Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic.

The Zika epidemic in the Americas has challenged surveillance and control. As the epidemic appears to be waning, it is unclear whether transmission is still ongoing, which is exacerbated by discrepancies in reporting. To uncover locations with lingering outbreaks, we investigated travel-associated Zika cases to identify transmission not captured by reporting. We uncovered an unreported outbreak in Cuba during 2017, a year after peak transmission in neighboring islands. By sequencing Zika virus, we show that the establishment of the virus was delayed by a year and that the ensuing outbreak was sparked by long-lived lineages of Zika virus from other Caribbean islands. Our data suggest that, although mosquito control in Cuba may initially have been effective at mitigating Zika virus transmission, such measures need to be maintained to be effective. Our study highlights how Zika virus may still be "silently" spreading and provides a framework for understanding outbreak dynamics. VIDEO ABSTRACT.

Transmission Dynamics and Rare Clustered Transmission Within an Urban University Population Before Widespread Vaccination.

BACKGROUND: Universities returned to in-person learning in 2021 while SARS-CoV-2 spread remained high. At the time, it was not clear whether in-person learning would be a source of disease spread. METHODS: We combined surveillance testing, universal contact tracing, and viral genome sequencing to quantify introductions and identify likely on-campus spread. RESULTS: Ninety-one percent of viral genotypes occurred once, indicating no follow-on transmission. Less than 5% of introductions resulted in >3 cases, with 2 notable exceptions of 40 and 47 cases. Both partially overlapped with outbreaks defined by contact tracing. In both cases, viral genomics eliminated over half the epidemiologically linked cases but added an equivalent or greater number of individuals to the transmission cluster. CONCLUSIONS: Public health interventions prevented within-university transmission for most SARS-CoV-2 introductions, with only 2 major outbreaks being identified January to May 2021. The genetically linked cases overlap with outbreaks identified by contact tracing; however, they persisted in the university population for fewer days and rounds of transmission than estimated via contact tracing. This underscores the effectiveness of test-trace-isolate strategies in controlling undetected spread of emerging respiratory infectious diseases. These approaches limit follow-on transmission in both outside-in and internal transmission conditions.

Organ donation and HIV: Awareness and willingness to be a living donor among people with HIV in Uganda.

BACKGROUND: HIV+-to-HIV+ organ transplantation has demonstrated promise and is now authorized for research purposes in certain countries. However, organ transplantation is dependent on the availability of organ donors. We assessed the awareness and willingness to donate organs among people with HIV (PWH) in Uganda. METHODS: We conducted a multicenter cross-sectional study between October 2023 and January 2024 in four large HIV clinics in Northern Uganda. The study population consisted of PWH. A structured questionnaire was used to collect data regarding awareness, willingness, and beliefs regarding organ donation. Organ donation was defined as the willingness to be a living donor of a solid organ. We conducted multivariable logistic regression to assess for an association between willingness to donate organs and selected exposures. Data were analyzed in Stata version 15.0. Results are expressed as adjusted odds ratio (AOR) with 95% confidence intervals (CI). RESULTS: A total of 232 participants were recruited. The mean age ± standard deviation of the participants was 42.2±11.8 years. All participants were on antiretroviral therapy. Sixty-two (26.7%) had a CD4 count less than or equal to 200 cells/mm3. The majority (80.6%, n = 187) had ever heard of organ donation. Slightly more than a third (34.9%, n = 81) were willing to donate organs. Factors associated with willingness to be a living organ donor included being female (AOR: 1.56; 95% CI: 1.15-2.11), having a tertiary education level (AOR: 1.79; 95% CI: 1.03-3.11), average monthly income >500 000 UGX (135.1USD) (AOR: 5.5; 95% CI: 1.97-15.40), ever heard about organ donation (AOR: 5.4; 95% CI: 1.67-17.8), and attending an organ donation campaign (AOR: 2.0; 95% CI: 1.07-3.74). CONCLUSIONS: Awareness about organ donation was high but the willingness to be a living organ donor was low among PWH in Uganda. There is a need to sensitize the community about the need and benefits of organ donation with the involvement of media and the healthcare workers.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Viral Dynamics of Omicron and Delta Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants With Implications for Timing of Release from Isolation: A Longitudinal Cohort Study.

