Evolutionary and Historical Aspects of the Burden of Malaria - Case Study Example

INTRODUCTION: MALARIA - OLD DISEASE IN MODERN WORLD With approximately 2.2 billion people living under the threat of infection, malaria is considered a global burden which affects a third of the world’s population (Snow et al, 2005). An infectious disease that is transmitted by the female Anopheles mosquito and caused by the parasite Plasmodium falciparum, malaria results in between 700,000 and 2.7 million deaths annually (Greenwood et al, 2005). Four species of malaria commonly infect humans and cause various forms of disease (Gilles and Warrell, 1993, 124). Plasmodium falciparum is the most prevalent species and is responsible for nearly all malaria-related deaths (Snow et al, 2005). P. vivax is more benign and widely distributed in temperate and tropical zones (Keusch and Migasena, 1982). P. ovale is found primarily in Africa, but also occurs in the West Pacific (Keusch and Migasena, 1982). And, P. malariae is a mild species that has a spotty occurrence throughout the world (Keusch and Migasena, 1982). There is epidemiological variation of each Plasmodium species even within small geographic areas, depending on a range of factors; the immunologic and genetic makeup of the population; the mosquito species that occurs within the human community; climate: breeding site availability and distribution; and, parasitic resistance to drugs and various chemical control measures (White and Breman 1995). Most deaths from malaria occur from infection with P. falciparum, but other species, particularly P. vivax, may lie dormant in the liver, causing the reappearance of symptoms after many months or years (Despommier, Gwadz, and Hotez 1995, 174-89). Clinical disease is very complicated. Malaria is sometimes referred to as the “great umbrella” because its symptoms are shared with those of so many other diseases. The symptoms are flu-like and may include fever, chills, muscle aches, headache, and nausea. In the most severe cases, the parasites travel to vital organs such as the brain, which swells, leading to seizures, coma and in 20-50% of these cases, death. MALARIA LIFE CYCLE AND PATHOLOGY Despite the massive prevalence eof the disease worldwide, the pathology of malaria which leads to death is highly varied and poorly understood. Plasmodium falciparum grows in red blood cells and alters these red blood cells in during its 48 hour asexual life cycle. One effect of these alterations is to reduce the ability of infected red blood cells to deform and hinders the infected cells from traversing capillary constrictions (Snow et al, 2005). The reduced deformability of infected red blood cells is one aspect of disease pathology thought to lead to mortality. Previously, a microfluidic study described that freshly infected red blood cells were less likely to obstruct capillary constrictions that late stage parasitized cells (Shelby et al, 2003). The deformability limit of a red blood cell was hypothesized to have geometric constraints defined by the cell’s surface area and volume (Shelby et al, 2003). The complete life cycle of the malaria is distributed between two hosts (see Figure 1). The parasites primary host (where sexual reproduction occurs) is the female Anopholies mosquito. While an infected female mosquite take a blood meal, she injects sporozoites into the human host (Sherman, 1998). These sporozoites migrate to the liver and invade hepatocytes. The parasite then transforms the hepatocyte and grows to form a schizont with hundreds of daughter cell merozoites (Sherman, 1998). These merozoites are released into the blood stream where they invade red blood cells and beging the asexual cycle of reproduction. The parasite continues to grow within the red blood cell host forming what is terms as trophozoites and then schizonts. During schizogony the parasite produces 10 to 30 merozoites daughter cells (Sherman, 1998). These merozoites once released form ring stage cells and the cycle repeats. Figure 1. The Life cycle of Plasmodium falciparum. Retrieved from The pathology which leads to mortality occurs during the asexual blood stage of the malaria life cycle. Symptoms of blood stage infection can be asymptomatic but usually occur with a cyclic fever. The fever may progress to severe symptoms which include hypoglycemia, severe anemia, respiratory distress, acidosis, jaundice, rental failure, shock, or the onset of the