CONTROL AND PREVENTION OF MALARIA

Malaria has had a greater impact on world history than any other infectious disease. More
than 300 to 500 million individuals worldwide are infected with Plasmodium spp, and 1.5 to
2.7 million people a year, most of whom are children, die from the infection. Malaria is
endemic in over 90 countries in which 2400 million people live; this represents 40% of the
world's population. Approximately 90% of malaria deaths occur in Africa (1). This potentiate
the need for adequate prevention mechanisms against malaria.

Control & prevention of malaria is broadly categorized into 4 groups which include;

- Primary - Secondary – Tertiary – Quatenary

PRIMARY LEVEL
This phase consists of measures aimed at susceptible populations or group of people
with risk factors for malaria. The ultimate purpose of the level is to prevent the
occurrence of malaria in the predisposed group. Strategies within the scope of this
phase include;
- Health education : Considering the pathophysiology and the mode of
transmission of malaria, it is of no doubt that adequate sensitization of the
general public, especially the less-priviledged, the poor and the uneducated
community will go a long way in drastically reducing the incidence of malaria.
This can be achieved via medical outreaches, health awareness programs and
government initiatives. Health education intervention in all age group has
improved knowledge about various malaria prevention strategies and malaria
control can be significantly improved in rural areas if the caregivers are
adequately empowered through appropriate health education intervention
though change in attitude and belief may require a longer and persistent
effort (2)

- Environmental Sanitation: As poor environmental hygiene is a key modulator

of Femele Anopheles Mosquito breeding and proliferation, the prospects of
environmental management and sanitation (EMS) as a vector control
strategy, looks promisingly high, pertinent, and workable and a likelihood
game changer of winning the fight against malaria due to the residual
transmission that is happening outdoors. Government support and/or
political/NGO will by investing in environmental sanitation infrastructure,
creating the enabling environment for strict enforcement of environmental
sanitation bye-laws by Environmental Health Officers/Health Inspectors,
effective and efficient collaboration among key stakeholders and organization
of communal labor activities is likely to help reduce the majority of the
mosquito breeding sites (3).
- Mosquito Nets & Insecticides: Long-lasting insecticidal nets (LLINs) are one of the
main vector control strategies recommended by the World Health Organization for the
control and elimination of malaria (4). The correct use of mosquito nets—and
consequently the protection of the population—needs to be supported by health
promotion actions. The alphacypermethrin-impregnated LLIN was found to be more
effective than the LLIN impregnated with permethrin (5). These initiatives are
considered to be essential for the success of this vector control strategy. In addition,
studies have also shown Significant reduction in abundance of peridomestic
mosquitoes (Culicidae) and Culicoides midges (Ceratopogonidae) after chemical
intervention using insecticides (6).

- Prompt Antenatal care: Tens of millions of pregnant women are at risk of malaria
every year. But controlling malaria in this population is challenging due to the
placental sequestration of parasites and concerns over the safety of interventions
which is why early and prompt antenatal care is encouraged. One hundred and
twenty-five million women in malaria-endemic areas become pregnant each year(7).
Chloroquine prophylaxis was once a safe approach to prevention but has been
abandoned because of drug-resistant parasites. Howeever, intermittent presumptive
treatment (IPT) with sulfadoxine–pyrimethamine is currently used to protect pregnant
Monthly dihydroartemisinin–piperaquine has similarly shown promise for reducing
poor pregnancy outcomes due to malaria (7).

- Vaccine: Malaria vaccines have been in development for almost 60 years. In 2021
the World Health Organization (WHO) approved the first malaria vaccine,
RTS,S/AS01 vaccine (Mosquirix™), for widespread use. The RTS,S/AS01 vaccine is
however not sufficient as a stand-alone solution. Multi-component vaccines may be a
useful addition to other malaria control techniques in achieving eradication of malaria
(8).
SECONDARY LEVEL

This level entails early detection and treatment of malaria most often before manifestation,
thereby minimizing complications/morbidity. This phase entails screening and treatment
modalities

- Screening methods for malaria

A. Microscopic tests

- Blood Film for Malaria Parasite: This is WHO gold standard for the diagnosis of malaria
(9). Thick film is used for detecting the presence of malaria parasite while thin film is
used for identification of the causative specie.

WHO Plus system

1-10 parasites per 100 HPF ----- +

11-100 parasites per 100 HPF ----- ++

1-10 parasites per HPF ----- +++

>10 parasites per HPF ----- ++++

HPF (high power field)

- Quantitative Buffy coat: buffy coat thick films are useful and can detect malarial
parasites in 27.8% of patients whose conventional thick films show negative
 parasitemia (10). Patient blood is mixed with acridine orange and centrifuged.
Malaria parasite binds acridine orange in the nucleus and cytoplasm consequently
projecting green and red fluorescence indicating parasite morphology.

