LLIN evaluation in Uganda project (LLINEUP2): association between housing construction and malaria burden in 32 districts.

BACKGROUND: Well-built housing limits mosquito entry and can reduce malaria transmission. The association between community-level housing and malaria burden in Uganda was assessed using data from randomly selected households near 64 health facilities in 32 districts. METHODS: Houses were classified as 'improved' (synthetic walls and roofs, eaves closed or absent) or 'less-improved' (all other construction). Associations between housing and parasitaemia were made using mixed effects logistic regression (individual-level) and multivariable fractional response logistic regression (community-level), and between housing and malaria incidence using multivariable Poisson regression. RESULTS: Between November 2021 and March 2022, 4.893 children aged 2-10 years were enrolled from 3.518 houses; of these, 1.389 (39.5%) were classified as improved. Children living in improved houses had 58% lower odds (adjusted odds ratio = 0.42, 95% CI 0.33-0.53, p < 0.0001) of parasitaemia than children living in less-improved houses. Communities with > 67% of houses improved had a 63% lower parasite prevalence (adjusted prevalence ratio 0.37, 95% CI 0.19-0.70, p < 0.0021) and 60% lower malaria incidence (adjusted incidence rate ratio 0.40, 95% CI 0.36-0.44, p < 0.0001) compared to communities with < 39% of houses improved. CONCLUSIONS: Improved housing was strongly associated with lower malaria burden across a range of settings in Uganda and should be utilized for malaria control.

LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda.

BACKGROUND: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. METHODS: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020-2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017-2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. RESULTS: Approximately 70% of the study population received LLINs later than scheduled in 2020-2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. CONCLUSIONS: The model results suggest that the disruptions in the 2020-2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas.

Perinatal care and its association with perinatal death among women attending care in three district hospitals of western Uganda.

BACKGROUND: Provision of effective care to all women and newborns during the perinatal period is a viable strategy for achieving the Sustainable Development Goal 3 targets on reducing maternal and neonatal mortality. This study examined perinatal care (antenatal, intrapartum, postpartum) and its association with perinatal deaths at three district hospitals in Bunyoro region, Uganda. METHODS: A cross-sectional study was conducted in which a questionnaire was administered consecutively to 872 postpartum women before discharge who had attended antenatal care and given birth in the study hospitals. Data on care received during antenatal, labour, delivery, and postpartum period, and perinatal outcome were extracted from medical records of the enrolled postnatal women using a pre-tested structured tool. The care received from antenatal to 24 h postpartum period was assessed against the standard protocol of care established by World Health Organization (WHO). Poisson regression was used to assess the association between care received and perinatal death. RESULTS: The mean age of the women was 25 years (standard deviation [SD] 5.95). Few women had their blood tested for hemoglobin levels, HIV, and Syphilis (n = 53, 6.1%); had their urine tested for glucose and proteins (n = 27, 3.1%); undertook an ultrasound scan (n = 262, 30%); and had their maternal status assessed (n = 122, 14%) during antenatal care as well as had their uterus assessed for contraction and bleeding during postpartum care (n = 63, 7.2%). There were 19 perinatal deaths, giving a perinatal mortality rate of 22/1,000 births (95% Confidence interval [CI] 8.1-35.5). Of these 9 (47.4%) were stillbirths while the remaining 10 (52.6%) were early neonatal deaths. In the antenatal phase, only fetal examination was significantly associated with perinatal death (adjusted prevalence ratio [aPR] = 0.22, 95% CI 0.1-0.6). No significant association was found between perinatal deaths and care during labour, delivery, and the early postpartum period. CONCLUSION: Women did not receive all the required perinatal care during the perinatal period. Perinatal mortality rate in Bunyoro region remains high, although it's lower than the national average. The study shows a reduction in the proportion of perinatal deaths for pregnancies where the mother received fetal monitoring. Strategies focused on strengthened fetal status monitoring such as fetal movement counting methods and fetal heart rate monitoring devices during pregnancy need to be devised to reduce the incidence of perinatal deaths. Findings from the study provide valuable information that would support the strengthening of perinatal care services for improved perinatal outcomes.

The role of social support in antiretroviral therapy uptake and retention among pregnant and postpartum women living with HIV in the Greater Accra region of Ghana.

