Antibiotic resistance trends for common bacterial aetiologies of childhood diarrhoea in low- and middle-income countries: A systematic review.

Background: Diarrhoea is the second most common cause of death among children under the age of five worldwide. The World Health Organization (WHO) recommends treating diarrhoea with oral rehydration therapy, intravenous fluids for severe dehydration, and zinc supplements. Antibiotics are only recommended to treat acute, invasive diarrhoea. Rising antibiotic resistance has led to a decrease in the effectiveness of treatments for diarrhoea. Methods: A systematic literature review in PubMed, Web of Science, and EMBASE was conducted to identify articles relevant to antibiotic-resistant childhood diarrhoea. Articles in English published between 1990 to 2020 that described antibiotic resistance patterns of common pathogens causing childhood diarrhoea in low- and middle-income countries were included. The studies were limited to papers that categorized children as 0-5 years or 0-10 years old. The proportion of isolates with resistance to major classes of antibiotics stratified by major WHO global regions and time was determined. Results: Quantitative data were extracted from 44 articles that met screening criteria; most focused on children under five years. Escherichia coli isolates had relatively high resistance rates to ampicillin and tetracycline in the African (AFR), American (AMR), and Eastern Mediterranean Regions (EMR). There was moderate to high resistance to ampicillin and third generation cephalosporins among Salmonella spp in the AFR, EMR, and the Western Pacific Region (WPR). Resistance rates for ampicillin, co-trimoxazole, and chloramphenicol for Shigella in the AFR started at an alarmingly high rate ( ~ 90%) in 2006 and fluctuated over time. There were limited antibiotic resistance data for Aeromonas, Yersinia, and V. cholerae. The 161 isolates of Campylobacter analysed showed initially low rates of fluoroquinolone resistance with high rates of resistance in recent years, especially in the Southeast Asian Region. Conclusions: Resistance to inexpensive antibiotics for treatment of invasive diarrhoea in children under ten years is widespread (although data on 6- to 10-year-old children are limited), and resistance rates to fluoroquinolones and later-generation cephalosporins are increasing. A strong regional surveillance system is needed to carefully monitor trends in antibiotic resistance, future studies should include school-aged children, and interventions are needed to reduce inappropriate use of antibiotics for the treatment of community-acquired, non-invasive diarrhoea. Registration: This systematic review was registered in Prospero (registration number CRD42020204004) in August 2020.

Travel-Related Diagnoses Among U.S. Nonmigrant Travelers or Migrants Presenting to U.S. GeoSentinel Sites - GeoSentinel Network, 2012-2021.

