Understanding the fine-scale heterogeneity and spatial drivers of malaria transmission in Kenya using model-based geostatistical methods

Malaria remains a public health concern. Monitoring the fine-scale heterogeneity of the malaria burden enables more targeted control efforts. Although malaria indicator surveys (MIS) have been crucial in evaluating the progress of malaria control interventions, they are only designed to provide a cross-sectional national and regional malaria disease burden. Recent advances in geostatistical methods allow us to interpolate national survey data to describe subnational disease burden that is crucial in informing targeted control. A binomial geostatistical model employing Markov chain Monte Carlo (MCMC) parameter estimation methods is used to understand the spatial drivers of malaria risk in Kenya and to predict malaria risk at a fine-scale resolution, including identifying hotspots. A total of 11,549 children aged six months to 14 years from 207 clusters were sampled in this survey and used in the present analysis. The national malaria prevalence based on the data was 8.4%, with the highest in the lake endemic zone (18.1%) and the lowest in the low-risk zone (<1%). The analysis shows that elevation, proportion of insectcide treated net (ITN) distributed, rainfall, temperature and urbanization covariates are all significant predictors of malaria transmission. The 5x5 Km resolution maps show that malaria is heterogeneous in Kenya, with hotspot areas in the lake endemic area, the coastal areas, and some parts of the shores of Lake Turkana and Kajiado. The high-resolution malaria prevalence maps produced as part of the analysis have shown that Kenya has additional malaria hotspots, especially in areas least expected. These findings call for a rethinking of malaria burden classification in some regions for effective planning, implementation, resource mobilization, monitoring, and evaluation of malaria interventions in the country

Isoniazid preventive therapy-related adverse events among Malawian adults on antiretroviral therapy: A cohort study.

Adverse events may be a cause of observed poor completion of isoniazid preventive therapy (IPT) among people living with HIV in high tuberculosis burden areas. Data on IPT-related adverse events (AE) from sub-Saharan Africa are scarce. We report IPT-related AEs, associated clinical characteristics, and IPT discontinuations in adults who were stable on antiretroviral therapy (ART) when they initiated IPT. Cohort study nested within a randomized, controlled, clinical trial of cotrimoxazole and chloroquine prophylaxis in Malawians aged ≥ 18 years and virologically suppressed on ART. Eight hundred sixty-nine patients were followed for a median of 6 months after IPT initiation. IPT relatedness of AEs was determined retrospectively with the World Health Organization case-causality tool. Frailty survival regression modeling identified factors associated with time to first probably IPT-related AE. The overall IPT-related AE incidence rate was 1.1/person year of observation. IPT relatedness was mostly uncertain and few AEs were severe. Most common were liver and hematological toxicities. Higher age increased risk of a probably IPT-related AE (aHR = 1.02; 95% CI 1.00-1.06; P = .06) and higher weight reduced this risk (aHR = 0.98; 95% CI 0.96-1.00; P = .03). Of 869 patients, 114 (13%) discontinued IPT and 94/114 (82%) discontinuations occurred at the time of a possibly or probably IPT-related AE. We observed a high incidence of mostly mild IPT-related AEs among individuals who were stable on ART. More than 1 in 8 persons discontinued IPT. These findings inform strategies to improve implementation of IPT in adults on ART, including close monitoring of groups at higher risk of IPT-related AEs

“Kuteteza”: A community-engaged COVID-19 Prevention and Protection Initiative in Southern Malawi

