Malaria Mosquito Borne Infectious Disease Biology Essay

Malaria Mosquito Borne Infectious Disease Biology EssayMalaria is a mosquito-borne pathogenic disease of humans and other animals attemptd by spongers of the genus plasmodium. It begins with a bite from an infected womanish mosquito (more than 30 anopheline species), which introduces the parasite via its saliva into the circulatory system, and ultimately to the colored where they mature and reproduce. The disease causes symptoms that typically include fever, chills and headache, which in severe flakes disregard progress to coma or death. Malaria is widespread in tropical and subtropical regions in a broad band around the equator, including much of Sub Saharan Africa, asia and the Americas.There argon five species of parasites of the genus Plasmodium that affect humans and of which only 3 species be set in motion in India. These be Plasmodium malariae (Laveran, 1881), Plasmodium vivax (Grassi and Feletti, 1890), Plasmodium falciparum (Welch, 1897), Plasmodium ovale (Stephen s, 1922) and Plasmodium knowlesi (Robert Knowels, 1932). Malaria due to P. falciparum is the tight-fittingly deadly, and it predominates in Africa. P. vivax is slight dangerous entirely more widespread, and the other species atomic number 18 found much less frequently. P. knowlesi is the fifth major human malaria parasite (following the di imaging of plasmodium ovale into 2 species). This is an emerging transmittance system that was reported for the first time in humans in 1965 and it accounts for up to 70% of malaria cases in certain aras in South East Asia where it is mostly found. memoirMalaria has great impact on social and economic development of humans. Malaria was linked with poisonous vapours of swamps or stagnant weewee and named by the Italians in the eighteenth century as Malaria (from the Italian mala bad and aria air). In the fifth century B.C., the greek physician Hippocrates described the clinical manifestations and some of the complications of Malaria. The f irst major disc everyplacey in understanding the etiology of the disease was in 1880, when Laveran, a French army surgeon in Algeria, described exflagellated gametocytes of Plasmodium falciparum in a seraphic telephone circuit film from a patient with Malaria. It was only in 1897, that Ronald Ross, a British army surgeon in India, conclusively established the major features of the flavor round of plasmodia by a careful series of experiments in naturally infected sparrows.During the 20th Century, progress was do in vector control engine room and in 1955 potent synthetic compound called DDT was found and a eagle-eyed with other residual insecticides, the World Health Organization (WHO) launched a earthly concernwide computer program of malaria eradication. This ambitious program was hindered by the development of DDT resistance among vector and chloroquine resistance in some strains of Plasmodium falciparum. Soon it was accepted by the world that Malaria was here to stay and subsequently in 1978, the World health assembly changed its focus from eradication to control.EPIDEMIOLOGY OF MALARIAGlobal ScenarioBased on documented cases, the WHO estimates that there were 216 trillion cases of malaria in 2010 resulting in 655,000 deaths. This is equivalent to roughly 2000 deaths every day. A 2012 study estimated the number of documented and undocumented deaths in 2010 as 1.24 cardinal. An estimated 3.3 billion people were at risk of Malaria in 2010, although of all geographical regions, macrocosms living in Sub-Saharan Africa acquit the highest risk of acquiring Malaria in 2010, 81% of cases and 91% of deaths are estimated to have occurred in the WHO African region.The majority of cases (65%) occur in children under 15 years of age. Pregnant women are also especially vulnerable rough one hundred twenty-fivemillion pregnant women are at risk of infection for each one year. In Sub-Saharan Africa, maternal malaria is associated with up to 200,000 estimated infant deaths y azoic. There are about 10,000 malaria cases per year in Western Europe, and 1300-1500 in the United States. Both the global relative incidence of disease and resulting death rate has declined in recent years. According to the WHO, deaths attributable to malaria in 2010 were reduced by over a third from a 2000 estimate of 985,000, largely due to the widespread use of insecticide-treated nets and artemisinin- found combination therapies.Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa however, it is in Sub-Saharan Africa where 85-90% of malaria fatalities occur. As of 2010, about 106 countries have endemic malaria. both year, 125 million international travelers visit these countries, and more than 30,000 contract the disease. The geographic distribution of malaria inside large regions is complex, and malaria- smitten and malaria-free areas are often found close to each other. Malaria i s prevalent in tropical and subtropical regions because of rainfall, consistent high temperatures and high humidity, along with stagnant water supplys in which mosquito larvae readily mature, providing them with the environment they need for constant breeding.Regional ScenarioOut of the 11 countries of SEAR, 10 are malaria endemic. Maldives has no endogenous infection since 1984. SEAR accounts for 30% of global morbidity and 8% of global mortality due to malaria. An estimated 82.8% of the make out population is at risk and about 2.5 million cases are reported annually in the region. India contributes to more than three-fourths of the total cases in the South East Asian Region. Since 2004, there has been an increasing number of reports of the incidence of P. knowlesi among humans in various countries in South East Asia, including Malaysia, Thailand, Singapore, the Philippines, Vietnam, Myanmar and Indonesia.Country ScenarioMalaria transmission occurs in almost all areas of India except areas above 1800 meters sea level. Countrys 95% population lives in malaria risk prone areas and 80% of malaria reported in the ground is confined to areas consisting 20% of population i.e. residing in tribal, hilly, difficult and inaccessible areas. Directorate of National Vector Borne Disease pull wires Programme (NVBDCP) has framed technical guidelines/ policies and provides most of the resources for the programme.The case load, around 2 million cases annually in the late nineties, has shown a declining trend since 2002. At low levels of surveillance, the Slide Positivity Rate (SPR) may be a better indicator. The SPR has shown gradual decline from 3.32 in 1995 to 1.41 in 2010 (3). The reported Pf cases declined from 1.14 million in 1995 to 0.77 million cases in 2010. However, the Pf % has gradually increased from 39% in 1995 to 52.12% in 2010. Number of reported deaths has been leveling around 1000 per year.Currently, 80.5% of the population of India lives in malaria ri sk areas. Since 1970s, in India, areas with an API above 2 cases per 1000 population per year have been classified as high risk and thereby eligible for vector control. The current situation of Malaria in India is shown in figure of speech 6.1.Malaria in India is unevenly distributed with a risk of increase in cases in epidemic forms every 7-10 yrs expecting on the immune status of the population, breeding potential of the mosquitoes and the rainfall pattern. In North-East states efficient malaria transmission is maintained during most months of the year. Intermediate level of stability is maintained in the plains of India in the woodss and forest fringes, predominantly tribal settlements in 8 states (AP, Gujarat, Jharkhand, MP, Chattisgarh, Maharashtra, Orissa and Rajasthan).The largest number of cases in the country is reported in Orissa, followed by Chhattisgarh, West Bengal, Karnataka, Jharkhand, Madhya Pradesh, Uttar Pradesh, Assam, Gujarat and Rajasthan. The largest numbers of deaths are reported in Orissa, followed by West Bengal, Assam, Maharashtra, Meghalaya, Mizoram, Karnataka, Jharkhand and Madhya Pradesh Fig 6.2.Annually about 100 million fever cases are being screened by inception smears. There are 3.12 lakh Drug dispersal Centers, 1.17 lakh Fever Treatment Depots and 13 thousand Malaria Clinics functioning in the country.IMPORTANT TIMELINE1947 At the time of independence, malaria was responsible for an estimated 75 million cases and 0.8 million deaths annually.1953 National Malaria Control Programme was launched.1958 With its overwhelming success, GOI launched National Malaria Eradication Programme.1965-66 Due to concerted implementation of strategies, particularly spraying with DDT, the number of annual cases was successfully brought down to 100,000 and deaths were eliminated.1971 Since the resurgence of malaria in early 1970s, urban malaria has been recognised as an important problem contributing to overall malaria morbidity in the countr y. To assist the states in control of malaria in urban areas, Urban Malaria Scheme (UMS) was launched in 1971. The scheme is being implemented in 131 towns in the country. Urban malaria poses problems because of haphazard expansion of urban areas. The urban malaria vector, An. stephensi breeds in stored water and domestic obligateers. Construction activities and aggregation of labour provide ideal opportunities for vector to breed and transmit malaria in urban areas.1976 However, in the following years, the Programme face up various technical obstacles as well as financial and administrative constraints, which led to countrywide increase in malaria incidence to 6.47 million cases.1977 Modified syllabus of Operation (MPO) under NMEP was launched as a contingency plan to effectively control malaria by preventing deaths, reducing morbidity so as to improve the health status of the people. With the adoption of the MPO strategy, the total malaria cases decreased significantly. Present ly, about 2 million cases are being reported in the country annually, about half of which are P. falciparum cases.1982 The National Anti-malaria Drug Policy was drafted in 1982 to combat the increasing level of resistance to chloroquine detected in Pf.1997 The name of the programme was changed to National Anti Malaria Programme. enhance Malaria Control Project (EMCP) was launched in April 1997 with the assistance of the World Bank. This is directly benefiting the six crore Tribal Population of the eight peninsular states covering 100 districts and 19 urban areas.2003 National