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Abstract Background Tuberous sclerosis complex (TSC) is a rare multisystem disorder caused by mutations in the TSC1 or TSC2 gene. More than 90% of patients with TSC develop neurological and/or neuropsychiatric manifestations. The aim of the present study was to determine the developmental and cognitive long-term outcomes of pediatric TSC patients. Methods This cross-sectional, monocenter study included pediatric TSC patients who received multidisciplinary long-term care with a last visit between 2005 and 2019. Neurological manifestations and cognitive development (BSID, K-ABC) were analyzed in relation to age and type of mutation. Results Thirty-five patients aged 13.5 ± 7.8 years were included in the study. Diagnosis was confirmed genetically in 65.7% of patients (TSC1, 26.1%; TSC2, 65.2%; NMI, 8.7%). Mean age at diagnosis was 1.3 ± 3.5 years; 74.3% of the patients had been diagnosed within the first year of life due to seizures (62.9%) or/and cardiac rhabdomyomas (28.6%). The most common TSC manifestations included structural brain lesions (cortical tubers, 91.4%; subependymal nodules, 82.9%), epilepsy (85.7%), and cardiac rhabdomyomas (62.9%). Mean age at seizure onset was 1.5 ± 2.3 years, with onset in 80.0% of patients within the first two years of life. Infantile spasms, which were the first seizure type in 23.3% of the patients, developed earlier (0.6 ± 0.4 years) than focal seizures (1.8 ± 2.5 years). Refractory epilepsy was present in 21 (70.0%) patients, mild or severe intellectual impairment in 66.6%, and autism spectrum disorders in 11.4%. Severe cognitive impairment (33.3%) was significantly associated with epilepsy type and age at seizure onset (p

Abstract Background Understanding factors affecting adoption of an innovation is critical to its long-term success. Maternity waiting homes (MWHs) increase access to facility-based delivery in low-resourced settings; yet, quality issues deter utilization of this innovative approach. We sought to understand how attributes that are thought to promote diffusion of innovations (e.g., relative advantage, compatibility, observability, complexity, etc.) affected MWH use after implementation of an improved quality MWH model in rural Zambia compared to standard of care. Methods We conducted 158 in-depth interviews (IDIs) with randomly selected rural-living women who had delivered a baby in the prior 12 months. Half lived in catchment areas where new quality MWHs were constructed, half in catchment areas with standard of care (ranging from low quality community structures to no MWH). We applied content analysis to identify themes. Results Utilization of MWHs was higher among intervention (65.4%) than control women (42.5%). Respondents in both study arms perceived relative advantages to pregnant women staying at MWHs compared to going directly to health facilities when labor begins. MWH stays allowed for clinical staff to routinely check on and educate women, and address complications immediately. Compatibility of the homes with cultural values and needs depended on implementation. While some women from intervention sites complained about overcrowding, women in control sites more often perceived the lack of cleanliness, amenities, and safety as deterrents to utilization. Women at intervention sites received sensitization about MWHs from a wider range of sources, including traditional leaders. Required preparations needed to stay at MWHs (e.g. delivery supplies, food, and childcare) made adoption complex and may have deterred utilization. Conclusions The improved MWH model addressed most community concerns around quality. Having opinion leaders who communicate the relative advantage of MWHs to pregnant women and their social networks may facilitate MWH utilization. The complexity of decisions and resources needed to stay at MWHs remains a critical barrier to use. To facilitate equitable adoption of MWHs among the most vulnerable women, planners should explore how to support women during their delivery preparations and MWH stays, particularly regarding food security and lack of social support for childcare. Trial registration clinicaltrials.gov, NCT02620436, Registered 02 December 2015, https://clinicaltrials.gov/study/NCT02620436?term=NCT02620436&rank=1

Antimicrobial resistance (AMR) is a global health challenge and there is increasing recognition of the role of the environment, particularly wastewater, in the development and spread of AMR. Although trace metals are common contaminants in wastewater, the quantitative effects of trace metals on AMR in wastewater settings remain understudied. We experimentally determined the interactions between common antibiotic residues and metal ions found in wastewater and investigated their effects on the development of antibiotic resistance in Escherichia coli over time. These data were then used to expand on a previously developed computational model of antibiotic resistance development in continuous flow settings to incorporate the effects of trace metals acting in combination with multiple antibiotic residues. We found that copper and iron, interact with both ciprofloxacin and doxycycline at wastewater relevant concentrations. This can significantly affect resistance development due to antibiotic chelation of the metal ions causing a reduction in the antibiotics’ bioactivity. Furthermore, modeling the effect of these interactions in wastewater systems showed the potential for metal ions in wastewater to significantly increase the development of antibiotic resistant E. coli populations. These results demonstrate the need to quantitatively understand the effects of trace metal-antibiotic interactions on AMR development in wastewater.

Background Implementation fidelity measures are critical for understanding complex interventions. Though maternity waiting homes (MWHs) are recommended by the WHO and have been used to help pregnant women access health facilities for decades, a gap exists regarding fidelity studies on MWHs. To better understand intervention outcomes results, we assessed the fidelity of implementation of an improved Core MWH Model in 10 facilities in rural Zambia.Methods We analysed indicators for fidelity employing a widely used conceptual framework. We compared performance from October 2016 to July 2018 to goals set out during intervention design. The Core MWH Model consists of three pillars—infrastructure, policies and linkages to care—each designed to be culturally appropriate and responsive to community standards for safety and comfort.Results 70% of sites exhibited high adherence to the Core MWH Model components. User experience corroborated poorer performing elements: insufficient lighting, small cooking spaces, non-locking cabinets and few educational classes. Mission statements and governing documents were not always visible or available. The proportion of 3206 users who came from>10 km away was higher than the proportion of the surrounding population living at that distance except in two sites with low populations of remote-living women. Women stayed for just below the target of 14 nights. MWH occupancy rate overall was lower (52%) than the target (80%). MWH users reported high quality and satisfaction. Only three MWHs reached 50% female membership on their governance committees but met other key indicators for community ownership and engagement.Conclusions This fidelity evaluation of an MWH model in rural Zambia helps bridge the evidence–practice gap for the WHO’s recommendation on implementing MWHs and adds to the expanding body of literature on implementation fidelity studies in global health.Trial registration number NCT02620436.

Notwithstanding the obvious interconnection between humans and the world that they share with non-human inhabitants, the impact of our changing climate on certain aspects of the public health ecosystem has been under-investigated. We briefly describe some of the possible climate-induced changes in the procurement, distribution, access and use of medications, including those for animals generally and livestock specifically. A fuller understanding of the effect of climate change on medicine supply, access, use and quality, including how these affect antimicrobial resistance, would contribute to the further development of the “One Health” and “One Health Systems” concepts. We suggest that this understanding is not yet available, even though the changing incidence of infectious diseases due to changing climate has been studied. There is a need for improved understanding of the impact of extremes of humidity and heat on medication quality and research into heat-stable medicines as well as strategies for the improving resilience of the pharmaceutical supply and distribution system in complex public health emergencies caused by aberrant weather patterns.

