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Comments on the article 'Public and Private Bureaucracies: A Transaction Cost Economics Perspective,' by Oliver Williamson. Contributions on transaction costs economics to the problem of public versus private provisions of services; Influence of the existence of transaction costs on the creation of profitable opportunities for individuals.

OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331) FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1. Copyright © 2005 World Health Organization [ABSTRACT FROM AUTHOR]

Objective: To ascertain the microbiological consequences of WHO's recommendation for presumptive co-trimoxazole prophylaxis for infants with perinatal HIV exposure.Methods: Using a longitudinal cohort design, we followed HIV-exposed and HIV-unexposed infants trimonthly for up to 18 months per infant. HIV-exposed infants received daily co-trimoxazole prophylaxis from 6 weeks to >/= 12 months of age. Using Streptococcus pneumoniae as our sentinel pathogen, we measured how co-trimoxazole altered nasopharyngeal colonization, pneumococcal resistance to antibiotics and serotype distribution as a function of co-trimoxazole exposure.Findings: From 260 infants followed for 3096 patient-months, we detected pneumococci in 360/1394 (25.8%) samples. HIV-exposed infants were colonized more frequently than HIV-unexposed infants (risk ratio, RR: 1.4; 95% confidence interval, CI: 1.0-1.9, P = 0.04). Co-trimoxazole prophylaxis reduced colonization by ca 7% but increased the risk of colonization with co-trimoxazoleresistant pneumococci within 6 weeks of starting prophylaxis (RR: 3.2; 95% CI: 1.3-7.8, P = 0.04). Prophylaxis with co-trimoxazole led to a small but statistically significant increase of nasopharyngeal colonization with pneumococci not susceptible to clindamycin (RR: 1.6; 95% CI: 1.0-2.6, P = 0.04) but did not increase the risk of non-susceptibility to penicillin (RR: 1.1; 95% CI: 0.7-1.7), erythromycin (RR: 1.0; 95% CI: 0.6-1.7), tetracycline (RR: 0.9; 95% CI: 0.6-1.5) or chloramphenicol (RR: 0.8; 95% CI: 0.3-2.3). Co-trimoxazole prophylaxis did not cause the prevailing pneumococcal serotypes to differ from those that are targeted by the 7-valent conjugate pneumococcal vaccine (RR: 1.0; 95% CI: 0.7-1.6).Conclusion: Co-trimoxazole prophylaxis modestly suppresses pneumococcal colonization but accelerates infant acquisition of co-trimoxazole- and clindamycin-resistant pneumococci. Co-trimoxazole prophylaxis appears unlikely to compromise the future efficacy of conjugate vaccines. Copyright © 2008 World Health Organization [ABSTRACT FROM AUTHOR]

Background: The continued increase in global migration compels clinicians to be aware of specific health problems faced by refugees, immigrants, and migrants (RIM). This analysis aimed to characterize RIM evaluated at GeoSentinel sites, their migration history, and infectious diseases detected through screening and diagnostic workups., Methods: A case report form was used to collect data on demographics, migration route, infectious diseases screened, test results, and primary infectious disease diagnosis for RIM patients seen at GeoSentinel sites. Descriptive statistics were performed., Results: Between October 2016 and November 2018, 5,319 RIM patients were evaluated at GeoSentinel sites in 19 countries. Africa was the region of birth for 2,436 patients (46 %), followed by the Americas (1,644, 31 %), and Asia (1,098, 21 %). Tuberculosis (TB) was the most common infection screened and reported as positive (853/2,273, 38 % positive by any method). TB, strongyloidiasis, and hepatitis B surface antigen positivity were observed across all migration administrative categories and regions of birth. Chagas disease was reported only among RIM patients from the Americas (393/394, 100 %) and schistosomiasis predominantly in those from Africa (480/510, 94 %). TB infection (694/5,319, 13 %) and Chagas disease (524/5,319, 10 %) were the leading primary infectious disease diagnoses., Conclusions: Several infections of long latency (e.g. TB, hepatitis B, and strongyloidiasis) with potential for long-term sequelae were seen among RIM patients across all migration administrative categories and regions of origin. Obtaining detailed epidemiologic information from RIM patients is critical to optimize detection of diseases of individual and public health importance, particularly those with long latency periods., Competing Interests: Declaration of competing interest Dr. Barnett receives royalties from UpToDate for her contribution to Evaluation of Newly Arrived Adult Immigrants. Dr. Greenaway acknowledges prior investigator initiated grant funding from Gilead and consulting to produce educational material on hepatitis C for AbbVie. Dr. Walker receives partial chapter royalties from UpToDate for her contribution to Evaluation of Newly Arrived Adult Immigrants. Dr. Grobusch received a speaker fee paid to his institution. Dr. Hamer receives salary support from the GeoSentinel Cooperative Agreement between the USCenters for Disease Control and Prevention and the International Society of Travel Medicine. Dr. Stauffer receives partial chapter royalties from UpToDate and a honorarium from Haymarket for continuing medical educational development; he serves as a consultant for Massachusetts General Hospital on a grant and BCT Partners, a minority-owned business, working on equity and diversity in business and healthcare. All remaining authors have declared no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and lower respiratory tract infections in children in their first year of life, disproportionately affecting infants in developing countries. Previous studies have found that the nasopharyngeal (NP) microbiome of infants with RSV infection has specific characteristics that correlate with disease severity, including lower biodiversity, perturbations of the microbiota and differences in relative abundance. These studies have focused on infants seen in clinical or hospital settings, predominantly in developed countries., Methods: We conducted a nested case control study within a random sample of 50 deceased RSV+ infants with age at death ranging from 4 days to 6 months and 50 matched deceased RSV- infants who were all previously enrolled in the Zambia Pertussis and RSV Infant Mortality Estimation (ZPRIME) study. All infants died within the community or within 48 hours of facility admittance. As part of the ZPRIME study procedures, all decedents underwent one-time, postmortem NP sampling. The current analysis explored the differences between the NP microbiome profiles of RSV+ and RSV- decedents using the 16S ribosomal DNA sequencing., Results: We found that Moraxella was more abundant in the NP microbiome of RSV+ decedents than in the RSV- decedents. Additionally, Gemella and Staphylococcus were less abundant in RSV+ decedents than in the RSV- decedents., Conclusions: These results support previously reported findings of the association between the NP microbiome and RSV and suggest that changes in the abundance of these microbes are likely specific to RSV and may correlate with mortality associated with the disease., Competing Interests: Supported by the Bill and Melinda Gates Foundation. W.E.J. and J.M. were funded in part by NIH grant R01 GM127430. W.E.J. and A.R.O.M. were supported in part by the NIH under grant R21 AI154387. The other authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Diarrhoea is the second most common cause of death among children under the age of five worldwide. The World Health Organization (WHO) recommends treating diarrhoea with oral rehydration therapy, intravenous fluids for severe dehydration, and zinc supplements. Antibiotics are only recommended to treat acute, invasive diarrhoea. Rising antibiotic resistance has led to a decrease in the effectiveness of treatments for diarrhoea., Methods: A systematic literature review in PubMed, Web of Science, and EMBASE was conducted to identify articles relevant to antibiotic-resistant childhood diarrhoea. Articles in English published between 1990 to 2020 that described antibiotic resistance patterns of common pathogens causing childhood diarrhoea in low- and middle-income countries were included. The studies were limited to papers that categorized children as 0-5 years or 0-10 years old. The proportion of isolates with resistance to major classes of antibiotics stratified by major WHO global regions and time was determined., Results: Quantitative data were extracted from 44 articles that met screening criteria; most focused on children under five years. Escherichia coli isolates had relatively high resistance rates to ampicillin and tetracycline in the African (AFR), American (AMR), and Eastern Mediterranean Regions (EMR). There was moderate to high resistance to ampicillin and third generation cephalosporins among Salmonella spp in the AFR, EMR, and the Western Pacific Region (WPR). Resistance rates for ampicillin, co-trimoxazole, and chloramphenicol for Shigella in the AFR started at an alarmingly high rate ( ~ 90%) in 2006 and fluctuated over time. There were limited antibiotic resistance data for Aeromonas, Yersinia, and V. cholerae. The 161 isolates of Campylobacter analysed showed initially low rates of fluoroquinolone resistance with high rates of resistance in recent years, especially in the Southeast Asian Region., Conclusions: Resistance to inexpensive antibiotics for treatment of invasive diarrhoea in children under ten years is widespread (although data on 6- to 10-year-old children are limited), and resistance rates to fluoroquinolones and later-generation cephalosporins are increasing. A strong regional surveillance system is needed to carefully monitor trends in antibiotic resistance, future studies should include school-aged children, and interventions are needed to reduce inappropriate use of antibiotics for the treatment of community-acquired, non-invasive diarrhoea., Registration: This systematic review was registered in Prospero (registration number CRD42020204004) in August 2020., Competing Interests: Disclosure of interest: The authors have completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2023 by the Journal of Global Health. All rights reserved.)

Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104-4591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences., (© 2023. The Author(s).)

Background: There is very little information on the beliefs and perceptions of mothers about SIDS and its related risk factors in Africa. To better understand parental decisions about infant sleep practices and other risk factors for SIDS, we conducted focus group discussions (FGDs) with mothers of infants in Lusaka, Zambia., Methods: FGDs involved 35 purposively sampled mothers aged 18-49 years. FGDs were conducted using a semi-structured interview guide in the local language, Nyanja. These were translated, transcribed verbatim into English, and then coded and analyzed using thematic analysis in NVivo 12., Results: Six FGDs were conducted with 35 mothers in April-May 2021 across two study sites. FGD Participants were generally aware of sudden unexplained infant deaths, with several describing stories of apparent SIDS in the community. The side sleeping position was preferred and perceived to be safer for the infant with most believing the supine position posed an aspiration or choking risk to the infant. Bedsharing was also preferred and perceived to be convenient for breastfeeding and monitoring of the infant. Experienced family members such as grandmothers and mothers-in-law, and health care workers were frequently cited as sources of information on infant sleep position. A heightened awareness of the infant's sleeping environment was suggested as a mechanism to prevent SIDS and smothering., Conclusions: Decisions about bedsharing and infant sleep position were guided by maternal beliefs and perceptions about what is convenient for breastfeeding and safer for the infant. These concerns are vital to designing tailored interventions to address sleep-related sudden infant losses in Zambia. Public health campaigns with tailored messages that address these concerns are likely to be effective at ensuring optimal uptake of safe sleep recommendations., (© 2023. The Author(s).)

Background: South Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed. Standard care only allows for suboptimal adherence detection when routine testing indicates unsuppressed virus. Several adherence interventions are known to improve HIV outcomes, yet few are implemented in routinely due to the resources required. Therefore, determining scalable evidence-based adherence support interventions for resource-limited settings (RLS) is a priority. The multiphase optimization strategy (MOST) framework allows for simultaneous evaluation of multiple intervention components and their interactions. We propose to use MOST to identify the intervention combination with the highest levels of efficacy and cost-effectiveness that is feasible and acceptable in primary care clinics in Cape Town., Methods: We will employ a fractional factorial design to identify the most promising intervention components for inclusion in a multi-component intervention package to be tested in a future randomized controlled trial. We will recruit 512 participants initiating ART between March 2022 and February 2024 in three Cape Town clinics and evaluate acceptability, feasibility, and cost-effectiveness of intervention combinations. Participants will be randomized to one of 16 conditions with different combinations of three adherence monitoring components: rapid outreach following (1) unsuppressed virus, (2) missed pharmacy refill collection, and/or (3) missed doses as detected by an electronic adherence monitoring device; and two adherence support components: (1) weekly check-in texts and (2) enhanced peer support. We will assess viral suppression (<50 copies/mL) at 24 months as the primary outcome; acceptability, feasibility, fidelity, and other implementation outcomes; and cost-effectiveness. We will use logistic regression models to estimate intervention effects with an intention-to-treat approach, employ descriptive statistics to assess implementation outcomes, and determine an optimal intervention package., Discussion: To our knowledge, ours will be the first study to use the MOST framework to determine the most effective combination of HIV adherence monitoring and support intervention components for implementation in clinics in a RLS. Our findings will provide direction for pragmatic, ongoing adherence support that will be key to ending the HIV epidemic., Trial Registration: ClinicalTrials.gov NCT05040841. Registered on 10 September 2021., (© 2023. The Author(s).)

Objectives: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors., Methods: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors., Results: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32)., Conclusion: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines., Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set., Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males., Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: YBN is staff member of the World Health Organization., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Objectives: To determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia., Design: A systematic, postmortem prevalence study., Setting: A busy, inner-city morgue in Lusaka., Participants: We sampled a random subset of all decedents who transited the University Teaching Hospital morgue. We sampled the posterior nasopharynx of decedents using quantitative PCR. Prevalence was weighted to account for age-specific enrolment strategies., Interventions: Not applicable-this was an observational study., Primary Outcomes: Prevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time., Secondary Outcomes: Shifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates., Results: From 1118 decedents enrolled between January and June 2021, COVID-19 was detected among 32.0% (358/1116). Roughly four COVID-19+ community deaths occurred for every facility death. Antemortem testing occurred for 52.6% (302/574) of facility deaths but only 1.8% (10/544) of community deaths and overall, only ~10% of COVID-19+ deaths were identified in life. During peak transmission periods, COVID-19 was detected in ~90% of all deaths. We observed three waves of transmission that peaked in July 2020, January 2021 and ~June 2021: the AE.1 lineage and the Beta and Delta variants, respectively. PCR signals were strongest among those whose deaths were deemed 'probably due to COVID-19', and weakest among children, with an age-dependent increase in PCR signal intensity., Conclusions: COVID-19 was common among deceased individuals in Lusaka. Antemortem testing was rarely done, and almost never for community deaths. Suspicion that COVID-19 was the cause of deaths was highest for those with a respiratory syndrome and lowest for individuals <19 years., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Having infants sleep with their parents and sleeping face down or on their sides are the two most proximate and modifiable risk factors for sudden infant death syndrome (SIDS). Little is known about the burden of SIDS or the prevalence of these risk factors in Africa. Our primary objective was to determine the prevalence of modifiable risk factors of SIDS in Lusaka, Zambia., Methods: We conducted cross-sectional surveys with recent mothers of infants aged < 1 year across two busy urban clinic sites in Lusaka, Zambia. We used log-binomial regression analysis to identify factors predictive of bedsharing and prone sleeping., Results: Surveys were conducted with 478 mothers between April-May 2021. The sleep-related risk factors, bedsharing and side sleeping, were widely prevalent. 89.5% of respondents indicated that they share a bed with the infant during sleep, 73.0% preferred putting their baby on its side, and 19.9% preferred the prone position. Only 6.7% of respondents described using the safer, supine position. Age of infant was the only factor which was predictive of prone sleeping. Infants > 2 months old were twice as likely to be put to sleep in a prone position compared to infants aged less than 2 months old. Mothers reported that they rarely (24.1%) received advice from medical caregivers to use the supine position. Maternal use of alcohol (12.0%) and tobacco (0.8%) during pregnancy were uncommon., Conclusions: Bedsharing and placing the infant to sleep on the side were commonly reported among the mothers we interviewed. Whether this represents an opportunity to reduce SIDS in Zambia is unclear since accurate data on the burden of SIDS in Zambia is not available. There is a need for increased awareness of SIDS and more prospective data collection on its burden and related risk factors in these African populations., (© 2022. The Author(s).)

