Using an Antibiogram Profile to Improve Infection Control and Rational Antimicrobial Therapy in an Urban Hospital in The Gambia, Strategies and Lessons for Low- and Middle-Income Countries.

Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making in a sub-Saharan African county. This retrospective cross-sectional descriptive study used 3 years of cumulative data from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardized methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard manual microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines. A total of 14,776 non-duplicate samples were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E. coli (n = 315) S. aureus (n = 232), and K. pneumoniae (n = 96) were the leading cause of disease. Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), and amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase (ESBL) resistance was present in 23% (71/315) vs. 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%. This antibiogram has shown that improvement in combination therapy is warranted in The Gambia.

Genomic diversity and antimicrobial resistance among non-typhoidal Salmonella associated with human disease in The Gambia.

Non-typhoidal Salmonella associated with multidrug resistance cause invasive disease in sub-Saharan Africa. Specific lineages of serovars Typhimurium and Enteritidis have been implicated. Here we characterized the genomic diversity of 100 clinical non-typhoidal Salmonella collected from 93 patients in 2001 from the eastern, and in 2006-2018 from the western regions of The Gambia respectively. A total of 93 isolates (64 invasive, 23 gastroenteritis and six other sites) representing a single infection episode were phenotypically tested for antimicrobial susceptibility using the Kirby-Bauer disc diffusion technique. Whole genome sequencing of 100 isolates was performed using Illumina, and the reads were assembled and analysed using SPAdes. The Salmonella in Silico Typing Resource (SISTR) was used for serotyping. SNP differences among the 93 isolates were determined using Roary, and phylogenetic analysis was performed in the context of 495 African strains from the European Nucleotide Archive. Salmonella serovars Typhimurium (26/64; 30.6 %) and Enteritidis (13/64; 20.3 %) were associated with invasive disease, whilst other serovars were mainly responsible for gastroenteritis (17/23; 73.9 %). The presence of three major serovar Enteritidis clades was confirmed, including the invasive West African clade, which made up more than half (11/16; 68.8 %) of the genomes. Multidrug resistance was confined among the serovar Enteritidis West African clade. The presence of this epidemic virulent clade has potential for spread of resistance and thus important implications for systematic patient management. Surveillance and epidemiological investigations to inform control are warranted.

Evolution of Mycobacterium tuberculosis complex lineages and their role in an emerging threat of multidrug resistant tuberculosis in Bamako, Mali.

In recent years Bamako has been faced with an emerging threat from multidrug resistant TB (MDR-TB). Whole genome sequence analysis was performed on a subset of 76 isolates from a total of 208 isolates recovered from tuberculosis patients in Bamako, Mali between 2006 and 2012. Among the 76 patients, 61(80.3%) new cases and 15(19.7%) retreatment cases, 12 (16%) were infected by MDR-TB. The dominant lineage was the Euro-American lineage, Lineage 4. Within Lineage 4, the Cameroon genotype was the most prevalent genotype (n = 20, 26%), followed by the Ghana genotype (n = 16, 21%). A sub-clade of the Cameroon genotype, which emerged ~22 years ago was likely to be involved in community transmission. A sub-clade of the Ghana genotype that arose approximately 30 years ago was an important cause of MDR-TB in Bamako. The Ghana genotype isolates appeared more likely to be MDR than other genotypes after controlling for treatment history. We identified a clade of four related Beijing isolates that included one MDR-TB isolate. It is a major concern to find the Cameroon and Ghana genotypes involved in community transmission and MDR-TB respectively. The presence of the Beijing genotype in Bamako remains worrying, given its high transmissibility and virulence.

Hepcidin-guided screen-and-treat interventions against iron-deficiency anaemia in pregnancy: a randomised controlled trial in The Gambia.

