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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. [ABSTRACT FROM AUTHOR]

Background The Gambia, located in West Africa, is one of 7 country sites conducting the Enterics for Global Health (EFGH) Shigella Surveillance Study to establish incidence and consequence of Shigella -associated medically attended diarrhea among children 6–35 months old. Methods Here we describe the study site and research experience, sociodemographic characteristics of the study catchment area, facilities of recruitment for diarrhea case surveillance, and known care-seeking behavior for diarrheal illness. We also describe The Gambia's healthcare system and financing, current vaccine schedule and Shigella vaccine adaptation, local diarrhea management guidelines and challenges, and antibiotic resistance patterns in the region. Conclusions The EFGH study in The Gambia will contribute to the multisite network of Shigella surveillance study and prepare the site for future vaccine trials. In addition, the data produced will inform policy makers about prevention strategies and upcoming Shigella vaccine studies among children in this setting. [ABSTRACT FROM AUTHOR]

'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 FROM AUTHOR]

Key Points: Question: Does azithromycin administered orally during labor reduce neonatal sepsis and mortality? Findings: This randomized trial in West Africa included 11 983 birthing parents and their infants. The incidence of the composite end point of neonatal sepsis or neonatal mortality was similar in the azithromycin (2.0%) and placebo (1.9%) groups. However, the incidence of noninvasive infections during the subsequent 4 weeks was reduced for newborns (skin infections) and parents (puerperal fever and mastitis) in the azithromycin group. Meaning: These results do not support routine introduction of oral intrapartum azithromycin to reduce neonatal sepsis or mortality. Importance: Neonatal sepsis is a leading cause of neonatal mortality. New interventions are needed to decrease neonatal sepsis and mortality in regions with highest burden. Objective: To evaluate the efficacy of intrapartum azithromycin to reduce neonatal sepsis or mortality, as well as neonatal and maternal infections. Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial enrolled and followed up birthing parents and their infants at 10 health facilities in The Gambia and Burkina Faso, West Africa, between October 2017 and May 2021. Interventions: Participants were assigned at random to receive oral azithromycin (2 g) or placebo (ratio 1:1) during labor. Main Outcomes and Measures: The primary outcome was a composite of neonatal sepsis or mortality, with the former defined based on microbiologic or clinical criteria. Secondary outcomes were neonatal infections (skin, umbilical, eye and ear infections), malaria, and fever; postpartum infections (puerperal sepsis, mastitis), fever, and malaria; and use of antibiotics during 4-week follow-up. Results: The trial randomized 11 983 persons in labor (median age, 29.9 years). Overall, 225 newborns (1.9% of 11 783 live births) met the primary end point. The incidence of neonatal mortality or sepsis was similar in the azithromycin and placebo groups (2.0% [115/5889] vs 1.9% [110/5894]; risk difference [RD], 0.09 [95% CI, −0.39 to 0.57]), as was the incidence of neonatal mortality (0.8% vs 0.8%; RD, 0.04 [95% CI, −0.27 to 0.35]) and neonatal sepsis (1.3% vs 1.3%; RD, 0.02 [95% CI, −0.38 to 0.43]). Newborns in the azithromycin group compared with the placebo group had lower incidence of skin infections (0.8% vs 1.7%; RD, −0.90 [95% CI, −1.30 to −0.49]) and need for antibiotics (6.2% vs 7.8%; RD, −1.58 [95% CI, −2.49 to −0.67]). Postpartum parents in the azithromycin group had lower incidence of mastitis (0.3% vs 0.5%; RD, −0.24 [95% CI, −0.47 to −0.01]) and puerperal fever (0.1% vs 0.3%; RD, −0.19 [95% CI, −0.36 to −0.01]). Conclusions and Relevance: Azithromycin administered orally during labor did not reduce neonatal sepsis or mortality. These results do not support routine introduction of oral intrapartum azithromycin for this purpose. Trial Registration: ClinicalTrials.gov Identifier: NCT03199547 This randomized trial compares the efficacy of intrapartum azithromycin vs placebo to reduce neonatal sepsis or mortality, as well as neonatal and maternal infections, among birthing parents and their infants in West Africa. [ABSTRACT FROM AUTHOR]