Background: The COVID-19 epidemic in Malawi involved almost 90,000 recorded cases and 2,638 deaths. Data suggest that the Malawi epidemic developed largely in urban settings, but the extent of rural spread – exposing older adults in particular – is unclear. This concern led us, to develop the ‘Kuteteza’ partnership project: a community-based Public Health intervention involving the shielding of older adults and additional strategies to mitigate COVID-19 impacts in rural Malawi. We now present the results of a realist project evaluation. Methods Clinicians, Public Health professionals, and researchers collaborated with government and district level staff in two Malawi districts. After engagement with local structures, willing older adults (>60 years) and their communities made arrangements for supported 'shielding'. Masks, handwashing stations, and soap were also provided, and government partnerships allowed additional support for vulnerable groups. Finally, context-responsive community engagement reinforced COVID-19 prevention during peak risk periods. Our realist evaluation included collation of anonymised descriptive data and qualitative structured observations and focus groups – involving community members and volunteers – in each setting. Results The project involved 25 villages. Multi-level stakeholder engagement was pivotal in developing and establishing the work, and strong District Health Office support was integral to implementation. Team members contributed to national meetings, aligning the project with national guidance and stakeholder actions. Established partnerships with relevant ministries resulted in the incorporation of shielding in the Malawi COVID-19 response plan. In Kuteteza villages, handwashing stations and soap were used, and there was awareness of COVID-19 prevention measures. Further experiences and evaluation results are presented, including learning points for future outbreak responses. Conclusions Through effective stakeholder engagement and contribution to national response strategy, the Kuteteza project raised awareness and supported populations at a critical time in the pandemic. These approaches can be incorporated in future epidemic and emergency responses

Extended follow-up of children in a phase2b trial of the GMZ2 malaria vaccine.

BACKGROUND: The GMZ2/alum candidate malaria vaccine had an efficacy of 14% (95% confidence interval [CI]: 3.6%, 23%) against clinical malaria over 6 months of follow-up in a phase2b multicentre trial in children 1-5 years of age. Here we report the extended follow up of safety and efficacy over 2 years. METHODS: A total of 1849 (GMZ2 = 926, rabies = 923) children aged 12-60 months were randomized to receive intramuscularly, either 3 doses of 100 μg GMZ2/alum or 3 doses of rabies vaccine as control 28 days apart. The children were followed-up for 24 months for clinical malaria episodes and adverse events. The primary endpoint was documented fever with parasitaemia of at least 5000/μL. RESULTS: There were 2,062 malaria episodes in the GMZ2/alum group and 2,115 in the rabies vaccine group in the intention-to-treat analysis, vaccine efficacy (VE) of 6.5% (95%: CI -1.6%, 14.0%). In children aged 1-2 years at enrolment, VE was 3.6% (95 %CI: -9.1%, 14.8%) in the first year and -4.1% (95 %CI: -18.7%, 87%) in the second year. In children aged 3-5 years at enrolment VE was 19.9% (95 %CI: 7.7%, 30.4%) in the first year and 6.3% (95 %CI: -10.2%, 20.3%) in the second year (interaction by year, P = 0.025, and by age group, P = 0.085). A total of 187 (GMZ2 = 91, rabies = 96) serious adverse events were recorded in 167 individuals over the entire period of the study. There were no GMZ2 vaccine related serious adverse events. CONCLUSIONS: GMZ2/alum was well tolerated. Follow-up over 2 years confirmed a low level of vaccine efficacy with slightly higher efficacy in older children, which suggests GMZ2 may act in concert with naturally acquired immunity

Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022

Background Malaria remains a public health problem in Malawi and has a serious socio-economic impact on the population. In the past two decades, available malaria control measures have been substantially scaled up, such as insecticide-treated bed nets, artemisinin-based combination therapies, and, more recently, the introduction of the malaria vaccine, the RTS,S/AS01. In this paper, we describe the epidemiology of malaria for the last two decades to understand the past transmission and set the scene for the elimination agenda. Methods A collation of parasite prevalence surveys conducted between the years 2000 and 2022 was done. A spatio-temporal geostatistical model was fitted to predict the yearly malaria risk for children aged 2–10 years (PfPR 2–10) at 1×1 km spatial resolutions. Parameter estimation was done using the Monte Carlo maximum likelihood methods. District level prevalence estimates adjusted for population are calculated for the years 2000 to 2022. Results A total of 2,595 sampled unique locations from 2000 to 2022 were identified through the data collation exercise. This represents 70,565 individuals that were sampled in the period. In general, the PfPR2_10 declined over the 22 years. The mean modeled national PfPR2_10 in 2000 was 43.93 % (95% CI:17.9 to 73.8%) and declined to 19.2% (95%CI 7.49 to 37.0%) in 2022. The smoothened estimates of PfPR2_10 indicate that malaria prevalence is very heterogeneous with hotspot areas concentrated on the southern shores of Lake Malawi and the country's central region. Conclusions The last two decades are associated with a decline in malaria prevalence, highly likely associated with the scale up of control interventions. The country should move towards targeted malaria control approaches informed by surveillance data

The Enterics for Global Health (EFGH) Shigella Surveillance Study in Malawi

Background: Malawi is among 7 countries participating in the Enterics for Global Health (EFGH) Shigella surveillance study, which aims to determine the incidence of medically attended diarrhea attributed to Shigella, a leading bacterial cause of diarrhea in children in low-resource settings. Methods: We describe the EFGH study site in the densely populated informal settlement of Ndirande Township, Blantyre, Malawi. We explore the site’s geographical location, demographic characteristics, and the healthcare-seeking behavior of its population, particularly for childhood diarrhea. We also describe the management of childhood diarrhea at the health facility, and the associated challenges to attaining optimum adherence to local and national guidelines at the site. Conclusions: Our overarching aim is to improve global health through understanding and mitigating the impact of diarrhea attributed to Shigella

Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study

Background: Accurate estimation of diarrhea incidence from facility-based surveillance requires estimating the population at risk and accounting for case patients who do not seek care. The Enterics for Global Health (EFGH) Shigella surveillance study will characterize population denominators and healthcare-seeking behavior proportions to calculate incidence rates of Shigella diarrhea in children aged 6–35 months across 7 sites in Africa, Asia, and Latin America. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will use a hybrid surveillance design, supplementing facility-based surveillance with population-based surveys to estimate population size and the proportion of children with diarrhea brought for care at EFGH health facilities. Continuous data collection over a 24 month period captures seasonality and ensures representative sampling of the population at risk during the period of facility-based enrollments. Study catchment areas are broken into randomized clusters, each sized to be feasibly enumerated by individual field teams. Conclusions: The methods presented herein aim to minimize the challenges associated with hybrid surveillance, such as poor parity between survey area coverage and facility coverage, population fluctuations, seasonal variability, and adjustments to care-seeking behavior

Adolescent pregnancy outcomes at Queen Elizabeth Central Hospital, Malawi: a cross-sectional study

Introduction Malawi has a growing population with a high Maternal Mortality Ratio (MMR) of 439 per 100,000 live births to which adolescents contribute 25%. Current data suggests adolescent pregnancies in low resource settings are at an increased risk of both maternal and neonatal morbidity. Objectives This study assessed the pregnancy outcomes amongst adolescents while using women from the early adulthood (20 - 24-year-old) and advanced maternal age (35 years old and above) groups as reference.Methods This was a cross-sectional study, carried out at the Chatinkha maternity (labour) and post-natal wards at QECH, and included all adolescents (10 – 19 years old) and women between 20 - 24 years old (early adulthood) and 35 years old or older (advanced maternal age), presenting in labor, at any gestational age ≥ 28 weeks or with a birth weight of 1000 grams or above. Results The study found the prevalence of adolescent pregnancy to be 20.4% (N=5035) out of all the deliveries during the recruitment period. Sexually transmitted infections were proportionally higher in the adolescent group, with 12% testing HIV seroreactive and 10% syphilis seroreactive. Neonatal outcomes of birth asphyxia (3.5%), low birth weight (5%), prematurity (4.3%) and early neonatal death (4.3%) were not statistically different from the outcomes of the older age groups. The major causes of maternal morbidity were determined to be a high caesarean section rate of 31.9% and intrapartum diagnosis of urinary tract infection (7.4%), malaria (7.4%) and hypertensive disorders (14.5%). Conclusions Adolescents are a significant proportion of the pregnant population in Malawi. These adolescents are at increased risk of some pregnancy and peripartum complications when compared to women of older age groups. However, our study determined that these outcomes appear to be more likely related to the peripartum care received and not solely specific to maternal age

