitic drugs, with visceral leishmaniasis potentially fatal if left untreated.
Leishmania parasites primarily affect macrophages, immune cells, and can
evade the immune system by infecting macrophages and manipulating the host's
immune response. They are transmitted to humans through the bite of infected female
sandflies, which enter the bloodstream and infect various tissues and organs.
Symptoms of leishmaniasis vary depending on the infection type but may include skin
sores, ulcers, fever, weight loss, enlarged spleen and liver, and in severe cases, anemia
and immune suppression.
Leishmaniasis is one of the most important tropical neglected diseases according
to the World Health Organization. Even after more than a century, we still have few
drugs for the disease therapy and their great toxicity and side effects put in check the
treatment control program around the world. Moreover, the emergence of strains
resistant to conventional drugs, co-infections such as HIV/Leishmania spp., the small
therapeutic arsenal (pentavalent antimonials, amphotericin B and formulations, and
miltefosine), and the low investment for the discovery/development of new drugs force
researchers and world health agencies to seek new strategies to combat and control
this important neglected disease. In this context, the aim of this review is to summarize
new advances and new strategies used on leishmaniasis therapy addressing alternative
and innovative treatment paths such as physical and local/topical therapies,
combination or multi-drug uses, immunomodulation, drug repurposing, and the
nanotechnology-based drug delivery systems.
References
Mann, S., Frasca, K., Scherrer, S., Henao-Martínez, A. F., Newman, S., Ramanan, P., & Suarez, J. A. (2021). A review of
leishmaniasis: current knowledge and future directions. Current tropical medicine reports, 8, 121-132.
Article No. 42 CRYPTOSPORIDIUM SPP.
Cryptosporidium spp. Diagnosis and Research in the 21st Century
Cryptosporidium spp. is a parasitic protozoan that causes gastrointestinal illness,
cryptosporidiosis. The disease is characterized by symptoms such as diarrhea, stomach
cramps, nausea, vomiting, fever, and weight loss. In healthy individuals, the illness is
usually self-limiting and resolves within a few weeks. However, in immunocompromised
individuals, such as those with HIV/AIDS or undergoing chemotherapy, it can be severe
and even life-threatening.
Prevention involves practicing good hygiene, especially when it comes to water
sources, and avoiding drinking untreated water from streams or lakes. Proper
handwashing is crucial in preventing the spread of the parasite. There is no specific
cure for cryptosporidiosis, and treatment typically involves managing symptoms and
providing supportive care. In immunocompromised individuals, anti-parasitic
medications may be prescribed to help clear the infection.
The gastrointestinal tract is the primary part of the body affected by
cryptosporidium infection, but it can also affect other organs in severe cases.
Cryptosporidium is found worldwide and is commonly present in environments
contaminated with fecal matter, such as untreated water sources, swimming pools, and
agricultural areas. Transmission occurs through ingestion of contaminated water or
food, and symptoms include watery diarrhea, stomach cramps, nausea, vomiting, fever,
and weight loss.
The protozoan parasite Cryptosporidium has emerged as a leading cause of
diarrhoeal illness worldwide, posing a significant threat to young children and
immunocompromised patients. While endemic in the vast majority of developing
countries, Cryptosporidium also has the potential to cause waterborne epidemics and
large scale outbreaks in both developing and developed nations. Anthroponontic and
zoonotic transmission routes are well defined, with the ingestion of faecally
contaminated food and water supplies a common source of infection. Microscopy, the
current diagnostic mainstay, is considered by many to be suboptimal. This has
prompted a shift towards alternative diagnostic techniques in the advent of the
molecular era. Molecular methods, particularly PCR, are gaining traction in a diagnostic
capacity over microscopy in the diagnosis of cryptosporidiosis, given the laborious and
often tedious nature of the latter. Until now, developments in the field of Cryptosporidium
detection and research have been somewhat hampered by the intractable nature of this
parasite. However, recent advances in the field have taken the tentative first steps
towards bringing Cryptosporidium research into the 21st century.
References
O'Leary, J. K., Sleator, R. D., & Lucey, B. (2021). Cryptosporidium spp. diagnosis and research in the 21st century. Food and
waterborne parasitology, 24, e00131.