Problem/Condition: During 2012-2021, the volume of international travel reached record highs and lows. This period also was marked by the emergence or large outbreaks of multiple infectious diseases (e.g., Zika virus, yellow fever, and COVID-19). Over time, the growing ease and increased frequency of travel has resulted in the unprecedented global spread of infectious diseases. Detecting infectious diseases and other diagnoses among travelers can serve as sentinel surveillance for new or emerging pathogens and provide information to improve case identification, clinical management, and public health prevention and response. Reporting Period: 2012-2021. Description of System: Established in 1995, the GeoSentinel Network (GeoSentinel), a collaboration between CDC and the International Society of Travel Medicine, is a global, clinical-care-based surveillance and research network of travel and tropical medicine sites that monitors infectious diseases and other adverse health events that affect international travelers. GeoSentinel comprises 71 sites in 29 countries where clinicians diagnose illnesses and collect demographic, clinical, and travel-related information about diseases and illnesses acquired during travel using a standardized report form. Data are collected electronically via a secure CDC database, and daily reports are generated for assistance in detecting sentinel events (i.e., unusual patterns or clusters of disease). GeoSentinel sites collaborate to report disease or population-specific findings through retrospective database analyses and the collection of supplemental data to fill specific knowledge gaps. GeoSentinel also serves as a communications network by using internal notifications, ProMed alerts, and peer-reviewed publications to alert clinicians and public health professionals about global outbreaks and events that might affect travelers. This report summarizes data from 20 U.S. GeoSentinel sites and reports on the detection of three worldwide events that demonstrate GeoSentinel's notification capability. Results: During 2012-2021, data were collected by all GeoSentinel sites on approximately 200,000 patients who had approximately 244,000 confirmed or probable travel-related diagnoses. Twenty GeoSentinel sites from the United States contributed records during the 10-year surveillance period, submitting data on 18,336 patients, of which 17,389 lived in the United States and were evaluated by a clinician at a U.S. site after travel. Of those patients, 7,530 (43.3%) were recent migrants to the United States, and 9,859 (56.7%) were returning nonmigrant travelers.Among the recent migrants to the United States, the median age was 28.5 years (range = <19 years to 93 years); 47.3% were female, and 6.0% were U.S. citizens. A majority (89.8%) were seen as outpatients, and among 4,672 migrants with information available, 4,148 (88.8%) did not receive pretravel health information. Of 13,986 diagnoses among migrants, the most frequent were vitamin D deficiency (20.2%), Blastocystis (10.9%), and latent tuberculosis (10.3%). Malaria was diagnosed in 54 (<1%) migrants. Of the 26 migrants diagnosed with malaria for whom pretravel information was known, 88.5% did not receive pretravel health information. Before November 16, 2018, patients' reasons for travel, exposure country, and exposure region were not linked to an individual diagnosis. Thus, results of these data from January 1, 2012, to November 15, 2018 (early period), and from November 16, 2018, to December 31, 2021 (later period), are reported separately. During the early and later periods, the most frequent regions of exposure were Sub-Saharan Africa (22.7% and 26.2%, respectively), the Caribbean (21.3% and 8.4%, respectively), Central America (13.4% and 27.6%, respectively), and South East Asia (13.1% and 16.9%, respectively). Migrants with diagnosed malaria were most frequently exposed in Sub-Saharan Africa (89.3% and 100%, respectively).Among nonmigrant travelers returning to the United States, the median age was 37 years (range = <19 years to 96 years); 55.7% were female, 75.3% were born in the United States, and 89.4% were U.S. citizens. A majority (90.6%) were seen as outpatients, and of 8,967 nonmigrant travelers with available information, 5,878 (65.6%) did not receive pretravel health information. Of 11,987 diagnoses, the most frequent were related to the gastrointestinal system (5,173; 43.2%). The most frequent diagnoses among nonmigrant travelers were acute diarrhea (16.9%), viral syndrome (4.9%), and irritable bowel syndrome (4.1%).Malaria was diagnosed in 421 (3.5%) nonmigrant travelers. During the early (January 1, 2012, to November 15, 2018) and later (November 16, 2018, to December 31, 2021) periods, the most frequent reasons for travel among nonmigrant travelers were tourism (44.8% and 53.6%, respectively), travelers visiting friends and relatives (VFRs) (22.0% and 21.4%, respectively), business (13.4% and 12.3%, respectively), and missionary or humanitarian aid (13.1% and 6.2%, respectively). The most frequent regions of exposure for any diagnosis among nonmigrant travelers during the early and later period were Central America (19.2% and 17.3%, respectively), Sub-Saharan Africa (17.7% and 25.5%, respectively), the Caribbean (13.0% and 10.9%, respectively), and South East Asia (10.4% and 11.2%, respectively).Nonmigrant travelers who had malaria diagnosed were most frequently exposed in Sub-Saharan Africa (88.6% and 95.9% during the early and later period, respectively) and VFRs (70.3% and 57.9%, respectively). Among VFRs with malaria, a majority did not receive pretravel health information (70.2% and 83.3%, respectively) or take malaria chemoprophylaxis (88.3% and 100%, respectively). Interpretation: Among ill U.S. travelers evaluated at U.S. GeoSentinel sites after travel, the majority were nonmigrant travelers who most frequently received a gastrointestinal disease diagnosis, implying that persons from the United States traveling internationally might be exposed to contaminated food and water. Migrants most frequently received diagnoses of conditions such as vitamin D deficiency and latent tuberculosis, which might result from adverse circumstances before and during migration (e.g., malnutrition and food insecurity, limited access to adequate sanitation and hygiene, and crowded housing,). Malaria was diagnosed in both migrants and nonmigrant travelers, and only a limited number reported taking malaria chemoprophylaxis, which might be attributed to both barriers to acquiring pretravel health care (especially for VFRs) and lack of prevention practices (e.g., insect repellant use) during travel. The number of ill travelers evaluated by U.S. GeoSentinel sites after travel decreased in 2020 and 2021 compared with previous years because of the COVID-19 pandemic and associated travel restrictions. GeoSentinel detected limited cases of COVID-19 and did not detect any sentinel cases early in the pandemic because of the lack of global diagnostic testing capacity. Public Health Action: The findings in this report describe the scope of health-related conditions that migrants and returning nonmigrant travelers to the United States acquired, illustrating risk for acquiring illnesses during travel. In addition, certain travelers do not seek pretravel health care, even when traveling to areas in which high-risk, preventable diseases are endemic. Health care professionals can aid international travelers by providing evaluations and destination-specific advice.Health care professionals should both foster trust and enhance pretravel prevention messaging for VFRs, a group known to have a higher incidence of serious diseases after travel (e.g., malaria and enteric fever). Health care professionals should continue to advocate for medical care in underserved populations (e.g., VFRs and migrants) to prevent disease progression, reactivation, and potential spread to and within vulnerable populations. Because both travel and infectious diseases evolve, public health professionals should explore ways to enhance the detection of emerging diseases that might not be captured by current surveillance systems that are not site based.

