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A sensitive and specific non-sputum-based test would be groundbreaking for the diagnosis of childhood tuberculosis. We assessed side by side the diagnostic accuracy of the urine-based lipoarabinomannan assays Fujifilm SILVAMP TB LAM (FujiLAM) and Alere Determine TB LAM Ag (AlereLAM) for detection of childhood tuberculosis. In this cross-sectional study, we tested urine samples from children younger than 15 years with presumed pulmonary tuberculosis. Children were consecutively recruited from four dedicated outpatient childhood tuberculosis clinics in The Gambia, Mali, Nigeria, and Tanzania. Biobanked urine samples were thawed and tested using FujiLAM and AlereLAM assays. We measured diagnostic performance against a microbiological reference standard (confirmed tuberculosis) and a composite reference standard (confirmed and unconfirmed tuberculosis). Sensitivity and specificity were estimated with bivariate random-effects meta-analyses. Between July 1, 2017, and Dec 1, 2018, we obtained and stored urine samples from 415 children. 63 (15%) children had confirmed tuberculosis, 113 (27%) had unconfirmed tuberculosis, and 239 (58%) were unlikely to have tuberculosis. 61 children were HIV-positive (prevalence 15%). Using the microbiological reference standard, the sensitivity of FujiLAM was 64·9% (95% CI 43·7–85·2; positive in 40 of 63 confirmed samples) and the sensitivity of AlereLAM was 30·7% (8·6–61·6; 19 of 63). The specificity of FujiLAM was 83·8% (95% CI 76·5–89·4; negative in 297 of 352 unconfirmed and unlikely samples) and the specificity of AlereLAM was 87·8% (79·0–93·7; 312 of 352). Against the composite reference standard, both assays had decreased sensitivity; the sensitivity of FujiLAM was 32·9% (95% CI 24·6–41·9; positive in 58 of 176 confirmed and unconfirmed samples) and the sensitivity of AlereLAM was 20·2% (12·3–29·4; 36 of 176). The specificity of FujiLAM was 83·3% (95% CI 71·8–91·7; negative in 202 of 239 unlikely samples) and the specificity of AlereLAM was 90·0% (81·6–95·6; 216 of 239). By comparison with AlereLAM, FujiLAM showed higher sensitivity and similar specificity. FujiLAM could potentially add value to the rapid diagnosis of tuberculosis in children. German Federal Ministry of Education and Research, the Global Health Innovative Technology Fund, the UK Research and Innovation Global Challenges Research Fund, and the UK Medical Research Council.

We conducted an ancillary study among individuals who had participated in a PCV-7 trial in rural Gambia, to determine the influence of season on the prevalence of pneumococcal carriage. 636 individuals above 30 months of age were followed from 4 to 20 months after vaccination with PCV-7 or meningococcal-conjugate-vaccine. Nasopharyngeal swabs were collected periodically between November 2006 and June 2008. Overall, 4,495 NPS were collected. Prevalence of pneumococcal nasopharyngeal carriage in the study subjects (median age 11 years) was 55.0%; this prevalence decreased linearly with increasing age (p = 0.001). Prevalence of carriage was significantly higher during the dry than the rainy season for any pneumococcal carriage [57.6% versus 47.8% (p<0.001)], pneumococcal vaccine serotype carriage [10.3% versus 6.5% (p< 0.001)] and non-vaccine serotype carriage [49.7% versus 42.7% (p<0.001)]. Differences remained significant in the adjusted analysis. In areas of Africa with marked variation in rainfall, seasonality of pneumococcal carriage needs to be considered when interpreting carriage data.

