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BACKGROUND: Assessment of the safety and efficacy of vaccines against the severe acute respiradetory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOxl nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5x1O10 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D6146 virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose. RESULTS: Between June 24 and November 9,2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid49 developed in 23 of 717 placebo recipients (3.296) and in 19 of750 vaccine recipients (2.596), for an efficacy of 21.9% (95% confidence interval ICI], -49.9 to 59.8). Among the 42 participants with Covid49, 39 cases (95.1% of 41 with sequencing data) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, 76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of the ChAdOxl nCoV-19 vaccine did not show protection against mild-to-moderate Covid49 due to the B.1.351 variant. [ABSTRACT FROM AUTHOR]

This study reviews the impact of eligibility policies in the early rollout of the COVID-19 vaccine on coverage and probable outcomes, with a focus on New York City. We conducted a retrospective ecological study assessing age  65+, area-level income, vaccination coverage, and COVID-19 mortality rates, using linked Census Bureau data and New York City Health administrative data aggregated at the level of modified zip code tabulation areas (MODZCTA). The population for this study was all individuals in 177 MODZCTA in New York City. Population data were obtained from Census Bureau and New York City Health administrative data. The total mortality rate was examined through an ordinary least squares (OLS) regression model, using area-level wealth, the proportion of the population aged 65 and above, and the vaccination rate among this age group as predictors. Low-income areas with high proportions of older people demonstrated lower coverage rates (mean vaccination rate 52.8%; maximum coverage 67.9%) than wealthier areas (mean vaccination rate 74.6%; maximum coverage 99% in the wealthiest quintile) in the first 3 months of vaccine rollout and higher mortality over the year. Despite vaccine shortages, many younger people accessed vaccines ahead of schedule, particularly in high-income areas (mean coverage rate 60% among those 45-64 years in the wealthiest quintile). A vaccine program that prioritized those at greatest risk of COVID-19-associated morbidity and mortality would have prevented more deaths than the strategy that was implemented. When rolling out a new vaccine, policymakers must account for local contexts and conditions of high-risk population groups. If New York had focused limited vaccine supply on low-income areas with high proportions of residents 65 or older, overall mortality might have been lower., (© 2024. The Author(s).)

Background: Rectovaginal group B Streptococcus (GBS) colonisation in pregnant individuals at the time of labour is a major risk factor for invasive GBS disease by age 7 days (early-onset disease). We aimed to investigate the prevalence of rectovaginal GBS colonisation at the time of labour among pregnant women and vertical transmission to their newborns across selected low-income and middle-income African and south Asian countries., Methods: This prospective, observational study was undertaken at 11 maternity and obstetric care facilities based in Ethiopia, Kenya, Mozambique, Nigeria, Mali, South Africa, Bangladesh, India, and Bhutan. HIV-negative pregnant women aged 18-45 years who were in the early stages of labour and at least 37 weeks' gestation were eligible for inclusion. Lower vaginal and rectal swabs and urine were collected from the women, and swabs of the umbilicus, outer ear, axillary fold, rectum, and throat were obtained from their newborns, for GBS culture. Standardised sampling and culture using direct plating and selective media broth for detection of GBS colonisation was undertaken at the sites. Serotyping of GBS isolates was done in South Africa. The primary outcome was the prevalence of rectovaginal GBS among pregnant women, analysed in participants with available data. This study is registered with the South African National Clinical Trials Register, number DOH-27-0418-4989., Findings: 6922 pregnant women were enrolled from Jan 10, 2016, to Dec 11, 2018, of whom 6514 (94·1%; 759-892 per country) were included in the analysis; data from Bhutan were not included in the study due to issues with specimen collection and processing. Overall, the prevalence of maternal GBS colonisation was 24·1% (95% CI 23·1-25·2; 1572 of 6514); it was highest in Mali (41·1% [37·7-44·6]; 314 of 764) and lowest in Ethiopia (11·6% [9·5-14·1]; 88 of 759). The overall rate of vertical transmission of GBS from women with rectovaginal GBS colonisation was 72·3% (70·0-74·4; 1132 of 1566); it was highest in Mozambique (79·2% [73·3-84·2]; 168 of 212) and lowest in Bangladesh (55·8%, 47·5-63·8; 77 of 138). The five most common GBS colonising serotypes were Ia (37·3% [34·9-39·7]; 586 of 1572), V (28·5% [26·3-30·8]; 448 of 1572), III (25·1% [23·0-27·3]; 394 of 1572), II (9·2% [7·8-10·7]; 144 of 1572), and Ib (6·5% [5·4-7·8]; 102 of 1572). There was geographical variability in serotype proportion distribution; serotype VII was the third most common serotype in India (8·6% [5·3-13·7]; 15 of 174) and serotype VI was mainly identified in Bangladesh (5·8% [3·0-11·0]; eight of 138) and India (5·7% [3·2-10·3]; ten of 174)., Interpretation: Our study reported a high prevalence of GBS colonisation in most settings, with some geographical variability even within African countries. Our findings suggest that serotypes not included in current multivalent capsular-polysaccharide GBS vaccines prevail in some regions, so vaccine efficacy and post-licensure effectiveness studies should assess the effect of vaccination on maternal GBS colonisation given the potential for replacement by non-vaccine serotypes., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SAM declares grant funding to his institution for research on GBS, separate from this study, from Pfizer, GlaxoSmithKline, and Minervax. GK declares grant funding to his institution for research on GBS from the Bill & Melinda Gates Foundation and PATH. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design., (© 2024. The Author(s).)

