Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses

Abstract

BackgroundWHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT). However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa.MethodsChildren 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days.ResultsOver the course of one year, 965 children were enrolled; 158 (16.4%) were RDT-positive and treated with artemether-lumefantrine and 807 (83.4%) were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6%) children became RDT-positive after enrolment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrolment. In addition, 12 (1.2%) children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9%) children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95%CI 96.9-98.7) and specificity of 96.3% (95%CI 96.3-98.4).ConclusionsUse of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive bacterial disease is uncommon in children with non-severe illness and most cases occurred in infants with a current fever.

Impact of introduction of rapid diagnostic tests for malaria on antibiotic prescribing: analysis of observational and randomised studies in public and private healthcare settings

“…In most similar settings where bacterial diagnosis has been undertaken, however, few patients have documented bacterial infections; fewer than 2% (and in virtually all reports <5%) of patients with uncomplicated febrile illness have positive results on blood cultures. [51][52][53] Not all bacterial causes of fever lead to bacteraemia, but, for example, in young children with uncomplicated febrile illness in Zanzibar, just 22% had an infection retrospectively considered to require antibiotics. 54 At a population level it is likely that relatively few patients in our studies had bacterial infections requiring antibiotic treatment, and the incidence is unlikely to be anywhere near the 69% suggested by antibiotic prescription to those with negative results of malaria tests.…”

Laboratory Diagnosis of Malaria: Conventional and Rapid Diagnostic Methods

“…The available data support use of these assays in children. 1,13,14 In the same way, relatively few controlled clinical evaluations of MRDTs have been conducted with women. For pregnant women, symptoms consistent with malaria are common, but in one study less than a third of these women had parasitemia.…”

Comparative Rapid Diagnostic Test Kit and Presumptive Treatment of Fever Cases in the Hohoe Municipality, Ghana

“…This could also be suggestive of the high prevalence of Malaria in the high transmission season and low in the low transmission season. Patient's age, Malaria transmission intensity and lack of symptoms have been demonstrated to influence the specificity and sensitivity of RDTs, which can in turn result in under or over diagnosis of the disease [7,9,13,14]. The were checked by field supervisors and a data manager for consistency and accuracy.…”