Survey showed that very few paediatric residents in Southwest Nigeria were interested in specialising in gastroenterology.

AIM: Paediatric gastroenterology remains an under-recognised sub-speciality in Africa. We determined the preferred sub-specialities among paediatric residents in Southwest Nigeria and what influenced whether they chose paediatric gastroenterology. METHODS: This was a cross-sectional survey of paediatric residents in seven teaching hospitals in Southwest Nigeria. A self-administered questionnaire was used to obtain information on their socio-demographics, educational attainment, choice of sub-speciality and the factors influencing that choice. RESULTS: Of 144 eligible paediatric residents, 124 (86.1%) completed the survey. Their mean age was 35.0 ± 1.7 years, and 83 (66.9%) were females. The majority (94.4%) had already chosen their sub-speciality, and nearly two-thirds (65.0%) made the decision during training. The most popular sub-speciality was neonatology (30.6%), and only three (2.4%) residents chose gastroenterology. Factors influencing the choice of sub-speciality were perceived ability (85.3%) and academic experience (83.8%). Financial reasons were less frequent (32.5%). Lack of diagnostic equipment (30.6%) and role models (21.0%) were the most frequent reasons for residents being disinterested in paediatric gastroenterology. CONCLUSION: Few residents were interested in paediatric gastroenterology and there is a need to encourage interest in this subject at an early stage in their training and provide more diagnostic equipment and greater mentorship.

Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study.

BACKGROUND: In Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine-artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa. METHODS AND FINDINGS: This single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine-artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine-artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine-artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated. CONCLUSIONS: Pyronaridine-artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine-artesunate as an operationally useful addition to the management of acute uncomplicated malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT03201770.

A four-helix bundle stores copper for methane oxidation.

Methane-oxidizing bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase. Certain methanotrophs are also able to switch to using the iron-containing soluble methane monooxygenase to catalyse methane oxidation, with this switchover regulated by copper. Methane monooxygenases are nature's primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and methane monooxygenases have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. Here we discover and characterize a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for particulate methane monooxygenase. Csp1 is a tetramer of four-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realized. Cytosolic homologues of Csp1 are present in diverse bacteria, thus challenging the dogma that such organisms do not use copper in this location.

Probiotics for treating acute infectious diarrhoea.

BACKGROUND: Probiotics may be effective in reducing the duration of acute infectious diarrhoea. OBJECTIVES: To assess the effects of probiotics in proven or presumed acute infectious diarrhoea. SEARCH METHODS: We searched the trials register of the Cochrane Infectious Diseases Group, MEDLINE, and Embase from inception to 17 December 2019, as well as the Cochrane Controlled Trials Register (Issue 12, 2019), in the Cochrane Library, and reference lists from studies and reviews. We included additional studies identified during external review. SELECTION CRITERIA: Randomized controlled trials comparing a specified probiotic agent with a placebo or no probiotic in people with acute diarrhoea that is proven or presumed to be caused by an infectious agent. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, assessed risk of bias, and extracted data. Primary outcomes were measures of diarrhoea duration (diarrhoea lasting ≥ 48 hours; duration of diarrhoea). Secondary outcomes were number of people hospitalized in community studies, duration of hospitalization in inpatient studies, diarrhoea lasting ≥ 14 days, and adverse events. MAIN RESULTS: We included 82 studies with a total of 12,127 participants. These studies included 11,526 children (age < 18 years) and 412 adults (three studies recruited 189 adults and children but did not specify numbers in each age group). No cluster-randomized trials were included. Studies varied in the definitions used for "acute diarrhoea" and "end of the diarrhoeal illness" and in the probiotic(s) tested. A total of 53 trials were undertaken in countries where both child and adult mortality was low or very low, and 26 where either child or adult mortality was high. Risk of bias was high or unclear in many studies, and there was marked statistical heterogeneity when findings for the primary outcomes were pooled in meta-analysis. Effect size was similar in the sensitivity analysis and marked heterogeneity persisted. Publication bias was demonstrated from funnel plots for the main outcomes. In our main analysis of the primary outcomes in studies at low risk for all indices of risk of bias, no difference was detected between probiotic and control groups for the risk of diarrhoea lasting ≥ 48 hours (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.91 to 1.09; 2 trials, 1770 participants; moderate-certainty evidence); or for duration of diarrhoea (mean difference (MD) 8.64 hours shorter, 95% CI 29.4 hours shorter to 12.1 hours longer; 6 trials, 3058 participants; very low-certainty evidence). Effect size was similar and marked heterogeneity persisted in pre-specified subgroup analyses of the primary outcomes that included all studies. These included analyses limited to the probiotics Lactobacillus rhamnosus GG and Saccharomyces boulardii. In six trials (433 participants) of Lactobacillus reuteri, there was consistency amongst findings (I² = 0%), but risk of bias was present in all included studies. Heterogeneity also was not explained by types of participants (age, nutritional/socioeconomic status captured by mortality stratum, region of the world where studies were undertaken), diarrhoea in children caused by rotavirus, exposure to antibiotics, and the few studies of children who were also treated with zinc. In addition, there were no clear differences in effect size for the primary outcomes in post hoc analyses according to decade of publication of studies and whether or not trials had been registered. For other outcomes, the duration of hospitalization in inpatient studies on average was shorter in probiotic groups than in control groups but there was marked heterogeneity between studies (I² = 96%; MD -18.03 hours, 95% CI -27.28 to -8.78, random-effects model: 24 trials, 4056 participants). No differences were detected between probiotic and control groups in the number of people with diarrhoea lasting ≥ 14 days (RR 0.49, 95% CI 0.16 to 1.53; 9 studies, 2928 participants) or in risk of hospitalization in community studies (RR 1.26, 95% CI 0.84 to 1.89; 6 studies, 2283 participants). No serious adverse events were attributed to probiotics. AUTHORS' CONCLUSIONS: Probiotics probably make little or no difference to the number of people who have diarrhoea lasting 48 hours or longer, and we are uncertain whether probiotics reduce the duration of diarrhoea. This analysis is based on large trials with low risk of bias.

