Malaria overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
Overview
Malaria is a vector-borne infectious disease caused by protozoan parasites. Malaria is one of the most common infectious diseases and an enormous public-health problem. The disease is caused by protozoan parasites of the genus Plasmodium. The most serious forms of the disease are caused by Plasmodium falciparum and Plasmodium vivax, but other related species (Plasmodium ovale, Plasmodium malariae, and sometimes Plasmodium knowlesi) can also infect humans. This group of human-pathogenic Plasmodium species is usually referred to as malaria parasites.
Historical Perspective
Malaria is considered one of the oldest infections known to mankind. The symptoms of malaria were first believed to be caused by noxious elements.[1] It was not until 1880 when Charles Louis Alphone Laveran discovered the Plasmodium parasite in blood smears of patients with malaria.[2] The role of mosquitos in the transmission of malaria to humans was discovered a few years later. Consequently, the entire life cycle of the Plasmodium parasite remained enigmatic until 1982.[3] Although malaria has always been treated using quinine, an alkaloid derived from barks of cinchona, the first synthetic quinine was produced in 1948.[4][5] In 2014, the first candidate for anti-malarial vaccine was developed.
Pathophysiology
Malaria in humans develops via two phases: an exoerythrocytic (hepatic) and an erythrocytic phase. When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver.
Classification
The classification of malaria can be made according to the strains of Plasmodium species. There are 5 common Plasmodium species that infect humans: P. falciparum, P. ovale, P. vivax, P. malariae, and P. knowlesi. Malaria can also be classified according to severity of infection: uncomplicated vs. severe.
Causes
Malaria is a vector-borne infectious disease caused by protozoan parasites. P. vivax is the most common cause of infection, responsible for about 80 % of all malaria cases. However, P. falciparum is the most important cause of disease, and responsible for about 15% of infections and 90% of deaths.[6]
Epidemiology and Demographics
Worldwide, 3.4 billion people live in areas at risk of malaria transmission in 106 countries and territories. The World Health Organization estimates that in 2012 malaria caused 207 million clinical episodes, and 627,000 deaths. An estimated 91% of deaths in 2010 were in the African Region.[7] The vast majority of cases of malaria occur in children under the age of 5 years.[8] Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur.[9] Where malaria is found depends mainly on climatic factors such as temperature, humidity, and rainfall.
Risk Factors
A risk factor for malaria is travel to endemic areas. For travelers, regions associated with the highest estimated relative risk of infection are West Africa and Oceania. Human behavior, often dictated by socioeconomic situations, can influence the risk of malaria for individuals and communities. In addition, children and pregnant women are at a higher risk of contracting malaria. Certain biologic characteristics can protect against particular types of malaria. Two genetic factors, the sickle cell trait and absence of Duffy blood group, have been shown to be epidemiologically significant.[10]
Diagnosis
Symptoms
The hallmark symptom of malaria is fever, which commonly occurs in paroxysms, separated by fever-free time intervals. The classical but rarely observed malaria attack lasts 6-10 hours, and it consists of a cold stage, hot stage, and sweating stage. Other common symptoms of malaria include chills, headache, nausea, vomiting, weakness, night sweats, flu-like symptoms, and myalgia. In the presence of a paroxysmal fever, travel history to a country where malaria is endemic is an important alert for the diagnosis.[11] Most importantly, malaria symptoms must be distinguished as to whether they reflect an uncomplicated or a severe course of infection. While uncomplicated infection is a benign process, severe malaria causes organ damage and is considered a medical emergency.
