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Background In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF). Aims To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa. Methods We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls. Results In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), ≥70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality. Conclusions Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia. [ABSTRACT FROM AUTHOR]

Background: Expanding antiviral therapy to people with chronic hepatitis B virus (HBV) infection who are ineligible to receive treatment under current international criteria has been increasingly debated. Evidence to support this approach is scarce, especially in Africa. We aimed to address this knowledge gap by analysing the clinical outcomes of people with chronic hepatitis B in The Gambia who were untreated and ineligible for antiviral therapy at diagnosis., Methods: Between Dec 7, 2011, and Jan 24, 2014, we implemented the prospective PROLIFICA cohort study in The Gambia. Participants with chronic hepatitis B aged 16 years or older were recruited after large-scale, community-based HBV screening; blood bank-based HBV screening in Edward Francis Small Teaching Hospital, Banjul; and prospective follow-up of HBsAg-positive individuals via historical, population-based HBsAg serosurveys in two rural villages (Keneba and Manduar). Participants underwent HBV serology and other laboratory tests, fasting FibroScan, and abdominal ultrasound. Survival data were collected between Dec 7, 2011, and Aug 17, 2021. Between Oct 9, 2018, and Aug 17, 2021, all HBsAg-positive participants enrolled in the 2011-14 cohort were invited for a reassessment. For this analysis, we included HBsAg-positive people and excluded all participants who were eligible for treatment according to the 2012 European Association for the Study of the Liver (EASL) criteria at baseline and those who were treated irrespective of treatment eligibility. The primary outcome was all-cause mortality, assessed in all treatment-ineligible and treatment-naive participants with follow-up data. The secondary outcome, analysed in those who were reassessed, was disease progression, defined as becoming eligible for antivirals per 2017 EASL criteria; having an increase in liver fibrosis of at least one stage; or having a clinical diagnosis of hepatic decompensation or hepatocellular carcinoma., Findings: 943 HBsAg-positive people with chronic hepatitis B were recruited to the PROLIFICA study. Of these 943, 58 (6%) fulfilled 2012 EASL treatment eligibility criteria at baseline, 35 (4%) were ineligible for treatment but received antiviral therapy, and 44 (5%) were immediately lost to follow-up. Thus, 806 (85%) participants were analysed for the primary outcome (486 [60%] were male and 320 [40%] were female). After a median follow-up of 6·11 years (IQR 5·34-6·80), 708 (88%) participants were confirmed to be alive at last surveillance, 71 (9%) were lost to follow-up and were censored, and 27 (3%) died, giving an all-cause mortality rate of 582 per 100 000 person-years (95% CI 399-849). Of the 27 people who died, five (19%) had liver-related deaths. Of 708 participants confirmed to be alive, 544 (77%) attended follow-up and were assessed for the secondary outcome. Disease progression occurred in 36 (7%) participants: five (1%) became newly eligible for antiviral therapy per EASL 2017 criteria without liver fibrosis progression; 18 (3%) had liver fibrosis progression alone; 13 (2%) had liver fibrosis progression and newly fulfilled the treatment criteria; and none had hepatic decompensation or developed hepatocellular carcinoma. In multivariable analysis adjusted for sex and age, only a baseline HBV DNA of 20 000 IU/mL or more, compared with the baseline HBV DNA of 2000 IU/mL or lower as the reference, was significantly associated with liver disease progression (odds ratio 5·39, 95% CI 1·37-21·23)., Interpretation: Among people with chronic hepatitis B who were ineligible for antiviral therapy in The Gambia, all-cause mortality and liver disease progression were low. The clinical benefit of expanding antiviral therapy in this subgroup of patients remains uncertain., Funding: European Commission, Medical Research Council UK Research and Innovation, and Gilead Sciences., Competing Interests: Declaration of interests ML, YS, MT, and GN received research funding and consultancy fees from Gilead Sciences and Abbott. ML received consultancy fees from Cepheid and Abbott and is the recipient of the funding. YS received research materials from Fujirebio and Abbott. GC is an employee of Abbott. PI received consultancy fees from Gilead, AbbVie, and ViiV Healthcare. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Liver abscess is endemic in resource-limited countries such as The Gambia where access to advanced imaging techniques or modern treatment modalities is limited. Despite this, mortality in this cohort was low. Therefore antibiotic therapy combined with percutaneous abscess drainage remains a reasonable treatment strategy of liver abscess in resource-poor settings., (© 2024. The Author(s).)