Thermoplastics starches are plastics made from renewable resources like plants that are fully bio-based and biodegradable. The aim of this study was to produce and characterize thermoplastic using starches extracted from cassava and sweet potato. The effect of variable amounts of glycerol used as plasticizer and acetic acid used for hydrolysis of the starch polymer were investigated. The intermolecular interaction between the starch and glycerol was ascertained using FT-IR spectroscopy. The biodegradability test conducted on both cassava thermoplastic starch (TPSc) and potato thermoplastic starch (TPSp) were found to lose 36% and 23% respectively of their initial weights after seven days of soil burial. The result showed that as plasticizer concentration increased from 50 to 80%, there was an increase in both moisture and oil uptake but a decrease in water uptake. However, an increase in acetic acid concentration from 2.5% to 7.5% resulted in a decrease in oil uptake, water uptake and moisture uptake of the thermoplastics. Findings in this study reveal increase in the amount of glycerol plasticizer in both thermoplastics increases moisture contents retention however the observed oil uptake and biodegradability properties suggest the thermoplastic starches especially the potato thermoplastic starch is generally suitable for making eco-friendly thermoplastics. [ABSTRACT FROM AUTHOR]

This study was conducted to determine the associations between the socio-demographics, clinical profile and therapy options received by cervical cancer (CC) patients in Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto and Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. The study used a prospective longitudinal design with retrieved data for 157 eligible CC patients. Pearson's correlation was used to test for association between patients' socio-demographics, clinical characteristics and number of therapy options received while comparisons of proportions were carried out using Pearson's Chi square. Results show that the mean age of the patients was 50.7±9.0 years and 43.3% of patients earned less than 50,000.00 per month. The results also reveal most of the 47.1% of patients presented with clinical stage III. Per Vaginal Bleeding (PVB) was the symptoms recorded for 88.5% of the patients while most patients (49.7%) received Chemotherapy (CT) as the major therapy option. There were significant associations between the level of income, (r=0.412, p<0.001), baseline number of symptoms, (r=0.200, p=0.012), number of symptoms after therapy, (r= -0.584, p<0.001) and the number of therapies received by the patients. Clinical disease-stage, baseline number of symptoms and level of income were found to be associated with the therapy options received by the patients. [ABSTRACT FROM AUTHOR]

Summary: Provocative studies have proposed that the common 9 carbon lipid oxidation product, 4‐hydroxy‐2‐nonenal (HNE), increases myoglobin (Mb) autoxidation. Oxidised Mb (Fe3+ Mb or metMb) formation leads to an unappealing meat discoloration. Since Mb also facilitates lipid oxidation, an HNE induced increase in Mb autoxidation would constitute a positive feedback loop. However, NMR studies have noted that only fatty acids with carbon chain length exceeding 10 can significantly bind to Mb. They predict that HNE should not interact with Mb. The present study has used optical and NMR spectroscopy methods to determine if HNE interacts with Mb and if that interaction leads to an increased oxidation of Mb. The study finds no convincing evidence that HNE interacts with Mb and accelerates Mb autoxidation or oxidation by electron transfer. However, the presence of ethanol in the solution will increase Mb oxidation. [ABSTRACT FROM AUTHOR]

Background: The 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. Methods: Population-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. Results: We 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 <2-month age group, 56 per 100,000 in the 2–23-month age group, but lower at 5 per 100,000 in the 5–14-year age group. The most common causes of ABM were Streptococcus pneumoniae (n = 44), Neisseria meningitidis (n = 42), and Gram-negative coliform bacteria (n = 26). Eighteen of 22 cases caused by pneumococcal serotypes included in PCV13 occurred prior to vaccine introduction and four afterwards. The overall case fatality ratio for ABM was 29% (49/169) and was highest in the <2-month age group 37% (10/27). The case fatality ratio was 8.6% (18/209) for suspected non-bacterial meningitis and 12.8% (134/1049) for clinically suspected meningitis cases. Conclusions: Gambian 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. [ABSTRACT FROM AUTHOR]

