A Mixed Methods Study of a Health Worker Training Intervention to Increase Syndromic Referral for Gambiense Human African Trypanosomiasis in South Sudan

BACKGROUND: Active screening by mobile teams is considered the most effective method for detecting gambiense-type human African trypanosomiasis (HAT) but constrained funding in many post-conflict countries limits this approach. Non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases for testing based on symptoms. We tested a training intervention for HCWs in peripheral facilities in Nimule, South Sudan to increase knowledge of HAT symptomatology and the rate of syndromic referrals to a central screening and treatment centre. METHODOLOGY/PRINCIPAL FINDINGS: We trained 108 HCWs from 61/74 of the public, private and military peripheral health facilities in the county during six one-day workshops and assessed behaviour change using quantitative and qualitative methods. In four months prior to training, only 2/562 people passively screened for HAT were referred from a peripheral HCW (0 cases detected) compared to 13/352 (2 cases detected) in the four months after, a 6.5-fold increase in the referral rate observed by the hospital. Modest increases in absolute referrals received, however, concealed higher levels of referral activity in the periphery. HCWs in 71.4% of facilities followed-up had made referrals, incorporating new and pre-existing ideas about HAT case detection into referral practice. HCW knowledge scores of HAT symptoms improved across all demographic sub-groups. Of 71 HAT referrals made, two-thirds were from new referrers. Only 11 patients completed the referral, largely because of difficulties patients in remote areas faced accessing transportation. CONCLUSIONS/SIGNIFICANCE: The training increased knowledge and this led to more widespread appropriate HAT referrals from a low base. Many referrals were not completed, however. Increasing access to screening and/or diagnostic tests in the periphery will be needed for greater impact on case-detection in this context. These data suggest it may be possible for peripheral HCWs to target the use of rapid diagnostic tests for HAT

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015:a systematic review and modelling study

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population. Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group

Incremental cost effectiveness of pneumococcal vaccination in Kenya and sensitivity analysis of the impact of indirect effects for PCV10 and PCV13.

*<p>All costs, pneumococcal episodes and deaths are discounted at an annual rate of 3%.</p

Parameters used in the base case analysis for pneumococcal vaccination in Kenyan infants born in 2010 *BCV- Base case value.

<p>NA- Not applicable.</p

Percentage contribution to variance of uncertain parameters in base case analysis (cost per DALY averted for PCV10).

<p>Percentage contribution to variance of uncertain parameters in base case analysis (cost per DALY averted for PCV10).</p

Application of a pneumococcal serotype-specific urinary antigen detection test for identification of pediatric pneumonia in Burkina Faso

Background: Serotype-specific diagnosis of pneumococcal community-acquired pneumonia in children under age 5 years would mark a major advancement for understanding pneumococcal epidemiology and supporting vaccine decision-making. Methods: A Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and subsequently validated in adults, but its applicability to children is unknown. This study aimed to set appropriate cutoffs for use of the UAD in a healthy pediatric population and apply these cutoffs in children with pneumonia in sub-Saharan Africa. The cutoffs were determined by assessing 379 urines obtained from healthy children under age 5 years from the Bobo-Dioulasso area for serotypes included in 13-valent pneumococcal conjugate vaccine (UAD-1) and the 11 other serotypes unique to 23-valent pneumococcal polysaccharide vaccine (UAD-2). Results: Based on the assigned cutoff values, among 108 children who met the World Health Organization consolidation endpoint criteria, UAD-1 and UAD-2 were positive in 23.3% and 8.3%, respectively; among 364 children with clinically suspected pneumonia who did not meet the World Health Organization criteria, UAD-1 and UAD-2 were positive for 6.6% and 3.6%, respectively. Pneumococcal carriage prevalence was similar among pneumonia cases (30%) versus controls (35%) as was semiquantitative carriage density. Conclusions: UAD-1 and UAD-2 were able to distinguish community controls from children with pneumonia, particularly pneumonia with consolidation. Future studies are needed to confirm these results and more fully assess the contribution of pneumococcal carriage and concurrent viral infection

Assessment of health benefits and cost-effectiveness of 10-valent and 13-valent pneumococcal conjugate vaccination in Kenyan children.

