DIAGNOSIS

Approach
Diagnosis of this potentially fatal disease rests on a high index of suspicion in a patient
with suggestive symptoms and an appropriate travel history. Whilst epidemiological maps
of malaria endemicity may be useful in determining risk for the purpose of pre-travel
advice regarding prophylaxis, such an approach may be dangerous in the setting of
managing a febrile patient returning from an area bordering a malaria area; conditions on
the ground can change.

The differential diagnosis is broad and includes other travel-related infections. In

resource-poor settings a presumptive diagnosis is often made on clinical grounds alone.
However, as symptoms are non-specific, clinical diagnosis is unreliable. Therefore, where
laboratory testing is available, confirmation of malaria infection should always be sought
as soon as possible.

Treatment depends on the infecting species, the parasite burden, and the clinical status
of the patient; thus, history, examination, and laboratory tests should focus on determining
these factors.

Most countries require reporting of malaria so that epidemiological data can be collected.
In the US, healthcare providers should report all cases of laboratory-confirmed malaria
occurring in the US and its territories to their local or state health department.

History
Most patients with Plasmodium falciparum infection present in the first month after
exposure; almost all present within 3 months of exposure. P vivax or P ovale infections
commonly present later than 3 months after exposure, and presentation may even be
delayed for 1 year or more. [24]

Symptoms are non-specific and common to many other infections. Fever, or history of
fever, is universal. Characteristic paroxysms of chills and rigors followed by fever and
sweats may be described. Patterns of fever are rarely diagnostic at presentation but may
develop over time: fevers occurring at regular intervals of 48 to 72 hours may be
associated with P vivax , P ovale , or P malariae infections. Other very common
symptoms include headache, weakness, myalgia, and arthralgia. Less common
symptoms include anorexia, nausea, vomiting, diarrhoea, and abdominal pain. Many
children present only with influenza-like respiratory symptoms. [46] History should also
focus on whether risk factors for severe disease are present (e.g., low host immunity,
pregnancy, child <5 years of age, immunocompromise, older age).

History of travel to an endemic area is the key diagnostic factor in patients presenting with
fever in non-endemic countries. However, travel history is frequently overlooked. History
of travel to a malaria endemic area in the past 12 months should be elicited if a patient
presents with non-specific symptoms. If travel history is positive, the patient should be
asked if antimalarial prophylaxis was taken. If taken, the specific drug should be
determined and whether it was taken in the correct manner. As reporting is often
unreliable, the use of prophylaxis does not exclude malaria infection; however, it may
influence selection of the treatment regimen if malaria is confirmed.

Physical examination
Clinical status of the patient should be assessed. There are very few physical signs to
elicit that are specific for malaria. It is important to determine whether a complication of
severe malaria is present (suggested by jaundice, confusion or altered level of
consciousness, seizures, hypotension, respiratory distress, or anuria/oliguria) or whether
there is concurrent bacterial infection (suggested by presence of focal signs: e.g.,
crackles on lung auscultation suggesting super-imposed pneumonia). Signs often present
include hepatosplenomegaly (although not common at time of initial presentation in the
first-world setting) and/or pallor (suggesting anaemia).

Laboratory examination
Light microscopy

 The detection of malaria parasites in the blood is essential. In skilled hands, the most
sensitive and specific test readily available is light microscopy of Giemsa-stained blood
smears, and this is the diagnostic test of choice. Wright or Field stains are alternatives to
Giemsa. When to use these alternatives is a laboratory decision and may vary locally.
Thick films enable a relatively large amount of blood to be screened for parasites, but
species determination may be difficult as red cells are lysed and parasite morphology may
be distorted. Thin film preparations allow speciation, which will affect treatment decisions.
The percentage of parasitaemia can be assessed using a simple formula but may be
extremely low, and false-negative thick smears may occur. [47] If there is a strong
suspicion of malaria, the test should be repeated daily for 3 days.

