Childhood malaria case incidence in Malawi between 2004 and 2017:Spatio-temporal modelling of climate and non-climate factors

Introduction Malaria transmission is influenced by a complex interplay of factors including climate, socio-economic, environmental factors and interventions. Malaria control efforts across Africa have shown a mixed impact. Climate driven factors may play an increasing role with climate change. Efforts to strengthen routine facility-based monthly malaria data collection across Africa create an increasingly valuable data source to interpret burden trends and monitor control programme progress. A better understanding of the association with other climatic and non-climatic drivers of malaria incidence over time and space may help guide and interpret the impact of interventions. Methods Routine monthly paediatric outpatient clinical malaria case data were compiled from 27 districts in Malawi between 2004 and 2017, and analysed in combination with data on climatic, environmental, socio-economic and interventional factors and district level population estimates. A spatio-temporal generalized linear mixed model was fitted using Bayesian inference, in order to quantify the strength of association of the various risk factors with district-level variation in clinical malaria rates in Malawi, and visualised using maps. Results Between 2004 and 2017 reported childhood clinical malaria case rates showed a slight increase, from 50 to 53 cases per 1000 population, with considerable variation across the country between climatic zones. Climatic and environmental factors, including average monthly air temperature and rainfall anomalies, normalized difference vegetative index (NDVI) and RDT use for diagnosis showed a significant relationship with malaria incidence. Temperature in the current month and in each of the 3 months prior showed a significant relationship with the disease incidence unlike rainfall anomaly which was associated with malaria incidence at only three months prior. Estimated risk maps show relatively high risk along the lake and Shire valley regions of Malawi. Conclusion Our modelling approach can identify locations likely to have unusually high or low risk of malaria incidence across Malawi, and distinguishes between contributions to risk that can be explained by measured risk-factors and unexplained residual spatial variation. Also, spatial statistical methods applied to readily available routine data provides an alternative information source that can supplement survey data in policy development and implementation to direct surveillance and intervention efforts

Tryptophan End-Tagging Confers Antifungal Activity on a Tick-Derived Peptide by Triggering Reactive Oxygen Species Production

WHO has identified several Candida species including Candida albicans as critical priority fungal pathogens due to greater infection prevalence and formation of recalcitrant biofilms. Novel antifungal agents are urgently needed, and antimicrobial peptides (AMPs) are being considered as potential alternatives, but inactivity in physiological salt environments, serum, and plasma often limits further therapeutic development. Tryptophan end-tagging is a strategy to overcome these limitations and is thought to selectively enhance membrane permeabilization in both fungal and bacterial plasma membranes. Here, we show that C-terminal tryptophan end-tagging of the tick-derived peptide Os-C transforms an inactive peptide into Os-C(W5), an antifungal peptide capable of preventing the formation of C. albicans biofilms. Mechanistic insight is provided by circular dichroism spectroscopy and molecular dynamics simulations, which demonstrate that tryptophan end-tagging alters the secondary structure of Os-C, while the latter reveals that end-tagging reduces interactions with, and insertion into, a model C. albicans membrane but promotes peptide aggregation on its surface. Interestingly, this leads to the induction of reactive oxygen species production rather than membrane permeabilization, and consequently, oxidative stress leads to cell wall damage. Os-C(W5) does not induce the hemolysis of human erythrocytes. Reduced cell adhesion and viability contribute to decreased biofilm extracellular matrix formation which, although reduced, is retained in the serum-containing medium. In this study, tryptophan end-tagging was identified as a promising strategy for enhancing the antifungal activity, including the biofilm inhibitory activity of Os-C against C. albicans in physiological salt environments.</p

A pragmatic health centre-based evaluation comparing the effectiveness of a PCV13 schedule change from 3+0 to 2+1 in a high pneumococcal carriage and disease burden setting in Malawi: a study protocol