Background: As a result of the lack of screening programs and the difficulty in making a proper diagnosis, the majority of hepatocellular carcinoma (HHC) patients present late in low-resource countries. The study therefore assesses the clinical features, stage and prognostic variables of patients with HCC in The Gambia., Methods: From December 2015 to January 2019, patients with a confirmed diagnosis of HCC were enrolled. All patients' medical history, ultrasound scan, FibroScan and laboratory details were collected., Results: Two hundred and sixty (260) patients were enrolled. The mean age of HCC patients was 40 years, and 210 (80.7%) of them were male. The most common gastrointestinal symptoms were early satiety 229 (88.1%) and abdominal pain 288 (87.7%), while the most common constitutional symptoms were weight loss 237 (91.2%) and easy fatiguability 237 (91.2%). Hepatomegaly 205 (78.8%) was the most common sign. On ultrasound scan, lesions were mostly multifocal 175 (67.3%), and the median FibroScan score was 75 kPa. The median fibrosis 4 and aspartate transferase platelet ratio index were 4.6 and 2.2, respectively. Hepatitis B surface antigen (HBsAg) was positive in 170 (65.4%) patients, and the median AFP level was 3263 ng/ml. HCC patients with positive HBsAg were more likely to be male 145 (85.3%) vs 62 (72.1%) (p = 0.011), much younger 39.9 vs 51.4 yrs (p =  < 0.0001), more likely to have abdominal pain 156 (91.8%) vs 68 (79.1%) (p = 0.002), jaundice 78 (45.9%) vs 29 (33.7%) (p = 0.042), dark urine 117 (68.8%) vs 46 (53.5%) (p = 0.018), raised transaminases (Aspartate transaminases 224.5 (32-7886) vs 153 (18-610), p =  < 0.01, Alanine transferases 71 (5-937) vs 47 (8-271), p =  < 0.001) and decreased platelet count 207 (33-941) vs 252 (52- 641) (p = 0.021) compared to patients with HCC who were HBsAg-negative., Conclusions: The prognosis of patients with HCC is poor in developing countries such as The Gambia, where screening programs and treatment modalities are scarce. Young males are disproportionately affected, and HBV is a major cause of HCC in The Gambia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Malaria remains a major public health concern in The Gambia. The study assessed the trend of malaria admissions and outcome of adult patients admitted after the start of the COVID-19 pandemic in a tertiary hospital in The Gambia., Methods: This was a retrospective hospital-based study and data was collected from the 18th October 2020 to 28th February 2023. Demographic data, clinical features, investigations, treatment, and outcomes were recorded., Results: A total of 499 malaria cases were admitted to the hospital over the 29 months of the study period. Data from 320 (67.2% of the total cases) adult patients admitted into the internal medicine department were analysed. The median age was 22 years, range (15-90) and 189 (59.1%) cases were youth with a youth (15-24 years) to older adult (> 24 years) ratio of 1.4:1. The majority of the patients were male 199 (62.2) with a male to female ratio of 1.6:1. The total number of malaria cases admitted into the internal medicine department increased from 103 cases in 2021 to 182 cases in 2022and admission peaked in November in both years. The total number of admitted malaria cases during the peak of the malaria season also increased from 92 patients between September 2021 and December 2021 to 132 patients from September 2022 to December 2022.There was also an increase in both severe and uncomplicated malaria during the same period. The total mortality was 31 (9.7%) and the rate was similar in 2021 9 (8.7%) and 2022 15 (8.4%). Patients with impaired consciousness were more likely to die when compared to those without impaired consciousness [19 (23.6%) vs 12 (5%), p  ≤ 0.001]. Patients with acute kidney injury were also more likely to die when compared with those without acute kidney injury [10 (20.4%) vs 15 (7.7%), p = 0.009]., Conclusion: The findings show an emerging and consistent trend of malaria admissions and the outcome in the youth and older adult population after the start of the COVID-19 pandemic in The Gambia. This, therefore, suggests the need for the implementation of targeted malaria prevention interventions in this population to further prevent the spread of the disease to the more vulnerable population., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chronic liver disease is a major cause of premature death in sub-Saharan Africa. Efficacy of antiviral therapy among patients with hepatitis B virus (HBV)-related cirrhosis is not well established in Africa. We described the clinical characteristics and outcomes of patients with cirrhosis and hepatocellular carcinoma in The Gambia and assessed the impact of tenofovir disoproxil fumarate (TDF) on survival of HBV-infected patients with cirrhosis., Methods: In this prospective cohort study, we followed up adults who were consecutively diagnosed with cirrhosis or hepatocellular carcinoma between 2012 and 2015 in The Gambia, west Africa. Patients with chronic HBV infection and cirrhosis, without hepatocellular carcinoma, were offered TDF. Primary outcome was overall survival. To determine the effect of TDF on survival, we performed a Cox proportional hazard regression model with inverse probability of treatment weighting (IPTW) based on propensity score., Findings: Of 529 patients enrolled in this study, 336 patients (252 with hepatocellular carcinoma and 84 with cirrhosis) were analysed. Patients were predominantly male (253 [75%] men and 83 [25%] women), with a median age of 42 years (IQR 33-55). 276 (84%) of 327 of patients with data were positive for HBV biomarkers, 31 (10%) of 311 were positive for hepatitis C virus antibodies, and 22 (10%) of 223 were positive for hepatitis D virus antibodies. 64% of patients with hepatocellular carcinoma had multifocal tumour, with a median size of 7·5 cm (IQR 5·4-10·8). 173 patients with hepatocellular carcinoma and 70 patients with cirrhosis were included in the survival analysis. Median survival was 1·5 months (95% CI 1·1-2·0) in patients with hepatocellular carcinoma and 17·1 months (11·2-24·0) in patients with cirrhosis (log-rank p<0·0001). In patients with hepatocellular carcinoma, ascites (hazard ratio [HR] 1·78, 95% CI 1·21-2·60), partial or complete portal thrombosis (HR 2·61, 1·58-4·30), and platelet count (HR 1·80, 1·19-2·70) were independent predictive factors of mortality at baseline. In HBV-infected patients with cirrhosis, median turnaround time between cirrhosis diagnosis and TDF initiation was 4·9 months (IQR 3·2-7·3). In IPTW analysis, TDF treatment was associated with improved survival in patients with HBV-related cirrhosis (adjusted HR 0·14, 0·06-0·34; p<0·0001)., Interpretation: These results highlight poor survival of patients with cirrhosis or hepatocellular carcinoma as well as the effectiveness of TDF in reducing the premature mortality of patients with cirrhosis and HBV infection. Interventions for early diagnosis and treatment of cirrhosis as well as screening programmes for hepatocellular carcinoma are urgently required in Africa., Funding: European Commission and Medical Research Council UK., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests ML, YS, PI, and GN received research funding and consultancy fees from Gilead Sciences. PI reports speaker's honoraria not related to the published work from Gilead France, AbbVie Germany, ViiV Germany, and Eiger France. ML reports consulting fees from Abbott; consulting fees and payments from Gilead for participation on a scientific advisory board and for lectures; and receiving tenofovir from Gilead Sciences for PROLIFICA. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors declare no competing interests.