Abstract Background Cutaneous leishmaniasis (CL) is a wide-reaching infection of major public health concern. Iran is one of the six most endemic countries in the world. This study aims to provide a spatiotemporal visualization of CL cases in Iran at the county level from 2011 to 2020, detecting high-risk zones, while also noting the movement of high-risk clusters. Methods On the basis of clinical observations and parasitological tests, data of 154,378 diagnosed patients were obtained from the Iran Ministry of Health and Medical Education. Utilizing spatial scan statistics, we investigated the disease’s purely temporal, purely spatial, spatial variation in temporal trends and spatiotemporal patterns. At P = 0.05 level, the null hypothesis was rejected in every instance. Results In general, the number of new CL cases decreased over the course of the 9-year research period. From 2011 to 2020, a regular seasonal pattern, with peaks in the fall and troughs in the spring, was found. The period of September–February of 2014–2015 was found to hold the highest risk in terms of CL incidence rate in the whole country [relative risk (RR) = 2.24, P

Abstract Background Compared to 2017, India achieved a significant reduction in malaria cases in 2020. Madhya Pradesh (MP) is a tribal dominated state of India with history of high malaria burden in some districts. District Mandla of MP state showed a considerable decline in malaria cases between 2000 and 2013, except in 2007. Subsequently, a resurgence of malaria cases was observed during 2014 and 2015. The Malaria Elimination Demonstration Project (MEDP) was launched in 2017 in Mandla with the goal to achieve zero indigenous malaria cases. This project used: (1) active surveillance and case management using T4 (Track fever, Test fever, Treat patient, and Track patient); (2) vector control using indoor residual sprays and long-lasting insecticidal nets; (3) information education communication and behaviour change communication; and (4) regular monitoring and evaluation with an emphasis on operational and management accountability. This study has investigated malaria prevalence trends from 2008 to 2020, and has predicted trends for the next 5 years for Mandla and its bordering districts. Methods The malaria prevalence data of the district Mandla for the period of January 2008 to August 2017 was obtained from District Malaria Office (DMO) Mandla and data for the period of September 2017 to December 2020 was taken from MEDP data repository. Further, the malaria prevalence data for the period of January 2008 to December 2020 was collected from DMOs of the neighbouring districts of Mandla. A univariate time series and forecast analysis was performed using seasonal autoregressive integrated moving average model. Findings Malaria prevalence in Mandla showed a sharp decline [− 87% (95% CI − 90%, − 84%)] from 2017 to 2020. The malaria forecast for Mandla predicts zero cases in the next 5 years (2021–2025), provided current interventions are sustained. By contrast, the model has forecasted a risk of resurgence of malaria in other districts in MP (Balaghat, Dindori, Jabalpur, Seoni, and Kawardha) that were not the part of MEDP. Conclusion The interventions deployed as part of MEDP have resulted in a sustainable zero indigenous malaria cases in Mandla. Use of similar strategies in neighbouring and other malaria-endemic districts in India could achieve similar results. However, without adding extra cost to the existing intervention, sincere efforts are needed to sustain these interventions and their impact using accountability framework, data transparency, and programme ownership from state to district level.

Abstract Background Postnatal care (PNC) is an important set of services offered to the mother and her newborn baby immediately after birth for the first six weeks to prevent maternal and neonatal complications and death. This qualitative study explored user and provider perspectives on quality of PNC services in the selected health facilities within the context of the Maternity Homes Access in Zambia project in the Saving Mothers Giving Life districts in rural Zambia. Methods Between October 2018 and February 2019, forty focus group discussions (FGDs) (n = 160 participants) and twelve in-depth interviews (IDIs) were conducted in four districts in Southern and Eastern provinces. FGDs comprised women who delivered within the last year, fathers, community elders, and volunteers. IDIs comprised health workers at facility, district, and provincial levels. Data were analysed using content analysis guided by the international quality of care domains derived from the World Health Organization quality of care framework. Findings were triangulated to understand perceptions. Results Overall, study participants perceived PNC services to be beneficial. Nevertheless, respondents had mixed feelings on the quality of PNC services and expressed a stark difference in their perception of factors affecting service quality. Service users described challenges arising from ineffective communication about the new PNC guidelines, and non-adherence of service providers to quality standards regarding respect, preservation of dignity and emotional support. Other factors were long waiting hours, small examination rooms providing inadequate privacy, and low levels of confidentiality. In contrast, service providers attributed poor service quality to various health system-related factors including low staffing levels, dysfunctional referral services, low supply of essential medicines, supplies, vaccines and equipment for optimal routine emergency obstetric and newborn care and management of complications. Conclusion These findings highlight important intervention opportunities to improve quality of PNC services in Zambia through better communication and raising awareness on PNC guidelines, respect, preservation of dignity and emotional support to mothers. Interventions should also focus on addressing contextual health system challenges including staffing levels, supply chain for essential medicines and commodities, shortening waiting time, and ensuring functional referral system.

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.

BackgroundAdolescents make up roughly a quarter of the population in Zambia; however, most nutrition-related programming is targeted at the under-five population. Understanding the scale of undernutrition in older children and adolescents is fundamental to alleviating food insecurity and addressing undernutrition across all age groups.MethodsA cross-sectional survey was performed in four low-income, peri-urban compounds in Chilanga District which included anthropometric measurements of children between ages 6 months-19 years and a household-level diet diversity and food security questionnaire. Wasting was used for children under 5 and thinness for children 5–19 years. Descriptive analysis and multivariate logistic regression were conducted to quantify the prevalence and distribution of malnutrition and understand the impact of food security.ResultsWe surveyed 393 households and 1,004 children between the ages of 6 months and 19 years. Children aged 6–9 years had the highest prevalence of severe thinness (5.2%) and adolescents (10–19 years) had the highest rates of moderate thinness (6.5%). Across all age groups, more than 75% of children were in households that worried about running out of food in the previous month. 24.9% of adolescents and 28.4% of older children were in households were more likely to go a whole day without eating compared to 16.9% of children under 5.ConclusionOur survey indicated that malnutrition in adolescents and older children living in Chilanga district was comparable to those under 5. Interventions to address undernutrition must be targeted at older children and adolescents in order to ameliorate this burden.

Background Utilizing maternity waiting homes (MWHs) is a strategy to improve access to skilled obstetric care in rural Zambia. However, out-of-pocket (OOP) expenses remain a barrier for many women. We assessed deliveryrelated expenditure for women who used MWHs and those who did not who delivered at a rural health facility. Methods During the endline of an impact evaluation for an MWH intervention, household surveys (n = 826) were conducted with women who delivered a baby in the previous 13 months at a rural health facility and lived >10 km from a health facility in seven districts of rural Zambia. We captured the amount women reported spending on delivery. We compared OOP spending between women who used MWHs and those who did not. Amounts were converted from Zambian kwacha (ZMW) to US dollar (USD). Results After controlling for confounders, there was no significant difference in delivery-related expenditure between women who used MWHs (US$40.01) and those who did not (US$36.66) (P = .06). Both groups reported baby clothes as the largest expenditure. MWH users reported spending slightly more on accommodation compared to those did not use MWHs, but this difference represents only a fraction of total costs associated with delivery. Conclusion Findings suggest that for women coming from far away, utilizing MWHs while awaiting delivery is not costlier overall than for women who deliver at a health facility but do not utilize a MWH.