In combatting COronaVIrus Disease 2019 (COVID-19), immunization is the most prominent strategy. However, vaccination hesitancy-meaning delays in accepting or denying inoculation regardless of availability-has been identified as an essential threat to global health. Attitudes and perceptions play a pivotal role in vaccine acceptability. Meanwhile, uptake in South Africa's rollout has been particularly disappointing among youths. For that reason, we explored attitudes and perceptions of COVID-19 in 380 youths in Soweto and Thembelihle, South Africa, between April and June 2022. A staggering hesitancy rate of 79.2 percent was recorded (301/380). We found negative attitudes and confounded perceptions of COVID-19 to be fueled by medical mistrust and misinformation, with online channels as the main sources of non- and counterfactual claims stemming mostly from unregulated social media popular with youths. Understanding its underpinnings-and enhancing means of curbing vaccine hesitancy-will be paramount in boosting uptake in South Africa's immunization program, particularly among youths.

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.)

Vaccines against SARS-CoV-2 have been pivotal in overcoming the COVID-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g., people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibody-mediated angiotensin converting enzyme 2 (ACE2) binding blockade, against the SARS-CoV-2 spike (S) proteins after 1 and 2 doses of the ChAdOx1 nCoV-19 vaccine in a population of Black PLWH. Here, we report that PLWH (N = 103) did not produce an anti-S IgA response after infection or vaccination, however, anti-S IgG was detected in response to vaccination and infection, with the highest level detected for infected vaccinated participants. The anti-IgG and ACE2 blockade assays revealed that both vaccination and infection resulted in IgG production, however, only vaccination resulted in a moderate increase in ACE2 binding blockade to the ancestral S protein. Vaccination with a previous infection results in the greatest anti-S IgG and ACE2 blockade for the ancestral S protein. In conclusion, PLWH produce an anti-S IgG response to the ChAdOx1 nCoV-19 vaccine and/or infection, and ChAdOx1 nCoV-19 vaccination with a previous infection produced more neutralizing antibodies than vaccination alone.

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.)

Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-287/coif). CF has received honoraria for participation in Advisory Boards and Speaker’s Bureaus for MSD and Pfizer. CF reports that the development of this document and its recommendations was funded by an unrestricted educational grant from Pifzer to the Federation of Infectious Diseases Societies of Southern Africa. SD has received payment for Speaker’s Bureaus for the following organizations in the last 36 months, Pfizer, MSD, ABBVIE, and SANOFI. All these speaker activities were for educational meetings or conferences. In addition, SD has participated in Advisory Board for the following organizations, MSD, ViiV, Health/GSK, Adcock Ingram and Jansen. GAR has received honoraria for Speaker’s Bureaus from Pfizer and MSD-None recently however. MM has acted on the speaker’s bureaus of MSD, Pfizer, J&J, Aspen, Mylan and Cipla, and on the Advisory Boards of Pfizer, MSD, J&J and Mylan, has also received fully paid travel expenses to international conferences and advisory boards, and had leadership or fiduciary roles in SAHIVSOC and AVCS. MYSM has received consulting fees from Johnson & Johnson, Cipla, MSD, ViiV, 360 pharmaceuticals and Mylan, and participated on data safety monitoring boards or advisory boards for EnACT, NTZ versus SOF/DCV Study, and The CARES Study, and acts on the Southern African HIV Clinicians Society. JP has received speaker’s fees from Sanofi, Novartis and Janssen, and participated on the advisory board for Sanofi. CvV has acted on the Speaker’s Bureaus of Mylan and Viatris. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background: Preeclampsia is a considerable cause of maternal and infant morbidity and mortality. Although its etiology is unknown, preeclampsia has been described as a state of exaggerated maternal inflammatory response. Therefore, it has been hypothesized that preeclampsia would occur less commonly in states of immune deficiency., Objective: This study aimed to compare the prevalence of treated and untreated HIV infections among preeclamptic cases and controls, determine infant outcomes, and evaluate the association between HIV and preeclampsia after adjusting for known predictor variables, including maternal age, gravidity, body mass index, and smoking., Study Design: This case-control study investigated the association between preeclampsia and HIV infection using secondary data from an unrelated study. We defined preeclamptic cases as pregnant women who were normotensive until 20 weeks of gestation and thereafter had at least 1 high blood pressure measurement either before or at delivery and proteinuria, defined as protein excretion of ≥300 mg within 24 hours or >2 protein on dipstick urinalysis. The prevalence of HIV infection was compared between cases and controls. Multivariate logistic regression analysis was used to assess the association between preeclampsia and potential confounding variables and reported using odds ratios and 95% confidence intervals., Results: There were 571 cases with preeclampsia and 596 normotensive controls included in this study. The median age was 27 years for cases and 26 years for controls ( P =.008). Most participants (69%) had ≥2 previous pregnancies with no difference between the cases and controls ( P =.176). Overall, 43% of the participants were obese, with a mean body mass index of 29 (interquartile range, 24.5-34.2), with higher proportions of women who were overweight and obese in the group with preeclampsia ( P =.031). The prevalence of HIV was significantly lower in cases than in controls (24% vs 30%, respectively; P =.014). Compared with 16% of infants born preterm to normotensive controls, 48% of infants were born preterm born to women with preeclampsia ( P <.001). Compared with 14% of infants born with low birthweight to normotensive controls, 53% of infants were born with low birthweight to women with preeclampsia ( P <.0001). Untreated HIV infection was negatively associated with preeclampsia (unadjusted odds ratio, 0.330; 95% confidence interval, 0.197-0.552; P <.0001), whereas factors associated with preeclampsia were advanced maternal age (odds ratio, 1.673; 95% confidence interval, 1.209-2.316; P =.002) and obesity (odds ratio, 1.611; 95% confidence interval, 1.023-2.537; P =.040). After adjusting for maternal age, gravidity, smoking, and body mass index in the multivariate regression, only obesity remained significantly associated with preeclampsia (adjusted odds ratio, 1.624; 95% confidence interval, 1.024-2.575; P =.039)., Conclusion: Before the large-scale rollout of antiretroviral therapy in a setting with a high burden of HIV and preeclampsia, untreated HIV infection was found to have a protective effect against preeclampsia. The protective effect against preeclampsia was not apparent for HIV infection treated with antiretroviral therapy., (© 2022 The Authors.)

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.)

Despite the significant benefits of maternal immunisation, uptake remains low in many parts of the world. In this qualitative study, we aimed to assess the factors that influence pregnant women's decision to engage with maternal immunisation in rural KwaZulu-Natal, South Africa. We conducted in-depth interviews with a total of 28 purposively sampled pregnant women and key informants using semi-structured topic guides. Data analysis was conducted using a modified Health Belief Model framework that included constructs of barriers to action, modifying factors of cue to action and perceived social norms. The findings show that traditional customs and institutional barriers such as low-quality health service delivery, long queues, and distance to the health facilities, immunisation vaccine stockouts and low levels of maternal knowledge influence the choice and decision to engage with maternal immunisation. Understanding health-related behaviours and addressing barriers to care is important in facilitating vaccination uptake. This study contributes to the understanding of maternal immunisation uptake in low-resource settings.

