MALARIA

An Introduction

Malaria since its fatal disease,is the most difficult of all to encouneter.Because of the habit of increasing resistance to the insecticides ,of the female anopheline species.Its  highly endemic in nature and is charecerised by imminent dangers and complications.Its turning into a growing hazard in the developing countries.Being a common communicable disease with increased morbidity and mortality,it’s the focus of concern and included in the IDSP diseases as well.

 Problem statement

  • Internationally: Malaria is a major health problem in Africa, Asia, Central America, Oceania, and South America. About 40% of the world's population lives in areas where malaria is common. Approximately 300-500 million cases of malaria occur every year, and 1-2 million deaths occur, most of them in young children.

  • Nationally:Among all the states Chennai is the most endemic,for the disease.About 1000 cases are recorded per year in the country.40% of all the cases end up in mortality.

Host Factors

Race: People of all races are affected, with some exceptions. People of West African origin who do not have the Duffy blood group are not susceptible to P vivax malaria.

Sex: Malaria affects females and males equally.

Age: Children of all ages living in nonmalarious areas are equally susceptible to malaria. In endemic areas, children younger than 5 years have repeated and often serious attacks of malaria. The survivors develop partial immunity. Thus, older children and adults often have asymptomatic parasitemia, ie, presence of plasmodia in the bloodstream without clinical manifestations of malaria. Most deaths resulting from malaria occur in children younger than 5 years. 

Agent

  • Malaria is caused by Plasmodium species, which are protozoal blood parasites. Four species can infect humans.

    • P vivax

    • P falciparum

    • P malariae

    • P ovale

  • Most malaria acquired in Africa is due to P falciparum. P vivax dominates in Asia and the Americas.

  • Transmission of malaria

    • The bite of an infected female Anopheles mosquito transmits malaria. Species of mosquito capable of transmitting malaria are found in all 48 of the contiguous states of the United States.

    • Malaria can be transmitted through blood transfusion. Among people living in malarious areas, semi-immunity to malaria allows donors to have parasitemia without any fever or other clinical manifestations. The malaria transmitted is by the merozoites, which do not enter the liver cells. Because the liver stage is not present, curing the acute attack results in complete cure.

    • Organ transplantation may transmit malaria.

    • Transplacental malaria (ie, congenital malaria) can be significant in populations who are semi-immune to malaria. The mother may have placental parasitemia, peripheral parasitemia, or both, without any fever or other clinical manifestations. Vertical transmission of this infestation may be as high as 40% and is associated with anemia in the baby.


Aetiopathogenesis

The bite of an infected mosquito introduces asexual forms of the parasite, called sporozoites, into the bloodstream. Sporozoites enter the hepatocytes and form schizonts, which are also asexual forms. Schizonts undergo a process of maturation and multiplication known as preerythrocytic or hepatic schizogony. In Plasmodium vivax and Plasmodium ovale infection, some sporozoites convert to dormant forms called hypnozoites, which can cause disease after months or years.

Preerythrocytic schizogony takes 6-16 days, and results in the host cell bursting and releasing thousands of merozoites into the blood. Merozoites enter the erythrocytes and initiate another asexual reproductive cycle, known as erythrocytic schizogony. The parasite passes successively through the stages of trophozoite and schizont, ultimately giving rise to several merozoites. On maturation of these merozoites, the erythrocyte ruptures, releasing the merozoites and multiple antigenic and pyrogenic substances into the bloodstream. These merozoites again infect new erythrocytes. After a few cycles of this erythrocytic schizogony, some merozoites differentiate into the sexual forms: the male and female gametocytes. A mosquito that takes a blood meal from a patient with gametocytemia acquires these sexual forms and plays host to the sexual stage of the plasmodial life cycle.

Rupture of a large number of erythrocytes at the same time releases a large amount of pyrogens, which causes the paroxysms of malarial fever. The periodicity of malarial fever depends on the time required for the erythrocytic cycle and is definite for each species. Plasmodium malariae needs 72 hours for each cycle, leading to the name quartan malaria. The other 3 species each take 48 hours for one cycle and cause fever on alternate days (tertian malaria). However, this periodicity requires all the parasites to be developing and releasing simultaneously; if this synchronization is absent, periodicity is not observed.

