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A one hour old baby boy presented to the Special Care Baby Unit (SCBU) of the Ahmadu Bello University Teaching Hospital (ABUTH), Shika, Zaria, on account of respiratory distress noticed from birth. He was a product of supervised pregnancy, delivered at 37 weeks gestation via emergency caeserien section performed due to severe pre eclampsia and fetal distress. APGAR scores were 2 and 7 at one and five minutes respectively. He weighed 1850 grams and was found to be dusky, inactive, hypothermic (T = 35.50C) and in severe respiratory distress (SPO2 ranged between 60 % and 72 %). He was tachypnoeic with respiratory rate persistently above 80 cycles/ min, and had reduced air entry in the mid and lower zones of the lungs bilaterally with wide spread coarse crepitations. A diagnosis of perinatal asphyxia was entertained with differential diagnoses of pulmonary hypoplasia, hyaline membrane disease and group B streptococcal (GBS) pneumonia. He had a full sepsis screen including chest radiograph and was commenced on supplemental oxygen via nasal cannula, antibiotics and other supportive measures. The patient however continued to have laboured breathingand subsequently had an apnoeic attack. He was resuscitated and commenced on bubble nasal CPAP.He did remarkably well and was weaned off CPAP after a total of 60 hours. A repeat chest radiograph showed remarkable aeration of the lungs as against an earlier one which showed a reticulogranular (ground glass) appearance.

Abstract Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18–50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.

‘Query’ (Q) fever is a neglected but emerging or re-emerging zoonotic disease caused by the bacterium Coxiella (C.) burnetii. Several host species are considered or speculated to be the primary reservoir hosts for human infection. In the past, several research groups in Nigeria have evaluated the prevalence of C. burnetii in various vertebrate and invertebrate hosts. Currently, there is a paucity of knowledge regarding the epidemiology of the pathogen in Nigeria with limited or no attention to control and prevention programs. Therefore, this review was undertaken to comprehend the current situation of C. burnetii infection in human, domestic and peri-domestic animals, and some tick species in Nigeria since 1960 with the aim to help identify future research priorities for the country. A comprehensive literature search was performed using the PRISMA guidelines on five scientific databases including Google Scholar, PubMed, AJOL, Science Direct, and Scopus for articles published from Nigeria dealing with the screening of blood, milk, or tick DNA for evidence of C. burnetii using any standard diagnostic approach. Of the 33 published articles subjected to full-text evaluation, more than 48% of the articles met the inclusion criteria and were thus included in this review. We observed different ranges of prevalence for C. burnetii antibodies from four vertebrate hosts including cattle (2.5–23.5%), sheep (3.8–12.0%), goats (3.1–10.9%), and humans (12.0–61.3%). Additionally, the use of molecular diagnostics revealed that the DNA of C. burnetii has been amplified in eight tick species including Hyalomma (Hy) dromedarii, Hy. truncatum, Hy. impeltatum, Hy. rufipes, Hy. impressum, Amblyomma (Am.) variegatum, Rhipicephalus (Rh.) evertsi evertsi, and Rh. annulatus. Two rodent’s species (Rattus rattus and Rattus norvegicus) in Nigeria were documented to show evidence of the bacterium with the detection of the DNA of C. burnetii in these two mammals. In conclusion, this review has provided more insight on the prevalence of C. burnetii and its associated host/vector in Nigeria. Domestic animals, peri-domestic animals, and ticks species harbor C. burnetii and could be a source of human infections. Due to the paucity of studies from southern Nigeria, we recommend that research groups with interest on vector-borne diseases need to consider more epidemiological studies in the future on C. burnetii prevalence in diverse hosts to help unravel their distribution and vector potentials in Nigeria as a whole.