INTRODUCTION: The role of social support in antiretroviral therapy (ART) uptake and retention among pregnant and postpartum women in Ghana's capital, Accra, has received limited attention in the literature. This cross-sectional study extends existing knowledge by investigating the role of social support in ART adherence and retention among pregnant and postpartum women in Accra. METHODS: We implemented a cross-sectional study in eleven (11) public health facilities. Convenience sampling approach was used to recruit 180 participants, out of which 176 with completed data were included in the study. ART adherence in the three months preceding the survey (termed consistent uptake), and ART retention were the outcomes of interest. Initial analysis included descriptive statistics characterized by frequencies and percentages to describe the study population. In model building, we included all variables that had p-values of 0.2 or lesser in the bivariate analysis to minimize negative confounding. Overall, a two-sided p-value of < 0.05 was considered statistically significant. Data were analyzed using Stata version 14.1 (College Station, TX). RESULTS: In the multivariate model, we realized a lower odds trend between social support score and consistent ART adherence, however, this was insignificant. Similarly, both the univariate and multivariate models showed that social support has no relationship with ART retention. Meanwhile, urban residents had a higher prevalence of ART adherence (adjusted Prevalence ratio (aPR) = 2.04, CI = 1.12-3.73) relative to rural/peri-urban residents. As compared to those below age 30, women aged 30-34 (aPR = 0.58, CI = 0.34-0.98) and above 35 (aPR = 0.48, CI = 0.31-0.72) had lower prevalence of ART adherence Women who knew their partner's HIV status had lower prevalence of ART adherence compared to those who did not know (aPR = 0.62, CI = 0.43-0.91). Also, having a rival or co-wife was significantly associated with ART retention such that higher prevalence of ART adherence among women with rivals relative to those without rivals (aOR = 1.98, CI = 1.16-3.36). CONCLUSION: Our study showed that social support does not play any essential role in ART adherence among the surveyed pregnant and postpartum women. Meanwhile, factors such as having a rival and being under the age of thirty play an instrumental role. The study has signaled the need for ART retention scale-up interventions to have a multi-pronged approach in order to identify the multitude of underlying factors, beyond social support, that enhance/impede efforts to achieve higher uptake and retention rates.

Mobility is Associated with Higher-risk Sexual Partnerships Among Both Men and Women in Co-resident Couples in Rural Kenya and Uganda: A Longitudinal Cohort Study.

Population mobility is associated with higher-risk sexual behaviors in sub-Saharan Africa and is a key driver of the HIV epidemic. We conducted a longitudinal cohort study to estimate associations between recent mobility (overnight travel away from home in past six months) or migration (changes of residence over defined geopolitical boundaries) and higher-risk sexual behavior among co-resident couples (240 couples aged ≥ 16) from 12 rural communities in Kenya and Uganda. Data on concurrent mobility and sexual risk behaviors were collected every 6-months between 2015 and 2020. We used sex-pooled and sex-stratified multilevel models to estimate associations between couple mobility configurations (neither partner mobile, male mobile/female not mobile, female mobile/male not mobile, both mobile) and the odds of higher-risk (casual, commercial sex worker/client, one night stand, inherited partner, stranger) and concurrent sexual partnerships based on who was mobile. On average across all time points and subjects, mobile women were more likely than non-mobile women to have a higher-risk partner; similarly, mobile men were more likely than non-mobile men to report a higher-risk partnership. Men with work-related mobility versus not had higher odds of higher-risk partnerships. Women with work-related mobility versus not had higher odds of higher-risk partnerships. Couples where both members were mobile versus neither had greater odds of higher-risk partnerships. In analyses using 6-month lagged versions of key predictors, migration events of men, but not women, preceded higher-risk partnerships. Findings demonstrate HIV risks for men and women associated with mobility and the need for prevention approaches attentive to the risk-enhancing contexts of mobility.

Provider implicit and explicit bias in person-centered maternity care: a cross-sectional study with maternity providers in Northern Ghana.

BACKGROUND: Person-centered maternity care (PCMC) has become a priority in the global health discourse on quality of care due to the high prevalence of disrespectful and lack of responsive care during facility-based childbirth. Although PCMC is generally sub-optimal, there are significant disparities. On average, women of low socioeconomic status (SES) tend to receive poorer PCMC than women of higher SES. Yet few studies have explored factors underlying these inequities. In this study, we examined provider implicit and explicit biases that could lead to inequitable PCMC based on SES. METHODS: Data are from a cross-sectional survey with 150 providers recruited from 19 health facilities in the Upper East region of Ghana from October 2020 to January 2021. Explicit SES bias was assessed using situationally-specific vignettes (low SES and high SES characteristics) on providers' perceptions of women's expectations, attitudes, and behaviors. Implicit SES bias was assessed using an Implicit Association Test (IAT) that measures associations between women's SES characteristics and providers' perceptions of women as 'difficult' or 'good'. Analysis included descriptive statistics, mixed-model ANOVA, and bivariate and multivariate linear regression. RESULTS: The average explicit bias score was 18.1 out of 28 (SD = 3.60) for the low SES woman vignette and 16.9 out of 28 (SD = 3.15) for the high SES woman vignette (p < 0.001), suggesting stronger negative explicit bias towards the lower SES woman. These biases manifested in higher agreement to statements such as the low SES woman in the vignette is not likely to expect providers to introduce themselves and is not likely to understand explanations. The average IAT score was 0.71 (SD = 0.43), indicating a significant bias in associating positive characteristics with high SES women and negative characteristics with low SES women. Providers with higher education had significantly lower explicit bias scores on the low SES vignette than those with less education. Providers in private facilities had higher IAT scores than those in government hospitals. CONCLUSIONS: The findings provide evidence of both implicit and explicit SES bias among maternity providers. These biases need to be addressed in interventions to achieve equity in PCMC and to improve PCMC for all women.