Background: Malaria is a major public health concern in The Gambia. There is limited data on the clinical manifestation and outcome of severe malaria in adult patients in The Gambia. The study therefore assessed the clinical manifestations and outcome of severe malaria in adult patients admitted at the Edward Francis Small Teaching Hospital., Methods: The study retrospectively reviewed the records of all malaria patients admitted from 18th October 2020 to 2nd February 2022. Demographic data, clinical features, investigations, treatment, and outcomes were recorded., Results: A total of 131 confirmed malaria patients were recruited into the study. The median age was 21 yrs, range (15-90) and most of them were within the youth age group (15-24yrs) 85 (64.9%). The majority of the patients were also male 88 (67.2%) with a male to female ratio of 2:1. The most common symptom at presentation was fever 119 (90.8%) and the most common sign was pallor 48 (36.6%). Seventy-six patients (58.1%) and 55 (41.9%) patients met the criteria for severe malaria and uncomplicated malaria diagnosis, respectively. The most common clinical feature amongst patients with severe malaria were impaired consciousness 34 (44.7%), severe anaemia 26 (34.2%) and acute kidney injury 20 (26.3%). Patients with severe malaria were younger with mean age of 22.9 vs. 29 yrs (p = 0.004), more likely to be referred from a lower-level health facility 62 (81.6%) vs. 34 (61.8%) (p = 0.012), to have a longer duration of admission (p = 0.024) and to die 13 (17.1%) vs. 0 (0%) (p = 0.001) as compared to patients with uncomplicated malaria. The total mortality was 13 (9.9%) and all the patients who died had severe malaria. Mortality was higher in patients with impaired consciousness 9 (26.5%) and there was a significant relationship between death and impaired consciousness 9 (69.3%) vs. 25 (21.4%) p = 0.001., Conclusion: Severe malaria still affects young adults in an endemic area with significant mortality. This suggests the need for targeted malaria prevention, surveillance, case management and control strategies in this population group in The Gambia to help reduce morbidity and mortality of malaria., (© 2022. The Author(s).)