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).

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.

Validation of visual estimation of neonatal jaundice in low-income and middle-income countries: a multicentre observational cohort study.

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.

Household Costs Associated with Hospitalization of Children with Severe Pneumonia in Quito, Ecuador.

Pneumonia remains a leading cause of morbidity and mortality in young children. The total cost of pneumonia-related hospitalization, including household-level cost, is poorly understood. To better understand this burden in an urban setting in South America, we incorporated a cost study into a trial assessing zinc supplements in treatment of severe pneumonia among children aged 2-59 months at a public hospital in Quito, Ecuador, which provides such treatment at no charge. Data were collected from children's caregivers at hospitalization and discharge on out-of-pocket payments for medical and nonmedical items, and on employment and lost work time. Analyses encompassed three categories: direct medical costs, direct nonmedical costs, and indirect costs, which covered foregone wages (from caregivers' self-reported lost earnings) and opportunity cost of caregivers' lost time (based on the unskilled labor wage in Ecuador). Caregivers of 153 children completed all questionnaires. Overall, 57% of children were aged less than 12 months, and 46% were female. Just over 50% of mothers and fathers had completed middle school. Most reported direct costs, which averaged $33. Most also reported indirect costs, the mean of which was $74. Fifty-seven reported lost earnings (mean = $79); 29 reported lost time (estimated mean cost = $37). Stratified analyses revealed similar costs for children < 12 months and ≥ 12 months, with variations for specific items. Costs for hospital-based treatment of severe pneumonia in young children represent a major burden for households in low- to middle-income settings, even when such treatment is intended to be provided at no cost.

Prevention and treatment of malaria in pregnancy: what do pregnant women and health care workers in East India know and do about it?

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.

Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis-1997-2016.

Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.

Listening to the community: Using formative research to strengthen maternity waiting homes in Zambia.

