A simulation-based method to inform serosurvey design for estimating the force of infection using existing blood samples.

The extent to which dengue virus has been circulating globally and especially in Africa is largely unknown. Testing available blood samples from previous cross-sectional serological surveys offers a convenient strategy to investigate past dengue infections, as such serosurveys provide the ideal data to reconstruct the age-dependent immunity profile of the population and to estimate the average per-capita annual risk of infection: the force of infection (FOI), which is a fundamental measure of transmission intensity. In this study, we present a novel methodological approach to inform the size and age distribution of blood samples to test when samples are acquired from previous surveys. The method was used to inform SERODEN, a dengue seroprevalence survey which is currently being conducted in Ghana among other countries utilizing samples previously collected for a SARS-CoV-2 serosurvey. The method described in this paper can be employed to determine sample sizes and testing strategies for different diseases and transmission settings.

[Schätzung der Wirksamkeit der Grippeimpfung anhand von Sekundärdaten: Eine Kohortenstudie und Propensity-Score-Matching-Analyse von Leistungsdaten aus Baden-Württemberg]. / Estimation of Influenza Vaccine Effectiveness using Secondary Data: A Cohort Study and Propensity Score-Matched Analysis of Claims Data from Baden-Wuerttemberg.

Ziel war es die Wirksamkeit der Influenza-Impfung (VE) für die Grippesaison 2014/2015 auf Grundlage von Routinedaten aus Krankenkassendatensatz zu schätzen und zu replizieren. Zusätzlich sollten methodische Aspekte untersucht werden. Es wurden Abrechnungsdaten von 2,64 Millionen Versicherten der AOK Baden-Württemberg mit dortigem Wohnsitz ab 15 Jahren analysiert. Basierend auf Abrechnungsdaten für die Influenza-Impfung 2014, wurden die Teilnehmer als ungeimpft oder geimpft klassifiziert. Kovariablen, die den Zusammenhang zwischen Impfung und Influenzainfektion beeinträchtigen könnten, wurden berücksichtigt. Hierzu gehörten Alter, Geschlecht, Wohnort sowie Kovariablen, die auf den Gesundheitszustand und die Inanspruchnahme von Gesundheitsdienstleistungen hinweisen. Der primäre Endpunkt war ein Krankenhausaufenthalt wegen Influenza während der Grippesaison 2015. Zu den sekundären Endpunkten gehörten unter anderem Krankenhausaufenthalte wegen Lungenentzündung und die Gesamtmortalität. Um eine vergleichbare Gruppe von geimpften und ungeimpften Teilnehmern zu ermitteln, wurde ein Propensity-Score-Matching (PSM) durchgeführt. Es wurde eine Bias-Analyse durchgeführt, bei der die VE vor und nach der Grippesaison geschätzt wurde, also zu Zeitpunkten, in denen angenommen wurde, dass die Influenza nicht in der Bevölkerung zirkulierte und die Impfung nicht wirken konnte. Insgesamt konnten 839.706 Teilnehmer 1:1 gematcht werden. Die geschätzte VE (basierend auf Influenza bedingten Krankenhausaufenthalten) betrug 27% [95%Konfidenzintervall (KI): 17%; 36%], was der Schätzung des RKI für dieselbe Saison (27% [95%KI: -1%; 47%]) entspricht. Die Bias-Analyse zeigte, dass das Ergebnis teilweise durch residuale Konfundierung erklärt werden kann, was zu einer potenziellen Überschätzung des zugrunde liegenden Effekts führt. Die Ergebnisse der sekundären Endpunkte zeigten ähnliche Ergebnisse, obwohl sie wahrscheinlich in höherem Maße durch residuale Konfundierung bedingt sind. Zusammenfassend zeigt sich, dass (1) sekundäre Daten der deutschen Krankenkassen verwendet werden können, um plausible VE-Schätzungen abzuleiten, und dass (2) das PSM eine nützliche und transparente Methode zur Ableitung dieser Schätzungen ist. Darüber hinaus ist (3) residuale Konfundierung ein relevantes Problem in Beobachtungsstudien zu VE und (4) Bias-Analysen vor- und nach der Grippesaison sind eine wesentliche Ergänzung für die Interpretation der Ergebnisse.