Clinical Features

Young children manifest this disease in many different ways, but the classic picture of malaria, with periodic fever, shivering, and sweating, is not observed. Malaria can mimic any febrile illness and should be suspected in any febrile child who has been in a malarious area recently. Older children may manifest the classic periodicity of fever with chills and shivering.

  • Prodrome: After the mosquito bite, children are asymptomatic while the parasites complete the liver cycle and one erythrocytic cycle, which takes 8-18 days, depending on the species. Children then become restless, drowsy, apathetic, and anorexic. Older children may report aching body, headache, and nausea.

  • Fever: Fever is usually continuous and may be very high (40°C) from the first day.

  • Respiratory symptoms: Many children have only flu-like respiratory symptoms at presentation, with mild cough and cold. These symptoms abate in 1-2 days, with or without treatment.

  • Gastrointestinal symptoms: Vomiting is very common in children with malaria, and it may make oral therapy ineffective. Mild diarrhea is often observed, with dark green mucoid stools. Occasionally, profuse diarrhea with dehydration and circulatory failure is observed.

  • Febrile convulsions: Seizures are common and may occur at the onset of the disease, even before high fever has set in. Differentiating postictal impairment of consciousness from cerebral malaria is often difficult.

  • Congenital malaria: Parasitemia in neonates within 7 days of birth implies transplacental transmission. This congenital malaria is usually associated with placental parasitemia, which sometimes persists even after adequate treatment with antimalarial drugs. Babies have fever, are irritable, refuse feeds, and often develop anemia, jaundice, and hepatosplenomegaly.

  • Malaria in immune children: Children living in an area where malaria is endemic have repeated frequent infections and develop and maintain partial immunity. These children often develop only a low-grade fever, anemia, poor appetite, and malaise. Tiredness, restlessness, cough, and diarrhea are other symptoms that may occur.

  • Relapses and recrudescences: Depending on the species of Plasmodium involved, relapses and recrudescences vary in their effects. P vivax and P ovale both give rise to hypnozoites in the liver. P vivax malaria may relapse for up to 3 years and P ovale for 1-1.5 years. P falciparum and P malariae do not form hypnozoites, so they do not have true relapses. However, the disease recrudesces because of surviving erythrocytic forms. While P falciparum can recrudesce for up to 1 year, P malariae may continue to cause clinical malarial attacks even 20 years after the original infection. Only the sporozoites (introduced by the mosquitoes themselves) can penetrate the liver cells. Thus, if malaria is acquired by blood transfusion or transplacentally, no infection of the liver occurs and relapses do not occur.

Physical:

  • Fever: Fever can be very high from the first day. Temperatures of 40°C and higher are often observed. Fever is usually continuous or irregular. Classic periodicity may be established after some days.

  • Hepatomegaly: The liver may be slightly tender.

  • Splenomegaly: Splenomegaly takes many days, especially in the first attack in nonimmune children. In children from an endemic area, huge splenomegaly sometimes occurs.

  • Anemia: Prolonged malaria can cause anemia, and malarial anemia causes significant mortality.

  • Jaundice: With heavy parasitemia and large-scale destruction of erythrocytes, mild jaundice may occur.

  • Dehydration: High fever, poor oral intake, and vomiting all contribute to dehydration.

Lab Studies:

  • Examination of blood smear

    • Demonstration of the parasite in a smear of the blood definitely establishes the presence of malaria.

    • A negative finding on examination does not rule out malaria. Only 50% of children with malaria are smear positive, even on repeated examination.

    • A positive finding on examination does not confirm malaria, especially in patients from an endemic area, in whom asymptomatic parasitemia often exists.

    • Both thick and thin films are essential. If the parasitemia is light, a thin film examination may miss the diagnosis. Thick films save time in diagnosis of scanty infections but make species identification of the parasite difficult.

    • At least 100-200 fields of a thick film should be scrutinized before a slide is reported as negative for malaria. In doubtful cases, the examination can be repeated after 4 hours.

    • Various techniques to enhance the diagnostic utility of the peripheral blood smear examination are in use. Fluorescent staining and microscopy, centrifugation, selective magnetic separation techniques, and other techniques have been used but have only a moderate effect.

  • Serological tests

    • Serological tests provide confirmation of past malaria in patients and are valuable for epidemiological studies. These tests are also useful for screening donated blood and diagnosing hyperactive malarial splenomegaly. Among the tests used are the indirect fluorescent antibody test (IFAT), indirect hemagglutination antibody (IHA) test, enzyme-linked immunosorbent assay (ELISA), and the immuno-chromatographic test (ICT) for filariasis.