Unravelling the impact of insecticide-treated bed nets on childhood malaria in Malawi

Abstract Background To achieve malaria elimination it is essential to understand the impact of insecticide-treated net (ITNs) programmes. Here, the impact of ITN access and use on malaria prevalence in children in Malawi was investigated using Malaria Indicator Survey (MIS) data. Methods MIS data from 2012, 2014 and 2017 were used to investigate the relationship between malaria prevalence in children (6–59 months) and ITN use. Generalized linear modelling (GLM), geostatistical mixed regression modelling and non-stationary GLM were undertaken to evaluate trends, spatial patterns and local dynamics, respectively. Results Malaria prevalence in Malawi was 27.1% (95% CI 23.1–31.2%) in 2012 and similar in both 2014 (32.1%, 95% CI 25.5–38.7) and 2017 (23.9%, 95% CI 20.3–27.4%). ITN coverage and use increased during the same time period, with household ITN access growing from 19.0% (95% CI 15.6–22.3%) of households with at least 1 ITN for every 2 people sleeping in the house the night before to 41.7% (95% CI 39.1–44.4%) and ITN use from 41.1% (95% CI 37.3–44.9%) of the population sleeping under an ITN the previous night to 57.4% (95% CI 55.0–59.9%). Both the geostatistical and non-stationary GLM regression models showed child malaria prevalence had a negative association with ITN population access and a positive association with ITN use although affected by large uncertainties. The non-stationary GLM highlighted the spatital heterogeneity in the relationship between childhood malaria and ITN dynamics across the country. Conclusion Malaria prevalence in children under five had a negative association with ITN population access and a positive association with ITN use, with spatial heterogeneity in these relationships across Malawi. This study presents an important modelling approach that allows malaria control programmes to spatially disentangle the impact of interventions on malaria cases

Prevalence and correlates of common mental disorders among children and adolescents in Blantyre-Urban, Malawi

BackgroundThe high global prevalence of mental disorders justifies the need to quantify their burden in the sub-Saharan Africa where there is a dearth of information. These mental disorders are linked to different socio-demographic factors.ObjectiveTo determine the prevalence of, and factors associated with mental disorders among children and adolescents in Blantyre City, Malawi.Methods Children and adolescents aged 6 to 17 years were interviewed to determine their socio-demographic characteristics and assess their mental health status using the Strengths and Difficulties Questionnaire (SDQ) and Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Associations between mental disorders and socio-demographic characteristics were tested using Chi-square and logistic regression analysis.ResultsThe prevalence of symptoms of psychopathology on the SDQ was 7.3% (95%CI 4.8-10.5%) while for the K-SADS was 5.9% (95% CI 3.7%-8.9%). The prevalence of mental disorders across the age ranges of 6 to 12 years and 13 to 17 years was 5.4% and 7.9 % respectively. Males had a higher prevalence (7.1%) compared to females (4.7%). Conduct disorder was most prevalent (3.4%), followed by either type of ADHD- Attention Deficit Hyperactive Disorders (2.0%). Having a single parent (p&lt;0.001), staying with a nonbiological guardian (p&lt;0.030), engaging in paid work (p&lt;0.039), not attending school (p&lt;0.019) and having teacher difficulties(p&lt;0.028) were positively associated with a mental disorder.ConclusionThe socio-demographic factors associated with the risk of developing mental disorders may be important targets for mental health intervention programs