Exposure to violence and PTSD symptoms among Somali women

Posttraumatic stress disorder (PTSD) symptoms, exposure to traumatic stressors, and health care utilization were examined in 84 women attending a primary health care clinic in Mogadishu, Somalia. The Somalia-Posttraumatic Diagnostic Scale was used in this active warzone to measure symptoms. Nearly all women reported high levels of confrontations with violence; half described being exposed to a potentially traumatizing event. Nearly one third had significant PTSD symptoms. Compared to those who did not, women who reported exposure to a traumatic stressor reported more confrontations with violence (7.1 vs. 3.3; p < . 001), health complaints (3.8 vs. 2.9; p = .03), and nearly 3 times as much (p = .03) health service utilization. A potentially traumatizing event was found to be a simplified proxy for assessing mental health distress in women attending a primary health care facility in highly insecure, unpredictable, resource-limited settings

Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation

Streptococcus agalactiae (Group B streptococcus, GBS) is a coloniser of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterised by Clonal Complexes (CCs) with different invasive potentials. CC17 for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with co-morbidities. The genetic basis of GBS virulence and to what extent different CCs have adapted to different host environments remain uncertain. We have therefore applied a pan-genome wide association study approach to 1988 GBS strains isolated from different hosts and countries. Our analysis identified 279 CC-specific genes associated with virulence, disease, metabolism and regulation of cellular mechanisms that may explain the differential virulence potential of particular CCs. In CC17 and CC23 for example, we have identified genes encoding for pilus, quorum sensing proteins, and proteins for the uptake of ions and micronutrients which are absent in less invasive lineages. Moreover, in CC17, carriage and disease strains were distinguished by the allelic variants of 21 of these CC-specific genes. Together our data highlight the lineage-specific basis of GBS niche adaptation and virulence, and suggest that human-associated GBS CCs have largely evolved in animal hosts before crossing to the humans and then spreading clonally

Influenza-like illness is associated with high pneumococcal carriage density in Malawian children.

Background High pneumococcal carriage density is a risk factor for invasive pneumococcal disease (IPD) and transmission, but factors that increase pneumococcal carriage density are still unclear. Methods We undertook a cross-sectional study to evaluate the microbial composition, cytokine levels and pneumococcal carriage densities in samples from children presenting with an influenza-like illness (ILI) and asymptomatic healthy controls (HC). Results The proportion of children harbouring viral organisms (Relative risk (RR) 1.4, p=0.0222) or ≥4 microbes at a time (RR 1.9, p<0.0001), was higher in ILI patients than HC. ILI patients had higher IL-8 levels in nasal aspirates than HC (median [IQR], 265.7 [0 – 452.3] vs. 0 [0 – 127.3] pg/ml; p = 0.0154). Having an ILI was associated with higher pneumococcal carriage densities compared to HC (RR 4.2, p<0.0001). Conclusion These findings suggest that children with an ILI have an increased propensity for high pneumococcal carriage density. This could in part contribute to increased susceptibility to IPD and transmission in the community

Evaluation of Pneumococcal Serotyping of Nasopharyngeal-Carriage Isolates by Latex Agglutination, Whole-Genome Sequencing (PneumoCaT), and DNA Microarray in a High-Pneumococcal-Carriage-Prevalence Population in Malawi.

Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease

Evaluation of pneumococcal serotyping in nasopharyngeal carriage isolates by latex agglutination, whole genome sequencing (PneumoCaT) and DNA microarray in a high pneumococcal carriage prevalence population in Malawi

BACKGROUND: Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for the evaluation and formulation of pneumococcal vaccines and informing vaccine policy. METHODS: We evaluated pneumococcal serotyping concordance between latex agglutination, PneumoCaT by whole genome sequencing (WGS) and DNA microarray using samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected, following WHO recommendations, between 2015 and 2017, using stratified random sampling among study populations. Participants included healthy children 3–6 years old (PCV13 vaccinated as part of EPI), healthy children 5–10 years (age-ineligible for PCV13), and HIV-infected adults (18–40yrs) on ART. For phenotypic serotyping we used a 13-valent latex kit (SSI, Denmark). For genomic serotyping we applied PneumoCaT pipeline to whole genome sequence libraries. For molecular serotyping by microarray we used the BUGS Bioscience Senti-SP microarray. RESULTS: 1347 samples were analysed. Concordance was 90.7% (95% CI: 89.0–92.2) between latex and PneumoCaT; 95.2% (93.9–96.3) between latex and microarray; and 96.6% (95.5–97.5) between microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococcus carried at low relative abundance (median 8%), microarray increased VT detection by 31.5% compared to latex serotyping. CONCLUSION: All three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine-serotypes and requires the least expertise and resources for field-implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories while investigating the importance of VT in low relative abundance in transmission and disease

Varying efficacy of artesunate+amodiaquine and artesunate+sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in the Democratic Republic of Congo: a report of two in-vivo studies