[Figure caption and citation for the preceding image starts]:Giemsa-stained slide
revealing Plasmodium falciparum , P ovale , P malariae, and P
vivax gametocytesCenters for Disease Control and Prevention Image Library; used with
permission[Citation ends].
Rapid diagnostic tests (RDTs)

 Rapid diagnostic tests are immunochromatographic tests that detect the presence of
parasite antigens on a finger prick sample. Different types detect either P falciparum -
specific histidine-rich protein-2 (HRP-2) or species-specific parasite lactate
dehydrogenase (pLDH). [48] A number of tests have been evaluated in returned
travellers, with most generating sensitivity and specificity values for P falciparum of over
85% to 90%. [48]Problems have included poor detection of species other than P
falciparum and false-negative results at lower parasite burden. [48] [49] However, some
studies have shown that performance of RDTs can be equivalent to expert
microscopy. [50] [51]
 The main advantage of RDTs is that they provide a means for rapid diagnosis, especially
in health resource-limited areas where microscopy is not available or reliable. Their
incorporation into treatment algorithms may substantially reduce prescribing of
antimalarials when compared with clinical diagnosis alone, although an improvement in
health outcomes has not been proven. [52]
 The disadvantages of RDTs include the inability to distinguish between active infection
and recently treated infection. In addition, even with a positive RDT, a blood film is still
necessary for confirmation of species (non-falciparum) and for a parasite count to help
guide treatment (falciparum).
 The choice between RDTs and microscopy depends on local circumstances, including
the skills available, patient caseload, epidemiology of malaria, and the possible use of
microscopy for the diagnosis of other diseases. [53] A systematic review found that pLDH
tests had a higher specificity, whereas the HRP-2 tests had better sensitivity and slightly
greater accuracy, when compared to each other. [54] A combination of both tests, if
possible, may be more reliable.
Polymerase chain reaction (PCR)

 PCR is usually only available in reference laboratories. It may be used to confirm the
diagnosis of malaria in cases where microscopy is negative but there is a high clinical
suspicion of disease, [55] [56] or to determine the species when it is not possible to
distinguish on light microscopy.
 PCR can play a useful role in the diagnosis of malaria in pregnancy, as sequestration of
parasites in the placenta can lead to a parasite count in the peripheral blood below the
threshold for microscopic detection in blood films. [57]
Loop-mediated isothermal amplification (LAMP)

 LAMP is a new commercial molecular assay. It is more sensitive than microscopy or

antigen-detecting RDTs, so is more reliable in detecting low parasitaemia. It provides
faster results than microscopy or PCR, requires less training, is less costly compared with
PCR, and has been evaluated in both high- and low-resource settings. [58][59] It is still
considered an emerging test.

Other baseline tests

 Baseline tests include an FBC, a clotting profile, renal and liver function tests,
blood glucose, and urinalysis. In cases of severe malaria, blood gas analysis is
 necessary to exclude metabolic or lactic acidosis. HIV testing is usually indicated,
as malaria may be more severe in the presence of HIV infection. If concurrent
bacterial infection is suspected, blood, sputum, and urine cultures should be
requested. Lumbar puncture may be indicated to exclude meningitis. In addition,
PCR of nasopharyngeal swabs may be considered to exclude influenza infection,
which can present in an identical manner.

Imaging
A chest x-ray helps exclude other diagnoses (e.g., pneumonia, legionnaires' disease,
pulmonary tuberculosis) when investigating patients returning from abroad with a fever.
In addition, a chest x-ray is indicated if there is suspicion of severe malaria, particularly
with respiratory symptoms or signs, or if consciousness level is reduced (to exclude
aspiration).

CT of the head is an important investigation to seek focal lesions or haemorrhage if there

are focal neurological signs, impaired level of consciousness, or seizures.

History and exam

Key diagnostic factors
COMMON

presence of risk factors for acquiring malaria

Key risk factors include travel to an endemic area, inadequate or absent
chemoprophylaxis, and non-use of an insecticide-treated bed net in an endemic area.

presence of risk factors for severe disease

Low host immunity: patients who did not grow up in an endemic area or who have not
had previous malaria are more likely to have severe disease.