Serology describes a profile of declining malaria transmission in Farafenni, The Gambia.

BACKGROUND: Malaria morbidity and mortality has declined in recent years in a number of settings. The ability to describe changes in malaria transmission associated with these declines is important in terms of assessing the potential effects of control interventions, and for monitoring and evaluation purposes. METHODS: Data from five cross-sectional surveys conducted in Farafenni and surrounding villages on the north bank of River Gambia between 1988 and 2011 were compiled. Antibody responses to MSP-119 were measured in samples from all surveys, data were normalized and expressed as seroprevalence and seroconversion rates (SCR) using different mathematical models. RESULTS: Results showed declines in serological metrics with seroprevalence in children aged one to 5 years dropping from 19 % (95 % CI 15-23 %) in 1988 to 1 % (0-2 %) in 2011 (p value for trend in proportions < 0.001) and the SCR dropping from 0.069 year(-1) (0.059-0.080) to 0.022 year(-1) (0.017-0.028; p = 0.004). The serological data were consistent with previously described drops in both parasite prevalence in children aged 1-5 years (62 %, 57-66 %, in 1988 to 2 %, 0-4 %, in 2011; p < 0.001), and all-cause under five mortality rates (37 per 1000 person-years, 34-41, in 1990 to 17, 15-19, in 2006; p = 0.059). CONCLUSIONS: This analysis shows accurate reconstruction of historical malaria transmission patterns in the Farafenni area using anti-malarial antibody responses. Demonstrating congruence between serological measures, and conventional clinical and parasitological measures suggests broader utility for serology in monitoring and evaluation of malaria transmission.

Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insufficient data to reliably assess effectiveness. We aimed to do a pragmatic efficacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria, with a total of 6 × 10(10) organisms, one per day for 21 days, or an identical placebo. Patients, study staff, and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This trial is registered, number ISRCTN70017204. FINDINGS: Of 17,420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%) participants in the microbial preparation group and 153 (10·4%) participants in the placebo group (relative risk [RR] 1·04; 95% CI 0·84-1·28; p=0·71). CDD was an uncommon cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34-1·47; p=0·35). 578 (19·7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial. INTERPRETATION: We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies. FUNDING: Health Technology Assessment programme; National Institute for Health Research, UK.

