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BackgroundRespiratory 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 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.MethodsWe 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, post-mortem nasopharyngeal sampling. The current analysis explored the differences between the nasopharyngeal microbiome profiles of RSV+ and RSV-decedents using 16S ribosomal DNA sequencing.ResultsWe found thatMoraxellawas more abundant in the nasopharyngeal microbiome of RSV+ decedents than in RSV-decedents. Additionally,GemellaandStaphylococcuswere less abundant in RSV+ decedents than in RSV-decedents.ConclusionThese results support previously reported findings of the association between the nasopharyngeal 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.

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 between 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 for monitoring of the infant. Experienced family members and health care workers were frequently cited as sources of information on infant sleep position. Maternal alertness and vigilance were suggested as mechanisms to prevent SIDS and smothering. Conclusions: Maternal beliefs and perceptions about the infant’s sleep environment guided decisions about bedsharing and infant sleep positions. 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.

ObjectivesTo determine the prevalence of COVID-19 postmortem setting in Lusaka, Zambia.DesignA systematic, postmortem prevalence study.SettingA busy, inner-city morgue in Lusaka.ParticipantsWe 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.InterventionsNot applicable—this was an observational study.Primary outcomesPrevalence of COVID-19 detections by PCR. Results were stratified by setting (facility vs community deaths), age, demographics and geography and time.Secondary outcomesShifts in viral variants; causal inferences based on cycle threshold values and other features; antemortem testing rates.ResultsFrom 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.ConclusionsCOVID-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

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 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.

Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections and child mortality. While RSV disease burden is highest in low- and middle-income countries, most knowledge about risk factors for fatal RSV disease comes from high-income settings. Methods Among infants aged 4 days to Results From 720 infant deaths, 6% (44) were RSV-positive, 70% were Conclusions Other than congenital cardiac conditions, we found a lack of association between RSV and underlying risk factors. This differs from high-income settings, where RSV mortality is concentrated among high-risk infants. In this population, birth-related outcomes are the highest mortality risk factors. Improved neonatal care remains crucial in the fight against neonatal mortality.

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.

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.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.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.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.

IntroductionExisting 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.MethodsWe 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.ResultsA 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).ConclusionsThe 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.

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

Background: The contribution of sudden unexpected infant death (SUID) has received little attention in global health. The objective of this study was to estimate the burden of SUID in Lusaka, Zambia. Methods: Verbal autopsies were conducted on infants who died in Lusaka, between 2017 and 2020. From these, we performed a qualitative analysis of the free text narratives of the final series of events leading to each infant’s death and classified these as symptomatic deaths or SUID. Any narrative that described an infant who was otherwise healthy with no antecedent illness prior to death and found dead in bed after a sleep episode was classified as SUID. We used logistic regression to test for statistical differences between asymptomatic deaths and SUIDs on key infant, maternal and other risk factors of SUIDs. Results: Eight hundred and nine verbal autopsies were conducted with families of decedent infants younger than six months of age. A total of 92.6% (749/809) had presented with symptoms prior to death, whereas 7.4% (60/809) died without preceding symptoms or obvious cause of death. Of these, 16/60 were compatible with accidental suffocation deaths, and 54/60 appeared to be sudden infant death syndrome. SUID deaths were concentrated in infants younger than two months of age with peak age of one to two months. Age at death was the only significant factor in multivariate analysis. Infants aged between one and two months had 2.84 increased odds of suspected SUIDs compared to infants in the first month of life (aOR = 2.84, 95% CI: 1.31, 6.16). Conclusions: Our findings suggest SUID could be accounting for a significant proportion of infant deaths in Zambia, but this cause of infant mortality is going unrecognized. Public health interventions in Zambia, and Africa more broadly, are likely overlooking SUIDs as an important cause of infant mortality.

BackgroundInfants suffering from lower respiratory tract infections (LRTIs) have distinct nasopharyngeal (NP) microbiome profiles that correlate with severity of disease. Whether these profiles precede the infection or a consequence of it, is unknown. In order to answer this question, longitudinal studies are needed.MethodsWe conducted an analysis of a longitudinal prospective cohort study of 1,981 Zambian mother-infant pairs who underwent NP sampling from 1-week through 14-weeks of age at 2-3-week intervals. Ten of the infants in the cohort developed LRTI and were matched 3:1 with healthy comparators. We completed 16S rRNA gene sequencing on the samples each of these infants contributed, as well as from baseline samples of the infants’ mothers, and characterized the normal maturation of the healthy infant NP microbiome, compared to infants who developed LRTI.ResultsThe infant NP microbiome maturation was characterized by transitioning from Staphylococcus dominant to respiratory-genera dominant profiles during the first three months of life, similar to what is described in the literature. Interestingly, infants who developed LRTI had NP dysbiosis before infection, in most cases as early as the first week of life. Dysbiosis was characterized by the presence of Novosphingobium, Delftia, high relative abundance of Anaerobacillus, Bacillus, and low relative abundance of Dolosigranulum, compared to the healthy controls. Mothers of infants with LRTI also had low relative abundance of Dolosigranulum in their baseline samples compared to mothers of infants that did not develop an LRTI.ConclusionsOur results suggest that NP microbiome dysbiosis precedes LRTI in young infants and may be present in their mothers as well. Early dysbiosis may play a role in the causal pathway leading to LRTI or could be a marker of other pathogenic forces that directly lead to LRTI.FundingThis work was supported by The Southern Africa Mother Infant Pertussis Study – Nasopharyngeal Carriage (SAMIPS-NPC). PI Gill. Funder NIH/NIAID (1R01AI133080). WEJ and TF were supported by funds from the NIH, U01CA220413 and R01GM127430.

