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Malaria: Prevention remains our best measure for controlling the disease
Author:
Naomi Cheng
Supervisor:
Professor Julia Ling
Affiliation:
The Chinese University of Hong Kong
Is malaria still a cause of concern in the 21st century?
Although malaria is recognized world-wide as a tropical disease that is only rarely
found in most industrialized countries, such as in the United States, it remains a major health
concern in Africa, Asia, Central America, Oceania, and South America.
Epidemiological studies have shown malaria to cause approximately 3000 deaths each
day, of which 90% are in Africa.(1) This, together with the vast majority of the remaining
10% being in the South East Asian region has proved alarming to both developed and lessdeveloped nations worldwide, especially since morbidity and mortality due to the disease are
still rife in endemic countries (the top three of which were India, Indonesia and Myanmar in
2003) despite the substantial healthcare budgets that have been implemented to manage
patients with malaria.
In the past, especially before the nationwide introduction of the malaria control
program in 1955, malaria had been a major cause of morbidity and mortality in certain areas
of China. In fact, some localities reported infection rates as high as 800 cases per 1000
population.(2) Today, due to the vigilance in maintaining an efficient and effective
surveillance system for the control of the Anopheles mosquito vector, malaria has almost
been eradicated from provinces in central China. Considering that the number of confirmed
malaria cases has decreased from over 75,000 in 1992 to fewer than 30,000 in 2002, and that
the incidence of malaria during the same period decreased from over 0.06 to under 0.02 per
1,000 population, China has indeed progressed immensely since the olden days in controlling
the spread of this once-immensely prevalent disease. Despite this, mortality rates due to
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malaria remain relatively unchanged during this same 10-year period (from approximately 50
to 40 cases from 1992-2002 with a peak of 65 cases in 1999). The 0.67 fatalities per 1,000
cases in 1992 and 1.33 in 2002 calculated from these figures indicate that there were still
more deaths due to malaria in 2002 than in 1992., and therefore, reinforces the fact that it is a
disease that still remains endemic in the Hainan and the southern Chinese provinces. This is
most probably due to the yet unregulated population movement into and among these areas,
which therefore makes it difficult for the authorities to trace and control the movement and
development of the disease. China is not alone -this problem of imported malaria exists in
almost every country in the world.
Thus, malaria has become a recognized global problem, and together with the fact that
mortality rates can be as high as 10% among infected infants and young children in endemic
countries, it is important for all individuals at risk to become acquainted with the deadly
nature of this disease, and even more importantly, to learn thoroughly the various methods of
mosquito, hence malarial prevention.
How does a normal person contract malaria?
Malaria is caused by four different species of the Plasmodium parasite.
1. P. falciparum is most common in Africa and Melanesia (Papua New Guinea and the
Solomon Islands)
2. P. vivax is usually found in Central and South America, North Africa, the Middle East
and the Indian subcontinent
3. P. ovale is most prevalent in West Africa and Asia
4. P. malariae is found worldwide(3)
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However, the above geographical distribution of the four Plasmodium species does
not imply that those are the only areas in which each species is found. This is because ever
since air travel became an everyday commodity, malaria, regardless of the infective species,
has been rapidly transported to almost any place in the world.
Malaria is transmitted by blood and blood products. Human infection results from the
bite of an affected Anopheles mosquito, during which the Plasmodium sporozoites are
transferred from the mosquito to the human bloodstream. From then on, these sporozoites
undergo schizogony (or an asexual phase), where they multiply in the liver parenchymal cells
and become merozoites. Below is a diagram illustrating the life cycle of the malaria parasite
after it enters the human body:
Schizogony in Humans:
Sporozoites from
mosquito injected
into human host
Multiplication in
the liver
parenchymal cells
Merozoites
Mature schizont
Enter red cells
Immature schizont
Ring trophozoite
Mature trophozoite
Human blood enters
mosquito
Differentiation into male
and female gametocytes
It is when the merozoites enter the red blood cells in the schizogony cycle that the clinical
symptoms of malaria start to appear.
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Malaria can also be contracted by blood transfusions, organ transplantations and from
the mother to the fetus via the placenta.
How is malaria recognised?
Malaria can present in a variety of ways, depending on the circulation of infected red
cells to different organs and tissues. In adults, it has been observed that the disease presents
classically with periodic fever, shivering and sweating. However, these features are not
frequently observed in young children who, from endemic areas, may present with signs and
symptoms of cerebral malaria (convulsions, respiratory distress and severe anaemia) instead.