BACKGROUND: Very few data on anti-malarial efficacy are available from the Democratic Republic of Congo (DRC). DRC changed its anti-malarial treatment policy to amodiaquine (AQ) and artesunate (AS) in 2005. METHODS: The results of two in vivo efficacy studies, which tested AQ and sulphadoxine-pyrimethamine (SP) monotherapies and AS+SP and AS+AQ combinations in Boende (Equatorial province), and AS+SP, AS+AQ and SP in Kabalo (Katanga province), between 2003 and 2004 are presented. The methodology followed the WHO 2003 protocol for assessing the efficacy of anti-malarials in areas of high transmission. RESULTS: Out of 394 included patients in Boende, the failure rates on day 28 after PCR-genotyping adjustment of AS+SP and AS+AQ were estimated as 24.6% [95% CI: 16.6-35.5] and 15.1% [95% CI: 8.6-25.7], respectively. For the monotherapies, failure rates were 35.9% [95% CI: 27.0-46.7] for SP and 18.3% [95% CI: 11.6-28.1] for AQ. Out of 207 patients enrolled in Kabalo, the failure rate on day 28 after PCR-genotyping adjustment was 0 [1-sided 95% CI: 5.8] for AS+SP and AS+AQ [1-sided 95% CI: 6.2]. It was 19.6% [95% CI: 11.4-32.7] for SP monotherapy. CONCLUSION: The finding of varying efficacy of the same combinations at two sites in one country highlights one difficulty of implementing a uniform national treatment policy in a large country. The poor efficacy of AS+AQ in Boende should alert the national programme to foci of resistance and emphasizes the need for systems for the prospective monitoring of treatment efficacy at sentinel sites in the country

High residual prevalence of vaccine-serotype Streptococcus pneumoniae carriage after introduction of a pneumococcal conjugate vaccine in Malawi: a prospective serial cross-sectional study

Background: There are concerns that pneumococcal conjugate vaccines (PCV) in sub-Saharan Africa sub-optimally interrupt vaccine-serotype (VT) carriage and transmission, thus limiting vaccine-induced direct and indirect protection. We assessed carriage in vaccinated children and unvaccinated populations targeted for indirect protection, between 4 and 7 years after Malawi’s November 2011 introduction of PCV13 using a 3+0 schedule. / Methods: We conducted sequential prospective nasopharyngeal carriage surveys between 2015 and 2018 among healthy PCV-vaccinated and PCV-unvaccinated children, and HIV-infected adults. VT and NVT carriage risk by age was analysed by non-linear regression. / Results: Among PCV-vaccinated children, there was a 24% relative reduction in carriage, from a mean 21.1% to 16.1%; 45% reduction among older PCV-unvaccinated children, from 27.5% to 15.2%; 41.4% reduction among adults, from 15.2% to 8.9%. Using carriage data from children 3.6 to 10 years of age, VT carriage probability declined with age, with a similar prevalence half-life among PCV-vaccinated (3.34 years) and PCV-unvaccinated (3.26 years) children. / Conclusion: Compared to high-income settings, the 3+0 schedule in Malawi has led to a sub-optimal reduction in pneumococcal carriage prevalence. This is likely due to recolonisation of vaccinated children with waning vaccine-induced immunity, resulting in insufficient indirect protection of unvaccinated populations. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns is required

Hepatitis B vaccination impact and the unmet need for antiviral treatment in Blantyre, Malawi

BACKGROUND: Hepatitis B is the leading cause of cirrhosis and liver cancer in sub-Saharan Africa. To reduce hepatitis-associated mortality, antiviral treatment programmes are needed. We estimated prevalence, vaccine impact and need for antiviral treatment in Blantyre, Malawi to inform an effective public health response. METHODS: We conducted a household study in Blantyre in 2016-2018. We selected individuals from a census using random sampling and estimated age-sex-standardised HBsAg seroprevalence. Impact of infant hepatitis B vaccination, which began in 2002, was estimated by binomial log-linear regression comparing individuals born before and after vaccine implementation. In HBsAg-positive adults, eligibility for antiviral therapy was assessed. RESULTS: Of 97,386 censused individuals, 6,073 (median age 18 years; 56.7% female) were sampled. HBsAg seroprevalence was 5.1% (95% CI 4.3-6.1) among adults and 0.3% (0.1-0.6) among children born after vaccine introduction. Estimated vaccine impact was 95.8% (70.3-99.4). Of HBsAg-positive adults, 26% were HIV-positive. Among HIV-negative individuals, 3%, 6% and 9% were eligible for hepatitis B treatment by WHO, European and American hepatology association criteria, respectively. CONCLUSIONS: Infant HBV vaccination has been highly effective in reducing HBsAg prevalence in urban Malawi. Up to 9% of HBsAg-positive HIV-negative adults are eligible, but have an unmet need, for antiviral therapy

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

Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children.

BACKGROUND: Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy. METHODS: Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only. RESULTS: Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702), artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706) and artemether-lumefantrine (AL, N = 518).Using method (1a), the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference) and the others were: (i) method 1b = 1.3% [0 to 24.8], (ii) method 2a = 1.1% [0 to 21.5], and (iii) method 2b = 0% [-38 to 19.3].The standard per-protocol method (1a) tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a). It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size was lost when failures were classified on the first day of parasite recurrence and survival analytical methods were used. CONCLUSION: The primary purpose of an in vivo study should be to provide a precise estimate of the risk of antimalarial treatment failure due to drug resistance. Use of survival analysis is the most appropriate way to estimate failure rates with parasitological recurrence classified as treatment failure on the day it occurs