Study Question: What are the intentions of men and women of reproductive age in the UK regarding reproduction and family building?Summary Answer: We identified six main categories of people; Avoiders, Betweeners, Completers, Desirers, Expectants and Flexers, for whom reproduction education strategies should be tailored differently to suit intentions.What Is Known Already: Several studies have highlighted poor fertility awareness across men and women of reproductive age. As the average age of first-time parents continues to rise, there has been a concerted effort from educators, healthcare professionals, charities, reproductive health groups and government policymakers, to improve fertility awareness. In order to ensure that these messages are effective and to deploy the best strategies, it is important to understand people's reproductive health needs. This study therefore aimed to explore different reproductive intentions to aid tailoring of information to help individuals and couples achieve their family building desires.Study Design, Size, Duration: We conducted a mixed-method study via a UK-wide cross-sectional survey with 1082 participants and semi-structured interviews of 20 women and 15 men who agreed to follow-up interviews. Interviews lasted an hour on average. Ethics approval from UCL Research Ethics Committee.Participants/materials, Setting, Methods: Survey participants were recruited nationwide via online newspaper and social media adverts. Interviewees were purposely sampled to include men and women from the reproductive age range (18-45 years), varying ethnicity and education background. Survey data were analysed using the Minitab statistical software package. Interview data were transcribed and analysed using the framework method.Main Results and the Role Of Chance: From the survey and interviews, we identified six key categories of people, grouped alphabetically, in a user-friendly manner to highlight a spectrum of reproductive intentions: Avoiders describes respondents who have no children and do not want to have children in the future; Betweeners describes those who already have child(ren) and want more in the future but are not actively trying to conceive; Completers describes those who have child(ren) but do not want more; Desirers describes those who are actively trying to conceive or plan to have child(ren) in the future; Expectants describes those who were pregnant at the time of the study; and Flexers describes those who may or may not already have and are unsure but or open to having child(ren) in the future. Analysis of survey data identified the following proportions in our study: Avoiders, 4.7%; Betweeners, 11.3%; Completers, 13.6%; Desirers, 36.9%; Expectants, 4.1%; and Flexers 28.4% and 2.4% preferring not to answer. There was one 'other' group from qualitative analysis, who would like to have children in the future but were unsure whether they could or had changing views. We recommend classifying as 'Desirers' or 'Flexers' for the purposes of fertility education. A majority of the survey population were trying to get pregnant; were pregnant; or planning to have a child in the future-whether actively, passively or simply open to the idea, with interviews providing deep insights into their family building decision-making.Limitations, Reasons For Caution: Due to the online recruitment method, there may be a bias towards more educated respondents.Wider Implications Of the Findings: We developed a user-friendly, alphabetical categorization of reproductive intentions, which may be used by individuals, healthcare professionals, educators, special interest groups, charities and policymakers to support and enable individuals and couples in making informed choices to achieve their desired intentions, if and when they choose to start a family.Study Funding/competing Interest(s): There was no external funding for this study. The authors report no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

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Introduction: Risk factors for mortality associated with COVID-19 have been reported to include increased age, male sex and certain comorbidities. Fracture neck of femur (NOF) patients is high-risk surgical patients, often with multiple comorbidities and advanced age. We quantify the 30-day mortality rate in fractured NOF patients with a positive peri-operative COVID-19 antigen test and identify risk factors for increased mortality. Methods: This is a retrospective multi-centre review of all patients admitted with a fractured NOF and a confirmed laboratory diagnosis of COVID-19 between 1 March and 26 April 2020. Demographic data, comorbidities, ASA grade and date of death (if applicable) were collected. Results: There were 64 patients in the cohort with an overall 30-day mortality rate of 32.8% (n = 21). Thirty-five (55%) were female, and mean age was 83 (SD 9, range 46–100) years. There was significantly increased mortality for those with a history of myocardial infarction (p = 0.03). Sixty-four percent of patients underwent surgery within the 36-h target, which is comparable to previous data for the same time of year. Overall mortality increased to 50% (n = 32) at 45 days post-operatively. Conclusion: This is a large review of 30-day mortality in NOF patients with concurrent COVID-19 infection. We report a substantial increase from the pre-COVID-19 mean 30-day mortality rate (6.5% in 2019). We highlight the need for counselling patients when presenting with a NOF in relation to peri-operative COVID-19 infection and the associated increased risks. [ABSTRACT FROM AUTHOR]