Article No. 43 FRANCISELLA TULARENSIS
Francisella tularensis, Tularemia and Serological Diagnosis
Francisella tularensis is a bacterium that causes tularemia, also known as rabbit
fever or deer fly fever, which primarily affects mammals, including humans. Tularemia
can manifest in various forms, including ulceroglandular, glandular, oculoglandular,
oropharyngeal, pneumonic, and typhoidal. Symptoms vary depending on the form of
tularemia. Prevention involves avoiding exposure to wild animals, wearing protective
clothing, and using insect repellents. Tularemia can be treated with antibiotics like
streptomyin, gentamicin, doxycycline, or ciprofloxacin.
The loci effect refers to the phenomenon where certain genetic loci affect an
individual's susceptibility to a particular disease. Tularemia affects various parts of the
body, including the skin, lymph nodes, eyes, throat, lungs, and sometimes other organs.
The bacteria infect immune system cells and can spread throughout the body, causing
systemic infection. Tularemia can be transmitted to humans through direct contact with
infected animals or their tissues, contaminated water or soil, inhalation of contaminated
aerosols, or bites from infected insects.
Symptoms of tularemia include fever, chills, headache, muscle aches, joint pain,
skin ulcers, swollen lymph nodes, sore throat, cough, and difficulty breathing. Tularemia
can be a serious illness if not promptly diagnosed and treated, but with appropriate
antibiotic therapy, most patients recover completely. Early recognition and treatment are
crucial for a favorable outcome.
Tularemia is a zoonotic disease caused by the bacterium Francisella tularensis.
The predominant sources, routes of infection, and clinical manifestations of human
infections greatly vary according to the geographic area considered. Moreover, clinical
suspicion of tularemia is often tricky because of the lack of specificity of the clinical
manifestations. Because F. tularensis isolation is tedious and detection of its DNA
usually requires removal of infected tissues, serological techniques are most often used
for diagnostic confirmation. However, these techniques are varied and poorly
standardized. The microagglutination test (MAT), the indirect immunofluorescence
assay (IFA), and ELISA tests are currently the most frequently used techniques. These
home-made and commercial tests are mainly used for tularemia diagnosis but also
seroprevalence studies. ELISA tests detect specific antibodies within two weeks of
disease evaluation, compared to 2–3 weeks for MAT and IFA. However, more false-
positive results are usually reported with ELISA. The long-term persistence of anti-F.
tularensis antibodies in patients with past tularemia infection hampers the diagnostic
specificity of all these tests. Also, cross-reacting antibodies have been described
(especially with Brucella and Yersinia species), although usually at a low level. The
immunoblotting technique can highlight these serological cross-reactions. Tularemia
remains an underdiagnosed disease in most endemic areas, and the clinical
presentations of this disease are evolving. It is necessary to improve further speed and
accuracy of tularemia diagnosis, as well as the standardization of diagnostic
procedures.
References
Maurin, M. (2020). Francisella tularensis, tularemia and serological diagnosis. Frontiers in Cellular and Infection Microbiology, 10,
512090.

Article No. 44 CAMPYLOBACTER JEJUNI

Virulence factors of foodborne pathogen Campylobacter jejuni
Campylobacter jejuni is a bacterium that causes Campylobacteriosis, a common
gastrointestinal tract infection in humans. Symptoms include diarrhea, abdominal pain,
fever, and vomiting. In severe cases, it can lead to complications like Guillain-Barré
syndrome, an autoimmune disorder affecting the peripheral nervous system. Prevention
measures include proper food handling and cooking, hand hygiene, avoiding
unpasteurized milk and untreated water, and avoiding cross-contamination.
Most cases of Campylobacteriosis are self-limiting and do not require specific
treatment. However, in severe cases or those with compromised immune systems,
antibiotics may be prescribed to shorten the illness duration and reduce symptoms.
Campylobacter jejuni primarily targets the gastrointestinal tract and can also affect the
nervous system, leading to complications like Guillain-Barré syndrome.
Campylobacter jejuni infects the body through the consumption of contaminated
food or water, particularly raw or undercooked poultry, unpasteurized milk, and
untreated water. Once ingested, the bacteria colonize the gastrointestinal tract, multiply,
and cause inflammation of the intestinal lining, leading to symptoms of infection. The
bacteria is commonly found in the intestines of animals, and human infections often
occur through the consumption of contaminated food products, contact with infected
animals, and contaminated water sources.