Pregnancy: all types of malaria increase the risk of miscarriage. Pregnancy leads to
higher percentage parasitaemia and anaemia in Plasmodium falciparum infection.

Age <5 years: children are less likely than adults to complain of chills, myalgia, or
headaches, and more likely to present with non-specific symptoms.

Immunocompromise: people with comorbidities, including HIV infection, are susceptible

to developing severe malaria infection.

Older adults: susceptible to severe disease, particularly due to subtle immunodeficiency

associated with ageing.

fever or hx of fever
Fever, or history of fever, is universal. Characteristic paroxysms of chills and rigors
followed by fever and sweats may be described. Usually associated tachycardia.
Patterns of fever are rarely diagnostic at presentation but may develop over time: fevers
occurring at regular intervals of 48 to 72 hours may be associated with P vivax , P ovale ,
or P malariae infections. In most patients there is no specific fever pattern.

Other diagnostic factors

COMMON

headache
Non-specific but common complaint.

weakness
Non-specific but common complaint.

myalgia
Non-specific but common complaint.

arthralgia
Non-specific but common complaint.

anorexia
Non-specific symptom.

diarrhoea
Non-specific symptom.

UNCOMMON

seizures
Suggests falciparum infection, which is almost always the cause of severe disease.
However, febrile illnesses reduce seizure threshold in known epileptic patients.

nausea and vomiting

Non-specific symptom.

abdominal pain
Non-specific symptom.
 pallor
Anaemia is often present.

hepatosplenomegaly
Common presenting sign, although not common at time of initial presentation in the first-
world setting.

jaundice
Suggests falciparum infection, which is almost always the cause of severe disease.

altered level of consciousness

Suggests falciparum infection, which is almost always the cause of severe disease.
However, any febrile illness can cause confusion in an older patient.

hypotension
Suggests falciparum infection, which is almost always the cause of severe disease.
Circulatory shock may indicate concurrent sepsis.

anuria/oliguria
Suggests falciparum infection, which is almost always the cause of severe disease.

influenza-like respiratory symptoms

May occur in children without other symptoms.

Risk factors
STRONG

travel to endemic area

Each year, 25 million to 30 million people from the US and Europe travel to the tropics, of
whom approximately 10,000 to 30,000 acquire malaria. [13]

inadequate or absent chemoprophylaxis

The incidence of Plasmodium falciparum malaria in travellers who do not take
prophylactic drugs is highest in West Africa (52 cases/1000 years exposed). [14] In South
America, India, and Pakistan, a low risk of 1 case per 2000-3000 years exposed
exists. [26] [27] Chemoprophylaxis significantly reduces mortality rates. [28]
 insecticide-treated bed net not used in endemic area
Pyrethroid-treated mosquito nets are recommended for travellers to endemic areas, to
reduce risk of mosquito bites.

settled migrants returning from travel to endemic area of origin

Constitutes two-thirds of all imported malaria, with most patients not taking malaria
chemoprophylaxis. [29] This may be due to a number of reasons: if they grew up not
taking prophylaxis they may not see it as important or may not consider it; they may take
incorrect prophylaxis; they may perceive the risk as low, especially if only visiting a major
city.

low host immunity (for severe disease)

People who have little or no immunity (i.e., individuals living in non-endemic areas) are
most at risk for disease and developing serious illness. [12]

pregnancy (for severe disease)

Pregnant women remain one of the most susceptible patient groups to disease in
endemic areas. Pregnant women infected with P falciparum are susceptible to
complications of pregnancy as the parasites sequester in the placenta. In addition, the
prevalence of P vivax infection and parasite density increases during pregnancy, due to
the reticulocytosis of pregnancy ( P vivax exclusively invades reticulocytes). [25] [30]

age <5 years (for severe disease)

Children <5 years of age remain one of the most susceptible patient groups to disease in
endemic areas. They are more likely to have infection and complications of malaria. [31]

immunocompromise (for severe disease)