BackgroundEffective integration of home visit interventions focused on early childhood development into existing service platforms is important for expanding access in low- and middle-income countries (LMICs). We designed and evaluated a home visit intervention integrated into community health worker (CHW) operations in South Africa.Methods and findingsWe conducted a cluster-randomized controlled trial in Limpopo Province, South Africa. CHWs operating in ward-based outreach teams (WBOTs; clusters) and caregiver-child dyads they served were randomized to the intervention or control group. Group assignment was masked from all data collectors. Dyads were eligible if they resided within a participating CHW catchment area, the caregiver was at least 18 years old, and the child was born after December 15, 2017. Intervention CHWs were trained on a job aid that included content on child health, nutrition, developmental milestones, and encouragement to engage in developmentally appropriate play-based activities, for use during regular monthly home visits with caregivers of children under 2 years of age. Control CHWs provided the local standard of care. Household surveys were administered to the full study sample at baseline and endline. Data were collected on household demographics and assets; caregiver engagement; and child diet, anthropometry, and development scores. In a subsample of children, electroencephalography (EEG) and eye-tracking measures of neural function were assessed at a lab concurrent with endline and at 2 interim time points. Primary outcomes were as follows: height-for-age z-scores (HAZs) and stunting; child development scores measured using the Malawi Developmental Assessment Tool (MDAT); EEG absolute gamma and total power; relative EEG gamma power; and saccadic reaction time (SRT)-an eye-tracking measure of visual processing speed. In the main analysis, unadjusted and adjusted impacts were estimated using intention-to-treat analysis. Adjusted models included a set of demographic covariates measured at baseline. On September 1, 2017, we randomly assigned 51 clusters to intervention (26 clusters, 607 caregiver-child dyads) or control (25 clusters, 488 caregiver-child dyads). At endline (last assessment June 11, 2021), 432 dyads (71%) in 26 clusters remained in the intervention group, and 332 dyads (68%) in 25 clusters remained in the control group. In total, 316 dyads attended the first lab visit, 316 dyads the second lab visit, and 284 dyads the third lab visit. In adjusted models, the intervention had no significant impact on HAZ (adjusted mean difference (aMD) 0.11 [95% confidence interval (CI): -0.07, 0.30]; p = 0.220) or stunting (adjusted odds ratio (aOR) 0.63 [0.32, 1.25]; p = 0.184), nor did the intervention significantly impact gross motor skills (aMD 0.04 [-0.15, 0.24]; p = 0.656), fine motor skills (aMD -0.04 [-0.19, 0.11]; p = 0.610), language skills (aMD -0.02 [-0.18, 0.14]; p = 0.820), or social-emotional skills (aMD -0.02 [-0.20, 0.16]; p = 0.816). In the lab subsample, the intervention had a significant impact on SRT (aMD -7.13 [-12.69, -1.58]; p = 0.012), absolute EEG gamma power (aMD -0.14 [-0.24, -0.04]; p = 0.005), and total EEG power (aMD -0.15 [-0.23, -0.08]; p < 0.001), and no significant impact on relative gamma power (aMD 0.02 [-0.78, 0.83]; p = 0.959). While the effect on SRT was observed at the first 2 lab visits, it was no longer present at the third visit, which coincided with the overall endline assessment. At the end of the first year of the intervention period, 43% of CHWs adhered to monthly home visits. Due to the COVID-19 pandemic, we were not able to assess outcomes until 1 year after the end of the intervention period.ConclusionsWhile the home visit intervention did not significantly impact linear growth or skills, we found significant improvement in SRT. This study contributes to a growing literature documenting the positive effects of home visit interventions on child development in LMICs. This study also demonstrates the feasibility of collecting markers of neural function like EEG power and SRT in low-resource settings.Trial registrationPACTR 201710002683810; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2683; South African Clinical Trials Registry, SANCTR 4407.

Abstract Background Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. Methods This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. Results Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). Conclusion Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.

The COVID-19 pandemic has increased social and emotional stressors globally, increasing mental health concerns and the risk of psychiatric illness worldwide. To date, relatively little is known about the impact of the pandemic on vulnerable groups such as women and children in low-resourced settings who generally have limited access to mental health care. We explore two rounds of data collected as part of an ongoing trial of early childhood development to assess mental health distress among mothers of children under 5-years-old living in two rural areas of Zambia during the COVID-19 pandemic. We examined the prevalence of mental health distress among a cohort of 1105 mothers using the World Health Organization’s Self-Reporting Questionnaire (SRQ-20) before the onset of the COVID-19 pandemic in August 2019 and after the first two infection waves in October-November 2021. Our primary outcome was mental health distress, defined as SRQ-20 score above 7. We analyzed social, economic and family level characteristics as factors modifying to the COVID-19 induced changes in the mental health status. At baseline, 22.5% of women were in mental health distress. The odds of mental health distress among women increased marginally over the first two waves of the pandemic (aOR1.22, CI 0.99–1.49). Women under age 30, with lower educational background, with less than three children, and those living in Eastern Province (compared to Southern Province) of Zambia, were found to be at highest risk of mental health deterioration during the pandemic. Our findings suggest that the prevalence of mental health distress is high in this population and has further worsened during COVID-19 pandemic. Public health interventions targeting mothers’ mental health in low resource settings may want to particularly focus on young mothers with limited educational attainment.

Despite reductions in the number of under-five deaths since the release of the Sustainable Development Goals, the proportion of neonatal deaths among all under-five deaths has remained high. Neonatal health is linked to newborn care practices which are tied to distinct cultural perceptions of health and illness. We assessed how community beliefs in Zambia’s Southern Province influence newborn care behaviors, perception of illness, and care-seeking practices, using qualitative data collected between February and April 2010. A total of 339 women participated in 36 focus group discussions (FGDs), with 9 FGDs conducted in each of the four study districts. In addition, 42 in-depth interviews (IDIs) were conducted with various key informants, with 11 IDIs conducted in Choma, 11 IDIs in Monze, 10 IDIs in Livingstone, and 10 IDIs in Mazabuka. The FGDs and IDIs indicate that beliefs among the Tonga people regarding postnatal illness prevention and management influence perceptions of newborn illness and care-seeking practices. Care seeking behaviors including when, why, and where parents seek newborn care are intimately tied to perception of disease among the Tonga people. These beliefs may stem from both indigenous and Western perspectives in Zambia’s Southern Province. Findings are consistent with other analyses from Southern Province that highlighted the benefit of integrating local practices with Western biomedical care. Health systems models, led by policy makers and program designers, could aim to find synergies between community practices and formal health systems to support positive behavior change and satisfy multiple stakeholders.

Maternity waiting homes (MWHs) are one strategy to improve access to skilled obstetric care in low resource settings such as Zambia. The Maternity Homes Access in Zambia project built 10 MWHs at rural health centers in Zambia for women awaiting delivery and postnatal care (PNC) visits. The objective of this paper is to summarize the costs associated with setup of 10 MWHs, including infrastructure, furnishing, stakeholder engagement, and activities to build the capacity of local communities to govern MWHs. We do not present operational costs after setup was complete. We used a retrospective, top-down program costing approach. We reviewed study documentation to compile planned and actual costs by site. All costs were annuitized using a 3% discount rate and organized by cost categories: (1) Capital: infrastructure and furnishing, and (2) Installation: capacity building activities and stakeholder engagement. We assumed lifespans of 30 years for infrastructure; 5 years for furnishings; and 3 years for installation activities. Annuitized costs were used to estimate cost per night stayed and per visit for delivery and PNC-related stays. We also modeled theoretical utilization and cost scenarios. The average setup cost of one MWH was $85,284 (capital: 76%; installation: 24%). Annuitized setup cost per MWH was USD$12,516 per year. At an observed occupancy rate of 39%, setup cost per visit to the MWH was USD$70, while setup cost per night stayed was USD$6. The cost of stakeholder engagement activities was underbudgeted by half at the beginning of this project.This analysis serves as a planning resource for governments and implementers that are considering MWHs as a component of their overall maternal and child health strategy. Planning considerations should include the annuitized cost, value of capacity building and stakeholder engagement, and that cost per bed night and visit are dependent upon utilization.

Objective Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship.Methods Five sites in Bangladesh, India and Pakistan enrolled mother–child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0–59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build a Bayesian partial latent class model (PLCM) capable of attributing the probable cause of each infant’s infection in the ANISA study. The collected risk factors from all mother–child pairs were classified and analysed against the PLCM using bivariate and stepwise logistic multivariable regression modelling to determine risk factors of probable bacterial infection.Results Among 63 114 infants born, 14 655 were assessed and 6022 had signs of pSBI; of these, 81% (4859) provided blood samples for culture, 71% (4216) provided blood samples for quantitative PCR (qPCR) and 86% (5209) provided respiratory qPCR samples. Risk factors associated with bacterial-attributed infections included: low (relative risk (RR) 1.73, 95% credible interval (CrI) 1.42 to 2.11) and very low birth weight (RR 5.77, 95% CrI 3.73 to 8.94), male sex (RR 1.27, 95% CrI 1.07 to 1.52), breathing problems at birth (RR 2.50, 95% CrI 1.96 to 3.18), premature rupture of membranes (PROMs) (RR 1.27, 95% CrI 1.03 to 1.58) and being in the lowest three socioeconomic status quintiles (first RR 1.52, 95% CrI 1.07 to 2.16; second RR 1.41, 95% CrI 1.00 to 1.97; third RR 1.42, 95% CrI 1.01 to 1.99).Conclusion Distinct risk factors: birth weight, male sex, breathing problems at birth and PROM were significantly associated with the development of bacterial sepsis across South Asian community settings, supporting refined clinical discernment and targeted use of antimicrobials.

