Malaria

life cycle

(i) Asexual cycle: The asexual cycle begins when an infected mosquito bites a person and injects sporozoites. A considerable amount of new knowledge about the parasite's life cycle has become available in recent years, concerning almost all phases of the cycle (7). A brief description is as follows four phases are described in the human cycle: (a) HEPATIC PHASE: The sporozoites disappear within 60 minutes from the peripheral circulation (8). Many of them are destroyed by phagocytes, but some reach the liver cells. After 1-2 weeks of development (depending upon the species), they become hepatic schizonts, which eventually burst releasing a shower of merozoites. The number of merozoites produced from a single sporozoite varies considerably with the infecting species. A single P. falciparum sporozoite may form as many as 40,000 merozoites, whereas sporozoites from other species of plasmodia produce only 2,000 to 15,000 merozoites (8). In the case of P. falciparum, the intrahepatic schizonts rupture almost simultaneously and there is no persistent tissue phase (the so-called exo-erythrocytic phase). On the contrary, the intrahepatic schizonts of the other plasmodia do not burst all at the same time. Some hepatic forms persist and remain dormant in the hepatocytes for considerable periods before they begin to grow and undergo pre-erythrocytic schizogony, thus liberating merozoites into the blood stream causing relapses of these infections. P. vivax and P. ovale may continue to relapse for 2 to 3 years and P. malariae may persist for 10 to 20 years or more. Once the parasites enter the RBC, they do not reinvade the liver. (b) ERYTHROCYTIC PHASE: Many of the merozoites are quickly destroyed, but a significant number attach to specific receptor sites on the RBC. The merozoites then penetrate the RBC and pass through the stages of trophozoite and schizont. The erythrocytic phase ends with the liberation of merozoites, which infect fresh red blood cells. The cycle is repeated over and over again until it is slowed down by the immune response of the host (9). The duration of the erythrocytic cycle is constant for each species of malaria parasite- 48 hours for P. fa/ciparum, P. vivax and P. ovale; and 72 hours for P. malariae. (c) GAMETOGENY: In all species of malaria some erythrocytic forms do not divide but become male and female gametocytes. These are the sexual forms of the parasite which are infective to mosquito. (ii) Sexual cycle: The mosquito cycle (sporogony) begins when gametocytes are ingested by the vector mosquito when feeding on an infected person. The gametocytes continue further development in the mosquito. The first event to take place in the stomach of the mosquito is exflagellation of the male gametocyte; 4-8 thread-like filaments called "micro-gametes" are developed. The female gametocyte undergoes a process of maturation and becomes a female gamete or "macrogamete". By a process of chemotaxis, microgametes are attracted towards the female gamete, and one of which (microgamete) causes fertilization of the female gamete. The resulting zygote is at first a motionless body, but within 18-24 hours, it becomes motile. This is known as Ookinete, which penetrates the stomach wall of the mosquito and develops into an oocyst on the outer surface of the stomach. The oocyst grows rapidly and develops within it numerous sporozoites. When mature, the oocyst bursts and liberates sporozoites into the body cavity of mosquito. Many of the sporozoites migrate to the salivary glands of the mosquito, and the mosquito now becomes infective to man. The period of time required for the development of the parasite from the gametocyte to sporozoite stage in the body of the mosquito is about 10-20 days depending upon favourable conditions of atmospheric temperature and humidity. This period is also referred to as the "extrinsic incubation period".

(a) VECTOR TRANSMISSION

: Malaria is transmitted by the bite of certain species of infected, female, anopheline mosquitoes. A single infected vector, during her life time, may infect several persons. The mosquito is not infective unless the sporozoites are present in its salivary glands. (b) DIRECT TRANSMISSION: Malaria may be induced accidentally by hypodermic intramuscular and intravenous injections of blood or plasma, e.g., blood transfusion, malaria in drug addicts (16, 17). Blood transfusion poses a problem because the parasites keep their infective activity for at least 14 days in blood bottles stored at 4 deg.C (16). Persons who have lived in an endemic area (including those who have been taking antimalarials prophylactically) and anyone who has had malaria should not be accepted as blood donor until 3 years afterwards (18). (c) CONGENITAL MALARIA: Congenital infection of the newborn from an infected mother may also occur, but it is comparatively rare.