BACKGROUND: In January 2022, US guidelines shifted to recommend isolation for 5 days from symptom onset, followed by 5 days of mask-wearing. However, viral dynamics and variant and vaccination impact on culture conversion are largely unknown. METHODS: We conducted a longitudinal study on a university campus, collecting daily anterior nasal swabs for at least 10 days for reverse-transcription polymerase chain reaction (RT-PCR) testing and culture, with antigen rapid diagnostic testing (RDT) on a subset. We compared culture positivity beyond day 5, time to culture conversion, and cycle threshold trend when calculated from diagnostic test, from symptom onset, by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and by vaccination status. We evaluated sensitivity and specificity of RDT on days 4-6 compared with culture. RESULTS: Among 92 SARS-CoV-2 RT-PCR-positive participants, all completed the initial vaccine series; 17 (18.5%) were infected with Delta and 75 (81.5%) with Omicron. Seventeen percent of participants had positive cultures beyond day 5 from symptom onset, with the latest on day 12. There was no difference in time to culture conversion by variant or vaccination status. For 14 substudy participants, sensitivity and specificity of day 4-6 RDT were 100% and 86%, respectively. CONCLUSIONS: The majority of our Delta- and Omicron-infected cohort culture-converted by day 6, with no further impact of booster vaccination on sterilization or cycle threshold decay. We found that rapid antigen testing may provide reassurance of lack of infectiousness, though guidance to mask for days 6-10 is supported by our finding that 17% of participants remained culture-positive after isolation.

Early Introduction and Rise of the Omicron Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant in Highly Vaccinated University Populations.

BACKGROUND: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible in vaccinated and unvaccinated populations. The dynamics that govern its establishment and propensity toward fixation (reaching 100% frequency in the SARS-CoV-2 population) in communities remain unknown. Here, we describe the dynamics of Omicron at 3 institutions of higher education (IHEs) in the greater Boston area. METHODS: We use diagnostic and variant-specifying molecular assays and epidemiological analytical approaches to describe the rapid dominance of Omicron following its introduction into 3 IHEs with asymptomatic surveillance programs. RESULTS: We show that the establishment of Omicron at IHEs precedes that of the state and region and that the time to fixation is shorter at IHEs (9.5-12.5 days) than in the state (14.8 days) or region. We show that the trajectory of Omicron fixation among university employees resembles that of students, with a 2- to 3-day delay. Finally, we compare cycle threshold values in Omicron vs Delta variant cases on college campuses and identify lower viral loads among college affiliates who harbor Omicron infections. CONCLUSIONS: We document the rapid takeover of the Omicron variant at IHEs, reaching near-fixation within the span of 9.5-12.5 days despite lower viral loads, on average, than the previously dominant Delta variant. These findings highlight the transmissibility of Omicron, its propensity to rapidly dominate small populations, and the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

Evaluation of a community health worker home visit intervention to improve child development in South Africa: A cluster-randomized controlled trial.

BACKGROUND: Effective 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 FINDINGS: We 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. CONCLUSIONS: While 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 REGISTRATION: PACTR 201710002683810; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2683; South African Clinical Trials Registry, SANCTR 4407.

Zika virus infection in European travellers returning from Thailand in 2022: A GeoSentinel case series.

Zika virus is a mosquito-borne flavivirus which caused major epidemics in the Pacific and the Americas between 2013 and 2015. International travellers have previously acted as a sentinel population for Zika virus transmission in endemic areas, where local transmission may be incompletely captured by local surveillance systems. We report five recent European travellers returning from Thailand with Zika virus infection, highlighting the risk of ongoing endemic transmission in this popular tourist destination.

Evaluation of the model malaria elimination strategy in Mandla district along with its neighbouring districts: a time series analysis from 2008 to 2020.

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.

Associations between maternal and infant selenium status and child growth in a birth cohort from Dhaka, Bangladesh.