Individuals with comorbidities, including HIV infection, are more susceptible to developing
severe malaria infection.

older age (for severe disease)

Malaria is potentially fatal if not treated promptly, as life-threatening complications can
develop quickly in patients who initially appear well, and even short delays increase
morbidity and mortality. [32] This is especially the case in certain risk groups, including
older adults. [12] [33] [34]
WEAK

iron administration (children)

While iron administration to prevent anaemia in children living in endemic areas has been
claimed to increase the risk of malaria (or severe malaria), [35] one Cochrane review
found that iron treatment does not increase the risk of clinical malaria when regular
malaria prevention or management services are in place. [36]

Investigations
1st investigations to order
TEST RESULT
Giemsa-stained thick and thin blood smears detection of asexual
or sexual forms of
Considered the test of choice to identify parasites.The most the parasites inside
common asexual form seen is the trophozoite erythrocytes

.
[Figure caption and citation for the preceding image
starts]:Thin-film Giemsa-stained micrographs showing ring-
form Plasmodium vivaxand P
falciparum trophozoitesCenters for Disease Control and
Prevention Image Library/Steven Glenn, Laboratory &
Consultation Division; used with permission[Citation ends].

In the case of Plasmodium falciparum , sexual forms infectious to

mosquitoes, known as gametocytes, can often be seen and may
persist in the blood even after effective treatment has ended.

[Figure caption and citation for the preceding image

starts]:Giemsa-stained slide revealing Plasmodium
falciparum , P ovale , P malariae, and P
vivax gametocytesCenters for Disease Control and
Prevention Image Library; used with permission[Citation
ends].

Thick films are more sensitive for detection of parasites than thin
films, as they allow for a greater volume of blood to be examined.
Non-immune individuals may be symptomatic at very low parasite
densities that may initially be undetectable. Therefore, if clinical
suspicion is high, smears should be repeated daily on 3
occasions. Thin blood smears permit species identification and
calculation of the parasitaemia (percentage of parasitised red
blood cells), both of which are necessary to determine appropriate
treatment.
[Figure caption and citation for the preceding image
starts]:Thick-film Giemsa-stained micrograph showing two
mature Plasmodium vivax schizonts, each containing
merozoitesCenters for Disease Control and Prevention
Image Library; used with permission[Citation ends].

A high parasitaemia (>2% of erythrocytes parasitised) is itself a

sign of more severe disease, although severe disease may occur
at any level of parasitaemia. In addition, the presence of schizonts
or pre-schizonts on the blood smear may designate a patient with
the potential to suddenly deteriorate.
rapid diagnostic tests (RDTs) detection of parasite
antigen or enzymes
These immunochromatographic tests detect the presence of
malaria antigen or enzyme and typically give a visible band after
15 minutes if positive.

Problems have included poor detection of species other than P

falciparumand false-negative results at lower parasite
burden. [48] [49] However, some studies have shown that
performance of RDTs can be equivalent to expert
microscopy. [50] [51]

The main advantage of RDTs is that they provide a means for

rapid diagnosis, especially in health resource-limited areas where
microscopy is not available or reliable. Their incorporation into
treatment algorithms may substantially reduce prescribing of
antimalarials when compared with clinical diagnosis alone,
although an improvement in health outcomes has not been
proven. [52]

A disadvantage of histidine-rich protein-2 (HRP-2) RDTs is their

inability to distinguish between active infection and recently
treated infection. Alternative devices using lactate
dehydrogenase (LDH) and HRP-2 detection can identify active
from treated infections. In addition, even with a positive RDT, a
blood film is still necessary for confirmation of species (non-
falciparum) and for a parasite count to help guide treatment
(falciparum).

One systematic review found that pLDH tests had a higher

specificity, whereas the HRP-2 tests had better sensitivity and
slightly greater accuracy, when compared to each other. [54] A
combination of both tests, if possible, may be more reliable.

