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Indian Journal of Community Medicine

Malaria-Resurgence and Problems

Author(s): J. Dutta, Z. Singh, A.K. Verma, M.S. Bishnoi

Vol. 29, No. 4 (2004-10 - 2004-12)

Introduction

In August 1897, Sir Ronald Ross conclusively demonstrated the role of the Anopheline mosquito as a vector in the transmission of malaria in Secunderabad. One hundred years later, however, despite painstaking research leading to accurate knowledge on the subject, we are still grappling with the problem of malaria control not only in India but in other countries as well. The problem with malaria control is not that we do not know enough about the disease, its cause, the parasites and mosquito vectors involved in its transmission, its pathogenesis and manifestations; is complications; its chemotherapy and more importantly, its prevention, but that we are unable to utilize the knowledge and technology already available or newly acquired and to apply them properly.

Extent of Problem

Malaria is essentially a disease of the poor countries and is included under 'Tropical Diseases' by WHO. Of the estimated 500 million episodes and 2.7 million deaths occur from malaria every year, over 90 per cent occur in the African subcontinent and two-thirds of the rest are concentrated in just six countries viz., India, Brazil, Sri Lanka, Vietnam, Cambodia and the Solomon Islands. In south-east Asia, India contributes 60% of the total followed by Sri Lanka (9.7%) and Thailand (9.2%). Inadequate reporting, particularly in areas known to be highly endemic and often out of the reach of well-established health services, makes it difficult to obtain accurate information on the incidence of this disease. It is estimated, therefore, that the global incidence of malaria may be in the order of 300-500 million clinical cases each year1. Over 2,000 milion people in about 95 countries of 3 continents (Asia, Africa and America) are at risk of getting malaria.

Resurgence

The malaria situation till the 1950s was very grave in India with over 75 million cases occurring with 0.8 million deaths. The near-elimination of malaria in the 1960s through the extensive use of insecticides and antimalarials (when the number of cases in India dropped from 75 million to just 0.1 million) proved to be the turning point in malaria control. Lulled into a sense of false security, malaria control operations were virtually put on hold resulting in its re-emergence in the 1970s. Countries of the Southeast Asian region experienced a resurgence of the disease in the mid 1970s and have switched from the eradication to the control concept by decentralizing the programs through their primary health care systems. This approach produced good results and the rising trend of malaria was stablized to around 3 million cases annually for about 5 to 6 years. However, the incidence of Plasmodium falciparum (Pf) infections continued to rise. In 1970 these constituted 20% of the total cases but in 1991 they had risen to 41%2.

Malaria transmission in NE Region of the country has always been an epidemiological challenge as its spatial distribution is not homogeneous and its transmission dynamics and intensity is governed by a large number of stable and unsatble, biotic and abiotic factors in different paradigms. On the basis of existing malaria situation, following paradigms of malaria are distinguishable in the NE Region of India3.

a) Tribal Area Malaria-existing in hilly areas with deep forests and forest fringes, rich in bio-diversity, criss-crossed by hilly streams with low population density. An dirus, An minimus and An fluviatilis are the major vectors which are refractory to control.

b) Deep Forest Malaria-in tropical ever-green forests with high humidity favouring growth of trees with shady canopy. Malaria is transmitted chiefly by An dirus amongst timber collectors, who return to their villages after short stays in forest camps.

c) Forest Fringe Malaria-amongst peope engaged in cultivation of forest cleared areas with disturbed ecology. Malaria is endemic with wide fluctuations.

d) Border Area Malaria-Border areas with neighbouring countries like Myanmar, Bhutan and Bangladesh are covered with thick forests with poor communications and health infrastructure. Twang district bordering China is free from malaria but malaria is hyper to holo-endemic along the rest of the border areas which are populated with people of varying levels of immunity. Inducted populations of Armed Forces and Border Roads are particularly vulnerable groups in these areas and contribute to enhanced local transmission.

e) Organized Sector Malaria -NE Region employs a large work force for mineral extraction and tea plantation along with development projects. The organizations have their own health systems which are primarily curative and no systematic record keeping is followed. Tea sector has high Pf pre-ponderance with chloroquine resistance.

Malaria control is now recognized as a complex exercise influenced by various factors such as rapid urbanization, industrialization, deforestation resulting in a change of the vector behavior. Apart from increasing insecticide resistance by the mosquito vector, the malarial parasite has also demonstrated resistance to all the major anti-malarial drugs, necessitating the use of newer drugs4.

Clinical

The first symptoms of malaria are non-specific: lack of well-doing, headache, fatigue and muscle pain followed by fever. In some patients headache, chest pain, abdominal pain, arthralgia, myalgia or diarrhea may be prominent and suggest an alternative diagnosis. The classic malarial paroxysms in which fever spikes (with chills and rigors) at regular intervals are not common in P-faciparum (Pf) infections but tertian periodicity is often seen in Plasmodium vivax (Pv) infections after an initial phase of irregular fever. Most patients with uncomplicated infections have few signs other than mild anemia and, in some cases, a palpable spleen.