Purpose: South Africa's National Health Laboratory Service (NHLS) National HIV Cohort was established in 2015 to facilitate monitoring, evaluation and research on South Africa's National HIV Treatment Programme. In South Africa, 84.8% of people living with HIV know their HIV status; 70.7% who know their status are on ART; and 87.4% on ART are virologically suppressed., Participants: The NHLS National HIV Cohort includes the laboratory data of nearly all patients receiving HIV care in the public sector since April 2004. Patients are included in the cohort if they have received a CD4 count or HIV RNA viral load (VL) test. Using an anonymised unique patient identifier that we have developed and validated to linked test results, we observe patients prospectively through their laboratory results as they receive HIV care and treatment. Patients in HIV care are seen for laboratory monitoring every 6-12 months. Data collected include age, sex, facility location and test results for CD4 counts, VLs and laboratory tests used to screen for potential treatment complications., Findings to Date: From April 2004 to April 2018, 63 million CD4 count and VL tests were conducted at 5483 facilities. 12.6 million unique patients had at least one CD4 count or VL, indicating they had accessed HIV care, and 7.1 million patients had a VL test indicating they had started antiretroviral therapy. The creation of NHLS National HIV Cohort has enabled longitudinal research on all lab-monitored patients in South Africa's national HIV programme, including analyses of (1) patient health at presentation; (2) care outcomes such as 'CD4 recovery', 'retention in care' and 'viral resuppression'; (3) patterns of transfer and re-entry into care; (4) facility-level variation in care outcomes; and (5) impacts of policies and guideline changes., Future Plans: Continuous updating of the cohort, integration with available clinical data, and expansion to include tuberculosis and other lab-monitored comorbidities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early and exclusive breastfeeding have been shown to protect young infants from all-cause and diarrhoea-related mortality. Ideally breastfeeding should be initiated within the first hour of birth. Despite efforts to increase rates of early and exclusive breastfeeding in low- and middle-income countries (LMICs), challenges with uptake remain. This analysis reviews trends in early and exclusive breastfeeding, and the impact of infant feeding interventions in reducing childhood diarrhoea., Methods: We conducted a detailed review of articles written in English between 1990 and 2020 on the impact and efficacy of breastfeeding and complementary feeding on diarrhoea in children aged 0-2 years in LMICs. Using data from 86 countries and all WHO global regions collected from the mid-1980s through 2018 obtained from publicly available Demographic Health Surveys, we assessed trends in five-year intervals of timing of breastfeeding initiation, exclusive breastfeeding, median and mean duration of exclusive breastfeeding, and complementary feeding., Results: The literature search identified ten articles that described variable rates of early initiation of breastfeeding from 20% in Pakistan to 76% in Egypt. An analysis of 288 DHS studies found that the proportion of women who reported initiating breastfeeding within an hour of birth increased from 32% in the early 1990s to 55% between 2016 and 2020. Exclusive breastfeeding increased from 20% in the late 1980s to 48% between 2016 and 2020 and the mean duration of exclusive breastfeeding of 2-to-4-month-old infants doubled. Early initiation of breastfeeding and exclusive breastfeeding was associated with reductions in diarrhoea prevalence in the South East Asian, Western Pacific, Eastern Mediterranean, and African regions. Eight studies evaluating the effectiveness of different maternal education interventions, health care worker training, and media campaigns demonstrated improvements in exclusive breastfeeding, and most resulted in reductions in the incidence or duration of diarrhoea., Conclusions: During the last two decades, early and exclusive breastfeeding have increased. Nevertheless, the uptake of this basic, low-cost intervention remains suboptimal across all global regions. Given the potential benefits the in reduction of diarrhoea and diarrhoea-associated mortality, interventions for improving the uptake of early and exclusive breastfeeding in different sociological contexts need to be designed, implemented, and evaluated., Competing Interests: Disclosure of interest: The authors have completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Introduction: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings., Methods: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool., Results: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84)., Conclusions: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We report the PAEDLINK randomized trial results on the effect of motivational interviewing (MI) retention counseling on the adherence of postpartum women to the early infant diagnostic human immunodeficiency virus (HIV) testing schedule., Methods: HIV positive women and their babies were enrolled 3 to 6 days after delivery at 4 midwife obstetric units in the Gauteng province of South Africa and randomized into (A) MI retention counseling and telephonic tracing, (B) biannual telephonic tracing, and (C) standard care. Mother-baby pairs were followed up for 18 months via medical records. The uptake of child HIV tests and maternal retention in the 0 to 6 and 7 to 18 month periods were modeled using Log-binomial regression., Results: Overall, 501/711 enrolled mother-baby pairs received a second HIV polymerase chain reaction test by 6 months (70.0%, 70.5%, and 70.0% in groups A, B, and C, respectively). A higher proportion of intervention children (60.9%) were tested at 7 to 90 days than group B (48.1%, adjusted risk ratio [aRR] 0.8 for B vs A, 95% confidence interval [CI]: 0.7-0.9) and group C children (52.7%, aRR 0.9 for C vs A, 95% CI: 0.9-1.0). Child testing between 7 and 18-months was also higher in group A than C (10.7% A, vs 5.5% C, RR 2.0, 95% CI: 1.0-3.7). However, maternal retention was similar across groups, with 41.6% and 16.3% retained during the 0 to 6 and the 7 to 18-months periods, respectively., Conclusion: MI retention counseling can reduce delays in the early infant diagnosis testing schedule for HIV-exposed infants. However, further support is necessary to maximize later HIV tests and maternal retention., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and a key driver of childhood mortality. Previous RSV burden of disease estimates used hospital-based surveillance data and modelled, rather than directly measured, community deaths. Given this uncertainty, we conducted a 3-year post-mortem prevalence study among young infants at a busy morgue in Lusaka, Zambia-the Zambia Pertussis RSV Infant Mortality Estimation (ZPRIME) study., Methods: Infants were eligible for inclusion if they were aged between 4 days and less than 6 months and were enrolled within 48 h of death. Enrolment occurred mainly at the University Teaching Hospital of the University of Zambia Medical School (Lusaka, Zambia), the largest teaching hospital in Zambia. We extracted demographic and clinical data from medical charts and official death certificates, and we conducted verbal autopsies with the guardian or next of kin. RSV was identified using reverse transcriptase quantitative PCR and stratified by age, time of year, and setting (community vs facility deaths). By combining the PCR prevalence data with syndromic presentation, we estimated the proportion of all infant deaths that were due to RSV., Findings: The ZPRIME study ran from Aug 31, 2017, to Aug 31, 2020, except for from April 1 to May 6, 2020, during which data were not collected due to restrictions on human research at this time (linked to COVID-19). We enrolled 2286 deceased infants, representing 79% of total infant deaths in Lusaka. RSV was detected in 162 (7%) of 2286 deceased infants. RSV was detected in 102 (9%) of 1176 community deaths, compared with 10 (4%) of 236 early facility deaths (<48 h from admission) and 36 (5%) of 737 late facility deaths (≥48 h from admission). RSV deaths were concentrated in infants younger than 3 months (116 [72%] of 162 infants), and were clustered in the first half of each year and in the poorest and most densely populated Lusaka townships. RSV caused at least 2·8% (95% CI 1·0-4·6) of all infant deaths and 4·7% (1·3-8·1) of community deaths., Interpretation: RSV was a major seasonal cause of overall infant mortality, particularly among infants younger than 3 months of age. Because most RSV deaths occurred in the community and would have been missed through hospital-based surveillance, the global burden of fatal RSV has probably been underestimated., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests CJG and LM report grants from the US National Institutes of Health and from Merck, paid to Boston University. CJG also reports receiving fees for participation on data safety and monitoring boards for Takeda, Moderna, and CureVac, all outside the submitted work. LM reports receiving financial support from the Bill & Melinda Gates Foundation to attend meetings on respiratory syncytial virus. RL reports research awards from Pfizer, paid to her institution, and honoraria for participation in pneumococcal advisory boards and consulting fees from Pfizer, paid to her, outside the submitted work. AL reports employment with Manpower Professional Services, which was contracted by Merck to complete work for the Global Vaccines Public Policy & Partnerships team, and fees from Merck for consultancy services, outside the submitted work. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: While sudden infant death syndrome (SIDS) has long been recognized as a leading preventable cause of infant mortality in high-income countries, little is known about the burden of SIDS in Africa. To address this knowledge gap, we conducted the first systematic review of SIDS-related publications in Africa. Our objective was to assess the prevalence of SIDS and its risk factors in Africa., Methods: We systematically searched PubMed, Embase, Web of Science, Cochrane, and Google Scholar to identify studies published until December 26, 2020. Review authors screened titles and abstracts, and selected articles independently for full-text review. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) or a modification. Data on the proportion of infants who died of SIDS and reported prevalence of any risk factors were extracted using customized data extraction forms in Covidence., Results: Our analysis rested on 32 peer-reviewed articles. Nine studies presented prevalence estimates on bedsharing and prone sleeping, suggesting near-universal bedsharing of infants with parents (range, 60 to 91.8%) and frequent use of the prone sleeping position (range, 26.7 to 63.8%). Eleven studies reported on the prevalence of SIDS, suggesting high rates of SIDS in Africa. The prevalence of SIDS ranged from 3.7 per 1000 live births in South Africa, 2.5 per 1000 live births in Niger, and 0.2 per 1000 live births in Zimbabwe. SIDS and other sudden infant deaths accounted for between 2.5 to 21% of infant deaths in South Africa and 11.3% in Zambia., Conclusions: Africa may have the highest global rate of SIDS with a high burden of associated risk factors. However, majority of the studies were from South Africa which limits generalizability of our findings to the entire continent. There is an urgent need for higher quality studies outside of South Africa to fill this knowledge gap., Protocol Registration: Prospero Registration Number: CRD42021257261., Competing Interests: Competing interest: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Background: Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia., Methods: We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR., Results: From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point <40. When expanding the PCR threshold to 40 ≤ cycle threshold (Ct) ≤ 45, we identified 1 additional case. Most cases were male and occurred in the community The median age at death was 47 years (range 40-64). Human immunodeficiency virus (HIV)/AIDS, tuberculosis, and diabetes were more common among the COVID-19+ cases. Diffuse alveolar damage and interstitial pneumonitis were common among COVID-19+ cases; nonspecific findings of hepatic steatosis and acute kidney injury were also prevalent in the COVID-19+ group. Vascular thrombi were rarely detected., Conclusions: Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Respiratory syncytial virus (RSV) is a major cause of infant deaths. Its epidemiology in low- and middle-income countries is poorly understood. Risk factors associated with RSV-associated infant deaths that occur in community settings are incompletely known., Methods: Community deaths for infants aged 4 days to 6 months were identified during a 3-year postmortem RSV prevalence study at the main city morgue in Lusaka, Zambia, where 80% of deaths are registered. This analysis focuses on the subset of deaths for which an abbreviated verbal autopsy was available and intended to sort deaths into respiratory or nonrespiratory causes by clinical adjudication. Posterior nasopharyngeal swab samples were collected within 48 hours of death and tested for RSV using quantitative reverse-transcription polymerase chain reaction. Associations between potential risk factors were determined as relative risks with 95% confidence intervals (CIs)., Results: We prospectively enrolled 798 community infant deaths with verbal autopsies and RSV laboratory results, of which 62 results were positive. The mean age of the infants was 10 weeks, and 41.4% of them were male. Of all deaths, 44% were attributed to respiratory causes. RSV was detected in 7.8% of the community infants and was significantly associated with respiratory deaths (risk ratio, 4.0 [95% CI, 2.2-7.1]). Compared with older infants, those aged 0-8 weeks had a 2.83 (95% CI, 1.30-6.15) increased risk of dying with RSV. The risk of RSV for the 0-8-week age group increased to 5.24 (1.56-33.14) with adjustment for demographics, parental education, and geography. RSV deaths were increased with domiciliary overcrowding and were concentrated in poor and dense neighborhoods in Lusaka (risk ratio, 2.00 [95% CI, 1.22-3.27])., Conclusion: RSV is a significant contributor to community respiratory deaths in this population, particularly in the first 3 months of life and in the more poor and dense parts of Lusaka., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Recent pertussis resurgence in numerous countries may be driven by asymptomatic infections. Most pertussis surveillance studies are cross-sectional and cannot distinguish asymptomatic from pre-symptomatic infections. Longitudinal surveillance could overcome this barrier, providing more information about the true burden of pertussis at the population level. Here we analyze 17,442 nasopharyngeal samples from a longitudinal cohort of 1320 Zambian mother/infant pairs. Our analysis has two elements. First, we demonstrate that the full range of IS481 qPCR CT values provides insight into pertussis epidemiology, showing concordance of low and high CT results over time, within mother/infant pairs, and in relation to symptomatology. Second, we exploit these full-range qPCR data to demonstrate a high incidence of asymptomatic pertussis, including among infants. Our results demonstrate a wider burden of pertussis infection than we anticipated in this population, and expose key limitations of threshold-based interpretation of qPCR results in infectious disease surveillance., Competing Interests: CG, CG, WM, LM, DT, RP, GK, ZM, PR No competing interests declared, (© 2021, Gill et al.)

