Cluster-randomized study of intermittent preventive treatment for malaria in infants (IPTi) in southern Tanzania: evaluation of impact on survival

Abstract

BackgroundIntermittent Preventive Treatment for malaria control in infants (IPTi) consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204].MethodsAfter baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12) or not (n = 12). Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived.ResultsSurvival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P < 0.0001). Over the three years of the study there was a marked improvement in survival in both groups. Between 2001-4 and 2005-7, mortality rates in two-11 month olds fell from 34.1 to 23.6 per 1,000 person-years in intervention areas and from 32.3 to 20.7 in comparison areas. In 2007, divisions implementing IPTi had a 14% (95% CI -12%, 49%) higher mortality rate in two-11 month olds in comparison with non-implementing divisions (P = 0.31).ConclusionThe lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

Effectiveness of a Home-Based Counselling Strategy on Neonatal Care and Survival: A Cluster-Randomised Trial in Six Districts of Rural Southern Tanzania

“…Baseline neonatal mortality and newborn care practices were assessed through a survey of all households in five of the six study districts in 2007 (excluding Mtwara Rural) as part of a study assessing the effect of intermittent preventive treatment of malaria in infants [ 18 , 27 ]. In 2013 we did a representative household survey, including 185,000 households from all 132 wards.…”

Brokering the boundary between science and advocacy: the case of intermittent preventive treatment among infants

“…The results from an evaluation of implementing IPTi in five districts in Southern Tanzania showed no effects on child survival attributable to the intervention (Schellenberg et al 2011). Translating evidence into practice depends on systems and situations that are different from trial conditions.…”

“…Translating evidence into practice depends on systems and situations that are different from trial conditions. As Schellenberg et al say (2011), there are ‘real-life’ challenges in health systems (e.g. low coverage, late administration) that can act as significant constrain to the replication of trial results.…”

“…In the context of increasing interest on malaria and greater availability of funding for malaria, but few effective interventions, the results of the first IPTi study reported in 2001 (Schellenberg et al ) generated enthusiasm among the core group of scientists involved in the trial. This research group alongside others formed the IPTi Consortium in 2003 following new trials that were initiated in Gabon, Ghana and Mozambique in 2002 and 2003 to test the intervention.…”

Pediatric Cerebral Malaria: A Scourge of Africa

“…In a meta-ana lysis of six trials of IPTi using SP, the intervention decreased malaria episodes by 30%, anemia by 21%, malaria hospital admissions by 38% and overall hospital admissions by 23% [121]. However, a randomized clinical trial of IPTi using mortality as an outcome showed no benefit [122]. The WHO conditionally recommends IPTi for children in moderate-tohigh transmission areas where resistance to SP is less than 50% [123].…”