Multidrug resistant Salmonella enterica Serotype Typhi are genetically homologous and coexist with antibiotic- sensitive strains as distinct independent clones

The goal of this study was to report the molecular analysis of antibiotic-sensitive and multidrug resistant (MDR) strains of Salmonella Typhi, using pulsed-field gel electrophoresis (PFGE), with a particular emphasis on the co-existence of these strains in a typhoid-endemic region of Karachi, Pakistan. One hundred isolates of S. typhi in humans (50 MDR and 50 antibiotic-sensitive isolates) from sporadic cases of typhoid fever were analyzed by Vi-phage typing, antibiogram, and PFGE. The MDR S. typhi strains were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Analysis by PFGE showed that 50 MDR isolates of S. typhi had a single, homogeneous PFGE profile, which was distinctly different from that of the 50 antibiotic-sensitive isolates obtained in the same time frame from the same area. This latter group of isolates showed much greater diversity of PFGE profiles, as has been observed in other endemic regions. Multidrug-resistant and antibiotic-susceptible strains of S. typhi can coexist in endemic area as epidemiologically independent pathogens and are not in competition for continued persistence and transmission

Wear Performance Analysis of Ni-Al2O3 Nanocomposite Coatings under Nonconventional Lubrication

This article presents the wear study of Ni-Al2O3 nanocomposite coatings in comparison to uncoated steel contacts under reciprocating motion. A ball-on-flat type contact configuration has been used in this study in which a reciprocating flat steel sample has been used in coated and uncoated state against a stationary steel ball under refrigerant lubrication. The next generation of environmentally friendly refrigerant HFE-7000 has been used as lubricant in this study without the influence of any external lubricant. The thermodynamic applications and performance of HFE-7000 is being studied worldwide as it is replacing the previous generation of refrigerants. No work however has been performed to evaluate the wear performance of HFE-7000 using nanocomposite coatings. The wear scar developed on each of the flat and ball samples was studied under a Scanning Electron Microscope (SEM). The micrographs show that a combination of adhesive and abrasive wear occurs when using uncoated steel samples. Micro-delamination is observed in the case of Ni-Al2O3 nanocomposite coatings accompanied by adhesive and abrasive wear. Wear volume of the wear track was calculated using a White Light Interferometer. Energy-Dispersive X-ray Spectroscopic (EDS) Analysis of the samples reveal fluorine and oxygen on the rubbing parts when tested using coated as well as uncoated samples. The formation of these fluorinated and oxygenated tribo-films help reduce wear and their formation is accelerated by increasing the refrigerant temperature. Ni-Al2O3 nanocomposite coatings show good wear performance at low and high loads in comparison to uncoated contacts. At intermediate loads the coated contacts resulted in increased wear especially at low loads. This increase in wear is associated with the delamination of the coating and the slow formation of protective surface films under these testing conditions

Health care seeking for maternal and newborn illnesses in low- and middle-income countries: a systematic review of observational and qualitative studies [version 1; peer review: 2 approved]

First published: 19 Feb 2019Background: In low- and middle-income countries, a large number of maternal and newborn deaths occur due to delays in health care seeking. These delays occur at three levels i.e. delay in making decision to seek care, delay in access to care, and delay in receiving care. Factors that cause delays are therefore need to be understand to prevent and avoid these delays to improve health and survival of mothers and babies.    Methods: A systematic review of observational and qualitative studies to identify factors and barriers associated with delays in health care seeking. Results: A total of 159 observational and qualitative studies met the inclusion criteria. The review of observational and qualitative studies identified social, cultural and health services factors that contribute to delays in health care seeking, and influence decisions to seek care. Timely recognition of danger signs, availability of finances to arrange for transport and affordability of health care cost, and accessibility to a health facility were some of these factors. Conclusions: Effective dealing of factors that contribute to delays in health care seeking would lead to significant improvements in mortality, morbidity and care seeking outcomes, particularly in countries that share a major brunt of maternal and newborn morbidity and mortality. Registration: PROSPERO CRD42012003236.Zohra S. Lassi, Philippa Middleton, Zulfiqar A. Bhutta, Caroline Crowthe

Born too soon: care before and between pregnancy to prevent preterm births: from evidence to action