Objectives: In Zambia, a significant number of infants die in the community. It is hypothesized that delays in care contribute to many of these so-called "brought in dead" infants., Methods: We analyzed free-text narratives from verbal autopsies, in which families narrate the final series of events leading to each infant's death. Using the 3-delays model framework and working iteratively to achieve consensus, we coded each narrative using NVivo software to identify, characterize, and quantify the contribution of delays and other factors to the fatal outcome., Results: Verbal autopsies were collected from 230 families of brought in dead infants younger than 6 months of age. As many as 82.8% of infants had 1 or more delays in care. The most-common delay was in the family's decision to seek care (54.8%), even as severe symptoms were frequently described. Similarly, 27.8% of infants died en route to a health care facility. Delays in receiving adequate care, including infants dying while waiting in line at a clinic or during referral from a clinic to a hospital, occurred in 24.7% of infants. A third of infants had been previously evaluated by a clinician in the days before their death., Conclusions: Delays in care were the rule rather than the exception in this population of Zambian infants. Accessing care requires families to navigate significant logistic barriers, and balance complex forces in deciding to seek care. Strategies to avoid such delays could save many infants lives., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Reliable information on rates of up-to-date coverage and timely administration of routine childhood immunisations are critical for guiding public health efforts worldwide, yet prospective observation of vaccination programmes within individual communities is rare. Here, we provide a longitudinal analysis of the directly observed administration of a three-dose primary vaccination series to infants in a low-resource community in Lusaka, Zambia., Methods: Throughout 2015, we recruited a longitudinal birth cohort of mother/infant pairs (initial enrolment, 1981 pairs; attending, 1497 pairs) from the periurban informal settlement of Chawama compound, located in Lusaka, Zambia. We prospectively monitored the administration of scheduled diphtheria-tetanus-pertussis (DTP) vaccinations across the first 14-18 weeks of life. We analysed study attendance and vaccine coverage, both overall and stratified by age group. We employed Kaplan-Meier analyses to estimate delays in age-appropriate administration of vaccine doses. We also assessed schedule timing violations, including early and compressed dose administration., Results: At study completion, first dose (DTP1) rates were high (92.9% of attending), whereas third dose completion (DTP3) rates were far lower (61.9%). Missed vaccinations and study dropout both contributed to the low DTP3 completion rates. DTP1 was administered very late (at or after 10 weeks) to 61 infants (4.1%). DTP1 was administered too early to 64 infants (4.3%), and 77 (5.1%) received consecutive doses below the minimum recommended spacing of 28 days., Conclusions: We observe substantial individual variation in the timing of early childhood DTP doses, though following this birth cohort proved challenging. Our results indicate that timely administration of both DTP1 and DTP3 remains a challenge in this community. These directly-observed, individual-based results provide an important counterpoint to more course-grained, survey-based national and province estimates of up-to-date vaccine coverage. This study also highlights the challenges of vaccine hesitancy and suboptimal utilisation of (no-cost) healthcare services in a low-resource urban setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Introduction: In South Africa, HIV patients with an elevated viral load (VL) should receive repeat VL testing after adherence counselling. We set out to use a national HIV Cohort to describe time to repeat viral load testing across South Africa and identify predictors of time to repeat testing., Methods: We conducted a cohort study of prospectively collected laboratory data. HIV treatment guidelines have changed over time in South Africa, but call for repeat VL testing within six months if 400 to 1000 copies/mL and two to three months if >1000 copies/mL. We included patients with suppressed viral loads (indicating they are on ART) and a first elevated VL (>400 copies/mL) between April 2004 and December 2014. Follow-up began at first elevated VL and continued until repeat testing, loss to follow-up or December 2016. We calculated adjusted hazard ratios (aHR) using Cox proportional hazard models., Results: Of 371,648 patients with a VL > 400, 83.9% (311,790) had a repeat VL, in a median (IQR) of 7.0 (4.1 to 12.2) months. Of those with a first viral load 400 to 1000 copies/mL, 56.4% had a repeat VL within guideline recommended six months (defined as up to nine months), whereas among those >1000 copies/mL only 47.7% had a repeat viral load within guideline recommended two to three months (defined as up to six months). We found a small increase in repeat testing associated with higher VL value (aHR 1.11; 95% CI: 1.10 to 1.12 comparing >1000 vs 400 to 1000 copies/mL) and very low CD4 counts at first elevated VL (aHR 1.16; 95% CI: 1.13 to 1.19 comparing CD4 < 50 vs <500 cells/mm 3 ). We also found strong variation in time to repeat VL testing by province., Conclusions: Median time to repeat viral load testing for those with an elevated viral load was longer than guidelines recommend. Future work should identify whether delays are due to patient or provider factors., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Background: Despite progress made over the past twenty years, child mortality remains high, with 5.3 million children under five years having died in 2018 globally. Pneumonia, diarrhoea, and malaria remain among the commonest causes of under-five mortality; contributing 15%, 8%, and 5% of global mortality respectively. Recent evidence shows that integrated community case management (iCCM) of pneumonia, diarrhoea, and malaria can reduce under-five mortality. However, despite growing evidence of the effectiveness of iCCM, there are implementation challenges, especially stock out of iCCM commodities and inadequate supportive supervision of community health workers (CHWs). This study aimed to address these two key challenges to successful iCCM implementation by using mobile health (mHealth) technology., Methods: This cluster randomised controlled trial compared health centre catchment areas (clusters) where CHWs and their supervisors implemented mHealth-enhanced iCCM supportive supervision and supply chain management vs clusters implementing iCCM as per current Zambian guidelines. CHWs in intervention clusters used community DHIS2 platform on mobile phones to report on a weekly basis children with iCCM conditions and make requisitions for iCCM commodities. Their supervisors received electronic reports on disease caseloads and monthly automated supervision reminders. The supervisors on receipt of requisitions, organized the medical supplies and notified CHWs for collection. Intention-to-treat analysis on the primary outcome, the percentage of children aged 2-59 months receiving appropriate treatment for malaria, pneumonia, or diarrhoea from an iCCM trained CHW, was performed using a generalized linear model. Prevalence ratios and 95% confidence intervals comparing the prevalence of appropriate treatment in the intervention and control groups were calculated using log binomial regression with an exchangeable correlation matrix, adjusted for clustering by health facility., Results: In the intervention clusters, 61.3% (98/160) of expected monthly supervision visits took place vs 52.0% (78/150) in the controls. A total of 3690 children 2-59 months old presented with malaria, diarrhoea, or pneumonia. In the intervention group, 65.9% (1,252/1,899) of children received appropriate care for iCCM conditions, compared to 63.3% (1,134/1,791) in the control group. The mHealth intervention was associated with 18.0% improvement in supportive supervision and 21.0% increase in appropriate treatment for pneumonia; these changes were not statistically significant. There was a 2-3-fold increase in the proportion of CHWs receiving supplies ordered: prevalence ratios ranged from 2.82 (confidence interval (CI) = 1.50, 5.30) to 3.01 (95% CI = 1.29, 7.00) depending on the particular commodity., Conclusion: This study was unable to determine whether using mHealth technology would strengthen supervision and supply chain management of iCCM commodities for community-level workers. There was no statistically significant effect of mHealth enhanced iCCM on appropriate diagnosis and treatment for children with malaria, pneumonia, and diarrhoea in rural Zambia. Longer term longitudinal studies are required to determine the impact of mHealth enhanced iCCM on health outputs and outcomes., Trial Registration: ClinicalTrials.gov, NCT02866097., Competing Interests: Competing interests: The authors have completed the ICMJE Unified Conflict of Interest Form (available upon request from the corresponding author) and declare that they have no competing interests., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