Diagnosis

Despite the simple technology and relatively low direct cost, microscopical diagnosis still requires an adequate infrastructure to purchase and maintain supplies and equipment, to train health workers and to ensure proper quality assurance of the service. A new, simple and quick antigen based diagnostic technique for P falciparum has been evaluated by WHO/TDR and WHO/SEARO in Brazil, India, Malawi, Sri Lanka, Thailand and Venezuela. The results of these evaluations sugest that the technique has potential for use in the diagnosis of malaria, if accuracy can be assured and the test made affordable for those in need. Low cost immunological tests need to be developed to address the problem of delay in diagnosis.

Drug Resistance and Newer Drugs

The increasing numbers of drug resistant parasite strains has made prophylaxis and treatment of the disease a therapeutic challenge. With increasing levels of chloroquine reistance all over the world, and fears of toxicity and decreased efficacy for sulfa drug/pyrimethamine combinations, there is a need for an affordable, effective and safe chloroquine replacement. In the short term, amodiaquine can be reconsidered as a first-or second-line drug in areas of chloroquine resistance. Pyronaridine, a Chinese compund, is, however, under international development by WHO as a potential affordable replacement for chloroquine in Africa. Studies are also being carried out on the combination of short half-life antifolates, e.g. chlorproguanil and dapsone, as safer and effective alternatives to sulfadoxine or sulfalene pyrimethamine combinations.

Artemisinin and its derivatives show no cross-resistance with known antimalarials and, as such, are increasingly being used for the treatment of both uncomplicated and severe malaria in areas of multi-drug resistance in South-East Asia and South America. WHO/TDR has conducted randomized, multi-center trials with intramuscular artemether to support its use outside China. WHO/TDR is also evaluating artesunate suppositories for the management of severe malaria in children at the periphery. A combination of atovaquone, a hydroxynapthoquinone, with proguanil was registered in the United Kingdom in 1997 for the treatment of uncomplicated falciparum malaria. This combination is active against multi-drug resistant malaria. WR 238 605, an 8-aminoquinoline, is being developed by the Walter Reed Army Institute of Research in Washington. It is considerably more active than primaquine.

Mefloquine: Mefloquine, a quinolinemethanol, chemically related to quinine, is a potent long acting blood schizonticide. It is also effective in a single oral dose (usually 15 mg/kg base) and so avoids patient non-complicance.

Artemisinin: This is an antimalarial compound which was isolated in China from the aerial parts of the plant Artemisia annua. A number of derivatives such as artemether, arteether and artesunate are available. Data from 23 trials (on 1891 patients), comparing an artemisinin derivative wth other antimalarials have shown that the fever clearance time compared with intravenous quinine was shortened by 17% (to 7.7 hours) and parasite clearance by 32% (19.8 hours). Artesunate appears to have a more rapid action than the other derivatives.

Antibiotics: Certain antibiotics (tetracyclines and clindamycin) have useful antimalarial properties. Erythromycin, chloramphenicol and rifampicin have antimalarial activity in vitro but have not yet found clinical application6.

Vaccines: Three main types of vaccines are currently under development viz (i) 'Anti-sporozoite' vaccines, designed to prevent infection; (ii) 'Transmission-blocking' vaccines, designed to arrest the development of the parasite in the mosquito, thereby reducing or eliminating transmission of the disease; (iii) 'Antisexual blood stage' vaccine designed to reduce severe and complicated manifestations of the disease. The development of these types of vaccines is given priority by WHO/TDR and several such vaccines are currently undergoing clinical and field-testing. At present, it is difficult to predict when such a vaccine will become available.

Chemoprophylaxis Chloroquine is the best and safest drug for prophylaxis. It prevents the clinical signs and symptoms and is a suppressive prophylactic. Daily proguanil in a dose of 200 mg in addition to chloroquine is more effective in regions where chloroquine resistance occurs. Prophylactic drugs are indicated for only special risk groups such as pregnant women, non-immune travelers and non-immune persons living in endemic areas for fixed periods (e.g. Laboru forces and police and army units)7.

References

  1. World Health Organisation. World malaria situation in 1993. Wkly Epidemiol Rec 1996:3:17-22.
  2. Sharma VP. Reemergence of malaria in India. India J Med Res 1996; 103:26-45.
  3. ICMR Bulletin. Malaria Paradigms in NE Region. Vol. 28, No. 1, Mar. 1998.
  4. World Health Organisation A Global Strategy for Malaria Control, Geneva WHO 1993:30.
  5. White NJ, Plorde JJ Malaria. In: Wilson JD, Braunwald E, Isselbacher KJ, Petersdorf RG (eds). Harrison's principles of internal medicine. New York; McGraw-Hill, 1991: 782-8.
  6. Fundamental aspects of chemotherapy of malaria. In: Bruce-Chwatt Lj (ed). Geneva: World Health Organizaiton, 1986.
  7. Report of a WHO scientific group. Practical chemotherapy of malaria. WHO Tech Rep. Ser. 1990.
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