profound effects of celebral malaria (Sherman, 1998). At the onset of severe symptoms of celebral malaria, the treatments available are very limited. In most areas where malaria is endemic, the population does not have the resources of advanced medical care. Even in the presence of hospitals with advanced resources the prognosis of treating severe cerebral malaria is based on chemotherapy. The most common treatment for cerebral malaria is a massive dose of quinine (Sherman, 1998). The prognosis recovery from cerebral malaria with current chemotherapy treatment is anywhere from 20 to 50% (Sherman, 1998). After alleviating the symptoms of cerebral malaria, parasites are still observed in peripheral circulation for many days requiring continued treatment. MALARIA: DISTRIBUTION AND IMPACT From the statistical perspective, the period of 1900-2000 has been marked with a significant reduction in the overall distribution of malaria, though there has been an overall increase in the incidence of disease (Hay et al, 2004, see Figure 2). Figure 2. Malaria endemic regions of the world over the past 100 years (Hay et al, 2004). Malaria is not evenly distributed, both geographically and among social groups, around the world. Nine of every ten cases each year occur in sub-Saharan Africa, while at least 1 million of all deaths are of children there who are less than five years old because their immunity is not fully developed (see Figure 3). Figure 3. Predicted proportional age-specific malaria mortality in Africa, by Hospital Admission (Rogan et al, 2005). Another vulnerable group is pregnant women, whose immunity levels drop through biological changes during pregnancy. As a result, malaria is a major cause of death of first-time mothers. In addition, malaria and anemia in pregnant mothers have been linked to low birthweights in newborns in up to 40% of the births in some areas (Rogan et al, 2005). Malaria very often occurs with other debilitating health conditions, including respiratory disease, anemia, malnutrition, and poverty is an underlying feature of the great majority affected. Small-scale epidemiological variation and large-scale prevalence add to the complexity of malaria. Malaria is a global problem, but its profile reflects the unique environmental, epidemiological, cultural, political, and economic factors of a particular area. Back in 1837, Hackett (1937, 122) noted: “Everything about malaria is so moulded and altered by local conditions chat it becomes a chousand different diseases and epidemiological puzzles.” The environment appears to be a leading factor in the distribution of disease. The World Health Organization estimates that 90% of the global burden of disease is attributable to environmental factors (WHO 1997, 147). For example, the patterns of rainfall, temperature and humidity help to determine the availability and distribution of larval breeding sites. Some vectors are more efficient at transmitting malaria parasites than others. In most areas of Sub-Saharan Africa, where malaria transmission is stable, the most important vector species is Anopheles gambiae, which is the most efficient vector because it is highly anthropophilic - it prefers to bite humans (Sherman, 1998). In addition, tropical conditions tavor longevity of the mosquito and a shorter development time of the parasite within the vector. P. falciparum is the most common plasmodium species in the tropics and subtropics (Gilles and Warrell 1993). These factors facilitate the transmission of malaria and provide a high-risk environment that is unmatched anywhere else in the world. Malaria is one of the most studied socioeconomic diseases which limit the capacity for development. The population at the highest risk for malaria is considered as the world’s poorest. In 1987, the total direct and indirect economic cost of malaria in Africa was US$791 million ($2.34 per capita and 0.6% of sub-Saharan Africa GDP) and was expected to be four times this amount by the year 2000 (Shepard et al. 1991). The Organization of African Unity (OAU) reported that the African economy was projected to have a US$3.6 billion deficit by the year 2000 as a result of treatment costs and hours of productivity lost to malaria (Smith, 2000). Families with malaria spend more than a quarter of their income on treatment and prevention, and lose income as a result of being incapacitated by disease. Over the last 35 years, malaria has caused a 