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Background: In Malawi, the national pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than the USA, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any other serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy., Methods: Healthy adults aged 18-40 were randomly assigned PCV13 (n=98) or saline (n=106), followed by intranasal SPN 6B inoculation at 20,000 (n=40), 80,000 (n=74), or 160,000 (n=90) CFU/100µl, 28 days post-vaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 post-inoculation using culture and multiplex qPCR targeting lytA/cpsA genes and compared carriage rates by vaccination status., Results: Of 204 participants, 19.6% (40) exhibited experimental carriage, detected by culture and 25.5% (52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n=10/98) compared to the placebo group (28.3%, n=30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13=8% n=6/75 vs. placebo=25.9%, n=21/81) compared to those with natural carriage (PCV13=14.8%, n=4/27 vs. placebo=26.5%, n=9/34). Using a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had a lower VE of 52% compared to participants with no natural carriage (VE=69%)., Conclusion: We have shown that PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers compared to those without natural carriage at the inoculation visit., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Pneumococcal carriage is the primary reservoir for transmissionand a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage., Methods: We vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA)., Results: PCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not., Conclusion: This study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier India Pvt Ltd. All rights reserved.)

Background: As well as suffering a high burden of pneumococcal disease people living with HIV (PLHIV) may contribute to community transmission in sub-Saharan African (sSA) settings. Pneumococcal vaccination is not currently offered to PLHIV in sSA but may prevent disease and reduce transmission. More evidence of vaccine effectiveness against carriage in PLHIV is needed. An Experimental Human Pneumococcal Carriage model (EHPC) has been safely and acceptably used in healthy adults in Malawi to evaluate pneumococcal vaccines against carriage and to identify immune correlates of protection from carriage. This study will establish the same model in PLHIV and will be the first controlled human infection model (CHIM) in this key population. Methods: Healthy participants with and without HIV will be inoculated intranasally with Streptococcus pneumoniae serotype 6B. Sequential cohorts will be challenged with increasing doses to determine the optimal safe challenge dose to establish experimental carriage. Nasal fluid, nasal mucosal, and blood samples will be taken before inoculation and on days 2, 7, 14, and 21 following inoculation to measure pneumococcal carriage density and identify immune correlates of protection from carriage. The vast majority of natural pneumococcal carriage events in PLHIV do not result in invasive disease and no invasive disease is expected in this study. However, robust participant safety monitoring is designed to identify signs of invasive disease early should they develop, and to implement treatment immediately. Participants will complete a Likert-style questionnaire at study-end to establish acceptability. Interpretations: We expect the EHPC model to be safely and acceptably implemented in PLHIV. The CHIM can then be used to accelerate pneumococcal vaccine evaluations in this population, and an evidence-based pneumococcal vaccination policy for PLHIV in sSA., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Doherty K et al.)

Background: The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage., Methods: We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18-40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed., Findings: Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7-80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci., Interpretation: This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination., Funding: Wellcome Trust., Competing Interests: Declaration of interests DF declares grant funding from Pfizer to her institution for separate projects and consulting fees from Pfizer, MSD, and Sanofi. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens., Methods: The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests., Results: Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3., Conclusion: Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations., Clinical Trial Registration: ClinicalTrials.gov , NCT01061151., Competing Interests: Financial Disclosure Debika Bhattacharya reports research support from the National Institutes of Health for the submitted work. She also reports research support from Gilead Sciences and clinical trial support from AbbVie and Regeneron, outside the submitted work. Marion G. Peters reports personal fees from Wainright, Silberback, Excision BioTherapeutics, Aligos, and Antios, as well as spousal employment with Roche, outside the submitted work. Camlin Tierney reports grants from the NIH during the conduct of the study. Mary Glenn Fowler reports IMPAACT Leadership LOC support for the present manuscript. Judith S. Currier reports research support from Resverologix and Merck and Company outside the submitted work. Vani Govender reports support from DAIDS. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

There is a high burden of critical illness in low-income countries (LICs), adding pressure to already strained health systems. Over the next decade, the need for critical care is expected to grow due to ageing populations with increasing medical complexity; limited access to primary care; climate change; natural disasters; and conflict. In 2019, the 72nd World Health Assembly emphasised that an essential part of universal health coverage is improved access to effective emergency and critical care and to "ensure the timely and effective delivery of life-saving health care services to those in need". In this narrative review, we examine critical care capacity building in LICs from a health systems perspective. We conducted a systematic literature search, using the World Heath Organisation (WHO) health systems framework to structure findings within six core components or "building blocks": (1) service delivery; (2) health workforce; (3) health information systems; (4) access to essential medicines and equipment; (5) financing; and (6) leadership and governance. We provide recommendations using this framework, derived from the literature identified in our review. These recommendations are useful for policy makers, health service researchers and healthcare workers to inform critical care capacity building in low-resource settings., (© 2023. The Author(s).)