Some P falciparum parasites lack the pfhrp2 gene, which means

that the parasite cannot produce HRP-2. The prevalence of this
mutation varies between and within countries, and has been
identified in Peru and Africa. The World Health Organization
(WHO) recommends that suspected false-negative RDT results
should be investigated further. [66]
FBC may show
thrombocytopenia,
Thrombocytopenia is very common with P falciparum infection, anaemia, variable
and platelet count may be very low. Despite this, bleeding white cell count
complications are rare. Platelet counts typically recover quickly
after treatment.

A mild degree of anaemia is common with all species. Severe

anaemia is more common in children and is due to a combination
of red cell destruction, autoimmune haemolysis, and disturbed
marrow function.

White blood cell count may be high, low, or normal.

Clotting Profile prothrombin time
may be moderately
Bleeding complications are rare. prolonged

Serum Electrolytes, Urea And Creatinine usually normal or

mildly impaired;
Fever and volume depletion may lead to mild pre-renal renal failure may be
impairment, which responds well to rehydration. present in severe
infection
Sodium is often low. A number of mechanisms have been
proposed for this. [67] For example, administration of hypotonic
fluids, syndrome of inappropriate anti-diuretic hormone secretion
(SIADH), cerebral salt wasting, losses through sweat and the GI
tract, renal losses, and the sick cell syndrome. However, no
consensus has been reached as to their relative contribution.

In severe malaria, renal failure may develop due to microvascular

obstruction, filtration of free haemoglobin and myoglobin, volume
depletion, and hypotension, with reduced urine output and
proteinuria.
serum LFTs may show elevated
bilirubin or elevated
Hyperbilirubinaemia is typically unconjugated. Jaundice is aminotransferases
generally mild, and total serum bilirubin is usually <5 mg/dL (<86
micromol/L). However, bilirubin may at times be >50 mg/dL (>855
micromol/L).

Hepatic aminotransferases are often mildly elevated, but ALT

does not reach the level seen in viral hepatitis.
Serum Blood Glucose hypoglycaemia or
hyperglycaemia
Hypoglycaemia is probably cytokine-mediated and may
subsequently be due to quinine therapy. Blood glucose should be
monitored regularly.

In diabetic patients, any febrile illness may lead to poor control of

blood sugars.
Urinalysis may show trace to
moderate protein;
In severe P falciparum infections, massive haemolysis combined urobilinogen and
with acute tubular necrosis produce acute renal failure with conjugated bilirubin
haemoglobinuria and proteinuria. may be present

Arterial Blood Gas may demonstrate

metabolic acidosis
In severe malaria, tissue hypoxia due to microvascular or lactic acidosis in
obstruction, impaired red cell deformability, anaemia, severe disease
hypovolaemia, and hypotension can lead to lactic acidosis, which
may contribute to impaired level of consciousness.
Investigations to consider
TEST RESULT
PCR blood for malaria detection of
parasites at very low
Useful in specimens where parasitaemia may be below the levels; species
detectable level of blood film examination. [55] [56] Can also play identification if
a useful role in the diagnosis of malaria in pregnancy when difficulties on
sequestration of parasites in the placenta can lead to a parasite microscopy
count in the peripheral blood below the threshold for microscopic
detection in blood films. [57]

Can be performed only in reference laboratories and should be

reserved for specific instances (e.g., back-up or confirmation of
microscopyy, species determination, pregnancy, hyper-reactive
malaria splenomegaly syndrome).
chest x-ray features of
pneumonia,
May indicate an alternative diagnosis (e.g., pneumonia, pulmonary oedema,
legionnaires' disease, pulmonary tuberculosis). or ARDS may be
present
May demonstrate a complication of severe malaria or sepsis such
as pulmonary oedema due to aggressive rehydration or local
cytokine release leading to acute respiratory distress syndrome
(ARDS).
Blood Culture typically no
abnormal growth
May be useful to search for other causes of fever when the
diagnosis is in doubt, or to demonstrate concurrent bacterial
sepsis.
Urine Culture typically no
abnormal growth
May be useful to search for other causes of fever when the
diagnosis is in doubt, or to demonstrate concurrent bacterial
sepsis
Sputum Culture typically no
abnormal growth
May be useful to search for other causes of fever when the
diagnosis is in doubt, or to demonstrate concurrent bacterial
sepsis
Lumbar Puncture usually normal in
cerebral malaria;
Considered to exclude the possibility of bacterial meningitis. CSF lactate
sometimes elevated
Occasionally CSF protein may be mildly elevated, and there may
be a mild increase in the number of CSF lymphocytes (usually
<10, rarely up to 50 cells/mL).