BACKGROUND: The WHO recommends maternity waiting homes (MWH) as one intervention to improve maternal and newborn health. However, persistent structural, cultural and financial barriers in their design and implementation have resulted in mixed success in both their uptake and utilization. Guidance is needed on how to design a MWH intervention that is acceptable and sustainable. Using formative research and guided by a sustainability framework for health programs, we systematically collected data from key stakeholders and potential users in order to design a MWH intervention in Zambia that could overcome multi-dimensional barriers to accessing facility delivery, be acceptable to the community and be financially and operationally sustainable. METHODS AND FINDINGS: We used a concurrent triangulation study design and mixed methods. We used free listing to gather input from a total of 167 randomly sampled women who were pregnant or had a child under the age of two (n = 59), men with a child under the age of two (n = 53), and community elders (n = 55) living in the catchment areas of four rural health facilities in Zambia. We conducted 17 focus group discussions (n = 135) among a purposive sample of pregnant women (n = 33), mothers-in-law (n = 32), traditional birth attendants or community maternal health promoters (n = 38), and men with a child under two (n = 32). We administered 38 semi-structured interviews with key informants who were identified by free list respondents as having a stake in the condition and use of MWHs. Lastly, we projected fixed and variable recurrent costs for operating a MWH. Respondents most frequently mentioned distance, roads, transport, and the quality of MWHs and health facilities as the major problems facing pregnant women in their communities. They also cited inadequate advanced planning for delivery and the lack of access to delivery supplies and baby clothes as other problems. Respondents identified the main problems of MWHs specifically as over-crowding, poor infrastructure, lack of amenities, safety concerns, and cultural issues. To support operational sustainability, community members were willing to participate on oversight committees and contribute labor. The annual fixed recurrent cost per 10-bed MWH was estimated as USD543, though providing food and charcoal added another $3,000USD. Respondents identified water pumps, an agriculture shop, a shop for baby clothes and general goods, and grinding mills as needs in their communities that could potentially be linked with an MWH for financial sustainability. CONCLUSIONS: Findings informed the development of an intervention model for renovating existing MWH or constructing new MWH that meets community standards of safety, comfort and services offered and is aligned with government policies related to facility construction, ownership, and access to health services. The basic strategies of the new MWH model include improving community acceptability, strengthening governance and accountability, and building upon existing efforts to foster financial and operational sustainability. The proposed model addresses the problems cited by our respondents and challenges to MWHs identified by in previous studies and elicits opportunities for social enterprises that could serve the dual purpose of meeting a community need and generating revenue for the MWH.

Etiology of severe pneumonia in Ecuadorian children.

BACKGROUND: In Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador. METHODS: This observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2-59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction. Risk factors for specific respiratory pathogens were also evaluated. RESULTS: Among 406 children tested, 159 (39.2%) had respiratory syncytial virus (RSV), 71 (17.5%) had human metapneumovirus (hMPV), and 62 (15.3%) had adenovirus. Streptococcus pneumoniae was identified in 37 (9.2%) samples and Mycoplasma pneumoniae in three (0.74%) samples. The yearly circulation pattern of RSV (P = 0.0003) overlapped with S. pneumoniae, (P = 0.03) with most cases occurring in the rainy season. In multivariable analysis, risk factors for RSV included younger age (adjusted odds ratio [aOR] = 1.9, P = 0.01) and being underweight (aOR = 1.8, P = 0.04). Maternal education (aOR = 0.82, P = 0.003), pulse oximetry (aOR = 0.93, P = 0.005), and rales (aOR = 0.25, P = 0.007) were associated with influenza A. Younger age (aOR = 3.5, P = 0.007) and elevated baseline respiratory rate were associated with HPIV-3 infection (aOR = 0.94, P = 0.03). CONCLUSION: These results indicate the importance of RSV and influenza, and potentially modifiable risk factors including undernutrition and future use of a RSV vaccine, when an effective vaccine becomes available. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00513929.

Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.

AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania. We randomly allocated equal numbers of participants to 2,500 IU of vitamin A, 25 mg of zinc, both 2,500 IU of vitamin A and 25 mg of zinc, or a placebo until delivery. A total of 625 participants were allocated to each treatment group. Our primary outcome, placental malaria infection (past or current), was assessed in all randomized participants for whom placental samples were obtained at delivery (N = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer (N = 2,266). Birth outcomes were obtained for 2,434 of the 2,500 randomized participants. Secondary outcomes included small for gestational age (SGA) births and prematurity. All analyses were intent to treat. Those who received zinc had a lower risk of histopathology-positive placental malaria compared with those who did not receive zinc (risk ratio = 0.64, 95% confidence interval = 0.44, 0.91), but neither nutrient had an effect on polymerase chain reaction-positive malaria, SGA, or prematurity. No safety concerns were identified. We recommend additional studies in other geographic locations to confirm these findings.

Etiology, Antibiotic Resistance and Risk Factors for Neonatal Sepsis in a Large Referral Center in Zambia.