Background: Prevalence and clinical outcomes of occult hepatitis B infection (OBI) have been poorly studied in Africa., Methods: Using the PROLIFICA cohort, we compared the prevalence of OBI between hepatitis B surface antigen (HBsAg)-negative healthy adults screened from the general population (controls) and HBsAg-negative patients with advanced liver disease (cases), and estimated the population attributable fraction for the effect of OBI on advanced liver disease., Results: OBI prevalence was significantly higher among cases (15/82, 18.3%) than controls (31/330, 9.4%, P = .03). After adjusting for age, sex, and anti-hepatitis C virus (HCV) serology, OBI was significantly associated with advanced liver disease (odds ratio, 2.8; 95% confidence interval [CI], 1.3-6.0; P = .006). In HBsAg-negative people, the proportions of advanced liver disease cases attributable to OBI and HCV were estimated at 12.9% (95% CI, 7.5%-18.1%) and 16.9% (95% CI, 15.2%-18.6%), respectively., Conclusions: OBI is endemic and an independent risk factor for advanced liver disease in The Gambia, West Africa. This implies that HBsAg-negative people with liver disease should be systematically screened for OBI. Moreover, the impact of infant hepatitis B immunization to prevent end-stage liver disease might be higher than previous estimates based solely on HBsAg positivity., Competing Interests: Potential conflicts of interest. M. L., M. T., and Y. S. received consultancy fees and research funding support from Gilead US company. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Introduction: adequate knowledge on hepatitis B virus (HBV) infection is important among patients with the infection as this impacts their health-seeking behavior. This study therefore assessed the knowledge and attitude among patients infected with HBV in The Gambia., Methods: this cross-sectional study was conducted at the main liver clinic, Medical Research Council Gambia at London School of Hygiene and Tropical Medicine (MRCG@LSHTM). A questionnaire was administered on a one-on-one basis to assess the level of knowledge and attitude of people with chronic HBV., Results: a total of 152 HBV patients were recruited into the study. Majority of the participants were male 136 (89.5%), within the 30-39 years age group. Sixty-four (42.1%) of the patients attained secondary education and 72 (47.4%) were working as civil servants. The mean knowledge score was 11.09/20 (standard deviation = 4.89). HBV patients having tertiary level education (p-value =0.001) or HBV diagnosis greater than 1 year (p-value =0.031) were more likely to have adequate knowledge of HBV infection. No significant associations were found between the socio-demographic and clinical characteristic variables and attitude. However, majority of the participants (56.6%) reported been worried about having HBV infection ever since being diagnosed., Conclusion: this study has highlighted the need for more patient health education especially for those with lower levels of education and newly diagnosed patients. It also further confirms the need for cultural and appropriate language consideration in providing education and information for HBV patients in The Gambia at the point of diagnosis., Competing Interests: The authors declare no competing interests., (Copyright: Landing Jarju et al.)

Background: The Gambia has one of the lowest survival rates for breast cancer in Africa. Contributing factors are late presentation, delays within the healthcare system, and decreased availability of resources. We aimed to characterize the capacity and geographic location of healthcare facilities in the country and calculate the proportion of the population with access to breast cancer care., Methods: A facility-based assessment tool was administered to secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia. GPS coordinates were obtained, and proximity of service availability and population analysis were performed. Distance thresholds of 10, 20, and 45 km were chosen to determine access to screening, pathologic diagnosis, and surgical management. An additional population analysis was performed to observe the potential impact of targeted development of resources for breast cancer care., Results: All 102 secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia were included. Breast cancer screening is mainly performed through clinical breast examination and is available in 52 facilities. Seven facilities provide pathologic diagnosis and surgical management of breast cancer. The proportion of the Gambian population with access to screening, pathologic diagnosis, and surgical management is 72, 53, and 62%, respectively. A hypothetical targeted expansion of resources would increase the covered population to 95, 62, and 84%., Conclusions: Almost half of the Gambian population does not have access to pathologic diagnosis and surgical management of breast cancer within the distance threshold utilized in the study. Mapping and population analysis can identify areas for targeted development of resources to increase access to breast cancer care., (© 2021. The Author(s).)