High seroprevalence of SARS-CoV-2 in Burkina-Faso, Ghana and Madagascar in 2021: a population-based study.

BACKGROUND: The current COVID-19 pandemic affects the entire world population and has serious health, economic and social consequences. Assessing the prevalence of COVID-19 through population-based serological surveys is essential to monitor the progression of the epidemic, especially in African countries where the extent of SARS-CoV-2 spread remains unclear. METHODS: A two-stage cluster population-based SARS-CoV-2 seroprevalence survey was conducted in Bobo-Dioulasso and in Ouagadougou, Burkina Faso, Fianarantsoa, Madagascar and Kumasi, Ghana between February and June 2021. IgG seropositivity was determined in 2,163 households with a specificity improved SARS-CoV-2 Enzyme-linked Immunosorbent Assay. Population seroprevalence was evaluated using a Bayesian logistic regression model that accounted for test performance and age, sex and neighbourhood of the participants. RESULTS: Seroprevalence adjusted for test performance and population characteristics were 55.7% [95% Credible Interval (CrI) 49·0; 62·8] in Bobo-Dioulasso, 37·4% [95% CrI 31·3; 43·5] in Ouagadougou, 41·5% [95% CrI 36·5; 47·2] in Fianarantsoa, and 41·2% [95% CrI 34·5; 49·0] in Kumasi. Within the study population, less than 6% of participants performed a test for acute SARS-CoV-2 infection since the onset of the pandemic. CONCLUSIONS: High exposure to SARS-CoV-2 was found in the surveyed regions albeit below the herd immunity threshold and with a low rate of previous testing for acute infections. Despite the high seroprevalence in our study population, the duration of protection from naturally acquired immunity remains unclear and new virus variants continue to emerge. This highlights the importance of vaccine deployment and continued preventive measures to protect the population at risk.

Hepatitis E seroprevalence and viremia rate in immunocompromised patients: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Hepatitis E is an infectious disease of the liver caused by the hepatitis E virus (HEV). Immunocompromised patients present a particular risk group, as chronification of hepatitis E leading to life-threatening cirrhosis occurs when these patients are infected. Therefore, this study aims to estimate and compare the anti-HEV seroprevalence and the rate of HEV RNA positivity in transplant recipients and patients with human immunodeficiency virus (HIV). METHODS: This systematic review and meta-analysis involved a literature search (PubMed, Scopus; 1,138 studies) including 120 studies from 1996 to 2019, reporting anti-HEV seroprevalence and/or HEV-RNA positivity. Statistical analysis was performed using a linear mixed-effects meta regression model. RESULTS: Anti-HEV seroprevalence in 14 626 transplant recipients ranged from 6% (95% CI: 1.9-17.2) to 29.6% (95% CI: 21.6-39.) in different commercially available assays and did not differ significantly compared to 20 825 HIV positive patients (range: 3.5% (95% CI: 0.9-12.8) - 19.4% (95% CI: 13.5-26.9). In contrast, HEV-RNA positivity rate was significantly higher in transplant recipients than in HIV positive patients (1.2% (95% CI: 0.9-1.6) vs 0.39% (95% CI: 0.2-0.7); P-value = 0.0011). CONCLUSION: Anti-HEV seroprevalence did not differ significantly between transplant recipients and HIV positive patients. Interestingly, rates of HEV-RNA positivity, indicating ongoing infection, were significantly higher in transplant recipients. These findings demonstrate that transplant patients have an elevated risk of chronic infection in comparison to HIV patients at comparable risk of HEV-exposure.

Cytokine Profile Distinguishes Children With Plasmodium falciparum Malaria From Those With Bacterial Blood Stream Infections.