Due to the gradual extinction of the extended family system, many Nigerian elderly now live in geriatric homes. The main objective of the study was to assess the level of life satisfaction of the elderly living in a geriatric home; while the specific ones were to identify the factors responsible for their level of satisfaction, the antecedents of being residents of the home, and their perception of living in a geriatric home. This study was conducted in a geriatric home at Akobo, Ibadan North Local Government, Oyo State, Nigeria. An exploratory, descriptive design was used to elicit data from thirteen participants using In-depth Interview. Out of the twenty-two elderly persons in the home: fifteen met the inclusion criteria and two declined to participate. Hence, only thirteen were interviewed. The mean level of life satisfaction of the participants was 23.60 + 4.09, which meant majority of them were generally satisfied; Illness, childlessness and loneliness were found to affect their life satisfaction. All the participants said either chronic illness or loneliness was the major reason for them residing in the home; and 53.8% of the participants had poor perception about the home, mainly due to movement restriction in the home and lack of a private life. In conclusion, all participants hope to leave the home to re-unite and live with their loved ones. It is therefore imperative for all stakeholders to put necessary measures in place, to strengthen family institution, monitor operation of geriatric homes and elaborate the training of health professionals in geriatric care. [ABSTRACT FROM AUTHOR]

Background: Cryptosporidium 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. Methods: We recruited children <5 years of age with moderate-to-severe diarrhea (MSD) for 3 years (2008–2010), and children with either MSD or less severe diarrhea (LSD) for one year (November 2011-November 2012) at sentinel health centers. One or more randomly selected controls were matched to each case. Stool samples were tested to identify Cryptosporidium by immunoassay. A subset of randomly selected case-controls pairs were tested for Cryptosporidium species. We investigated the epidemiology of, and evaluated possible risk factors for, Cryptosporidium-positive diarrhea. Results: We 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. Conclusion: Cryptosporidium-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. [ABSTRACT FROM AUTHOR]

Background: Nigeria has the highest burden of paediatric HIV infection, and the success of control efforts in the country is crucial to the global control of the HIV epidemic. However, defaults from schedules of care pose a threat to paediatric HIV control in Nigeria. This study was conducted in a pioneer facility for the implementation of the National HIV Prevention and Treatment Programmes.Objective: The objective of this study was to explore factors that facilitate adherence to clinic appointments from perspectives of child caregivers and service providers.Methods: This is a qualitative study using in-depth, face-to-face interviews conducted in 2016. Thirty-five participants were purposely sampled to comprise types of caregivers of HIV-exposed/infected children receiving care and from categories of service providers. The interviews were audio recorded, transcribed, thematically analysed and presented using a socioecological model.Results: The themes that emerged from participants' narratives included advanced education, affluence and residing close to the clinic at the intrapersonal level. Stable family dynamics and support, HIV status disclosure and being a biologic parent or grandparent as caregiver emerged at the interpersonal level. At the community level, disclosure and support were identified, while at the health facility level, positive staff attitude, quality of healthcare and peer support group influence were factors identified to facilitate regular clinic attendance.Conclusion: The factors that enable retention of children in care are multidimensional and intricately connected. Programme improvement initiatives should include regular assessment of clients' perspectives to inform implementation of strategies that could reinforce caregiver confidence in the health system. [ABSTRACT FROM AUTHOR]