BACKGROUND: In sub-Saharan Africa, there is scanty data on the causes of neonatal sepsis and antimicrobial resistance among common invasive pathogens that might guide policy and practice. METHODS: A cross-sectional observational prevalence and etiology study of neonates with suspected sepsis admitted to the neonatal intensive care unit, University Teaching Hospital, Lusaka, Zambia, between October 2013 and May 2014. Data from blood cultures and phenotypic antibiotic susceptibility testing were compared with multivariate analysis of risk factors for neonatal sepsis. RESULTS: Of 313 neonates with suspected sepsis, 54% (170/313) were male; 20% (62/313) were born to HIV-positive mothers; 33% (103/313) had positive blood cultures, of which 85% (88/103) were early-onset sepsis. Klebsiella species was the most prevalent isolate, accounting for 75% (77/103) of cases, followed by coagulase-negative staphylococci [6% (7/103)], Staphylococcus aureus [6% (6/103)], Escherichia coli [5% (5/103)] and Candida species [5% (5/103)]. For Klebsiella species, antibiotic resistance ranged from 96%-99% for World Health Organization-recommended first-line therapy (gentamicin and ampicillin/penicillin) to 94%-97% for third-generation cephalosporins. The prevalence of culture-confirmed sepsis increased from 0 to 39% during the period December 2013 to March 2014, during which time mortality increased 29%-47%; 93% (14/15) of late-onset sepsis and 82% (37/45) of early-onset sepsis aged 4-7 days were admitted >2 days before the onset of symptoms. Culture results for only 25% (26/103) of cases were available before discharge or death. Maternal HIV infection was associated with a reduced risk of neonatal sepsis [odds ratio, 0.46 (0.23-0.93); P = 0.029]. CONCLUSIONS: Outbreaks of nosocomial multiantibiotic-resistant infections are an important cause of neonatal sepsis and associated mortality. Reduced risk of neonatal sepsis associated with maternal HIV infection is counterintuitive and requires further investigation.

Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. OBJECTIVE: We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly. DESIGN: This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 µg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. RESULTS: Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, in the zinc group than in the placebo group (P = 0.007) when baseline zinc concentrations were controlled for. In addition, controlling for baseline C-reactive protein, copper, or albumin did not change the results. However, supplementation of participants with ≤60 µg serum Zn/dL failed to increase their serum zinc to ≥70 µg/dL. Zinc supplementation also significantly increased anti-CD3/CD28 and phytohemagglutinin-stimulated T cell proliferation, and the number of peripheral T cells (P < 0.05). When proliferation was expressed per number of T cells, the significant differences between groups were lost, suggesting that the zinc-induced enhancement of T cell proliferation was mainly due to an increase in the number of T cells. CONCLUSIONS: Zinc supplementation at 30 mg/d for 3 mo is effective in increasing serum zinc concentrations in nursing home elderly; however, not all zinc-deficient elderly reached adequate concentrations. The increase in serum zinc concentration was associated with the enhancement of T cell function mainly because of an increase in the number of T cells.

A Cluster Randomised Trial on the Impact of Integrating Early Infant HIV Diagnosis with the Expanded Programme on Immunization on Immunization and HIV Testing Rates in Rural Health Facilities in Southern Zambia.

BACKGROUND: We assessed the integration of early infant HIV diagnosis with the expanded programme for immunization in a rural Zambian setting with the aim of determining whether infant and postpartum maternal HIV testing rates would increase without harming immunization uptake. METHODS: In an unblinded, location stratified, cluster randomised controlled trial, 60 facilities in Zambia's Southern Province were equally allocated to a control group, Simple Intervention group that received a sensitization meeting and the resupply of HIV testing commodities in the event of a stock-out, and a Comprehensive Intervention group that received the Simple Intervention as well as on-site operational support to facilitate the integration of HIV testing services with EPI. FINDINGS: The average change in number of first dose diphtheria, pertussis, and tetanus vaccine (DPT1) provided per month, per facility was approximately 0.86 doses higher [90% confidence interval (CI) -1.40, 3.12] in Comprehensive Intervention facilities compared to the combined average change in the Simple Intervention and control facilities. The interventions resulted in a 16.6% [90% CI: -7%, 46%, P-value = 0.26] and 10% [90% CI: -10%, 36%, P-value = 0.43] greater change in average monthly infant DBS testing compared to control for the Simple and Comprehensive facilities respectively. We also found 15.76 (90% CI: 7.12, 24.41, P-value < 0.01) and 10.93 (90% CI: 1.52, 20.33, P-value = 0.06) additional total maternal re-tests over baseline for the Simple and Comprehensive Facilities respectively. CONCLUSIONS: This study provides strong evidence to support Zambia's policy of integration of HIV testing and EPI services. Actions in line with the interventions, including HIV testing material supply reinforcement, can increase HIV testing rates without harming immunization uptake. In response, Zambia's Ministry of Health issued a memo to remind health facilities to provide HIV testing at under-five clinics and to include under-five HIV testing as part of district performance assessments. TRIAL REGISTRATION: ClinicalTrials.gov REGISTRATION NUMBER: NCT02479659.

