Rapid diagnostic tests to improve treatment of malaria and other febrile illnesses: patient randomised effectiveness trial in primary care clinics in Afghanistan

Abstract

Objective: To assess the impact of rapid diagnostic tests on the diagnostic accuracy and treatment of malaria and non-severe fever in an Asian setting.

Design: Patient randomised trial in primary level clinics.

Setting: Two areas of Afghanistan where Plasmodium vivax and Plasmodium falciparum are endemic; one area with moderate transmission (eastern region) and one with low transmission (northern region).

Participants: 5794 patients of all ages with suspected malaria enrolled by 80 clinicians in 22 clinics.

Interventions: Malaria rapid diagnostic tests were compared with clinical diagnosis where no parasite diagnostic test was available, longer established field microscopy, and recently introduced microscopy.

Main outcome measures: Proportion of patients appropriately treated with an antimalarial, defined as patients with P vivax who received chloroquine, patients with P falciparum who received artemisinin based combination therapy, and patients with no malaria parasites who did not receive an antimalarial. Secondary outcomes included diagnostic test accuracy and the proportion of patients negative for malaria who received antibiotics and antimalarials.

Results: In the low transmission area, comparing rapid diagnostic tests with clinical diagnosis, 65% (212/325) versus 12% (40/321) of febrile patients were appropriately treated for malaria (adjusted odds ratio 92.7, 95% confidence interval 12.4 to 694.1, P<0.001). The proportion of patients who were negative for malaria and received an antibiotic was 57% (185/325) in the rapid diagnostic test arm compared with 14% (46/321) in the clinical diagnosis arm (16.9, 3.8 to 75.4, P<0.001). In the comparison of rapid diagnostic test with microscopy in the moderate transmission area, 83.6% (1696/2028) versus 76.3% (1512/1983) of patients were appropriately treated for malaria (1.70, 1.30 to 2.23, P<0.001). A higher proportion of P falciparum cases received appropriate treatment with artemisinin based combination therapy when malaria was diagnosed by rapid diagnostic test (82%, 58/71 v 32%, 24/76; 9.2, 3.88 to 21.66, P<0.001).

Conclusions: In South and central Asian regions of low to moderate malaria transmission where clinics lack capacity for diagnosis with rapid diagnostic tests or microscopy, the introduction of the tests should be considered to improve clinical care, reduce the overuse of antimalarials, and improve disease surveillance.

Trial registration: ClinicalTrials.gov NCT00935688.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: the research was funded by the Bill and Melinda Gates Foundation and Sponsored by the London School of Hygiene and Tropical Medicine; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

© Leslie et al 2014.

Figures

Fig 1 Patient flow through trial in low transmission area (north region) in five clinics that lacked microscopy and used clinical signs and symptoms to diagnose malaria

Fig 2 Patient flow through trial in moderate transmission area (east region) in 12 clinics that used microscopy to diagnose malaria

Fig 3 Patient flow through trial in low transmission area (north region) in five clinics that used microscopy to diagnosis malaria

Fig 4 Forest plot showing relative odds for appropriate malaria treatment in clinics in low transmission area using clinical diagnosis versus rapid diagnostic test (RDT). Clinic 5 was excluded because of zero events (no patients appropriately treated in control arm)

Fig 5 Forest plot showing relative odds for appropriate malaria treatment in clinics in low transmission area using microscopy versus rapid diagnostic test (RDT)

Fig 6 Forest plot showing relative odds for appropriate malaria treatment in clinics in moderate transmission area using microscopy versus rapid diagnostic test (RDT)