Background: To eliminate hepatitis B virus (HBV) infection, it is essential to scale up testing and treatment. However, conventional tools to assess treatment eligibility, particularly nucleic acid testing (NAT) to quantify HBV DNA, are hardly available and affordable in resource-limited countries. We therefore assessed the performance of a novel immunoassay, hepatitis B core-related antigen (HBcrAg), as an inexpensive (US$ <15/assay) alternative to NAT to diagnose clinically important HBV DNA thresholds (≥2000, ≥20 000, and ≥200 000 IU/mL) and to select patients for antiviral therapy in Africa., Methods: Using a well-characterized cohort of treatment-naive patients with chronic HBV infection in The Gambia, we evaluated the accuracy of serum HBcrAg to diagnose HBV DNA levels and to indicate treatment eligibility determined by the American Association for the Study of Liver Diseases, based on reference tests (HBV DNA, hepatitis B e antigen, alanine aminotransferase, liver histopathology, and/or FibroScan)., Results: A total of 284 treatment-naive patients were included in the analysis. The area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of serum HBcrAg were 0.88 (95% confidence interval [CI], .82-.93), 83.3%, and 83.9%, respectively, to diagnose HBV DNA ≥2000 IU/mL; and 0.94 (95% CI, .88-.99), 91.4%, and 93.2% for ≥200 000 IU/mL. A simplified treatment algorithm using HBcrAg without HBV DNA showed high AUROC (0.91 [95% CI, .88-.95]) with a sensitivity of 96.6% and specificity of 85.8%., Conclusions: HBcrAg might be an accurate alternative to HBV DNA quantification as a simple and inexpensive tool to identify HBV-infected patients in need of antiviral therapy in low- and middle-income countries., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q-MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case-control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha-foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q-MAC, western blot and RNA assays. We evaluated separate cut-offs of the Q-MAC assay for predicting anti-HDV and RNA positivity. Q-MAC correctly identified 29/29 subjects who were western blot-positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA-positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA-; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV-HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti-HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74-11.98) and HBV-HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97-134.95). In this Gambian population, HDV Q-MAC had high sensitivity and specificity for both anti-HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia., (© 2019 John Wiley & Sons Ltd.)

Hepatitis B virus (HBV) is a major cause of chronic liver disease worldwide. HBV infection is diagnosed by serological tests, while real-time polymerase chain reaction (qRT-PCR) assays are used to quantify viral load, which is a crucial parameter to determine viral replication and to monitor antiviral treatments. However, measuring viral load in resource-limited countries remains nonsystematic, due to the high cost of commercial kits. Here, we describe the development, validation and implementation of a low-cost, in-house qRT-PCR assay to monitor HBV viral load in chronic carriers enrolled in the PROLIFICA programme in the Gambia and Senegal. Over 1500 HBsAg-positive patients, including 210 chronically infected HBV patients, who were given antiviral treatment (tenofovir), were monitored by qRT-PCR using the SYBR Green- and HBV-specific primers. Twenty-four tenofovir-treated patients were followed up and their viral load was tested every 3 months over the 12-month experimental time course. Compared to commercial assays, our in-house assay was shown to be (i) highly reliable, with good intra- and interassay reproducibility over a wide range (45-4.5 × 10 8 copies mL -1 ), (ii) very similar in the viral loads detected (R 2  = .90), (iii) highly sensitive, as it detected loads as low as 30 copies mL -1 (~5 IU mL -1 ), (iv) cheaper (2- to 3-fold), (v) easier to implement and (vi) more rapid. Based on our experience, we recommend this assay as a reliable alternative to commercial assays, for monitoring HBV viraemia in resource-limited, highly endemic countries to reduce the cost and technical obstacles associated with commercial kits., (© 2016 John Wiley & Sons Ltd.)

Background & Aims: Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity., Methods: The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63)., Results: HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04)., Conclusions: Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatitis B virus (HBV) infection is a leading cause of death in sub-Saharan Africa (SSA). Point-of-care tests for hepatitis B surface antigen (HBsAg) could be an ideal tool for a large-scale HBV screening/treatment program in SSA. Using data from the PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) program, we conducted a cross-sectional study to assess the diagnostic accuracy of three point-of-care tests (Determine, Vikia, and Espline) for the detection of HBsAg in the field or a laboratory setting in the Gambia. In the field, we used finger-prick whole blood for the Determine and Vikia tests and dried blood spots for the reference standard test (AxSYM HBsAg enzyme-linked immunosorbent assay [ELISA]). In the laboratory we used serum for the Determine, Espline, and reference test (Architect chemiluminescent microparticle immunoassay). Of 773 participants recruited at the community and 227 known chronic HBV carriers (1,000 subjects in total), 293 were positive for HBsAg. The sensitivity and specificity of the Determine test were 88.5% and 100% in the field and 95.3% and 93.3% in the laboratory setting, respectively. The sensitivity and specificity were 90.0% and 99.8% for the Vikia test (in the field) and 93.9% and 94.7% for the Espline test (in the laboratory). There was no evidence that one kit was better than another. Most of the patients with false-negative results (18/19) were classified as inactive chronic carriers. In summary, the three point-of-care tests had acceptable ranges of diagnostic accuracy. These tests may represent accurate, rapid, and inexpensive alternatives to serology testing for the screening of HBV infection at field level in SSA., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Objective: To estimate the prevalence of antibodies against Coxiella burnetii (Q fever) among children in eight villages in The Gambia, West Africa., Methods: Sera of 796 children aged 1-15 years were tested for presence of antibodies against phase II of C. burnetii by ELISA., Results: IgG and/or IgM phase II antibodies against C. burnetii were detectable in 8.3% (66/796) of all serum samples analysed with significant differences in seroprevalence between villages. Highest prevalence was found in the age group 1-4 years., Conclusions: Exposure to C. burnetii is considerable in the early years of life in The Gambia, and further studies are warranted to estimate the role of Q fever in acute febrile illness in The Gambia and elsewhere in Africa., (© 2013 Blackwell Publishing Ltd.)