Treatment
Medical Therapy
Active malaria infection with P. falciparum is a medical emergency requiring hospitalization. Infection with P. vivax, P. ovale or P. malariae can often be treated on an outpatient basis. Treatment of malaria involves supportive measures as well as specific antimalarial drugs. When properly treated, someone with malaria can expect a complete cure.[12]
Primary Prevention
Although some are under development, no vaccine is currently available for malaria; preventative drugs must be taken continuously to reduce the risk of infection. These prophylactic drug treatments are often too expensive for most people living in endemic areas. Most adults from endemic areas have a degree of long-term recurrent infection and also of partial resistance; the resistance reduces with time and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Malaria infections are treated through the use of antimalarial drugs, such as quinine or artemisinin derivatives, although drug resistance is increasingly common.
Secondary Prevention
Malaria transmission can be reduced by preventing mosquito bites with mosquito nets and insect repellents, or by mosquito control measures such as spraying insecticides inside houses and draining standing water where mosquitoes lay their eggs.
Cost-Effectiveness of Therapy
Although effective anti-malarial drugs are on the market, the disease remains a threat to people living in endemic areas who have no proper and prompt access to effective drugs. Access to pharmacies and health facilities, as well as drug costs, are major obstacles. Médecins Sans Frontières estimates that the cost of treating a malaria-infected person in an endemic country was between US $0.25 and $2.40 per dose in 2002.[13]
Future or Investigational Therapies
RTS,S is considered the first anti-malaria vaccine candidate. The phase 3 trial for the vaccine involving young African children demonstrated significant efficacy beyond the efficacy observed by the use of conventional preventative measures, proving further benefit in preventing malaria. On July 24 2014, GSK submitted a regulatory application to the European Medicines Agency (EMA) for approval of the vaccine. If granted, the World Health Organization (WHO) intends to recommend the RTS,S malaria vaccine in 2015. Other vaccines are also in the making, but still require further validation of their clinical efficacy.
References
- ↑ Cox FE (2010). "History of the discovery of the malaria parasites and their vectors". Parasit Vectors. 3 (1): 5. doi:10.1186/1756-3305-3-5. PMC 2825508. PMID 20205846.
- ↑ Laveran CL (1982). "Classics in infectious diseases: A newly discovered parasite in the blood of patients suffering from malaria. Parasitic etiology of attacks of malaria: Charles Louis Alphonse Laveran (1845-1922)". Rev Infect Dis. 4 (4): 908–11. PMID 6750753.
- ↑ Krotoski WA, Collins WE, Bray RS, Garnham PC, Cogswell FB, Gwadz RW; et al. (1982). "Demonstration of hypnozoites in sporozoite-transmitted Plasmodium vivax infection". Am J Trop Med Hyg. 31 (6): 1291–3. PMID 6816080.
- ↑ Seeman JI (2007). "The Woodward-Doering/Rabe-Kindler total synthesis of quinine: setting the record straight". Angew Chem Int Ed Engl. 46 (9): 1378–413. doi:10.1002/anie.200601551. PMID 17294412.
- ↑ Kaufman TS, Rúveda EA (2005). "The quest for quinine: those who won the battles and those who won the war". Angew Chem Int Ed Engl. 44 (6): 854–85. doi:10.1002/anie.200400663. PMID 15669029.
- ↑ Mendis K, Sina B, Marchesini P, Carter R (2001). "The neglected burden of Plasmodium vivax malaria" (PDF). Am J Trop Med Hyg. 64 (1-2 Suppl): 97–106. PMID 11425182.
- ↑ Malaria Facts. CDC.gov accessed on 07/24/2014 [1]
- ↑ Greenwood BM, Bojang K, Whitty CJ, Targett GA (2005). "Malaria". Lancet. 365: 1487–1498. PMID 15850634.
- ↑ Layne SP. "Principles of Infectious Disease Epidemiology /" (PDF). EPI 220. UCLA Department of Epidemiology. Retrieved 2007-06-15.
- ↑ Factors. CDC.gov Accessed on 7/24/2014
- ↑ Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
- ↑ If I get malaria, will I have it for the rest of my life? CDC publication, Accessed 14 Nov 2006
- ↑ Medecins Sans Frontieres, "What is the Cost and Who Will Pay?"