Background Over 500 million people live with chronic respiratory diseases globally and approximately 4 million of these, mostly from the low- and middle-income countries including sub-Saharan Africa, die prematurely every year. Despite high CRD morbidity and mortality, only very few studies describe CRDs and little is known about the economic, social and psychological dimensions of living with CRDs in sub-Saharan Africa. We aimed to gain an in-depth understanding of the social, livelihood and psychological dimensions of living with CRD to inform management of CRDs in Sudan and Tanzania. Method We conducted 12 in-depth interviews in 2019 with people with known or suspected CRD and 14 focus group discussions with community members in Gezira state, Sudan and Dodoma region, Tanzania, to share their understanding and experience with CRD. The data was analysed using thematic framework analysis. Results People with CRD in both contexts reported experiences under two broad themes: impact on economic wellbeing and impact on social and psychological wellbeing. Capacity to do hard physical work was significantly diminished, resulting in direct and indirect economic impacts for them and their families. Direct costs were incurred while seeking healthcare, including expenditures on transportation to health facility and procurement of diagnostic tests and treatments, whilst loss of working hours and jobs resulted in substantial indirect costs. Enacted and internalised stigma leading to withdrawal and social exclusion was described by participants and resulted partly from association of chronic cough with tuberculosis and HIV/AIDS. In Sudan, asthma was described as having negative impact on marital prospects for young women and non-disclosure related to stigma was a particular issue for young people. Impaired community participation and restrictions on social activity led to psychological stress for both people with CRD and their families. Conclusion Chronic respiratory diseases have substantial social and economic impacts among people with CRD and their families in Sudan and Tanzania. Stigma is particularly strong and appears to be driven partly by association of chronic cough with infectiousness. Context-appropriate measures to address economic impacts and chronic cough stigma are urgently needed as part of interventions for chronic respiratory diseases in these sub-Saharan African contexts.

There is growing concern that interventions that alter microbial ecology can adversely affect health. We characterised the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal carriage and the bacterial component of the nasopharyngeal microbiome during infancy. Newborns were recruited into three groups as follows: Group1 (n = 33) was the control group and comprised infants who received PCV7 after 6 months and came from unvaccinated communities. Group 2 (n = 30) came from unvaccinated communities and Group 3 (n = 39) came from vaccinated communities. Both group 2 and 3 received PCV7 at 2, 3 and 4 months. Culture and 16 S rRNA gene sequencing were performed on nasopharyngeal specimens collected at regular intervals from infants. Nasopharyngeal carriage of PCV7 serotypes in Group 1 was significantly higher than in Group 2 and 3 (p < 0.01). However, pneumococcal carriage remained comparable due to an expansion of non-vaccine serotypes in Groups 2 and 3. Determination of phylogenetic dis(similarities) showed that the bacterial community structures were comparable across groups. A mixed effects model showed no difference in community richness (p = 0.15) and Shannon α -diversity (p = 0.48) across the groups. Immediate replacement of pneumococcal vaccine serotypes with non-vaccine serotypes may mitigate the impact of PCV7 on nasopharyngeal bacterial community structure and ecology.

Background Chronic lung diseases (CLDs), responsible for 4 million deaths globally every year, are increasingly important in low- and middle-income countries where most of the global mortality due to CLDs currently occurs. As existing health systems in resource-poor contexts, especially sub-Saharan Africa (SSA), are not generally oriented to provide quality care for chronic diseases, a first step in re-imagining them is to critically consider readiness for service delivery across all aspects of the existing system. Methods We conducted a mixed-methods assessment of CLD service readiness in 18 purposively selected health facilities in two differing SSA health system contexts, Tanzania and Sudan. We used the World Health Organization’s (WHO) Service Availability and Readiness Assessment checklist, qualitative interviews of key health system stakeholders, health facility registers review and assessed clinicians’ capacity to manage CLD using patient vignettes. CLD service readiness was scored as a composite of availability of service-specific tracer items from the WHO service availability checklist in three domains: staff training and guidelines, diagnostics and equipment, and basic medicines. Qualitative data were analysed using the same domains. Results One health facility in Tanzania and five in Sudan, attained a CLD readiness score of ≥ 50 % for CLD care. Scores ranged from 14.9 % in a dispensary to 53.3 % in a health center in Tanzania, and from 36.4 to 86.4 % in Sudan. The least available tracer items across both countries were trained human resources and guidelines, and peak flow meters. Only two facilities had COPD guidelines. Patient vignette analysis revealed significant gaps in clinicians’ capacity to manage CLD. Key informants identified low prioritization as key barrier to CLD care. Conclusions Gaps in service availability and readiness for CLD care in Tanzania and Sudan threaten attainment of universal health coverage in these settings. Detailed assessments by health systems researchers in discussion with stakeholders at all levels of the health system can identify critical blockages to reimagining CLD service provision with people-centered, integrated approaches at its heart.