Background: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. Methods: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. Results: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). Conclusions: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting. publishedVersion

Background: Previous studies of infants born to HIV-positive mothers have linked HIV exposure to poor outcomes from gastrointestinal and respiratory illnesses, and to overall increased mortality rates. The mechanism behind this is unknown, but it is possible that differences in the nasopharyngeal (NP) microbiome between HIV-unexposed and HIV-exposed infants could play a role in perpetuating some outcomes. Methods: We conducted a longitudinal analysis of 170 NP swabs of healthy HIV-exposed, uninfected (HEU; n=10) infants and their HIV(+) mothers and HIV-unexposed, uninfected (HUU; n=10) infants and their HIV(-) mothers. These swabs were identified from a sample library collected in Lusaka, Zambia between 2015 and 2016. Using 16S rRNA gene sequencing, we characterized the maturation of the microbiome over the first 14 weeks of life to determine what quantifiable differences exist between HEU and HUU infants, and what patterns are reflected in the mothers' NP microbiomes. Results: In both HEU and HUU infants, Staphylococcus and Corynebacterium began as primary colonizers of the NP microbiome but were in time replaced by Dolosigranulum, Streptococcus, Moraxella and Haemophilus. When studying differences between infants, the microbe Staphylococcus haemolyticus indicated a distinctive high association with HIV exposure at birth, even when accounting for the interaction between HIV exposure status and time of sampling. When comparing infants to their mothers with paired analyses, HEU infants’ NP microbiome composition was only slightly different from their HIV(+) mothers at birth or 14 weeks, including in their carriage of S. pneumoniae, H. influenzae, and S. haemolyticus. Conclusions: Our analyses indicate that the HEU infants in our study exhibit subtle differences in the NP microbial composition throughout the sampling interval. Given our results and the sampling limitations of our study, we believe that further research must be conducted in order to confidently understand the relationship between HIV exposure and infants’ NP microbiomes.

PurposeSouth 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.ParticipantsThe 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 dateFrom 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 plansContinuous updating of the cohort, integration with available clinical data, and expansion to include tuberculosis and other lab-monitored comorbidities.

Summary Background The number of South African adolescents receiving HIV care and treatment in South Africa is growing. By use of routinely collected laboratory data from South Africa's National HIV Programme, we aimed to quantify the numbers of adolescents accessing HIV care and treatment over time, characterise the role of perinatal infection in these trends, and estimate proportions of adolescents seeking HIV care and antiretroviral therapy (ART) in South Africa's public sector. Methods We did a retrospective, descriptive cohort study of children and adolescents aged 1–19 years accessing care in South Africa's public sector HIV treatment programme from 2005 to 2016 with a CD4 cell count or viral load recorded in South Africa's National Health Laboratory Service database. We estimated the total number of children and adolescents entering HIV care with a CD4 cell count or viral load test result by calendar period, as well as the proportion in care and receiving ART with at least one viral load test result. We stratified analyses by gender and by whether the patient entered care at younger than 15 years (probably perinatally infected) or at 15–19 years (probably infected in adolescence). Findings We identified 730 882 patients aged 1–19 years at entry to care between Jan 1, 2005, and Dec 31, 2016. 209 205 (54%) of 388 439 patients entering care younger than 15 years and 301 242 (88%) of 342 443 patients entering care aged 15–19 were female. During the study period, the number of virologically monitored patients aged 15–19 years receiving ART increased from 7949 in 2005–08 to 80 918 in 2013–16. 92 783 (66%) of 140 028 patients aged 15–19 years seeking care started ART by 2016, well below UNAID's target of ART for 90% of those diagnosed. We project that the number of adolescents on ART will continue to rise. Interpretation The many adolescents aged 15–19 years receiving ART reflect the ageing of children entering care at ages 1–14 years, and increases in care-seeking among horizontally infected adolescents aged 15–19 years. However, many adolescents seeking care do not start ART, suggesting an urgent need for interventions to increase uptake of ART and improve services for this population. Funding US National Institutes of Health, and the President's Emergency Plan for AIDS Relief through the US Agency for International Development.

