Parenteral artemisinins are associated with reduced mortality and neurologic deficits and improved long-term behavioral outcomes in children with severe malaria

Background: In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM. Methods: From 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up. Results: 346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07-0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine. Conclusions: Treatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria

Rapid reduction of malaria following introduction of vector control interventions in Tororo District, Uganda: a descriptive study

This article was published by BioMed Central in Malaria Journal;16:227. DOI 10.1186/s12936-017-1871-3Background: In 2012, Tororo District had the highest malaria burden in Uganda with community Plasmodium prevalence of 48%. To control malaria in the district, the Ministry of Health introduced universal distribution of long lasting insecticide-treated nets (LLINs) in 2013 and added indoor residual spraying (IRS) in 2014. This study assessed malaria incidence, test positivity rates and outpatient (OPD) attendance due to malaria before and after vector control interventions. Methods: This study was based on analysis of Health Management Information System (HMIS) secondary malaria surveillance data of 2,727,850 patient records in OPD registers of 61 health facilities from 2012 to 2015. The analysis estimated monthly malaria incidence for the entire population and also separately for <5- and ≥5-year-olds before and after introduction of vector control interventions; determined laboratory test positivity rates and annual percentage of malaria cases in OPD. Chi square for trends was used to analyse annual change in malaria incidence and logistic regression for monthly reduction. Results: Following universal LLINs coverage, the annual mean monthly malaria incidence fell from 95 cases in 2013 to 76 cases per 1000 in 2014 with no significant monthly reduction (OR = 0.99, 95% CI 0.96–1.01, P = 0.37). Among children <5 years, the malaria incidence reduced from 130 to 100 cases per 1000 (OR = 0.98, 95% CI 0.97–1.00, P = 0.08) when LLINs were used alone in 2014, but declined to 45 per 1000 in 2015 when IRS was combined with LLINs (OR = 0.94, 95% CI 0.91–0.996, P < 0.0001). Among individuals aged ≥5 years, mean monthly malaria incidence reduced from 59 to 52 cases per 1000 (OR = 0.99, 95% CI 0.97–1.02, P = 0.8) when LLINs were used alone in 2014, but reduced significantly to 25 per 1000 in 2015 (OR = 0.91, 95% CI 0.88–0.94, P < 0.0001). Malaria test positivity rate reduced from 57% in 2013 to 30% (Chi = 15, P < 0.0001) in 2015. Slide positivity rate reduced from 45% in 2013 to 21% in 2015 (P = 0.004) while RDT positivity declined from 69 to 40%. Conclusions: A rapid reduction in malaria incidence was observed in Tororo District following the introduction of IRS in addition to LLINs. There was no significant reduction in malaria incidence following universal distribution of LLINs to communities before introduction of IRS

Malaria incidence among children less than 5 years during and after cessation of indoor residual spraying in Northern Uganda

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: In June 2015, a malaria epidemic was confirmed in ten districts of Northern Uganda; after cessation of indoor residual spraying (IRS). Epidemic was defined as an increase in incidence per month beyond one standard deviation above mean incidence of previous 5 years. Trends in malaria incidence among children-under-5-years were analysed so as to describe the extent of change in incidence prior to and after cessation of IRS. Methods: Secondary data on out-patient malaria case numbers for children-under-5-years July 2012 to June 2015 was electronically extracted from the district health management information software2 (DHIS2) for ten districts that had IRS and ten control districts that didn’t have IRS. Data was adjusted by reporting rates, cleaned by smoothing and interpolation and incidence of malaria per 1000 population derived. Population data obtained from 2002 and 2014 census reports. Data on interventions obtained from malaria programme reports, rainfall data obtained from Uganda National Meteorological Authority. Three groups of districts were created; two based on when IRS ended, the third not having IRS. Line graphs were plotted showing malaria incidence vis-à-vis implementation of IRS, mass net distribution and rainfall. Changes in incidence after withdrawal of IRS were obtained using incidence rate ratios (IRR). IRR was calculated as incidence for each month after the last IRS divided by incidence of the IRS month. Poisson regression was used to test statistical significance. Results: Incidence of malaria declined between spray activities in districts that had IRS. Decline in IRR for 4 months after last IRS month was greater in the sprayed than control districts. On the seventh month following cessation of IRS, incidence in sprayed districts rose above that of the last spray month [1.74: 95% CI (1.40–2.15); and 1.26: 95% CI (1.05–1.51)]. Rise in IRR continued from 1.26 to 2.62 (95% CI 2.21–3.12) in June 2015 for districts that ended IRS in April 2014. Peak in rainfall occurred in May 2015. Conclusion: There was sustained control of malaria incidence during IRS implementation. Following withdrawal and peak in rainfall, incidence rose to epidemic proportions. This suggests a plausible link between the malaria epidemic, peak in rainfall and cessation of IRS