Staphylococcus aureus Bacteremia in Children of Rural Areas of The Gambia, 2008-2015.

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.

The emerging threat of pre-extensively drug-resistant tuberculosis in West Africa: preparing for large-scale tuberculosis research and drug resistance surveillance.

BACKGROUND: Drug-resistant tuberculosis (TB) is a global public health problem. Adequate management requires baseline drug-resistance prevalence data. In West Africa, due to a poor laboratory infrastructure and inadequate capacity, such data are scarce. Therefore, the true extent of drug-resistant TB was hitherto undetermined. In 2008, a new research network, the West African Network of Excellence for Tuberculosis, AIDS and Malaria (WANETAM), was founded, comprising nine study sites from eight West African countries (Burkina Faso, The Gambia, Ghana, Guinea-Bissau, Mali, Nigeria, Senegal and Togo). The goal was to establish Good Clinical Laboratory Practice (GCLP) principles and build capacity in standardised smear microscopy and mycobacterial culture across partnering laboratories to generate the first comprehensive West African drug-resistance data. METHODS: Following GCLP and laboratory training sessions, TB isolates were collected at sentinel referral sites between 2009-2013 and tested for first- and second-line drug resistance. RESULTS: From the analysis of 974 isolates, an unexpectedly high prevalence of multi-drug-resistant (MDR) strains was found in new (6 %) and retreatment patients (35 %) across all sentinel sites, with the highest prevalence amongst retreatment patients in Bamako, Mali (59 %) and the two Nigerian sites in Ibadan and Lagos (39 % and 66 %). In Lagos, MDR is already spreading actively amongst 32 % of new patients. Pre-extensively drug-resistant (pre-XDR) isolates are present in all sites, with Ghana showing the highest proportion (35 % of MDR). In Ghana and Togo, pre-XDR isolates are circulating amongst new patients. CONCLUSIONS: West African drug-resistance prevalence poses a previously underestimated, yet serious public health threat, and our estimates obtained differ significantly from previous World Health Organisation (WHO) estimates. Therefore, our data are reshaping current concepts and are essential in informing WHO and public health strategists to implement urgently needed surveillance and control interventions in West Africa.

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae.

Is the absolute requirement for informed consent before HIV testing a barrier to public health? A case report and management challenges.

Clinicians in sub-Saharan Africa are faced with a major challenge of parental refusal to test their children for HIV. We present a case of a nine-month-old child with a clinical presentation suggestive of HIV infection whose mother persistently declined HIV testing of the child or herself. The case illustrates the difficulties faced by the clinicians caring for the child in an isolated location in West Africa. While not eliminating these difficulties, an opt-out approach to paediatric HIV testing in sub-Saharan Africa may increase the proportion of children who access treatment when they need it, particularly when this is backed by the development of more effective national and regional clinical and legislative frameworks for HIV testing in children.

The effectiveness of conjugate Haemophilus influenzae type B vaccine in The Gambia 14 years after introduction.

BACKGROUND: The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction. METHODS: Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to <2 years, Hib antibody levels in children aged <5 years, and Hib vaccine coverage and timing in children aged 1 to <2 years. RESULTS: The incidence of Hib meningitis remained low (averaging 1.3 per 100 000 children aged <5 years annually), as did the Hib oropharyngeal carriage rate (0.9%). Hib antibody levels were protective in >99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1-2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively. CONCLUSIONS: Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries.

Immunogenic Mycobacterium africanum strains associated with ongoing transmission in The Gambia.

In West Africa, Mycobacterium tuberculosis strains co-circulate with M. africanum, and both pathogens cause pulmonary tuberculosis in humans. Given recent findings that M. tuberculosis T-cell epitopes are hyperconserved, we hypothesized that more immunogenic strains have increased capacity to spread within the human host population. We investigated the relationship between the composition of the mycobacterial population in The Gambia, as measured by spoligotype analysis, and the immunogenicity of these strains as measured by purified protein derivative-induced interferon-γ release in ELISPOT assays of peripheral blood mononuclear cells. We found a positive correlation between strains with superior spreading capacity and their relative immunogenicity. Although our observation is true for M. tuberculosis and M. africanum strains, the association was especially pronounced in 1 M. africanum sublineage, characterized by spoligotype shared international type 181, which is responsible for 20% of all tuberculosis cases in the region and therefore poses a major public health threat in The Gambia.