Treatment for depression is complex, requiring decisions that may involve trade-offs between exploiting treatments with the highest expected value and experimenting with treatments with higher possible payoffs. Using patient claims data, we show that among skilled doctors, using a broader portfolio of drugs predicts better patient outcomes, except in cases where doctors' decisions violate loose professional guidelines. We introduce a behavioral model of decision making guided by our empirical observations. The model's novel feature is that the trade-off between exploitation and experimentation depends on the doctor's diagnostic skill. The model predicts that higher diagnostic skill leads to greater diversity in drug choice and better matching of drugs to patients even among doctors with the same initial beliefs regarding drug effectiveness. Consistent with the finding that guideline violations predict poorer patient outcomes, simulations of the model suggest that increasing the number of possible drug choices can lower performance.

In 2012, approximately 5.6 million Zambians did not have access to improved sanitation and around 2.1 million practiced open defecation. The Zambia Sanitation and Hygiene Program (ZSHP), featuring community-led total sanitation, began in November 2011 to increase the use of improved sanitation facilities and adopt positive hygiene practices. Using a pre- and post-design approach with a population-level survey, after 3 years of implementation, we evaluated the impact of ZSHP in randomly selected households in 50 standard enumeration areas (representing 26 of 65 program districts). We interviewed caregivers of children younger than 5 years old (1,204 and 1,170 female caregivers at baseline and end line, respectively) and inspected household toilet facilities and sites for washing hands. At end line, 80% of households had access to improved sanitation facilities versus 64.1% at baseline (prevalence ratio [PR] = 1.25; 95% CI: 1.18-1.31) and 14.1% did not have a toilet facility compared with 19.4% at baseline. At end line, 10.6% of households reported living in an open defecation-free certified village compared with 0.3% at baseline (PR = 32.0; 95% CI: 11.9-86.4). In addition, at end line, 33.4% of households had a specific place for washing hands and 61.4% of caregivers reported handwashing with a washing agent after defecation or before preparing food compared with 21.1% (PR = 1.59; 95% CI: 1.39-1.82) and 55.2% (PR = 1.11; 95% CI: 1.04-1.19) at baseline, respectively. Community-led total sanitation implementation in Zambia led to improvements in access to improved sanitation facilities, reduced open defecation, and better handwashing practices. There is however a need for enhanced investment in sanitation and hygiene promotion.