A milder form of the disease, such as that caused by P. vivax, P. malariae or P. ovale,
may present with rigors, fever and sweating that may be accompanied by other flu-like
symptoms and diarrhea. However, some patients, especially those infected by P. falciparum,
may have severe malaria and will develop an impaired consciousness, jaundice and renal
impairment, though they will not experience convulsions as do patients with cerebral malaria.
Since it may sometimes be difficult to determine whether a patient is suffering from a
milder form of malaria, or whether he/she just happened to catch the flu, it is essential for the
doctor to take a thorough history from the patient or from his/her parents, paying special
attention to the patient’s recent travel history to endemic areas, or if the patient were a
neonate, whether the mother has malaria or has any recent signs and symptoms suggestive of
this disease. It must also be determined whether the patient’s fever started to appear shortly
after blood transfusion, organ transplantation or a needlestick injury. In addition to the
history, physical examination of the patient with findings of fever, anaemia, jaundice and
hepatosplenomegaly will also strongly support a diagnosis of malaria.
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Are there any tests to diagnose malaria?
In a suspected case of malaria, the following tests can be carried out to confirm the
diagnosis.
1. Blood film: Parasites in the form of trophozoites, gametocytes and schizonts can be
identified on a Giemsa stained thick and thin film. A positive film is diagnostic of
malaria. However, one must bear in mind that in endemic areas a positive smear could
also indicate a patient with an asymptomatic manifestation of the infection. A
minimum of three films should be taken and examined before malaria is declared
unlikely. Even then, a negative examination is at most inconclusive, since only 50%
of children infected with malaria are smear positive.
2. Serological tests: These have no diagnostic value but are carried out for
epidemiological purposes. This is because the tests are used to detect patients that
were previously infected. Such tests include the indirect fluorescent antibody test
(IFAT) and enzyme linked immunosorbent assay (ELISA).
3. Malaria rapid diagnostic tests (RDTs): These antigen detection tests are particularly
useful in resource-poor settings, especially where good-quality blood films are not
available. Although it is highly recommended that test results are correlated with the
clinical presentation of the patient before any management decisions are carried out,
RDTs have detection capabilities that are generally comparable to those of blood film
microscopy and are proven to contribute positively towards the prognosis of the
patient with malaria, provided medical professionals follow the post-test protocols,
that are included with these kits, closely.(1) They are available as a dipstick, cassette
or a card. The dipstick is the most affordable among the three, but the cassette and
card tend to be more user-friendly. These tests have the advantages of being fast to
produce results (in approximately 15 minutes), easy to use, and to have a clear post-
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test management protocol. The major disadvantage is that although high in sensitivity
and specificity, some can only detect P. falciparum. They are also unable to determine
whether the patient has clinical malaria or just parasitaemia from the Plasmodium
infection, and may still render positive results even after a previously infected patient
has received successful drug treatment.
What should be done to manage a patient with malaria?
In addition to the prescription of antimalarial drugs, it is important that patients also
receive adequate holistic care. The management of a patient with malaria focuses on two
broad area: supportive therapy and drug therapy.
1. Supportive therapy: Oral paracetamol or sponging with tepid water should be given
to lower the temperature, and all patients should be assessed for signs of dehydration
and encouraged to increase fluid intake or given fluid supplementation if required. If
the patient continues to vomit, antiemetics such as metoclopramide should also be
prescribed.
2. Drug therapy: The first line administration of antimalarials should always be in the
form of a blood schizonticide, and among these is chloroquine to which most of the
Plasmodium species except some Oceanic strains of P. vivax are sensitive. Despite
this, it has become increasingly common for some African and Asia strains of P.
falciparum to develop resistance against chloroquine (which is reported to be over
50% in most affected regions(4)) and for these patients, pyrimethamine-sulphadoxine,
an antifolate and blood schizonticide drug combination can be given instead to
especially target this schizont subtype. Likewise, patients with a chloroquine resistant
P. vivax infection should be given quinine instead of either of the former two drugs.
Blood smears should then be repeated 24-48 hours after drug administration to ensure
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that the drug is effective, and in the case of a positive smear, the drug effect is
suboptimal and a different drug should be prescribed as quickly as possible.
Primaquine, a uniquely broad-spectrum schizonticide is currently used to prevent the
relapse of malaria and in endemic areas it is also used as a gametocytocide to prevent
the infection of mosquitoes and up to now there have been no confirmed cases of
developed malarial resistance towards this drug.