LLIN Evaluation in Uganda Project (LLINEUP2)-Factors associated with coverage and use of long­lasting insecticidal nets following the 2020-21 national mass distribution campaign: a cross-sectional survey of 12 districts.

BACKGROUND: In 2020-2021, long-lasting insecticidal nets (LLINs) were distributed nationwide in Uganda during the COVID-19 pandemic. A cross-sectional survey was conducted in 12 districts to evaluate the impact of the campaign 1-5 months after LLIN distribution. METHODS: During April-May 2021, households were randomly selected from target areas (1-7 villages) surrounding 12 government-run health facilities established as Malaria Reference Centres; at least 50 households were enrolled per cluster. Outcomes included household ownership of LLINs distributed through the universal coverage campaign (UCC) (at least one UCC LLIN), adequate coverage of UCC LLINs (at least one UCC LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Multivariate logistic regression models were used to identify household- and individual-level factors associated with outcomes, controlling for clustering around health facilities. RESULTS: In total, 634 households, with 3342 residents and 1631 bed-nets, were included. Most households (93.4%) owned at least 1 UCC LLIN, but only 56.8% were adequately covered by UCC LLINs. In an adjusted analysis, the factor most strongly associated with adequate coverage by UCC LLINs was fewer household residents (1-4 vs 7-14; adjusted odds ratio [aOR] 12.96, 95% CI 4.76-35.26, p < 0.001; 5-6 vs 7-14 residents; aOR 2.99, 95% CI 1.21-7.42, p = 0.018). Of the 3166 residents of households that owned at least one UCC LLIN, only 1684 (53.2%) lived in adequately covered households; 89.9% of these used an LLIN the previous night, compared to 1034 (69.8%) of 1482 residents living in inadequately covered households. In an adjusted analysis, restricted to residents of inadequately covered households, LLIN use was higher in children under-five than those aged 5-15 years (aOR 3.04, 95% CI 2.08-4.46, p < 0.001), and higher in household heads than distantly-related residents (aOR 3.94, 95% CI 2.38-6.51, p < 0.001). CONCLUSIONS: Uganda's 2021-21 campaign was successful, despite the COVID-19 pandemic. In future campaigns, strategies should be adopted to ensure high LLIN coverage, particularly for larger households. A better understanding of the drivers of LLIN use within households is needed to guide future interventions, educational messages, and behaviour change communication strategies; school-aged children and distantly-related residents appear vulnerable and could be targeted.

Gender difference in the incidence of malaria diagnosed at public health facilities in Uganda.

BACKGROUND: Routine malaria surveillance data in Africa primarily come from public health facilities reporting to national health management information systems. Although information on gender is routinely collected from patients presenting to these health facilities, stratification of malaria surveillance data by gender is rarely done. This study evaluated gender difference among patients diagnosed with parasitological confirmed malaria at public health facilities in Uganda. METHODS: This study utilized individual level patient data collected from January 2020 through April 2021 at 12 public health facilities in Uganda and cross-sectional surveys conducted in target areas around these facilities in April 2021. Associations between gender and the incidence of malaria and non-malarial visits captured at the health facilities from patients residing within the target areas were estimated using poisson regression models controlling for seasonality. Associations between gender and data on health-seeking behaviour from the cross-sectional surveys were estimated using poisson regression models controlling for seasonality. RESULTS: Overall, incidence of malaria diagnosed per 1000 person years was 735 among females and 449 among males (IRR = 1.72, 95% CI 1.68-1.77, p < 0.001), with larger differences among those 15-39 years (IRR = 2.46, 95% CI 2.34-2.58, p < 0.001) and over 39 years (IRR = 2.26, 95% CI 2.05-2.50, p < 0.001) compared to those under 15 years (IRR = 1.46, 95% CI 1.41-1.50, p < 0.001). Female gender was also associated with a higher incidence of visits where malaria was not suspected (IRR = 1.77, 95% CI 1.71-1.83, p < 0.001), with a similar pattern across age strata. These associations were consistent across the 12 individual health centres. From the cross-sectional surveys, females were more likely than males to report fever in the past 2 weeks and seek care at the local health centre (7.5% vs. 4.7%, p = 0.001) with these associations significant for those 15-39 years (RR = 2.49, 95% CI 1.17-5.31, p = 0.018) and over 39 years (RR = 2.56, 95% CI 1.00-6.54, p = 0.049). CONCLUSIONS: Females disproportionately contribute to the burden of malaria diagnosed at public health facilities in Uganda, especially once they reach childbearing age. Contributing factors included more frequent visits to these facilities independent of malaria and a higher reported risk of seeking care at these facilities for febrile illnesses.