Vector Borne Diseases Control Programme was envisaged as an umbrella programme for prevention and control of Malaria and other vector borne diseases such as Filariasis, Dengue, Japanese encephalitis and Kala-azar.2008 the global malaria action plan (GMAP) was launched by the roll back malaria partnership (RBM) as a blueprint for the control, elimination and eventual eradication of malaria, setting as its objec tive the reduction of the number of preventable malaria deaths worldwide to near zero by 2015.2010 The year 2010 was an important milestone on the way to achievement of internationally agreed goals and targets for malaria Control. It was the date set by the World Health Assembly in 2005 to ensure reduction of the malaria encumbrance by at least 50% compared to the levels in 2000. The aim was to make indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINS) available to all people at risk of malaria, and for all public health facilities to be able to provide reliable diagnosis and effective give-and-take for malaria.2011 In the light of progress made by 2010, RBM updated the GMAP targets in June 2011. Maintaining an overall vision of a malaria-free world, the targets are now to (i) reduce global malaria deaths to near zero by end-2015, (ii) reduce global malaria cases by 75% from 2000 levels by end-2015, and (iii) eliminate malaria by end-2015 in 10 new countries si nce 2008, including in the WHO European Region. These targets will be met by achieving and sustaining universal access to and utilization of preventive measures achieving universal access to case management in the public and private sectors and in the areas where public health facilities are able to provide a parasitological test for all suspected malaria cases, near zero malaria deaths is defined as no more than 1 confirmed malaria death per 100,000 population at risk.SOCIOECONOMIC IMPACTMalaria affects everyday life of the afflicted persons and is one of the major causes of loss of income and absenteeism in schools. It is thus, directly linked with socio-economic development and referred to as both a disease of poverty and a cause of poverty. Economists intrust that malaria is responsible for a growth penalty of up to 1.3 percent per year in some African countries. When compounded over the years, this penalty leads to substantial differences in GDP between countries with and with out malaria and severely restrains the economic growth.The direct costs of malaria include a combination of personal and public expenditures on both prevention and treatment of the disease. The collateral costs of malaria include lost productivity or income associated with illness or premature death. Although difficult to express in financial terms, another indirect cost of malaria is the human suffering caused by the disease.J. A. Sinton estimated a loss of Rs.7, 500 million per year to the Indian economy on account of malaria in 1935. The Indian Institute of Management Ahmedabad reason that each rupee spent on the malaria programme since 1953-54 has brought in a benefit of Rs.9.27 to the nation. According to an estimate by MRC-ICMR, Delhi, in 1994, every rupee invested in malaria control produces a direct return of Rs. 22.10. The calculations do not include the hidden but large savings on account of the labour days, which is many times higher than that of the direct savings of a n individual. In terms of Disability Adjusted Life Years (DALYs), malaria in India contributes to 1.86 million years. Among the females, DALYs lost were 0.786 million as against 1.074 million in the males. The maximum DALYs lost (53.25%) were in the middle productive ages from 15 to 44 years followed by children 45 years of age.Transmission dynamics of malariaA large number of factors related to Agent, Host, Vector and Environment have a role in determining the transmission dynamics.Host factorsAge All ages are equally affected. Children are commonly effective carriers of gametocytes. In areas with high falciparum transmission, newborns will be protected during the first hardly a(prenominal) months of life due to maternal antibodies transferred to them through the placenta.Gender Gender does not affect the incidence or severity of malaria infection and disease per se, but because they are often related to frequency of exposure (via occupation, social behaviour, and migration).In nate Immunity whatever persons residing in highly malarious areas do not acquire infection. This may be due to innate immunity of the individual. Such immunity is mainly due to antibodies and T-lymphocytes specific for Plasmodium, which result in reduced illness despite infection.Blood aggroup There are other factors, which determine immunity against malaria. Genetic characteristics of the erythrocytes and presence of haemoglobinopathies usually confer some sort of protection against infection with malaria parasite. Individuals lacking in Duffy contrast group antigen are refractory to P.vivax infection. This points to the fact that Duffy coating on the erythrocyte wall may modify receptors in respect of P.vivax merozoites. Haemoglobin HbS sickle cell trait and Haemoglobin C have a protective effect against P.falciparum.Economic Status Economic