[This corrects the article DOI: 10.1371/journal.pmed.1002589.].

Background: Systematic reviews have described high rates of attrition in patients with HIV receiving antiretroviral therapy (ART). However, migration and clinical transfer may lead to an overestimation of attrition (death and loss to follow-up). Using a newly linked national laboratory database in South Africa, we assessed national retention in South Africa's national HIV program., Methods and Findings: Patients receiving care in South Africa's national HIV program are monitored through regular CD4 count and viral load testing. South Africa's National Health Laboratory Service has maintained a database of all public-sector CD4 count and viral load results since 2004. We linked individual laboratory results to patients using probabilistic matching techniques, creating a national HIV cohort. Validation of our approach in comparison to a manually matched dataset showed 9.0% undermatching and 9.5% overmatching. We analyzed data on patients initiating ART in the public sector from April 1, 2004, to December 31, 2006, when ART initiation could be determined based on first viral load among those whose treatment followed guidelines. Attrition occurred on the date of a patient's last observed laboratory measure, allowing patients to exit and reenter care prior to that date. All patients had 6 potential years of follow-up, with an additional 2 years to have a final laboratory measurement to be retained at 6 years. Data were censored at December 31, 2012. We assessed (a) national retention including all laboratory tests regardless of testing facility and (b) initiating facility retention, where laboratory tests at other facilities were ignored. We followed 55,836 patients initiating ART between 2004 and 2006. At ART initiation, median age was 36 years (IQR: 30-43), median CD4 count was 150 cells/mm3 (IQR: 81-230), and 66.7% were female. Six-year initiating clinic retention was 29.1% (95% CI: 28.7%-29.5%). After allowing for transfers, national 6-year retention was 63.3% (95% CI: 62.9%-63.7%). Results differed little when tightening or relaxing matching procedures. We found strong differences in retention by province, ranging from 74.2% (95% CI: 73.2%-75.2%) in Western Cape to 52.2% (95% CI: 50.6%-53.7%) in Mpumalanga at 6 years. National attrition was higher among patients initiating at lower CD4 counts and higher viral loads, and among patients initiating ART at larger facilities. The study's main limitation is lack of perfect cohort matching, which may lead to over- or underestimation of retention. We also did not have data from KwaZulu-Natal province prior to 2010., Conclusions: In this study, HIV care retention was substantially higher when viewed from a national perspective than from a facility perspective. Our results suggest that traditional clinical cohorts underestimate retention., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Severe and fatal pertussis infections are concentrated among infants who are too young to be protected through routine vaccinations. Maternal Tdap (mTdap), which is now the standard of care in the US and UK, is considered to be the most effective way to address this gap in preventative care. Little is known about how pregnant women in low-resource settings might view mTdap. To inform strategies for mTdap implementation in these contexts, public health researchers sought to understand knowledge, attitudes, and beliefs toward pertussis and maternal vaccines and assess the barriers to vaccine acceptance., Methods: We conducted focus group discussions (FGDs) among mothers who participated in a longitudinal birth cohort study at the Chawama primary health center in Lusaka, Zambia. Since SAMIPS was not a clinical trial, but instead an observational cohort study, registration on clinicaltrials.gov was not required. Trained interviewers conducted the FGDs in January 2016 using a semi-structured interview guide, exploring participants' knowledge, attitudes and beliefs toward pertussis and vaccines. We analyzed the transcripts using Nvivo v.11 software., Results: Fifty mothers participated across 7 FGDs. Mothers had limited knowledge of pertussis and vaccines, yet expressed generally positive views of vaccinating themselves and their children. Participants conveyed very little vaccine hesitancy around maternal vaccinations, and discussed how they could protect their children's health. Mothers also highlighted barriers and facilitators to vaccine uptake, which included partner involvement, feelings of maternal authority over healthcare decision-making, and community rumors about Western medicine., Conclusion: Mothers viewed vaccinations as an important method to keep their children healthy, despite cultural myths and misconceptions about pertussis and vaccines. FGD results suggest that vaccine acceptability is high in Zambia, which is a critical factor to vaccine uptake. A strategy addressing myths and misconceptions should be prioritized if and when mTdap is introduced across low-resource settings., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The South African national HIV program has increased antiretroviral therapy (ART) coverage over the last decade, supported by policy changes allowing for earlier ART initiation. However, many patients still enter care with advanced (<200 cells/μL) and very advanced (<100 cells/μL) HIV disease. We assessed disease progression at entry to care using nationwide laboratory data., Methods: We constructed a national HIV cohort using laboratory records containing HIV RNA loads and CD4 counts from 2004 to 2016 to determine entry into care. We estimated numbers and proportions of adults with the first CD4 count <100 cells/ μL or 100-199 cells/μL. We calculated relative risks of presenting with advanced disease associated with male sex., Results: 8.04 million first CD4 results were identified. From 2005 to 2011, the proportion of patients entering into care with CD4 count <200 cells/μL declined from 46.8% to 35.6%. From 2011 onward, the proportion of patients entering ART with advanced HIV disease has remained relatively unchanged. In 2016, we estimated that of 654 868 patients entering care, 32.9% had advanced HIV disease, and 16.8% had very advanced HIV disease. Men were almost twice as likely as women (23.1% vs 12.6% ) to enter care with very advanced HIV disease., Conclusions: The proportion of patients presenting with advanced HIV disease in South Africa remains consistently high despite ART scale-up, representing a large and avoidable burden of morbidity. Early HIV diagnosis, rapid linkage to ART and approaches to attract men into early ART initiation should be prioritized.

Point-of-care (POC) technologies for HIV diagnosis in infants have the potential to overcome logistical challenges that delay treatment initiation and prevent improvements in morbidity and mortality. This study aimed to evaluate the performance of two POC technologies against the current standard-of-care (SOC) laboratory-based assay in South Africa, when operated by nurses in a hospital environment. Children <18 months of age who were treatment naive (excluding prophylaxis) and in whom an HIV PCR test was indicated were eligible for the study. To increase the rate of enrollment of HIV PCR-positive children, HIV-exposed neonates at high risk of mother-to-child transmission and children requiring confirmatory HIV testing were preferentially enrolled. The two POC technologies demonstrated excellent concordance, with 315 (97.8%) results consistent with the SOC result. The POC technologies yielded 102 positive and 220 negative tests each. The SOC assay had 101 positive, 214 negative, 4 indeterminate, 1 invalid, and 2 specimen-rejected results. To include the indeterminate results in sensitivity/specificity calculations, a sensitivity analysis was performed, which yielded a simulated sensitivity of 0.9904 (interquartile range [IQR], 0.9808 to 0.9904) and a specificity of 0.9954 (IQR, 0.9954 to 1.0). This study confirmed that both POC technologies can be successfully used outside the laboratory environment to yield precise sensitivity/specificity values for pediatric, including neonatal, HIV testing., (Copyright © 2017 American Society for Microbiology.)