Relationships between test positivity rate, total laboratory confirmed cases of malaria, and malaria incidence in high burden settings of Uganda: an ecological analysis.

BACKGROUND: Malaria surveillance is critical for monitoring changes in malaria morbidity over time. National Malaria Control Programmes often rely on surrogate measures of malaria incidence, including the test positivity rate (TPR) and total laboratory confirmed cases of malaria (TCM), to monitor trends in malaria morbidity. However, there are limited data on the accuracy of TPR and TCM for predicting temporal changes in malaria incidence, especially in high burden settings. METHODS: This study leveraged data from 5 malaria reference centres (MRCs) located in high burden settings over a 15-month period from November 2018 through January 2020 as part of an enhanced health facility-based surveillance system established in Uganda. Individual level data were collected from all outpatients including demographics, laboratory test results, and village of residence. Estimates of malaria incidence were derived from catchment areas around the MRCs. Temporal relationships between monthly aggregate measures of TPR and TCM relative to estimates of malaria incidence were examined using linear and exponential regression models. RESULTS: A total of 149,739 outpatient visits to the 5 MRCs were recorded. Overall, malaria was suspected in 73.4% of visits, 99.1% of patients with suspected malaria received a diagnostic test, and 69.7% of those tested for malaria were positive. Temporal correlations between monthly measures of TPR and malaria incidence using linear and exponential regression models were relatively poor, with small changes in TPR frequently associated with large changes in malaria incidence. Linear regression models of temporal changes in TCM provided the most parsimonious and accurate predictor of changes in malaria incidence, with adjusted R2 values ranging from 0.81 to 0.98 across the 5 MRCs. However, the slope of the regression lines indicating the change in malaria incidence per unit change in TCM varied from 0.57 to 2.13 across the 5 MRCs, and when combining data across all 5 sites, the R2 value reduced to 0.38. CONCLUSIONS: In high malaria burden areas of Uganda, site-specific temporal changes in TCM had a strong linear relationship with malaria incidence and were a more useful metric than TPR. However, caution should be taken when comparing changes in TCM across sites.

Impact of COVID-19 on routine malaria indicators in rural Uganda: an interrupted time series analysis.

BACKGROUND: In March 2020, the government of Uganda implemented a strict lockdown policy in response to the COVID-19 pandemic. Interrupted time series analysis (ITSA) was performed to assess whether major changes in outpatient attendance, malaria burden, and case management occurred after the onset of the COVID-19 epidemic in rural Uganda. METHODS: Individual level data from all outpatient visits collected from April 2017 to March 2021 at 17 facilities were analysed. Outcomes included total outpatient visits, malaria cases, non-malarial visits, proportion of patients with suspected malaria, proportion of patients tested using rapid diagnostic tests (RDTs), and proportion of malaria cases prescribed artemether-lumefantrine (AL). Poisson regression with generalized estimating equations and fractional regression was used to model count and proportion outcomes, respectively. Pre-COVID trends (April 2017-March 2020) were used to predict the'expected' trend in the absence of COVID-19 introduction. Effects of COVID-19 were estimated over two six-month COVID-19 time periods (April 2020-September 2020 and October 2020-March 2021) by dividing observed values by expected values, and expressed as ratios. RESULTS: A total of 1,442,737 outpatient visits were recorded. Malaria was suspected in 55.3% of visits and 98.8% of these had a malaria diagnostic test performed. ITSA showed no differences between observed and expected total outpatient visits, malaria cases, non-malarial visits, or proportion of visits with suspected malaria after COVID-19 onset. However, in the second six months of the COVID-19 time period, there was a smaller mean proportion of patients tested with RDTs compared to expected (relative prevalence ratio (RPR) = 0.87, CI (0.78-0.97)) and a smaller mean proportion of malaria cases prescribed AL (RPR = 0.94, CI (0.90-0.99)). CONCLUSIONS: In the first year after the COVID-19 pandemic arrived in Uganda, there were no major effects on malaria disease burden and indicators of case management at these 17 rural health facilities, except for a modest decrease in the proportion of RDTs used for malaria diagnosis and the mean proportion of malaria cases prescribed AL in the second half of the COVID-19 pandemic year. Continued surveillance will be essential to monitor for changes in trends in malaria indicators so that Uganda can quickly and flexibly respond to challenges imposed by COVID-19.

Associations between environmental covariates and temporal changes in malaria incidence in high transmission settings of Uganda: a distributed lag nonlinear analysis.

