Malaria diagnosis and treatment

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Malaria causes around 600,000 deaths each year, mainly in children in sub-Saharan Africa, and families, governments, and donors spend considerable amounts of money on diagnosis, treatment and prevention. To ensure this money is spent wisely, The Cochrane Collaboration conduct independent reviews of the evidence in prevention and treatment.  

Prompt diagnosis and treatment with effective drugs will reduce malaria deaths.

Diagnosing malaria

Rapid diagnostic tests for diagnosing uncomplicated P. falciparum malaria in endemic countries
The World Health Organization now recommends that malaria is always confirmed with a diagnostic test before treatment. The gold standard test is light microscopy, but this is often unavailable in rural areas of Africa. Rapid Diagnostic Tests (RDTs) are simple to use diagnostic kits which do not require laboratory facilities or extensive training, and can provide a simple positive or negative result within 20 minutes. This review assesses the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia compared to light microscopy and presents data by test type and brand.

Rapid diagnostic tests versus clinical diagnosis for managing people with fever in malaria endemic settings 
Rapid diagnostic tests (RDTs) are the most feasible way of achieving universal access to a diagnostic test, especially in rural areas of Africa where health workers have often had to rely on clinical symptoms alone. For policy makers considering RDTs, this review aims to evaluate whether introducing RDTs into clinical algorithms improves patient health outcomes, and reduces the unnecessary overuse of anti-malarials. For health workers, this review also aims to evaluate the safety of withholding anti-malarials from people with a negative RDT.

Treating uncomplicated P. falciparum malaria

Artemisinin-based combination therapy for treating uncomplicated malaria
Uncomplicated malaria is the mild form of the disease, which typically causes fever with headache, tiredness, muscle pains, abdominal pains, rigors, and nausea and vomiting. The World Health Organization now recommends that uncomplicated malaria is treated with a combination of two drugs to reduce the development of drug resistance. This review evaluates the relative benefits and harms of five artemisinin-based combinations and was published in 2009. It is no longer updated as new combinations will be evaluated in individual reviews.

Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria 
Dihydroartemisinin-piperaquine (DHA-P) is one of five artemisinin-based combination therapies (ACTs) recommended by the World Health Organization to treat uncomplicated malaria. This review assesses the relative benefits and harms of DHA-P compared to other ACTs.

Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria 
Artesunate plus pyronaridine is a new artemisinin-based combination therapy (ACT) being considered for use in people with non-severe malaria. This review assesses the benefits and harms of artesunate plus pyronaridine compared to the ACTs currently recommended by the World Health Organization.

Azithromycin for treating uncomplicated malaria
Azithromycin is an antibiotic with antimalarial properties which could be a useful additional option for antimalarial therapy. This review assessess the benefits and harms of azithromycin (alone or in combination with other antimalarial drugs) compared to alternative antimalarial drugs.

Atovaquone-proguanil for treating uncomplicated malaria
Atovaquone-proguanil is a non-artemisinin based combination therapy which is not recommended by the WHO for use in endemic areas, but is sometimes used in travellers returning from endemic areas. This review assesses the relative benefits and harms of atovaquone-proguanil compared to other antimalarial drugs and combinations.

Antipyretic measures for treating fever in malaria
Fever control measures are commonly used in treating malaria. In the past, some researchers suggested that fever reduction may prolong malaria illness. This review assesses whether antipyretic measures in malaria influences outcome, measured by length of illness, parasitaemia, and occurrence of convulsions.

Oral iron supplements for children in malaria-endemic areas
Iron-deficiency anaemia is common during childhood, particularly in rural areas of Africa, but there have been concerns that iron supplementation might increase the risk of malaria. This review assesses whether this concern is true, and assesses the effect of iron supplementation on malaria and deaths.