Symptoms typically appear within 2 to 5 days after exposure and may include
diarrhea, abdominal pain, fever, nausea and vomiting, muscle pain, headache, and
fatigue. In severe cases or those with compromised immune systems, Campylobacter
infection can lead to complications like Guillain-Barré syndrome.
Campylobacter jejuni is a highly frequent cause of gastrointestinal foodborne
disease in humans throughout the world. Disease outcomes vary from mild to severe
diarrhea, and in rare cases the Guillain-Barré syndrome or reactive arthritis can develop
as a post-infection complication. Transmission to humans usually occurs via the
consumption of a range of foods, especially those associated with the consumption of
raw or undercooked poultry meat, unpasteurized milk, and water-based environmental
sources. When associated to food or water ingestion, the C. jejuni enters the human
host intestine via the oral route and colonizes the distal ileum and colon. When it
adheres and colonizes the intestinal cell surfaces, the C. jejuni is expected to express
several putative virulence factors, which cause damage to the intestine either directly,
by cell invasion and/or production of toxin(s), or indirectly, by triggering inflammatory
responses. This review article highlights various C. jejuni characteristics — such as
motility and chemotaxis — that contribute to the biological fitness of the pathogen, as
well as factors involved in human host cell adhesion and invasion, and their potential
role in the development of the disease. We have analyzed and critically discussed
nearly 180 scientific articles covering the latest improvements in the field.
References
Lopes, G. V., Ramires, T., Kleinubing, N. R., Scheik, L. K., Fiorentini, Â. M., & da Silva, W. P. (2021). Virulence factors of foodborne
pathogen Campylobacter jejuni. Microbial pathogenesis, 161, 105265.

Article No. 45 LISTERIA MONOCYTOGENES

Listeria monocytogenes, a model in infection biology
Listeria monocytogenes is a bacterium that causes the infectious disease
listeriosis, which can manifest in various forms depending on an individual's health
status and the severity of the infection. Symptoms can range from mild fever to severe
meningitis, septicemia, and even miscarriage in pregnant women. To prevent listeriosis,
it is crucial to properly cook and handle foods, avoid cross-contamination, and use
separate cutting boards and utensils for raw and cooked foods.
Antibiotics like ampicillin, penicillin, or trimethoprim-sulfamethoxazole are
commonly used to treat listeriosis, but hospitalization may be necessary in severe
cases. Listeria monocytogenes can affect various parts of the body, including the central
nervous system, bloodstream, placenta, and fetus. It can invade and multiply within
cells, evade the immune system, and produce toxins that can damage host cells.
Listeria monocytogenes can be found in various environments, including soil,
water, and some animals, and can be transmitted through foodborne, vertical, or
nosocomial transmission. Symptoms can include fever, muscle aches, nausea,
vomiting, diarrhea, headache, stiff neck, confusion, loss of balance, and convulsions. In
pregnant women, symptoms may be mild, but infection can lead to miscarriage,
stillbirth, premature delivery, or serious newborn illness.
Listeria monocytogenes causes listeriosis, a systemic infection which manifests
as bacteremia, often complicated by meningoencephalitis in immunocompromised
individuals and the elderly, and fetal-placental infection in pregnant women. It has
emerged over the past decades as a major foodborne pathogen, responsible for
numerous outbreaks in Western countries, and more recently in Africa. L.
monocytogenes' pathogenic properties have been studied in detail, thanks to
concomitant advances in biological sciences, in particular molecular biology, cell biology
and immunology. L. monocytogenes has also been instrumental to basic advances in
life sciences. L. monocytogenes therefore stands both a tool to understand biology and
a model in infection biology. This review briefly summarises the clinical and some of the
pathophysiological features of listeriosis. In the context of this special issue, it highlights
some of the major discoveries made by Pascale Cossart in the fields of molecular and
cellular microbiology since the mid-eighties regarding the identification and
characterisation of multiple bacterial and host factors critical to L. monocytogenes
pathogenicity.
References
Lecuit, M. (2020). Listeria monocytogenes, a model in infection biology. Cellular microbiology, 22(4), e13186

Article No. 46 ADENOVIRUS

Adenovirus Structure: What Is New?