Knowing the target oxygen saturation (SpO 2 ) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO 2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO 2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO 2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO 2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO 2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO 2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Herbst, Goel, Beane, Brotherton, Dula, Ely, Gordon, Haniffa, Hedt-Gauthier, Limbani, Lipnick, Lyon, Njoki, Oduor, Otieno, Pisani, Rylance, Shrime, Uwamahoro, Vanderburg, Waweru-Siika, Twagirumugabe and Riviello.)

Background: Neural tube closure defect (NTD) such as spinal bifida and anencephaly are serious neurological disabilities that occur when the neural tube does not close completely within 28 days of conception. Even though Folic acid supplementation during and before pregnancy is proved to significantly reduces the risk of NTDs. Currently only 23% of folic acid preventable NTD achieved Worldwide; mainly due to lack of awareness about folic acid supplementation. This study was aimed to assess the knowledge of Folic acid supplementation among pregnant women attending antenatal care at public health facilities in Hawassa Ethiopia., Methods: Institution based cross-sectional study was employed among 358 pregnant women attending antenatal care. Data were collected using an interviewer-administered structured questionnaire and analyzed using SPSS version 22. The knowledge of Folic acid supplementation was assessed using six multiple-choice questions. The association between the dependent and independent variables were analyzed using Binary Logistic regression model and statistically significant predictors at p-value <.05 at 95% CI., Results: This study indicated that only 7.5% (95% CI, 5.3-10.1) of pregnant women had good knowledge of Folic acid supplementation. The pregnant women who had a history of at least one previous pregnancy loss AOR = 12.64 (95% CI: 4.98, 32.08) and those who had preconception consultation AOR = 11.77 (95% CI: 3.01, 46.07) were more likely to have good knowledge of periconceptional folic acid supplementation as compared to their counterpart., Conclusions: The knowledge of periconceptional folic acid supplementation among pregnant women was worryingly low in the study area. Alternative and more effective strategies are needed if the population of Ethiopia is to benefit fully from the folic acid prevention of NTDs. Thus, in Ethiopia the future strategies should focus on the possible way to reach the last group through fortification of staple foods with folic acid along with improving women's awareness on folic acid importance in reducing Neural tube defects., (© 2023 Wiley Periodicals LLC.)

Background: Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome., Methods: We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinION™ in Blantyre., Results: We enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen (22.7% [17/75] vs. 58.6% [140/239], p < 0.001) and steroids (38.7% [29/75] vs. 70.3% [167/239], p < 0.001) in the Omicron wave compared with the other waves. Multivariable logistic-regression demonstrated a trend toward increased mortality in the Delta wave (OR 4.99 [95% CI 1.0-25.0 p = 0.05) compared to the first wave of infection., Conclusions: Our data show that each wave of patients hospitalised with SARS-CoV-2 was infected with a distinct viral variant. The clinical data suggests that patients with severe COVID-19 disease were more likely to die during the Delta wave., (© 2023. The Author(s).)

Background: There are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV., Methods: The PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly., Results: Of 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc )., Conclusion: With HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring., Competing Interests: D.B. and F.M. report research grant support from Gilead Sciences Inc, under award numbers IN-US-987-5950 and GPHA 07844 respectively). M.G.P. has been a consultant to Aligos and Antios. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health (NIH), under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), and by NICHD contract number HHSN275201800001I. Additional funding from NIAID UM1AI069465 to A.G., NIAID R01 01AI100748-01 and NICHD R01 HD085862 to D.B. Study products were provided free by AbbVie, Gilead Sciences, Boehringer Ingelheim, and ViiV/GlaxoSmithKline. Award Numbers UM1AI068632-15 (IMPAACT LOC), UM1AI068616-15 (IMPAACT SDMC) and UM1AI106716-15 (IMPAACT LC), and by NICHD contract number HHSN275201800001I. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The other authors have no conflicts of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome., Methods: We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinIONâ"¢ in Blantyre., Results: We enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen (22.7% [17/75] vs. 58.6% [140/239], p<0.001) and steroids (38.7% [29/75] vs. 70.3% [167/239], p<0.001) in the Omicron wave compared with the other waves. Multivariable logistic-regression demonstrated a trend toward increased mortality in the Delta wave (OR 4.99 [95% CI 1.0-25.0 p=0.05) compared to the first wave of infection., Conclusions: Our data show that each wave of patients hospitalised with SARS-CoV-2 was infected with a distinct viral variant. The clinical data suggests that patients with severe COVID-19 disease were more likely to die during the Delta wave., Summary: We used genome sequencing to identify the variants of SARS-CoV-2 causing disease in Malawi, and found that each of the four waves was caused by a distinct variant. Clinical investigation suggested that the Delta wave had the highest mortality.