Summary: Contact tracing and genomic data, approaches often used separately, have both been important tools in understanding the nature of SARS-CoV-2 transmission. Linked analysis of contact tracing and sequence relatedness of SARS-CoV-2 genomes from a regularly sampled university environment were used to build a multilevel transmission tracing and confirmation system to monitor and understand transmission on campus. Our investigation of an 18-person cluster stemming from an athletic team highlighted the importance of linking contact tracing and genomic analysis. Through these findings, it is suggestive that certain safety protocols in the athletic practice setting reduced transmission. The linking of traditional contact tracing with rapid-return genomic information is an effective approach for differentiating between multiple plausible transmission scenarios and informing subsequent public health protocols to limit disease spread in a university environment.

ABSTRACT: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) sublineage B.1.617.2 or Delta, a variant that began circulating in India and is becoming dominant in the USA, has been responsible for significant morbidity and mortality. In May 2021, the Delta variant was upgraded to a variant of concern by international authorities. This article reports a cluster of SARS-CoV-2 Delta cases detected in Boston, Massachusetts, in May 2021 involving a recent traveller from India and subsequent transmission to two of three close contacts. All three close contacts experienced the same primary exposure events but differed in vaccination status. The two close contacts that eventually tested positive were unvaccinated. The other close contact had received one dose of the BNT162b (Pfizer-BioNTech) vaccine prior to exposure, and received their second dose 2 days after exposure. This case series illustrates the effectiveness of partial vaccination in blocking transmission of the Delta variant to vaccinated individuals under circumstances where the probability of transmission for unvaccinated individuals is high.

Abstract Background Malaria infection during pregnancy has negative health consequences for both mothers and offspring. Sub-microscopic malaria infection during pregnancy is common in most African countries. We sought to identify factors associated with sub-microscopic placental malaria, and its association with adverse pregnancy outcomes among HIV-negative pregnant women in Dar es Salaam, Tanzania. Methods We recruited a cohort of pregnant women during their first trimester and assessed for the occurrence of placental malaria and pregnancy outcomes. The follow-up was done monthly from recruitment until delivery. Histopathology placental malaria positive results were defined as the presence of malaria pigment or parasitized erythrocytes on the slide (histology-positive (HP)), and the sub-microscopic placental infection was defined as positive Plasmodium falciparum DNA by polymerase chain reaction (DNA PCR) amplification in a negative histopathology test. Adverse pregnancy outcomes investigated included low birth weight (birth weight below 2.5 kg), prematurity (live birth below 37 weeks), and small-for-gestational-age (SGA) (live born with a birth weight below 10th percentile for gestational age and sex). Weighted baseline category logit, log-binomial, and log-Poisson models were used to assess factors associated with placental malaria, and its association with adverse pregnancy outcomes. Results Among 1115 women who had histopathology and DNA PCR performed, 93 (8%) had HP placental infection, and 136 (12%) had the sub-microscopic placental infection. The risk of sub-microscopic placental malaria was greater in women who did not use mosquito prevention methods such as bed nets, fumigation, or mosquito coils (odds ratio (OR) = 1.75; 95% confidence interval (CI): 1.05–2.92; P = 0.03) and in women who were anemic (OR = 1.59; 95% CI: 1.20–2.11; P = 0.001). Women who were underweight had reduced odds of sub-microscopic placental malaria infection (OR = 0.33; 95% CI: 0.17–0.62; P = 0.001). Women who were overweight/obese had 1.48 times higher the odds of HP placental malaria compared to normal weight (OR = 1.48; 95% CI: 1.03–2.11; P = 0.03). HP placental malaria infection was associated with an increased risk of SGA births (RR = 1.30, 95% CI: 0.98–1.72, P = 0.07). In contrast, the sub-microscopic infection was associated with a reduced risk of SGA births (RR = 0.61, 95% CI: 0.43–0.88, P = 0.01). Placental malaria was not associated with low birth weight or prematurity. Conclusion Malaria prevention methods and maternal nutrition status during early pregnancy were important predictors of sub-microscopic placental malaria. More research is needed to understand sub-microscopic placental malaria and the possible mechanisms mediating the association between placental malaria and SGA.

Objective: The aim of this observational study was to determine the optimal timing of interleukin-6 receptor inhibitor (IL6ri) administration for coronavirus disease 2019 (COVID-19). Methods: Patients with COVID-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into two groups: those requiring ≤45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. The main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Results: A total of 255 COVID-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than those treated in stage III (adjusted hazard ratio (aHR) 0.24, 95% confidence interval (CI) 0.08–0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR 1.43, 95% CI 1.06–1.93) and were less likely to be intubated (aHR 0.43, 95% CI 0.24–0.79). Conclusions: IL6ri administration prior to >45% FiO2 requirement was associated with improved COVID-19 outcomes. This can guide clinical management pending results from randomized controlled trials.

Abstract Background Infants in the neonatal intensive care unit (NICU) are particularly susceptible to healthcare-associated infections (HAIs). NICUs in low- and middle income countries face additional challenges to HAI prevention. There is a need to better understand the role of the implementation context surrounding infection prevention interventions in low- and middle income countries. Aim The aim of this study was to identify NICU healthcare worker perceptions of an intervention to reduce bloodstream infections in a large Zambian NICU. Methods Semi-structured interviews were conducted with NICU staff during a prospective cohort study examining the impact of an infection prevention bundle on bloodstream infections. Interviews were analyzed using an integrated approach, combining inductive theme generation with an application of the Consolidated Framework for Implementation Research (CFIR). Results Interviews were conducted with 17 NICU staff (5 physicians and 12 nurses). Respondents believed the bundle elements were easy to use, well-designed and facilitated improved performance. Four organizational characteristics that facilitated HAI transmission were identified – (1) lack of NICU admission protocols; (2) physical crowding; (3) understaffing; and (4) equipment shortages. Respondents suggested that NICU resource constraints reflected a societal ethos that devalued the medical care of infants. Despite the challenges, respondents were highly motivated to prevent HAIs and believed this was an achievable goal. They enthusiastically welcomed the bundle but expressed serious concern about sustainability following the study. Conclusions By eliciting healthcare worker perceptions about the context surrounding an infection prevention intervention, our study identified key organizational and societal factors to inform implementation strategies to achieve sustained improvement.

BackgroundApproximately 6 million people worldwide are affected by Chagas disease, with many in the chronic phase of the disease (CCD). It is crucial to evaluate the effectiveness of benznidazole for CCD treatment.Methods/principal findingsWe updated a meta-analysis published in 2009 up to February 2021, including controlled trials (RCT) and prospective observational studies (OBS) that compared benznidazole vs placebo/no-treatment (P/nT). Main outcomes evaluated were clinical progression (CP) and seroreversion with subgroup analysis performed according to study design and participants' age. Parasitological response and safety were also described. We identified 879 articles and selected nine for inclusion (corresponding to eight studies). After adding the nine articles from the previous meta-analysis, 17 studies were analyzed corresponding to 6640 patients. The odds ratio (OR) for seroreversion in children treated with benznidazole vs P/nT was 38.3 (95%CI: 10.7-137) and 34.9 (95%CI: 1.96-624.09) in RCT and OBS, respectively. In adults the OR for seroreversion in OBS was 17.1 (95%CI: 2.3-129.1). CP was only evaluated in adults, where benznidazole did not demonstrate a beneficial effect: OR 0.93 (95%CI: 0.8-1.1) and OR 0.49 (95%CI:0.2-1.2) for RCT and OBS, respectively. Most outcomes were deemed to have a low level of certainty, except for the beneficial effect in children and the low efficacy in adults (moderate certainty).ConclusionsBenznidazole should be recommended for CCD in children, though this is only based on serological response and a moderate grade of evidence, while in adults benznidazole efficacy remains uncertain. More data on clinical efficacy of benznidazole in CCD is needed in both children and adults.