ABSTRACT Enteropathogenic Escherichia coli (EPEC) and Shigella are etiologic agents of diarrhea in children

BackgroundThe introduction in many countries of conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has led to significant reductions in acute bacterial meningitis (ABM) in children. However, recent population-based data on ABM in sub-Saharan Africa are limited.MethodsPopulation-based surveillance for meningitis was carried out in a rural area of The Gambia under demographic surveillance from 2008 to 2017, using standardised criteria for referral, diagnosis and investigation. We calculated incidence using population denominators.ResultsWe diagnosed 1,666 patients with suspected meningitis and collected cerebrospinal fluid (n = 1,121) and/or blood (n = 1,070) from 1,427 (88%) of cases. We identified 169 cases of ABM, 209 cases of suspected non-bacterial meningitis (SNBM) and 1,049 cases of clinically suspected meningitis (CSM). The estimated average annual incidence of ABM was high at 145 per 100,000 population in the ConclusionsGambian children continue to experience substantial morbidity and mortality associated with suspected meningitis, especially acute bacterial meningitis. Such severely ill children in sub-Saharan Africa require improved diagnostics and clinical care.

Shigellosis remains a major public health problem around the world; it is one of the leading causes of diarrhoeal disease in low- and middle-income countries, particularly in young children. The increasing reports of Shigella cases associated with anti-microbial resistance are an additional element of concern. Currently, there are no licensed vaccines widely available against Shigella, but several vaccine candidates are in development. It has been demonstrated that the incidence of disease decreases following a prior Shigella infection and that serum and mucosal antibody responses are predominantly directed against the serotype-specific Shigella O-antigen portion of lipopolysaccharide membrane molecules. Many Shigella vaccine candidates are indeed O-antigen-based. Here we present the journey towards the development of a potential low-cost four-component Shigella vaccine, eliciting broad protection against the most prevalent Shigella serotypes, that makes use of the GMMA (Generalized Modules for Membrane Antigens) technology, a novel platform based on bacterial outer membranes for delivery of the O-antigen to the immune system.

Typhoid fever is caused by the bacterium Salmonella Typhi. Here, Park et al. analyse the genomes of 249 S. Typhi isolates from 11 sub-Saharan African countries, identifying genes and plasmids associated with antibiotic resistance and showing that multi-drug resistance is highly pervasive in sub-Saharan Africa.

BackgroundCryptosporidium is a major pathogen associated with diarrheal disease in young children. We studied Cryptosporidium diarrhea in children enrolled in the Global Enteric Multicenter Study (GEMS) in rural Gambia.MethodsWe recruited children ResultsWe enrolled 1938 cases (1381 MSD, 557 LSD) and 2969 matched controls; 231/1929 (12.0%) of diarrhea cases and 141/2962 (4.8%) of controls were positive for Cryptosporidium. Most Cryptosporidium diarrhea cases (85.7%, 198/231) were aged 6-23 months, and most (81.4%, 188/231) occurred during the rainy season. Cryptosporidium hominis (C. hominis) was the predominant (82.6%) species. We found associations between increased risk of Cryptosporidium-positive MSD or LSD, or both, with consumption of stored drinking water and certain animals living in the compound-cow, cat (MSD only) and rodents (LSD only). Larger households, fowl living in the compound, and the presence of Giardia infection were associated with decreased risk of Cryptosporidium MSD and LSD.ConclusionCryptosporidium-positive diarrhea is prevalent in this setting, especially at 6-23 months of age. The preponderance of Cryptosporidium infection in the rainy season and increased risk of Cryptosporidium-positive diarrhea with consumption of stored drinking water suggest water-borne transmission. Further investigation is needed to clarify the role of animals and contamination of stored drinking water in Cryptosporidium transmission.

Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p

We have captured an 8.7 A conformational change that takes place in the cleavage site of the hammerhead ribozyme during self-cleavage, using X-ray crystallography combined with physical and chemical trapping techniques. This rearrangement brings the hammerhead ribozyme from the ground state into a conformation that is poised to form the transition state geometry required for hammerhead RNA self-cleavage. Use of a 5’-C-methylated ribose adjacent to the cleavage site permits this ordinarily transient conformational change to be kinetically trapped and observed crystallographically after initiating the hammerhead ribozyme reaction in the crystal. Cleavage of the corresponding unmodified hammerhead ribozyme in the crystal under otherwise identical conditions is faster than in solution, indicating that we have indeed trapped a catalytically relevant intermediate form of this RNA enzyme