Little is known about the factors that contribute to the losses during stages of the HIV continuum of care (CoC) and specifically during the latter stages of antiretroviral (ART) adherence and retention in HIV care among adolescents living with HIV/AIDS (ALHA) in sub-Saharan Africa. We conducted a mixed-methods study: six focus group discussions with 43 ALHA (age 17-19); in-depth interviews with four (age 18-19): and survey-based interviews with 330 ALHA (age 18-19) to identify, understand, and describe factors contributing to the losses in the latter stages of the CoC among ALHA in Zambia. Through focus group discussions and in-depth interviews, ALHA identified barriers at the intrapersonal level (e.g., poverty; lack of adequate nutrition; fear of stigma), interpersonal level (e.g., stigma; disrespectful treatment by providers), institutional/facility level (e.g., lack of adolescent specific services), and community level (e.g., lack of collaboration among organizations; social norms). In quantitative interviews, we found that 46% (101/220) of ALHA reported missing any clinic appointments in the past three months, and about 19% (41/221) reporting missing one or more doses of ART in the last week. Logistic regressions indicate that walking to the site of appointment and being currently employed were predictive of missed visits. Findings highlight the complexity of the multiple factors that are unique to ALHA in Zambia, which should be addressed to improve adherence to ART and retention in HIV.

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.

ObjectivesLimited SARS CoV 2 testing in many African countries has constrained availability of data on the impact of COVID-19 (CV19). To address this gap, we conducted a systematic post-mortem surveillance study to directly measure the fatal impact of CV19 in an urban African population.DesignWe enrolled deceased individuals at the University Teaching Hospital (UTH) Morgue in Lusaka, Zambia. We obtained nasopharyngeal swabs for testing via reverse-transcriptase quantitative PCR (RT-qPCR) against the SARS-2 Coronavirus. We stratified deaths by CV19 status, by location, age, sex, and underlying risk factors.SettingUTH is Zambia’s largest tertiary care referral hospital and its morgue registers ∼80% of Lusaka’s deaths.ParticipantsParticipants of all ages were enrolled if within 48 hours of death and if the next of kin or representative provided written informed consent.ResultsWe enrolled 372 participants between June and September 2020, and had PCR results for 364 (99.5%). CV19 was detected in 70/364 (19.2%). The median age for CV19+ deaths was 48 years (IQR 36-72 years) and 70% were male. Most CV19+ deaths (51/70, 72.8%) occurred in the community; none had been tested for CV19 antemortem. Among the 19/70 facility deaths, six were tested antemortem. Among the 52/70 CV19 deaths with symptoms data, 44/52 had typical symptoms of CV19 (cough, fever, shortness of breath), of whom only five were tested antemortem. We identified CV19 among seven children; only one had been tested antemortem. The proportion of CV19+ deaths increased with age, but 75.7% of CV19+ deaths were aged ConclusionsContrary to expectations, CV19+ deaths were common in Lusaka. The majority occurred in the community where testing capacity is lacking. Yet few who died at facilities were tested, despite presenting with typical symptoms of CV19. Therefore, CV19 cases were under reported because testing was rarely done, not because CV19 was rare. If our data are generalizable, the impact of CV19 in Africa has been vastly underestimated.

IntroductionReliable 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.MethodsThroughout 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.ResultsAt 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.ConclusionsWe 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.

Despite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to the cross-sectional nature of most pertussis surveillance studies. In addition, modern pertussis surveillance relies on quantitative PCR (qPCR) using fixed diagnostic thresholds to identify cases.To address this gap, we present a longitudinal analysis of 17,442 nasopharyngeal samples collected from a cohort of 1,320 Zambian mother/infant pairs. Using full-range cycle threshold (CT) values from IS481 qPCR assays, we document widespread asymptomatic infections among mothers and also, surprisingly, among young infants. From an initial group of eight symptomatic infants who tested positive by qPCR, we identify frequent contemporaneous subclinical infections in mothers. Within the full cohort, we observe strong temporal correlation between low- and high-intensity qPCR signals. We compute a single time-averaged score for each individual summarizing the evidence for pertussis infection (EFI), and show that EFI strongly clusters within mother/infant pairs, and is strongly associated with clinical symptomatology and antibiotic use.Overall, the burden of pertussis here is substantially underestimated when restricting diagnostic criteria to IS481 CT≤35. Rather, we find that full-range CT values provide valuable insights into pertussis epidemiology in this population, and illuminate the infection arc within individuals. These findings have significant implications for quantifying asymptomatic pertussis prevalence and its contribution to overall transmission. Our results also expose limitations of threshold-based interpretations of qPCR assays in infectious disease surveillance.IMPORTANCE STATEMENTCurrent pertussis epidemiology rests largely on cross-sectional surveys that use diagnostic thresholds to interpret qPCR results as positive or negative, and thus fail to capture arcs of infection within individuals or populations. By longitudinally monitoring a cohort of African mother/infant pairs and using full-range qPCR results, we quantify the otherwise-hidden evidence for pertussis infection (EFI) in individuals. We demonstrate strong clustering of EFI within mother/infant pairs and quantify the association between EFI and both pertussis symptoms and antibiotic use. Critically, we find strong evidence that asymptomatic pertussis is common in both infants and mothers, indicating that the burden of pertussis has been significantly underestimated in this population. Our results also inform qPCR-based monitoring of other pathogens, such as SARS-CoV-2.