Recently, with the full support of the World Health Organisation, China has also
proposed a range of new drugs for the treatment of malaria based on derivatives of “qing haosu” (artemisinin), an ancient Chinese herb.(5) Current clinical trials have found these drugs to
have over 95% cure for malaria in South East Asians, as well as the fact that they apparently
have several notable advantages over the current antimalarials. Firstly, they only need to be
taken for three days. Secondly, they consist of compounds that malarial parasites are now not
resistant to, and more importantly they are cheap and affordable (Coartem, one of these
drugs, is currently being sold at US$2.40 per adult treatment, and it is likely that the
forthcoming drugs will cost even less.) However, there is still limited information concerning
the safety of these drugs outside South East Asia.
Can malaria really be prevented?
The prevention of malaria can be categorized into two main areas of interest: vector
control and chemoprophylaxis. Since ignorance of the disease contributes significantly
towards the ever-present substantial figures of malaria world-wide, it is vital that all travelers
to malarious areas, people who live in endemic regions and all those who are at risk of
contracting malaria are properly educated on both of these preventative measures.
1. Vector control: It is of foremost importance for people who travel to or live in an
endemic area to know of and implement adequate mosquito prevention methods. In
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fact, the prevention of mosquito bites is the single most effective method of
preventing malaria in individuals. Measures include the use of insecticides, mosquito
nets, insect repellents, avoiding outdoor activities during the evening when
mosquitoes are most active and habitually wearing long sleeves and trousers, just to
name a few. Insecticide treated nets (ITNs) have been found to effectively decrease
overall child mortality and clinical malaria within a two-year period,(6) the effect of
which are found to be particularly pronounced in the children and pregnant women of
Kenya.(7) In view of their effectiveness, it appears to be less of a burden for poorer
families to buy a set of these nets only once, provided these nets are made more
durable by incorporating insecticide directly into their fibres.
2. Chemoprophylaxis: Reassuring though this may sound, it has not been proven that
prophylaxis with chloroquine and mefloquine are fully effective in the prevention of
malaria. Another commonly used chemoprophylactic regimen consists of giving
doxycycline daily, though the major disadvantage of this is the inability of pregnant
women to use this drug, due to safety concerns. Taking all this into account, mosquito
bite prevention still remains the single most effective prophylactic measure. Although
chemoprophylaxis is recommended to travelers to endemic countries and is able to
substantially decrease malaria-induced morbidity and mortality in children, it is
impractical to sustain over long periods of time. The fact that it also encourages the
development of drug resistance as well as potentially hampers a person’s ability to
produce natural immunity towards the parasite limits its usefulness.(8) Vaccines
targeted at preventing sporozoites from entering the hepatocytes and at destroying
infected hepatocytes have been investigated for some years. However, current
endeavors have proven unsatisfactory since antibodies produced are inadequate and
short-lived.
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Last words
Mosquito prevention remains a very important role in the control of the spread of
malaria. Both patients and potential patients should be adequately educated on the nature and
seriousness of the disease, as well as the various preventative measures that they themselves
can implement to effectively decrease their risk of contracting malaria in the first place.
However, since the effect of malarial vaccines is still being researched on, in the event of
inadequate or failed prevention it remains important for patients to be properly diagnosed and
treated for malaria, not only by the use of conventional anti-malarial drugs, but also by proper
anti-pyretic and rehydration methods. The problem of widespread drug resistance is actively
being addressed and tested in the form of artemisinin-containing compounds, and results
among the South East Asian population prove promising for a cheaper and more effective
antimalarial cure in the near future.
References
1. World Health Organisation, Regional Office for South East Asia, 2005.
2. World Health Organisation, West Pacific Region, 2005.
3. Cohen & Powderly: Infectious Diseases, 2nd ed., Copyright © 2004 Elsevier, Chapter
166.
4. Baird JK. Drug therapy: Effectiveness of antimalarial drugs. New England Journal of
Medicine. 2005; 352:1565-77.
5. World Health Organization Regional Office for the Western Pacific 2005.
6. Lengeler C. Insecticide-treated bednets and curtains for preventing malaria. Cochrane
Database Syst Rev 2004; 2: CD000363.
7. Phillips-Howard PA, Nahlen BJ, Kolczak MS, et al. Efficacy of permethrin-treated
bed nets in the prevention of mortality in young children in an area of high perennial
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malaria transmission in western Kenya. Am J Trop Med Hyg 2003; 68 (suppl 4): 23–
29.
8. Greenwood BM. The use of anti-malarial drugs to prevent malaria in the population
of malaria-endemic areas. Am J Trop Med Hyg 2004; 70: 1–7.