Malaria: Prevention remains our best measure for controlling the disease

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Bathsheba Dickerson
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1 Malaria: 1/10 Malaria: Prevention remains our best measure for controlling the disease Author: Supervisor: Affiliation: Naomi Cheng Professor Julia Ling 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

2 Malaria: 2/10 malaria remain relatively unchanged during this same 10-year period (from approximately 50 to 40 cases from 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)

3 Malaria: 3/10 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.

4 Malaria: 4/10 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.

5 Malaria: 5/10 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-

6 Malaria: 6/10 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 hours after drug administration to ensure

7 Malaria: 7/10 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

8 Malaria: 8/10 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.

9 Malaria: 9/10 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, World Health Organisation, West Pacific Region, Cohen & Powderly: Infectious Diseases, 2nd ed., Copyright 2004 Elsevier, Chapter Baird JK. Drug therapy: Effectiveness of antimalarial drugs. New England Journal of Medicine. 2005; 352: World Health Organization Regional Office for the Western Pacific Lengeler C. Insecticide-treated bednets and curtains for preventing malaria. Cochrane Database Syst Rev 2004; 2: CD 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

10 Malaria: 10/10 malaria transmission in western Kenya. Am J Trop Med Hyg 2003; 68 (suppl 4): 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.

Invest in the future, defeat malaria

Invest in the future, defeat malaria Malaria is caused by parasites from the genus Plasmodium, which are spread to people by infected mosquitoes. There are five species of Plasmodium that can infect humans.