Background: Maternity waiting homes (MWH) allow pregnant women to stay in a residential facility close to a health center while awaiting delivery. This approach can improve health outcomes for women and children. Health planners need to consider many factors in deciding the number of beds needed for an MWH. Objective: The objective of the study is to review experience in Zambia in planning and implementing MWHs, and consider lessons learned in determining optimal capacity. Methods: We conducted a study of 10 newly built MWH in Zambia over 12 months. For this case study analysis, data on beds, service volume, and catchment area population were examined, including women staying at the homes, bed occupancy, and average length of stay. We analyzed bed occupancy by location and health facility catchment area size, and categorized occupancy by month from very low to very high. Findings: Most study sites were rural, with 3 of the 10 study sites rural-remote. Four sites served small catchment areas (11 000) size populations. Annual occupancy was variable among the sites, ranging from 13% (a medium rural site) to 151% (a large rural-remote site). Occupancy higher than 100% was accommodated by repurposing the MWH postnatal beds and using extra mattresses. Most sites had between 26–69% annual occupancy, but monthly occupancy was highly variable for reasons that seem unrelated to catchment area size, rural or rural-remote location. Conclusion: Planning for MWH capacity is difficult due to high variability. Our analysis suggests planners should try to gather actual recent monthly birth data and estimate capacity using the highest expected utilization months, anticipating that facility-based deliveries may increase with introduction of a MWH. Further research is needed to document and share data on MWH operations, including utilization statistics like number of beds, mattresses, occupancy rates and average length of stay.

Introduction: Early reading interventions hold promise for increasing language and literacy development in young children and improving caregiver-child interactions. To engage rural caregivers and young children in home reading, Zambian child psychologists and education specialists developed a culturally representative, local language children’s book targeted at pre-grade 1 children. Objectives: We qualitatively assessed community acceptability and use of the book distributed to households with young children in two provinces of Zambia. Methods: We conducted 15 focus group discussions (FGDs) with women (n=117) who received the “Zambian folktales adapted stories for young children” book. A codebook was created a priori, based on established themes in the guide; content analysis was conducted in Nvivo v12. Data were interpreted against the Theoretical Framework on Acceptability. Findings: Respondents described wide acceptability of the children’s book across multiple framework constructs. Respondents believed the book was culturally appropriate for its folktale structure and appreciated the morals and lessons provided by the stories. Respondents described using the book in multiple ways including reading in one-on-one or group settings, asking the child questions about the narrative or pictures, and providing additional commentary on the actions or figures in the pictures. Respondents believed the books were helping children grow their vocabulary and early literacy skills. The book’s simple vocabulary facilitated use by less educated caregivers. The primary concern voiced was the ability of low literacy caregivers to utilize the book for reading. Discussion: The children’s book was widely considered acceptable by rural Zambian communities. It provided a platform for an additional method of caregiver-child interactions in these households for reading, dialogue, and oral storytelling. Shared reading experiences have potentially substantial benefits for the language development and emergent literacy of young children. Programs to develop and deliver culturally acceptable books to households with limited access should be considered by governments and funders.

At our university based high throughput screening program, we test all members of our community weekly using RT-qPCR. RT-qPCR cycle threshold (CT) values are inversely proportional to the amount of viral RNA in a sample and are a proxy for viral load. We hypothesized that CT values would be higher, and thus the viral loads at the time of diagnosis would be lower, in individuals who were infected with the virus but remained asymptomatic throughout the course of the infection. We collected the N1 and N2 target gene CT values from 1633 SARS-CoV-2 positive RT-qPCR tests of individuals sampled between August 7, 2020, and March 18, 2021, at the BU Clinical Testing Laboratory. We matched this data with symptom reporting data from our clinical team. We found that asymptomatic patients had CT values significantly higher than symptomatic individuals on the day of diagnosis. Symptoms were followed by the clinical team for 10 days post the first positive test. Within the entire population, 78.1% experienced at least one symptom during surveillance by the clinical team (n = 1276/1633). Of those experiencing symptoms, the most common symptoms were nasal congestion (73%, n = 932/1276), cough (60.0%, n = 761/1276), fatigue (59.0%, n = 753/1276), and sore throat (53.1%, n = 678/1276). The least common symptoms were diarrhea (12.5%, n = 160/1276), dyspnea on exertion (DOE) (6.9%, n = 88/1276), foot or skin changes (including rash) (4.2%, n = 53/1276), and vomiting (2.1%, n = 27/1276). Presymptomatic individuals, those who were not symptomatic on the day of diagnosis but became symptomatic over the following 10 days, had CT values higher for both N1 (median = 27.1, IQR 20.2–32.9) and N2 (median = 26.6, IQR 20.1–32.8) than the symptomatic group N1 (median = 21.8, IQR 17.2–29.4) and N2 (median = 21.4, IQR 17.3–28.9) but lower than the asymptomatic group N1 (median = 29.9, IQR 23.6–35.5) and N2 (median = 30.0, IQR 23.1–35.7). This study supports the hypothesis that viral load in the anterior nares on the day of diagnosis is a measure of disease intensity at that time.

Introduction In the early parts of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) were implemented worldwide, including in sub-Saharan Africa, to prevent and control SARS-CoV-2 transmission. This mixed-methods study examines adherence to and enforcement of NPIs implemented to curb COVID-19 in Nigeria, Rwanda, and Zambia, leading up to the 10,000th case of laboratory-confirmed COVID-19 in each country. Additionally, we aim to evaluate the relationship between levels and changes of NPIs over time and changes in COVID-19 cases and deaths. Methods This mixed-methods analysis utilized semi-structured interviews and a quantitative dataset constructed using multiple open data sources, including the Oxford COVID-19 Government Response Tracker. To understand potential barriers and facilitators in implementing and enforcing NPIs qualitative data were collected from those involved in the COVID-19 response and analyzed using NVivo. Quantitative results were analyzed using descriptive statistics, plots, ANOVA, and post hoc Tukey. Results Individual indicator scores varied with the COVID-19 response in all three countries. Nigeria had sustained levels of strict measures for containment and closure NPIs, while in Rwanda there was substantial variation in NPI score as it transitioned through the different case windows for the same measures. Zambia implemented moderate stringency throughout the pandemic using gathering restrictions and business/school closure measures but maintained low levels of strictness for other containment and closure measures. Rwanda had far more consistent and stringent measures compared to Nigeria and Zambia. Rwanda’s success in implementing COVID-related measures was partly due to strong enforcement and having a population that generally follow the recommendations of their government. Conclusion Various forces either facilitated or hindered adherence and compliance to COVID-19 control measures. The lessons learned and recommendations gleaned through interviews with experts involved in the COVID-19 pandemic and quantitative analysis of NPI implementation can be applied to future outbreaks, epidemics, and pandemics. Recommendations include engaging communities, using a risk-based approach to implement containment and closure NPIs, and providing social and economic support to citizens during periods of lockdowns and other measures that interrupt the ability to make a living.