Reasons for home delivery and use of traditional birth attendants in rural Zambia: a qualitative study.

BACKGROUND: Despite the policy change stopping traditional birth attendants (TBAs) from conducting deliveries at home and encouraging all women to give birth at the clinic under skilled care, many women still give birth at home and TBAs are essential providers of obstetric care in rural Zambia. The main reasons for pregnant women's preference for TBAs are not well understood. This qualitative study aimed to identify reasons motivating women to giving birth at home and seek the help of TBAs. This knowledge is important for the design of public health interventions focusing on promoting facility-based skilled birth attendance in Zambia. METHODS: We conducted ten focus group discussions (n = 100) with women of reproductive age (15-45 years) in five health centre catchment areas with the lowest institutional delivery rates in the district. In addition, a total of 30 in-depth interviews were conducted comprising 5 TBAs, 4 headmen, 4 husbands, 4 mothers, 4 neighbourhood health committee (NHC) members, 4 community health workers (CHWs) and 5 nurses. Perspectives on TBAs, the decision-making process regarding home delivery and use of TBAs, and reasons for preference of TBAs and their services were explored. RESULTS: Our findings show that women's lack of decision- making autonomy regarding child birth, dependence on the husband and other family members for the final decision, and various physical and socioeconomic barriers including long distances, lack of money for transport and the requirement to bring baby clothes and food while staying at the clinic, prevented them from delivering at a clinic. In addition, socio-cultural norms regarding childbirth, negative attitude towards the quality of services provided at the clinic, made most women deliver at home. Moreover, most women had a positive attitude towards TBAs and perceived them to be respectful, skilled, friendly, trustworthy, and available when they needed them. CONCLUSION: Our findings suggest a need to empower women with decision-making skills regarding childbirth and to lower barriers that prevent them from going to the health facility in time. There is also need to improve the quality of existing facility-based delivery services and to strengthen linkages between TBAs and the formal health system.

Iron Supplementation in Iron-Replete and Nonanemic Pregnant Women in Tanzania: A Randomized Clinical Trial.

IMPORTANCE: Anemia is common in pregnancy and increases the risk of adverse outcomes. Iron deficiency is a leading cause of anemia in sub-Saharan Africa, and iron supplementation is the standard of care during pregnancy; however, recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions. There is limited evidence on the safety of iron supplementation during pregnancy in these areas. OBJECTIVE: To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region. DESIGN, SETTING, AND PARTICIPANTS: We conducted a randomized, double-blind, placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam, Tanzania, from September 28, 2010, through October 4, 2012. Iron-replete, nonanemic women were eligible if they were uninfected with human immunodeficiency virus, primigravidae or secundigravidae, and at or before 27 weeks of gestation. Screening of 21,316 women continued until the target enrollment of 1500 was reached. Analyses followed the intent-to-treat principle and included all randomized participants. INTERVENTIONS: Participants were randomized to receive 60 mg of iron or placebo, returning every 4 weeks for standard prenatal care, including malaria screening, prophylaxis with the combination of sulfadoxine and pyrimethamine, and treatment, as needed. MAIN OUTCOMES AND MEASURES: The primary outcomes were placental malaria, maternal hemoglobin level at delivery, and birth weight. RESULTS: Among 1500 study participants (750 randomized for each group), 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental samples included in the analysis. Maternal characteristics were similar at baseline in the iron and placebo groups, and 1354 (91.7%) used malaria control measures. The risk of placental malaria was not increased by maternal iron supplementation (relative risk [RR], 1.03; 95% CI, 0.65-1.65), and iron supplementation did not significantly affect birth weight (3155 vs 3137 g, P = .89). Compared with placebo, iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin (0.1 vs -0.7 g/dL, P < .001) and serum ferritin (41.3 vs 11.3 µg/L, P < .001). Iron supplementation significantly decreased the risk of anemia at delivery by 40% (RR, 0.60; 95% CI, 0.51-0.71) but not severe anemia (RR, 0.68; 95% CI, 0.41-1.14). Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52% (RR, 0.48; 95% CI, 0.32-0.70) and the risk of iron deficiency anemia by 66% (RR, 0.34; 95% CI, 0.19-0.62). CONCLUSIONS AND RELEVANCE: Prenatal iron supplementation among iron-replete, nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control. Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group. These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01119612.