Background The blended learning (BL) approach to training health care professionals is increasingly adopted in many countries because of high costs and disruption to service delivery in the light of severe human resource shortage in low resource settings. The Covid-19 pandemic increased the urgency to identify alternatives to traditional face-to-face (f2f) education approach. A four-day f2f antenatal care (ANC) and postnatal care (PNC) continuous professional development course (CPD) was repackaged into a 3-part BL course; (1) self-directed learning (16 h) (2) facilitated virtual sessions (2.5 h over 3 days) and (3) 2-day f2f sessions. This study assessed the feasibility, change in healthcare providers’ knowledge and costs of the BL package in Nigeria, Tanzania, and Kenya. Methods A mixed methods design was used. A total of 89 healthcare professionals, were purposively selected. Quantitative data was collected through an online questionnaire and skills assessments, analyzed using STATA 12 software. Qualitative data was collected through key informant interviews and focus group discussions, analysed using thematic analysis. Results Majority of participants (86%) accessed the online sessions using a mobile phone from home and health facilities. The median (IQR) time of completing the self-directed component was 16 h, IQR (8, 30). A multi-disciplinary team comprising of 42% nurse-midwives, 28% doctors, 20% clinical officers and 10% other healthcare professionals completed the BL course. Participants liked the BL approach due to its flexibility in learning, highly educative/relevant content, mixing of health worker cadres and CPD points. Aspects that were noted as challenging were related to personal log-in details and network connectivity issues during the self-directed learning and facilitated virtual sessions respectively. Conclusion The blended learning approach to ANC-PNC in-service training was found to be acceptable, feasible and cost less to implement compared to face-to-face training approach in the study settings. The BL training approach was effective in improving the knowledge and skills of healthcare providers who participated in the training.

ObjectivesChronic respiratory diseases (CRD) are among the top four non-communicable diseases globally. They are associated with poor health and approximately 4 million deaths every year. The rising burden of CRD in low/middle-income countries will strain already weak health systems. This study aimed to explore the perspectives of healthcare workers and other health policy stakeholders on the barriers to effective diagnosis and management of CRD in Kenya, Malawi, Sudan, Tanzania and Uganda.Study designQualitative descriptive study.SettingsPrimary, secondary and tertiary health facilities, government agencies and civil society organisations in five sub-Saharan African countries.ParticipantsWe purposively selected 60 national and district-level policy stakeholders, and 49 healthcare workers, based on their roles in policy decision-making or health provision, and conducted key informant interviews and in-depth interviews, respectively, between 2018 and 2019. Data were analysed through framework approach.ResultsWe identified intersecting vicious cycles of neglect of CRD at strategic policy and healthcare facility levels. Lack of reliable data on burden of disease, due to weak information systems and diagnostic capacity, negatively affected inclusion in policy; this, in turn, was reflected by low budgetary allocations for diagnostic equipment, training and medicines. At the healthcare facility level, inadequate budgetary allocations constrained diagnostic capacity, quality of service delivery and collection of appropriate data, compounding the lack of routine data on burden of disease.ConclusionHealth systems in the five countries are ill-equipped to respond to CRD, an issue that has been brought into sharp focus as countries plan for post-COVID-19 lung diseases. CRD are underdiagnosed, under-reported and underfunded, leading to a vicious cycle of invisibility and neglect. Appropriate diagnosis and management require health systems strengthening, particularly at the primary healthcare level.

