Tropical Health Matters

A variety of rapid diagnostic tests (RDTs) have been developed to detect malaria parasites in primary care settings.  RDTs are in part a response to the higher costs of artemisinin-based combination therapies (ATCs) and the need to reduce wholesale use of ACTs for any fever in hopes of preserving efficacy longer. Because of the great threat of malaria to children under five years of age, most endemic countries still permit presumptive treatment with ACTs for these children.  RDTs therefore, can be an important component of case management in adult populations.

Even though the cost of arthmether-lumefantrine (AL) have been brought down, and efforts are underway to achieve similar cost reductions for artesunate-amodiaquine products, there still exists justification for RDTs from the standpoint of preserving efficacy.  Charlotte Zikusooka and colleagues have documented that, “Compared to treating patients on the basis of clinical diagnosis, the use of RDTs in all clinically diagnosed malaria cases results in cost savings only when 29% and 52% or less of all suspected malaria cases test positive for malaria and are treated with AS+SP and AL, respectively.” The cost savings is obviously also dependent on the relative price of RDTs compared to adult dose costs of ACTs.

These researchers ultimately conclude that, “While the use of RDTs in all suspected cases has been shown to be cost-saving when parasite prevalence among clinically diagnosed malaria cases is low to moderate, findings show that targeting RDTs at the group older than six years and treating children less than six years on the basis of clinical diagnosis is even more cost-saving. In semi-immune populations, young children carry the highest risk of severe malaria and many healthcare providers would find it harder to deny antimalarials to those who test negative in this age group.”

The study benefits hinge on health worker judgement: “This result holds true only if health workers prescribe and or dispense antimalarials to only the patients that are found to be malaria test positive.”  Discussion with primary care clinic staff in Mozambique recently showed that this may be a major stumbling block.  Apparently they administer the RDTs, but do not trust the results, so send the client to the laboratory. Then regardless of the lab results, they tend to treat with antimalarial drugs, because ‘one never knows.’

While RDTs have an advantage among adult patients (assuming a country actually makes provision of ACTs for adults a priority), their implementation cannot be effective without proper training and follow-up supervision to reinforce correct use.

In Mali, ‘shocking levels’ of malaria misdiagnosis are being reported. “The discrepancy between real and assumed cases has reached “shocking” levels all over Africa … Malaria diagnostics in Mali rely on expensive equipment which most health clinics, particularly in rural areas, cannot afford and do not have the trained staff to use … As a result most doctors “make assumptions based on suspicion,” he said, leading to over-treatment of malaria cases … most people who develop a fever in Mali do not visit a health clinic at all either because they live too far away, or are unwilling to pay up to US$0.95 for a consultation.”

They self diagnose and treat instead.” IRIN reports that, “Up to 70 percent of cases of feverish illness in children are diagnosed and treated at home.” In contrast, “Laboratories the gold standard. Mali needs more and better-equipped laboratories to combat mass misdiagnosis.”

Although the news release about Mali does not give numbers, they may be quite substantial. Two years ago a medical officer working for a major corporation in Nigeria discussed the experiences from their company’s employee/family clinics and showed that without laboratory tests at least 75% of patients whom clinicians diagnosed as having malaria were free of parasites. The company thought that lab tests resulted in a major savings for the company in terms of malaria pharmaceuticals.

Many diseases present with malaria-like symptoms, including dengue fever, which is poorly recognized in Africa. Nordstrand et al. (2007) report that in the absence of laboratory diagnosis, tickborne relapsing fever is treated as malaria in Togo.

There are concerns about the cost of laboratory diagnosis. Rapid Diagnostic Tests (RDTs), though not without expense, are a solution in low resource settings. Hopkins et al. (2008) report that “Based on the high PPV (positive predictive value: 93%) and NPV (negative predictive value: >97%), HRP2(histidine-rich protein 2)-based RDTs are likely to be the best diagnostic choice for areas with medium-to-high malaria transmission rates in Africa.”

Even when laboratory diagnosis is available, it may not be used. As Polage and colleagues observed in Ghana, “Perhaps the most significant barrier to laboratory use was physicians’ reliance on clinical judgment.”

A lesson here is that clinical diagnosis may be no better that self-diagnosis. An interesting question is by how much would the world’s burden of malaria be reduced simply by performing an accurate diagnosis in a laboratory or with RDTs?

A few years ago a colleague who works for a large corporation in Nigeria showed me malaria diagnosis laboratory results from their company clinics.  The company was able to test workers and family members in their labs after a clinical diagnosis of malaria and before dispensing drugs. Over a span of 5 years only 20-25% of patients were found to be parasitaemic, and without the tests, most people would have been given malaria treatment.  Those were the days when the company was still dispensing cheap chloroquine. Today with ACTs that cost 10-50 times more than chloroquine, these lab tests are even more important.

Zurovac et al. (2006) found that when both clinical and laboratory skills were improved, major cost savings resulted in malaria treatment. Ochola et al. (2006) concluded that dipsticks can perform better than standard microscopy in clinical (field) settings in endemic areas.  Rennie et al. (2006) reported that community health workers can be trained to perform rapid diagnostic tests.

Reyburn et al. (2007) compared RDTs with microscopy in Tanzania among clinic attenders.  Patients were assigned equally to receive one or the other form of test.  In both groups approximately 80% of patients had complained of fever within 48 hours.  Fourteen percent of patients in the microscopy group were found to have malaria parasites, while 16% in the RDT group tested positive. Clinical diagnosis might have overestimated the proportion of malaria case by three or four times.

The reality is that few front line health facilities in malaria-endemic have laboratory services, and thus rapid diagnostic tests are being considered. RDTs are estimated to cost between US$0.60 – $1.00, and as implied from research mentioned above, the cost savings from reducing over-prescribed ACTs could be substantial and might offset these costs.   The question is whether malaria control programs will be able to adopt, buy and distribute rapid test materials to front line facilities. Hopefully financial resources like GFATM and PMI can help address this question.