Background: The prevalence of HIV/hepatitis co-infection in sub-Saharan Africa is not well documented, while both HIV and HBV are endemic in this area., Objective: The aim of this study is to determine the seroprevalence of HBV and HCV virus in HIV-infected subjects in the Gambia., Methods: Plasma samples from HIV infected patients (190 individuals with clinically defined AIDS and 382 individuals without AIDS) were tested retrospectively for the presence of HBV sero-markers and for serum HBV DNA, screened for HCV infection by testing for anti-HCV antibody and HCV RNA., Results: HBsAg prevalence in HIV-positive individuals is 12.2%. HIV/HBV co-infected individuals with CD4 count of <200 cells µL⁻¹ have a higher HBV DNA viral load than patients with higher CD4 count (log 4.0 vs. log 2.0 DNA copies/ml, p < 0.05). Males (OR = 1.8, 95% CI: 1.0, 3.2) were more likely to be HBsAg positive than female. HCV seroprevalence was 0.9% in HIV-positive individuals., Conclusion: The prevalence of HBsAg carriage in HIV- infected Gambians is similar to that obtained in the general population. However co-infected individuals with reduced CD4 levels, indicative of AIDS had higher prevalence of HBeAg retention and elevated HBV DNA levels compared to non-AIDS patients with higher CD4 count.

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.

Background: To investigate how intense Plasmodium falciparum infection predisposes to Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL), we analyzed the effect of acute malaria on existing EBV-host balance., Methods: EBV genome loads in peripheral blood mononuclear cells were assayed by quantitative polymerase chain reaction, and EBV-specific CD8(+) T cell responses were assayed by interferon-gamma enzyme-linked immunospot assay., Results: Gambian children, from whom samples were obtained during an acute malaria attack and again up to 6 weeks later, had extremely high viral loads, reaching levels that in the United Kingdom are seen only in patients with infectious mononucleosis. Gambian control subjects (children and adults with no recent history of malaria) had lower median viral loads, although they were still >10-fold above the median for healthy UK adults. Limited experiments with EBV epitope peptides (restricted through the HLA-B 3501 and HLA-B 5301 alleles) also suggested an impairment of virus-specific CD8(+) T cell function in children with malaria, but only during acute disease., Conclusions: Acute malaria is associated with sustained increase in EBV load and, possibly, a transient decrease in EBV-specific T cell surveillance. We infer that the unusually high set point of virus carriage in P. falciparum-challenged populations, allied with the parasite's capacity to act as a chronic B cell stimulus, probably contributes to the pathogenesis of endemic BL.

Background: Although AIDS is less frequent following HIV-2 than HIV-1 infection, it is unclear whether the clinical picture and clinical course of AIDS are similar in the two infections., Objectives: To compare the pattern of AIDS-defining events, CD4 cell count at the time of AIDS diagnosis, survival from time of AIDS, and CD4 cell count near time of death in HIV-1 and HIV-2-infected patients., Methods: Adult patients with AIDS who attended the clinics of the MRC in The Gambia were enrolled. AIDS was diagnosed according to the expanded World Health Organization case definition for AIDS surveillance (1994)., Results: Three hundred and forty-one AIDS patients with HIV-1 and 87 with HIV-2 infection were enrolled. The most common AIDS-defining events in both infections were the wasting syndrome and pulmonary tuberculosis. The median CD4 cell count at AIDS was 109 cells/microl in HIV-1 and 176 in HIV-2 (P = 0.01) and remained significantly higher in HIV-2 after adjustment for age and sex (P = 0.03). The median time to death was 6.3 months in HIV-1 and 12.6 months in HIV-2-infected patients (P = 0.03). In a multivariable analysis adjusting for age, sex and CD4 cell count, the mortality rates of HIV-1 and HIV-2-infected patients were similar (P = 0.25). The median CD4 cell count near time of death was 62 and 120 cells/microl in HIV-1 and HIV-2-infected patients, respectively (P = 0.02)., Conclusions: HIV-2 patients have a higher CD4 cell count at the time of AIDS, and a longer survival after AIDS. The mortality after an AIDS diagnosis is more influenced by CD4 cell count than HIV type.