In the near future, the food insecurity risk is escalating if the surging population is not followed by increasing youth farmers while arable land is on a declining trend. Only 4 per cent (less than 3.5 million) youth aged 15-35 work as a farmer in Indonesia since the current general perspective of working in agriculture sector seems unpromising for most youth. This worsens the state of food insecurity unless there is a breakthrough to ignite youth interest. While the proportion of youth population both in rural and urban Indonesia are relatively similar (23 per cent and 25 per cent respectively in 2018), different approaches might be needed. Fortunately, many initiatives have been commenced to appeal to more youth. These approaches allow youth to acquire agriculture skills, from enabling land access to exposing the sector to the digital world. Using the available information acquired from secondary data and interviews, this study aims to identify, compare, and define the most viable approach amongst the existing initiatives, including land access, crop insurance, and incentive for youth farmers in rural area; and mainstreaming digital platform such as peer-to-peer lending, local product promotion, and vertical farming to engage urban youth. Eventually, the recommendation from this study will optimize youth role in improving the state of food security

Due to its complex and often difficult nature, suboptimal lands are either under-utilized and left as abandoned space or over-utilized and generate environment problems. In reality, it can be the answer to the future challenge in 2050, where the growing population needs more food to survive. It results in intense competition in land conversion to agricultural and nonagricultural purposes. This paper introduces Water Management Trinity as an integrated water management system applied to exert the highest benefits from sustainable suboptimal lands cultivation in Pulau Burung District for at least the last 50 years. The three main components: the canal, the dike, also the dam and water gate principally regulate the freshwater from the precipitation events. With a cumulative length of more than 4000 km, the canals hold a volume of at least 45 million m3 of freshwater. Combined with the soil technology, the current agriculture practice is proven to reduce environmental damage by maintaining the land humidity so that the fire and flooding risk are both diminished while the land subsidence rate is kept under 0-4 cm/year in the last ten years. Simultaneously, the local socioeconomic sector flourishes as the system secures the water requirement for plant commodities production and supports freshwater supply.

In 2012, an outbreak of Neisseria meningitidis serogroup W135 occurred in The Gambia. The attack rate was highest among young children. The associated risk factors were male sex, contact with meningitis patients, and difficult breathing. Enhanced surveillance facilitates early epidemic detection, and multiserogroup conjugate vaccine could reduce meningococcal epidemics in The Gambia.

Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings.

Background. Establishing the pattern of infection and antimicrobial sensitivities in the local environment is critical to rational use of antibiotics and the development of management algorithms. Methods. Morbidity history and physical examination of 140 children with severe acute malnutrition were recorded. Their blood, stool, and urine samples were cultured and antibiotic sensitivity patterns determined for any bacterial pathogens isolated. Results. Thirty-eight children had a pathogen isolated from blood culture, 60% of which were considered contaminants. Coagulase negative staphylococcus was the predominant contaminant, while the major causes of bacteraemia were nontyphoidal Salmonella (13%), S. pneumoniae (10%), and E. coli (8%). E. coli accounted for 58% of the urinary isolates. No pathogen was isolated from stool. In vitro sensitivity by disk diffusion showed that 87.5% of the isolates were sensitive to ampicillin and/or gentamicin and 84.4% (27/32) to penicillin and/or gentamicin. Conclusions. A combination of ampicillin and gentamicin provides adequate antibiotic cover for severely malnourished children in The Gambia.

BACKGROUND:Non-Typhoidal Salmonella (NTS) is an important cause of invasive bacterial disease and associated with mortality in Africa. However, little is known about the environmental reservoirs and predominant modes of transmission. Our study aimed to study the role of domestic animals in the transmission of NTS to humans in rural area of The Gambia. METHODOLOGY:Human NTS isolates were obtained through an active population-based case-control surveillance study designated to determine the aetiology and epidemiology of enteric infections covering 27,567 Gambian children less than five years of age in the surveillance area. Fourteen children infected with NTS were traced back to their family compounds and anal swabs collected from 210 domestic animals present in their households. Identified NTSs were serotyped and genotyped by multi-locus sequencing typing. PRINCIPAL FINDINGS:NTS was identified from 21/210 animal sources in the households of the 14 infected children. Chickens carried NTS more frequently than sheep and goats; 66.6%, 28.6% and 4.8% respectively. The most common NTS serovars were S. Colindale in humans (21.42%) and S. Poona in animals (14.28%). MLST on the 35 NTS revealed four new alleles and 24 sequence types (ST) of which 18 (75%) STs were novel. There was no overlap in serovars or genotypes of NTS recovered from humans or animal sources in the same household. CONCLUSION:Our results do not support the hypothesis that humans and animals in close contact in the same household carry genotypically similar Salmonella serovars. These findings form an important baseline for future studies of transmission of NTS in humans and animals in Africa.