Adenovirus is a group of viruses that can cause various illnesses in humans,
including respiratory infections, conjunctivitis, gastroenteritis, and urinary tract
infections. Prevention involves hand hygiene, avoiding close contact, vaccination, and
disinfecting surfaces. Treatment involves supportive care, such as rest, hydration, and
over-the-counter medications, and antiviral medications in severe cases or for
immunocompromised individuals.
Adenovirus can affect various parts of the body, including the respiratory tract,
eyes, gastrointestinal tract, and urinary tract. It spreads through respiratory droplets,
coughing or sneezing, or by touching contaminated surfaces. Symptoms of adenovirus
infection vary depending on the affected part of the body but can include runny nose,
sore throat, cough, congestion, fever, redness, itching, discharge, swelling of the eyes,
diarrhea, vomiting, abdominal pain, and fever.
Adenovirus works by attaching to specific receptors on cell surfaces and
hijacking the cell's machinery to replicate itself, leading to cell death and infection
spread. The immune response to adenovirus infection can vary, and in some cases, the
virus may establish persistent infections, particularly in individuals with weakened
immune systems. Adenovirus infections are common worldwide, with various strains
circulating within populations.
Adenoviruses are large (~950 Å)
and complex non-enveloped, dsDNA
icosahedral viruses. They have a
pseudo-T = 25 triangulation number
with at least 12 different proteins
composing the virion. These include
the major and minor capsid proteins, core proteins, maturation protease, terminal
protein, and packaging machinery. Although adenoviruses have been studied for more
than 60 years, deciphering their architecture has presented a challenge for structural
biology techniques. An outstanding event was the first near-atomic resolution structure
of human adenovirus type 5 (HAdV-C5), solved by cryo-electron microscopy (cryo-EM)
in 2010. Discovery of new adenovirus types, together with methodological advances in
structural biology techniques, in particular cryo-EM, has lately produced a considerable
amount of new, high-resolution data on the organization of adenoviruses belonging to
different species. In spite of these advances, the organization of the non-icosahedral
core is still a great unknown. Nevertheless, alternative techniques such as atomic force
microscopy (AFM) are providing interesting glimpses on the role of the core proteins in
genome condensation and virion stability. Here we summarize the current knowledge on
adenovirus structure, with an emphasis on high-resolution structures obtained since
2010.
References
Gallardo, J., Pérez-Illana, M., Martín-González, N., & San Martín, C. (2021). Adenovirus structure: what is new?. International
journal of molecular sciences, 22(10), 5240.
Article No. 47 DENGUE VIRUS
Current Understanding of the Pathogenesis of Dengue Virus Infection
Dengue fever is a mosquito-borne viral infection caused by the dengue virus. It
can lead to severe forms such as dengue hemorrhagic fever (DHF) and dengue shock
syndrome (DSS), which can be life-threatening. Prevention involves controlling
mosquito breeding sites and using insecticides to kill adult mosquitoes. Personal
protection includes using mosquito repellents, wearing long sleeves and pants, and
using mosquito nets. Vaccines are being developed to prevent dengue, but availability
may vary depending on the region.
There is no specific cure for dengue fever, but treatment focuses on managing
symptoms such as fever and pain. In severe cases, patients may require hospitalization
for supportive care, including intravenous fluids. The loci effect refers to the virus's
impact on the immune system, causing symptoms such as fever, headache, muscle and
joint pain, rash, and in severe cases, hemorrhage and organ failure. The virus is
transmitted through the bite of infected Aedes mosquitoes, blood transfusions, organ
transplantation, and from mother to child during childbirth. Symptoms include high fever,
severe headache, pain behind the eyes, joint and muscle pain, nausea and vomiting,
and rash.
The pathogenesis of dengue virus infection is attributed to complex interplay
between virus, host genes and host immune response. Host factors such as antibody-
dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1
antibodies, autoimmunity as well as genetic factors are major determinants of disease
susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be
responsible for pathogenesis of severe dengue. The cytokine response of cross-
reactive CD4+ T cells might be altered by the sequential infection with different DENV
serotypes, leading to further elevation of pro-inflammatory cytokines contributing a
detrimental immune response. Fcγ receptor-mediated antibody-dependent
enhancement (ADE) results in release of cytokines from immune cells leading to
vascular endothelial cell dysfunction and increased vascular permeability. Genomic
variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host
immune response are viral determinants of disease severity. Dengue infection can lead
to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E
proteins, which can cross-react with several self-antigens such as plasminogen,
integrin, and platelet cells. Apart from viral factors, several host genetic factors and
gene polymorphisms also have a role to play in pathogenesis of DENV infection. This
review article highlights the various factors responsible for the pathogenesis of dengue
and also highlights the recent advances in the field related to biomarkers which can be
used in future for predicting severe disease outcome.