Deficiency of essential trace element, Se, has been implicated in adverse birth outcomes and in child linear growth because of its important role in redox biology and associated antioxidant effects. We used data from a randomised controlled trial conducted among a cohort of pregnant and lactating women in Dhaka, Bangladesh to examine associations between Se biomarkers in whole blood (WBSe), serum and selenoprotein P (SEPP1) in maternal delivery and venous cord (VC) blood. Associations between Se biomarkers, birth weight and infant growth outcomes (age-adjusted length, weight, head circumference and weight-for-length z-scores) at birth, 1 and 2 years of age were examined using regression analyses. WB and serum Se were negatively associated with birth weight (adjusted ß, 95 % CI, WBSe delivery: −26·6 (­44·3, −8·9); WBSe VC: −19·6 (­33·0, −6·1)); however, delivery SEPP1 levels (adjusted ß: −37·5 (­73·0, −2·0)) and VC blood (adjusted ß: 82·3 (30·0, 134·7)) showed inconsistent and opposite associations with birth weight. Positive associations for SEPP1 VC suggest preferential transfer from mother to fetus. We found small associations between infant growth and WBSe VC (length-for-age z-score ß, 95 % CI, at birth: −0·05 (­0·1, −0·01)); 12 months (ß: −0·05 (­0·08, −0·007)). Weight-for-age z-score also showed weak negative associations with delivery WBSe (at birth: −0·07 (­0·1, −0·02); 12 -months: −0·05 (­0·1, −0·005)) and in WBSe VC (at birth: −0·05 (­0·08, −0·02); 12 months: −0·05 (­0·09, −0·004)). Given the fine balance between essential nutritional and toxic properties of Se, it is possible that WB and serum Se may negatively impact growth outcomes, both in utero and postpartum.

The effect of iron supplementation on maternal iron deficiency anemia does not differ by baseline anemia type among Tanzanian pregnant women without severe iron deficiency anemia.

PURPOSE: Whether anemia type modifies the risk of pregnancy and newborn outcomes and the effectiveness of iron supplementation is unclear. We examined the association of iron deficiency anemia (IDA) and non-iron deficiency anemia (NIDA) on the risks of these outcomes and the extent to which anemia type modifies the impact of prenatal iron supplementation. METHODS: This was a secondary analysis of a placebo-controlled trial of iron supplementation among 1450 HIV-negative women in Tanzania. Eligibility criteria included gestational age < 27 weeks, hemoglobin > 85 g/L, and ferritin > 12 µg/L. Individuals were categorized as non-anemia, IDA or NIDA using hemoglobin, ferritin and CRP. Analyses were conducted using regression models and likelihood ratio tests. RESULTS: Compared to the non-anemia group, delivery hemoglobin was lower by 15 g/L (95% CI 10.9, 19.3) in the baseline IDA group, and 7.3 g/L (95% CI 3.1, 11.5) in the baseline NIDA group. The RRs of anemia severity, iron deficiency, placental malaria, stillbirths, perinatal mortality, birthweight, and preterm birth were not different among women in the baseline NIDA group (vs. non-anemia) compared to the baseline IDA group (vs. non-anemia). The difference in the mean delivery hemoglobin for iron supplementation and placebo arms was 8 g/L (95% CI 6, 11) in the non-anemia group, 7 g/L (95% CI 2, 13) in the NIDA group, and 16 g/L (95% CI 10, 22) in the IDA group. CONCLUSION: Iron supplementation is effective even among pregnant women with NIDA. TRIAL REGISTRATION: NCT01119612 (May 7, 2010).

Postnatal care services in rural Zambia: a qualitative exploration of user, provider, and community perspectives on quality of care.

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.

Real-time Feedback to Improve HIV Treatment Adherence in Pregnant and Postpartum Women in Uganda: A Randomized Controlled Trial.

We assessed an intervention aimed at improving adherence to antiretroviral therapy (ART) among pregnant and postpartum women living with HIV (PPWLH). We randomized 133 pregnant women initiating ART in Uganda to receive text reminders generated by real time-enabled electronic monitors and data-informed counseling through 3 months postpartum (PPM3) or standard care. Intention-to-treat analyses found low adherence levels and no intervention impact. Proportions achieving ≥95% adherence in PPM3 were 16.4% vs. 9.1% (t = -1.14, p = 0.26) in intervention vs. comparison groups, respectively; 30.9% vs. 29.1% achieved ≥80% adherence. Additional analyses found significant adherence declines after delivery, and no effect on disease progression (CD4-cell count, viral load), though treatment interruptions were significantly fewer in intervention participants. Per-protocol analyses encompassing participants who used adherence monitors as designed experienced better outcomes, suggesting potential benefit for some PPWLH. The study was registered on ClinicalTrials.Gov (NCT02396394).

Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh.

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.

Care-Seeking Behavior for Newborns in Rural Zambia.

OBJECTIVES: Mothers in resource-limited areas face barriers in initiating care for ill newborns, leading to delays that may contribute to newborn mortality. This qualitative study conducted in rural Lufwanyama District in Zambia aimed to (1) explore mothers' healthcare-seeking related to newborn illness and (2) identify reasons for delaying care-seeking for ill newborns. METHODS: We examined the perspectives of 60 mothers and 77 grandmothers of children under three years of age in 14 focus group discussions as part of the Lufwanyama Integrated Neonatal and Child Health Program study. We conducted a thematic analysis of verbatim transcripts using dedicated software. RESULTS: Mothers and grandmothers were generally able to identify newborn danger signs and established a hierarchy of care-seeking based on the perceived severity of danger signs. However, inability to afford transportation, inaccessible health care facilities, high costs of medication prescribed at the health clinics, lack of respectful treatment and fear of newborns dying in the hospital prevented participants from seeking timely care. As traditional birth attendants (TBAs) and community health care workers (CHWs) have limited roles in newborns care beyond the immediate delivery setting, mothers often resorted to traditional healers for newborn care. CONCLUSIONS: Based on cultural beliefs and influenced by traditions, mothers in Lufwanyama have developed hierarchical strategies to seek care for ill newborns. Barriers to treatment at health facilities often resulted in traditional care. Training both TBAs and CHWs in providing community-based newborn care and appropriate referrals could improve care-seeking and prevent newborn mortality in rural Zambia.

Postpartum Mental Health in Rural South Africa: Socioeconomic Stressors and Worsening Mental Health.

OBJECTIVES: This study aimed to characterize patterns of worsening mental health during the postpartum period among women in rural areas of Limpopo Province, South Africa, and to identify correlates with household demographic factors. METHODS: We collected data on maternal mental health symptoms shortly after birth and then again 7 months postpartum using the World Health Organization self-reporting questionnaire (SRQ-20) from December 2017 to November 2018. The absolute change in SRQ-20 symptom score was calculated to determine worsening mental health over the postpartum period. Linear regressions were performed to investigate factors associated with mental health symptom scores at varying postpartum time points. RESULTS: We found increased reporting of poor mental health symptoms at 7 months postpartum as compared to shortly after birth (n = 224). Worsening maternal mental health over the postpartum period was associated with higher SRQ-20 symptom score shortly after birth (p < 0.001) and reported food insecurity at 7 months (p < 0.001). SRQ-20 symptom scores in the postpartum period were not associated with breastfeeding in the past 24 h reported at 7 months postpartum (p = 0.08). CONCLUSIONS FOR PRACTICE: Women in rural South Africa, like women in many settings, may be vulnerable to worsening postpartum mental health when they lack sufficient socioeconomic resources and when they have pre-existing depressive/anxiety symptoms.

Comparison of Culture, Antigen Test, and Polymerase Chain Reaction for Pneumococcal Detection in Cerebrospinal Fluid of Children.

BACKGROUND: Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance. METHODS: CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested. RESULTS: Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for >10 weeks. CONCLUSIONS: While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.

Components of clean delivery kits and newborn mortality in the Zambia Chlorhexidine Application Trial (ZamCAT): An observational study.

BACKGROUND: Neonatal 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 FINDINGS: A 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 (<24 hours). Reduction in risk of early newborn death (1-6 days) was associated with use of gloves, cord clamps, plastic sheets, and razor blades. In examining perinatal mortality (stillbirth plus neonatal death in the first 7 days of life), similar patterns were observed. There was no significant reduction in risk of late newborn mortality (7-28 days) with CDK use. Study limitations included potential recall bias of CDK use and inability to establish causality, as this was a secondary observational study. CONCLUSIONS: CDK 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 REGISTRATION: Name of trial: Zambia Chlorhexidine Application Trial (ZamCAT) Name of registry: Clinicaltrials.gov Trial number: NCT01241318.

Direct maternal morbidity and the risk of pregnancy-related deaths, stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries.

BACKGROUND: Maternal 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 FINDINGS: This 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. CONCLUSIONS: Our 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 REGISTRATION: The study is not a clinical trial.

Epidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel Analysis.

Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.