    • All these tests produce positive results several days after malaria parasites appear in the blood and so do not help in the diagnosis of the acute infection for treatment purposes.

  • Dipstick tests

    • This is now commercially available as the Parasite F dipstick. It is based on the detection of P falciparum histidine-rich protein-2 (PfHRP-2) antigen, which is specific for P falciparum and so does not detect the other 3 species.

    • The test has high sensitivity and specificity, requires no special equipment or training, and produces results rapidly. Findings remain positive for a week or more after treatment and cure, creating false-positive results in this situation.

  • Molecular biological detection tests: Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) probes and polymerase chain reaction (PCR) have good sensitivity and specificity but require sophisticated expensive equipment.

 Procedures:

  • Obtaining thick and thin blood films at the bedside is important.

    • These films may have to be taken repeatedly for diagnosis.

    • Earlobe or finger prick is used for older children; the great toe is used in infants.

    • Take a large drop of blood on one end of a clean slide, spread uniformly, and air-dry. A smaller drop should be spread thinly so that the end of the smear does not reach the end of the slide.

    • Giemsa staining is suitable for identifying malaria parasites in these films.

Histologic Findings: The appearance of the parasite varies in the thick and thin films. The thick unfixed film shows only leucocytes and parasites; erythrocytes are destroyed in the staining process. The parasites themselves are also altered. Young trophozoites appear as incomplete rings or spots of blue cytoplasm with discrete red nuclei. In mature trophozoites, the cytoplasm may be fragmented, and the various characteristics of the different species are often indistinct. Gametocytes and schizonts usually retain their characteristic appearances. Thin film examination is essential for the accurate identification of plasmodial species, which has an important bearing on treatment.

Medical Care:

  • Children who are fully conscious, who have low-to-moderate fever, and who are maintaining their nutrition and hydration orally can be treated on an outpatient basis.

  • Oral paracetamol (acetaminophen) is safe and effective for fever and should be used in doses of 10 mg/kg. This dose can be repeated 3-6 times a day, as required. If the child has hyperpyrexia, tepid sponging can bring the temperature down rapidly.

  • Many children with malaria develop anemia. Because onset is gradual, the child withstands a low level of hemoglobin quite well, and blood transfusions are rarely needed. Standard hematinic therapy is effective.

  • If repeated vomiting has led to dehydration, the child needs appropriate parenteral fluids to correct it. Glucose-containing fluids help counter the hypoglycemia that sometimes accompanies severe malaria.

  • Vomiting is common in malaria. Although antiemetics such as domperidone and metoclopramide are used, antimalarials should be continued. Vomiting stops when the malaria is cured.

  • Indications for immediate hospitalization include the following:

    • Intractable vomiting

    • Dehydration

    • Seizures

    • Altered consciousness or coma

    • Repeated convulsions

    • Difficulty in breathing or acidotic breathing

    • Severe pallor (indicating severe anemia)

    • Hypoglycemia (blood glucose <2.5 mmol/L or 3 mmol/L in malnourished children)

    • Oliguria or anuria, signifying renal affliction

    • Shock

    • Hyperparasitemia

    • Bleeding diathesis

Diet:

  • No restrictions are needed in the diet for patients well enough for outpatient management. Indeed, the appetite and activity level are remarkably well preserved for the degree of fever.

  • Advise increased fluid intake.

 Management

Blood schizonticides are the first-line drugs for the treatment of malaria and must be started as soon as the diagnosis is made or even suspected. They act on the asexual forms in the erythrocytes and interrupt clinical attacks. Delay in treatment of P falciparum malaria can lead to development of severe malaria, which has a poorer prognosis than uncomplicated malaria. Chloroquine, quinine, quinidine, mefloquine, halofantrine, and artemisinin compounds are the rapidly acting drugs that can terminate an acute malaria attack. While chloroquine acts rapidly, resistance is widespread and an accurate travel history should be obtained before choosing the antimalarial drug.

P vivax and P ovale have dormant stages (hypnozoites) in the liver, and the treatment of an episode of malaria requires eradication of these forms also. The classic treatment is a 3-day course of chloroquine, followed by a 14-day course of primaquine. A shorter course of 5 days of primaquine, started with chloroquine, has been described but is associated with higher relapse rates.