Background: Lack of accessible laboratory infrastructure limits HIV antiretroviral therapy (ART) initiation, monitoring, and retention in many resource-limited settings. Point-of-care testing (POCT) is advocated as a mechanism to overcome these limitations. We executed a pragmatic, prospective, randomized, controlled trial comparing the impact of POCT vs. standard of care (SOC) on treatment initiation and retention in care., Methods: Selected POC technologies were embedded at 3 primary health clinics in South Africa. Confirmed HIV-positive participants were randomized to either SOC or POC: SOC participants were venesected and specimens referred to the laboratory with patient follow-up as per algorithm (∼3 visits); POC participants had phlebotomy and POCT immediately on-site using Pima CD4 to assess ART eligibility followed by hematology, chemistry, and tuberculosis screening with the goal of receiving same-day adherence counseling and treatment initiation. Participant outcomes measured at recruitment 6 and 12 months after initiation., Results: Four hundred thirty-two of 717 treatment eligible participants enrolled between May 2012 and September 2013: 198 (56.7%) SOC; 234 (63.6%) POC. Mean age was 37.4 years; 60.5% were female. Significantly more participants were initiated using POC [adjusted prevalence ratio (aPR) 0.83; 95% confidence interval (CI): 0.74 to 0.93; P < 0.0001], the median time to initiation was 1 day for POC and 26.5 days for SOC. The proportion of patients in care and on ART was similar for both arms at 6 months (47 vs. 50%) (aPR 0.96; 95% CI: 0.79 to 1.16) and 12 months (32 vs. 32%) (aPR 1.05; 95% CI: 0.80 to 1.38), with similar mortality rates. Loss to follow-up at 12 months was higher for POC (36% vs. 51%) (aPR 0.82; 95% CI: 0.65 to 1.04)., Conclusions: Adoption of POCT accelerated ART initiation but once on treatment, there was unexpectedly higher loss to follow-up on POC and no improvement in outcomes at 12 months over SOC.

AbstractThis prospective cohort study describes travelers' diarrhea (TD) and non-TD gastrointestinal (GI) symptoms among international travelers from the Boston area, the association of TD with traveler characteristics and dietary practices, use of prescribed antidiarrheal medications, and the impact of TD and non-TD GI symptoms on planned activities during and after travel. We included adults who received a pre-travel consultation at three Boston-area travel clinics and who completed a three-part survey: pre-travel, during travel, and post-travel (2-4 weeks after return). TD was defined as self-reported diarrhea with or without nausea/vomiting, abdominal pain, or fever. Demographic and travel characteristics were evaluated by χ 2 test for categorical and Wilcoxon rank-sum test for continuous variables. Analysis of dietary practices used logistic generalized estimating equation models or logistic regression models. Of 628 travelers, 208 (33%) experienced TD and 45 (7%) experienced non-TD GI symptoms. Of 208 with TD, 128 (64%), 71 (36%), and 123 (62%) were prescribed ciprofloxacin, azithromycin, and/or loperamide before travel, respectively. Thirty-nine (36%) of 108 took ciprofloxacin, 20 (38%) of 55 took azithromycin, and 28 (28%) of 99 took loperamide during travel. Of 172 with TD during travel, 24% stopped planned activities, and 2% were hospitalized. Of 31 with non-TD GI symptoms during travel, six (13%) stopped planned activities. International travelers continue to experience diarrhea and other GI symptoms, resulting in disruption of planned activities and healthcare visits for some. Although these illnesses resulted in interruption of travel plans, a relatively small proportion took prescribed antibiotics.

Objective: To evaluate current practices and standards of evaluation and treatment of childhood febrile illness in Southern Province, Zambia., Methods: From November to December 2013, we conducted a cross-sectional survey of facilities and health workers and we observed the health workers' interactions with febrile children and their caregivers. The facility survey recorded level of staffing, health services provided by the facility, availability and adequacy of medical equipment, availability of basic drugs and supplies and availability of treatment charts and guidelines. The health worker survey assessed respondents' training, length of service, access to national guidelines and job aids for managing illnesses, and their practice and knowledge on management of neonatal and child illnesses. We also conducted exit interviews with caregivers to collect information on demographic characteristics, chief complaints, counselling and drug dispensing practices., Findings: This study included 24 health facilities, 53 health workers and 161 children presenting with fever. Facilities were insufficiently staffed, stocked and equipped to adequately manage childhood fever. Children most commonly presented with upper respiratory tract infections (46%; 69), diarrhoea (31%; 27) and malaria (10%; 16). Health workers insufficiently evaluated children for danger signs, and less than half (47%; 9/19) of children with pneumonia received appropriate antibiotic treatment. Only 57% (92/161) were tested for malaria using either rapid diagnostic tests or microscopy., Conclusion: Various health system challenges resulted in a substantial proportion of children receiving insufficient management and treatment of febrile illness. Interventions are needed including strengthening the availability of commodities and improving diagnosis and treatment of febrile illness.

Objective: To inform future interventions for advising travelers., Patients and Methods: We prospectively collected data on travelers seen at the Boston Area Travel Medicine Network, a Boston area research collaboration of 5 travel medicine clinics. Data from 15,440 travelers were collected from March 1, 2008, through July 31, 2010. We compared traveler and trip characteristics and differences in demographic characteristics and travel plans across the 5 clinics, including an analysis of pretravel preparations for certain high-risk destinations., Results: More than half of the 15,440 travelers were female (8730 [56.5]), and 72.4% (10,528 of 14,545) were white; the median age was 34 years, and 29.4% of travelers (3077 of 10,483) were seen less than 2 weeks before their departure date. Substantial variation in racial background, purpose of travel, and destination risk existed across the 5 clinics. For example, the proportion of travelers visiting friends and relatives ranged from 7.6% (184 of 2436) to 39.0% (1029 of 2639) (18.7% [2876 of 15,360] overall), and the percentage of travelers to areas with malaria risk ranged from 23.7% (333 of 1403) to 52.0% (1306 of 2512). Although most clinics were likely to have prescribed certain vaccines for high-risk destinations (eg, yellow fever for Ghana travel), there was wide variability in influenza vaccine use for China travel., Conclusion: Substantial differences in clinic populations can occur within a single metropolitan area, highlighting why individual physicians and travel clinics need to understand the specific needs of the travelers they serve in addition to general travel medicine.

Expert performance is often evaluated assuming that good experts have good outcomes. We examine expertise in medicine and develop a model that allows for two dimensions of physician performance: decision making and procedural skill. Better procedural skill increases the use of intensive procedures for everyone, while better decision making results in a reallocation of procedures from fewer low-risk to high-risk cases. We show that poor diagnosticians can be identified using administrative data and that improving decision making improves birth outcomes by reducing C-section rates at the bottom of the risk distribution and increasing them at the top of the distribution.

We conducted a prospective study to measure dengue virus (DENV) antibody seroconversion in travelers to dengue-endemic areas. Travelers seen in the Boston Area Travel Medicine Network planning to visit dengue-endemic countries for ≥ 2 weeks were enrolled from 2009 to 2010. Pre- and post-travel blood samples and questionnaires were collected. Post-travel sera were tested for anti-DENV IgG by indirect IgG enzyme-linked immunosorbent assay (ELISA) and anti-DENV IgM by capture IgM ELISA. Participants with positive post-travel anti-DENV IgG or IgM were tested for pre-travel anti-DENV IgG and IgM; they were excluded from the seroconversion calculation if either pre-travel anti-DENV IgG or IgM were positive. Paired sera and questionnaires were collected for 62% (589/955) of enrolled travelers. Most participants were 19-64 years of age, female, and white. The most common purposes of travel were tourism and visiting friends and relatives; most trips were to Asia or Africa. Median length of travel was 21 days. DENV antibody seroconversion by either anti-DENV IgM or IgG ELISA was 2.9-6.8%; lower range percent excluded potential false-positive anti-DENV IgG due to receipt of yellow fever or Japanese encephalitis vaccines at enrollment; upper range percent excluded proven false-positive anti-DENV IgM. Eighteen percent of those with seroconversion reported dengue-like symptoms. Seroconversion was documented for travel to Africa as well as countries and regions known to be highly dengue endemic (India, Brazil, southeast Asia). Given widespread risk of dengue, travel medicine counseling should include information on risk of dengue in endemic areas and advice on preventing insect bites and seeking prompt medical attention for febrile illness., (© The American Society of Tropical Medicine and Hygiene.)