Background: In less well-resourced settings, where access to radiology services is limited, point-of-care ultrasound (POCUS) can be used to assess patients and guide clinical management. The aim of this study was to describe ultrasound practice in the assessment of medical inpatients at Queen Elizabeth Central Hospital, Blantyre, Malawi, and evaluate uptake and impact of POCUS following the introduction of a training programme at the college of Medicine, Blantyre, Malawi., Methods: : A weekly prospective record review of sequential adult medical inpatients who had received an ultrasound examination was conducted., Results: Of 835 patients screened, 250 patients were included; 267 ultrasound examinations were performed, of which 133 (50%) were POCUS (defined as performed by a clinician at the bedside). The time from request to performance of examination was shorter for POCUS examinations than radiology department ultrasound (RDUS) (median 0 [IQR 0-2, range 0-11] vs 2 [IQR 1-4, range 0-15] d, p=0.002); 104/133 (78.2%) POCUS and 90/133 (67.7%) RDUS examinations were deemed to have an impact on management., Conclusion: Following the introduction of a training programme in POCUS, half of all ultrasound examinations were delivered as POCUS. POCUS was performed rapidly and impacted on patient management. POCUS may relieve the burden on radiology services in less well-resourced settings., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background : Recent studies show that ART is associated with an adverse birth outcome in HIV-infected women. Aim : To compare rates of low birthweight (LBW) and preterm birth (PTB) between HIV-infected women receiving lifelong ART and HIV-uninfected women giving birth in low- and high-risk settings in Malawi. Methods : This observational, registry study was conducted from January 2016 to August 2017 in one large, tertiary referral hospital and four primary healthcare (PHC) facilities in Blantyre, Malawi. Women who delivered singleton live births or stillbirths of ≥20 weeks gestation were included in the analysis. Descriptive and stratified analyses were conducted using χ 2 tests and multivariable logistic models to control for maternal age, gravidity and health facility. Results : A total of 14,233 births were included in the analysis (7715 from the tertiary hospital and 6518 from PHC facilities). In the univariable analysis, there were no differences in rates of LBW (6.7% vs 6.4%) and PTB (42.5% vs 42.0%) between HIV-infected and -uninfected women delivering in PHC facilities. However, differences in LBW were significantly higher in HIV-infected women in multivariable analysis (LBW aOR 1.40, 95% CI 1.01-1.95). Rates of LBW and PTB were significantly higher in HIV-infected women than in uninfected women delivering at the tertiary hospital (LBW 17.6% vs 13.2%, aOR 1.53, 95% CI 1.27-1.85; PTB 28.2% vs 24.9%, aOR 1.37, 95% CI 1.17-1.60) Conclusion : Rates of adverse birth outcomes are significantly higher in HIV-infected women than in HIV-uninfected women, and this is more apparent in high-risk hospital settings than in low-risk PHC settings.

