Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Improved appetite of pregnant rats and increased birth weight of newborns following feeding with probiotic Lactobacillus rhamnosus GR-1 and L. fermentum RC-14

Malnutrition and pathogenic colonization of the vagina are two major contributors to preterm labour, newborn survival and low birth babies at high risk of long term poor quality of life. It was hypothesized that use of probiotics as a food supplement would improve the appetite and health of the mother and newborn babies. Two probiotic strains, Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 were tested in a Sprague-Dawley albino rat model. The probiotic preparations (1X109cfu/ml) were administered to rats in group A, as supplementation in drinking water for 30 days. Feed intake and the birth weight of the newborns were measured. There was a significant improvement in appetite for the lactobacilli treated animals with a mean weight of 31.16g of feed, compared with 27.16g for the controls, P\u3c0.01. The mortality rate for the control animals was 6% while no death occurred in the probiotic group. There was significantly increased birth weight among 37 newborns whose mothers had been fed probiotics (6.5g), compared to controls (4.5g) (P\u3c0.01). There was a two log increase in total lactobacilli recovered from the stool of the probiotic treated animals with significant presence of the two lactobacilli treatment strains. No adverse effects were noted in the animals. This is the first report of nutritional appetite benefits of probiotics during pregnancy and of improvements in weight of newborn babies. Considering well nourished babies born within the normal weight range have a considerably better long term prognosis, if the present findings were to be duplicated in pregnant women, the implications for health especially of mothers and babies in developing countries could be very significant

Reducing Urogenital Infections including HIV/AIDS in Africa; can probiotics be a viable paradigm?

The use of probiotics defined as “live microorganisms which when administered in adequate amounts, confer health benefits on the host” (WHO/FAO, 2001), for the maintenance of health is already in use in developed countries. Probiotics are yet to be adopted in sub-Saharan Africa by health care providers. There is clinical evidence to show that probiotics can play a significant role in resolving diarrhea, boost immune system and prevent recurrent urogenital infections including bacterial vaginosis, which is a risk factor in HIV acquisition. The aim of this chapter is to highlight the burden of urogenital infections in Africa, impact of abnormal vaginal microbiota, clinical evidence on the use of probiotics for urogenital health care and last but not the least, the rationale for suggesting the use of probiotics in the management of HIV infection in sub-Saharan Africa

Receptivity for probiotic products among pre-menopausal female students in an African university

OBJECTIVE: The objective of this study was to examine the receptivity for probiotic products among premenopausal female students in an African university. GOAL: The goal of this study was to determine the local knowledge in Nigeria of probiotics and the willingness of young women to use them should they be introduced. STUDY: Closed-ended questionnaires were administered to a sample of 280 participants and these addressed age, marital status, perceived risk of HIV infection for the next 3 years, and history of urogenital infections. The participants were also asked whether they would welcome a probiotic product in oral/vaginal form and in milk-based food products, willingness to purchase and use, how often they would use these products, preference of form, price, and where they would like to buy the products. The second questionnaire was open-ended. It asked the participants to freely list any concerns or worries they had in relation to probiotic products. RESULTS: Of the 280 participants, 55.3% indicated that they believed they were at risk of acquiring HIV within the next 3 years, illustrating the enormity of the problem in Africa and the feelings among women that they cannot easily control sexual relationships and have partners use condoms. Eighty-two percent of the subjects stated they would welcome probiotic products in capsular form for vaginal instillation or to be taken orally to improve vaginal health. Over one third (36%) of women indicated they would be willing to use the probiotic products as part of their daily self-care. One hundred nine (39.6%) respondents were willing to purchase the probiotic products at a reasonable price of 0.08 US dollars per dose, whereas 71.5% were willing to pay up to 0.38 US dollars. Some subjects (25%) raised some concern over safety of probiotics. CONCLUSIONS: The findings revealed that female university students are receptive to probiotic products in Nigeria and indicate strongly a need to consider women\u27s concerns about urogenital health. Furthermore, the study identified a need for appropriate educational materials about probiotics, including benefits and safety information, in an African country suffering severely from the HIV epidemic

Feeding probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 does not significantly alter hematological parameters of Sprague-Dawley rats

The potential use of probiotics in restoring the urogenital and gastrointestinal health has received tremendous interest in the last decade, while few safety concerns are still being debated. In order to demonstrate the safety of the probiotic strains, Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14, we designed a study in an animal model to investigate the effects of feeding probiotics on the haematological parameters of rats. The rats were fed daily with 109CFU/ml of the probiotic strains orally with an oro-gastric tube for 21 days. Blood samples were collected by carotid artery cannulation for terminal bleeding into potassium EDTA containers. Twelve parameters were determined using auto-haematological analyzer. Results shows that all the haematological parameters, both white blood cells and red blood cells obtained from the probiotic fed rats did not alter significantly when compared with the controls. The findings, further indicate that ingestion of the tested probiotics strains in healthy subjects does not affect peripheral blood cells

Lactobacillus vaginal microbiota of women attending a reproductive health care service in Benin City, Nigeria.

