Now let's discuss malaria. Pathophysiology, clinical manifestations and treatment. The magnitude of the problem with malaria is huge. There are an estimated 210 million cases in 2012. These were accompanied by 627,000 deaths of which 91% occurred in Africa. The pathophysiology of malaria is related to structural, biochemical and mechanical modification of red blood cells when they're parasitized by plasmodia. This leads alter deformability and fragility of red blood cells, which can to cytoadherence. Altered endothelial activation and dysfunction and altered thrombostasis. This is further complicated by parasite biomass and inflammatory responses. The pathology of malaria can evolve the bone marrow, which can be reactive due to anemia. Splenomegaly may occur due to the removal of aberrant red blood cells. Capillary obstruction can occur due to sequestration of red blood cells, which can affect any organ but especially the central nervous system. And finally, there can be uncontrolled inflammation with secondary organ damage. The clinical manifestations of malaria typically begin 7 to 30 days after a bite from an infected mosquito. The symptoms are nonspecific and include fever, chills, sweats, headache, myalgias, cough, nausea, vomiting, diarrhea, back pain and dizziness. Physical findings may include fever, tachycardia, tachypnea, hypotension, confusion, focal neurologic signs and coma. The laboratory manifestations of malaria may also be quite nonspecific. They can include anemia, low platelet count, increased bilirubin, renal insufficiency and hypoglycemia. Diagnostic testing for malaria is imperative, because an early diagnosis can relate to an improved prognosis. Establishing the diagnosis of malaria involves looking at blood smears. Blood smears remain the gold standard. Thick smears are more sensitive, because of the greater numbers of red blood cells and thin smears allow for species identification and determination of parasite density. In suspected cases where pretest probability is low, blood smears should be repeated every 12 to 24 hours times 3. And if all smears are negative, the malaria diagnosis is unlikely. In suspected cases where the pretest probability is high, you should initiate empiric treatment while the result is pending. And of course, blood smear's quality depends on laboratory competence. So with regard to establishing the diagnosis of malaria, there are now available rapid diagnostic tests. These offer the advantage of 15-minute response time. These rapid diagnostic tests are reliable for plasmodium falciparum, but less certain for other species. PCR assays, polymerase chain reaction assays are also sensitive and specific, but require a specialized lab. They may be very useful for confirmation of species and drug resistance testing, but as yet are not all that useful in clinical practice. Indirect fluorescent antibody test may be useful for blood banking, but again are not commonly used to support diagnosis. Here's an example of a rapid diagnostic test, which is increasingly available in resource limited settings and across Sub-Saharan Africa. It's important to assess the severity of malaria, because the severity is related to prognosis. Uncomplicated malaria has an excellent prognosis. By contrast, severe malaria, which is defined in having impaired consciousness or coma. Severe anemia with a hemoglobin less than seven, renal failure, adult respiratory distress syndrome, hypotension, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria, jaundice, repeated seizures or a parasitemia density of greater than 5%. Each of these factors defines severe malaria and portends for the patient a worse prognosis. So in terms of treatment of malaria, uncomplicated malaria is typically treated with artemether/lumefantrine, known by the brand name Coartem. Alternative oral treatments include atovaquone/proguanil, known by the trade name Malarone and quinine sulfate plus doxycycline. For severe malaria, the treatment is typically intravenous. It may include IV quinine or quinidine gluconate. If quinidine gluconate is used, you need careful dosing and cardiac monitoring if possible. Another alternative is artenusate. IV treatment with any of these medications should be followed by oral treatment. For plasmodium vivax and plasmodium ovale infection, you must extend treatment to eliminate hypozoites in the liver with primaquine for 14 days. So now, let's consider a case history. A six-year old boy presents to clinic with a history of fever and chills. On exam, his temperature is 39.6, pulse 140 and respiratory rate 40. His lethargic and only intermittently responds to commands. On the lab evaluation, his hemoglobin is 6.5, platelets 50,000 and bilirubin 5.3. In your differential diagnosis, you consider severe malaria, bacterial meningitis or Chikungunya fever. A thick peripheral blood smear is positive. Thin smear reveals morphology suggestive of plasmodium falciparum. You diagnose severe malaria and immediately initiate a quinine drip for three days followed by oral artemether/lumefantrine. He recovers well and is discharged one week later to complete his oral treatment.