Serogroup W135 meningococcal disease, The Gambia, 2012.

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.

Antimicrobial susceptibility and resistance patterns among Helicobacter pylori strains from The Gambia, West Africa.

Helicobacter pylori is a globally important and genetically diverse gastric pathogen that infects most people in developing countries. Eradication efforts are complicated by antibiotic resistance, which varies in frequency geographically. There are very few data on resistance in African strains. Sixty-four Gambian H. pylori strains were tested for antibiotic susceptibility. The role of rdxA in metronidazole (Mtz) susceptibility was tested by DNA transformation and sequencing; RdxA protein variants were interpreted in terms of RdxA structure. Forty-four strains (69%) were resistant to at least 8 µg of Mtz/ml. All six strains from infants, but only 24% of strains from adults, were sensitive (P = 0.0031). Representative Mtz-resistant (Mtz(r)) strains were rendered Mtz susceptible (Mtz(s)) by transformation with a functional rdxA gene; conversely, Mtz(s) strains were rendered Mtz(r) by rdxA inactivation. Many mutations were found by Gambian H. pylori rdxA sequencing; mutations that probably inactivated rdxA in Mtz(r) strains were identified and explained using RdxA protein's structure. All of the strains were sensitive to clarithromycin and erythromycin. Amoxicillin and tetracycline resistance was rare. Sequence analysis indicated that most tetracycline resistance, when found, was not due to 16S rRNA gene mutations. These data suggest caution in the use of Mtz-based therapies in The Gambia. The increasing use of macrolides against respiratory infections in The Gambia calls for continued antibiotic susceptibility monitoring. The rich variety of rdxA mutations that we found will be useful in further structure-function studies of RdxA, the enzyme responsible for Mtz susceptibility in this important pathogen.

Incidence of Haemophilus influenzae type b disease in The Gambia 14 years after introduction of routine Haemophilus influenzae type b conjugate vaccine immunization.

OBJECTIVE: Haemophilus influenzae type b (Hib) conjugate vaccine was first introduced in Africa in The Gambia in 1997 as a primary 3-dose course in infancy with no booster, and was followed by the disappearance of invasive Hib disease by 2002. A cluster of cases detected non-systematically in post-infant children in 2005-2006 raised the question of the need for a booster dose. The objective of this study was to determine the incidence of invasive Hib disease in Gambian children 14 years after the introduction of Hib conjugate vaccine. STUDY DESIGN: This hospital-based clinical and microbiological Hib disease surveillance in 3 hospitals in the western region of The Gambia was undertaken between October 2007 and December 2010 applying the same methods used in a previous Hib vaccine effectiveness study in 1997-2002. RESULTS: The annual incidences of Hib meningitis and all invasive Hib disease in children aged <5 years remained below 5 cases per 100,000 children during 2008-2010. The median age of patients with any invasive Hib disease was 5 months. CONCLUSION: Hib conjugate vaccination as a primary 3-dose course in The Gambia remains highly effective in controlling invasive Hib disease, and current data do not support the introduction of a booster dose.

Rebalancing the research equation in Africa: principles and process.

BACKGROUND: Many examples of research excellence in Africa have been driven by partnerships led by the global North and have involved localised infrastructure improvements to support the best of international research practice. OBJECTIVE: In this article, we explore a possible mechanism by which local research networks, appropriately governed, could begin to support national African research programmes by allying research delivery to clinical service. SUMMARY: This article explores the concept that sustainable research effort needs a well-trained and mentored workforce, working to common standards, but which is practically supported by a much developed information technology (IT) infrastructure throughout the continent. CONCLUSIONS: The balance of investment and ownership of such a research programme needs to be shared between local and international funding, with the emphasis on developing global South-South collaborations and research strategies which address the environmental impact of medical research activity and mitigate the impact of climate change on African populations. Healthcare must be embedded in the post-COVID-19 approach to research development.

Etiology of Kidney Diseases With Proteinuria in the Gambia/West Africa.