OBJECTIVE: The objective of this study was to determine whether Lactobacillus species found in African women differ substantially to those of Caucasian decent, described in previous studies. The vaginal microbiota play an important role in female health, and when the naturally dominant lactobacilli are displaced resulting in bacterial vaginosis (BV), the host is more at risk of acquiring sexually transmitted diseases, including HIV. METHODS: Vaginal samples were collected from 241 healthy, pre-menopausal Nigerian women, which were then Gram stained for Nugent scoring. Microbial DNA was extracted, amplified using PCR and Lactobacillus primers, and processed by Denaturing Gradient Gel Electrophoresis (DGGE). Lactobacillus species were identified by DNA sequencing and BLAST algorithm. RESULTS: Of the samples, 207 (85.8%) had PCR products for lactobacilli, while 34 (14.2%) showed absence of lactobacilli which correlated to the BV Nugent scores. Upon sequencing of amplicons, 149 subjects (72%) had sequence homologies to lactobacilli. Most women (64%) were colonized by L. iners as the predominant strain similar to previous findings in Canadian and Swedish women. L. gasseri was found in 7.3% samples, followed by L. plantarum, L. suntoryeus, L. crispatus, L. rhamnosus and other species. CONCLUSION: The findings indicate that even with geographical, racial and other differences, the predominant vaginal Lactobacillus species is similar to species in women from Northern countries

Association between absence of vaginal lactobacilli PCR products and Nugent scores interpreted as bacterial vaginosis

Context: The most common cause of abnormal vaginal discharge in women of childbearing age is due to bacterial vaginosis (BV). This condition predisposes women to increased susceptibility to sexually transmitted diseases, including human immunodeficiency virus (HIV) infections and preterm birth. The diagnostic methods currently adopted in the evaluation of patient samples for BV are arguably Amsel criteria, and Nugent score that require microscopy and expert interpretation. The use of polymerase chain reaction (PCR) with group specific lactobacillus primers, in combination with Nugent criteria has not been widely used in the developing countries such as Nigeria. Objective: The aim of the present study was to examine the relationship between vaginal Lactobacilli using PCR with group specific lactobacillus primers and Nugent Score criteria for bacterial vaginosis. Study Design, Setting, Subjects, and Methods: We evaluated 241 vaginal samples from apparently healthy premenopausal women in Benin City for the presence of Lactobacilli with group specific primers in a polymerase chain reaction master cycler and bacterial vaginosis using the Nugent score criteria. Results: Of the 241 vaginal samples that were Gram stained for Nugent rating, 84 (34.8%) had Normal rating (0-3), 123 (51%) had Intermediate score (4-6), while 34 (14.2%) had Bacterial vaginosis, with Nugent score (7-10). There was a positive association between absence of lactobacilli PCR product and Nugent scores interpreted as BV (85.8% vs. 14.2%. ÷2 [2]= 4.12, P=0.05). Conclusion: The study has demonstrated a strong relationship between bacterial vaginosis and absence or depletion of vaginal lactobacilli using molecular techniques

16S rRNA gene sequence and phylogenetic tree of lactobacillus species from the vagina of healthy Nigerian women

Lactobacilli are ubiquitous in nature and in humans they play a very significant role in the general health maintenance of the host. Identification of Lactobacilli has previously been based on cultutre-dependent methods and recently molecular techniques involving gene sequencing are now the ‘gold standard’. Scarce information exists in Africa on the real identity of Lactobacillus species, albeit phylogenetic distances among the species present in the human vagina. 185 vaginal swabs were collected from healthy premenopausal women (18-48 years). Bacterial DNA was extracted, amplified using PCR, with group specific Lactobacillus primers, and processed by denaturing gradient gel electrophoresis (DGGE). DGGE bands were excised, re-amplified, purified, V2-V3 region of 16S rRNA gene sequenced with ABI prism (3730xl) BigDye Terminator. Phylogenetic tree was constructed with the sequences by the Tree Top-Phylogenetic Tree prediction program. Results shows two distinct divisions among the Lactobacillus species as revealed by the phylogenetic tree. Lactobacillus iners, from both the cluster and topological algorithms, is closely related to L .vaginalis and L. fermentum. L. gasseri, L. suntoryeus, L. johnsonii, L. plantarum, L. rhamnosus, L. crispatus and L. helveticus are closely related in their phylogenetic distances. The study presents a new understanding of the nature of the Lactobacillus vaginal microbiota of women in Nigeria, which may lead to the design of probiotic-lactobacilli for biotherapy