HIV test may be positive

Usually indicated, as malaria may be more severe in the presence

of HIV. In addition, there is a global drive to test all patients for
HIV, as prevalence studies indicate many HIV-positive patients
are unaware of their status, and every opportunity for testing
should be taken
PCR nasopharyngeal swabs for influenza typically negative in
malaria
Very useful to exclude infection with influenza, which may present
in an identical manner
CT head usually normal

An important investigation to look for focal lesions or

haemorrhage if there is impaired level of consciousness or
seizures.

Emerging tests
TEST RESULT
Loop-mediated isothermal amplification detection of
parasites at very low
New commercial molecular assay. levels

More sensitive than microscopy or antigen-detecting RDTs, so

more reliable in detecting low parasitaemia.

Provides faster results than microscopy or PCR, requires less

training, is less costly compared with PCR, and has been
evaluated in both high- and low-resource settings. [58] [59]

DIFFERENTIAL
Dengue fever
SIGNS / SYMPTOMS INVESTIGATIONS
Abrupt onset of symptoms. Headache and eukopenia and
retrobulbar pain that worsens with eye movements is thrombocytopenia are common.
typical. A rash may be present in about half of
patients and may be petechial or otherwise PCR may detect dengue virus in
haemorrhagic. serum early in the illness.
Isolation of virus by tissue
culture is less common.
Antibodies may be detected
after resolution of the illness but
are not helpful in the acute
phase

Zika virus infection

SIGNS / SYMPTOMS INVESTIGATIONS
Residence in/travel from Zika-endemic region or Reverse transcriptase-
unprotected sexual contact with infected individual. polymerase chain reaction (RT-
PCR) is positive for Zika.
Maculopapular, pruritic rash is characteristic.
Serology is positive for Zika.
Non-purulent conjunctivitis or conjunctival
hyperaemia may be present.

Often asymptomatic.

Chikungunya virus
SIGNS / SYMPTOMS INVESTIGATIONS
Residence in/travel from chikungunya-endemic ELISA/indirect fluorescent
region. antibody is positive for
chikungunya antibodies.
Prominent joint symptoms (e.g., polyarthritis and
carpal tunnel syndrome are common). RT-PCR is positive for
chikungunya viral RNA.
Hyperpigmentation of skin and intertriginous lesions
are common.

Ocular symptoms (e.g., photophobia, retro-ocular

pain, conjunctival inflammation).

Yellow fever
SIGNS / SYMPTOMS INVESTIGATIONS
Residence in/travel from yellow fever-endemic RT-PCR is positive for yellow
region. fever virus RNA in viraemic
phase (within 5 days of
Lack of yellow fever immunisation. symptom onset).
Haemorrhagic complications. Serology is positive for yellow
fever virus antibodies and
Biphasic illness (i.e., acute febrile illness lasting 2-6 increasing IgG titers in
days, followed by a 24-48 hour remission period, postviraemic phase (day 5
and then a more severe form of illness in some onwards).
patients, with jaundice, renal failure, hepatic failure,
and haemorrhagic complications). Both RT-PCR and serology are
recommended for samples
taken between days 5 and 7.