BACKGROUND: WHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron. METHODS: We did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18-45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation [UNIMMAP] containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was <2·5 µg/L or UNIMMAP without iron if hepcidin was ≥2·5 µg/L), or a 30 mg screen-and-treat approach (ie, daily UNIMMAP containing 30 mg iron for 7 days if weekly hepcidin was <2·5 µg/L or UNIMMAP without iron if hepcidin was ≥2·5 µg/L). We used a block design stratified by amount of haemoglobin at enrolment (above and below the median amount of haemoglobin on every enrolment day) and stage of gestation (14-18 weeks vs 19-22 weeks). Participants and investigators were unaware of the random allocation. The primary outcome was the amount of haemoglobin at day 84 and was measured as the difference in haemoglobin in each screen-and-treat group compared with WHO's recommended regimen; the non-inferiority margin was set at -5·0 g/L. The primary outcome was assessed in the per-protocol population, which comprised all women who completed the study. This trial is registered with the ISRCTN registry, number ISRCTN21955180. FINDINGS: Between June 16, 2014, and March 3, 2016, 498 participants were randomised, of whom 167 were allocated to WHO's recommended regimen, 166 were allocated to the 60 mg per day screen-and-treat approach, and 165 were allocated to the 30 mg per day screen-and-treat approach. 78 participants were withdrawn or lost to follow-up during the study; thus, the per-protocol population comprised 140 women assigned to WHO's recommended regimen, 133 allocated to the 60 mg screen-and-treat approach, and 147 allocated to the 30 mg screen-and-treat approach. The screen-and-treat approaches did not exceed the non-inferiority margin. Compared with WHO's recommended regimen, the difference in the amount of haemoglobin at day 84 was -2·2 g/L (95% CI -4·6 to 0·1) with the 60 mg screen-and-treat approach and -2·7 g/L (-5·0 to -0·5) with the 30 mg screen-and-treat approach. Adherence, reported side-effects, and adverse events were similar between the three groups. The most frequent side-effect was stomachache, which was similar in the 60 mg screen-and-treat group (82 cases per 1906 person-weeks) and with WHO's recommended regimen (81 cases per 1974 person-weeks; effect 1·0, 95% CI 0·7 to 1·6); in the 30 mg screen-and-treat group the frequency of stomachache was slightly lower than with WHO's recommended regimen (58 cases per 2009 person-weeks; effect 0·7, 95% CI 0·5 to 1·1). No participants died during the study. INTERPRETATION: The hepcidin-guided screen-and-treat approaches had no advantages over WHO's recommended regimen in terms of adherence, side-effects, or safety outcomes. Our results suggest that the current WHO policy for iron administration to pregnant women should remain unchanged while more effective approaches continue to be sought. FUNDING: Bill & Melinda Gates Foundation and the UK Medical Research Council.

Community-acquired Invasive Bacterial Disease in Urban Gambia, 2005-2015: A Hospital-based Surveillance.

BACKGROUND: Invasive bacterial diseases cause significant disease and death in sub-Saharan Africa. Several are vaccine preventable, although the impact of new vaccines and vaccine policies on disease patterns in these communities is poorly understood owing to limited surveillance data. METHODS: We conducted a hospital-based surveillance of invasive bacterial diseases in The Gambia where blood and cerebrospinal fluid (CSF) samples of hospitalized participants were processed. Three surveillance periods were defined in relation to the introduction of pneumococcal conjugate vaccines (PCVs), before (2005- 2009), during (2010-2011) and after (2012-2015) PCV introduction. We determined the prevalences of commonly isolated bacteria and compared them between the different surveillance periods. RESULTS: A total of 14 715 blood and 1103 CSF samples were collected over 11 years; overall, 1045 clinically significant organisms were isolated from 957 patients (972 organisms [6.6%] from blood and 73 [6.6%] from CSF). The most common blood culture isolates were Streptococcus pneumoniae (24.9%), Staphylococcus aureus (22.0%), Escherichia coli (10.9%), and nontyphoidal Salmonella (10.0%). Between the pre-PCV and post-PCV eras, the prevalence of S. pneumoniae bacteremia dropped across all age groups (from 32.4% to 16.5%; odds ratio, 0.41; 95% confidence interval, .29-.58) while S. aureus increased in prevalence, becoming the most prevalent bacteria (from 16.9% to 27.2%; 1.75; 1.26-2.44). Overall, S. pneumoniae (53.4%), Neisseria meningitidis (13.7%), and Haemophilus influenzae (12.3%) were the predominant isolates from CSF. Antimicrobial resistance to common antibiotics was low. CONCLUSIONS: Our findings demonstrate that surveillance data on the predominant pathogens associated with invasive disease is necessary to inform vaccine priorities and appropriate management of patients.

Prevalence of intimate partner violence and abuse and associated factors among women enrolled into a cluster randomised trial in northwestern Tanzania.

BACKGROUND: Intimate partner violence (IPV) is recognised as an important public health and social problem, with far reaching consequences for women's physical and emotional health and social well-being. Furthermore, controlling behaviour by a partner has a similar impact on women's well-being, yet little is known about the prevalence of this type of behaviour and other related abuses in Tanzania and in other sub-Saharan African countries. METHODS: We conducted a cross-sectional study to determine the lifetime and past 12-month prevalence of physical and sexual IPV, economic abuse, emotional abuse and controlling behaviour among ever-partnered women in Mwanza, Tanzania. Women (N = 1049) were enrolled in an ongoing trial (Maisha study) to assess the impact of microfinance combined with gender training on participants' experience IPV, and other related outcomes. Interviews were conducted by same sex interviewers to collect information about socio-demographic characteristics, experiences of specific acts of IPV and abuse, and symptoms of poor mental health status. RESULTS: Overall, about 61% of women reported ever experiencing physical and/or sexual IPV (95% CI: 58-64%) and 27% (95% CI: 24-29%) experienced it in the past 12 months. Partner controlling behaviour was the most prevalent type of abuse with 82% experiencing it in their lifetime and 63% during the past 12 months. Other types of abuses were also common, with 34% of women reporting economic abuse and 39% reporting emotional abuse during the past 12 months. The prevalence of IPV and abuses varied by socio-demographic characteristics, showing much higher prevalence rates among younger women, women with young partners and less educated women. After we adjusted for age and socio-economic status, physical violence (OR = 1.8; 95% CI: 1.3-2.7) and sexual violence (OR = 2.8; 95% CI: 1.9-4.1) were associated with increased reporting of symptoms of poor mental health. Similarly, experience of abuse during the past 12 months was associated with increased reporting of symptoms of poor mental health. CONCLUSIONS: The high prevalence of IPV and abuses and its strong links with symptoms of poor mental health underline the urgent need for developing and testing appropriate interventions in settings like Tanzania to tackle both violence and abusive behaviours among intimate partners. TRIAL REGISTRATION: ClinicalTrials.gov - ID NCT02592252 , registered retrospectively on 13 August 2015.

