Clinical malaria recurrence and associated factors in infancy following IPTp-DP versus IPTp-SP in Busia, Uganda; a secondary analysis using the Conditional Frailty model

BACKGROUND: In sub-Saharan Africa, malaria remains a leading cause of morbidity and mortality in children under five. Recurrent malaria not only increases the risk of severe anaemia and developmental delays in infants, but also presents unique challenges for statistical modelling, as episodes are often correlated. Studies have explored malaria dynamics in infants but gaps remain in contextualizing specific risk factors and how they influence malaria recurrence using appropriate modelling techniques that account for correlation. This study compared malaria recurrence among study infants and explored associated risk factors. METHODS: This was a secondary analysis of data from the PROMOTE trial conducted in Busia district, Uganda. A total of 640 infants born to women who received IPTp-DP or IPTp-SP were followed-up for 12 months. These infants experienced a total of 997 malaria episodes. To also assess dependence in malaria episodes and between-infant heterogeneity, the conditional frailty model was used. The PWP-gap time and Frailty only models were used to confirm the true underlying type of event dependence. RESULTS: IPTp-DP was associated with a modest but non-statistically significant reduction in recurrent malaria hazard compared with IPTp-SP (HR = 0.94, 95% CI 0.82-1.07). Compared with infants whose mothers had no education, infants born to mothers with primary, secondary and higher education had 21%, 42%, and 48% lower hazards of malaria recurrence. Infants whose mothers were 30-45 years had a 28% lower hazard of malaria recurrence compared to those of mothers 16-19 years (HR = 0.72, 95% CI 0.53-0.97). Multigravida mothers had 36% increased hazard of malaria recurrence in their infants compared with primi-gravida mothers (HR = 1.36, 95% CI 1.02-1.80). Infants living 3-5 km from a health facility had 40% greater hazard of malaria recurrence compared with infants in less than 1km (HR = 1.40, 95% CI 1.11-1.77). Malaria episodes were correlated but there was weak non-statistically significant evidence of residual between-infant heterogeneity. CONCLUSIONS: Compared with IPTp-SP, IPTp-DP did not significantly reduce malaria recurrence in infants. Maternal education, maternal age, and distance to health center were associated with the hazard of malaria recurrence in infants. Recurrent malaria episodes were correlated, with evidence of event dependence across successive episodes.