BACKGROUND: Malaria presents with unspecific clinical symptoms that frequently overlap with other infectious diseases and is also a risk factor for coinfections, such as non-Typhi Salmonella. Malaria rapid diagnostic tests are sensitive but unable to distinguish between an acute infection requiring treatment and asymptomatic malaria with a concomitant infection. We set out to test whether cytokine profiles could predict disease status and allow the differentiation between malaria and a bacterial bloodstream infection. METHODS: We created a classification model based on cytokine concentration levels of pediatric inpatients with either Plasmodium falciparum malaria or a bacterial bloodstream infection using the Luminex platform. Candidate markers were preselected using classification and regression trees, and the predictive strength was calculated through random forest modeling. RESULTS: Analyses revealed that a combination of 7-15 cytokines exhibited a median disease prediction accuracy of 88% (95th percentile interval, 73%-100%). Haptoglobin, soluble Fas-Ligand, and complement component C2 were the strongest single markers with median prediction accuracies of 82% (with 95th percentile intervals of 71%-94%, 62%-94%, and 62%-94%, respectively). CONCLUSIONS: Cytokine profiles possess good median disease prediction accuracy and offer new possibilities for the development of innovative point-of-care tests to guide treatment decisions in malaria-endemic regions.

Investigating the utility of Google trends for Zika and Chikungunya surveillance in Venezuela.

INTRODUCTION: Chikungunya and Zika Virus are vector-borne diseases responsible for a substantial disease burden in the Americas. Between 2013 and 2016, no cases of Chikungunya or Zika Virus were reported by the Venezuelan Ministry of Health. However, peaks of undiagnosed fever cases have been observed during the same period. In the context of scarce data, alternative surveillance methods are needed. Assuming that unusual peaks of acute fever cases correspond to the incidences of both diseases, this study aims to evaluate the use of Google Trends as an indicator of the epidemic behavior of Chikungunya and Zika. METHODS: Time-series cross-correlations of acute fever cases reported by the Venezuelan Ministry of Health and data on Google search queries related to Chikungunya and Zika were calculated. RESULTS: A temporal distinction has been made so that acute febrile cases occurring between 25th of June 2014 and 23rd of April 2015 were attributed to the Chikungunya virus, while cases occurring between 30th of April 2015 and 29th of April 2016 were ascribed to the Zika virus. The highest cross-correlations for each disease were shown at a lag of 0 (r = 0.784) for Chikungunya and at + 1 (r = 0.754) for Zika. CONCLUSION: The strong positive correlation between Google search queries and official data on acute febrile cases suggests that this resource can be used as an indicator of endemic urban arboviruses activity. In the Venezuelan context, Internet search queries might help to overcome some of the gaps that exist in the national surveillance system.

Laboratory Findings, Compassionate Use of Favipiravir, and Outcome in Patients With Ebola Virus Disease, Guinea, 2015-A Retrospective Observational Study.

BACKGROUND: In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. METHODS: To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. RESULTS: The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. CONCLUSIONS: Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

Development of breast cancer mortality considering the implementation of mammography screening programs - a comparison of western European countries.

BACKGROUND: Triggered by the successive implementation of organized mammography screening programs (MSPs) throughout western European countries over the last decades, there is an ongoing debate questioning their effectiveness. Since it is difficult to assess the effect of MSPs on a population level, we rather aim to assess the impact of the implementation itself on breast cancer mortality rates utilizing an ecological study design. METHODS: We analyzed age group-specific (50-59, 60-69 and 70-79 years) female breast cancer mortality rates in 14 western European countries between 1980 and 2017 using Joinpoint regression, interrupted time series (ITS) regression and multivariable Poisson regression. RESULTS: The Joinpoint analysis demonstrated decreasing trends resulting in annual percentage changes ranging from - 1.5% to - 5.4% (50-59), - 0.2% to - 8.1% (60-69) and 0% to - 7.1% (70-79) depending on the country within 3 years after MSP implementation. The ITS analysis results in highly significant interaction terms (calendar year * binary MSP indicator) for all age groups. The multivariable regression using "calendar year", "year of MSP implementation" and "years with MSP" as independent variables yielded a significant yearly decrease for "years with MSP" ranging from 0.9 to 1.2%. CONCLUSIONS: The results of this study suggest a positive association between the implementation of MSPs and the (accelerated) reduction of breast cancer mortality rates. Measuring and quantifying the isolated effect of MSPs on a population level will require additional studies using individual data.