INTRODUCTION: Streptococcus pneumoniae (the pneumococcus) is commonly carried as a commensal bacterium in the nasopharynx but can cause life-threatening disease. Transmission occurs by human respiratory droplets and interruption of this process provides herd immunity. A 2017 WHO Consultation on Optimisation of pneumococcal conjugate vaccines (PCV) Impact highlighted a substantial research gap in investigating why the impact of PCV vaccines in low-income countries has been lower than expected. Malawi introduced the 13-valent PCV (PCV13) into the national Expanded Programme of Immunisations in 2011, using a 3+0 (3 primary +0 booster doses) schedule. With evidence of greater impact of a 2+1 (2 primary +1 booster dose) schedule in other settings, including South Africa, Malawi's National Immunisations Technical Advisory Group is seeking evidence of adequate superiority of a 2+1 schedule to inform vaccine policy. METHODS: A pragmatic health centre-based evaluation comparing impact of a PCV13 schedule change from 3+0 to 2+1 in Blantyre district, Malawi. Twenty government health centres will be randomly selected, with ten implementing a 2+1 and 10 to continue with the 3+0 schedule. Health centres implementing 3+0 will serve as the direct comparator in evaluating 2+1 providing superior direct and indirect protection against pneumococcal carriage. Pneumococcal carriage surveys will evaluate carriage prevalence among children 15-24 months, randomised at household level, and schoolgoers 5-10 years of age, randomly selected from school registers. Carriage surveys will be conducted 18 and 33 months following 2+1 implementation. ANALYSIS: The primary endpoint is powered to detect an effect size of 50% reduction in vaccine serotype (VT) carriage among vaccinated children 15-24 months old, expecting a 14% and 7% VT carriage prevalence in the 3+0 and 2+1 arms, respectively. ETHICS AND DISSEMINATION: The study has been approved by the Malawi College of Medicine Research Ethics Committee (COMREC; Ref: P05.19.2680), the University College London Research Ethics Committee (Ref: 8603.002) and the University of Liverpool Research Ethics Committee (Ref: 5439). The results from this study will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04078997

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread “natural experiment” of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic

Integrating vector control within an emerging agricultural system in a region of climate vulnerability in southern Malawi: A focus on malaria, schistosomiasis, and arboviral diseases

Infectious diseases are emerging at an unprecedented rate while food production intensifies to keep pace with population growth. Large-scale irrigation schemes have the potential to permanently transform the landscape with health, nutritional and socio-economic benefits; yet, this also leads to a shift in land-use patterns that can promote endemic and invasive insect vectors and pathogens. The balance between ensuring food security and preventing emerging infectious disease is a necessity; yet the impact of irrigation on vector-borne diseases at the epidemiological, entomological and economic level is uncertain and depends on the geographical and climatological context. Here, we highlight the risk factors and challenges facing vector-borne disease surveillance and control in an emerging agricultural ecosystem in the lower Shire Valley region of southern Malawi. A phased large scale irrigation programme (The Shire Valley Transformation Project, SVTP) promises to transform over 40,000 ha into viable and resilient farmland, yet the valley is endemic for malaria and schistosomiasis and experiences frequent extreme flooding events following tropical cyclones. The latter exacerbate vector-borne disease risk while simultaneously making any empirical assessment of that risk a significant hurdle. We propose that the SVTP provides a unique opportunity to take a One Health approach at mitigating vector-borne disease risk while maintaining agricultural output. A long-term and multi-disciplinary approach with buy-in from multiple stakeholders will be needed to achieve this goal

Geostatistical analysis of Malawi’s changing malaria transmission from 2010 to 2017 [version 1; peer review: awaiting peer review]

Background: The prevalence of malaria infection in time and space provides important information on the likely sub-national epidemiology of malaria burdens and how this has changed following intervention. Model-based geostatitics (MBG) allow national malaria control programmes to leverage multiple data sources to provide predictions of malaria prevalance by district over time. These methods are used to explore the possible changes in malaria prevalance in Malawi from 2010 to 2017. Methods: Plasmodium falciparum parasite prevalence (PfPR) surveys undertaken in Malawi between 2000 and 2017 were assembled. A spatio-temporal geostatistical model was fitted to predict annual malaria risk for children aged 2–10 years (PfPR2–10) at 1×1 km spatial resolutions. Parameter estimation was carried out using the Monte Carlo maximum likelihood methods. Population-adjusted prevalence and populations at risk by district were calculated for 2010 and 2017 to inform malaria control program priority setting. Results: 2,237 surveys at 1,834 communities undertaken between 2000 and 2017 were identified, geo-coded and used within the MBG framework to predict district malaria prevalence properties for 2010 and 2017. Nationally, there was a 47.2% reduction in the mean modelled PfPR2-10 from 29.4% (95% confidence interval (CI) 26.6 to 32.3%) in 2010 to 15.2% (95% CI 13.3 to 18.0%) in 2017. Declining prevalence was not equal across the country, 25 of 27 districts showed a significant decline ranging from a 3.3% reduction to 79% reduction. By 2017, 16% of Malawi’s population still lived in areas that support PfPR2-10 ≥ 25%. Conclusions: Malawi has made substantial progress in reducing the prevalence of malaria over the last seven years. However, Malawi remains in meso-endemic malaria transmission risk. To sustain the gains made and continue reducing the transmission further, universal control interventions need to be maintained at a national level