BACKGROUND: Environmental factors such as temperature, rainfall, and vegetation cover play a critical role in malaria transmission. However, quantifying the relationships between environmental factors and measures of disease burden relevant for public health can be complex as effects are often non-linear and subject to temporal lags between when changes in environmental factors lead to changes in malaria incidence. The study investigated the effect of environmental covariates on malaria incidence in high transmission settings of Uganda. METHODS: This study leveraged data from seven malaria reference centres (MRCs) located in high transmission settings of Uganda over a 24-month period. Estimates of monthly malaria incidence (MI) were derived from MRCs' catchment areas. Environmental data including monthly temperature, rainfall, and normalized difference vegetation index (NDVI) were obtained from remote sensing sources. A distributed lag nonlinear model was used to investigate the effect of environmental covariates on malaria incidence. RESULTS: Overall, the median (range) monthly temperature was 30 °C (26-47), rainfall 133.0 mm (3.0-247), NDVI 0.66 (0.24-0.80) and MI was 790 per 1000 person-years (73-3973). Temperature of 35 °C was significantly associated with malaria incidence compared to the median observed temperature (30 °C) at month lag 2 (IRR: 2.00, 95% CI: 1.42-2.83) and the increased cumulative IRR of malaria at month lags 1-4, with the highest cumulative IRR of 8.16 (95% CI: 3.41-20.26) at lag-month 4. Rainfall of 200 mm significantly increased IRR of malaria compared to the median observed rainfall (133 mm) at lag-month 0 (IRR: 1.24, 95% CI: 1.01-1.52) and the increased cumulative IRR of malaria at month lags 1-4, with the highest cumulative IRR of 1.99(95% CI: 1.22-2.27) at lag-month 4. Average NVDI of 0.72 significantly increased the cumulative IRR of malaria compared to the median observed NDVI (0.66) at month lags 2-4, with the highest cumulative IRR of 1.57(95% CI: 1.09-2.25) at lag-month 4. CONCLUSIONS: In high-malaria transmission settings, high values of environmental covariates were associated with increased cumulative IRR of malaria, with IRR peaks at variable lag times. The complex associations identified are valuable for designing strategies for early warning, prevention, and control of seasonal malaria surges and epidemics.

Factors associated with concurrent wasting and stunting among children 6-59 months in Karamoja, Uganda.

Children with concurrent wasting and stunting (WaSt) and children with severe wasting have a similar risk of death. Existing evidence shows that wasting and stunting share similar causal pathways, but evidence on correlates of WaSt remains limited. Research on correlates of WaSt is needed to inform prevention strategies. We investigated the factors associated with WaSt in children 6-59 months in Karamoja Region, Uganda. We examined data for 33,054 children aged 6-59 months using June 2015 to July 2018 Food Security and Nutrition Assessment in Karamoja. We defined WaSt as being concurrently wasted (weight-for-height z-scores <-2.0) and stunted (height-for-age z-score <-2.0). We conducted multivariate mixed-effect logistic regression to assess factors associated with WaSt. Statistical significance was set at p < 0.05. In multivariate analysis, being male (adjusted odds ratio [aOR] = 1.79; 95% confidence interval [CI] [1.60-2.00]), aged 12-23 months (aOR = 2.25; 95% CI [1.85-2.74]), 36-47 months (aOR = 0.65; 95% CI [0.50-0.84]) and 48-59 months (aOR = 0.71; 95% CI [0.54-0.93]) were associated with WaSt. In addition, acute respiratory infection (aOR = 1.30; 95% CI [1.15-1.48]), diarrhoea (aOR = 1.25; 95% CI [1.06-1.48]) and malaria/fever (aOR = 0.83; 95% CI [0.73-0.96]) episodes were associated with WaSt. WaSt was significantly associated with maternal underweight (body mass index <18.5 kg/m2 ), short stature (height <160 cm), low mid-upper arm circumference (MUAC <23 cm) and having ≥4 live-births. WaSt was prevalent in households without livestock (aOR = 1.30; 95% CI [1.13-1.59]). Preventing the occurrence of WaSt through pragmatic and joint approaches are recommended. Future prospective studies on risk factors of WaSt to inform effective prevention strategies are recommended.

Intermittent preventive treatment of malaria delivered to primary schoolchildren provided effective individual protection in Jinja, Uganda: secondary outcomes of a cluster-randomized trial (START-IPT).