status is inversely related to incidence of malaria mainly because of poor housing. Ill ventilated and poorly lighted houses provide i deal resting places for mosquitoes.Migration Large scale migration of population from one part of the country for sowing, transplant and harvesting of crops results in spread of malaria. Tropical aggregation of labour is associated with malaria. The labour migrating from malarious to non-malarious areas bring immune and non-immune population together coupled with local and imported parasite reservoir at the site of temporary camps. Focal outbreaks can be explosive in such situations. They also bring different strains of malaria parasite to the bulge out site including drug resistant strains.Environmental factorsWeather There are whileal variations in mosquito stringency, resting, feeding and biting habits, longevity and flight capabilities. Malaria is therefore, seasonal in most parts of the country. In most of the states the maximum transmission is during the period July to November.Temperature and Humidity Optimal conditions for malaria transmission occur when the temperatur e is between 20C and 30C and the mean relative humidity is at least 60%. Sporogony does not occur at temperatures below 16C or at temperatures higher than 33C. Water temperatures regulate the duration of the aquatic breeding cycle of the mosquito vector. A high relative humidity increases mosquito longevity and therefore increases the fortune that an infected mosquito will survive long enough to become infective. The forest cover of an area keeps humidity levels at high level resulting in long survival of all vector mosquitoes.Altitude Transmission decreases with increasing altitude and as a rule and it stops above the heights of 2000 m.Man made malaria Construction of roads, railways, irrigation works, dams and barrages, deforestation and other engineering projects have resulted in creation of mosquito breeding place in many new areas. The proximity of human abode to breeding sites directly influences vector human contact and, therefore, transmission. Agriculture and irrigation have an intricate role in malaria transmission. In areas where irrigation channels are not in good club maintained, high vector mosquito density is discovered. Temporary hutments in agriculture fields result in increased exposure to mosquitoes. Wells, overhead tanks, ornamental tanks, roof gutters, water storage containers, construction sites, room coolers, valve chambers etc. are important breeding places for A.stephensi. Use of disposable cups, bottles and other items, which can collect water, increase the risks of mosquito breeding. The slums within the town and its periphery are the worst affected areas because of lack of water management and appropriate anti-larval operations.Agent factorsGenus The disease is caused by the haemoparasites of genus Plasmodium, family Plasmodiidae, suborder Haemosporidiidae, order Coccidia.Life cycle The life cycle of the plasmodium occurs in two stages, the sexual cycle (sporogony) in the mosquitoes and asexual cycle (schizogony) in the huma n waiter. Within the vertebrate host, schizogony is found both within erythrocytes (erythrocytic schizogony) and in other wavers (exo erythrocytic schizogony). The development of asexual cycle in man, its duration and course of infection are determined by the transmissible composition of the malaria parasite.Sporozoites (microscopic, motile forms of malarial parasite) are released into personal credit line of the human host from the saliva of infected female mosquito when it bites him/ her. Within minutes, these attach to and invade liver cells by binding to hepatocyte receptor for the serum proteins thrombospondin and properdin. The sporozoites multiply in the hepatocytes and get released in batches from them in form of merozoites, which are the asexual, haploid forms.The human red birth cells contain sialic acid residues on the glycophorin molecules attached to their surface. The plasmodium merozoites attach to these sialic acid residues by a parasite lectin like molecule. I n the RBCs, the parasites grow in a membrane bound digestive vacuole, hydrolyzing hemoglobin through secreting enzymes. This stage is called the trophozoite and contains a single chromatin mass. The next stage is the schizont (erythrocytic schizont) with multiple chromatin masses, each of which develops into a voguish merozoite. The schizont forms after about 48 hr of intra-erythrocytic life (72 hr for P. malariae) and is characterized by consumption of almost all the hemoglobin and occupation of most of the RBC cavity.The RBC ruptures and a new batch of merozoite is released from it, which infects other RBCs. This cycle repeats itself till the host immune mechanisms come into play. Some schizonts mature into sexual forms called the gametocytes that infect the mosquitoes when they take their store meal.During the hepatic phase, a proportion of sporozoites do not devide but remain dormant for a period ranging from 3 weeks to a year longer onwards reproduction. These dormant forms are called hypnozoites and are the cause of relapses that occur in P. vivax and P. ovale.After being ingested in the blood meal of the biting female