Improving gut health and growth in early life: a protocol for an individually randomised, two-arm, open-label, controlled trial of a synbiotic in infants in Kaffrine District, Senegal.

INTRODUCTION: Infants exposed to enteropathogens through poor sanitation and hygiene can develop a subclinical disorder of the gut called environmental enteric dysfunction (EED), characterised by abnormal intestinal histology and permeability. EED can contribute to stunting through reduced digestion and absorption of nutrients, increased susceptibility to infections, increased systemic inflammation and inhibition of growth hormones. EED can be apparent by age 12 weeks, highlighting the need for early intervention. Modulating the early life gut microbiota using synbiotics may improve resistance against colonisation of the gut by enteropathogens, reduce EED and improve linear growth. METHODS AND ANALYSIS: An individually randomised, two-arm, open-label, controlled trial will be conducted in Kaffrine District, Senegal. Infants will be recruited at birth and randomised to either receive a synbiotic containing two Bifidobacterium strains and one Lactobacillus strain, or no intervention, during the first 6 months of life. The impact of the intervention will be evaluated primarily by comparing length-for-age z-score at 12 months of age in infants in the intervention and control arms of the trial. Secondary outcome variables include biomarkers of intestinal inflammation, intestinal integrity and permeability, gut microbiota profiles, presence of enteropathogens, systemic inflammation, growth hormones, epigenetic status and episodes of illness during follow-up to age 24 months. DISCUSSION: This trial will contribute to the evidence base on the use of a synbiotic to improve linear growth by preventing or ameliorating EED in a low-resource setting. TRIAL REGISTRATION NUMBER: PACTR202102689928613.

Correction: Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

[This corrects the article DOI: 10.1371/journal.pone.0244109.].

Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya.

BACKGROUND: Preterm (born < 37 weeks' gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnerable infants in sub-Saharan Africa. AIM: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries. METHODS: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds. RESULTS: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value <0.001), gestational age (1.77; 0.72 to 2.81; <0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; <0.002) and necrotising enterocolitis (4.31; 1.00 to 7.62; <0.011). CONCLUSION: The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcomes.

Influence of solution chemistry on Cr(VI) reduction and complexation onto date-pits/tea-waste biomaterials.

Tea waste (TW) and Date pits (DP) were investigated for their potential to remove toxic Cr(VI) ions from aqueous solution. Investigations showed that the majority of the bound Cr(VI) ions were reduced to Cr(III) after biosorption at acidic conditions. The electrons for the reduction of Cr(VI) may have been donated from the TW and DP biomasses. The experimental data obtained for Cr(VI)-TW and Cr(VI)-DP at different solution temperatures indicate a multilayer type biosorption, which explains why the Sips isotherm accurately represents the experimental data obtained in this study. The Sips maximum biosorption capacities of Cr(VI) onto TW and DP were 5.768 and 3.199 mmol/g at 333 K, respectively, which is comparatively superior to most other low-cost biomaterials. Fourier transform infrared spectroscopic analysis of the metal loaded biosorbents confirmed the participation of -COOH, -NH(2) and O-CH(3) groups in the reduction and complexation of chromium. Thermodynamic parameters demonstrated that the biosorption of Cr(VI) onto TW and DP biomass was endothermic, spontaneous and feasible at 303-333 K. The results evidently indicated that tea waste and date pits would be suitable biosorbents for Cr(VI) in wastewater under specific conditions.

Participant perceptions and experiences of a novel community-based respiratory longitudinal sampling method in Liverpool, UK: A mixed methods feasibility study.

Longitudinal, community-based sampling is important for understanding prevalence and transmission of respiratory pathogens. Using a minimally invasive sampling method, the FAMILY Micro study monitored the oral, nasal and hand microbiota of families for 6 months. Here, we explore participant experiences and opinions. A mixed methods approach was utilised. A quantitative questionnaire was completed after every sampling timepoint to report levels of discomfort and pain, as well as time taken to collect samples. Participants were also invited to discuss their experiences in a qualitative structured exit interview. We received questionnaires from 36 families. Most adults and children >5y experienced no pain (94% and 70%) and little discomfort (73% and 47% no discomfort) regardless of sample type, whereas children ≤5y experienced variable levels of pain and discomfort (48% no pain but 14% hurts even more, whole lot or worst; 38% no discomfort but 33% moderate, severe, or extreme discomfort). The time taken for saliva and hand sampling decreased over the study. We conducted interviews with 24 families. Families found the sampling method straightforward, and adults and children >5y preferred nasal sampling using a synthetic absorptive matrix over nasopharyngeal swabs. It remained challenging for families to fit sampling into their busy schedules. Adequate fridge/freezer space and regular sample pick-ups were found to be important factors for feasibility. Messaging apps proved extremely effective for engaging with participants. Our findings provide key information to inform the design of future studies, specifically that self-sampling at home using minimally invasive procedures is feasible in a family context.

