Malaria: An infection with global impact

Malaria is a major public health problem in developing countries and is the top ranked priority tropical disease of the World Health Organization. It is a leading cause of disease and death among children under five years, pregnant women and non-immune travellers/immigrants. Every year, there are about 500 million clinical attacks of malaria. Of these, 2-3 million are severe and about 1 million people die (about 3000 deaths every day). Malaria in pregnancy accounts for about 25% of cases of severe maternal anemia and 10-20% of low birth weight. About 40% of the world's population is at risk of malaria. According to the World Malaria Report, malaria is prevalent in 108 countries of the tropical and semitropical world (Africa; Amazon, central and southern America; central, south and southeast Asia; Pacific). The economic burden of malaria is huge, estimated to be $12 billion a year in Africa alone. Known since millennia, malaria continues to upsurge in incidence till date due to a variety of factors including but not limited to drug resistance, global climate change, changing agricultural practices, insecticide resistance mosquitoes, population movements and poverty, and political instability. Malaria is caused by the protozoa Plasmodium (P) and transmitted by the bite of an infected female anopheline mosquito. There are five species known to cause infection namely, P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. Infection due to P species other than P. falciparum is called non-falciparum malaria. P. falciparum causes the most severe disease and patients with this form of malaria may progress to lifethreatening illness within hours. The P life cycle consists of an exoerythrocytic (asymptomatic) stage and erythrocytic (symptomatic) stage. Several human genetic polymorphisms and mutations have been observed to influence either clinical attack or severity of the disease, particularly hemoglobin and red cell antigens. Individuals living in endemic areas appear to develop partial immunity to malaria following repeated infections. Although malaria classically presents as a febrile paroxysm with headache, myalgia, nausea, vomiting, malaise, splenomegaly, anemia and thrombocytopenia, it is a great imitator and trickster with varied and dramatic manifestations especially in endemic regions. Malaria diagnostic tools include clinical criteria, light microscopy, rapid diagnostic tests (RDTs), and molecular diagnostic techniques. Light microscopy remains the gold standard for diagnosis of malaria; it permits determination of the infecting species as well as quantification of parasitemia, facilitating monitoring the response to therapy. Malarial target antigen for RDTs includes histidine-rich protein 2 of P. falciparum, a pan-malarial Plasmodium aldolase, and the parasite specific lactate dehydrogenase. Molecular technologies have been developed to improve the diagnosis of malaria, although these methods are limited by a number of factors including specialized equipment, continuing supplies, operator expertise, turnaround time and cost. Treatment of chloroquine sensitive non-falciparum malaria comprises administration of chloroquine followed by standard course of primaquine for radical cure. Therapeutic options for chloroquine resistance non-falciparum malaria include mefloquine, atovaquone-proguanil or a combination of quinine and tetracycline or doxycycline. Parenteral antimalarial is often required for falciparum malaria and includes artmisinin derivative or qunine/quinidine along with doxycycline or clindamycin. Artesunate is the preferred therapy for treatment of severe falciparum malaria in adults and children wherever intravenous artesunate is available. Strategies for malaria control include mosquito vector control, personal protection from mosquito bites and chemoprophylaxis. Malaria vaccine is still under trial. Although mortality is rare with non-falciparum malaria, for patients with complicated falciparum malaria the mortality approaches 10-20%. Medico-legal autopsies in cases of sudden unexpected natural deaths have revealed malaria as the cause of death in a few cases. In a study conducted at Government Wenlock District Hospital in Mangalore, a malaria endemic area in South India, autopsy files revealed 5 cases of sudden death due to malaria diagnosed by histopathology between September 2004 and August 2008. Cerebral malaria, acute renal insufficiency, acute pulmonary edema and acute respiratory distress syndrome are possible mechanisms of sudden death due to malaria.