The implementation of malaria intermittent preventive trialtreatment with sulphadoxine-pyrimethamine in infants reduced all-cause mortality in the district of Kolokani, Mali: results from a cluster randomized control

Abstract

BackgroundMalaria intermittent preventive treatment of malaria in infant with sulphadoxine-pyrimethamine (IPTi-SP) reduced the incidence of malaria and anaemia by 30% and 20% respectively. The strategy is now a recommended policy for malaria control. However, there was no published study on the impact of the strategy on mortality. The present study assessed the impact of the implementation of IPTi-SP in health services in Mali on all-cause mortality.MethodsThe 22 health sub-districts of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The IPTi-SP was implemented for two years starting December 2006. Information on births and deaths through 31 March, 2009 was collected on all children who reached four months of age on 1 December, 2006, likely to be exposed to the intervention in 75 localities randomly selected in each zone.ResultsA total of 5,882 children (2,869 from the intervention zone and 3,013 from the nonintervention zone) who reached four months of age between 1 December, 2006 and 1 December, 2008 were surveyed between the age of four months to the age of 18 months from 1 December, 2006 to 31 March, 2009. In the cohort of four to 18 months of age, the mortality rate per 1,000 children was 2.53 in the intervention zone compared to 3.46 in the nonintervention zone, gender and season adjusted mortality rate ratio (MRR) = 0.73 (95% CI 0.55-0.97, p = 0.029). In the cohort of the four to 12 months of age, mortality rates per 1,000 children were 2.22 in the intervention zone and 3.13 in the non-intervention zone, MRR = 0.71 (95% CI 0.49-1.02, p = 0.064) adjusted for gender and season.ConclusionThe implementation of the IPTi-SP resulted in a substantial reduction in all-cause mortality in children. The results of this study support the adoption and the implementation of IPTi-SP as malaria control strategy.Trial RegistrationClinicalTrials.govNCT00766662

Intermittent preventive treatment for malaria in infants

“…We included 12 RCTs that enrolled 17,530 infants. Three of the included RCTs had a cluster‐randomized trial design (Armstrong Schellenberg 2010 TZA; Chandramohan 2005 GHA; Dicko 2012 MLI), and the remaining nine RCTs randomized individuals.…”

“…Nine trials compared IPT to placebo, while the remaining three trials had no IPT as the control arm (Armstrong Schellenberg 2010 TZA; Bigira 2014 UGA; Dicko 2012 MLI). Ten trials co‐administered IPT with routine EPI vaccinations (Armstrong Schellenberg 2010 TZA; Chandramohan 2005 GHA; Dicko 2012 MLI; Gosling 2009 TZA; Kobbe 2007 GHA; Macete 2006 MOZ; Massaga 2003 TZA; Mockenhaupt 2007 GHA; Odhiambo 2010 KEN; Schellenberg 2001 TZA). Two trials administered iron to all enrolled infants (Chandramohan 2005 GHA; Schellenberg 2001 TZA).…”

“…Two trials administered iron to all enrolled infants (Chandramohan 2005 GHA; Schellenberg 2001 TZA). Nine trials administered IPT with sulfadoxine‐pyrimethamine (SP) (Armstrong Schellenberg 2010 TZA; Chandramohan 2005 GHA; Dicko 2012 MLI; Gosling 2009 TZA; Grobusch 2007 GAB; Kobbe 2007 GHA; Macete 2006 MOZ; Mockenhaupt 2007 GHA; Schellenberg 2001 TZA). Alternative drug combinations to SP evaluated in the included trials were amodiaquine (AQ) (Massaga 2003 TZA), chlorproguanil‐dapsone (CD) (Gosling 2009 TZA; Odhiambo 2010 KEN), dihydroartemisinin‐piperaquine (DHAP) (Bigira 2014 UGA), and mefloquine (MQ) (Gosling 2009 TZA).…”

“…The length of follow‐up was until 24 months of age in eight trials (Bigira 2014 UGA; Chandramohan 2005 GHA; Gosling 2009 TZA; Grobusch 2007 GAB; Kobbe 2007 GHA; Mockenhaupt 2007 GHA; Odhiambo 2010 KEN; Schellenberg 2001 TZA). In the remaining four trials infants were followed‐up after the discontinuation of the intervention up to a maximum of 18 months of age (Armstrong Schellenberg 2010 TZA; Dicko 2012 MLI; Macete 2006 MOZ; Massaga 2003 TZA).…”

Malarial pathocoenosis: beneficial and deleterious interactions between malaria and other human diseases

“…This combination drastically reduced both life expectancy at birth and adult life expectancy in areas where malaria was endemic.” While this is not absolute proof that malaria was the most important component of past pathocoenoses (including not only those of the classical antiquity), strong arguments exist in support of this hypothesis, suggesting that malaria was the most frequent fatal disease due to both direct and indirect effects. Several indirect empirical studies support the Grmek's hypothesis suggesting that the prevalence of a disease could depend on that of “all other diseases.” Indeed, in numerous well-documented cases, effective malaria-specific interventions (e.g., insecticide spraying, insecticide-impregnated bed-net programs or implementation of preventive treatments) have lead to reductions in mortality several-fold greater than would have been expected on the basis of the estimation of malaria-related mortality (e.g., Shanks et al, 2008 ; Dicko et al, 2012 ). For example, in Guyana, in the 1940–50s, the number of deaths from all causes (including non-vector transmitted diseases) decreased with deaths from malaria and followed the elimination of the mosquito vector (Giglioli, 1972 ).…”