In West Africa, kidney diseases are frequently seen, but diagnostic and therapeutic options are poor due to limited access to specialized facilities. To unravel the etiology and develop clinical guidelines, we collected clinical data and results of kidney biopsies in 121 pediatric and mostly young adult patients with edema and proteinuria in The Gambia. Workup included clinical examination, urine and serum analysis, and kidney biopsy findings. Selected cases were treated with steroids. Results: The median age was 14.9 years (range 1.8-52.0) at presentation. The most frequent underlying histologies were post-infectious glomerulonephritis (PIGN) in 38%, focal-segmental glomerulosclerosis (FSGS) in 30%, minimal change nephrotic syndrome (MCNS) in 15%, and membranous glomerulonephritis (MGN) in 10% of cases. Patients with PIGN were significantly younger and had less proteinuria and higher serum albumin levels than the other three. Infected scabies was seen more often in cases with PIGN. Clinical parameters could not distinguish patients with FSGS, MCNS, and MGN. Steroid response was prompt in patients with MCNS (remission in 10/10 cases) compared to FSGS (4/19) and MGN (0/4). In summary, the clinical histopathological correlation allows a better approach to therapy and can be the basis for urgently needed interventional studies in steroid-resistant cases.

Reaching millennium development goal 4 - the Gambia.

UNLABELLED: To describe how, through a DSS in a rural area of The Gambia, it has been possible to measure substantial reductions in child mortality rates and how we investigated whether the decline paralleled the registered fall in malaria incidence in the country. METHODS: Demographic surveillance data spanning 19.5 years (1 April 1989-30 September 2008) from 42 villages around the town of Farafenni, The Gambia, were used to estimate childhood mortality rates for neonatal, infant, child (1-4 years) and under-5 age groups. Data were presented in five a priori defined time periods, and annual rates per 1000 live births were derived from Kaplan-Meier survival probabilities. RESULTS: From 1989-1992 to 2004-2008, under-5 mortality declined by 56% (95% CI: 48-63%), from 165 (95% CI: 151-181) per 1000 live births to 74 (95% CI: 65-84) per 1000 live births. In 1- to 4-year-olds, mortality during the period 2004-2008 was 69% (95% CI: 60-76%) less than in 1989-1992. The corresponding mortality decline in infants was 39% (95% CI: 23-52%); in neonates, it was 38% (95% CI: 13-66%). The derived annual under-5 mortality rates declined from 159 per 1000 live births in 1990 to 45 per 1000 live births in 2008, thus implying an attainment of MDG4 seven years in advance of the target year of 2015. CONCLUSION: Achieving MDG4 is possible in poor, rural areas of Africa through widespread deployment of relatively simple measures that improve child survival, such as immunisation and effective malaria control.

Possible Reasons Why Sub-Saharan Africa Experienced a Less Severe COVID-19 Pandemic in 2020.

Both scientific authorities and governments of nations worldwide were found lacking in their COVID-19 response and management, resulting in significant distrust by the general public in 2020. Scientific and medical bodies often failed to give the right counsel on the appropriate course of action on COVID-19, because proven steps were not known, while many governments around the world took ineffective, late or inappropriate COVID-19 control and containment strategies. If the 2020 COVID-19 incidence rates are to be believed, much of sub-Saharan Africa had a lower disease prevalence than expected. We put forward six factors peculiar to much of sub-Saharan Africa that may have accounted for the pandemic landscape there in 2020. We also discuss why the situation has become more serious in 2021.

Impact of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease and pneumonia in The Gambia: 10 years of population-based surveillance.

BACKGROUND: The Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence. METHODS: We did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008-May 11, 2010) and post-vaccine years (2016-2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time. FINDINGS: We identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2-59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69-87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64-1·21). We detected zero cases of vaccine-type IPD in the 2-11 month age group in 2016-17. Incidence of radiological pneumonia decreased by 33% (95% CI 24-40), from 10·5 to 7·0 per 1000 person-years in the 2-59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22-31). In the 5-14 year age group, IPD incidence declined by 69% (95% CI -28 to 91) and radiological pneumonia by 27% (95% CI -5 to 49). INTERPRETATION: Routine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses. FUNDING: Gavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

Presence of a multidrug-resistance mutation in an HIV-2 variant infecting a treatment-naive individual in Caio, Guinea Bissau.

We report the possible transmission of drug-resistant human immunodeficiency virus type 2. A 66-year-old woman from rural Guinea Bissau who had no obvious antiretroviral exposure was found to harbor a variant with the multidrug-resistance mutation Q151M. Finding this mutation among a drug-naive population presents an important public health issue that needs to be addressed for treatment to be effective.

Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis.