mosquito, the male and female gametocytes form a zygote in the insects gut wass. The resulting oocyst expands by asexual division until it bursts to release a myriad of motile sporozoites, which then migrate in the hemolymph to the salivary gland of the mosquito to await inoculation into other human at the next feeding episode.Parasite load The parasite load and the gametocyte production are influenced by development of immunity in human host. The difference in parasitaemia levels observed in P.vivax and P.falcipatum are attributed to the fact that P.vivax plys to invade younger RBCs charm the P.falciparum invades all RBCs irrespective of their age.Reservoir The source of infection is a malaria case with adequate number of mature viable gametocytes circulating in the blood. It has been estimated that in order to infect a mosquito, the blood of a human carrier must contain at least 12 gametocytes per mm3 and the number of female gametocytes must be more than the male gametocytes. The human case of malaria becomes infective to mosquito when mature, viable gametocytes develop in the blood of the patient in suitable density.Bionomics of malaria vectorsThere are many species of anopheline mosquitoes in India but only 6 are regarded as primary vectors and another 3 or 4 as substitute(prenominal) or local vectors. The following characteristics of vector mosquitoes play an important role in the epidemiology of malaria.Breeding Habits The breeding habits of mosquitoes show a lot of variation. Hence, vector mosquitoes tend to be confined to certain geographical areas only. genus Anopheles sundaicus prefers to breed in brackish waters. The main urban vector Anopheles stephensi commonly breeds in wells, cisterns and over head tanks. Tanks, pools, burrow pits and ditches are the preferred breeding spots for Anopheles a nnularis and Anopheles philippinensis while Anopheles dirus is usually found breeding in forest pools, streams and slit trenches. A.culicifacies is the major vector of rural malaria. It breeds in different ground water collections. During the rainy season, breeding places are numerous. Hence the density is at its height in the rainy season. The other major vectors are A.minimus and A.fluviatilis. They breed in running channels with clear water. Therefore the densities reach the peak after the monsoon season when streams and channels have slow moving clear water.Density For effective transmission of malaria in a locality, the mosquito vector must attain and maintain a certain density. This is called critical density and it varies from one mosquito to another and also under different environmental conditions. Anopheles culicifacies needs a very high density for transmission of malaria.Longevity A mosquito, after an infective blood meal, must live for at least 10 days to complete th e development of malaria parasites.Tropism Some mosquitoes like Anopheles fluviatilis, Anopheles minimus prefer human blood and are called anthropophilic. Others like Anopheles culicifacies preferably feed on animal blood and are called zoophilic. When the densities are high or when the man cattle ratio is higher, they feed on humans too. This preferential feeding habit is called tropism. It has obvious bearing on the transmission of malaria.Biting and resting behaviour Some vector mosquitoes bite at or soon after dusk, others either during late night or early hours of the morning. However, some species may be lively at two different periods during the same night. Control strategies should consider such habits of mosquitoes. Use of impregnated bed nets would definitely be more effective when there are late biters in that area. A female mosquito rests either indoors (endophilic) or outdoors (exophilic) after a blood meal for maturation of its eggs. The common resting places are ei ther human dwellings, cattle sheds or mixed dwellings.Flight Range The distribution and dispersal of vector species depend upon their flight range. This is important for tracing the source and planning control measures. Some have a short flight range e.g. Anopheles dirus, Anopheles annularis and Anopheles fluviatilis. The species with flight range upto Two km distance are Anopheles culicifacies and Anopheles stephensi. Anopheles sundaicus may fly upto 8 or 10 km. personal manner OF TRANSMISSIONThe most prevalent mode of Transmission of malaria is through the bite of the infected Female anopheles mosquito. The mosquito is infective only if the sporozoites are present in its salivary glands. However, malaria can also be transmitted by intravenous or intramuscular Injection of infected blood or plasma in an otherwise healthy person. The parasite can stay alive for nearly two weeks at 4c in bottled blood. Rarely transmission can also occur from Infected mother to the newborn.Malaria S URVEILLANCEMalaria surveillance connotes the maintenance of an on-going watch/ vigil over the status of malaria in a group or community. The main purpose of surveillance is to detect changes in trends or distribution in malaria in order to initiate investigative or control measures.1. biweekly Domiciliary visitsThe active case detection is carried out by multipurpose health workers (male) under primary health care