We compared phagocytic activity of macrophages of monocyte origin and Kupffer cells under the influence of M1 and M2 inducers and without activation. Cultures of monocyte-derived macrophages and Kupffer cells were characterized by intensive expression of CD68 that was not affected by activation factors. At the same time, these cultures demonstrated different dynamics of phagocytic activity. Monocyte-derived macrophages initially had more pronounced absorption capacity that gradually increased during the experiment. Kupffer cells were characterized by abrupt fluctuations of phagocytic activity: sharp growth and rapid saturation. Despite these differences, the endosomes produced by monocyte-derived macrophages and Kupffer cells had similar degrees of maturity. [ABSTRACT FROM AUTHOR]

We compared phagocytic activity of macrophages of monocyte origin and Kupffer cells under the influence of M1 and M2 inducers and without activation. Cultures of monocyte-derived macrophages and Kupffer cells were characterized by intensive expression of CD68 that was not affected by activation factors. At the same time, these cultures demonstrated different dynamics of phagocytic activity. Monocyte-derived macrophages initially had more pronounced absorption capacity that gradually increased during the experiment. Kupffer cells were characterized by abrupt fluctuations of phagocytic activity: sharp growth and rapid saturation. Despite these differences, the endosomes produced by monocyte-derived macrophages and Kupffer cells had similar degrees of maturity. [ABSTRACT FROM AUTHOR]

Heel pain presents frequently to primary care, commonly affecting athletic and elderly patients. Its presentation can be a common source of confusion for clinicians given the wide variety of differential diagnoses and the similarities in presenting symptoms and signs. This review classifies heel pain according to site of pain and explores the common pathologies clinicians may encounter. A brief summary of common imaging modalities used is provided. The literature is reviewed to guide evidence-based practice and to provide a framework to help clinicians investigate and manage heel pain before onward referral for specialist intervention. A linked article detailing the imaging of heel pain is included in this issue (https://doi.org/10.12968/hmed.2019.80.4.192). [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia is a substantial cause of childhood disease and death, but few studies have described its epidemiology in developing countries. Using a population-based surveillance system for pneumonia, sepsis, and meningitis, we estimated S. aureus bacteremia incidence and the case-fatality ratio in children <5 years of age in 2 regions in the eastern part of The Gambia during 2008-2015. Among 33,060 children with suspected pneumonia, sepsis, or meningitis, we performed blood culture for 27,851; of 1,130 patients with bacteremia, 198 (17.5%) were positive for S. aureus. S. aureus bacteremia incidence was 78 (95% CI 67-91) cases/100,000 person-years in children <5 years of age and 2,080 (95% CI 1,621-2,627) cases/100,000 person-years in neonates. Incidence did not change after introduction of the pneumococcal conjugate vaccine. The case-fatality ratio was 14.1% (95% CI 9.6%-19.8%). Interventions are needed to reduce the S. aureus bacteremia burden in The Gambia, particularly among neonates. [ABSTRACT FROM AUTHOR]

The role of the lungs and kidneys in liver regeneration after subtotal hepatectomy was studied on a rat model. It was found that production of hepatocyte growth factor (HGF) in the lungs and kidneys and expression of cytokine genes Il1b, Il6, Il10, and tnfa significantly increased. Analysis of the dynamics of lung macrophage population showed that accumulation of HGF and the increase in the expression of cytokine genes in the lungs were accompanied by simultaneous increase in the number of CD68+ cells, which attested to the leading role of macrophages in activation of HGF synthesis in the lungs. Macrophage content in the kidneys after subtotal hepatectomy did not increase. [ABSTRACT FROM AUTHOR]

Expression of il1b, il6, il10, tnfa, hgf, tgfb, vegf, and fgf2 genes in the lungs and kidneys was examined on rat model of liver regeneration after subtotal hepatectomy. Enhanced expression of il6, il10, tnfa, hgf, and fgf2 genes was detected at the early terms after 80% liver resection. [ABSTRACT FROM AUTHOR]

In the liver of rats subjected to subtotal liver resection (80% organ weight), the expression of sox9 gene and SOX9 protein content increased and cells with hepatocyte morphology expressing SOX9 appeared; the proportion of cells expressing cytokeratin-19 also increased. Based on these data, we cannot completely exclude the involvement of resident progenitor cells and hepatocyte reprogramming in liver regeneration after subtotal resection, however, the contribution of these processes seems to be insignificant. The leading mechanism of liver mass recovery after subtotal resection is proliferation of hepatocytes. [ABSTRACT FROM AUTHOR]