Objective Determine the sensitivity and specificity of neonatal jaundice visual estimation by primary healthcare workers (PHWs) and physicians as predictors of hyperbilirubinaemia.Design Multicentre observational cohort study.Setting Hospitals in Chandigarh and Delhi, India; Dhaka, Bangladesh; Durban, South Africa; Kumasi, Ghana; La Paz, Bolivia.Participants Neonates aged 1–20 days (n=2642) who presented to hospitals for evaluation of acute illness. Infants referred for any reason from another health facility or those needing immediate cardiopulmonary resuscitation were excluded.Outcome measures Infants were evaluated for distribution (head, trunk, distal extremities) and degree (mild, moderate, severe) of jaundice by PHWs and physicians. Serum bilirubin level was determined for infants with jaundice, and analyses of sensitivity and specificity of visual estimations of jaundice used bilirubin thresholds of >260 µmol/L (need for phototherapy) and >340 µmol/L (need for emergency intervention in at-risk and preterm babies).Results 1241 (47.0%) neonates had jaundice. High sensitivity for detecting neonates with serum bilirubin >340 µmol/L was found for ‘any jaundice of the distal extremities (palms or soles) OR deep jaundice of the trunk or head’ for both PHWs (89%–100%) and physicians (81%–100%) across study sites; specificity was more variable. ‘Any jaundice of the distal extremities’ identified by PHWs and physicians had sensitivity of 71%–100% and specificity of 55%–95%, excluding La Paz. For the bilirubin threshold >260 µmol/L, ‘any jaundice of the distal extremities OR deep jaundice of the trunk or head’ had the highest sensitivity across sites (PHWs: 58%–93%, physicians: 55%–98%).Conclusions In settings where serum bilirubin cannot be measured, neonates with any jaundice on the distal extremities should be referred to a hospital for evaluation and management, where delays in serum bilirubin measurement and appropriate treatment are anticipated following referral, the higher sensitivity sign, any jaundice on the distal extremities or deep jaundice of the trunk or head, may be preferred.

Abstract Background In low-income countries such as Zambia, where maternal mortality rates are persistently high, maternity waiting homes (MWHs) represent one potential strategy to improve access to safe delivery, especially for women living in remote areas. The Maternity Homes Access in Zambia project (MAHMAZ) is evaluating the impact of a MWH model on women’s access to safe delivery in rural Zambia. There is a growing need to understand not only the effectiveness of interventions but also the effectiveness of their implementation in order to appropriately interpret outcomes. There is little evidence to guide effective implementation of MWH for both immediate uptake and to promote sustainability in this context. This protocol describes a study that aims to investigate the effectiveness of the implementation of MAHMAZ by not only documenting fidelity but also identifying factors that influence implementation success and affect longer-term sustainability. Methods This study will use mixed methods to evaluate the implementation effectiveness and sustainability of the MAHMAZ intervention. In our study, “implementation effectiveness” means to expand beyond measuring fidelity to the MWH model and includes assessing both the adoption and uptake of the model and identifying those factors that facilitate or inhibit uptake. Sustainability is defined as the routine implementation of an intervention after external support has ended. Quantitative methods include extracting data from existing records at the MWHs and health facilities to analyze patterns of utilization, and conducting a routine health facility assessment to determine facility-level factors that may influence MWH implementation and woman-level outcomes. We will also conduct an experience survey with MWH users and apply a checklist to assess fidelity to the MWH model. Qualitative methods include in-depth interviews and focus group discussions with MWH users, community members and other stakeholders. Qualitative data will be analyzed using an integrated framework drawing constructs from the Consolidated Framework for Implementation Research and the Conceptual Framework for Sustainability. Discussion The findings from this evaluation will be shared with policymakers formulating policy affecting the implementation of MWH and may be used as evidence for programmatic decisions by the government and supporting agencies in deciding to take this model to scale. Trial registration NCT02620436 , Registered 3 December 2015, Prospectively registered (clinicaltrials.gov; for the overarching quasi-experimental impact study).

Background: Menstrual disorders, influenced by dietary habits like high fat intake and low fruit and vegetable consumption, are a global public health issue. This study assessed the prevalence of dysmenorrhea, premenstrual syndrome (PMS), and irregular menstrual cycle (IMC) among female university students in Bangladesh, focusing on food cravings and low vitamin A intake as risk factors. Methods: In this comprehensive study, data from randomly selected female university students were collected using a structured questionnaire. The associations were analyzed through chi-square tests and multivariable logistic regression, reported as adjusted odds ratios (AOR). Results: The most prevalent menstrual disorder was dysmenorrhea (68.3%) followed by PMS (33.8%), and IMC (24.3%). Food cravers for high-fat and sweet foods were likely to experience dysmenorrhea (AOR: 2.4, 95% CI: 1.5–3.9, P<0.001), suffer from PMS (AOR: 3.9, 95% CI: 2.3–6.6, P<0.001), and have IMC (AOR: 3.0, 95% CI: 1.6–5.3, P<0.001) vs. subjects who didn't. Subjects consuming vitamin A-rich plant foods had 40% (AOR: 0.6, 95% CI: 0.4–0.9, P < 0.01) and 60% (AOR: 0.4, 95% CI: 0.2–0.6, P<0.001) less likely suffering from dysmenorrhea and IMC vs. who didn't. Both underweight and overweight/obese subjects experienced more than 2-fold dysmenorrhea vs. normal-weight peers. The chance of IMC was nearly 3-fold among overweight/obese subjects. However, lower physical activity was associated with PMS and IMC whereas family history was associated with dysmenorrhea and PMS. Among the socio-demographic factors, maternal education, place of residence, and earlier menarche (≤12 years) were associated with dysmenorrhea while marital status was associated with IMC. Conclusion: This study indicates that increasing the intake of vitamin A-rich plant foods and reducing high-fat, sweet foods can lower the risk of dysmenorrhea and IMC. Additionally, it highlights the need for regular exercise to mitigate the increased risk of PMS and IMC. [ABSTRACT FROM AUTHOR]

Abstract Background Maternity waiting homes (MWHs) are a potential strategy to address low facility delivery rates resulting from access-associated barriers in resource-limited settings. Within a cluster-randomized controlled trial testing a community-generated MWH model in rural Zambia, we qualitatively assessed how MWHs affect the health workforce and maternal health service delivery at their associated rural health centers. Methods Four rounds of in-depth interviews with district health staff (n = 21) and health center staff (n = 73) were conducted at intervention and control sites over 24 months. We conducted a content analysis using a mixed inductive-deductive approach. Data were interpreted through the lens of the World Health Organzation Health Systems Framework. Results Nearly all respondents expressed challenges with understaffing and overwork and reported that increasing numbers of facility-based deliveries driven by MWHs contributed substantively to their workload. Women waiting at MWHs allow staff to monitor a woman’s final stage of pregnancy and labor onset, detect complications earlier, and either more confidently manage those complications at the health center or refer to higher level care. District, intervention, and control site respondents passionately discussed this benefit over all time points, describing it as outweighing challenges of additional work associated with MWHs. Intervention site staff repeatedly discussed the benefit of MWHs in providing a space for postpartum women to wait after the first few hours of clinical observation through the first 48 h after delivery. Additionally, intervention site staff perceived the ability to observe women for longer before and after delivery allowed them to better anticipate and plan their own work, adjust their workloads and mindset accordingly, and provide better and more timely care. When understaffing and overwork were frequently discussed, this satisfaction in providing better care was a meaningful departure. Conclusions MWHs may benefit staff at rural health centers and the health system more broadly, allowing for the provision of more timely and comprehensive obstetric care. We recommend future studies consider how MWHs impact the workforce, operations, and service delivery at their associated health facilities. Considering the limited numbers of skilled birth attendants available in rural Zambia, it is important to strategically select locations for new MWHs. Trial registration Clinicaltrials.gov, NCT02620436. Registered December 3, 2015, https://clinicaltrials.gov/ct2/show/NCT02620436