Second follow-up of a German cohort on childhood cancer incidence after exposure to postnatal diagnostic x-ray.

Studies on children exposed to ionising radiation by computed tomography (CT) indicate an increased risk of leukemia and central nervous system (CNS) tumors. Evidence of the risks associated with diagnostic x-ray examinations, the most frequent examination in pediatric radiology, in which the radiation dose is up to 750 times lower compared to CT examinations, is less clear. This study presents results of the second follow-up for the risk of childhood cancer in a cohort of children (<15 years) with diagnostic x-ray exposure at a large German hospital during 1976-2003 followed for additional 10 years until 2016. With a latency period of 6 months, 92 998 children contributed 794 549 person-years. The median effective dose was 7 µSv. Hundred incident cancer cases were identified: 35 leukemia, 13 lymphomas, 12 CNS tumors, 15 blastomas, 15 sarcomas and 10 other solid tumors, consisting of six germ cells tumors, three thyroid cancers and one adrenocortical carcinoma. For all cancer cases combined the standardised incidence ratio (SIR) was 1.14 (95% confidence interval (CI) 0.93-1.39), for leukemia 1.15 (95% CI 0.63-1.61), for lymphomas 1.03 (95% CI 0.55-1.76), for CNS tumors 0.65 (95% CI 0.34-1.14), for blastomas 1.77 (95% CI 0.91-2.91), for sarcomas 1.28 (95% CI 0.71-2.11) and for other solid tumors 2.38 (95% CI 1.14-4.38). Dose-response analysis using Poisson regression revealed no significant trend for dose groups. Results did not differ substantially with a latency period of 2 years for all cancer entities and 5 years for solid tumors in sensitivity analyses. Overall, the null results of the first follow-up were confirmed. Although an association between radiation exposure and a risk for certain solid tumors like thyroid cancer is known, the significantly increased SIR in the group of other solid tumors must be critically interpreted in the context of the small number of cases and the very low doses of radiation exposure in this group.

Timing of surgery in ulcerative colitis in the biologic therapy era-the patient's perspective.

BACKGROUND: There is no general consensus regarding the ideal timing of surgery in patients with refractory ulcerative colitis (UC). Decision-making and timing of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is influenced by treating physicians and patients themselves. The aim of this study was to determine whether or not patients would have preferred the operation to be performed earlier, at the same time, or at a later point of time and to determine the reasons for their preference. METHODS: Clinical data of 193 patients with UC who have undergone IPAA were documented in a prospective database at our institution between 2004 and 2015. From this database, 190 patients were identified and a standardized custom-made questionnaire was mailed for follow-up survey. Patients who did not respond were called by telephone and encouraged to complete the questionnaire. RESULTS: One hundred nine questionnaires were eligible for analysis (57.4%). Average time between diagnosis and surgery was 11.2 ± 10.8 years (mean ± SD). Indications for surgery were refractory disease (70.6%), colitis-associated colorectal cancer (11.0%), high-grade dysplasia or stenosis (11.9%), and septic complications of UC (6.4%); 39 of 77 patients (50.6%) with refractory UC reported to have preferred their operation to be carried out earlier as it was actually performed (16.8 ± 11.9 months). Refractory course of the disease was identified as a predictor for a retrospectively desired earlier surgical approach (p = 0.014). CONCLUSION: A substantial proportion of patients felt that they should have undergone surgery earlier than actually performed. It appears that timing of the decision to undergo surgery is suboptimal. This situation may be improved by earlier surgical consultation in the course of the disease.