BACKGROUND: Intermittent preventive treatment (IPT) of malaria is recommended as policy for certain high-risk populations, but not currently for schoolchildren. A cluster-randomized trial was conducted to evaluate the effect of IPT with dihydroartemisinin-piperaquine (DP) on primary schoolchildren in Jinja, Uganda. Results of the impact of IPT of schoolchildren on community-level transmission have been reported previously. Here, secondary outcomes from a school-based survey are presented. METHODS: Eighty-four clusters (one primary school plus 100 households) were randomized to intervention and control (1:1 ratio). Participants from intervention schools received monthly IPT with DP for up to 6 rounds (June-December 2014). At endline (November-December 2014), randomly selected children from all 84 schools were surveyed (13 per school) and thick blood smears were done. Those with fever or history of fever were tested with rapid diagnostic tests (RDTs) for malaria. Haemoglobin was measured in every fifth participant. Outcome measures included prevalence of asexual parasites and gametocytes (by microscopy), and prevalence of anaemia. Prevalence outcomes were analysed using generalized linear Poisson models with log link function, incorporating a cluster-level random intercept and quantified using prevalence risk ratios. RESULTS: Among 23,280 students listed on the 42 intervention school registers, 10,079 (43.3%) aged 5-20 years were enrolled into the IPT intervention and received at least one dose of DP; of these, 9286 (92.1%) received at least one full (3-day) course. In total, 1092 children were enrolled into the final school survey (546 per arm) and had a thick blood smear done; of these, 255 had haemoglobin measured (129 intervention, 126 control). Children in the intervention arm were less likely to have asexual parasites (9.2% intervention vs 44.1% control, adjusted risk ratio [aRR] 0.22 [95% CI 0.16-0.30] p < 0.001), gametocytes (3.1% intervention vs 9.5% control, aRR 0.34 [95% CI 0.20-0.56] p < 0.001), fever (20.2% intervention vs 56.2% control, aRR 0.35 [95% CI 0.25-0.50] p < 0.001), or symptomatic malaria (5.1% intervention vs 35.7% control, aRR 0.14 [95% CI 0.08-0.26] p < 0.001). Prevalence of anaemia and mean haemoglobin were similar in both study arms. CONCLUSIONS: School-aged children are a major reservoir of malaria parasites. Delivering IPT to schoolchildren would benefit individual children and may reduce transmission. School-based IPT could help to intensify malaria control toward elimination, and should be considered for policies and programmes. Trial registration Clinicaltrials.gov (NCT02009215), Registered 11 December 2013. https://clinicaltrials.gov/ct2/show/NCT02009215.

Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: a prospective cohort study.

BACKGROUND: Malaria in pregnancy is a major public health challenge, but its risk factors remain poorly understood in some settings. This study assessed the association between household and maternal characteristics and malaria among pregnant women in a high transmission area of Uganda. METHODS: A nested prospective study was conducted between 6th September 2016 and 5th December 2017 in Busia district. 782 HIV uninfected women were enrolled in the parent study with convenience sampling. Socioeconomic and house construction data were collected via a household survey after enrolment. Homes were classified as modern (plaster or cement walls, metal or wooden roof and closed eaves) or traditional (all other homes). Maternal and household risk factors were evaluated for three outcomes: (1) malaria parasitaemia at enrolment, measured by thick blood smear and qPCR, (2) malaria parasitaemia during pregnancy following initiation of IPTp, measured by thick blood smear and qPCR and (3) placental malaria measured by histopathology. RESULTS: A total of 753 of 782 women were included in the analysis. Most women had no or primary education (75%) and lived in traditional houses (77%). At enrolment, microscopic or sub-microscopic parasitaemia was associated with house type (traditional versus modern: adjusted risk ratio (aRR) 1.29, 95% confidence intervals 1.15-1.45, p < 0.001), level of education (primary or no education versus O-level or beyond: aRR 1.13, 95% confidence interval 1.02-1.24, p = 0.02), and gravidity (primigravida versus multigravida: aRR 1.10, 95% confidence interval 1.02-1.18, p = 0.009). After initiation of IPTp, microscopic or sub-microscopic parasitaemia was associated with wealth index (poorest versus least poor: aRR 1.24, 95% CI 1.10-1.39, p < 0.001), house type (aRR 1.14, 95% CI 1.01-1.28, p = 0.03), education level (aRR 1.19, 95% CI 1.06-1.34, p = 0.002) and gravidity (aRR 1.32, 95% CI 1.20-1.45, p < 0.001). Placental malaria was associated with gravidity (aRR 2.87, 95% CI 2.39-3.45, p < 0.001), but not with household characteristics. CONCLUSIONS: In an area of high malaria transmission, primigravid women and those belonging to the poorest households, living in traditional homes and with the least education had the greatest risk of malaria during pregnancy.

Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) has been shown to reduce the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (IPTp-SP). However, limited data exist on how IPTp regimens impact malaria risk during infancy. We conducted a double-blinded randomized controlled trial (RCT) to test the hypothesis that children born to mothers given IPTp-DP would have a lower incidence of malaria during infancy compared to children born to mothers who received IPTp-SP. METHODS AND FINDINGS: We compared malaria metrics among children in Tororo, Uganda, born to women randomized to IPTp-SP given every 8 weeks (SP8w, n = 100), IPTp-DP every 8 weeks (DP8w, n = 44), or IPTp-DP every 4 weeks (DP4w, n = 47). After birth, children were given chemoprevention with DP every 12 weeks from 8 weeks to 2 years of age. The primary outcome was incidence of malaria during the first 2 years of life. Secondary outcomes included time to malaria from birth and time to parasitemia following each dose of DP given during infancy. Results are reported after adjustment for clustering (twin gestation) and potential confounders (maternal age, gravidity, and maternal parasitemia status at enrolment).The study took place between June 2014 and May 2017. Compared to children whose mothers were randomized to IPTp-SP8w (0.24 episodes per person year [PPY]), the incidence of malaria was higher in children born to mothers who received IPTp-DP4w (0.42 episodes PPY, adjusted incidence rate ratio [aIRR] 1.92; 95% CI 1.00-3.65, p = 0.049) and nonsignificantly higher in children born to mothers who received IPT-DP8w (0.30 episodes PPY, aIRR 1.44; 95% CI 0.68-3.05, p = 0.34). However, these associations were modified by infant sex. Female children whose mothers were randomized to IPTp-DP4w had an apparently 4-fold higher incidence of malaria compared to female children whose mothers were randomized to IPTp-SP8w (0.65 versus 0.20 episodes PPY, aIRR 4.39, 95% CI 1.87-10.3, p = 0.001), but no significant association was observed in male children (0.20 versus 0.28 episodes PPY, aIRR 0.66, 95% CI 0.25-1.75, p = 0.42). Nonsignificant increases in malaria incidence were observed among female, but not male, children born to mothers who received DP8w versus SP8w. In exploratory analyses, levels of malaria-specific antibodies in cord blood were similar between IPTp groups and sex. However, female children whose mothers were randomized to IPTp-DP4w had lower mean piperaquine (PQ) levels during infancy compared to female children whose mothers received IPTp-SP8w (coef 0.81, 95% CI 0.65-1.00, p = 0.048) and male children whose mothers received IPTp-DP4w (coef 0.72, 95% CI 0.57-0.91, p = 0.006). There were no significant sex-specific differences in PQ levels among children whose mothers were randomized to IPTp-SP8w or IPTp-DP8w. The main limitations were small sample size and childhood provision of DP every 12 weeks in infancy. CONCLUSIONS: Contrary to our hypothesis, preventing malaria in pregnancy with IPTp-DP in the context of chemoprevention with DP during infancy does not lead to a reduced incidence of malaria in childhood; in this setting, it may be associated with an increased incidence of malaria in females. Future studies are needed to better understand the biological mechanisms of in utero drug exposure on drug metabolism and how this may affect the dosing of antimalarial drugs for treatment and prevention during infancy. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02163447.

Impact of antimalarial treatment and chemoprevention on the drug sensitivity of malaria parasites isolated from ugandan children.

Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and pfdhps polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased ex vivo lumefantrine sensitivity and increased prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively.

Increased morbidity in early childhood among HIV-exposed uninfected children in Uganda is associated with breastfeeding duration.

Human immunodeficiency virus (HIV)-exposed uninfected children (HEU) have an increased risk of morbidity and mortality compared with HIV-unexposed uninfected children (HUU); however, prior studies have not fully accounted for the role of both breastfeeding and age on this association. In this cohort of HEU and HUU in Uganda, non-breastfeeding HEU, from 6-11 months compared with non-breastfeeding HUU had a higher risk of hospitalizations [relative risk (RR): 10.1, 95% confidence interval (CI): 3.70-27.6], severe febrile illness (RR: 3.84, 95% CI: 2.06-7.17), severe diarrhea (RR: 6.37, 95% CI: 2.32-17.4) and severe malnutrition (RR: 18.4, 95% CI: 4.68-72.0). There were no differences between morbidity outcomes between breastfeeding HEU and HUU children, aged 6-11 months. In the 12-24 month age group, the only difference in morbidity outcomes among non-breast feeding children was an increased risk of severe malnutrition for HEU. These data suggest that the increased risk of morbidity among HEU aged 6-11 years is partially explained by early cessation of breastfeeding.

Mixed methods evaluation of the Caring for Providers to Improve Patient Experience intervention.

OBJECTIVE: To assess the impact of the Caring for Providers to Improve Patient Experience (CPIPE) intervention, which sought to improve person-centered maternal care (PCMC) by addressing two key drivers: provider stress and bias. METHODS: CPIPE was successfully piloted over 6 months in two health facilities in Migori County, Kenya, in 2022. The evaluation employed a mixed-methods pretest-posttest nonequivalent control group design. Data are from surveys with 80 providers (40 intervention, 40 control) at baseline and endline and in-depth interviews with 20 intervention providers. We conducted bivariate, multivariate, and difference-in-difference analysis of quantitative data and thematic analysis of qualitative data. RESULTS: In the intervention group, average knowledge scores increased from 7.8 (SD = 2.4) at baseline to 9.5 (standard deviation [SD] = 1.8) at endline for stress (P = 0.001) and from 8.9 (SD = 1.9) to 10.7 (SD = 1.7) for bias (P = 0.001). In addition, perceived stress scores decreased from 20.9 (SD = 3.9) to 18.6 (SD = 5.3) (P = 0.019) and burnout from 3.6 (SD = 1.0) to 3.0 (SD = 1.0) (P = 0.001), with no significant change in the control group. Qualitative data indicated that CPIPE had an impact at multiple levels. At the individual level, it improved provider knowledge, skills, self-efficacy, attitudes, behaviors, and experiences. At the interpersonal level, it improved provider-provider and patient-provider relationships, leading to a supportive work environment and improved PCMC. At the institutional level, it created a system of accountability for providing PCMC and nondiscriminatory care, and collective action and advocacy to address sources of stress. CONCLUSION: CPIPE impacted multiple outcomes in the theory of change, leading to improvements in both provider and patient experience, including for the most vulnerable patients. These findings will contribute to global efforts to prevent burnout and promote PCMC and equity.