BACKGROUND: Malaria is a major cause of morbidity and mortality in Africa. International effort and funding for control has been stepped up, with substantial increases from 2003 in the delivery of malaria interventions to pregnant women and children younger than 5 years in The Gambia. We investigated the changes in malaria indices in this country, and the causes and public-health significance of these changes. METHODS: We undertook a retrospective analysis of original records to establish numbers and proportions of malaria inpatients, deaths, and blood-slide examinations at one hospital over 9 years (January, 1999-December, 2007), and at four health facilities in three different administrative regions over 7 years (January, 2001-December, 2007). We obtained additional data from single sites for haemoglobin concentrations in paediatric admissions and for age distribution of malaria admissions. FINDINGS: From 2003 to 2007, at four sites with complete slide examination records, the proportions of malaria-positive slides decreased by 82% (3397/10861 in 2003 to 337/6142 in 2007), 85% (137/1259 to 6/368), 73% (3664/16932 to 666/11333), and 50% (1206/3304 to 336/1853). At three sites with complete admission records, the proportions of malaria admissions fell by 74% (435/2530 to 69/1531), 69% (797/2824 to 89/1032), and 27% (2204/4056 to 496/1251). Proportions of deaths attributed to malaria in two hospitals decreased by 100% (seven of 115 in 2003 to none of 117 in 2007) and 90% (22/122 in 2003 to one of 58 in 2007). Since 2004, mean haemoglobin concentrations for all-cause admissions increased by 12 g/L (85 g/L in 2000-04 to 97 g/L in 2005-07), and mean age of paediatric malaria admissions increased from 3.9 years (95% CI 3.7-4.0) to 5.6 years (5.0-6.2). INTERPRETATION: A large proportion of the malaria burden has been alleviated in The Gambia. Our results encourage consideration of a policy to eliminate malaria as a public-health problem, while emphasising the importance of accurate and continuous surveillance.

Virological response to highly active antiretroviral therapy in patients infected with human immunodeficiency virus type 2 (HIV-2) and in patients dually infected with HIV-1 and HIV-2 in the Gambia and emergence of drug-resistant variants.

Drug design, antiretroviral therapy (ART), and drug resistance studies have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1), resulting in limited information for patients infected with HIV-2 and for those dually infected with HIV-1 and HIV-2. In this study, 20 patients, 12 infected with HIV-2 and 8 dually infected with HIV-1 and HIV-2, all treated with zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV/r), were followed up longitudinally for about 3 years. For 19/20 patients, viral loads were reduced to undetectable levels; the patient whose viral load remained detectable reported adverse effects associated with LPV/r that had caused him to stop taking all the drugs. HIV-2 strains containing mutations in both the protease and the reverse transcriptase gene that may confer drug resistance were observed in two patients with viral rebound, as early as 130 days (4.3 months) after the initiation of therapy. We conclude that the combination of ZDV, 3TC, and LPV/r is able to provide efficient and durable suppression of HIV-1 and HIV-2 for as long as 3 years in HIV-2-infected and dually infected patients. However, the emergence of HIV-1 and HIV-2 strains containing drug-resistant mutations can compromise the efficacy of this highly active ART.

Meeting oxygen needs in Africa: an options analysis from the Gambia.

OBJECTIVE: To compare oxygen supply options for health facilities in the Gambia and develop a decision-making algorithm for choosing oxygen delivery systems in Africa and the rest of the developing world. METHODS: Oxygen cylinders and concentrators were compared in terms of functionality and cost. Interviews with key informants using locally developed and adapted WHO instruments, operational assessments, cost-modelling and cost measurements were undertaken to determine whether oxygen cylinders or concentrators were the better choice. An algorithm and a software tool to guide the choice of oxygen delivery system were constructed. FINDINGS: In the Gambia, oxygen concentrators have significant advantages compared to cylinders where power is reliable; in other settings, cylinders are preferable as long as transporting them is feasible. Cylinder costs are greatly influenced by leakage, which is common, whereas concentrator costs are affected by the cost of power far more than by capital costs. Only two of 12 facilities in the Gambia were found suitable for concentrators; at the remaining 10 facilities, cylinders were the better option. CONCLUSION: Neither concentrators nor cylinders are well suited to every situation, but a simple options assessment can determine which is better in each setting. Nationally this would result in improved supply and lower costs by comparison with conventional cylinders alone, although ensuring a reliable supply would remain a challenge. The decision algorithm and software tool designed for the Gambia could be applied in other developing countries.