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.

This paper reports on HIV related stigma based on results from an HIV legal environment assessment (LEA) within the Churches Health Association of Zambia HIV/AIDS program. We conducted 9 Focus Group Discussions and 20 Key Informant Interviews with key HIV/AIDS stakeholders that included representatives from network of Zambian people living with HIV. We administered a Survey Questionnaire to 337 people living with HIV (PLHIV) and 233 health workers. Quantitative data were analyzed using SAS v9.4; qualitative data was analyzed using QRS NVIVO version 11.0 Pro. Internalized stigma ranged between 20.8% and 31.8% of PLHIV; more among females than males. About one third (31%, n=104)) of the 337 participants reported that they were aware of being gossiped once, a few times, or often; more among females than males. 62.3%, 63.1%, and 55.1% of the 233 health workers said it was somewhat true or certainly true that in their catchment areas, PLHIV struggle to have an HIV test because of stigma, were hesitant to start ART due to stigma; told them that they had challenges taking their ARVs because of stigma respectively.

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.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.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.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.

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

This 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 χ2 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.

To evaluate current practices and standards of evaluation and treatment of childhood febrile illness in Southern Province, Zambia.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.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.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.Évaluer les pratiques et les normes actuelles d'évaluation et de traitement des maladies fébriles infantiles dans la Province méridionale de la Zambie.De novembre à décembre 2013, nous avons mené une enquête transversale auprès d‘établissements et de professionnels de santé et nous avons observé les interactions entre les professionnels de santé, les enfants fiévreux et leurs proches. L'enquête réalisée dans les établissements s'est intéressée à la dotation en personnel, aux services sanitaires dispensés par l'établissement, à la disponibilité et à la convenance des équipements médicaux, à la disponibilité de médicaments et de fournitures élémentaires et à la présence de directives et de feuilles d'observation. L'enquête réalisée auprès des professionnels de santé a analysé la formation des répondants, leur nombre d'années de service, leur accès aux directives nationales et aux aide-mémoires pour la prise en charge des maladies, ainsi que leur pratique et leurs connaissances en matière de prise en charge des maladies infantiles et néonatales. Nous avons également interrogé les proches à leur sortie afin de recueillir des informations sur les caractéristiques démographiques, les principales plaintes, les conseils et les pratiques d'administration des médicaments.Cette étude a examiné 24 établissements de santé, 53 professionnels de santé et 161 enfants atteints de fièvre. Les établissements manquaient de personnel, de produits en stock et d'équipements pour prendre en charge correctement les cas de fièvre infantile. Les enfants étaient le plus souvent atteints d'infections des voies respiratoires supérieures (46%; 69), de diarrhée (31%; 27) et de paludisme (10%; 16). Les professionnels de santé n'évaluaient pas suffisamment les signes de danger chez les enfants, et moins de la moitié (47%; 9/19) des enfants atteints de pneumonie ont reçu un traitement antibiotique adapté. Seuls 57% (92/161) ont fait l'objet d'un dépistage du paludisme, au moyen de tests de diagnostic rapide ou par microscopie.À cause des différents problèmes du système sanitaire, une part importante d'enfants ne bénéficie pas d'une prise en charge et d'un traitement suffisants des maladies fébriles. Des interventions sont nécessaires, notamment pour augmenter la disponibilité des produits et améliorer le diagnostic et le traitement des maladies fébriles.Evaluar las prácticas y los estándares de evaluación y tratamiento actuales de las enfermedades febriles en los niños en la Provincia del Sur, Zambia.De noviembre a diciembre de 2013, se realizó una encuesta transversal de centros y trabajadores sanitarios y se observaron las interacciones de los trabajadores sanitarios con niños con fiebre y sus cuidadores. La encuesta de los centros registró el nivel de personal y servicios de salud ofrecidos en el centro, la disponibilidad e idoneidad de los equipos médicos, la disponibilidad de medicamentos y suministros básicos y la disponibilidad de cronogramas y directrices de tratamiento. La encuesta a los trabajadores sanitarios evaluó la formación de los encuestados, la duración del servicio, el acceso a directrices nacionales y ayudas laborales para la gestión de enfermedades y su práctica y conocimiento acerca de la gestión de las enfermedades neonatales e infantiles. También se realizaron entrevistas de salida con cuidadores para recopilar información acerca de las características demográficas, los motivos de consulta, asesoramiento y prácticas de distribución de medicamentos.Este estudio abarcó 24 centros sanitarios, 53 trabajadores