Treating uncomplicated P. vivax malaria

Artemisinin-based combination therapy for treating uncomplicated Plasmodium vivax malaria
Plasmodium vivax is an important cause of malaria in many parts of Asia and South America. Chloroquine has been the standard treatment for P. vivax malaria for many years but resistance is now rising in some areas. This review assesses whether artemisinin-based combination therapies (ACTs) could replace chloroquine in areas with resistance.

Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine
Primaquine is the most widely used drug for treating the dormant liver stage of Plasmodium vivax, but several different dosing regimens have been used. This review evaluates the efficacy of different primaquine regimens for preventing relapses in people with P. vivax malaria.

Treating severe malaria

Artesunate versus quinine for treating severe malaria
Severe malaria occurs when infection with the malaria parasite causes serious failure of the body's major organs, and results in around 600,000 deaths every year. Artesunate is now the treatment of choice recommended by the World Health Organization, replacing the older drug quinine. This review presents the relative benefits and harms of artesunate and quinine.

Intramuscular arteether for treating severe malaria
Artesunate is currently the recommended treatment for severe malaria, but several other artemisinin-derivatives are available commercially. This review assesses the relative benefits and harms of intramuscular artemether, and later this year a review of intramuscular artemether will be published.

Blood transfusion for treating malarial anaemia
Blood transfusions are sometimes given to people with severe anaemia due to malaria, but has a number of risks including transfusion reactions, infection with blood borne diseases, and fluid overload. This review evaluates the benefits and harms of routine blood transfusion for severe anaemia in areas where malaria is common.

Routine anticonvulsants for treating cerebral malaria
Cerebral malaria is a common and potentially lethal complication of Plasmodium falciparum infection. People with cerebral malaria become unconscious, and often have convulsions. This review evaluates whether giving anticonvulsant drugs routinely to people with cerebral malaria will improve the outcome of treatment and prevent death.

Steroids for treating cerebral malaria
Cerebral malaria is associated with swelling of the brain. Corticosteroid drugs could reduce the harmful effects of this swelling, but they could also suppress host immunity to infection. This review assesses the effects of corticosteroid drugs in patients with cerebral malaria on death, life-threatening complications, and residual disability in survivors.

Mannitol and other osmotic diuretics as adjuncts for treating cerebral malaria
The main treatment for cerebral malaria is parenteral antimalarial drugs. Mannitol and urea are used as adjunct therapy for cerebral malaria, but the World Health Organization does not recommend them. This review compares mannitol or urea to placebo or no treatment for treating children and adults with cerebral malaria.

Improving access to treatment

Home- or community-based programmes for treating malaria
In many rural areas of Africa, children are unable to access effective malaria treatment because health services are either too far away or antimalarial drugs are too expensive. One strategy to overcome these problems is to train mothers, volunteers, or community health workers to recognise fever and provide antimalarial medicines at a low cost. This review evaluates whether these programmes reduce childhood deaths and increase the number of children who receive effective anti-malarials within the first 24 hours of their illness.

Pre-referral rectal artesunate for severe malaria (due for publication in May 2014)
Severe malaria is treated by giving artesunate injections, either into the vein or muscle, and treatment needs to be started as quickly as possible to reduce the risk of death and brain damage. However, in many places where malaria is common, people living in rural settings have to travel for several hours to reach healthcare clinics and hospitals, and many die before receiving treatment. In these settings, people without formal healthcare education could be trained to give artesunate rectal suppositories to start treating malaria while the patient is being transported. This was tested in a large trial, but the results were not straightforward. This review critically appraises this trial and provides an independent assessment of the results.

Acknowledgements: David Sinclair, Anne-Marie Stephani and Paul Garner for drafting the text and selecting the reviews. This work is funded by UKaid from the UK Government Department for International Development for the benefit of low and middle income countries.

Image credit: GODONG/BSIP/SCIENCE PHOTO LIBRARY/C014/2269

Date published: 25 April 2014

Contact: Cochrane Editorial Unit (editorial-unit@cochrane.org)

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