Assessment of readiness to transition from antenatal HIV surveillance surveys to PMTCT programme data-based HIV surveillance in South Africa: The 2017 Antenatal Sentinel HIV Survey

Objective: South Africa has used antenatal HIV surveys for HIV surveillance in pregnant women since 1990. We assessed South Africa\u27s readiness to transition to programme data based antenatal HIV surveillance with respect to PMTCT uptake, accuracy of point-of-care rapid testing (RT) and selection bias with using programme data in the context of the 2017 antenatal HIV survey. Methods: Between 1 October and 15 November 2017, the national survey was conducted in 1,595 public antenatal facilities selected using stratified multistage cluster sampling method. Results of point-of-care RT were obtained from medical records. Blood samples were taken from eligible pregnant women and tested for HIV using immunoassays (IA) in the laboratory. Descriptive statistics were used to report on: PMTCT uptake; agreement between HIV point-of-care RT and laboratory-based HIV-1 IA; and selection bias associated with using programme data for surveillance. Results: PMTCT HIV testing uptake was high (99.8%). The positive percent agreement (PPA) between RT and IA was lower than the World Health Organization (WHO) benchmark (97.6%) at 96.3% (95% confidence interval (CI): 95.9%–96.6%). The negative percent agreement was above the WHO benchmark (99.5%), at 99.7% (95% CI: 99.6%–99.7%) nationally. PPA markedly varied by province (92.9%–98.3%). Selection bias due to exclusion of participants with no RT results was within the recommended threshold at 0.3%. Conclusion: For the three components assessed, South Africa was close to meeting the WHO standard for transitioning to routine RT data for antenatal HIV surveillance. The wide variations in PPA across provinces should be addressed

Viral suppression and factors associated with failure to achieve viral suppression among pregnant women in South Africa

Objective:To describe viral load levels among pregnant women and factors associated with failure to achieve viral suppression (viral load ≤50 copies/ml) during pregnancy.Design:Between 1 October and 15 November 2017, a cross-sectional survey was conducted among 15-49-year-old pregnant women attending antenatal care (ANC) at 1595 nationally representative public facilities.Methods:Blood specimens were taken from each pregnant woman and tested for HIV. Viral load testing was done on all HIV-positive specimens. Demographic and clinical data were extracted from medical records or self-reported. Survey logistic regression examined factors associated with failure to achieve viral suppression.Result:Of 10052 HIV-positive participants with viral load data, 56.2% were virally suppressed. Participants initiating antiretroviral therapy (ART) prior to pregnancy had higher viral suppression (71.0%) by their third trimester compared with participants initiating ART during pregnancy (59.3%). Booking for ANC during the third trimester vs. earlier: [adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI):1.4-2.3], low frequency of ANC visits (AOR for 2 ANC visits vs. ≥4 ANC visits: 2.0, 95% CI:1.7-2.4), delayed initiation of ART (AOR for ART initiated at the second trimester vs. before pregnancy:2.2, 95% CI:1.8-2.7), and younger age (AOR for 15-24 vs. 35-49 years: 1.4, 95% CI:1.2-1.8) were associated with failure to achieve viral suppression during the third trimester.Conclusion:Failure to achieve viral suppression was primarily associated with late ANC booking and late initiation of ART. Efforts to improve early ANC booking and early ART initiation in the general population would help improve viral suppression rates among pregnant women. In addition, the study found, despite initiating ART prior to pregnancy, more than one quarter of participants did not achieve viral suppression in their third trimester. This highlights the need to closely monitor viral load and strengthen counselling and support services for ART adherence

Two decades of malaria control in Malawi: Geostatistical Analysis of the changing malaria prevalence from 2000-2022 [version 2; peer review: 1 approved, 3 approved with reservations]

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 method. 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 modelled 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