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BackgroundSAB-185, a novel fully human IgG polyclonal immunoglobulin product, underwent phase 2 evaluation for nonhospitalized adults with mild-moderate coronavirus disease 2019 (COVID-19).MethodsParticipants received intravenous SAB-185 3840 units/kg (low-dose) or placebo, or 10 240 units/kg (high-dose) or placebo. Primary outcome measures were nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA < lower limit of quantification (LLOQ) at study days 3, 7, and 14, time to symptomatic improvement, and safety through day 28.ResultsTwo-hundred thirteen participants received low-dose SAB-185/placebo (n = 107/106) and 215 high-dose SAB-185/placebo (n = 110/105). The proportions with SARS-CoV-2 RNA < LLOQ were higher for SAB-185 versus placebo at days 3 and 7 and similar at day 14, and significantly higher at day 7 for high-dose SAB-185 versus placebo only, relative risk 1.23 (95% confidence interval, 1.01-1.49). At day 3, SARS-CoV-2 RNA levels were lower with low-dose and high-dose SAB-185 versus placebo: differences in medians of -0.78 log10 copies/mL (P = .08) and -0.71 log10 copies/mL (P = .10), respectively. No difference was observed in time to symptom improvement: median 11/10 days (P = .24) for low-dose SAB-185/placebo and 8/10 days (P = .50) for high-dose SAB-185/placebo. Grade ≥3 adverse events occurred in 5%/13% of low-dose SAB-185/placebo and 9%/12% of high-dose SAB-185/placebo.ConclusionsSAB-185 was safe and generally well tolerated and demonstrated modest antiviral activity in predominantly low-risk nonhospitalized adults with COVID-19. Clinical Trials Registration. NCT04518410.

BackgroundThis research prioritization aimed to identify major research gaps in maternal, newborn, child and adolescent health (MNCAH) to help mitigate the direct and indirect effects of the COVID-19 pandemic.MethodsWe adapted the Child Health and Nutrition Research Initiative methodology. We defined scope, domains, themes and scoring criteria. We approached diverse global experts via email to submit their research ideas in MNCAH and MNCAH-related cross-cutting/health systems area. We curated the research ideas as research questions (RQs) and sent them to the consenting experts for scoring via the online link. For each RQ, the research priority score (RPS) was calculated as an average of individual criterion scores and ranked based on RPS in each area.ResultsWe identified top-ranked 10 RQs in each maternal, newborn, and child and adolescent health and 5 in the cross-cutting/health systems area. In maternal health, indirect effects on care, measures to improve care, health risks and outcomes, and preventing and managing SARS-CoV-2 infection/COVID-19 disease were priority RQs. In newborn health, clinical characterization and managing SARS-CoV-2 infection/COVID-19 disease, mode of transmission and interventions to prevent transmission were the focus. For child and adolescent health, top-ranked RQs were indirect effects on care, clinical status and outcomes, interventions to protect against SARS-CoV-2 infection/COVID-19 disease, and educational institute-related RQs. The cross-cutting RQs were the effects of the pandemic on availability, access, care-seeking and utilization of MNCAH services and potential solutions.ConclusionsWe call on partners, including governments, non-governmental organizations, research institutes, and donors, to address this urgent research agenda.

Background: This exploratory analysis investigates the prevalence and risk factors of neurocognitive toxicity in postpartum women on HIV treatment in response to a concern of an Isoniazid Preventive Therapy (IPT)/Efavirenz interaction. Trial Design: Pregnant women on HIV treatment from countries with high TB prevalence were randomized in IMPAACT P1078 to 28 weeks of IPT started either during pregnancy or at 12 weeks postpartum. Partway through study implementation, the Patient Health Questionnaire 9, the cognitive complaint questionnaire, and the Pittsburg Sleep Quality Index were added to evaluate depression, cognitive function, and sleep quality at postpartum weeks. Screening for peripheral neuropathy was conducted throughout the study. Methods: We summarized percentages of women with depression symptoms, cognitive dysfunction, poor sleep quality and peripheral neuropathy and assessed the association of 11 baseline risk factors of neurotoxicity using logistic regression, adjusted for gestational age stratum. Results: Of 956 women enrolled, 749 (78%) had at least one neurocognitive evaluation. During the postpartum period, the percentage of women reporting at least mild depression symptoms, cognitive complaint and poor sleep quality peaked at 13%, 8% and 10%, respectively, at 12 weeks, and the percentage of women reporting peripheral neuropathy peaked at 13% at 24 weeks. There was no evidence of study arm differences in odds of all four neurotoxic symptoms. Conclusions: Timing of IPT initiation and EFV use were not associated with symptoms of neurotoxicity. Further study is advised to formally assess risk factors of neurotoxicity. [ABSTRACT FROM AUTHOR]