sanitarios y 161 niños con fiebre. Los centros no contaban con personal, suministros y equipos suficientes para gestionar de forma adecuada la fiebre en niños. Las afecciones más comunes presentadas por los niños eran infecciones del tracto respiratorio superior (46%; 69), diarrea (31%; 27) y malaria (10%; 16). Los trabajadores sanitarios evaluaron a los niños de forma insuficiente en busca de signos de peligro, y menos de la mitad (47%; 9/19) de los niños con neumonía recibieron el tratamiento antibiótico adecuado. Solo el 57% (92/161) fue sometido a pruebas de malaria utilizando pruebas de diagnóstico rápido o microscópicas.Varios desafíos del sistema sanitario llevan a un gran porcentaje de niños que reciben una gestión y tratamiento insuficientes de las enfermedades febriles. Es necesario intervenir para fortalecer la disponibilidad de productos básicos y mejorar el diagnóstico y el tratamiento de las enfermedades febriles.تقييم الممارسات الحالية ومعايير التقييم ومعالجة مرض الحمى لدى الأطفال في المنطقة الجنوبية في زامبيا.في الفترة ما بين نوفمبر/تشرين الثاني إلى ديسمبر/كانون الأول 2013، قمنا بإجراء استقصاء مقطعي للمرافق الصحية والعاملين بمجال الصحة ولاحظنا تفاعلات العاملين بمجال الصحة مع الحمى لدى الأطفال ومقدمي الرعاية لهم. وكان المسح الذي تم على مرافق الرعاية الصحية قد سجّل مستوى التوظيف، والخدمات الصحية المقدمة من قبل المِرفق، وتوافر المعدات الطبية ومدى كفاءتها، ومدى توافر المستلزمات والأدوية الأساسية، وتوافر الجداول التوضيحية وإرشادات العلاج. كما عمل المسح الذي تم على العاملين في مجال الصحة على تقييم التدريب الذي خضع له المشاركون، ومدة الخدمة، وإمكانية الاطلاع على الإرشادات القومية والأدوات المساعدة على العمل للسيطرة على المرض، والإجراءات المتبعة من جانبهم، ومعرفتهم بإدارة أمراض الأطفال وحديثي الولادة. كما قمنا أيضًا بإجراء مقابلات نهائية مع مقدمي الرعاية لجمع المعلومات المتعلقة بالخصائص الديموغرافية، والشكاوى الأساسية، والاستشارة والإجراءات المتبعة لصرف الدواء.تضمنت هذه الدراسة 24 مرفقًا صحيًا، و53 عاملاً في مجال الصحة، و161 طفلاً معرضًا للحمى. وُجد أن المرافق لم يتوفر بها ما يكفي من الموظفين، وغير مؤهلة ولا مجهزة لإدارة الحمى لدى الأطفال بشكلٍ ملائم. أغلب الأطفال كانوا مصابين بالتهاب الجهاز التنفسي العلوي (‏46‏%، 69)، والإسهال (31‏%، 27)، والملاريا (10‏%، 16). ولم يقم العاملون في مجال الصحة بتقييم الأطفال للكشف عن الأعراض الخطيرة بشكلٍ كافِ، وكان أقل من نصف الأطفال (47‏%، 9/19) المصابين بالالتهاب الرئوي قد تلقوا علاجًا مناسبًا بالمضادات الحيوية. ولم يتم فحص إلا 57‏% (92/161) للكشف عن الإصابة بالملاريا باستخدام إما الاختبارات التشخيصية السريعة أو الاختبارات المجهرية.تؤدي التحديات المختلفة التي يتعرض لها النظام الصحي إلى وجود نسبة كبيرة من الأطفال ممن يتلقون علاجًا وإدارة غير كافية لمرض الحمى. ويلزم إجراء التدخلات بما في ذلك ما كان منها لتعزيز توافر التجهيزات وتحسين تشخيص مرض الحمى وعلاجه.旨在评估赞比亚南部省当前的小儿热病评估和治疗实践和标准。.我们从 2013 年 11 月到 12 月对医疗机构和医务人员进行了横断面调查，并且观察了医务人员与发热儿童及其看护人之间的互动。 医疗机构调查记录了人员配备水平、医疗机构提供的卫生服务、医疗设备的可用性和充足性、基本药物和用品的可用性以及治疗计划和指南的可用性。 医务人员调查评估了受访者的培训、服务时长、获取全国疾病管理指南和工作支持的机会，以及他们在新生儿和小儿疾病管理方面的实践和知识。 我们也对看护人进行了离职访问，以收集有关人口统计特征、主诉、咨询和配药实践的信息。.本次调查涵盖 24 家医疗机构，53 名医务人员和 161 名出现发热症状的儿童。 这些医疗机构存在人员、医疗用品和设备配备不足的情况，无法对儿童发热进行良好的管理。 儿童最常见的症状是上呼吸道感染 (46%; 69)、腹泻 (31%; 27) 和疟疾 (10%; 16)。 医务人员无法充分评估儿童的危险症状，只有不到一半 (47%; 9/19) 的肺炎儿童接受了适当的抗生素治疗。 只有 57% (92/161) 的儿童通过快速诊断测试或显微镜检查接受了疟疾检测。.卫生系统面临的多种挑战导致大部分儿童无法接受足够的热病管理和治疗。 需要在提高商品可用性、改善热病诊断和治疗等方面加强干预。.Оценить текущую практику и стандарты оценки и лечения детских заболеваний, сопровождающихся лихорадкой, в Южной провинции, Замбия.С ноября по декабрь 2013 года мы провели одномоментное обследование медицинских учреждений и медицинских работников, наблюдая за тем, как медицинские работники взаимодействуют с детьми, страдающими лихорадкой, и с лицами, осуществляющими за ними уход. В В ходе обследования медицинских учреждений фиксировался уровень укомплектованности кадрами и медицинских услуг, предоставляемых этими учреждениями, наличие и соответствие медицинского оборудования, наличие основных лекарств и расходных материалов, а также наличие руководств по лечению. В ходе обследования медицинских работников была проведена оценка их подготовки, стажа работы, доступа к национальным руководствам и инструкциям по лечению заболеваний, а также их практики и знаний относительно лечения болезней новорожденных и детей. Мы также провели беседы с лицами, ухаживающими за больными, для сбора информации о демографических характеристиках, основных жалобах, консультировании и практике выдачи лекарств.Это исследование включало 24 медицинских учреждения, 53 медицинских работника и 161 ребенка с лихорадкой. Учреждения были недостаточно укомплектованы персоналом и имели недостаточное оснащение и снабжение для осуществления надлежащего лечения лихорадки у детей. У детей чаще всего встречались инфекции верхних дыхательных путей (46%, 69), диарея (31%, 27) и малярия (10%, 16). Медицинские работники проводили недостаточное обследование детей на наличие опасных симптомов, и менее половины детей с пневмонией (47%, 9 из 19) получали соответствующее лечение антибиотиками. Только 57% (92 из 161) были протестированы на малярию с использованием либо экспресс-диагностических тестов, либо микроскопии.Различные проблемы системы здравоохранения приводят к тому, что значительная часть детей получает недостаточное лечение заболеваний, сопровождающихся лихорадкой. Необходимо принять меры, включая повышение доступности лекарств и оборудования, а также улучшение диагностики и лечения заболеваний, сопровождающихся лихорадкой.

