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. It was not until 1880 when Charles Louis Alphone Laveran discovered the Plasmodium parasite in blood smears of patients with malaria. 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. Although malaria has always been treated using quinine, an alkaloid derived from barks of cinchona, the first synthetic quinine was produced in 1948. 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.

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. The vast majority of cases of malaria occur in children under the age of 5 years. 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. Where malaria is found depends mainly on climatic factors such as temperature, humidity, and rainfall.

Risk Factors

Travel to endemic areas is a risk factor for malaria. 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.

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. 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.

Physical Examination

Physical findings in malaria may include fever, weakness, pallor, jaundice, and perspiration. Other findings on physical exam are tachycardia, tachypnea, splenomegaly, and hepatomegaly.

Laboratory Findings

The diagnosis of malaria is confirmed by the identification of the malaria parasite in the patient's blood under microscopy. Laboratory tests may also reveal anemia with decreased hemoglobin, hematocrit, and haptoglobin in addition to either a decreased or increased leukocyte count. Biochemistry may reveal hypoglycemia, elevated LDH, acidosis, and mild hyponatremia due to vomiting and diarrhea. In severe disease, elevated creatinine, proteinuria, and hemoglobinuria may be present secondary to renal failure. Other malaria-specific tests include: the antigen detection test, PCR, and serology test for the presence of antibodies against the plasmodium. Drug resistance tests should also be performed to assess the susceptibility of the microorganism to the antimalarial drugs.

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.

Primary Prevention

Although some are under development, no vaccine is currently available for malaria. RTS,S malaria vaccine has been proposed in July 2014 and is pending approval by the European Medicines Agency (EMA). Other more recent vaccine, such as PfSPZ malaria vaccine is currently being studied for clinical efficacy.

Preventative drugs must be taken continuously to reduce the risk of infection. Most adults from endemic areas have a degree of long-term recurrent infection and also of partial resistance; the resistance reduces with time and adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. Individuals are strongly recommended to take full precautions if they return to an endemic region.

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.

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.