References
Bhatt, P., Sabeena, S. P., Varma, M., & Arunkumar, G. (2021). Current understanding of the pathogenesis of dengue virus
infection. Current microbiology, 78(1), 17-32.
Article No. 48 RESPIRATORY SYNCYTIAL VIRUS (RSV)
Respiratory Syncytial Virus–Associated Hospitalizations Among Young Children:
2015–2016
Respiratory Syncytial Virus (RSV) is a common virus that primarily affects the
respiratory tract, particularly in young children and older adults. It causes diseases such
as bronchiolitis, pneumonia, and upper respiratory tract infections. Prevention involves
hand hygiene, avoiding close contact with individuals with respiratory infections, and
vaccination. Supportive care, hospitalization, and antiviral medications may be used in
some cases.
RSV primarily affects the nose, throat, windpipe, and lungs, leading to
inflammation and infection, causing symptoms ranging from mild cold-like symptoms to
severe respiratory distress. The virus infects the cells lining the airways, leading to
inflammation and swelling, making airways narrow, making it difficult to breathe. In
severe cases, it can lead to respiratory distress and even respiratory failure.
RSV is primarily transmitted through respiratory droplets when an infected
person coughs or sneezes and can also survive on surfaces for several hours.
Symptoms include a runny nose, cough, fever, sore throat, wheezing, difficulty
breathing, decreased appetite, and irritability. Severe symptoms are typically seen in
infants, older adults, and individuals with weakened immune systems. Seeking medical
attention is crucial for those experiencing severe respiratory symptoms, especially
difficulty breathing.
A study involving 2969 children hospitalized for acute respiratory illness (ARI)
found that respiratory syncytial virus (RSV) is a major cause of hospitalization. The
study involved active surveillance from November 1, 2015, to June 30, 2016, at seven
US pediatric hospital sites. The majority of children tested positive for RSV were under
two years old, with the highest rate observed in 1-month-old infants. RSV infection was
associated with one-third of ARI hospitalizations during the 2015-2016 season, with the
highest rates in infants under six months. Most children infected with RSV had no
history of prematurity or underlying medical conditions, suggesting that targeted
interventions against RSV could benefit all young children.
References
Rha, B., Curns, A. T., Lively, J. Y., Campbell, A. P., Englund, J. A., Boom, J. A., ... & Gerber, S. I. (2020). Respiratory syncytial virus–
associated hospitalizations among young children: 2015–2016. Pediatrics, 146(1).
Article No. 49 CYCLOSPORA CAYETANENSIS
The global prevalence of Cyclospora cayetanensis infection: A systematic review,
meta-analysis, and meta-regression
Cyclospora cayetanensis is a parasitic organism that causes gastrointestinal
infections, primarily causing watery diarrhea, abdominal cramping, bloating, nausea,
fatigue, weight loss, and fever. Symptoms typically develop about a week after ingestion
of contaminated food or water. Prevention involves proper hygiene practices, such as
washing hands with soap and water before eating or preparing food, and avoiding
untreated water. Treatment is typically antibiotics like trimethoprim-sulfamethoxazole
(TMP-SMX), with supportive care for severe symptoms.
The parasite primarily affects the small intestine, causing inflammation and
disruption of normal digestive functions. It reproduces within the intestinal lining cells,
leading to inflammation and symptoms. The parasite is commonly associated with
contaminated produce and can be transmitted through contaminated water sources.
The primary mode of transmission is through the fecal-oral route, where contaminated
water or food contains fecal matter containing Cyclospora oocysts. Symptoms typically
develop about a week after ingestion and can persist for several weeks if left untreated.