Simple robust approaches are needed to monitor the prevalence and incidence of HIV in Africa. The aim of this study was to evaluate the use of dried blood spot (DBS) as an alternative to serum or plasma for sentinel surveillance. Paired DBS and blood samples were obtained from 200 patients attending a genito-urinary medicine clinic in West Africa. The gold standard of diagnosis was based on the combination of 3 enzyme-linked immunosorbent assays (ELISA) using serum. The presence of HIV antibodies in eluates of dried blood spots was detected by ELISA, Gelatin Particle Assay (GPA) and Pepti-Lav 1-2 in 5 different testing strategies. All 200 eluates were tested individually, and in addition pools of 5 eluates each were tested. The sensitivity of the testing strategies ranged from 95.0% (83.1 - 99.4%) to 100% and the specificity from 97.5% (93.7 - 99.3%) to 100%. Testing in pools of 5 did not affect sensitivity. Dried blood spots were easy to work with. Test kit and laboratory consumable costs varied between 492 pounds and 1037 pounds (unpooled strategies) and 163 pounds and 421 pounds (pooled). The monospecific ELISAs used in this study are no longer in production; currently available differentiating assays need to be tested. DBS are recommended for sentinel surveillance in Africa.

Objectives: To estimate and compare the all-cause mortality rates among HIV-1-infected, HIV-2-infected, and uninfected women and to assess the predictive value of baseline plasma viral load (PVL) and CD4 cell percentage (CD4%) for mortality., Design: Cohort study., Methods: At presentation to antenatal clinics in The Gambia in 1993-1995, pregnant women were screened for antibodies to HIV-1 and HIV-2. Seropositive subjects and a similar number of seronegative controls were enrolled, and baseline PVL and CD4% were measured. Participants were visited regularly by field-workers until 18 months after delivery and again 4-7 years later., Results: Thirty-two of 101 women infected with HIV-1, 23 of 243 infected with HIV-2, and 9 of 468 seronegative women died during a median follow-up of 6.9 years. The mortality rate was 56 deaths per 1000 person years of observation (pyo) for HIV-1-infected, 16 deaths per 1000 pyo for HIV-2-infected, and 3.1 deaths per 1000 pyo for HIV-uninfected women. After 8 years of follow-up, >50% of HIV-1-infected women were still alive. In multivariate analysis, a 1-log increase of HIV-1 PVL was associated with a 1.8-fold higher rate of mortality (95% confidence interval [CI], 0.9-3.4). In HIV-2 infection, women with a high PVL (>10,000 copies/mL) had an 8.7-fold (95% CI, 2.8-28) higher rate of mortality than did those with a low PVL (<1000 copies/mL). A 10% decrease in CD4% was associated with higher mortality rates among HIV-1-infected (1.6-fold; 95% CI, 1.1-2.3) and HIV-2-infected (1.5-fold; 95% CI, 1.0-2.3) subjects., Discussion: Survival of HIV-1-infected women in The Gambia is similar to that in industrialized countries before the introduction of antiretroviral treatment. Survival of HIV-2-infected women is much better. However, women with high PVLs die as quickly as their HIV-1-infected counterparts.

Fewer people infected with human immunodeficiency virus (HIV) type 2 progress to acquired immunodeficiency syndrome, compared with those infected with HIV-1. To understand the immune mechanisms leading to slow progression in HIV-2 infection, cell-mediated immune responses were compared between the 2 infections in asymptomatic subjects with a CD4 cell count > or =20%. Interferon- gamma release from T lymphocytes and the cytotoxicity of CD8+ T lymphocytes were measured by ELISPOT and 51Cr release assays. The level of responses and the proportion of responders were similar in the 2 infections, despite a 20-fold difference in their geometric mean plasma virus loads. The proliferation of CD4+ T helper cells, which was evaluated by thymidine incorporation, was not different between the 2 infections. Contrary to widely held views, our results suggest that nonprogression in HIV-2 infection may not be due to more vigorous immune responses.