Background: Chlorhexidine umbilical cord washes reduce neonatal mortality in south Asian populations with high neonatal mortality rates and predominantly home-based deliveries. No data exist for sub-Saharan African populations with lower neonatal mortality rates or mostly facility-based deliveries. We compared the effect of chlorhexidine with dry cord care on neonatal mortality rates in Zambia., Methods: We undertook a cluster-randomised controlled trial in Southern Province, Zambia, with 90 health facility-based clusters. We enrolled women who were in their second or third trimester of pregnancy, aged at least 15 years, and who would remain in the catchment area for follow-up of 28 days post-partum. Newborn babies received clean dry cord care (control) or topical application of 10 mL of a 4% chlorhexidine solution once per day until 3 days after cord drop (intervention), according to cluster assignment. We used stratified, restricted randomisation to divide clusters into urban or two rural groups (located <40 km or ≥40 km to referral facility), and randomly assigned clusters (1:1) to use intervention (n=45) or control treatment (n=45). Sites, participants, and field monitors were aware of their study assignment. The primary outcomes were all-cause neonatal mortality within 28 days post-partum and all-cause neonatal mortality within 28 days post-partum among babies who survived the first 24 h of life. Analysis was by intention to treat. Neonatal mortality rate was compared with generalised estimating equations. This study is registered at ClinicalTrials.gov (NCT01241318)., Findings: From Feb 15, 2011, to Jan 30, 2013, we screened 42 356 pregnant women and enrolled 39 679 women (mean 436·2 per cluster [SD 65·3]), who had 37 856 livebirths and 723 stillbirths; 63·8% of deliveries were facility-based. Of livebirths, 18 450 (99·7%) newborn babies in the chlorhexidine group and 19 308 (99·8%) newborn babies in the dry cord care group were followed up to day 28 or death. 16 660 (90·0%) infants in the chlorhexidine group had chlorhexidine applied within 24 h of birth. We found no significant difference in neonatal mortality rate between the chlorhexidine group (15·2 deaths per 1000 livebirths) and the dry cord care group (13·6 deaths per 1000 livebirths; risk ratio [RR] 1·12, 95% CI 0·88-1·44). Eliminating day 0 deaths yielded similar findings (RR 1·12, 95% CI 0·86-1·47)., Interpretation: Despite substantial reductions previously reported in south Asia, chlorhexidine cord applications did not significantly reduce neonatal mortality rates in Zambia. Chlorhexidine cord applications do not seem to provide clear benefits for newborn babies in settings with predominantly facility-based deliveries and lower (<30 deaths per 1000 livebirths) neonatal mortality rates., Funding: Bill & Melinda Gates Foundation., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

When a patient arrives at the Emergency Room with acute myocardial infarction (AMI), the provider on duty must quickly decide how aggressively the patient should be treated. Using Florida data on all such patients from 1992 to 2014, we decompose practice style into two components: The provider's probability of conducting invasive procedures on the average patient (which we characterize as aggressiveness), and the responsiveness of the choice of procedure to the patient's characteristics. We show that within hospitals and years, patients with more aggressive providers have consistently higher costs and better outcomes. Since all patients benefit from higher utilization of invasive procedures, targeting procedure use to the most appropriate patients benefits these patients at the expense of the less appropriate patients. We also find that the most aggressive and responsive physicians are young, male, and trained in top 20 schools., (Copyright © 2016 Elsevier B.V. All rights reserved.)

We conducted a prospective cohort study to assess adherence to malaria chemoprophylaxis, reasons for nonadherence, and use of other personal protective measures against malaria. We included adults traveling to malaria-endemic countries who were prescribed malaria chemoprophylaxis during a pre-travel consultation at three travel clinics in the Boston area and who completed three or more surveys: pre-travel, at least one weekly during travel, and post-travel (2-4 weeks after return). Of 370 participants, 335 (91%) took malaria chemoprophylaxis at least once and reported any missed doses; 265 (79%) reported completing all doses during travel. Adherence was not affected by weekly versus daily chemoprophylaxis, travel purpose, or duration of travel. Reasons for nonadherence included forgetfulness, side effects, and not seeing mosquitoes. Main reasons for declining to take prescribed chemoprophylaxis were peer advice, low perceived risk, and not seeing mosquitoes. Of 368 travelers, 79% used insect repellent, 46% used a bed net, and 61% slept in air conditioning at least once. Because travelers may be persuaded to stop taking medication by peer pressure, not seeing mosquitoes, and adverse reactions to medications, clinicians should be prepared to address these barriers and to empower travelers with strategies to manage common side effects of antimalarial medications., (© The American Society of Tropical Medicine and Hygiene.)

Background: Japanese encephalitis (JE) and rabies are serious vaccine preventable diseases which are an important consideration for travelers to Asia., Methods: Five Boston-area travel clinics collected demographic data, trip information, and interventions for travelers to Asia seen at pre-travel consultations from March 1, 2008, through July 31, 2010. We evaluated travelers for proportion vaccinated for JE and rabies, those traveling for >1 month, and whether travelers had adequate time to complete the JE series (clinic visit ≥28 days before departure) and rabies pre-exposure prophylaxis (clinic visit ≥21 days before departure)., Results: Among 15,440 travelers from five Boston Area Travel Medicine Network travel clinics, Asia was the most common destination region, visited by 5,582 (36%) of travelers. Among these travelers, 4,810 (86%) planned to travel to only one Asian subregion. Median trip duration was 17 days, with more than 20% traveling for >1 month. The most common destinations were South (41%), Southeast (26%), and East (23%) Asia. Of those traveling to South, Southeast, or East Asia, over one-third with trips >1 month had insufficient time to complete a series for either JE or rabies vaccine. Overall, only 10% of travelers were vaccinated (past and pre-travel visit) for either JE or rabies, with lowest percentages among travelers visiting friends and relatives. Most travelers received advice on vector precautions (96%) and rabies prevention, which included avoiding animal contact, washing wounds, and obtaining appropriate post-exposure prophylaxis (88%)., Conclusion: Given the insufficient time for completion and relatively low vaccination rates, greater awareness of earlier pre-travel consultations, at least 4-6 weeks before travel, and accurate risk assessment for travelers are important. Effective counseling about vector avoidance, rabies, and animal bite prevention and management remains critical., (© 2015 International Society of Travel Medicine.)

Objective: Stunting affects 26.7% of children worldwide, and little is known about its effects on the outcomes of childhood pneumonia. We evaluated the effect of stunting on the outcomes of pneumonia among children enrolled in two large clinical trials., Methods: We analysed data from two WHO and USAID-sponsored inpatient treatment trials, the Severe Pneumonia Evaluation Antimicrobial Research study (n = 958) and the Amoxicillin Penicillin Pneumonia International Study (n = 1702), which enrolled children aged 2-59 months across 16 sites in LMICs. We assessed the effect of stunting (height-for-age Z score < -2) on treatment outcome and time to resolution of hypoxaemic pneumonia., Results: Among 2542 (96%) children with valid data for height, 28% were stunted and 12.8% failed treatment by 5 days. The failure rate among stunted patients was 16.0% vs. 11.5% among non-stunted patients [unadjusted RR = 1.24 (95% CI 1.08, 1.41); adjusted RR = 1.28 (95% CI 1.10, 1.48)]. An inverse relationship was observed between height and failure rates, even among non-stunted children. Among 845 patients with hypoxaemic pneumonia, stunting was associated with a lower probability of normalisation of respiratory rate [HR = 0.63 (95% CI 0.52, 0.75)] and oxygen saturation [HR = 0.74 (95% CI 0.61, 0.89)]., Conclusions: Stunting increases the risk of treatment failure and is associated with a longer course of recovery in children with pneumonia. Strategies to decrease stunting may decrease the burden of adverse outcomes in childhood pneumonia in low-resource settings., (© 2015 John Wiley & Sons Ltd.)