Background: Severe hepatotoxicity in people with human immunodeficiency virus (HIV) receiving efavirenz (EFV) has been reported. We assessed the incidence and risk factors of hepatotoxicity in women of childbearing age initiating EFV-containing regimens., Methods: In the Promoting Maternal and Infant Survival Everywhere (PROMISE) trial, ART-naive pregnant women with HIV and CD4 count ≥ 350 cells/μL and alanine aminotransferase ≤ 2.5 the upper limit of normal were randomized during the antepartum and postpartum periods to antiretroviral therapy (ART) strategies to assess HIV vertical transmission, safety, and maternal disease progression. Hepatotoxicity was defined per the Division of AIDS Toxicity Tables. Cox proportional hazards models were constructed with covariates including participant characteristics, ART regimens, and timing of EFV initiation., Results: Among 3576 women, 2435 (68%) initiated EFV at a median 121.1 weeks post delivery. After EFV initiation, 2.5% (61/2435) had severe (grade 3 or higher) hepatotoxicity with an incidence of 2.3 (95% confidence interval [CI], 2.0-2.6) per 100 person-years. Events occurred between 1 and 132 weeks postpartum. Of those with severe hepatotoxicity, 8.2% (5/61) were symptomatic, and 3.3% (2/61) of those with severe hepatotoxicity died from EFV-related hepatotoxicity, 1 of whom was symptomatic. The incidence of liver-related mortality was 0.07 (95% CI, .06-.08) per 100 person-years. In multivariable analysis, older age was associated with severe hepatotoxicity (adjusted hazard ratio per 5 years, 1.35 [95% CI, 1.06-1.70])., Conclusions: Severe hepatotoxicity after EFV initiation occurred in 2.5% of women and liver-related mortality occurred in 3% of those with severe hepatotoxicity. The occurrence of fatal events underscores the need for safer treatments for women of childbearing age., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Abstract: IMPAACT PROMISE 1077BF/FF was a sequentially randomized study of pregnant and postpartum women living with HIV to investigate the efficacy and safety of antiretroviral therapy (ART). This Maternal Health Component investigated efficacy for the risk of developing AIDS or death; and safety among women randomized to continue ART (CTART: N = 289) or discontinue ART (N = 268) after cessation of breastfeeding or after confirmation of infant infection. No AIDS-defining illnesses were reported during follow-up in either arm. Adverse events of grade 3 or higher were more frequent in the CTART arm [hazard ratio = 1.78, 95% confidence interval: (1.05 to 3.02), P-value = 0.03]. The difference in adverse events in the 2 groups was mostly driven by moderate weight loss for women on the CTART arm., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cancer has become one of the most common and the second leading cause of death. According to grounded theory, quality care is meeting all the needs of the patients. Low-quality nursing care relates omission of nursing care required to meet patients' need. Quality of nursing care in oncologic setting was nursing practice area where studies are limited., Objective: The aim of the study was to assess the perceived quality of nursing care among patients with cancer attending Hawassa University comprehensive specialized Hospital., Methods: A quantitative Cross-sectional study was conducted. Among the proposed 422 patients with cancer, using a simple random sampling technique 415 patients were included in this study. Seven data were discarded due to incompleteness and inconsistency between collected data and patient medical record. Data were collected using structured questionnaires and Quality of Oncology Nursing Care Scale. We carried out statistical analysis using SPSS V-20. We used descriptive analysis to examine the quality of oncology nursing care., Results: The mean age of patients was 42.51 (±14.24) years, among patients diagnosed with cancer more than one-third 148 (35.70%) had breast cancer. The majority of patients with cancer 173 (41.70%) were in stage-III. Nearly two-third 266 (64.10%) of patients were on chemotherapy. Among study participants on treatment, 249 (60.00%) perceived they received good quality of nursing care. The mean score related to the domain of support and confirmation is 62.73 ± 7.26. In terms of spiritual care, the mean score is 21.03 ± 5.37., Conclusion: The perceived quality of nursing care was high however not all domains of oncology care were achieved. We recommend Detail and focused study to explore important predictors' quality nursing care., Competing Interests: All authors declare that they have no conflicts of interest for this work., (© 2021 Deribe et al.)

Background: Adverse pregnancy outcomes such as preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA) remain major global problems. We compared pregnancy outcomes among HIV-infected women receiving antiretroviral treatment (ART) and with CD4 ≥350 cells, and HIV-uninfected women to assess whether disparities associated with HIV infection have been eliminated through use of ART., Setting: Observational study conducted at 5 health facilities in Blantyre, Malawi, during 2016-2017., Methods: HIV-infected women receiving the national ART regimen (efavirenz + lamivudine + tenofovir) and HIV-uninfected women were consented and enrolled at delivery. Data collected included sociodemographic and clinical; gestational age; BW; infant/maternal anthropometry; and laboratory results. We defined PTB as GA <37 weeks; LBW as BW <2·5 kg; and SGA as BW <10th percentile of GA. SGA infants were classified into proportionate and disproportionate based on ponderal index. Descriptive, stratified, and multivariate logistic and linear regression analyses were used., Results: Of 5423 women approached, 614 HIV-infected and 685 HIV-uninfected women were enrolled. Rates of PTB, LBW, and SGA were 10.6%, 7.2%, and 17.1% among HIV-infected women on ART and 9.5%, 5.0%, and 18.4% among HIV-uninfected women, respectively. None of these differences were statistically significant in univariate- or multivariate-adjusted analyses (P > 0.05). Of 231 SGA infants, 78.8% were proportionate and 21% were disproportionate. Of the 614 HIV-infected women on ART, 75% had undetectable virus at delivery., Conclusions: ART use has reduced the high rates of adverse pregnancy outcomes among HIV-infected women. However, the rates remain high irrespective of HIV infection and require appropriate interventions.

Background: IMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4+ T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery., Methods: Women with pre-ART CD4+ cell counts ≥350 cells/mm 3 who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat., Findings: 1611 women were enrolled (June 2011-October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4+ count 728 cells/mm 3 and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p = 0.37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p = 0.01). The arms did not differ with respect to the rate of grade 2, 3, or 4 safety events (p = 0.61)., Interpretation: Serious clinical events were rare among predominately breastfeeding women with high CD4+ cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.

Pott puffy tumor is an osteomyelitis of the frontal bone with the development of a subperiosteal abscess manifesting as a puffy swelling of the forehead or scalp. It is believed to occur as a complication of frontal sinusitis. The modern antibiotic era has made it a rarely encountered entity. This case describes a 4-year-old boy who presented in status epilepticus secondary to Pott puffy tumor.