Radiotherapy for childhood cancer and subsequent thyroid cancer risk: a systematic review.

Most of the pooled analyses and reviews reported an association between radiotherapy for childhood cancer and an increased thyroid cancer risk. Up to now this article presents the first systematic literature review on this association combined with a critical assessment of the methodological quality of the included articles. PubMed and Web of Science databases were searched for relevant articles until May 2016. We included peer-reviewed cohort and case-control studies that investigated an association between radiotherapy for childhood cancer and the occurrence of subsequent thyroid cancer. A systematic overview is presented for the included studies. We identified 17 retrospective cohort studies, and four nested case-control studies, representing 100,818 subjects. The age range at first cancer diagnosis was 0-25.2 years. Considerable variability was found regarding study sizes, study design, treatment strategies, dose information, and follow-up periods. 20 of the 21 identified studies showed increased thyroid cancer risks associated with childhood radiation exposure. The large majority showed an increased relative risk or odds ratio confirming the association between radiotherapy and thyroid cancer although the variation in results was large. Additionally to a pooled analysis that has been published recently, we systematically included 17 further studies, which allowed us to cover information from countries that were not covered by large-scale childhood cancer survivor studies. The methodological limitations of existing studies and inconsistencies in findings across studies yielded a large study heterogeneity, which made a detailed comparison of study results difficult. There is a need to strengthen standardisation for reporting.

Modeling Variables With a Spike at Zero: Examples and Practical Recommendations.

In most epidemiologic studies and in clinical research generally, there are variables with a spike at zero, namely variables for which a proportion of individuals have zero exposure (e.g., never smokers) and among those exposed the variable has a continuous distribution. Different options exist for modeling such variables, such as categorization where the nonexposed form the reference group, or ignoring the spike by including the variable in the regression model with or without some transformation or modeling procedures. It has been shown that such situations can be analyzed by adding a binary indicator (exposed/nonexposed) to the regression model, and a method based on fractional polynomials with which to estimate a suitable functional form for the positive portion of the spike-at-zero variable distribution has been developed. In this paper, we compare different approaches using data from 3 case-control studies carried out in Germany: the Mammary Carcinoma Risk Factor Investigation (MARIE), a breast cancer study conducted in 2002-2005 (Flesch-Janys et al., Int J Cancer. 2008;123(4):933-941); the Rhein-Neckar Larynx Study, a study of laryngeal cancer conducted in 1998-2000 (Dietz et al., Int J Cancer. 2004;108(6):907-911); and a lung cancer study conducted in 1988-1993 (Jöckel et al., Int J Epidemiol. 1998;27(4):549-560). Strengths and limitations of different procedures are demonstrated, and some recommendations for practical use are given.

Modeling continuous covariates with a "spike" at zero: Bivariate approaches.

In epidemiology and clinical research, predictors often take value zero for a large amount of observations while the distribution of the remaining observations is continuous. These predictors are called variables with a spike at zero. Examples include smoking or alcohol consumption. Recently, an extension of the fractional polynomial (FP) procedure, a technique for modeling nonlinear relationships, was proposed to deal with such situations. To indicate whether or not a value is zero, a binary variable is added to the model. In a two stage procedure, called FP-spike, the necessity of the binary variable and/or the continuous FP function for the positive part are assessed for a suitable fit. In univariate analyses, the FP-spike procedure usually leads to functional relationships that are easy to interpret. This paper introduces four approaches for dealing with two variables with a spike at zero (SAZ). The methods depend on the bivariate distribution of zero and nonzero values. Bi-Sep is the simplest of the four bivariate approaches. It uses the univariate FP-spike procedure separately for the two SAZ variables. In Bi-D3, Bi-D1, and Bi-Sub, proportions of zeros in both variables are considered simultaneously in the binary indicators. Therefore, these strategies can account for correlated variables. The methods can be used for arbitrary distributions of the covariates. For illustration and comparison of results, data from a case-control study on laryngeal cancer, with smoking and alcohol intake as two SAZ variables, is considered. In addition, a possible extension to three or more SAZ variables is outlined. A combination of log-linear models for the analysis of the correlation in combination with the bivariate approaches is proposed.