VECTOR INDICES

A malaria survey is not complete unless it includes investigations relating to the insect vector. Some of the important vector indices are: (a) HUMAN BLOOD INDEX : It is the proportion of freshly-fed female Anopheline mosquitoes whose stomach contains human blood. It indicates the degree of anthrophilism. (b) SPOROZOITE RATE : It is the percentage of female anophelines with sporozoites in their salivary glands. ( c) MOSQUITO DENSITY: It is usually expressed as the numberof mosquitoes per man-hour-catch. (d) MAN-BITING RATE (Biting density) : It is defined as the average incidence of anopheline bites per day per person. It is determined by standardized vector catches on human bait (e) INOCULATION RATE: The man-biting rate multiplied by the infective sporozoite rate is called the inoculation rate. All these rates are employed in the quantitative assessment of malaria and in building up a composite epidemiological picture of malaria.

important definition

Malaria control : reducing the malaria disease burden to a level at which it is no longer a public health problem. Malaria elimination : the interruption of local mosquitoborne malaria transmission; reduction to 'zero' of the incidence of infection caused by human malaria parasites in a defined geographical area as a result of deliberate efforts; continued measures to prevent re-establishment of transmission are required. Certification of malaria elimination : can be granted by WHO after it has been proven beyond reasonable doubt that the chain of local human maiaria transmission by Anopheles mosquitoes has been fully interrupted in an entire country for at least 3 consecutive years. Malaria eradication : permanent reduction to 'zero' of the worldwide incidence of infection caused by a specific agent; applies to a particular malaria parasite species. Intervention measures are no longer needed once eradication has been achieved.

definition

Malaria in man is caused· by four distinct species of the malaria parasite - P. vivax, P. falciparum, P. malariae and P. ovale. Plasmodium vivax has the widest geographic distribution throughout the world. In India, about 50 per cent of the infections are reported to be due to P. falciparum and 4-8 per cent due to mixed infection and rest due to P. vivax. P. malariae has a restricted distribution and is said to be responsible for less than 1 per cent of the infections in India. The largest focus of P. malariae in India is reported to be in Tumkur and Hassan districts in Karnataka. P. ovale is a very rare parasite of man, mostly confined to tropical Africa. It has also been reported in Vietnam. The severity of malaria is related to the species of the parasite.

Definition

Malaria is a protozoa! disease caused by infection with parasites of the genus Plasmodium and transmitted to man by certain species of infected female Anopheline mosquito. A typical attack comprises three ·distinct stages : cold stage, hot stage and sweating stage. The clinical features of malaria vary from mild to severe, and complicated, according to the species of parasite present, the patient's state of immunity, the intensity of the infection and also the presence of concomitant conditions such as malnutrition or other diseases. The febrile paroxysms occur with definite intermittent periodicity repeating every third or fourth day depending upon the species of the parasite involved.

Agent

Out of about 45 species of anopheline mosquitoes in India, only a few are regarded as the vectors of primary importance. These are: An. culicifacies, An. fluviatilis, An. stephensi, An. mm1mus, An. philippinensis, An. sundaicus, and An. maculatus. The vectors of major importance are An culicifacies in rural areas and An. stephensi in urban areas. In the absence of a vaccine, vector control is the only practical approach to malaria control. A knowledge of anopheline biology is essential for understanding the epidemiology of malaria and its prevention. The main factors which determine the vectorial importance of mosquitoes are: (a) DENSITY : To be an effective vector, a species must be present in adequate density in or near human habitations. A sudden increase in density of vectors, may be a cause of epidemic outbreaks .. For each vector, there is what is known as "critical density" below which effective transmission cannot be maintained in a community. This level varies with different species. In the case of An. culicifacies a high density is required for the propagation of malaria; in the case of An. fluviatilis which is very efficient vector, a much lower density would suffice. (b) LIFE SPAN: The key factor in the transmission of malaria is the life span of the vector. The vector mosquito must live for at least 10-12 days after an infective blood meal to become infective. The strategy in malaria eradication is to shorten the life span of mosquitoes to less than 10 days by insecticides. (c) CHOICE OF HOST : Some mosquitoes prefer human blood, some animal blood, and some show great variation in their feeding habits. The percentage of EPIDEMIOLOGY OF COMMUNICABLE DISEASES human blood feeds in the case of An. culicifacies, an important vector in India, has been found to vary from 2-80 per cent (8). In contrast, An. fluviatilis is a highly anthrophilic species. The anthrophilic species, i.e., those that have a high preference for human blood are better vectors of malaria than zoophilic species. (d) RESTING HABITS : After a blood meal, some mosquitoes rest indoors on the walls for quite sometime. This behaviour pattern is known as "endophily". But there are some species which rest outdoors (exophily). A knowledge of the resting habits (which must be under constant surveillance) is the basis for organizing rational anti-adult measures. In fact, the concept of malaria eradication is based on endophilism (indoor resting habits) of most malarial vectors. (e) BREEDING HABITS: The breeding habits of mosquitoes vary considerably. Some breed in moving water (An. fluviatilis), some in brackish water (An. sundaicus) and some in wells, cisterns, fountains and overhead tanks (An. stephensi). A knowledge of the breeding habits is required for conducting anti-larval operations. (f) TIME OF BITING : The majority of Indian mosquitoes bite at night excepting the Aedes mosquitoes. Anophiline mosquitoes have nocturnal feeding habits, between dusk and dawn. (g) VECTORIAL CAPACITY : The term vectorial capacity refers to the combined effect of the density of the vector population, its susceptibility to infection, life span and probability of feeding on man. It is distinct from physiological capacity to transmit infection. (h) RESISTANCE TO INSECTICIDES: A knowledge of the status of vector resistance to insecticides is also necessary. On this depends the choice of insecticides to be used. When an insect vector is resistant to