BACKGROUND: The GAVI Alliance supported 10-valent pneumococcal conjugate vaccine (PCV10) introduction in Kenya. We estimated the cost-effectiveness of introducing either PCV10 or the 13-valent vaccine (PCV13) from a societal perspective and explored the incremental impact of including indirect vaccine effects. METHODS: The costs and effects of pneumococcal vaccination among infants born in Kenya in 2010 were assessed using a decision analytic model comparing PCV10 or PCV13, in turn, with no vaccination. Direct vaccine effects were estimated as a reduction in the incidence of pneumococcal meningitis, sepsis, bacteraemic pneumonia and non-bacteraemic pneumonia. Pneumococcal disease incidence was extrapolated from a population-based hospital surveillance system in Kilifi and adjustments were made for variable access to care across Kenya. We used vaccine efficacy estimates from a trial in The Gambia and accounted for serotype distribution in Kilifi. We estimated indirect vaccine protection and serotype replacement by extrapolating from the USA. Multivariable sensitivity analysis was conducted using Monte Carlo simulation. We assumed a vaccine price of US$3.50 per dose. FINDINGS: The annual cost of delivering PCV10 was approximately US$14 million. We projected a 42.7% reduction in pneumococcal disease episodes leading to a US$1.97 million reduction in treatment costs and a 6.1$ 59 (95% CI 26-103) and US$1,958 (95$ 0.41 and 0.51, respectively. CONCLUSIONS: Introducing either PCV10 or PCV13 in Kenya is highly cost-effective from a societal perspective. Indirect effects, if they occur, would significantly improve the cost-effectiveness

Mortality in rural coastal Kenya measured using the Kilifi Health and Demographic Surveillance System: a 16-year descriptive analysis [version 2; peer review: 3 approved, 1 approved with reservations]

Background: The Kilifi Health and Demographic Surveillance System (KHDSS) was established in 2000 to define the incidence and prevalence of local diseases and evaluate the impact of community-based interventions. KHDSS morbidity data have been reported comprehensively but mortality has not been described. This analysis describes mortality in the KHDSS over 16 years. Methods: We calculated mortality rates from 2003–2018 in four intervals of equal duration and assessed differences in mortality across these intervals by age and sex. We calculated the period survival function and median survival using the Kaplan–Meier method and mean life expectancies using abridged life tables. We estimated trend and seasonality by decomposing a time series of monthly mortality rates. We used choropleth maps and random-effects Poisson regression to investigate geographical heterogeneity. Results: Mortality declined by 36% overall between 2003–2018 and by 59% in children aged <5 years. Most of the decline occurred between 2003 and 2006. Among adults, the greatest decline (49%) was observed in those aged 15–54 years. Life expectancy at birth increased by 12 years. Females outlived males by 6 years. Seasonality was only evident in the 1–4 year age group in the first four years. Geographical variation in mortality was ±10% of the median value and did not change over time. Conclusions: Between 2003 and 2018, mortality among children and young adults has improved substantially. The steep decline in 2003–2006 followed by a much slower reduction thereafter suggests improvements in health and wellbeing have plateaued in the last 12 years. However, there is substantial inequality in mortality experience by geographical location

Mortality in rural coastal Kenya measured using the Kilifi Health and Demographic Surveillance System: a 16-year descriptive analysis

Background: The Kilifi Health and Demographic Surveillance System (KHDSS) was established in 2000 to define the incidence and prevalence of local diseases and evaluate the impact of community-based interventions. KHDSS morbidity data have been reported comprehensively but mortality has not been described. This analysis describes mortality in the KHDSS over 16 years. Methods: We calculated mortality rates from 2003–2018 in four intervals of equal duration and assessed differences in mortality across these intervals by age and sex. We calculated the period survival function and median survival using the Kaplan–Meier method and mean life expectancies using abridged life tables. We estimated trend and seasonality by decomposing a time series of monthly mortality rates. We used choropleth maps and random-effects Poisson regression to investigate geographical heterogeneity. Results: Mortality declined by 36% overall between 2003–2018 and by 59% in children aged <5 years. Most of the decline occurred between 2003 and 2006. Among adults, the greatest decline (49%) was observed in those aged 15–54 years. Life expectancy at birth increased by 12 years. Females outlived males by 6 years. Seasonality was only evident in the 1–4 year age group in the first four years. Geographical variation in mortality was ±10% of the median value and did not change over time. Conclusions: Between 2003 and 2018, mortality among children and young adults has improved substantially. The steep decline in 2003–2006 followed by a much slower reduction thereafter suggests improvements in health and wellbeing have plateaued in the last 12 years. However, there is substantial inequality in mortality experience by geographical location

Replication Data for: Mortality in rural coastal Kenya measured using the Kilifi Health and Demographic Surveillance System: a 16-year descriptive analysis

This is a replication dataset for the manuscript titled: "Mortality in rural coastal Kenya measured using the Kilifi Health and Demographic Surveillance System: a 16-year descriptive analysis" submitted to the Wellcome Open Research journal. The dataset contains demographic data from the KHDSS used to describe the mortality experience of the underlying population over a period of 16 years