Short-term cell culturing on basement membrane matrix is a common and very convenient in vitro model of angiogenesis. We studied the possibility of interaction of multipotent stromal cells from the umbilical cord and Ea.hy926 endothelial cells on this model at the early and late periods of the experiment. Multipotent stromal cells alone and in combination with endothelial cells formed an unstable tubular network. Clusters formed after its disassembling later became the sprouting centers in co-culture of the two cell types, but not in pure culture of multipotent stromal cells. Multipotent stromal cells with CD31+ phenotype constitute the structural basis of newly formed stable 3D capillary-like network. Prolongation of the time of culturing and combination of the two in vitro models of angiogenesis (tubulogenesis and sprouting) allowed more complete assessment of the angiogenic potential of multipotent stromal cells. [ABSTRACT FROM AUTHOR]

Background: Streptococcus pneumoniae serotype 5 is among the most common serotypes causing invasive pneumococcal disease (IPD) in The Gambia. We anticipate that introduction of the 13-valent pneumococcal conjugate vaccine (PCV-13) into routine vaccination in The Gambia will reduce serotype 5 IPD. However, the emergence of new clones that have altered their genetic repertoire through capsular switching or genetic recombination after vaccination with PCV-13 poses a threat to this public health effort. In order to monitor for potential genetic changes post-PCV-13 vaccination, we established the baseline population structure, epidemiology, and antibiotic resistance patterns of serotype 5 before the introduction of PCV-13.Methods: Fifty-five invasive S. pneumoniae serotype 5 isolates were recovered from January 2009 to August 2011 in a population-based study in the Upper River Region of The Gambia. Serotyping was done by latex agglutination and confirmed by serotype-specific Polymerase Chain Reaction (PCR). Genotyping was undertaken using Multilocus Sequence Typing (MLST). Antimicrobial sensitivity was done using disc diffusion. Contingency table analyses were conducted using Pearson's Chi(2) and Fisher's exact test. Clustering was performed using Bionumerics version 6.5.Results: MLST resolved S. pneumoniae serotype 5 isolates into 3 sequence types (ST), namely ST 289(6/55), ST 3339(19/55) and ST 3404(30/55). ST 289 was identified as the major clonal complex. ST 3339, the prevalent genotype in 2009 [84.6% (11/13)], was replaced by ST 3404 [70.4% (19/27)] in 2010 as the dominant ST. Interestingly, ST 3404 showed lower resistance to tetracycline and oxacillin (P < 0.001), an empirical surrogate to penicillin in The Gambia.Conclusions: There has been an emergence of ST 3404 in The Gambia prior to the introduction of PCV-13. Our findings provide important background data for future assessment of the impact of PCV-13 into routine immunization in developing countries, such as The Gambia. [ABSTRACT FROM AUTHOR]

Background. There are large data gaps in the epidemiology of diseases caused by Salmonella enterica in West Africa. Regional surveillance of Salmonella infections is necessary, especially with the emergence and spread of multidrug-resistant clones. Methods. Data on Salmonella isolated from various clinical specimens from patients from across The Gambia were collected and analyzed retrospectively from 2005 to April 2015. Antibiotic sensitivity testing of Salmonella isolates was performed by disk diffusion method. Serotyping and serogrouping of Salmonella isolates was performed using standard microbiology techniques. Results. Two hundred three Salmonella isolates were isolated from 190 patients: 52% (106/203) from blood and 39% (79/203) from stool specimens. Salmonella was also isolated from urine, aspirates, cerebrospinal fluid, wounds, and abscesses. The prevalence of Salmonella in blood cultures was 0.8% (106/13 905). Of the serotyped salmonellae, 14% (21/152) were Salmonella enterica serovar Typhi, whereas 86% (131/152) were serovars other than Typhi (nontyphoidal Salmonella). Of the 102 typed NTS isolates, 40% (41) were Salmonella enterica serovar Typhimurium, 10% (10) were Salmonella enterica serovar Enteritidis, and 3% (3) were Salmonella enterica serovar Arizonae. Overall, 70% (142/203) of the salmonellae were pansusceptible. Multidrug resistance was found in 4% (9/203) of the isolates, 3 of which were Salmonella Enteritidis. Conclusions. Salmonellae are associated with a wide spectrum of invasive and noninvasive infections across all ages in The Gambia. There is evidence of multidrug resistance in salmonellae that warrants vigilant monitoring and surveillance. [ABSTRACT FROM AUTHOR]