32% lower Gross Domestic Product (GDP) in Africa today than would have occurred without the disease (Shepard et al. 1991). MALARIA TREATMENT AND CONROL STRATEGIES Malaria infection plagued the world for centuries with quinine as the only effective treatment. Quinine’s effectiveness against malaria was discovered accidentally. During the World War II, the Japanese took control of Java causing a shortage of quinine supply (Carter and Mendis, 2002). This shortage fuelled research aimed at synthesising quinine and discovering other antimalarials. A major relief was achieved with the synthesis and discovery of Chloroquine as an antimalarial agent in 1934 (Carter and Mendis, 2002). Chloroquine was cheap and very effective thus could be produced in large quantities and distributed even to the poorest villages in African countries. In combination with the use of methods to prevent transmission such as insecticide spraying, a campaign to eradicate malaria was launched by the World Health Organization in 1955 during the 8th World Health Assembly for all countries in which malaria is endemic except for Madagascar and sub-Sahara Africa (). Malaria eradication was achieved in about 37 out of 143 countries; most of the success was in Europe and America. The Global Malaria Eradication campaign was abandoned by 1973 when it was determined long-term measures were needed to achieve global eradication (Sherman, 1998). However, the morbidity and mortality caused by malaria infection started to increase again in 1980s as a result of spread of Plasmodium parasites that are resistant to Chloroquine treatment. Resistance to other antimalarials such as Pyrimethamine, Sulfadoxine and Mefloquine have also been reported (Hayton and Su, 2008). Although resistance to the oldest form of treatment has been reported, Quinine still remains effective against uncomplicated infection of P. falciparum (Hayton and Su, 2008). Modern malaria control incorporates the combination of prevention and treatment techniques. Primary method of reducing the morbidity and mortality due to malaria infection is by lowering the risk of malaria infection through minimizing contact between mosquitoes that transmit malaria and humans (Carter and Mendis, 2002). The increase use of long-lasting insecticidal nets (LLIN) and indoor residual spraying (IRS) for children, pregnant women and populations in high transmission areas have assisted in reducing the rate of malaria infection. From the clinical standpoint, the major objective of treating uncomplicated malaria is to cure the infection and stop the disease progression, while the major objective in cases of severe malaria is to prevent mortality (WHO, 2006). According to recommendations of WHO, in order to combat the threat of uncomplicated malaria and improve treatment outcomes, malaria can be treated with artemisininbased combination therapy (WHO, 2006). MALARIA AND DDT DEBATE WHO campaigns attempted to combat malaria in the middle of twentieth century with the utilisation of DDT were considered successful in terms of decreasing malaria mortality and morbidity (Sherman, 1998). In some developing countries DDT is still used for vector control. Practically, the distribution of the risks and benefits of DDT use are very different for different groups. People living in malaria endemic countries, especially those in rural areas (Curtis and Lines 2000), benefit greatly from the use of DDT in the numbers of lives saved from morbidity and mortality. They are also spared from secondary effects of malaria, such as anemia, which in turn can lead or contribute to various health complications, such as in pregnancy and bacterial infection (Najera and Hempel, 2000). Developed countries where malaria is not an endemic risk but a rare event gain no benefit from the continued use of DDT. There are no costs to them for using or phasing out DDT, since it has long been banned in large part. However, there are potential risks of foods contaminated with DDT and residues being transported from endemic areas to colder climates, affecting many more people than those intentionally exposed to combat malaria (Sherman, 1998). This large-scale distribution of exposure could result in differential and rare adverse effects that show up “impressively” (Curtis and Lines 2000). Chemical transport and epidemiological studies suggest possible adverse effects of exposures received over time. People at risk of malaria also are