South African guidelines recommend repeat viral load testing within 6 months when human immunodeficiency virus (HIV) viral loads exceed 1,000 copies/mL. We assessed whether South African facilities follow viral load monitoring guidelines and whether guidelines improve HIV-related outcomes, using a regression discontinuity design in a national HIV cohort of 174,574 patients (2013–2015). We assessed whether patients with viral loads just above versus just below 1,000 copies/mL were more likely to receive repeat testing in 6 months, and we compared differences in clinic transfers, retention, and viral suppression. The majority (67%) of patients with viral loads of >1,000 copies/mL did not receive repeat testing within 6 months, and these patients were 8.0% (95% confidence interval (CI): 6.2, 9.7) more likely to receive repeat testing compared with ≤1,000 copies/mL. Eligibility for repeat testing (>1,000 copies/mL) was associated with greater 12-month retention (risk difference = 2.9%, 95% CI: 0.6, 5.2) and combined suppression and retention (risk difference = 5.8%, 95% CI: 3.0, 8.6). Patients with viral loads of >1,000 copies/mL who actually received repeat testing were 85.2% more likely to be both retained and virally suppressed at 12 months (95% CI: 35.9, 100.0). Viral load monitoring might improve patient outcomes, but most patients with elevated viral loads do not receive monitoring within recommended timelines.