This article is part of the supplement: Born too soonProviding care to adolescent girls and women before and between pregnancies improves their own health and wellbeing, as well as pregnancy and newborn outcomes, and can also reduce the rates of preterm birth. This paper has reviewed the evidence based interventions and services for preventing preterm births; reported the findings from research priority exercise; and prescribed actions for taking this call further. Certain factors in the preconception period have been shown to increase the risk for prematurity and, therefore, preconception care services for all women of reproductive age should address these risk factors through preventing adolescent pregnancy, preventing unintended pregnancies, promoting optimal birth spacing, optimizing pre-pregnancy weight and nutritional status (including a folic acid containing multivitamin supplement, and ensuring that all adolescent girls have received complete vaccination. Preconception care must also address risk factors that may be applicable to only some women. These include screening for and management of chronic diseases, especially diabetes; sexually-transmitted infections; tobacco and smoke exposure; mental health disorders, notably depression; and intimate partner violence. The approach to research in preconception care to prevent preterm births should include a cycle of development and delivery research that evaluates how best to scale up coverage of existing, evidence-based interventions, epidemiologic research that assesses the impact of implementing these interventions, and discovery science that better elucidates the complex causal pathway of preterm birth and helps to develop new screening and intervention tools. In addition to research, policy and financial investment is crucial to increasing opportunities to implement preconception care, and rates of prematurity should be included as a tracking indicator in global and national maternal child health assessments.Sohni V Dean, Elizabeth Mary Mason, Christopher P Howson, Zohra S Lassi, Ayesha M Imam, and Zulfiqar A Bhutt

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age

Background: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation (VAS) for children aged 6 to 59 months. The last version of this review was published in 2017, and this is an updated version of that review. Objectives: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. Search methods: We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers up to March 2021. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies. Selection criteria: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation. Data collection and analysis: For this update, two review authors independently assessed studies for inclusion resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence. Main results: The updated search identified no new RCTs. We identified 47 studies, involving approximately 1,223,856 children. Studies were set in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most studies included equal numbers of girls and boys and lasted about one year. The mean age of the children was about 33 months. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for VAS compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-certainty evidence). Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 children; high-certainty evidence). There was no evidence of a difference for VAS on mortality due to measles (RR 0.88, 95% CI 0.69 to 1.11; 6 studies, 1,088,261 children; low-certainty evidence), respiratory disease (RR 0.98, 95% CI 0.86 to 1.12; 9 studies, 1,098,538 children; low-certainty evidence), and meningitis. VAS reduced the incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies, 77,946 children; low-certainty evidence), measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies, 19,566 children; moderate-certainty evidence), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 studies, 1,063,278 children; moderate-certainty evidence), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 studies, 22,972 children; moderate-certainty evidence), and VAD (RR 0.71, 95% CI 0.65 to 0.78; 4 studies, 2262 children, moderate-certainty evidence). However, there was no evidence of a difference on incidence of respiratory disease (RR 0.99, 95% CI 0.92 to 1.06; 11 studies, 27,540 children; low-certainty evidence) or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies, 10,541 children; moderate-certainty evidence). Authors' conclusions: This update identified no new eligible studies and the conclusions remain the same. VAS is associated with a clinically meaningful reduction in morbidity and mortality in children. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented VAD, it would be unethical to conduct placebo-controlled trials

Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years

Background: Zinc deficiency is prevalent in low- and middle-income countries, and is considered a significant risk factor for morbidity, mortality, and linear growth failure. The effectiveness of preventive zinc supplementation in reducing prevalence of zinc deficiency needs to be assessed. Objectives: To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged 6 months to 12 years. Search methods: A previous version of this review was published in 2014. In this update, we searched CENTRAL, MEDLINE, Embase, five other databases, and one trials register up to February 2022, together with reference checking and contact with study authors to identify additional studies. Selection criteria: Randomized controlled trials (RCTs) of preventive zinc supplementation in children aged 6 months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalized children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions. Data collection and analysis: Two review authors screened studies, extracted data, and assessed the risk of bias. We contacted study authors for missing information and used GRADE to assess the certainty of evidence. The primary outcomes of this review were all-cause mortality; and cause-specific mortality, due to all-cause diarrhea, lower respiratory tract infection (LRTI, including pneumonia), and malaria. We also collected information on a number of secondary outcomes, such as those related to diarrhea and LRTI morbidity, growth outcomes and serum levels of micronutrients, and adverse events. Main results: We included 16 new studies in this review, resulting in a total of 96 RCTs with 219,584 eligible participants. The included studies were conducted in 34 countries; 87 of them in low- or middle-income countries. Most of the children included in this review were under five years of age. The intervention was delivered most commonly in the form of syrup as zinc sulfate, and the most common dose was between 10 mg and 15 mg daily. The median duration of follow-up was 26 weeks. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes was affected by risk of bias. High-certainty evidence showed little to no difference in all-cause mortality with preventive zinc supplementation compared to no zinc (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.84 to 1.03; 16 studies, 17 comparisons, 143,474 participants). Moderate-certainty evidence showed that preventive zinc supplementation compared to no zinc likely results in little to no difference in mortality due to all-cause diarrhea (RR 0.95, 95% CI 0.69 to 1.31; 4 studies, 132,321 participants); but probably reduces mortality due to LRTI (RR 0.86, 95% CI 0.64 to 1.15; 3 studies, 132,063 participants) and mortality due to malaria (RR 0.90, 95% CI 0.77 to 1.06; 2 studies, 42,818 participants); however, the confidence intervals around the summary estimates for these outcomes were wide, and we could not rule out a possibility of increased risk of mortality. Preventive zinc supplementation likely reduces the incidence of all-cause diarrhea (RR 0.91, 95% CI 0.90 to 0.93; 39 studies, 19,468 participants; moderate-certainty evidence) but results in little to no difference in morbidity due to LRTI (RR 1.01, 95% CI 0.95 to 1.08; 19 studies, 10,555 participants; high-certainty evidence) compared to no zinc. There was moderate-certainty evidence that preventive zinc supplementation likely leads to a slight increase in height (standardized mean difference (SMD) 0.12, 95% CI 0.09 to 0.14; 74 studies, 20,720 participants). Zinc supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46; 5 studies, 35,192 participants; high-certainty evidence). We report a number of other outcomes, including the effect of zinc supplementation on weight and serum markers such as zinc, hemoglobin, iron, copper, etc. We also performed a number of subgroup analyses and there was a consistent finding for a number of outcomes that co-supplementation of zinc with iron decreased the beneficial effect of zinc. Authors' conclusions: Even though we included 16 new studies in this update, the overall conclusions of the review remain unchanged. Zinc supplementation might help prevent episodes of diarrhea and improve growth slightly, particularly in children aged 6 months to 12 years of age. The benefits of preventive zinc supplementation may outweigh the harms in regions where the risk of zinc deficiency is relatively high