exposed to DDT residues for long periods in their homes. Most epidemiological studies on the human health effects of DDT and other chemicals used for malaria control have focused on the cohort of vector control workers. The dose, frequency, and duration of their exposures can be more accurately accounted for by their job description. The nature of exposure to DDT applied to house walls and chemicals impregnating bednets can be very different for different groups of people. Vector control workers are exposed to higher doses, but intermittently, during preparation and application, while people living in sprayed homes experience more continuous and long-term exposure (Curtis and Lines 2000). Although the risks of indoor applications of DDT are not clear (Curtis and Lines 2000), the competing risk of malaria is certain and severe. Curtis and Lines (2000) argue that this conflict of interest is exacerbated by who is affected and those who would more clearly benefit from a ban tend to be from developed countries, and those who suffer the negative consequences are likely to be poor and marginalized. They tend to live in countries already limited in resources and infrastructure, unable to afford on their own to test alternatives in large field experiments. Smith (2000) makes the point that DDT might not be argued against so strongly if malaria was a developed country problem. These debates reflect differences in deeply held values and beliefs about how and when to act in the face of uncertainty to reduce risk. A precautionary and conservative approach adopts a preventive rather than reactive policy on issues where uncertainties are inherent in the risk assessment and there is potential for harm. If science reveals no harm from exposures, the policy can be flexible enough to accommodate change. Another position is based on the assertion that unproven dangers do not justify prevention, and the threshold of risk should be based on proof of harm, not speculation based on uncertainties. It is believed that unnecessary action could result in misallocation of limited resources and disincentives for the development of new and better technology. REFERENCES Carter, R., Mendis, K.N., 2002. Evolutionary and historical aspects of the burden of malaria. Clinical Microbiology Review 15, 564-594. Curtis, C.F. and J.D. Lines. 2000. Should DDT Be Banned By International Treaty? Parasitology Today 16: 119-21. Despommier, D., R.W. Gwadz, and P.J. Hotez. 1995. Parasitic Diseases. New York: Springer-Verlag. Gilles, H.M. and D.A. Warrell. 1993. Bruce-Chwat’'s Essential Malariology. New York: Oxford University Press. Hackett, L.W. 1937. Malaria in Europe. London: Oxford University Press. Hay, S.I. et al. 2004 “The global distribution and population at risk of malaria: past, present, and future.” The Lancet Infectious Diseases; 4: 327-336. Hayton, K., Su, X.Z., 2008. Drug resistance and genetic mapping in Plasmodium falciparum. Curr ent Genetics 54,223-239. Keusch G.T., Migasena P. 1982. Biological Implications of Polyparasitism. Reviews of Infectious Diseases; 4(4):880-882. Najera, J. and Hempel, J. 2000. The Burden of Malaria. Retrieved from Oct, 5, 2010 Rogan, W. J., Chen, A., et al. 2005. Health risks and benefits of bis (4-chlorophenyl) -1,1,1 trichloroethane (DDT). The Lancet; 366, 763-73. Snow, R. Guerra, C. Noor, A. Myint, H., Hay, S. 2005. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature, 434, 214-217 Greenwood, B. Bojang, K. Whitty, C. Targett, G. 2005. Malaria. The Lancet, 365, 1487-1498 Shelby, J.P., J. White, K. Ganesan, P.K. Rathod, and D. Chiu. 2003. A microfluidic model for single-cell capillary obstruction by Plasmodium falciparum-infected erythrocytes. PNAS. 100(25): p. 14618-14622. Sherman, I.W. 1998. Malaria: parasite biology, pathogenesis, and protection. ASM Press. Shepard, D.S., M.B. Ettling, U. Brinkmann, and R. Sauerborn. 1991. The Economic Cost of Malaria in Africa. Tropical Medicine and Parasitology 42, no. 3: 199-203 Smith, K. 2000. Environmental Health - For the Rich or For All? Bulletin of the World Health Organization 78, no. 9: 1156-7. White, N. and J.G. Breman. 1995. Malaria and Babesiosis. In Harrison’s Principles of Internal Medicine, ed. K..J. Isselbacher. New York: McGraw-Hill. WHO. 1997. Health and Environment in Sustainable Development. Geneva: WHO. World Health Organization. 2006. Guidelines for the treatment of malaria. In. Geneva: WHO Press. Retrieved from Read More