A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children.

BACKGROUND: A Tuberculin skin test (TST) survey was conducted to assess the prevalence of latent TB Infection (LTBI) and to estimate the annual risk of M. tuberculosis infection (ARTI) in Gambian school children. The results are expected to contribute to understanding of Tuberculosis epidemiology in The Gambia. METHODS: This was a nationwide, multi-cluster survey in children aged 6-11 years. Districts, 20 of 37, were selected by probability proportional to size and schools by simple random sampling. All TST were performed using the Mantoux method. Height and weight measurements were obtained for all participants. We calculated prevalence of LTBI using cut-off points of 10mm, the mirror and mixture modelling methods. RESULTS: TST readings were completed 13,386 children with median age of 9 years (interquartile range [IQR] 8-10 years). Mixture analysis yielded a cut-off point of 12 mm, and LTBI prevalence of 6.9% [95%CI 6.47-7.37] and the ARTI was 0.75% [95%CI 0.60-0.91]. LTBI was associated gender and urban residence (p <0.01). Nutritional status was not associated with non-reactive TST or sizes of TST indurations. ARTI did not differ significantly by age, gender, BCG vaccination or residence. CONCLUSIONS: This estimates for LTBI prevalence and ARTI were low but this survey provides updated data. Malnutrition did not affect estimates of LTBI and ARTI. Given the low ARTI in this survey and the overlapping distribution of indurations with mixture modelling, further surveys may require complementary tests such as interferon gamma release assays or novel diagnostic tools.

Malaria Prevalence among Young Infants in Different Transmission Settings, Africa.

The prevalence and consequences of malaria among infants are not well characterized and may be underestimated. A better understanding of the risk for malaria in early infancy is critical for drug development and informed decision making. In a cross-sectional survey in Guinea, The Gambia, and Benin, countries with different malaria transmission intensities, the overall prevalence of malaria among infants <6 months of age was 11.8% (Guinea, 21.7%; The Gambia, 3.7%; and Benin, 10.2%). Seroprevalence ranged from 5.7% in The Gambia to 41.6% in Guinea. Mean parasite densities in infants were significantly lower than those in children 1-9 years of age in The Gambia (p<0.0001) and Benin (p = 0.0021). Malaria in infants was significantly associated with fever or recent history of fever (p = 0.007) and anemia (p = 0.001). Targeted preventive interventions, adequate drug formulations, and treatment guidelines are needed to address the sizeable prevalence of malaria among young infants in malaria-endemic countries.

School-based countrywide seroprevalence survey reveals spatial heterogeneity in malaria transmission in the Gambia.

BACKGROUND: As the geographical distribution of malaria transmission becomes progressively clustered, identifying residual pockets of transmission is important for research and for targeting interventions. Malarial antibody-based surveillance is increasingly recognised as a valuable complement to classic methods for the detection of infection foci especially at low transmission levels. The study presents serological evidence for transmission heterogeneity among school children in The Gambia measured during the dry, non-transmission season. METHODS: Healthy primary school children were randomly selected from 30 schools across the country and screened for malaria infection (microscopy) and antimalarial antibodies (MSP119). Antibody distribution was modelled using 2-component finite mixture model with cut-off for positivity from pooled sera set at 2-standard deviation from the mean of the first component. Factors associated with a positive serological status were identified in a univariate model and then combined in a multilevel mixed-effects logistic regression model, simultaneously adjusting for variations between individuals and school. RESULTS: A total of 4140 children, 1897 (46%) boys, were enrolled with mean age of 10.2 years (SD 2.6, range 4-20 years). Microscopy results available for 3640 (87.9%) children showed that 1.9% (69) were positive for Plasmodium falciparum infections, most of them (97.1%, 67/69) asymptomatic. The overall seroprevalence was 12.7% (527/4140) with values for the schools ranging from 0.6% to 43.8%. Age (OR 1.12, 95% CI 1.07-1.16,) and parasite carriage (OR 3.36, 95% CI 1.95-5.79) were strongly associated with seropositivity. CONCLUSION: Serological responses to malaria parasites could identify individuals who were or had been infected, and clusters of residual transmission. Field-adapted antibody tests able to guide mass screening and treatment campaigns would be extremely useful.