Abstract Background In 2014, Vietnam was the first Southeast Asian country to commit to achieving the World Health Organization’s 90–90-90 global HIV targets (90% know their HIV status, 90% on sustained treatment, and 90% virally suppressed) by 2020. This pledge represented further confirmation of Vietnam’s efforts to respond to the HIV epidemic, one feature of which has been close collaboration with the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). Starting in 2004, PEPFAR supported community outreach programs targeting high-risk populations (people who inject drugs, men who have sex with men, and sex workers). To provide early evidence on program impact, in 2007–2008 we conducted a nationwide evaluation of PEPFAR-supported outreach programs in Vietnam. The evaluation focused on assessing program effect on HIV knowledge, high-risk behaviors, and HIV testing among high-risk populations—results relevant to Vietnam’s push to meet global HIV goals. Methods We used a mixed-methods cross-sectional evaluation design. Data collection encompassed a quantitative survey of 2199 individuals, supplemented by 125 in-depth interviews. Participants were members of high-risk populations who reported recent contact with an outreach worker (intervention group) or no recent contact (comparison group). We assessed differences in HIV knowledge, risky behaviors, and HIV testing between groups, and between high-risk populations. Results Intervention participants knew significantly more about transmission, prevention, and treatment than comparison participants. We found low levels of injection drug-use-related risk behaviors and little evidence of program impact on such behaviors. In contrast, a significantly smaller proportion of intervention than comparison participants reported risky sexual behaviors generally and within each high-risk population. Intervention participants were also more likely to have undergone HIV testing (76.1% vs. 47.0%, p

BackgroundMaternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.Methods and findingsThis is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman's self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes. Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.ConclusionsOur findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.Trial registrationThe study is not a clinical trial.

BackgroundNeonatal infection, a leading cause of neonatal death in low- and middle-income countries, is often caused by pathogens acquired during childbirth. Clean delivery kits (CDKs) have shown efficacy in reducing infection-related perinatal and neonatal mortality. However, there remain gaps in our current knowledge, including the effect of individual components, the timeline of protection, and the benefit of CDKs in home and facility deliveries.Methods and findingsA post hoc secondary analysis was performed using nonrandomized data from the Zambia Chlorhexidine Application Trial (ZamCAT), a community-based, cluster-randomized controlled trial of chlorhexidine umbilical cord care in Southern Province of Zambia from February 2011 to January 2013. CDKs, containing soap, gloves, cord clamps, plastic sheet, razor blade, matches, and candle, were provided to all pregnant women. Field monitors made a home-based visit to each participant 4 days postpartum, during which CDK use and newborn outcomes were ascertained. Logistic regression was used to study the association between different CDK components and neonatal mortality rate (NMR). Of 38,579 deliveries recorded during the study, 36,996 newborns were analyzed after excluding stillbirths and those with missing information. Gloves, cord clamps, and plastic sheets were the most frequently used CDK item combination in both home and facility deliveries. Each of the 7 CDK components was associated with lower NMR in users versus nonusers. Adjusted logistic regression showed that use of gloves (odds ratio [OR] 0.33, 95% CI 0.24-0.46), cord clamp (OR 0.51, 95% CI 0.38-0.68), plastic sheet (OR 0.46, 95% CI 0.34-0.63), and razor blade (OR 0.69, 95% CI 0.53-0.89) were associated with lower risk of newborn mortality. Use of gloves and cord clamp were associated with reduced risk of immediate newborn death (ConclusionsCDK use was associated with reductions in early newborn mortality at both home and facility deliveries, especially when certain kit components were used. While causality could not be established in this nonrandomized secondary analysis, given these beneficial associations, scaling up the use of CDKs in rural areas of sub-Saharan Africa may improve neonatal outcomes.Trial registrationName of trial: Zambia Chlorhexidine Application Trial (ZamCAT) Name of registry: Clinicaltrials.gov Trial number: NCT01241318.

Asymptomatic surveillance testing together with COVID-19-related research can lead to positive SARS-CoV-2 tests resulting not from true infections, but non-infectious, non-hazardous by-products of research (amplicons). Amplicons can be widespread and persistent in lab environments and can be difficult to distinguish for true infections. We discuss prevention and mitigation strategies.

Background: Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important. Methods: We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018. Findings: 103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998–2002) to 3.6% (2013–2018). The proportion of patients with seasonal influenza increased from zero in 1998–2002 to 0.9% in 2013–2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively. Interpretation: Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe. Funding: This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.

Background: Uganda has successfully reduced pediatric HIV infections through prevention of mother-to-child transmission of HIV (PMTCT) programs, yet little is known about adherence to infant-specific components of interventions. We hypothesized that infants born to mothers receiving the WiseMama (WM) electronic drug monitoring (EDM)-based adherence intervention would have increased uptake of six-week post-natal nevirapine (NVP) infant prophylaxis and better adherence to six-week early infant diagnosis (EID) HIV testing. Methods: At two sites in Uganda, the Wise Infant Study (WIN) prospectively followed an infant cohort. Infants were born to women enrolled in an RCT testing the effect of real-time reminders delivered via EDM on maternal adherence to antiretroviral therapy. We assessed intrapartum and discharge receipt of NVP prophylaxis using pharmacy and infant HIV DNA testing laboratory data. Results: Of 121 women eligible for WIN, 97 (80%) consented and enrolled; 46 had been randomized to control and 51 to intervention. There were no differences in receipt of a six-week NVP supply (control 87%, intervention 82%, p = 0.53). Receipt of any NVP prophylaxis did not vary by delivery location (p = 0.35), and although 12% of infants were delivered at non-study health facilities, they were not less likely to receive NVP at discharge (p = 0.37). Among infants with a completed HIV test, there was no difference in mean time to first test (control 52 days (SD 18), intervention 51 days (SD 15), p = 0.86). Only one infant, in the control group, tested positive for HIV. Conclusion and Global Health Implications: We found no significant differences in adherence to infant PMTCT practices between intervention and control infants with relatively high rates of NVP receipt albeit with suboptimal adherence to six-week EID testing. Further work is needed to ensure improved access, uptake, and follow-up of HIV-exposed infants in the Option B+ era. Key words: • Prevention of maternal to child transmission of HIV • HIV • Nevirapine • Antiretroviral therapy prophylaxis • Early infant diagnosis • HIV-exposed infants Copyright © 2020 Murillo et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in this journal, is properly cited.

Abstract Background Recent reports highlight malaria as a frequent diagnosis in migrants who originate from Eritrea. A descriptive analysis of GeoSentinel cases of malaria in Eritrean migrants was done together with a literature review to elucidate key attributes of malaria in this group with a focus on possible areas of acquisition of malaria and treatment challenges. Results A total of 146 cases were identified from the GeoSentinel database from 1999 through September 2017, with a marked increase in 2014 and 2015. All patients originated from Eritrea and the main reporting GeoSentinel sites were in Norway, Switzerland, Sweden, Israel and Germany. The majority of patients (young adult males) were diagnosed with malaria following arrival in the host country. All patients had a possible exposure in Eritrea, but may have been exposed in documented transit countries including Ethiopia, Sudan and possibly Libya in detention centres. Most infections were due to Plasmodium vivax (84.2%), followed by Plasmodium falciparum (8.2%). Two patients were pregnant, and both had P. vivax malaria. Some 31% of the migrants reported having had malaria while in transit. The median time to onset of malaria symptoms post arrival in the host country was 39 days. Some 66% of patients were hospitalized and nine patients had severe malaria (according to WHO criteria), including five due to P. vivax. Conclusions The 146 cases of mainly late onset, sometimes severe, P. vivax malaria in Eritrean migrants described in this multi-site, global analysis reflect the findings of single-centre analyses identified in the literature search. Host countries receiving asylum-seekers from Eritrea need to be prepared for large surges in vivax and, to a lesser extent, falciparum malaria, and need to be aware and prepared for glucose-6-phosphate dehydrogenase deficiency testing and primaquine treatment, which is difficult to procure and mainly unlicensed in Europe. There is an urgent need to explore the molecular epidemiology of P. vivax in Eritrean asylum-seekers, to investigate the area of acquisition of P. vivax along common transit routes and to determine whether there has been re-introduction of malaria in areas, such as Libya, where malaria is considered eliminated, but where capable vectors and Plasmodium co-circulate.

