Diagnosis and treatment of malariaBMJ 2007; 334 doi: https://doi.org/10.1136/bmj.39126.485370.BE (Published 22 February 2007) Cite this as: BMJ 2007;334:375
- Ambrose O Talisuna, assistant commissioner of health services 1,
- Denise Njama Meya, research coordinator2
- 1Uganda Ministry of Health, Epidemiological Surveillance Division, PO Box 7272, Kampala, Uganda
- 2Makerere University-University of California San Francisco Malaria Research Collaboration, PO Box 7475, Kampala, Uganda
Malaria is a major public health problem and is endemic in about 107 countries. The symptoms of uncomplicated malaria are non-specific and similar to many other disease syndromes, including minor viral illnesses. People living in areas where malaria is endemic are often familiar with these symptoms and frequently diagnose themselves, so that over-diagnosis is widespread.1
Prompt and accurate diagnosis of malaria is important for effective case management and if implemented well should reduce mortality from this disease.2 High sensitivity of diagnosis is crucial, and high specificity could reduce unnecessary treatment and improve the diagnosis of other febrile illness.3 In this week's BMJ, a randomised controlled trial by Reyburn et al assesses the effect of rapid diagnostic tests compared with microscopy for guiding treatment of acute febrile illness in outpatients in Tanzania.4
Light microscopy and rapid diagnostic tests are the two most commonly used methods of confirming a diagnosis of malaria. Microscopy, the gold standard, has several advantages including low cost and high sensitivity and specificity when used by well trained staff. Rapid diagnostic tests (which detect parasite antigens) are easier to perform by staff with basic training, have less waiting time and indirect costs, but are relatively more expensive. A recent decrease in their cost may make it possible to increase their use in sub-Saharan Africa.
Despite the availability of these two methods, presumptive treatment of malaria (without laboratory confirmation) remains common practice.5 Reyburn and colleagues found massive over-diagnosis of malaria.4 Surprisingly, rapid diagnostic tests combined with basic training did not reduce over-treatment for malaria. Of the 1193 and 1204 patients with complete data who were randomised to rapid diagnostic tests and microscopy, respectively, only 52% and 50% had a correct prescription. More than half the prescriptions for antimalarial drugs were given to people who had negative test results (blood smear or rapid diagnostic test).4 Furthermore, children with negative results of rapid diagnostic tests were more likely to be treated for malaria than those with a negative smear.
In the era of artemisinin combination treatments, we urgently need to improve parasitological confirmation of the diagnosis of malaria. Reasons include the relatively high cost of such treatments, which makes unnecessary treatment unsustainable; the need for better care in people who have parasite positive tests; the need to reduce the risk of adverse events and drug use to limit the selection of drug resistant parasites; the need for more robust health information; and the need to identify people with parasite negative tests in whom another diagnosis must be sought.
Reyburn and colleagues found that health workers continue to treat people for malaria even if the diagnostic test is negative,4 emphasising the need to change the behaviour of such workers. However, they also found that this is difficult to do. The practice of treating patients with a negative test may be due to traditional teaching in medical schools, which promotes treatment on the basis of the health worker's index of suspicion, and also due to ambiguous phrases in some national guidelines.
The World Health Organization's generic treatment guidelines recommend parasitological confirmation of the diagnosis of malaria where malaria transmission is low, moderate, or unstable.6 In settings where the incidence of malaria is low, WHO recommends that health workers should be trained to identify patients who have been exposed to malaria before they carry out a parasitological test. In stable high transmission settings, where malaria is a common cause of febrile illness in children, WHO recommends that antimalarial drugs should be given to children with fever (≥37.5oC) or a history of fever that has no other obvious cause. In children 5 years old and above, in pregnant women, and in settings with a high prevalence of HIV a diagnosis should have parasitological confirmation.
The WHO guidelines do not state that a patient with a negative test should be treated for malaria. However, some countries, such as Uganda, have adopted phrases like, “Any patient with fever or a history of fever within 24 hours without evidence of other disease should be treated for malaria even with a negative blood smear for malaria parasites.”7 Such recommendations are aimed at increasing antimalarial coverage and potentially reducing the risk of progression to severe disease and death.
However, recent evidence from the field does not support such practices. In Kenya, even with imperfect conditions for microscopy, implementation of revised clinical practice (routine blood test for all febrile adults and restricting treatment to only positive tests) reduced the financial costs for antimalarial drugs, antibiotics, microscopy, and errors from over-diagnosing malaria by almost 60%.8 A study in Uganda among febrile children with a negative smear test for malaria, who were followed up without being given an antimalarial drug, found that less than 1% developed uncomplicated malaria and identified no unfavourable outcomes.9 Withholding treatment for malaria in people with a negative test was safe and saved treatments for children in more urgent need.9
So what can we learn from the study by Reyburn and colleagues? Ideally the findings should “kick start” the process to change the behaviour of health workers. National and international guidelines should be explicit about how to treat patients with negative tests. The choice between rapid diagnostic tests or microscopy will depend on local circumstances, including available skills, the use of microscopy for the diagnosis of other diseases, and whether patients seek treatment from formal health facilities or from community health workers. Innovative approaches beyond basic training will be needed, including regular supervision and team building between laboratory and clinical staff, regular consensus reviews, surveillance and trend analysis for laboratory confirmed malaria and other common febrile illnesses, and interventions to increase public knowledge about the right way to diagnose malaria.
Competing interests: None declared.
Provenance and peer review: Commissioned; not externally peer reviewed.