Intrasplenic allogeneic transplantation of multipotent stromal cells from the umbilical cord stimulates hepatocyte proliferation and promotes recovery of liver weight in rats after subtotal resection (80% organ weight). It can be hypothesized that this effect of multipotent stromal cells is due to more rapid recovery of the number of mitochondria and normalization of mitochondrial function of liver hepatocytes. [ABSTRACT FROM AUTHOR]

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<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17-0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8-220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.-induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Author Summary: Salmonellosis is a neglected tropical disease causing serious dysentery and septicaemia particularly in young infants, elderly and immunocompromised individuals such as HIV patients and associated with substantial mortality in developing countries. Salmonellosis also constitutes a major public health problem as it is considered the most widespread bacterial zoonosis of food origin throughout the world. Many epidemiological data exist from developed countries concerning transmission of Non-Typhoidal Salmonella (NTS) but few are available from developing countries. In addition few studies in sub-Saharan Africa have considered the interface between humans and their environment in relation to animals present in the household and food hygiene. This study describes the prevalence of NTS among fourteen Gambian children and 210 domestic animals living in close proximity (household) to the children in a rural setting in The Gambia. We found that the domestic animals living in the same household as patients carried different NTS serovar and genotypes; indicating that zoonotic transmission does not occur in our setting. This study provides baseline data for future studies of transmission of NTS in rural Africa. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cryptosporidium is a common cause of gastroenteritis and is associated with severe life-threatening illness among immunocompromised individuals. This review aimed to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised patients. A search of Medline, Embase and other electronic databases was carried out up to August 2005. Two reviewers independently extracted data and assessed study quality. The relative risk for each intervention was calculated. Seven trials involving 169 participants were included. Nitazoxanide and paramomycin were associated with a relative risk (RR) of reduction in the duration and frequency of diarrhoea of 0.83 [95% confidence interval (CI) 0.36, 1.94] and 0.74 (95% CI 0.42, 1.31), respectively, showing no evidence of effectiveness. Nitazoxanide led to significant evidence of oocyst clearance compared with placebo with a RR of 0.52 (95% CI 0.30, 0.91). The effect was not significant for HIV-seropositive participants (RR 0.71, 95% CI 0.36, 1.37). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09, 0.80) based on a single study. No other intervention was associated with either a reduction in diarrhoea, mortality or a significant parasitological response. This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces load of parasites and may be useful in immunocompetent individuals. The absence of effective therapy highlights the importance of preventive interventions in this group of patients. [ABSTRACT FROM AUTHOR]

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An autoimplantation technique was adopted in the treatment of 50 cases of anogenital warts and was compared with the conventionally used podophyllin regimen in a matched group of 50 patients. They were assessed with 15 untreated subjects in a control group for the rate of clinical cure after 6 weeks, recurrence after 1 year follow up and for humoral and cell mediated immune responses before and after treatment. In the podophyllin group, 70% of patients were cured after 6 weeks while in autoimplantation, only 44% of patients were cured, and none in the control group had natural remission of warts without any treatment. After 1 year all the cured cases (100%) that completed follow up had recurrence of warts with podophyllin treatment, while none had recurrence of lesions in the autoimplantation group. Results of the humoral and cell mediated immune (CMI) response studies revealed that autoimplantation technique significantly augmented both humoral and CMI responses while there was not significant change in the immune status after podophyllin treatment (P > 0.001). [ABSTRACT FROM AUTHOR]