Epidemiology and multiple colonization of gastrointestinal pathogens in rural Tanzanian children with and without diarrhea: A case-control study.

Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic individuals in resource-limited countries have been repeatedly described. In this study, we assessed the differentiated effects of combined pathogen detections on recorded symptoms. A case-control study was conducted among 620 under-five-year-old children in rural northeastern Tanzania with emphasis of multiple detection. The median age of children was 11 months (IQR = 7, 20), and 52.1% were male. Cases (50.2%, n = 157) were less likely than controls (64.5%, n = 198) to have multiple colonization with gastrointestinal tract (GIT) pathogens. The children's age was positively associated with the likelihood of harboring multiple GIT pathogens [OR, 1.02, 95% CI = 1.01, 1.04]. Shigella spp./enteroinvasive Escherichia coli (EIEC) [OR = 2.80, 95% CI 1.62, 4.83] and norovirus [OR = 2.04, 95% CI 1.23, 3.39] were more common in cases and were strongly associated with diarrhea, while enteroaggregative E. coli (EAEC) [OR = 0.23, 95%CI 0.17-0.33] were more common in controls. Diarrheal diseases in under-five children from rural Tanzania are likely to be due to infections with Shigella spp./EIEC, and norovirus with strongly age-dependent associations.

Schistosome infection among pregnant women in the rural highlands of Madagascar: A cross-sectional study calling for public health interventions in vulnerable populations.

INTRODUCTION: Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa (SSA) with Madagascar being among the countries with highest burden of the disease worldwide. Despite WHO recommendations, suggesting treatment of pregnant women after the first trimester, this group is still excluded from Mass Drug Administration programs. Our study, had the objective to measure the prevalence of schistosome infection among pregnant women in Madagascar in order to inform public health policies for treatment in this vulnerable population. METHODS: Women were recruited for this cross-sectional study between April 2019 and February 2020 when attending Antenatal Care Services (ANCs) at one of 42 included Primary Health Care Centers. The urine-based upconverting reporter particle, lateral flow (UCP-LF) test detecting circulating anodic antigen was used for the detection of schistosome infections. To identify factors associated with the prevalence of schistosome infection crude and adjusted prevalence ratios and 95% CIs were estimated using mixed-effect Poisson regression. RESULTS: Among 4,448 participating women aged between 16 and 47 years, the majority (70.4%, 38 n = 3,133) resided in rural settings. Overall, the prevalence of schistosome infection was 55.9% (n = 2486, CI 95%: 53.3-58.5). A statistically significant association was found with age group (increased prevalence in 31-47 years old, compared to 16-20 years old (aPR = 1.15, CI 95%: 1.02-1.29) and with uptake of antimalaria preventive treatment (decreased prevalence, aPR = 0.85, CI 95%: 0.77-0.95). No other associations of any personal characteristics or contextual factors with schistosome infection were found in our multivariate regression analysis. DISCUSSION AND CONCLUSION: The high prevalence of schistosome infection in pregnant women supports the consideration of preventive schistosomiasis treatment in ANCs of the Malagasy highlands. We strongly advocate for adapting schistosomiasis programs in highly endemic contexts. This, would contribute to both the WHO and SDGs agendas overall to improving the well-being of women and consequently breaking the vicious cycle of poverty perpetuated by schistosomiasis.

What are the pathways between poverty and malaria in sub-Saharan Africa? A systematic review of mediation studies.