Malaria is a risk factor for invasive non-typhoidal Salmonella (NTS) infection in children. In the last 10 years, indices of malaria infection in The Gambia have fallen substantially.We compared temporal trends of childhood malaria and NTS infection in two Gambian locations. In Fajara, on the coast, the incidence of NTS infection at three time points between 1979 and 2005 was compared to the percentage of malaria positive outpatient thick blood films and the percentage of admissions associated with malaria over time. In Basse, in the eastern part of the country, the incidence of NTS infection at three time points between 1989 and 2008 was compared to the prevalence of malaria parasitaemia at four time points between 1992 and 2008.The estimated incidence of NTS infection in Fajara fell from 60 (1979-1984) to 10 (2003-05) cases per 100,000 person years. The proportion of outpatients in Fajara with suspected malaria who were parasitaemic fell from 33% (1999) to 6% (2007) while the proportion of admissions associated with malaria fell from 14.5% (1999) to 5% (2007). In Basse, the estimated incidence of NTS infection fell from 105 (1989-1991) to 29 (2008) cases per 100,000 person years while the prevalence of malaria parasitaemia fell from 45% (1992) to 10% (2008). The incidence of pneumococcal bacteraemia in Fajara and Basse did not fall over the study period.These data support an association between malaria and NTS infection. Reductions in malaria infection may be associated with reduced rates of invasive childhood NTS infection.

The introduction of molecular diagnostic methods is crucial for improved understanding of the aetiology and epidemiology of bacterial infections in communities in resource poor settings. A blood sample from a 7 month old patient diagnosed with malaria in 2001 in a Gambian outpatient clinic was reported as culture negative after it was subjected to traditional bacterial culture protocols. We re-addressed the analysis of the blood sample from this case more recently (after 6.5 years in archival storage) in pilot work establishing 16S rRNA PCR in our molecular laboratory. Initial 16S rRNA PCR results confirmed the presence of bacterial DNA in the sample. 16S rRNA sequence analysis identified the organism as Campylobacter spp. In light of the molecular evidence we successfully grew the organism using appropriate culture conditions and subsequently biochemically confirmed that the isolate was Campylobacter jejuni. PCR and DNA sequencing of a set of seven C. jejuni housekeeping genes and in silico Multilocus Sequence Typing (MLST) analysis revealed that the isolate exhibits a novel sequence type (ST) of C. jejuni (ST 2928) and belongs to ST-443 clonal complex. This study demonstrates the potential for molecular tools to enhance the diagnosis of bacterial infections, which remain a major killer globally, not least in children in the developing world. Improvements in diagnostics are needed, and will be important not only for sick individuals but also for populations, where better measures of disease burden will contribute significantly to the improvement of public health policy.

We have captured an 8.7 A conformational change that takes place in the cleavage site of the hammerhead ribozyme during self-cleavage, using X-ray crystallography combined with physical and chemical trapping techniques. This rearrangement brings the hammerhead ribozyme from the ground state into a conformation that is poised to form the transition state geometry required for hammerhead RNA self-cleavage. Use of a 5’-C-methylated ribose adjacent to the cleavage site permits this ordinarily transient conformational change to be kinetically trapped and observed crystallographically after initiating the hammerhead ribozyme reaction in the crystal. Cleavage of the corresponding unmodified hammerhead ribozyme in the crystal under otherwise identical conditions is faster than in solution, indicating that we have indeed trapped a catalytically relevant intermediate form of this RNA enzyme

The Tetrahymena ribozyme has been shown to catalyze an RNA polymerase-like reaction in which an RNA primer is extended by the sequential addition of pN nucleotides derived from GpN dinucleotides, where N = A, C, or U. Here, we show that this reaction is influenced by the presence of a template; bases that can form Watson-Crick base pairs with a template add as much as 25-fold more efficiently than mismatched bases. A mutant enzyme with an altered guanosine binding site can catalyze template-directed primer extension with all four bases when supplied with dinucleotides of the form 2-aminopurine-pN.