South American haemorrhagic fevers

SIGNS / SYMPTOMS INVESTIGATIONS
Residence in/travel from endemic region. RT-PCR is positive for Junin
virus, Guanarito virus, Machupo
Exposure to rodent excreta. virus, Chapare virus, or Sabia
virus RNA.
Haemorrhagic complications.
Serology is positive for IgM or
IgG to Junin virus, Guanarito
virus, or Machupo virus. Usually
ordered only when RT-PCR is
unavailable

Pneumonia
SIGNS / SYMPTOMS INVESTIGATIONS
Respiratory symptoms prominent, (e.g., cough, Neutrophilia is often present.
haemoptysis, dyspnoea, chest pain). CRP may be markedly elevated.

Respiratory examination may reveal focal coarse Chest x-ray may demonstrate
crackles or consolidation. Hypoxia is common. Signs infiltrates or consolidation with
of pleural effusion may be present (e.g., dullness to or without effusion.
percussion, decreased breath sounds over affected
area). Sputum culture may reveal the
causative organism.

Less commonly, blood cultures

may be positive
for Streptococcus pneumoniae .

Urinary antigen testing is

available for certain organisms.
Influenza
SIGNS / SYMPTOMS INVESTIGATIONS
Important to consider current epidemiological Viral culture of nasopharyngeal
situation, (e.g., pandemics, epidemics, winter swabs is disappearing from
months). May give history of ill contacts. Short practice. PCR, often including
incubation period (1 to 2 days) with abrupt onset. other respiratory viruses, is
Mild upper respiratory tract symptoms common commonly used, providing a
(e.g., non-productive cough, pharyngitis, coryza). rapid and sensitive diagnosis.

Wheezing or rhonchi may be audible on Serological diagnosis rests on

auscultation. demonstrating a change in titre
between acute and
convalescent samples and is not
helpful in the acute period.

Enteric fever (typhoid infection)

SIGNS / SYMPTOMS INVESTIGATIONS
Most common on Indian subcontinent. Incubation Isolation of Salmonella
period 1 to 3 weeks. Gradual onset of sustained typhi or S paratyphiin blood,
fever. Rigors uncommon. Abdominal pain and stool, or urine cultures.
headache common. Occasionally bone marrow
culture is necessary.
Relative bradycardia unreliable. May have a
blanching erythematous maculopapular rash (rose The Widal test is widely used
spots). but has poor sensitivity and
specificity.

Criteria
Uncomplicated disease
Presents with symptoms of malaria and a positive parasitological test (i.e., light
microscopy or rapid diagnostic test), but with no features of severe malaria (criteria for
severe disease below). [53]

Severe disease
Patients are classified as having severe malaria if they have one or more of the
following: [53]

Clinical features

 Impaired consciousness (i.e., Glasgow coma score <11 in adults or Blantyre coma score
<3 in children)
 Prostration (i.e., generalised weakness so that the patient is unable to walk or sit up
without assistance)
 Multiple convulsions (more than 2 episodes in 24 hours)
 Deep breathing, respiratory distress (acidotic breathing)
  Circulatory collapse or shock - systolic blood pressure <80 mmHg in adults and <70
mmHg in children (decompensated shock); capillary refill ≥3 seconds or temperature
gradient on leg (mid-to-proximal limb) without hypotension (compensated shock)
 Clinical signs of jaundice
 Significant bleeding (e.g., recurrent or prolonged bleeding from gums, nose, or
venepuncture sites; haematemesis; melaena)
 Pulmonary oedema (radiological finding, or oxygen saturation <92% on room air with a
respiratory rate >30 breaths/minute often with chest indrawing and crepitations on
auscultation)

Laboratory findings

 Hypoglycaemia (blood glucose <40 mg/dL [2.2 mmol/L])

 Metabolic acidosis (plasma bicarbonate <15 mEq/L [<15 mmol/L])
 Severe malarial anaemia (children <12 years of age: Hb ≤5 g/dL or haematocrit of ≤15%;
adults: Hb <7 g/dL or haematocrit of <20%) with a parasite count >10,000/microlitre
 Serum bilirubin >3 mg/dL [>50 micromol/L] with a parasite count >100,000/microlitre
 Hyperparasitaemia (>10%)
 Renal impairment (serum creatinine >3 mg/dL [265 micromol/L]).