BACKGROUND: Malaria remains a major burden in sub-Saharan Africa (SSA). While an association between poverty and malaria has been demonstrated, a clearer understanding of explicit mechanisms through which socioeconomic position (SEP) influences malaria risk is needed to guide the design of more comprehensive interventions for malaria risk mitigation. This systematic review provides an overview of the current evidence on the mediators of socioeconomic disparities in malaria in SSA. METHODS: We searched PubMed and Web of Science for randomised controlled trials, cohort, case-control and cross-sectional studies published in English between January 1, 2000 to May 31, 2022. Further studies were identified following reviews of reference lists of the studies included. We included studies that either (1) conducted a formal mediation analysis of risk factors on the causal pathway between SEP and malaria infections or (2) adjusted for these potential mediators as confounders on the association between SEP and malaria using standard regression models. At least two independent reviewers appraised the studies, conducted data extraction, and assessed risk of bias. A systematic overview is presented for the included studies. RESULTS: We identified 41 articles from 20 countries in SSA for inclusion in the final review. Of these, 30 studies used cross-sectional design, and 26 found socioeconomic inequalities in malaria risk. Three formal mediation analyses showed limited evidence of mediation of food security, housing quality, and previous antimalarial use. Housing, education, insecticide-treated nets, and nutrition were highlighted in the remaining studies as being protective against malaria independent of SEP, suggesting potential for mediation. However, methodological limitations included the use of cross-sectional data, insufficient confounder adjustment, heterogeneity in measuring both SEP and malaria, and generally low or moderate-quality studies. No studies considered exposure mediator interactions or considered identifiability assumptions. CONCLUSIONS: Few studies have conducted formal mediation analyses to elucidate pathways between SEP and malaria. Findings indicate that food security and housing could be more feasible (structural) intervention targets. Further research using well-designed longitudinal studies and improved analysis would illuminate the current sparse evidence into the pathways between SEP and malaria and adduce evidence for more potential targets for effective intervention.

Awareness and knowledge of female genital schistosomiasis in a population with high endemicity: a cross-sectional study in Madagascar.

Introduction: Female genital schistosomiasis (FGS) is a neglected disease with long-term physical and psychosocial consequences, affecting approximately 50 million women worldwide and generally representing an unmet medical need on a global scale. FGS is the chronic manifestation of a persistent infection with Schistosoma haematobium. FGS services are not routinely offered in endemic settings with a small percentage of women at risk receiving adequate care. Madagascar has over 60% prevalence of FGS and no guidelines for the management of the disease. This study aimed to determine FGS knowledge among women and health care workers (HCWs) in a highly endemic area of Madagascar. Methods: A convenience sampling strategy was used for this cross-sectional study. Descriptive statistics including proportions and 95% confidence intervals (CI) were calculated, reporting socio-demographic characteristics of the population. Knowledge sources were evaluated descriptively. Binary Poisson regression with robust standard errors was performed; crude (CPR) and adjusted prevalence ratio (APR) with 95% CIs were calculated. Results: A total of 783 participants were included in the study. Among women, 11.3% (n = 78) were aware of FGS while among the HCWs 53.8% (n = 50) were aware of FGS. The highest level of knowledge was observed among women in an urban setting [24%, (n = 31)] and among those with a university education/vocational training [23% (n = 13)]. A lower APR of FGS knowledge was observed in peri-urban [APR 0.25 (95% CI: 0.15; 0.45)] and rural [APR 0.37 (95% CI 0.22; 0.63)] settings in comparison to the urban setting. Most HCWs reported other HCWs [40% (n = 20)] while women mainly reported their family [32% (n = 25)] as being their main source of information in the 6 months prior to the survey. Discussion and conclusions: Our study shows limited awareness and knowledge of FGS among population groups in the highly endemic Boeny region of Madagascar. With this study we contribute to identifying an important health gap in Madagascar, which relates to a disease that can silently affect millions of women worldwide. In alignment with the targets of the NTD roadmap, addressing schistosomiasis requires a paradigm shift for its control and management including a greater focus on chronic forms of the disease.