Standardized case definitions strengthen post-marketing safety surveillance of new vaccines by improving generated data, interpretation and comparability across surveillance systems. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project developed standardized case definitions for 21 key obstetric and neonatal terms following the Brighton Collaboration (BC) methodology. In this prospective cohort study, we assessed the applicability of GAIA definitions for maternal immunization exposure and for low birth weight (LBW), preterm birth, small for gestational age (SGA), stillbirth, neonatal death, neonatal infection, and congenital microcephaly. We identified the missing data elements that prevented identified cases and exposures from meeting the case definition (level 1-3 of BC diagnostic certainty). Over a one-year period (2019-2020), all births occurring in 21 sites (mostly secondary and tertiary hospitals) in 6 Low Middle Income Countries and 1 High Income Country were recorded and the 7 perinatal and neonatal outcome cases were identified from routine medical records. Up to 100 cases per outcome were recruited sequentially from each site. Most cases recruited for LBW, preterm birth and neonatal death met the GAIA case definitions. Birth weight, a key parameter for all three outcomes, was routinely recorded at all sites. The definitions for SGA, stillbirth, neonatal infection (particularly meningitis and respiratory infection) and congenital microcephaly were found to be less applicable. The main barrier to obtaining higher levels of diagnostic certainty was the lack of sonographic documentation of gestational age in first or second trimester. The definition for maternal immunization exposure was applicable, however, the highest level of diagnostic certainty was only reached at two sites. Improved documentation of maternal immunization will be important for vaccine safety studies. Following the field-testing of these 8 GAIA definitions, several improvements are suggested that may lead to their easier implementation, increased standardization and hence comparison across studies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christine Guillard Maure reports financial support was provided by Bill & Melinda Gates Foundation., (© 2021 The Authors.)

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., Competing Interests: Competing interests: The authors have completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author), and declare no conflicts of interest. YBN is staff member of the World Health Organization., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Background: Maternal immunization has prevented millions of child deaths globally; nevertheless, incomplete vaccination remains a public health concern in South Africa, where almost half of child deaths occur during neonatal period. This study explored the knowledge and attitudes inhibiting vaccine acceptancy during pregnancy., Methods: Key informant and semi-structured interviews were conducted with pregnant women receiving antenatal care at community clinics, antenatal care staff, women enrolled in maternal immunization trials, community leaders and non-pregnant women residing in Soweto. Focus Group Discussions were also held with the mothers and husbands/partners of the pregnant women (n = 55)., Results: The study established good knowledge, a positive attitude and high acceptability of maternal immunization among pregnant women, non-pregnant women, antenatal staff as well as church and community leaders. Men were the least positive about maternal immunization. Aside from antenatal staff, there was poor knowledge regarding the types of vaccinations administered and the health benefits of immunization across all the study groups. Reasons adduced for poor knowledge about the types of vaccinations include lack of communication on maternal immunization during antenatal sessions or clinic visits and power dynamics that tend to exist between healthcare workers and patients., Conclusion: Ensuring that healthcare workers provide useful information on immunization during antenatal visits as well as include men in education sessions regarding the benefit of vaccination may increase patients' confidence and immunization uptake., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Background: The conserved, immuno-subdominant influenza virus hemagglutinin (HA) stalk region is a potential universal group-specific influenza virus vaccine epitope. We analyzed antibody responses to H1 hemagglutinin stalk domain (H1/stalk) following trivalent influenza inactivated vaccine (IIV3) immunization in pregnant women, and association with protection against influenza virus illness., Methods: One hundred forty-five human immunodeficiency virus (HIV)-uninfected pregnant women (68 IIV3 and 77 placebo recipients) and 140 pregnant women with HIV infection (72 IIV3 and 68 placebo recipients) were independently randomized in placebo-controlled efficacy trials of IIV3. Plasma samples were tested for H1/stalk immunoglobulin G (IgG) and hemagglutination inhibition (HAI) antibodies prevaccination and 1 month postvaccination. Women had weekly surveillance for influenza illness, confirmed by polymerase chain reaction., Results: Increases in H1/stalk IgG (and HAI) antibody levels were elicited post-IIV3, with responses being higher in HIV-uninfected women than in women living with HIV. Among HIV-uninfected vaccinees, there was no correlation (postvaccination) between H1/stalk and HAI antibody responses, whereas a strong correlation was observed in vaccinees with HIV. The H1/stalk IgG concentration was lower among women developing A/H1N1 illness (85.3 arbitrary units [AU]/mL) than those without A/H1N1 illness (219.6 AU/mL; P = .001). H1/stalk IgG concentration ≥215 AU/mL was associated with 90% lower odds (odds ratio, 0.09; P = .005) of A/H1N1 illness. Also, H1/stalk IgG was significantly lower among women with influenza B illness (93.9 AU/mL) than among their counterparts (215.5 AU/mL) (P = .04); however, no association was observed after adjusting for HAI titers., Conclusions: H1/stalk IgG concentration was associated with lower odds for A/H1N1 influenza virus illness, indicating its potential as an epitope for a universal vaccine against group 1 influenza virus., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objectives: Measles infection causes particularly severe disease in young children who, prior to vaccination, are dependent on maternal antibodies for protection against infection. Measles vaccination was introduced into the South African public immunization programme in 1983 and became widely available in 1992. The aim of this study was to determine measles-specific immunoglobulin G (IgG) levels in pregnant women living with and without HIV born before and after measles vaccine introduction in South Africa., Methods: Measles IgG antibody level from blood obtained at the time of delivery was compared between women who were born before 1983 (n = 349) and since 1992 (n = 349). Serum samples were tested for measles IgG antibody using an enzyme-linked immunosorbent assay. Geometric mean titres (GMTs) and the proportion with seronegative (<200 mIU/mL) or seropositive titres (≥275 mIU/mL) were compared., Results: Women born since 1992 had lower GMTs [379.7 mIU/mL (95% CI 352.7-448.6)] and fewer were seropositive (55.9%, 195/349) than women born before 1983 [905.8 mIU/mL (95% CI 784.7-1045.5); 76.8%, 268/349], for both comparisons p < 0.001., Conclusions: We found an association between measles vaccine implementation into the public immunization program in South Africa and peri-partum maternal measles immunity, where women born before vaccine introduction had higher measles IgG antibody titres and were more likely to be seropositive. These findings suggest a need to reconsider the infant measles immunization schedule in settings where women have derived immunity mainly from measles vaccine rather than wild-type virus exposure., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children., Methods: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard., Results: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard., Conclusions: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa.