A multicentre randomised controlled trial evaluating lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea in older people admitted to hospital: the PLACIDE study protocol.

BACKGROUND: Antibiotic associated diarrhoea complicates 5-39% of courses of antibiotic treatment. Major risk factors are increased age and admission to hospital. Of particular importance is C. difficile associated diarrhoea which occurs in about 4% of antibiotic courses and may result in severe illness, death and high healthcare costs. The emergence of the more virulent 027 strain of C. difficile has further heightened concerns. Probiotics may prevent antibiotic associated diarrhoea by several mechanisms including colonization resistance through maintaining a healthy gut flora. METHODS: This study aims to test the hypothesis that administration of a probiotic comprising two strains of lactobacilli and two strains of bifidobacteria alongside antibiotic treatment prevents antibiotic associated diarrhoea. We have designed a prospective, parallel group trial where people aged 65 years or more admitted to hospital and receiving one or more antibiotics are randomly allocated to receive either one capsule of the probiotic or a matching placebo daily for 21 days. The primary outcomes are the frequency of antibiotic associated and C. difficile diarrhoea during 8-12 weeks follow-up. To directly inform routine clinical practice, we will recruit a sufficient number of patients to demonstrate a 50% reduction in the frequency of C. difficile diarrhoea with a power of 80%. To maximize the generalizability of our findings and in view of the well-established safety record of probiotics, we will recruit a broad range of medical and surgical in-patients from two different health regions within the UK. DISCUSSION: Antibiotic associated diarrhoea constitutes a significant health burden. In particular, current measures to prevent and control C. difficile diarrhoea are expensive and disrupt clinical care. This trial may have considerable significance for the prevention of antibiotic associated diarrhoea in hospitals. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register ISRCTN70017204.

Dietary Therapy to Improve Nutrition and Gut Health in Paediatric Crohn's Disease; A Feasibility Study.

Bovine colostrum (BC) has anti-inflammatory, anti-infective, growth and intestinal repair factors that may be beneficial in Crohn's disease (CD). We assessed whether daily BC for up to 3 months was acceptable to children and young people (CYP) with CD in remission or of mild/moderate severity. CYP were randomised to receive either BC or matching placebo milk daily for 6 weeks (blinded phase); all received BC for the following 6 weeks (open phase). In 23 CYP, median (inter-quartile range) age was 15.2 (13.9-16.1) years and 9 (39.1%) were girls. A similar proportion of CYP in the BC and placebo arms completed the blinded phase (8/12, 75.0% and 9/11, 81.8% respectively). Twelve (70.6%) CYP completed the open phase with 7 (58.3%) tolerating BC for 3 months. Diaries in weeks 2, 6 and 12 revealed that most CYP took BC every day (5/7, 71.4%; 5/8, 62.5% and 6/11, 54.5% respectively). In interviews, opinions were divided as to preference of BC over the placebo milk and some preferred BC over other nutritional supplements. Symptoms, clinical and laboratory variables and quality of life were similar in the two arms. BC may be an acceptable nutritional supplement for daily, longer-term use in CYP with CD.

Enteral Feeding Practices for Very Preterm and Very Low Birth Weight Infants in Nigeria and Kenya.