Cyclospora cayetanensis (C. cayetanensis) is a significant pathogen that causes
diarrheal illness and causes large foodborne diarrhea outbreaks in the USA and
Canada. However, there is currently a lack of published meta-analysis on the
prevalence of C. cayetanensis infection in the global population. A real estimation of a
disease prevalence should always be done on the basis of studies designed for that
purpose. We conducted a comprehensive search of various databases for articles
pertaining to the prevalence of C. cayetanensis infection in humans, spanning from the
inception of these databases to March 10, 2023. Utilizing a random effects model, we
estimated the prevalence of C. cayetanensis infection in humans. Our analysis included
a total of 150 datasets sourced from 42 different countries, which were ultimately
selected for the final quantitative assessment. The prevalence of C. cayetanensis
infection in humans worldwide was estimated to be 3.4 % (5636/166,611). Notably,
Africa exhibited the highest prevalence rate at 5.9 % (606/11,068). Further subgroup
analysis revealed a significantly higher infection rate in humans residing in low-income
countries (7.6 %, 83/921) compared to those in lower-middle-income countries (4.8 %,
3280/48,852), upper-middle-income countries (2.9 %, 2194/99,419), and high-income
countries (0.4 %, 79/17,419). The results indicate that the global prevalence of C.
cayetanensis infection in humans is relatively low, despite its extensive geographical
distribution and children were found to be more susceptible to C. cayetanensis infection
compared to those adults. Sensitivity analysis revealed that one study significantly
affects the prevalence of C. cayetanensis, which was adjusted to 2.9 % (4017/160,049;
95 % CI: 2.7–3.1 %) by excluding this study. The findings highlight the relatively high
prevalence of C. cayetanensis infection in low-income countries and among humans
with diarrhea, particularly in Africa. Consequently, routine surveillance for intestinal
protozoa is crucial in these regions.
References

Chen, Y., Qin, Z., Li, J., Xiao, L., & Zhang, L. (2024). The global prevalence of Cyclospora cayetanensis infection: A systematic
review, meta-analysis, and meta-regression. Acta Tropica, 107175.

Article No. 50 ACANTHAMOEBA

Biological characteristics and pathogenicity of Acanthamoeba
Acanthamoeba is a genus of amoebae that can cause several diseases,
including Acanthamoeba keratitis and Granulomatous Amebic Encephalitis (GAE).
Acanthamoeba keratitis is an infection of the cornea, typically associated with contact
lens wearers, while GAE is a rare but severe infection of the central nervous system.
Preventive measures for Acanthamoeba keratitis include proper contact lens hygiene,
such as washing hands before handling lenses and avoiding water contact.
Training for Acanthamoeba keratitis typically involves antiseptic eye drops and, in
severe cases, may require surgical intervention. GAE is often fatal but may involve a
combination of antimicrobial drugs due to the blood-brain barrier. Acathamoeba
infections can affect various parts of the body, with Acanthamoeba keratitis affecting the
eyes and GAE affecting the central nervous system. The amoeba enters the body
through contact with contaminated water or soil, and transmission occurs through
contact with contaminated water or soil. Symptoms of Acanthamoeba keratitis include
severe eye pain, redness, blurred vision, sensitivity to light, and the sensation of a
foreign body in the eye.
Acanthamoeba is an opportunistic protozoan, which exists widely in nature and is
mainly distributed in soil and water. Acanthamoeba usually exists in two forms,
trophozoites and cysts. The trophozoite stage is one of growth and reproduction while
the cyst stage is characterized by cellular quiescence, commonly resulting in human
infection, and the lack of effective monotherapy after initial infection leads to chronic
disease. Acanthamoeba can infect several human body tissues such as the skin,
cornea, conjunctiva, respiratory tract, and reproductive tract, especially when the tissue
barriers are damaged. Furthermore, serious infections can cause Acanthamoeba
keratitis, granulomatous amoebic encephalitis, skin, and lung infections. With an
increasing number of Acanthamoeba infections in recent years, the pathogenicity of
Acanthamoeba is becoming more relevant to mainstream clinical care. This review
article will describe the etiological characteristics of Acanthamoeba infection in detail
from the aspects of biological characteristic, classification, disease, and pathogenic
mechanism in order to provide scientific basis for the diagnosis, treatment, and
prevention of Acanthamoeba infection.
References
Wang, Y., Jiang, L., Zhao, Y., & Li, M. (2023). Biological characteristics and pathogenicity of Acanthamoeba. Frontiers in Microbiology, 14, 1147077.