The continued occurrence of congenital syphilis is an indictment of the inadequate antenatal care services and poor quality of programmes to control sexually transmitted infections. More than 1 million infants are born with congenital syphilis each year. Despite national policies on antenatal testing and the widespread use of antenatal services, syphilis screening is still implemented only sporadically in many countries, leaving the disease undetected and untreated among many pregnant women. The weak organization of services and the costs of screening are the principal obstacles facing programmes. Decentralization of antenatal syphilis screening programmes, on-site testing and immediate treatment can reduce the number of cases of congenital syphilis. Antenatal syphilis screening and treatment programmes are as cost effective as many existing public health programmes, e.g. measles immunization. Diagnosis of congenital syphilis is problematic since more than half of all infants are asymptomatic, and signs in symptomatic infants may be subtle and nonspecific. Newer diagnostic tests such as enzyme immunoassays, polymerase chain reaction and immunoblotting have made diagnosis more sensitive and specific but are largely unavailable in the settings where they are most needed. Guidelines developed for better-resourced settings are conservative and err on the side of overtreatment. They are difficult to implement in, or inappropriate for, poorly-resourced settings because of the lack of investigative ability and the pressure on health facilities to discharge infants early. This paper offers recommendations for treating infants, including an approach based solely on maternal serological status and clinical signs of syphilis in the infant.

OBJECTIVE: To investigate the problems, benefits, feasibility, and sustainability of implementation of WHO guidelines on management of severe malnutrition. METHODS: A postal survey invited staff from 12 African hospitals to participate in the study. Five hospitals were evaluated and two were selected to take part in the study: a district hospital in South Africa and a mission hospital in Ghana. At an initial visit, an experienced paediatrician reviewed the situation in the hospitals and introduced the principles of the guidelines through a participatory approach. During a second visit about six months later, the paediatrician reviewed the feasibility and sustainability of the introduced changes and helped find solutions to problems. At a final visit after one year, the paediatrician reassessed the overall situation. FINDINGS: Malnutrition management practices improved at both hospitals. Measures against hypoglycaemia, hypothermia, and infection were strengthened. Early, frequent feeding was established as a routine practice. Some micronutrients for inclusion in the diet were not locally available and needed to be imported. Problems were encountered with monitoring of weight gain and introducing a rehydration solution for malnutrition. CONCLUSION: Implementation of the main principles of the WHO guidelines on severe malnutrition was feasible, affordable, and sustainable at two African hospitals. The guidelines could be improved by including suggestions on how to adapt specific recommendations to local situations. The guidelines are well supported by experience and published reports, but more information is needed about some components and their impact on mortality.

The Integrated Management of Childhood Illness (IMCI) strategy has been adopted by 102 countries including South Africa, as the preferred primary health care (PHC) delivery strategy for sick children under 5 years. Despite substantial investment to support IMCI in South Africa, its delivery remains sub-optimal, with varied implementation in different settings. There is scarce research globally, and in the local context, examining the effects of health system characteristics on IMCI implementation. This study explored key determinants of IMCI delivery in a South African province, with a specific focus on health system building blocks using a health system dynamics framework. In-depth interviews were conducted with 38 districts, provincial and national respondents involved with IMCI co-ordination and delivery, exploring their involvement in, and perceptions of, IMCI strategy implementation. Identified barriers included poor definition of elements of a service package for children and how IMCI aligned with this, incompetence of trained nurses exacerbated by inappropriate rotation practices, use of inappropriate indicators to track progress, multiple cadres coordinating similar activities with poor role delineation, and fragmented, vertical governance of programmes included within IMCI, such as immunization. Enabling practices in one district included the use of standardized child health records incorporating IMCI activities and stringent practice monitoring through record audits. Using IMCI as a case study, our work highlights critical health system deficiencies affecting service delivery for young children which need to be resolved to reposition IMCI within the broader child 'survive, thrive and transform' agenda. Recommendations for appropriate health system strengthening include the need for redefining IMCI within a broader PHC service package for children, prioritizing post-training supervision and mentoring of practitioners through appropriate duty allocation and rotation policies, strengthening IMCI monitoring with a specific focus on quality of care and building stronger clinical governance through workforce allocation, role delineation and improved accountability. [ABSTRACT FROM AUTHOR]