Eradication of Malaria

PRE-ERADICATION ERA In the pre-eradication era, the magnitude of the malaria problem in a country used to be determined mostly from the reports of the clinically diagnosed malaria cases. The classical malariometric measures are spleen rate, average enlarged spleen, parasite rate etc. In a control programme, the case detection machinery is weak. Therefore, the classical malariometric measures may provide the needed information, i.e. the trend of the disease. (a) SPLEEN RATE : It is defined as the percentage of children between 2 and 10 years of age showing enlargement of spleen. Adults are excluded from spleen surveys, because causes other than malaria frequently operate in causing splenic enlargement in them. The spleen rate is widely used for measuring the endemicity of malaria in a community. (b) AVERAGE ENLARGED SPLEEN: This is a further refinement of spleen rate, denoting the average size of the enlarged spleen (22). It is a useful malariometric index. (c) PARASITE RATE : It is defined as the percentage of children between the ages 2 and 10 years showing malaria parasites in their blood films. (d) PARASITE DENSITY INDEX : It indicates the average degree of parasitaemia in a sample of well-defined group of the population. Only the positive slides are included in the denominator (8). (e) INFANT PARASITE RATE : It is defined as the percentage of infants below the age of one year showing malaria parasites in their blood films. It is regarded as the most sensitive index of recent transmission of malaria in a locality. If the infant parasite rate is zero for 3 consecutive years in a locality, it is regarded as absence of malaria transmission even though, the Anopheline vectors responsible for previous transmission may remain. (f) PROPORTIONAL CASE RATE : Since the morbidity rate is difficult to determine, except in conditions when the diagnosis and reporting of each case is carried to perfection, proportional case rate is used (8). It is defined as the number of cases diagnosed as clinical malaria for every 100 patients attending the hospitals and dispensaries. This is. a crude index because the cases are not related to their time/ space distribution. ERADICATION ERA (current incidence levels) During the eradication era, the microscopic diagnosis of malaria cases became the main method of diagnosis. The parameters used for the measurement of malaria were mostly parasitological in nature; the commonly used parameters were API, ABER, SPR and SFR. The same parameters are being used at the present time. These parameters are unlikely to reveal the true epidemiological picture, unless the case detection machinery is fully supervised and very efficient. The following parameters are in use at present : a. Annual parasite incidence (API) b. Annual blood examination rate (ABER) c. Annual falciparum incidence (AFI) d. Slide positivity rate (SPR) e. Slide falciparum rate (SFR). a. Annual parasite incidence (API) API is given by the formula : Confirmed cases during one year API ~~~~~~~~~~~~xlOOO Population under surveillance API is a sophisticated measure of malaria incidence in a community. It is based on intensive active and passive surveillance, and cases are confirmed by blood examination. Areas with API :?: 2 per 1000 population per year have been classified as high risk areas in India, and thereby eligible for vector control. b. Annual blood examination rate (ABER) ABER is given by the formula: ABER Number of slides examined Population x 100 ABER is an index of operational efficiency. The annual parasite incidence (API) depends upon the annual blood collection and examination rates. A sufficient number of blood slides must be systematically obtained and examined for malaria parasite to work out accurately annual parasite incidence (API). At present, about 100 million fever cases are screened every year in India. The aim is to screen 10 per cent of the population even though the disease transmission is expected to reduce. The surveillan

