Newer Diagnostic tests for Malaria: To aid in rapid and precise diagnosis of malaria, recent advance in Newer diagnostic modalities have surfaced. This comprises of Quantitative Buffy Coat Method: basic principle lies in the fluoro chrome staining of plasmodial nucleic acid (sensitivity 42-94%) differentiating species to a fairly well (specificity P.vivax 52%, falciparum 93%). However the test demands, microscopist expertise, special centrifuging apparatus and is costly. PCR based detection methods with 100% specificity are expensive. Antigen detection serodiagnostic techniques consists of two tests (a) Histidien rich protein-2 (HRP-2) for P. Falciparum. It is a dipstick test which yields results within 10 minutes and has a specificity of 90%. (b) pLDH test which can detect any plasmodial species and which also a dipstick based test. It has comparable specificity and sensitivity. Cerebral Malaria: The principal manifestations of cerebral malaria are seizures and impaired consciousness, usually preceded by a severe headache. Neurologic examination may be unremarkable, or have findings that include contracted or unequal pupils, a Babinski sign, and absent or exaggerated deep tendon reflexes. Cerebrospinal fluid examination shows increased pressure, increased protein, and minimal or no pleocytosis. High fever, 41° to 42°C (106° to 108°F), with hot, dry skin as seen in heat stroke can occur. Ten to twelve percent of patients surviving cerebral malaria have persistent neurologic abnormalities upon discharge from hospital. Renal failure: Due to acute tubular necrosis, is a common complication of severe P. falciparum infections in non-immune persons. Failure of urine production is a poor prognostic sign, requiring peritoneal or hemodialysis. Pulmonary Edema: Often fatal, acute pulmonary edema can develop rapidly and is associated with excessive intravenous fluid therapy. Fast, labored respiration, with shortness of breath, a nonproductive cough, and physical findings of moist rales and rhonchi are usually present. Chest X-rays usually show increased broncho vascular markings. Gastroenteritis: Most patients with falciparum malaria complain of loss of appetite and nausea. However, in some patients (especially young children), additional symptoms including vomiting, abdominal pain, watery diarrhea, and jaundice are present leading to misdiagnosis of viral gastroenteritis or hepatitis. Anemia: Destruction of red blood cells upon merozoite release, and inhibition of hematopoiesis by tissue necrosis factor-cause the severe anemia often seen in P. falciparum infections. Severe anemia defined as a hematocrit of less than 21%, presents with dark brown or red urine (hemoglobinuria), decrease in urine production, and jaundice. Renal failure may be a complication. Another cause of hemolysis and hemoglobinuria in patients with malaria is destruction of G-6-PD deficient red blood cells by oxidant antimalarial drugs such as primaquine. Malaria due to P. vivax Infection Infections due to P. vivax are less severe than falciparum malaria, and parasite blood levels are lower. P. vivax forms a dormant stage in liver cells called hypnozoites. These parasites activate and cause delayed infections or a relapse . A relapse usually occurs within 6 months of an acute attack. Some hypnozoites remain dormant much longer, and are virtually undetectable. If there is any suspicion that P. vivax is endemic in the area of exposure, presumptive Differential Diagnosis of malaria Acute fever Heat stroke, hyperpyrexia of other causes, other infections, Fever and impaired consciousness other causes of fever (cerebral malaria) Viral, bacterial, fungal, protozoal (e.g. African trypanosomia sis) or helminthic meningoencephalitis, cerebral abscesses Head injury, cerebrovascular accident, intoxications (e.g. insecticides), poisonings (e.g. antimalarial drugs), meta bolic (diabetes, hypoglycaemia, uraemia, hepatic failure, hyponatraemia) Septicaemias Fever and convulsions Encephalitides, metabolic encephalopathies, hyperpyrexia, cerebrovascular accidents, epilepsy, drug and alcohol intoxications, poisoning, eclampsia, febrile convulsions, and Reye's syndrome (children) Fever and haemostatic distur- Septicaemias (e.g. meningococcaemia), viral haemorrhagic bances fever, rickettsial infection, relapsing fevers, leptospirosis Fever and jaundice Viral hepatitis, yellow fever, leptospirosis, relapsing fevers, septicaemias, haemolysis, biliary obstruction, hepatic necrosis (drugs, poisons) Fever with gastrointestinal Travellers' diarrhoea, dysentery, enteric fever, other bacterial symptoms infections, inflammatory bowel disease Fever with haemoglobinuria Drug-induced haemolysis (e.g. oxidant antimalarials in (`black water fever') glucose 6-phosphate-dehydrogenase-deficient patient), favism, transfusion reaction, dark urine of other causes (e.g. myoglobinuria, urobilinogen, porphobilinogen) Fever with acute renal failure Septicaemias, yellow fever, leptospirosis, drug intoxica tions, poisonings, prolonged hypotension Fever with shock (`algid malaria') Septicaemic shock, haemorrhagic shock (e.g. massive gastrointestinal bleed, ruptured spleen), perforated bowel, dehydration, hypovolaemia, myocarditis treatment must be given to prevent illness. Currently, the only available treatment is primaquine; . P. vivax fevers may be erratic or continuous in the initial phase of illness. After 3 to 4 days, if not treated, the fever develops into a synchronous cycle of afternoon temperature increases every 48 hours. The fever can be as high as 40°C(104°F), and symptoms during this stage have been described as worse than falciparum malaria. Physical findings usually include an enlarged, tender spleen, and a palpable liver present by the second week of infection. Deaths have been reported due to rupture of an enlarged spleen. Parasitemia levels are less for P. vivax because they infect only young red blood cells, unlike P. falciparum which can infect red blood cells of all ages. Malaria is one of the most important diseases that developing countries face .Annually , 300-500 million people suffer from malaria and several million die of which most are children under five. It has been calculated from epidemiological studies that 200-300 children die from malaria each hour despite world wide control strategies.