Abstract Background Limited qualitative research has been performed in India to investigate views and behaviours of pregnant women regarding malaria despite the threat of malaria-related adverse maternal and neonatal outcomes. To address this gap, a comprehensive study on malaria prevention and treatment attitudes, knowledge and behaviour among pregnant women in India was conducted. Methods Pregnant women and healthcare workers (HCWs), encompassing clinic-based providers, traditional birth attendants, and auxiliary nurse-midwives were enrolled for in-depth interviews (IDIs) at 7 hospital sites and nearby communities in Jharkhand and Chhattisgarh States. Questions addressed health concerns and attitudes, knowledge and practices regarding malaria prevention and treatment; probing covered modern and traditional approaches. Data were analyzed using a thematic approach. Results A total of 83 pregnant women and 119 HCWs participated in 202 IDIs, 90 in Jharkhand and 112 in Chhattisgarh. A majority of Jharkhand respondents, but only one-fourth in Chhattisgarh, named malaria among top health issues for pregnant women. Just over half of pregnant women were willing to try new prevention methods (especially insecticide-treated bed nets), although cost-related barriers to such methods were stressed. Most respondents voiced concerns about malaria treatment during pregnancy, mainly citing potential harm to the baby. Most knew that mosquitoes transmitted malaria, but a substantial minority, including among HCWs, described incorrect transmission modes. Most knew a proven prevention method (usually bed nets or coils); a few knew other methods. A minority of pregnant women, but most HCWs, knew about malaria treatment, although some HCWs described unproven treatments. Most respondents described use of modern prevention methods in their communities, typically bed nets, although probing revealed irregular use. Half (especially in Jharkhand and particularly HCWs) described use of traditional prevention approaches such as burning leaves and rubbing oils on the body; traditional remedies for malaria treatment were common, and varied by site and population. Conclusions Understanding of malaria varied as a concern for pregnant women, continued use of unproven malaria prevention and treatment strategies was evident in this population in India. These results highlight the need to educate both pregnant women and HCWs about effective malaria methods to protect pregnant women and their babies from malaria.

Abstract Background Community-centred health interventions, such as Safe Motherhood Action groups (SMAGs), have potential to lead to desired health behavioural change and favourable health outcomes. SMAGs are community-based volunteer groups that aim to reduce critical delays that occur at household level with regard to decision-making about seeking life-saving maternal care at health facilities. The aim of this study was to explore perspectives, roles, achievements and challenges of the SMAG programme in Kalomo, Zambia. Methods In-depth interviews (IDIs) were conducted in 7 health centres in Kalomo district between 1st April and 20th May, 2015 with 46 respondents comprising 22 SMAG members, 5 headmen, 10 mothers, 3 husbands, 5 nurses, and 1 district maternal and child health coordinator. Perspectives on the selection, training, roles, achievements and challenges of the SMAG programme were explored. Results Respondents were aware of the presence, selection, training and roles of the SMAG members and had a positive attitude towards the programme. They believed that the SMAG programme led to an increase in women’s risk perception about pregnancy and childbirth-related complications. Further, participants believed that the programme resulted in increased utilisation of facility-based antenatal, delivery and postnatal care, and improvement in maternal and newborn health outcomes. However, various challenges affected implementation of the SMAG programme. Among these were insufficient material and financial support to the programme, lack of refresher training for SMAG members, poor quality of care in health care facilities due to a lack of maternity waiting homes, low staffing levels in health facilities, the poor state and small size of the labour wards, and lack of equipment to handle obstetric emergencies. Conclusion The SMAG programme has potential to be an important community intervention for increasing utilisation of facility-based skilled care and improving maternal and newborn health outcomes.

Abstract Background More than 30,000 malaria cases are reported annually among international travellers. Despite improvements in malaria control, malaria continues to threaten travellers due to inaccurate perception of risk and sub-optimal pre-travel preparation. Methods Records with a confirmed malaria diagnosis after travel from January 2003 to July 2016 were obtained from GeoSentinel, a global surveillance network of travel and tropical medicine providers that monitors travel-related morbidity. Records were excluded if exposure country was missing or unascertainable or if there was a concomitant acute diagnosis unrelated to malaria. Records were analyzed to describe the demographic and clinical characteristics of international travellers with malaria. Results There were 5689 travellers included; 325 were children

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.

Abstract Background Residential accommodation for expectant mothers adjacent to health facilities, known as maternity waiting homes (MWH), is an intervention designed to improve access to skilled deliveries in low-income countries like Zambia where the maternal mortality ratio is estimated at 398 deaths per 100,000 live births. Our study aimed to assess the relationship between MWH quality and the likelihood of facility delivery in Kalomo and Choma Districts in Southern Province, Zambia. Methods We systematically assessed and inventoried the functional capacity of all existing MWH using a quantitative facility survey and photographs of the structures. We calculated a composite score and used multivariate regression to quantify MWH quality and its association with the likelihood of facility delivery using household survey data collected on delivery location in Kalomo and Choma Districts from 2011–2013. Results MWH were generally in poor condition and composite scores varied widely, with a median score of 28.0 and ranging from 12 to 66 out of a possible 75 points. Of the 17,200 total deliveries captured from 2011–2013 in 40 study catchment area facilities, a higher proportion occurred in facilities where there was either a MWH or the health facility provided space for pregnant waiting mothers compared to those with no accommodations (60.7% versus 55.9%, p

Abstract Background Although the association between the presence of maternity waiting homes (MWHs) and the personal and environmental factors that affect the use of MWHs has been explained in qualitative terms, it has never been tested in quantitative terms. The aim of this study was to test the association between the presence of MWHs and personal and environmental factors that affect the use of MWHs. Methods A cross-sectional study was conducted using an interviewer-administered questionnaire from 1st July to 31st August, 2014 among 340 women of reproductive age in 15 rural health centres in Kalomo district, Zambia. Tests of association (chi square, logistic regression analysis, odds ratio) were conducted to determine the strength of the association between the presence of MWHs and personal and environmental factors. Differences between respondents who used MWHs and those who did not were also tested. Results Compared to respondents from health centres without MWHs, those from centres with MWHs had higher odds of expressing willingness to use MWHs (adjusted odds ratio [aOR] = 4.58; 95% confidence interval [CI]:1.39–15.17), perceived more benefits from using a MWH (aOR =8.63; 95% CI: 3.13–23.79), perceived more social pressure from important others to use MWH (aOR =27.09; 95% CI: 12.23–60.03) and higher personal risk from pregnancy and childbirth related complications (aOR =11.63; 95% CI: 2.52–53.62). Furthermore, these respondents had higher odds of staying at a health centre before delivery (aOR =1.78; 95% CI: 1.05–3.02), giving birth at a health facility (aOR = 3.36; 95% CI: 1.85–6.12) and receiving care from a skilled birth attendant (aOR =3.24; 95% CI: 1.80–5.84). In contrast, these respondents had lower odds of perceiving barriers regarding the use of MWHs (aOR =0.27; 95% CI: 0.16–0.47). Factors positively associated with the use of MWHs included longer distances to the nearest health centre (p = 0.004), higher number of antenatal care (ANC) visits (p = 0.001), higher proportions of complications during ANC (p = 0.09) and women’s perception of benefits gained from staying in a MWH while waiting for delivery at the health centre (p = 0.001). Conclusion These findings suggest a need for health interventions that focus on promoting ANC use, raising awareness about the risk and severity of pregnancy complications, promoting family and community support, and mitigating logistical barriers.