Malaria over-diagnosis and over-treatment in Zambia

Malaria diagnostics are grossly underused and there is widespread over-treatment for malaria in patients with negative test results in Zambia, according to the findings of a cross-sectional survey published in the May 23-30^th edition of the Journal of American Medical Association. The study calls for the provision of new tools to reduce the overuse of expensive antimalarial treatments and recommends a major change in the treatment of fever in patients without malaria.

Microscopy is the mainstay of malaria diagnosis. However, it requires a relatively well-organised health system infrastructure with functioning microscopes, trained technicians, a regular supply of reagents, supervision, and quality control.

Low levels of parasites might be missed by trained technicians resulting in falsely negative blood smear results. This might have catastrophic consequences if antimalarial treatment is withheld on the basis of negative microscopy results.

Over-diagnosis and over-treatment of malaria, on the other hand, occurs when diagnosis is based on clinical grounds without regard for parasitological test results.

Studies in Tanzania, Kenya, and Zambia have highlighted the fact that microscopy results from diagnostic laboratories are often ignored by drug prescribers which results in over-treatment. This has significant economic considerations since many African countries have adopted the expensive artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria.

Empowering prescribers and health facilities with no microscopy with the capacity for point of care malaria diagnosis might significantly reduce over-prescription of costly ACTs. Rapid antigen detection diagnostic tests (RDTs) offer a cost-effective approach in this regard. But the performance of RDTs has not been investigated under routine field condition.

In order to address this short-coming, a team of US, UK, and Zambian investigators carried out a study to investigate the association between use of microscopy and RDT and the prescription of antimalarial drugs in Zambian health facilities.

In 2003 Zambia adopted the use of artemether-lumefantrine as well as a malaria diagnosis strategy in which malaria microscopy was to be provided in all health facilities to achieve a rate of at least 80% diagnostic testing for suspected malaria cases by 2008. RDTs were also rolled out to all districts by the first quarter of 2005 accompanied by country-wide training in the use of RDTs. It is against this background that the study was undertaken.

The study was a cross-sectional, cluster sample survey carried out between March and May 2006 during the high malaria transmission period. The study participants were outpatients treated during one working day at health facilities in four sentinel districts. The study team arrived unannounced at each facility. In health facilities with laboratories, RDTs were carried out by technicians; in the absence of a laboratory, RDTs were carried out by a health worker who also prescribed antimalarial treatment according to the test results.

When the patients had completed the clinical evaluation including diagnostic testing and receiving antimalarial treatment, patients or their care takers were interviewed by the study team after informed consent. The interviewers collected information about demographic patient characteristics, presenting complaints, a history of fever, the assessment by the health worker, and the drug-dispensing practices undertaken during the facility visit. Patient-held records were consulted for information about diagnostic procedures requested, results reported, and medications given. At the end of the exit interview, patients were weighed and their axillary temperatures taken. Each facility was also assessed for the availability of antimalarial drugs, microscopy and RDTs.

The analysis was restricted to health facilities with functional microscopy or RDTs and to patients whose weight and age were recorded.

An equipment survey revealed that 17 % of 104 health facilities surveyed had functional microscopy, 63% had RDT, and 73% had one or more diagnostics available.

The team evaluated 1,717 patients of all ages who had fever and were evaluated by 105 health workers at the 76 health facilities that could undertake a parasitological malaria diagnosis.

In all, 276 patients with fever were evaluated at health facilities with microscopy, 1,207 in health facilities with RDTs, and 234 in facilities with both.

Of the patients with fever, blood smears were carried out in 27.8% (95% confidence interval [CI], 13.1%-42.5%) of those treated in health facilities with functional microscopy; RDTs were used for 22.8 % (95% CI, 13.8%-31.8%) of patients in facilities with RDTs.

In facilities with both diagnostic tests available, no patient had both microscopy and RDT carried out. Malaria blood smears were positive in 45.4 % (95% CI, 27.2%-63.6%) of patients whereas RDTs were positive in 44.2 % (95% CI, 33.4%-55.0%).

An antimalarial was prescribed to all patients with positive microscopy (100 %) and nearly all who had positive RDT results (96.6 %).

Significantly, antimalarials were prescribed for 58.4% (95% CI, 36.7%-80.2%) of the patients with negative blood smear results and for 35.5% (95% CI, 16.0%-55.0%) of those with negative RDT results. Although many patients with fever (72.6 %) did not have any diagnostic test carried out, 65.9% of these were prescribed antimalarials.

In facilities with artemether-lumefantrine in stock, this antimalarial was prescribed not only to a large proportion of febrile patients with positive diagnostic test results (blood smear, 75.0% ; RDT, 70.4% ), but also to some patients with a negative test results (blood smear, 30.4%; RDT 26.7%). The use of artemether-lumefantrine in patients who did not have any parasitological diagnostic evaluation was 42.1 % overall.

The finding highlight the fact that despite efforts to improve malaria diagnosis in Zambia, microscopy and RDTs are grossly underused and patients with no malaria frequently receive antimalarials. This practice is not unique to Zambia alone and probably reflects the greater problem of over-treatment with antimalarials in Africa. This over-treatment in the era of costly ACTs probably constitutes a significant financial burden to the economies of resource-poor countries which have to address other pressing development problems.

The researchers conclude that during the implementation of ACTs for malaria control, a concerted effort must be made to increase the awareness of health workers and prescribers about the need for the use of malaria diagnostics and to prescribe treatment in only those patients with positive diagnostic test results.