Malian children with moderate acute malnutrition who are treated with lipid-based dietary supplements have greater weight gains and recovery rates than those treated with locally produced cereal-legume products: a community-based, cluster-randomized trial.

BACKGROUND: Moderate acute malnutrition (MAM), defined as weight-for-length z score between -3 and -2 or midupper arm circumference between 11.5 and 12.5 cm, affects ∼33 million children aged <5 y worldwide. OBJECTIVE: The objective was to compare the effects of 4 dietary supplements for the treatment of MAM. DESIGN: Twelve community health centers in rural Mali were randomly assigned to provide to 1264 MAM children aged 6-35 mo one of 4 dietary supplements containing ∼500 kcal/d for 12 wk: 1) ready-to-use, lipid-based supplementary food (RUSF); 2) special corn-soy blend (CSB++); 3) locally processed, fortified flour (Misola); or 4) locally milled flours plus oil, sugar, and micronutrient powder (LMF). RESULTS: In total, 1178 children (93.2%) completed the study. The adjusted mean (95% CI) change in weight (kg) from baseline was greater with RUSF than with the locally processed blends and was intermediate with CSB++ [1.16 (1.08, 1.24) for RUSF, 1.04 (0.96, 1.13) for CSB++, 0.91 (0.82, 0.99) for Misola, and 0.83 (0.74, 0.92) for LMF; P < 0.001]. For length change, RUSF and CSB++ differed significantly from LMF. Sustained recovery rates were higher with RUSF (73%) than with Misola (61%) and LMF (58%), P < 0.0001; CSB++ recovery rates (68%) did not differ from any of the other groups. CONCLUSIONS: RUSF was more effective, but more costly, than other dietary supplements for the treatment of MAM; CSB++ yielded intermediate results. The benefits of treatment should be considered in relation to product costs and availability.

Can a community health worker and a trained traditional birth attendant work as a team to deliver child health interventions in rural Zambia?

BACKGROUND: Teaming is an accepted approach in health care settings but rarely practiced at the community level in developing countries. Save the Children trained and deployed teams of volunteer community health workers (CHWs) and trained traditional birth attendants (TBAs) to provide essential newborn and curative care for children aged 0-59 months in rural Zambia. This paper assessed whether CHWs and trained TBAs can work as teams to deliver interventions and ensure a continuum of care for all children under-five, including newborns. METHODS: We trained CHW-TBA teams in teaming concepts and assessed their level of teaming prospectively every six months for two years. The overall score was a function of both teamwork and taskwork. We also assessed personal, community and service factors likely to influence the level of teaming. RESULTS: We created forty-seven teams of predominantly younger, male CHWs and older, female trained TBAs. After two years of deployment, twenty-one teams scored "high", twelve scored "low," and fourteen were inactive. Teamwork was high for mutual trust, team cohesion, comprehension of team goals and objectives, and communication, but not for decision making/planning. Taskwork was high for joint behavior change communication and outreach services with local health workers, but not for intra-team referral. Teams with members residing within one hour's walking distance were more likely to score high. CONCLUSION: It is feasible for a CHW and a trained TBA to work as a team. This may be an approach to provide a continuum of care for children under-five including newborns.