Birthing practices of traditional birth attendants in South Asia in the context of training programmes

Traditional Birth Attendants (TBA) training has been an important component of public health policy interventions to improve maternal and child health in developing countries since the 1970s. More recently, since the 1990s, the TBA training strategy has been increasingly seen as irrelevant, ineffective or, on the whole, a failure due to evidence that the maternal mortality rate (MMR) in developing countries had not reduced. Although, worldwide data show that, by choice or out of necessity, 47 percent of births in the developing world are assisted by TBAs and/or family members, funding for TBA training has been reduced and moved to providing skilled birth attendants for all births. Any shift in policy needs to be supported by appropriate evidence on TBA roles in providing maternal and infant health care service and effectiveness of the training programmes. This article reviews literature on the characteristics and role of TBAs in South Asia with an emphasis on India. The aim was to assess the contribution of TBAs in providing maternal and infant health care service at different stages of pregnancy and after-delivery and birthing practices adopted in home births. The review of role revealed that apart from TBAs, there are various other people in the community also involved in making decisions about the welfare and health of the birthing mother and new born baby. However, TBAs have changing, localised but nonetheless significant roles in delivery, postnatal and infant care in India. Certain traditional birthing practices such as bathing babies immediately after birth, not weighing babies after birth and not feeding with colostrum are adopted in home births as well as health institutions in India. There is therefore a thin precarious balance between the application of biomedical and traditional knowledge. Customary rituals and perceptions essentially affect practices in home and institutional births and hence training of TBAs need to be implemented in conjunction with community awareness programmes

Mapping disparities in education across low- and middle-income countries

Educational attainment is an important social determinant of maternal, newborn, and child health1–3. As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting4–6. The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness7,8; however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health9–11. Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but—to our knowledge—no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries12–14. By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations

The ethical contours of research in crisis settings: five practical considerations for academic institutional review boards and researchers.

The number of research studies in the humanitarian field is rising. It is imperative, therefore, that institutional review boards (IRBs) consider carefully the additional risks present in crisis contexts to ensure that the highest ethical standards are upheld. Ethical guidelines should represent better the specific issues inherent to research among populations grappling with armed conflict, disasters triggered by natural hazards, or health-related emergencies. This paper seeks to describe five issues particular to humanitarian settings that IRBs should deliberate and on which they should provide recommendations to overcome associated challenges: staged reviews of protocols in acute emergencies; flexible reviews of modification requests; addressing violence and the traumatic experiences of participants; difficulties in attaining meaningful informed consent among populations dependent on aid; and ensuring reviews are knowledgeable of populations' needs. Considering these matters when reviewing protocols will yield more ethically sound research in humanitarian settings and hold researchers accountable to appropriate ethical standards

Infectious aetiologies of neonatal illness in south Asia classified using WHO definitions: a primary analysis of the ANISA study

Background: Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only. Methods: Eligible infants were aged 0–59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology. Findings: There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58–82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding. Interpretation: Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions. Funding: The Bill and Melinda Gates Foundation