Malaria

Malaria is a devastating infectious disease transmitted by mosquitoes and caused by infection with small one-celled parasites of the Plasmodium genus. The parasites destroy host red blood cells, resulting in anemia, fever, and chills. The illness is a driving force for human evolution and has changed the course of history on many occasions. Even today, with recent and profound understanding of the vector and the pathogen, the disease causes an estimated 2 million deaths every year; hundreds of millions more are infected with the parasite but do not die from the disease.

Types

Types of malaria may be distinguished by the predominant species of the Plasmodium parasite; P. falciparum is the most common and important type. The disease may also be caused by coinfection by multiple species. Disease severity (asymptomatic, mild, moderate, or severe) provides another way to describe the type of malaria.

Signs and Symptoms

Bites from infected mosquitoes are no more bothersome than bites from uninfected mosquitoes. If enough malaria parasites are present to cause disease, patients usually experience malarial attacks that last several hours and feature fever, headache, muscular pain, and nausea. Between attacks, patients feel better but may become profoundly weak due to destruction of their red blood cells (RBCs). The attacks of chills and fever usually recur at around 48-hour intervals; symptoms caused by P. malariae recur at 72-hour intervals.

The large number of parasites and damaged RBCs in severe cases may cause problems with blood flow through small vessels and damage the kidneys or lungs. Parasites may also interfere with oxygen delivery to developing fetuses by damaging the placenta. A more severe form of the disease known as cerebral malaria results when damaged RBCs disrupt oxygen delivery to the brain; symptoms may include seizures, coma, or death.

Causes

A P. falciparum parasite among red blood cells, some of which show damage caused by the parasite. Source: CDC

Anopheles mosquito. Source:CDC

The parasite has a multi-step life cycle, and various forms engage in specific behaviors that allow progress to the next stage. After the parasite enters the host, it travels in the bloodstream and reaches the liver, where it invades liver cells and multiplies. The infected liver cell eventually bursts, releasing a new form of the parasite back into the blood; this new form is able to enter red blood cells (RBCs) and feed on the hemoglobin molecules inside (a behavior known as hematophagy.) After a growth and incubation period inside the RBCs that may last several days, many more parasites are released, destroying what remains of the RBC. Parasites then travel the circulation (parasitemia) and may invade other RBCs or may be picked up by subsequent mosquito bites.

The incubation period, when parasites are devouring hemoglobin within RBCs and multiplying, may be asymptomatic; however, the parasites often mature and enter the bloodstream simultaneously in large numbers, causing profound fever and chills. The destruction of RBCs causes anemia, which can result in extreme weakness or death due to lack of adequate oxygen delivery to vital organs.

Diagnosis

A presumptive diagnosis of malaria can be made based on a history of living in or travel to an endemic area, where a bite from an infected mosquito may have occurred, together with the symptoms of weakness and periodic fever and chills. Definitive diagnosis is based on identifying the parasite in the patient's blood. When making treatment decisions, more advanced tests may be necessary to determine the specific organism(s) involved and their sensitivity to various antimalarials.^[1]

Treatment

Several medicines are available to treat malaria. As with other infectious diseases, the organisms may become increasingly resistant to antimalarials with time, since drug-resistant organisms have a significant survival advantage over their drug-susceptible relatives; drug-resistant malaria parasites may also cause more severe disease.^[2]

Historically, chloroquine was used to treat malaria. The appearance of chloroquine-resistant organisms has led to the discovery and use of more advanced antibiotic regimens.^[3] Because malaria in the United States is so rare, physicians are well advised to obtain travel histories from patients with unexplained fever. Treatment recommendations depend in part on whether patients have visited areas where chloroqine-resistant parasites are prevalent. If so, atovaquone and proguanil or quinine plus tetracycline or doxycycline or clindamycin are the best treatment options.^[4]

Prevention

Although the impact of malaria is greatest in tropical and subtropical regions, prevention of of the disease is an important and ambitious goal of public health experts around the world.^[5] A multi-faceted approach to malaria prevention includes efforts to develop effective vaccines, better antimalarials, and deployment of insecticide-impregnated bed nets.^[6] Unfortunately, efforts to eradicate malaria are often complicated and overwhelmed by the magnitude of related societal problems such as poverty, lack of infrastructure, and political intransigence.

History

The word malaria derives from Italian words meaning "bad air" and alludes to an early observation that exposure to stagnant air in the swamps surrounding Rome was associated with the disease. Many key discoveries were necessary to lead to our current understanding of the cause of the disease, the complex interactions between the Plasmodium parasite and its mosquito and human hosts, and the steps necessary to control the disease.

Malaria has been with us throughout our existence as humans, and the parasites have evolved along with us; fossils of mosquitoes up to 30 million years have evidence of the malaria parasite. Hippocrates provided some of the earliest surviving descriptions of the disease; he related it to the time of year and to geographic areas. The earliest treatments were brought to Europe around 1649; these were derived from the Peruvian Chinchona tree's bark, which contains quinine as the active component. Alphonse Laveran, in 1889, discovered that the disease was caused by a parasite; soon after, Ronald Ross provided key observations of the blood of infected mosquitoes that revealed how the disease was spread.^[7]

The discovery of DDT as an insecticide by Paul Müller earned for him the Nobel Prize Laureate in Physiology or Medicine in 1948. DDT's early deployment in Italy in 1944 was a tremendous success and encouraged thoughts of eventual eradication of the disease. Unfortunately, many factors have conspired to frustrate these efforts—for instance, malaria is prevalent in areas of the world that are politically unstable, that have poor infrastructure and economic resources, and high rates of

References

1. ↑ Khalil I, Rønn AM, Alifrangis M, Gabar HA, Satti GM, Bygbjerg IC. Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole. Am J Trop Med Hyg. 2003 May;68(5):586-9. Abstract | Full Text | PDF
2. ↑ Talisuna AO, Okello PE, Erhart A, Coosemans M, D'Alessandro U. Intensity of malaria transmission and the spread of Plasmodium falciparum resistant malaria: a review of epidemiologic field evidence. Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):170-80 Abstract | Full Text | PDF
3. ↑ Mehta SR, Das S. Management of malaria: recent trends. J Commun Dis. 2006 Mar;38(2):130-8. Abstract
4. ↑ Griffith KS, Lewis LS, Mali S, Parise ME. Treatment of malaria in the United States: a systematic review. JAMA. 2007 May 23;297(20):2264-77. Abstract | Full Text | PDF
5. ↑ Bates N, Herrington J. Advocacy for malaria prevention, control, and research in the twenty-first century. Am J Trop Med Hyg. 2007 Dec;77(6 Suppl):314-20.Abstract | Full Text | PDF
6. ↑ Greenwood BM, Fidock DA, Kyle DE, et al. Malaria: progress, perils, and prospects for eradication. J Clin Invest. 2008 Apr;118(4):1266-76. Abstract | Full Text | PDF
7. ↑ Ross R., Smyth, M.D., On Some Peculiar Pigmented Cells Found in Two Mosquitos Fed on Malarial Blood. Br Med J 18 Dec 1897, 1786-8 PDF

External Links

Dr. B. Srinivas Kakkilaya maintains Malaria Site, which provides information on the disease and showcases malaria control efforts in Mangalore, South India.