system by conducting active case detection every fortnight by making domiciliary visits. Technical justification for a fortnightly blood smear collection is based on transmission dynamics of malaria. The incubation interval in case of P.vivax is approximately 22 days while for P.falciparum it is 35 days. Thus, surveillance cycle of less than one incubation interval will catch most of the secondary cases before the commencement of next cycle.2. Fever Treatment Depots (FTDs)Fever Treatment Depots are established in remote villages. The FTD holder is given training for one o r two days at the PHC in the collection of blood smears, political science of presumptive treatment, impregnation of bed nets, promotion of larvivorous fish, etc.3. Passive Case Detection (PCD)All Allopathic, Ayurvedic, Homeopathic, Siddha medicine dispensaries in the health sector are place and involved in passive case detection. All the fever cases attending the hospital should be screened for malaria and given presumptive treatment.4. Rapid Fever SurveyIn case of an epidemic outbreak, every house of the village in the suspected epidemic zone is visited and all fever cases are screened by taking blood smears.5. Mass surveyAs an alternative to Rapid Fever Survey, if possible mass survey of the entire population may be carried out in the suspected epidemic zone. Here all the population irrespective of age, sex or fever status is screened by taking blood smear.6. Drug Distribution Centre (DDC)If it is not possible to have FTD, the medical officer should establish DDC. The functions of DDCs are the same as those of FTDs, except that the DDCs do not take blood slides but administer drugs to fever cases.7. Annual blood smears examination rate and its validityAll fever cases occurring in the community are examined for malaria parasite, and then the total malaria parasite load is examined. The monthly blood examination rate (MBER) norms are 0.8 percent during non-transmission season and 1.2 to 1.8 percent during transmission season were laid down in the Indian Malaria Eradication Programme.ABER = No. of blood smears sedate during the year x 100Population covered under surveillanceMBER = No. of blood smears collected during the month x 100Population covered under surveillanceABER/ MBER is an index of operational efficacy of the programme. The Annual Parasite Incidence (API) depends upon the ABER. A sufficient number of blood slides should be systematically obtained and examined for malaria parasite to work out accurate API.8. Slide Positivity Rate (SPR)The Slide P ositivity Rate among the blood smears collected through both active and passive surveillance gives more accurate information on distribution of malaria infection in the community over a period of time. Trends in SPR can be use for predicting epidemic situations in the area. If monthly SPR exceeds by 2 times of the standard deviation observed in SPR of the preceding 3 years or preceding 3 months of the same year, an epidemic build up in the area can be suspected.SPR No. of blood smears found positive for malaria parasite X 100No. of blood smears examined9. Annual Parasite Incidence (API)This parameter measures the incidence of malaria. It is calculated asAPI = No. blood smears found positive for malaria parasite x 1000Total population under surveillanceAPI can be utilized for assessing the malaria endemicity in the area and impact of control operations. The level of API determines whether spray should be taken up in any area. In only those areas with API more than 2, continual ro unds of spray would be planned. API calcualtes incidence of malaria and based on this, areas are divided into high low risk zones.10. P. falciparum PercentageThis is calculated asP.f % = No. blood smears found positive for P.falciparum x 100 No. blood smears found positive for malaria parasitePf % is required to find out prevalence of P.falciparum infection, which can cause severe manifestations of malaria including death.PATHOPHYSIOLOGYP.vivax, P. ovale and P. malariae cause low level parasitemia, mild anaemia and in rare instances, splenic rupture and nephritic syndrome. P. Falciparum on the other hand usually cause high levels of parasitemis, severe anaemia, cerebral symptoms, renal failure, pulmonary edema and even death. Pathophysiology of malaria results from destruction of erythrocytes, the liberation of parasite and erythrocyte (Cytokines, Nitric Oxide etc) material into the circulation, and the host reaction to these events. P. falciparum malaria differs from the other hum an species of malaria parasite because infected erythrocytes also sequester in the microcirculation of vital organs, interfering with micro circulatory flow and host tissue metabolism, which results in severe organ damage.The P. falciparums greater pathogenicity is due to the following reasons(a) It is able to infect red cells of any age and maturity, leading to high parasite burden and profound anaemia. (compared to that caused by other species which infect only the young or very old RBCs)(b) P. falciparum causes infected RBCs to clump together (forming rosettes) and to stick to the vascular endothelium (sequestration) closure the blood flow. Ischemia due to poor perfusi