Background: Optimizing nutrition in very preterm (28-32 weeks gestation) and very low birth weight (VLBW; 1,000 g to <1,500 g) infants has potential to improve their survival, growth, and long-term health outcomes. Aim: To assess feeding practices in Nigeria and Kenya for very preterm and VLBW newborn infants. Methods: This was a cross-sectional study where convenience sampling was used. A standard questionnaire was sent to doctors working in neonatal units in Nigeria and Kenya. Results: Of 50 respondents, 37 (74.0%) were from Nigeria and 13 (26.0%) from Kenya. All initiated enteral feeds with breastmilk, with 24 (48.0%) initiating within 24 h. Only 28 (56.0%) used written feeding guidelines. Starting volumes ranged between 10 and 80 ml/kg/day. Median volume advancement of feeds was 20 ml/kg/day (IQR 10-20) with infants reaching full feeds in 8 days (IQR 6-12). 26 (52.0%) of the units fed the infants 2 hourly. Breastmilk fortification was practiced in 7 (14.0%) units, while folate, iron, calcium, and phosphorus were prescribed in 42 (84.0%), 36 (72.0%), 22 (44.0%), 5 (10.0%) of these units, respectively. No unit had access to donor breastmilk, and only 18 (36.0%) had storage facilities for expressed breastmilk. Twelve (24.0%) used wet nurses whilst 30 (60.0%) used formula feeds. Conclusion: Feeding practices for very preterm and VLBW infants vary widely within Nigeria and Kenya, likely because of lack of locally generated evidence. High quality research that informs the feeding of these infants in the context of limited human resources, technology, and consumables, is urgently needed.

Prospective observational study of the challenges in diagnosing common neonatal conditions in Nigeria and Kenya.

OBJECTIVES: Accurate and timely diagnosis of common neonatal conditions is crucial for reducing neonatal deaths. In low/middle-income countries with limited resources, there is sparse information on how neonatal diagnoses are made. The aim of this study was to describe the diagnostic criteria used for common conditions in neonatal units (NNUs) in Nigeria and Kenya. DESIGN: Prospective observational study. Standard case report forms for suspected sepsis, respiratory disorders, birth asphyxia and abdominal conditions were co-developed by the Neonatal Nutrition Network (https://www.lstmed.ac.uk/nnu) collaborators. Clinicians completed forms for all admissions to their NNUs. Key data were displayed using heatmaps. SETTING: Five NNUs in Nigeria and two in Kenya comprising the Neonatal Nutrition Network. PARTICIPANTS: 2851 neonates, which included all neonates admitted to the seven NNUs over a 6-month period. RESULTS: 1230 (43.1%) neonates had suspected sepsis, 874 (30.6%) respiratory conditions, 587 (20.6%) birth asphyxia and 71 (2.5%) abdominal conditions. For all conditions and across all NNUs, clinical criteria were used consistently with sparse use of laboratory and radiological criteria. CONCLUSION: Our findings highlight the reliance on clinical criteria and extremely limited use of diagnostic technologies for common conditions in NNUs in sub-Saharan Africa. This has implications for the management of neonatal conditions which often have overlapping clinical features. Strategies for implementation of diagnostic pathways and investment in affordable and sustainable diagnostics are needed to improve care for these vulnerable infants.

The impact of childhood malnutrition on mortality from pneumonia: a systematic review and network meta-analysis.

INTRODUCTION: Childhood malnutrition is widespread in low-income and middle-income countries (LMICs) and increases the frequency and severity of infections such as pneumonia. We aimed to identify studies investigating pneumonia deaths in malnourished children and estimate mortality risk by malnutrition severity. METHODS: We conducted a systematic review of MEDLINE, EMBASE and Global Health databases to identify relevant studies. We used a network meta-analysis to derive ORs of death from pneumonia for moderately and severely underweight children using low weight-for-age, the most reported measure of malnutrition. We compared meta-estimates of studies conducted before and after 2000 to assess changes in mortality risk over time. We estimated the prevalence of underweight hospitalised children from hospital-based cohort studies and calculated the population attributable fraction of in-hospital pneumonia deaths from being underweight using our results. RESULTS: Our network meta-analysis included 33 544 underweight children from 23 studies. The estimated OR of death from pneumonia was 2.0 (95% CI 1.6 to 2.6) and 4.6 (95% CI 3.7 to 5.9) for children moderately and severely underweight, respectively. The OR of death from pneumonia for those severely underweight was 5.3 (95% CI 3.9 to 7.4) pre-2000 and remained high post-2000 at 4.1 (95% CI 3.0 to 6.0). Prevalence of underweight children hospitalised with pneumonia varied (median 40.2%, range 19.6-66.3) but was high across many LMIC settings. We estimated a median 18.3% (range 10.8-34.6) and 40.9% (range 14.7-69.9) of in-hospital pneumonia deaths were attributable to being moderately and severely underweight, respectively. CONCLUSIONS: The risk of death from childhood pneumonia dramatically increases with malnutrition severity. This risk has remained high in recent years with an estimated over half of in-hospital pneumonia deaths attributable to child malnutrition. Prevention and treatment of all child malnutrition must be prioritised to maintain progress on reducing pneumonia deaths.

Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

OBJECTIVE: To describe the patient population, priority diseases and outcomes in newborns admitted <48 hours old to neonatal units in both Kenya and Nigeria. STUDY DESIGN: In a network of seven secondary and tertiary level neonatal units in Nigeria and Kenya, we captured anonymised data on all admissions <48 hours of age over a 6-month period. RESULTS: 2280 newborns were admitted. Mean birthweight was 2.3 kg (SD 0.9); 57.0% (1214/2128) infants were low birthweight (LBW; <2.5kg) and 22.6% (480/2128) were very LBW (VLBW; <1.5 kg). Median gestation was 36 weeks (interquartile range 32, 39) and 21.6% (483/2236) infants were very preterm (gestation <32 weeks). The most common morbidities were jaundice (987/2262, 43.6%), suspected sepsis (955/2280, 41.9%), respiratory conditions (817/2280, 35.8%) and birth asphyxia (547/2280, 24.0%). 18.7% (423/2262) newborns died; mortality was very high amongst VLBW (222/472, 47%) and very preterm infants (197/483, 40.8%). Factors independently associated with mortality were gestation <28 weeks (adjusted odds ratio 11.58; 95% confidence interval 4.73-28.39), VLBW (6.92; 4.06-11.79), congenital anomaly (4.93; 2.42-10.05), abdominal condition (2.86; 1.40-5.83), birth asphyxia (2.44; 1.52-3.92), respiratory condition (1.46; 1.08-2.28) and maternal antibiotics within 24 hours before or after birth (1.91; 1.28-2.85). Mortality was reduced if mothers received a partial (0.51; 0.28-0.93) or full treatment course (0.44; 0.21-0.92) of dexamethasone before preterm delivery. CONCLUSION: Greater efforts are needed to address the very high burden of illnesses and mortality in hospitalized newborns in sub-Saharan Africa. Interventions need to address priority issues during pregnancy and delivery as well as in the newborn.

Dietary supplementation with lactobacilli and bifidobacteria is well tolerated and not associated with adverse events during late pregnancy and early infancy.

Lactic acid bacteria and bifidobacteria are increasingly being administered to pregnant women and infants with the intention of improving health. Although these organisms have a long record of safe use, it is important to identify any adverse effects in potentially vulnerable populations. In a randomized, double-blinded, placebo-controlled trial, we evaluated the safety of a bacterial dietary supplement for the prevention of atopy in infants. Two strains of lactobacilli (Lactobacillus salivarius CUL61 and Lactobacillus paracasei CUL08) and bifidobacteria (Bifidobacterium animalis subsp. lactis CUL34 and Bifidobacterium bifidum CUL20) with a total of 1 x 10(10) colony-forming units were administered daily to women during the last month of pregnancy and to infants aged 0-6 mo. Adverse events (AE) were classified according to WHO International Statistical Classification of Diseases criteria. Common symptoms were recorded by regular questionnaires. Baseline characteristics of 220 mother-infant dyads in the treatment and 234 in the placebo group were similar. Compliance with the trial interventions, loss to follow-up, symptoms, drug usage, infant growth, method of feeding, visits to the doctor, and mothers' assessment of infant health were similar in the 2 groups. Fifteen (6.8%) mothers and 73 (33.2%) infants in the treatment group and 21 (9.0%) mothers and 75 (32.1%) infants in the placebo group reported AE (P = 0.49 and P = 0.84, respectively). Severe AE occurred in 18 mothers and 63 infants with a similar frequency in each group. None of the AE were attributed to the intervention. Our findings support the safe use of this consortium of organisms during pregnancy and early infancy.