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

Background Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa’s national HIV program using routine laboratory data. Methods and findings Data were extracted from South Africa’s National Health Laboratory Service (NHLS) Corporate Data Warehouse. All CD4 counts, viral loads (VLs), and other laboratory tests used in HIV monitoring were linked, creating a validated patient identifier. We constructed longitudinal HIV care cascades for all patients in the national HIV program, excluding data from the Western Cape and very small facilities. We then estimated for each facility in each year (2011 to 2015) the following cascade measures identified a priori as reflecting quality of HIV care: median CD4 count among new patients; retention 12 months after presentation; 12-month retention among patients established in care; viral suppression; CD4 recovery; monitoring after an elevated VL. We used factor analysis to identify an underlying measure of quality of care, and we assessed the persistence of this quality measure over time. We then assessed spatiotemporal variation and facility and population predictors in a multivariable regression context. We analyzed data on 3,265 facilities with a median (IQR) annual size of 441 (189 to 988) lab-monitored HIV patients. Retention 12 months after presentation increased from 42% to 47% during the study period, and viral suppression increased from 66% to 79%, although there was substantial variability across facilities. We identified an underlying measure of quality of HIV care that correlated with all cascade measures except median CD4 count at presentation. Averaging across the 5 years of data, this quality score attained a reliability of 0.84. Quality was higher for clinics (versus hospitals), in rural (versus urban) areas, and for larger facilities. Quality was lower in high-poverty areas but was not independently associated with percent Black. Quality increased by 0.49 (95% CI 0.46 to 0.53) standard deviations from 2011 to 2015, and there was evidence of geospatial autocorrelation (p < 0.001). The study’s limitations include an inability to fully adjust for underlying patient risk, reliance on laboratory data which do not capture all relevant domains of quality, potential for errors in record linkage, and the omission of Western Cape. Conclusions We observed persistent differences in HIV care and treatment outcomes across South African facilities. Targeting low-performing facilities for additional support could reduce overall burden of disease., Jacob Bor and co-workers use a new measure of care quality to report on facility-level variations in HIV care and outcomes in South Africa., Author summary Why was this study done? Health outcomes have improved as South Africa has expanded access to HIV treatment, yet gaps in the quality of care remain. We develop a measure of quality of HIV care for public sector health facilities in South Africa using harmonized routine data and describe variation in quality over time and space. What did the researchers do and find? We define a measure of quality of HIV care for facilities from 2011 to 2015 using data from the National Health Laboratory Service (NHLS) Corporate Data Warehouse, which have been deduplicated to enable longitudinal patient follow-up. Measures of care outreach, retention, CD4 recovery, viral monitoring, and viral suppression were combined into an index using factor analysis. The quality measure had high reliability across years. Quality improved over the 5 years of the study and was higher in clinics relative to hospitals, in larger facilities, and in rural facilities. High-quality facilities tended to cluster near one another geographically. Quality of care was lower in high-poverty areas, but was not independently correlated with racial composition. What do these findings mean? While quality of HIV care improved in South Africa over the 5 years of the study, there was large variation in quality across facilities. Understanding differences in quality of care over time and across space could guide interventions to achieve better health outcomes.

Objective To directly measure the fatal impact of coronavirus disease 2019 (covid-19) in an urban African population. Design Prospective systematic postmortem surveillance study. Setting Zambia’s largest tertiary care referral hospital. Participants Deceased people of all ages at the University Teaching Hospital morgue in Lusaka, Zambia, enrolled within 48 hours of death. Main outcome measure Postmortem nasopharyngeal swabs were tested via reverse transcriptase quantitative polymerase chain reaction (PCR) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deaths were stratified by covis-19 status, location, age, sex, and underlying risk factors. Results 372 participants were enrolled between June and September 2020; PCR results were available for 364 (97.8%). SARS-CoV-2 was detected in 58/364 (15.9%) according to the recommended cycle threshold value of Conclusions Contrary to expectations, deaths with covid-19 were common in Lusaka. Most occurred in the community, where testing capacity is lacking. However, few people who died at facilities were tested, despite presenting with typical symptoms of covid-19. Therefore, cases of covid-19 were under-reported because testing was rarely done not because covid-19 was rare. If these data are generalizable, the impact of covid-19 in Africa has been vastly underestimated.

IntroductionJanus kinases (JAK) inhibitors demonstrated to be effective in the treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA) but have been associated with serious cardiovascular and serious events. Two systematic reviews and network meta-analyses will be carried aiming to compare the relative safety of the different JAK inhibitors with regard to the risk of (1) cardiovascular and thromboembolic events and (2) serious infections in patients with RA.Methods and analysisPUBMED, Embase, Cochrane Controlled Register of Trials and ClinicalTrials.gov will be searched in order to identify randomised controlled trials evaluating the efficacy and safety of JAK inhibitors in patients with RA. The following events will be assessed: (1) any cardiovascular event; major adverse cardiovascular events and venous thromboembolism and (2) any infection; serious infections; herpes zoster infection and tuberculosis. Search terms will comprise RA and drugs names, including the thesaurus terms and the International Nonproprietary Names. The assessment of the methodological quality of the included studies will be performed through the RoB 2 tool: a revised Cochrane risk of bias tool for randomised trials. Network meta-analyses will be performed using STATA V.13.0. For each outcome, treatments will be ranked according to the probability of being the safest (best) alternative using the surface under the cumulative ranking curve.Ethics and disseminationEthical approval is not required as no primary data are collected. This systematic review will be disseminated through peer-reviewed publications and at conference meetings.