We applied a metabonomic strategy to identify host biomarkers in serum to diagnose paediatric tuberculosis (TB) disease. 112 symptomatic children with presumptive TB were recruited in The Gambia and classified as bacteriologically-confirmed TB, clinically diagnosed TB, or other diseases. Sera were analysed using 1 H nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Multivariate data analysis was used to distinguish patients with TB from other diseases. Diagnostic accuracy was evaluated using Receiver Operating Characteristic (ROC) curves. Model performance was tested in a validation cohort of 36 children from the UK. Data acquired using 1 H NMR demonstrated a sensitivity, specificity and Area Under the Curve (AUC) of 69% (95% confidence interval [CI], 56–73%), 83% (95% CI, 73–93%), and 0.78 respectively, and correctly classified 20% of the validation cohort from the UK. The most discriminatory MS data showed a sensitivity of 67% (95% CI, 60–71%), specificity of 86% (95% CI, 75–93%) and an AUC of 0.78, correctly classifying 83% of the validation cohort. Amongst children with presumptive TB, metabolic profiling of sera distinguished bacteriologically-confirmed and clinical TB from other diseases. This novel approach yielded a diagnostic performance for paediatric TB comparable to that of Xpert MTB/RIF and interferon gamma release assays.

This is the protocol for a Campbell systematic review. The objectives are as follows. The primary objective of this systematic review is to evaluate and synthesise both published and unpublished literature on the effectiveness of sexual and reproductive health blended learning approaches for capacity strengthening of healthcare practitioners in LMICs. Within this context, sexual and reproductive health interventions refer to any of the following four key interventions or services aimed at improving maternal and newborn health (Starrs et al. 2018): (a) antenatal, childbirth and postnatal care, including emergency obstetric and newborn care, (b) safe abortion services and treatment of the complications of unsafe abortion, (c) prevention and treatment of malaria, tuberculosis, HIV and other sexually transmitted infections in pregnant women and d) family planning. In this systematic review, blended learning is defined as any teaching and learning method that combines face‐to‐face learning with e‐learning or online learning. The component of face‐to‐face and online learning may include any of the components identified by Alammary (2019): (1) face‐to‐face instructor‐led, where students attend a class and an instructor presents teaching and learning materials, with little engagement from students; (2) face‐to‐face collaboration, where students work together in class, for example, in discussion groups; (3) online instructor‐led, where instruction is delivered online and facilitated by an instructor who sets the pace (e.g., virtual classrooms); (4) online collaboration, where students work together online with their peers, for example, online learning communities; and (5) online self‐paced, where students study at their own pace and time, and from their chosen location, for example, watching videos, online reading. Specifically, this systematic review will answer the following research questions: (1) What sexual and reproductive health blended learning approaches have been used in LMICs? (2) Does participating in sexual and reproductive health blended learning interventions alone (i.e., compared with no intervention) improve the effective provision of care among healthcare workers in LMICs? (3) Does participating in sexual and reproductive health blended learning interventions compared with non‐blended learning approaches (such as conventional face‐to‐face learning or pure e‐learning) facilitate the effective provision of care among healthcare workers in LMICs (measured by, e.g., self‐reports of effective maternal and neonatal care)? (4) What is the cost‐effectiveness of sexual and reproductive health blended learning compared with non‐blended learning approaches (i.e., face‐to‐face learning or e‐learning)? (5) What factors affect the effectiveness of sexual and reproductive health blended learning interventions (e.g., characteristics of participants, type of intervention, course content, setting and mode of delivery)? (6) Do sexual and reproductive health blended learning interventions targeted at healthcare practitioners working in LMICs lead to improvement in patient outcomes (e.g., reduced maternal and neonatal mortality, patient satisfaction reports)?