PROTOZOAL AND HELMINTIC DISEASES

MALARIA

Malaria is a disease of poverty and underdeveloped countries. Millions of children die of malaria in Africa every year. Malaria is a major public health problem in tropical areas, and it is estimated that malaria is responsible for 1 to 3 million deaths and 300—500 million infections annually. The vast majority of morbidity and mortality from malaria is caused by infection with P. falciparum, although P. vivax, P. ovale, and P. malariae also are responsible for human infections.

Etiology. Malaria caused by the intracellular protozoan parasite Plasmodium falciparum is a worldwide infection that affects 100 million and kills 1 to 1.5 million persons per year and so is the major parasitic cause of death. P. falciparum and the three other malaria parasites that infect humans (P. vivax, P. ovale, P. malariae) are transmitted by more than a dozen species of Anopheles mosquitoes widely distributed throughout Africa, Asia, and Latin America.

P. vivax and P. malariae cause mild anemia and, in rare instances, splenic rupture and nephrotic syndrome. Acute P. falciparum infections produce high

parasitemias, severe anemia, cerebral symptoms, renal failure, pulmonary edema, and death.

The Plasmodium Life Cycle and Pathogenesis. Mosquitoes inject parasites (sporozoites) into the subcutaneous tissue and less frequently directly into the bloodstream; from there, sporozoites travel to the liver. Recent evidence indicates that sporozoites pass through several hepatocytes before invasion is followed by parasite development. The co-receptor on sporozoites for invasion involves, in part, the thrombospondin domains on the circumsporozoite protein and on thrombospondin-related adhesive protein (TRAP). These domains bind specifically to heparin sulfate proteoglycans on hepatocytes in the region in apposition to sinusoidal endothelium and Kuppfer cells. Within the hepatocyte, each sporozoite develops into tens of housands of merozoites, each able to invade a RBC on release from the liver.

Disease begins only once the asexual parasite multiplies within RBC. This is the only gateway to disease. P. falciparum and P. vivax within RBC develop over 48 hours, producing around 20 merozoites in a mature parasite, each able to invade other RBC. A small proportion of asexual parasites converts to gametocytes that are critical for the transmission of the infection to others through female anopheline mosquitoes but cause no disease. Here the strategy of P. vivax differs from that of P. falciparum. P. vivax develops into gametocytes soon after release of

merozoites from the liver; P. falciparum gametocytes develop much later. Early treatment of clinical malaria attacks by anti-bloodstage chemotherapy for P. falciparum also kills the developing gametocytes; P. vivax transmits before the symptomatic stage of the disease.

Within the red blood cells, the parasites multiply in a membrane-bound digestive vacuole, hydrolyzing hemoglobin via secreted enzymes that include a heme polymerase. The latter neutralizes the potentially toxic heme by forming a hemozoin or malaria pigment, which may be phagocyted by macrophages with accumulation in the spleen, liver, lymphatic nodes.

Antibodies and the proinflammatory response protect against the asexual blood stages of some rodent malarias and probably also human malaria. The protection mediated by the proinflammatory response may relate to the cytokines TNF- and IFN- and the release of mediators such as nitric oxide (NO).

Morphology. In malaria congestion and enlargement of the spleen, which may eventually exceed 1000 gm in weight, develop. Parasites are present within red blood cells, and there is increased phagocytic activity of the reticuloendothelial cells. In chronic malaria infection, the spleen becomes increasingly fibrotic and brittle, with a thick capsule and fibrous trabeculae. The parenchyma is gray or black because of phagocytotic cells containing granular, brown-black, faintly birefringent hemozoin pigment.

The liver becomes progressively enlarged and pigmented with progression of malaria. Kupffer's cells are heavily laden with malarial pigment, parasites, and cellular debris, while some pigment is also present in the parenchymal cells. Pigmented phagocytic cells may be found dispersed throughout the bone marrow, lymph nodes, subcutaneous tissues, and lungs. The kidneys are often enlarged and congested with a dusting of pigment in the glomeruli and hemoglobin casts in the tubules.

Renal impairment is common in severe malaria in nonimmune adults, and the microscopic pathology is acute tubular necrosis: glomerulonephritis is rare. In some cases acute tubular necrosis may be precipitated by intravascular hemolysis. The pathogenesis in other cases is unclear. Patients may require short-term dialysis for acidosis, fluid overload, hyperkalemia, or rapidly rising creatinine.

Deteriorating respiratory function with widespread pulmonary edema may develop during the disease and carries a very poor prognosis. Some cases of pulmonary edema may be secondary to fluid overload and/or rapid correction of dehydration.

In malignant cerebral malaria caused by P. falciparum, brain vessels are plugged with parasitized red cells, each cell containing dots of hemozoin pigment. There are ring hemorrhages that are probably related to local hypoxia incident to the vascular stasis and small focal inflammatory reactions. With more severe hypoxia, there is degeneration of neurons, focal ischemic softening.

Coma is a very prominent feature of severe illness in nonimmunes, although neurological sequelae are recorded less frequently.

Disordered coagulation and clinical evidence of bleeding are not infrequent in adults, and patients may present with bleeding at injection sites, gums, or epistaxis. Hemoglobinuria secondary to intravascular hemolysis and jaundice are more common in adults than in children. As in children, concurrent bacteremia is common.

Rarely the heart may be involved to the pathological process.

Malaria in Pregnancy. During pregnancy, women are both more susceptible to malaria infection and also more likely to develop hypoglycemia and pulmonary edema. In pregnant women, malaria infection, often without fever, may nevertheless cause anemia and placental dysfunction. This effect is greatest in primigravidae and has been attributed to the adhesion of parasitized erythrocytes to chrondrotin sulfate A and hyaluronic acid in the placenta. Fetal growth is impaired and babies born to women with placental malaria are on average 100 g lighter than controls born to women without malaria. The subsequent contribution of malaria to infant mortality is substantial.

Complications: glomerulonephritis, amyloidosis, cachexia.

The death usually occurs in the tropical malaria due to coma.

DIPHYLLOBOTHRIASIS

Diphyllobothriasis is an ictic zoonosis acquired by humans when they accidentally ingest plerocercoids while eating raw, undercooked and sometimes smoked fish. Restricted to Northern Central Europe till past century, this disease has now spread to other temperate latitudes, and a human case was even described in India. Of all known species of Diphyllobothrium 3 are found in South America. Diphyllobothrium pacificum with marine cycle and Diphyllobothrium latum and Diphyllobothrium dendriticum with freshwater cycle, these latter two were brought to South America via European immigrants.

The first case of human diphyllobothriosis was registered in Argentina in 1911, in a young Russian immigrant who had just arrived in the country. Seventy years passed until the first autochthonous case was identified in 1982.

Etiology. Diphillobothriasis is found principally among fish-eating people in the Scandinavian countries, in Russia, and in parts of Asia. The infection is extremely rare in tropical areas. The causative agent, Diphillobothrium latum (fish tapeworm), measures between 3 and 10 m in length and is composed of 3000 or more proglottids. Humans and other mammals, especially dogs, acquire the infection by eating undercooked fish. The worm lives in the small intestine.

Pathology. Infected persons may be symptomless or may be asthenic and suffer from gastrointestinal disorders, especially abdominal pain. Rarely a megaloblastic anemia develops, especially when the worm is implanted high in the small intestine. Explanation for the anemia is connected with B12 vitamin deficiency.

Megaloblastic hyperactivity of the bone marrow and even central nervous system degeneration may be encountered in some patients.