B. Non-microscopic tests

a. Rapid Diagnostic Test: Malaria rapid diagnostic tests (RDTs) have had an enormous
global impact which contributed to the World Health Organization paradigm shift
from empiric treatment to obtaining a parasitological diagnosis prior to
treatment. Contrary to microscopy which is the gold standard, RDT does not
require electricity, reagents, equipment and high level of expertise, which makes
it an easier approach to malaria screening. Worldwide, there are over 200
different RDT brands that utilize three antigens: Plasmodium histidine-rich
protein 2 (PfHRP-2), Plasmodium lactate dehydrogenase (pLDH), and Plasmodium
aldolase (pALDO). pfHRP-2 is produced exclusively by Plasmodium falciparum and
is very Plasmodium falciparum sensitive. RDT sensitivity also decreases with low
parasitemia (<100 parasites/uL), genetic variability, and prozone effect. Thus,
proper RDT selection and understanding of test limitations are essential (9). A
new more highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium
falciparum malaria (Alere™/Abbott Malaria Ag P.f RDT [05FK140], now
called NxTek™ Eliminate Malaria Ag Pf) was launched in 2017 (11). HS-RDT is
found to be more sensitive in asymptomatic populations and could provide a
marginal improvement in clinical diagnosis and screening pregnant women (10).

- Polymerase chain reaction (PCR): The novel technology of the Sysmex XN-30 provides
a robust, rapid, automated and accurate platform for diagnosing malaria in a clinical
setting. The objective enumeration of red blood cells infected
with Plasmodium species makes it suitable for global use and allows monitoring of
 the parasite load once therapy has been initiated, thereby providing an early marker
of drug resistance (12).
- Serologic tests: including immunoflourescene, enzyme immunosorbent assay and
radioimmunoassay

TREATMENT OF MALARIA

Combination therapy using antimalarials is one of the best approaches that is currently used
to treat malaria, whereby two or more therapeutic agents are combined. Different
combination therapy strategies are used to overcome limitations such as drug resistance,
reduced bioavailability and poor intestinal absorption.
Classification of Antimalarial Drugs

Different types of antimalarial agents are classified on the basis of their chemical structure
and antiplasmodial activity in the malaria life cycle.

According to the antiplasmodial activity, five classes of antimalarial agents have been
categorized (13):

- Gametocidal: administered to inhibit the transfer of malaria from an infected person to

uninfected female Anopheles mosquito. Gametocytocides destroy female and male
gametocytes of the parasites in the blood stage of the malaria life cycle. Some examples of
gametocytocides include artemisinin 1 and chloroquine 2. (Fig1)

- Prophylaxis: administered for the prevention of malaria infections in people who are
travelling from nonmalaria countries to malaria-endemic countries, especially travelers with
low immune function. Prophylactic drugs include pyrimethamine 3, proguanil 4, and
primaquine 5 (Fig1)

- Blood schizonticides: disrupt asexual erythrocyte forms of the Plasmodium parasites and
stop the early symptoms of malaria. Some examples of blood schizonticides include
halofantrine 6, sulfadoxine 7, mefloquine 8, and quinine 9 (Fig1)

- Tissue schizonticides: prevent the relapse of P. ovale and P. vivax parasites caused by
hypnozoites in the liver stage of the plasmodium life cycle. Pyrimethamine 3 and
primaquine 5 are examples of tissue schizonticides.(Fig1)

- Sporontocides: inhibit the development of oocytes in the parasites in the mosquito stage
of the Plasmodium life cycle. Sporontocidal drugs include primaquine 5 and
pyrimethamine 3. (Fig1)
Fig1
 - As stated initially, monotherapy is no longer used and the new standard is
Artemisiline combination therapy (ACT) examples of which include;
-Artemeter Lumefantrine
-Arthesunate amodaquine
-Artesunate piperaquine

-Artesunate mefloquine

Antimalarials are also classified based on their structures, as shown in Fig1:

4-aminoquinolines (amodiaquine 10 and chloroquine 2);

8-aminoquinolines (primaquine 5);

hydroxynaphthoquinones (atovaquone 11);

artemisinin derivatives (Artemether 12a and artesunate 12b);

diaminopyrimidines (pyrimethamine 3);

quinolines-based cinchona alkaloids (quinine 9 and quinidine 13);

4-quinolinemethanols (mefloquine 8);

biguanides (proguanil 4 and chloroproguanil 14); and

sulfonamides (sulfadoxine 7) (13).

SOME ANTIMALARIALS AND THEIR ADVERSE EFFECTS

- Chloroquine: mild headache, confusion, psychosis, corneal damage, anorexia, nausea,

urticaria, hypotension, cardiac arrhythmia, endothelial damage (14)
- Mefloquine: nausea, vomiting, heartburn, insomnia, loose stool, mast cell apoptosis
(15)
- Primaquine: anorexia, nausea, cramps, hemolytic anemia, Methemoglobinemia (16)
- Quinine: cinchonism, allergic dermatitis, hypotension, renal damage (17)
- Amodaquine: hepatotoxicity(18), agranulocytosis
- Tafenoquine: acute hemolytic anemia (19)
 - Halofantrine: 2nd degree heart block (20)

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JAGUNMOLU HABIBLAH
FATOKUN OMOLARA