Female genital schistosomiasis, human papilloma virus infection, and cervical cancer in rural Madagascar: a cross sectional study.

BACKGROUND: Women's health in resource-limited settings can benefit from the integrated management of high-burden diseases, such as female genital schistosomiasis (FGS) and human papilloma virus (HPV)-related cervical cancer. In schistosomiasis-endemic countries such as Madagascar, data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions. This study aims to estimate the prevalence of FGS and HPV in rural Madagascar, and to examine associated risk factors to identify opportunities for improving women's health. METHODS: After initial community outreach activities, interested women aged 18-49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay. FGS was detected by colposcopy. Colposcopy images were double-blind reviewed by two independent specialists. A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing. Crude (CPR) and adjusted prevalence ratios (APR) of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95% confidence intervals (CIs). RESULTS: Among 500 women enrolled, 302 had complete information on FGS and HPV diagnosis, and were thus eligible for analysis. Within the sample, 189 (62.6%, 95% CI: 56.9-68.1) cases of FGS were detected. A total of 129 women (42.7%, 95% CI: 37.1-48.5) tested positive for HPV. In total, 80 women (26.5%, 95% CI: 21.6-31.8]) tested positive for both conditions. No association was observed between FGS and HPV positivity, while previous pregnancy (APR = 0.65, 95% CI: 0.43-0.78) and older age (APR = 0.59, 95% CI: 0.42-0.81) are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups. CONCLUSIONS: The results of the study show that FGS and HPV are highly prevalent in rural Madagascar. The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women's health, such as integrated services at primary level of care.

Prevalence and risk distribution of schistosomiasis among adults in Madagascar: a cross-sectional study.

BACKGROUND: The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals, including universal health coverage (UHC). Current control strategies focus on school-aged children, systematically neglecting adults. We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC. METHODS: In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina, Tsiroanomandidy and Ankazomborona in Madagascar, we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants. Univariable and multivariable logistic regression were performed to evaluate odd ratios. RESULTS: The highest prevalence of S. mansoni, S. haematobium and co-infection of both species was 59.5%, 61.3% and 3.3%, in Andina and Ankazomborona respectively. Higher prevalence was observed among males (52.4%) and main contributors to the family income (68.1%). Not working as a farmer and higher age were found to be protective factors for infection. CONCLUSIONS: Our findings provide evidence that adults are a high-risk group for schistosomiasis. Our data suggests that, for ensuring basic health as a human right, current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific, holistic and integrated approaches.

Cause of death distribution with InterVA and physician coding in a rural area of Burkina Faso.

OBJECTIVES: To compare the cause of death distribution using the Physician Coded Verbal Autopsy approach versus the Interpreting Verbal Autopsy model, based on information from a French verbal autopsy questionnaire, in rural north-western Burkina Faso. METHODS: Data from 5649 verbal autopsy questionnaires reviewed by local physicians at the Nouna Health and Demographic Surveillance Site between 1998 and 2007 were considered for analyses. Information from VA interviews was extracted to create a set of standard indicators needed to run the Interpreting Verbal Autopsy model. Cause-specific mortality fractions were used to compare Physician Coded Verbal Autopsy and Interpreting Verbal Autopsy results. RESULTS: At the population level, 62.5% of causes of death using the Interpreting Verbal Autopsy model corresponded with those determined by two or three physicians. Although seven of the 10 main causes of death were present in both approaches, the comparison of percentages of single causes of death shows discrepancies, dominated by higher malaria rates found in the Physician Coded Verbal Autopsy approach. CONCLUSION: Our results confirm that national mortality statistics, which are partly based on verbal autopsies, must be carefully interpreted. Difficulties in determining malaria as cause of death in holoendemic malaria regions might result in higher discrepancies than those in non-endemic areas. As neither Physician Coded Verbal Autopsy nor Interpreting Verbal Autopsy results represent a gold standard, uncertainty levels with either procedure are high.