Research Article: Universal versus conditional day 3 follow-up for children with non-severe unclassified fever at the community level in Ethiopia: A cluster-randomised non-inferiority trial

Date Published: April 17, 2018

Publisher: Public Library of Science

Author(s): Karin Källander, Tobias Alfvén, Tjede Funk, Ayalkibet Abebe, Abreham Hailemariam, Dawit Getachew, Max Petzold, Laura C. Steinhardt, Julie R. Gutman, Lars Åke Persson

Abstract: BackgroundWith declining malaria prevalence and improved use of malaria diagnostic tests, an increasing proportion of children seen by community health workers (CHWs) have unclassified fever. Current community management guidelines by WHO advise that children seen with non-severe unclassified fever (on day 1) should return to CHWs on day 3 for reassessment. We compared the safety of conditional follow-up reassessment only in cases where symptoms do not resolve with universal follow-up on day 3.Methods and findingsWe undertook a 2-arm cluster-randomised controlled non-inferiority trial among children aged 2–59 months presenting with fever and without malaria, pneumonia, diarrhoea, or danger signs to 284 CHWs affiliated with 25 health centres (clusters) in Southern Nations, Nationalities, and Peoples’ Region, Ethiopia. The primary outcome was treatment failure (persistent fever, development of danger signs, hospital admission, death, malaria, pneumonia, or diarrhoea) at 1 week (day 8) of follow-up. Non-inferiority was defined as a 4% or smaller difference in the proportion of treatment failures with conditional follow-up compared to universal follow-up. Secondary outcomes included the percentage of children brought for reassessment, antimicrobial prescription, and severe adverse events (hospitalisations and deaths) after 4 weeks (day 29). From December 1, 2015, to November 30, 2016, we enrolled 4,595 children, of whom 3,946 (1,953 universal follow-up arm; 1,993 conditional follow-up arm) adhered to the CHW’s follow-up advice and also completed a day 8 study visit within ±1 days. Overall, 2.7% had treatment failure on day 8: 0.8% (16/1,993) in the conditional follow-up arm and 4.6% (90/1,953) in the universal follow-up arm (risk difference of treatment failure −3.81%, 95% CI −∞, 0.65%), meeting the prespecified criterion for non-inferiority. There were no deaths recorded by day 29. In the universal follow-up arm, 94.6% of caregivers reported returning for reassessment on day 3, in contrast to 7.5% in the conditional follow-up arm (risk ratio 22.0, 95% CI 17.9, 27.2, p < 0.001). Few children sought care from another provider after their initial visit to the CHW: 3.0% (59/1,993) in the conditional follow-up arm and 1.1% (22/1,953) in the universal follow-up arm, on average 3.2 and 3.4 days later, respectively, with no significant difference between arms (risk difference 1.79%, 95% CI −1.23%, 4.82%, p = 0.244). The mean travel time to another provider was 2.2 hours (95% CI 0.01, 5.3) in the conditional follow-up arm and 2.6 hours (95% CI 0.02, 4.5) in the universal follow-up arm (p = 0.82); the mean cost for seeking care after visiting the CHW was 26.5 birr (95% CI 7.8, 45.2) and 22.8 birr (95% CI 15.6, 30.0), respectively (p = 0.69). Though this study was an important step to evaluate the safety of conditional follow-up, the high adherence seen may have resulted from knowledge of the 1-week follow-up visit and may therefore not transfer to routine practice; hence, in an implementation setting it is crucial that CHWs are well trained in counselling skills to advise caregivers on when to come back for follow-up.ConclusionsConditional follow-up of children with non-severe unclassified fever in a low malaria endemic setting in Ethiopia was non-inferior to universal follow-up through day 8. Allowing CHWs to advise caregivers to bring children back only in case of continued symptoms might be a more efficient use of resources in similar settings.Trial registrationwww.clinicaltrials.gov, identifier NCT02926625

Partial Text: Mortality in children under 5 years is estimated at 43/1,000 live births globally and 82/1,000 live births in sub-Saharan Africa. This corresponds to the death of 5.6 million children under 5 years old globally each year, 2.8 million in sub-Saharan Africa alone [1].

From December 1, 2015, to November 30, 2016, 4,784 children were eligible for enrolment; consent for enrolment was not obtained for 8 of these. In all, 4,776 children were enrolled (mean 191 per cluster [range 45–762]), but 181 were excluded due to enrolment violations (fever not reported/measured, presence of diarrhoea or pneumonia at enrolment, or outside the eligible age group) (Fig 1). The mean number of children enrolled per HEW was 20.8 (range 1–103) in the universal follow-up arm and 22.1 (range 1–166) in the conditional follow-up arm.

Conditional follow-up of children with non-severe unclassified fever in a low malaria transmission setting in Ethiopia was found to be non-inferior to universal follow-up through 1 week, with an average 2.7% of children across both arms having treatment failure at day 8. No deaths were recorded. While iCCM guidelines recommend universal follow-up for all children, regardless of symptom resolution, IMNCI guidelines recommend less intense conditional follow-up after 2 or 3 days (depending on malaria endemicity). To our knowledge, this study and a sister study in DRC [24] are the first to provide evidence that conditional follow-up is no less safe or marginally less safe than universal follow-up in children aged 2–59 months seen by CHWs.

Source:

http://doi.org/10.1371/journal.pmed.1002553

 

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