diagnosis

The diagnosis of malaria depends on demonstration of the parasite in the blood. Suspicion of the diagnosis is aroused by epidemiological and clinical evidence. 1. Microscopy Two types of blood films are useful in searching for and identification of malaria parasite. The "thin film" and the "thick film". It is recommended that both types of film be prepared on a single microscope glass slide. The thick film is more reliable in searching for parasite, as large volume of blood is examined under each microscope field. When scanty, parasite may be found about 20 times more rapidly in thick slide than in thin slide. The thin slide is more valuable for identifying the species of the parasite present. In . it they are seen more clearly. The advantage of microscopy are : The sensitivity is high. It is possible to detect malarial parasite at low densities. It also helps to quantify the parasite load; It is possible to distinguish the various species of malaria parasite and their different stages. 2. Serological test The malarial fluorescent antibody test usually becomes positive two weeks or more after primary infection, by which time the infection may have been cured. A positive test is therefore, not necessarily an indication of current infection. The test is of the greatest value in epidemiological studies and in determining whether a person has had malaria in the past (20). 3. Rapid diagnostic test (RDT) Rapid Diagnostic Tests are based on the detection of circulating parasite antigens with a simple dipstick format. Several types of RDTs are available. Some of them can only detect P. falciparum while others can detect other parasites also. The latter kits are expensive and temperature sensitive. RDTs are produced by different companies, so there may be differences in the contents and in the manner in which the test is done. The users manual should always be read properly to avoid false negative results (21).

about parasite

The malaria parasite undergoes 2 cycles of development the human cycle (asexual cycle) and the mosquito cycle (sexual cycle). Man is the intermediate host and mosquito the definitive host (Fig. 1).

clinical features

The primary fever is marked by paroxysms which correspond to the development of the parasites in the red blood cells. The peaks of the fever coincide with the release into the blood stream of successive broods of merozites. The typical attack comprises three distinct stages, i.e., the cold stage, the hot stage and the sweating stage. These are followed by an afebrile period in which the patient feels greately relieved. COLD STAGE : The onset is with lassitude, headache, nausea and chilly sensation followed in an hour or so by rigors. The temperature rises rapidly to 39-41°C. Headache is often severe and commonly there is vomiting. In early part of this stage, skin feels cold; later it becomes hot. Parasites are usually demonstrable in the blood. The pulse is rapid and may be weak. This stage lasts for 1/4-1 hour. HOT STAGE : The patient feels burning hot and casts off his clothes. The skin is hot and dry to touch. Headache is intense but nausea commonly diminishes. The pulse is full and respiration rapid. This stage lasts for 2 to 6 hours. SWEATING STAGE : Fever comes down with profuse sweating. The temperature drops rapidly to normal and skin is cool and moist. The pulse rate becomes slower, patient feels relieved and often falls asleep. This stage lasts for 2-4 hours. The febrile paroxysms occur with definite intermittent periodicity repeating every third or fourth day depending upon the species of the parasite involved. The classical 3 stages (cold, hot and sweating) may not always be observed due to maturation of generations of parasite at different times. Periods of latency may last several weeks or months (8, 19). The disease has a tendency to relapse and is characterized by enlargement of the spleen and secondary anaemia. Febrile herpes is common in all malarial patients. In patients with P. falciparum infection the primary fever in its first few days is usually irregular or even continuous and then the classical 48 hour periodicity becomes established or the fever may continue to be irregular and the hot and cold stages, so typical of other malarial infections are less clearly separated from one another. In persons with poor immunity the paroxysms are associated with marked prostration. Headache, nausea and vomiting are usually more severe, and there is greater tendency towards the development of delirium, haemolytic jaundice and anaemia. The mortality is much greater than in other forms of malaria. With P. vivax infection, symptoms are same but are usually milder and more regularly divided into "hot" and "cold" stages than in P. falciparum infections. P. ovale infections differ little from that of P. · vivax. However, they tend to be milder than P. uiuax and cease after a few paroxysms even if no treatment is given. Clinically, P. malariae attacks resemble those of P. vivax but the cycle is of 72 hours instead of 48 hours. The tendency for long-term relapses to occur is marked. The complications of P. falciparum malaria are cerebral malaria, acute renal failure, liver damage, gastro-intestinal symptoms, dehydration, collapse, anaemia, blackwater fever etc. The complications of P. uivax, P. ovale and P. malariae infections are anaemia, splenomegaly, enlargement of liver, herpes, renal complications etc.

Border malaria

These are the high malaria transmission belts along the international borders and state borders. These areas have their own problems in regard to malaria control becaμse of mixing of population and poor administrative control.

incubation period

This is the length of time between the infective mosquito bite and the first appearance of clinical signs of which fever is most common. This period is usually not less than 10 days. The duration of the incubation period varies with the species of the parasite, and in natural infections (in mosquito-transmitted malaria) this is 12 (9-14) days for falciparum malaria, 14 (8-17) days for vivax malaria, _28 (18-40) days for quartan malaria and 17 (16-18) days for ovale malaria. With some strains of P. vivax, the incubation period may be delayed for as long as 9 months; this may also occur with other species in persons who have been taking suppressive antimalarial drugs (8).