Summary: HLA*LA implements a new graph alignment model for human leukocyte antigen (HLA) type inference, based on the projection of linear alignments onto a variation graph. It enables accurate HLA type inference from whole-genome (99% accuracy) and whole-exome (93% accuracy) Illumina data; from long-read Oxford Nanopore and Pacific Biosciences data (98% accuracy for whole-genome and targeted data) and from genome assemblies. Computational requirements for a typical sample vary between 0.7 and 14 CPU hours per sample., Availability and Implementation: HLA*LA is implemented in C++ and Perl and freely available as a bioconda package or from https://github.com/DiltheyLab/HLA-LA (GPL v3)., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)

Background: There is a paucity of data on the burden of congenital cytomegalovirus (cCMV) infections in low- and middle-income countries, including their association with maternal human immunodeficiency virus (HIV) infections. We investigated the prevalence of cCMV in a patient population with a high rate of HIV and antiretroviral therapy (ART) use during pregnancy in Soweto, Johannesburg., Methods: Saliva from neonates were screened for cytomegalovirus (CMV) infection by polymerase chain reaction (PCR) at birth. Additional saliva and urine samples were tested within 3 weeks of birth to confirm positive saliva results. HIV PCR testing was done on the whole blood of HIV-exposed neonates. Maternal and neonatal data were extracted from clinical records., Results: Of 2685 neonates screened for cCMV, 828 (31%) were born to HIV-infected women, 95% of whom (790/828) were on ART at delivery. The overall prevalence of cCMV was 2.5% (95% confidence interval [CI] 1.9-3.2), with significantly higher cCMV prevalence in HIV-exposed neonates (5.2%, 95% CI 3.8-6.9) than HIV-unexposed neonates (1.4%, 95% CI 0.9-2.0). The risk of in utero HIV infection was 20-fold greater (odds ratio 20.1, 95% CI 6.09-66.46) in HIV-exposed, cCMV-infected neonates, and this increased risk was not associated with the maternal CD4+ T-cell count or the maternal duration of ART., Conclusions: The prevalence of cCMV in our setting is substantially higher than the global estimate of 0.64%, partly due to the increased susceptibility for cCMV in HIV-exposed neonates. The significantly increased risk of in utero HIV infection in neonates with cCMV indicates that CMV coinfection plays a major role in the residual burden of in utero HIV transmission, even in the era of ART., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)