Association between water insecurity and antiretroviral therapy adherence among pregnant and postpartum women in Greater Accra region of Ghana.

BACKGROUND: Adherence to antiretroviral therapy (ART) can substantially reduce morbidity and mortality among women living with HIV (WLWH) and prevent vertical transmission of HIV. However, in sub-Saharan Africa (SSA), more than 50% of new mothers discontinue ART and HIV care after childbirth. The role of water insecurity (WI) in ART adherence is not well-explored. We examined the relationship between WI and ART adherence among pregnant and postpartum WLWH in Greater Accra region of Ghana. METHODS: Using a cross-sectional survey, we recruited 176 pregnant and postpartum WLWH on ART across 11 health facilities. We examined the association between WI (measured using the Household Water Insecurity Experience Scale, and categorized as moderate and severe WI compard to low WI) and poor ART adherence (defined as scoring a below average observed CASE index score). Bivariate analysis was performed using chi-square test followed by multivariate logistic regression models. We included all variables with p-values less than 0.20 in the multivariate analysis. RESULTS: Most (79.5%) of the pregnant and postpartum WLWH enrolled on ART, were urban residents. Over 2/3 were aged 30 years and older. Overall, 33.5% of respondents had poor ART adherence. Proportion of poor ART adherence was 19.4% among those with low WI, 44.4% in those with moderate WI, and 40.0% among those with high WI. Respondents with moderate household water insecurity had a greater odds of reporting poor ART adherence, as compared to those with low water insecurity (adjusted Odds ratio (aOR) = 2.76, 95%CI: 1.14-6.66, p = 0.024), even after adjusting for food insecurity. Similarly, respondents with high WI had a greater odds of reporting poor ART adherence, as compared to those with low water insecurity (aOR = 1.49, 95%CI: 0.50-4.48, p = 0.479), even after adjusting for food insecurity. CONCLUSION: Water insecurity is prevalent among pregnant and postpartum WLWH and is a significant risk factor for poor ART adherence. Governments and other stakeholders working in HIV care provision should prioritize water security programming for WLWH along the HIV care continuum.

Health provider perspectives of Village Health Team-delivered oral HIV self-testing among men in Central Uganda: a qualitative evaluation using RE-AIM framework.

Background: HIV self-testing (HIVST) is a practical and effective way to provide HIV testing services to at-risk and underserved populations, particularly men. Utilizing Village Health Teams (VHTs) could enhance community-based delivery of oral HIVST to reach the last un-tested individuals who may be at-risk of infection. However, little is known about what VHTs and facility-based healthcare workers think about facilitating oral HIVST and delivery of subsequent HIV services. We investigated the views of health providers on oral HIVST delivered by VHTs among men in rural communities in Central Uganda. Methods: We conducted a qualitative study in Mpigi district, interviewing 27 health providers who facilitated oral HIV self-testing among men. The providers consisting of 15 VHTs and 12 facility-based health workers were purposively selected. All interviews were audio-recorded, transcribed verbatim, and translated to English for a hybrid inductive-deductive thematic analysis. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Implementation Science framework to generate and categorize open codes. Results: In terms of reaching men with HIV testing services, the providers considered HIVST to be a fast and convenient method, which could boost HIV testing. However, they also had concerns about its accuracy. In terms of effectiveness, HIVST was perceived as a reliable, user-friendly, and efficient approach to HIV testing. However, it depended on the user's preference for testing algorithms. Regarding adoption, HIVST was considered to enhance autonomy, well-suited for use in the community, and offered opportunities for linkage and re-linkage into care. However, at times HIVST faced hesitance. As for Implementation, VHTs had various support roles in HIVST but had concerns about social insecurities and delays in seeking subsequent facility-based services after HIVST. Regarding Maintenance, providers recommended several ways to improve oral HIVST including; optimizing tracking of HIVST distribution and use, improving linkage and retention in care after HIVST, diversifying HIVST for combined HIV prevention packages and including more languages, broadening sensitization among potential HIVST users and health providers, differentiating distribution models, and prioritizing targeted HIVST efforts. Conclusion: HIVST has the potential to increase testing rates and engagement of men in HIV services. However, for it to be implemented on a population-wide scale, continuous sensitization of potential users and health providers is necessary, along with streamlined structures for tracking kit distribution, use, and reporting of results. Further implementation research may be necessary to optimize the role of health providers in facilitating HIVST.