Background. Maternal vaccination with tetanus, reduced-dose diphtheria, and acellular pertussis vaccine (Tdap) could be an effective way of mitigating the high residual burden of infant morbidity and mortality caused by Bordetella pertussis. To better inform such interventions, we conducted a burden-of-disease study to determine the incidence of severe and nonsevere pertussis among a population of Zambian infants. Methods. Mother–infant pairs were enrolled at 1 week of life, and then seen at 2- to 3-week intervals through 14 weeks of age. At each visit, nasopharyngeal (NP) swabs were obtained from both, and symptoms were catalogued. Using polymerase chain reaction (PCR) to identify cases, and a severity scoring system to triage these into severe/nonsevere, we calculated disease incidence using person-time at risk as the denominator. Results. From a population of 1981 infants, we identified 10 with clinical pertussis, for an overall incidence of 2.4 cases (95% confidence interval [CI], 1.2–4.2) per 1000 infant-months and a cumulative incidence of 5.2 cases (95% CI, 2.6–9.0) per 1000 infants. Nine of 10 cases occurred within a 3-month window (May–July 2015), with highest incidence between birth and 6 weeks of age (3.5 cases per 1000 infant-months), concentrated among infants prior to vaccination or among those who had only received 1 dose of Diphtheria Tetanus whole cell Pertussis (DTwP). Maternal human immunodeficiency virus (HIV) modestly increased the risk of infant pertussis (risk ratio, 1.8 [95% CI, .5–6.9]). Only 1 of 10 infant cases qualified as having severe pertussis. The rest presented with the mild and nonspecific symptoms of cough, coryza, and/or tachypnea. Notably, cough durations were long, exceeding 30 days in several cases, with PCRs repeatedly positive over time. Conclusions. Pertussis is circulating freely among this population of Zambian infants but rarely presents with the classical symptoms of paroxysmal cough, whooping, apnea, and cyanosis. Maternal HIV appears to increase the risk, while lack of effective exposure to DTwP increased the risk.

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

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.

OBJECTIVE: Retention in HIV care particularly among postpartum women is a challenge to national antiretroviral therapy programs. Retention estimates may be underestimated because of unreported transfers. We explored mobility and clinic switching among patients considered lost to follow-up (LTFU). DESIGN: Observational cohort study. METHODS: Of 788 women initiating antiretroviral therapy during pregnancy at 6 public clinics in Johannesburg South Africa 300 (38.1%) were LTFU (no visit >/=3 months). We manually searched for these women in the South African National Health Laboratory Services database to assess continuity of HIV care. We used geographic information system tools to map mobility to new facilities. RESULTS: Over one-third (37.6%) of women showed evidence of continued HIV care after LTFU. Of these 67.0% continued care in the same province as the origin clinic. Compared with those who traveled outside of the province for care these same-province "clinic shoppers" stayed out-of-care longer {median 373 days [interquartile range (IQR): 175-790] vs. 175.5 days (IQR: 74-371)} and had a lower CD4 cell count on re-entry [median 327 cells/muL (IQR: 196-576) vs. 493 cells/muL (IQR: 213-557). When considering all women with additional evidence of care as engaged in care cohort LTFU dropped from 38.1% to 25.0%. CONCLUSIONS: We found evidence of continued care after LTFU and identified local and national clinic mobility among postpartum women. Laboratory records do not show all clinic visits and manual matching may have been under- or overestimated. A national health database linked to a unique identifier is necessary to improve reporting and patient care among highly mobile populations.

Objective In many resource-limited settings, people from rural areas migrate to urban hubs in search of work. Thus, urban public-sector HIV clinics in South Africa (SA) often cater to both local residents and patients from other provinces and/or countries. The objective of this analysis was to compare programmatic treatment outcomes by citizenship status in an urban clinic in SA. Setting An urban public-sector HIV treatment facility in Johannesburg, SA. Participants We included all antiretroviral therapy (ART)-naive, non-pregnant patients who initiated standard first-line treatment from January 2008 to December 2013. 12 219 patients were included and 59.5% were women. Primary outcome measure Patients were followed from ART initiation until death, transfer, loss to follow-up (LTF), or data set closure. We describe attrition (mortality and LTF) stratified by SA citizenship status (confirmed SA citizens (with national ID number), unconfirmed SA citizens (no ID), and foreign nationals) and model the risk of attrition using Cox proportional hazards regression. Results 70% of included patients were confirmed SA citizens, 19% were unconfirmed SA citizens, and 11% were foreign nationals. Unconfirmed SA citizens were far more likely to die or become LTF than other patients. A similar proportion of foreign nationals (18.2%) and confirmed SA citizens (17.7%) had left care at 1 year compared with 47.0% of unconfirmed SA citizens (adjusted hazard ratio (aHR) unconfirmed SA vs confirmed SA: 2.68; 95% CI 2.42 to 2.97). By the end of follow-up, 75.5% of unconfirmed SA citizens had left care, approximately twice that of any other group. Conclusions Unconfirmed SA citizens were more likely to drop out of care after ART initiation than other patients. Further research is needed to determine whether this observed attrition is representative of migration and/or self-transfer to another HIV clinic as such high rates of attrition pose challenges for the success of the national ART programme.