Background: The risk of mother-to-child transmission (MTCT) of HIV-2 is much lower than that of HIV-1, but the long-term prognosis of perinatally infected HIV-2 children is unknown. We re-visited children who were part of a large MTCT study in The Gambia (conducted during 1993-1997), in order to compare the long-term survival of children perinatally infected with HIV-2 with that of seronegative and of HIV-1 infected children., Methods: Five to eight years' follow-up of a cohort of children born to HIV-negative, HIV-1 positive, and HIV-2 positive mothers., Results: Seven hundred and seventy-four children were followed up for a median of 6.6 years. Of 17 perinatally HIV-1 infected children, three were still alive on 1 July 2001, two had been lost to follow-up, and 12 had died. The median survival was 2.5 years. Of eight HIV-2 infected children five were still alive, none were lost to follow-up and three had died. The mortality hazards ratio of both HIV-1 [9.9; 95% confidence interval (CI), 5.2-19], and of HIV-2 infected children (3.9; CI, 1.2-12) was significantly increased compared with children of seronegative mothers. The mortality hazards ratio of HIV uninfected children of HIV-1 or HIV-2 infected mothers was not significantly increased compared to that of children of seronegative mothers (P = 0.17 and P = 0.5 respectively)., Conclusions: Children with perinatally acquired HIV-2 infection have a higher mortality than children of seronegative mothers. Guidelines for treatment of HIV-1 infected children should be used for treatment of HIV-2 infected children.

Objective: To monitor HIV-1 and HIV-2 trends in The Gambia, West Africa., Methods: In 1993-1995 a nationwide survey among 29 670 pregnant women attending eight antenatal clinics estimated the seroprevalence of HIV-1 at 0.6%, and of HIV-2 at 1.1%. Five years later, sentinel surveillance in pregnant women was established, using unlinked anonymous testing in four clinics. A dried blood spot on filter paper was obtained and tested for HIV antibodies., Results: Between May 2000 and August 2001, 8054 analysable samples were collected at four sites. The prevalence of HIV-1 rose sharply in one rural area from 0.6 to 3.0% (P < 0.0001), but the increase was small and non-significant in two other rural sites and in the urban site. The prevalence of HIV-2 did not change significantly at any of the sites. The overall prevalence of HIV-1 was 1.0% [95% confidence interval (CI) 0.8-1.3%], and of HIV-2 0.8% (CI 0.6-1.0%). Site, nationality and higher age were significantly associated with HIV-1 infection, and higher parity and site were significantly associated with HIV-2 infection., Conclusion: Fifteen years after the first case of HIV-1 was described in The Gambia, the epidemic is still at a low level. There is heterogeneity within the country, with one rural area experiencing a fivefold increase in 6 years. The prevalence of HIV-2 in The Gambia is stable.

Objective: To examine baseline plasma viral loads according to the CD4 cell percentage (CD4%) in HIV-1, HIV-2 and dually infected patients (HIV-D), and to relate these measurements to survival., Patients and Methods: A total of 119 HIV-1, 137 HIV-2 and 81 HIV-D-infected patients attending the Medical Research Council clinic in The Gambia were recruited from 1991 according to baseline CD4%, and followed until death or the end of December 2000. HIV-1 and HIV-2 RNA levels were measured by in-house reverse transcriptase polymerase chain reaction assays., Results: The plasma viral load, which varied inversely with CD4%, was similar in HIV-1 singly and dually infected patients, but was significantly higher in HIV-1 than in HIV-2 singly infected patients, except in those with a CD4% less than 14%. HIV-2 plasma viral load in dually infected patients did not vary significantly with CD4%, but was significantly lower than in HIV-2 singly infected patients with CD4% less than 14%. Multivariate analysis showed that only CD4% was independently associated with survival in HIV-1 and HIV-D infections; whereas both CD4% and plasma viral load were independently associated with survival in HIV-2 infections. The mortality rate of HIV-D-infected patients was not significantly different from that of HIV-1-infected patients, but was significantly higher in the absence of HLA B58., Conclusion: HIV-2 infection does not alter HIV-1 replication or prolong survival in dually infected patients. In a clinical setting in Africa, where many patients present with advanced disease, CD4% may be a more important predictor of prognosis than plasma viral load.

Objectives: To determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia., Design: A blinded, prospective, community-based cohort study of 29.549 pregnant women attending the eight largest antenatal clinics in The Gambia., Methods: Women were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age., Results: The study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28-33], 41% (95% CI 39-42) and 47% (95% CI 45-49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15,100 copies x 10(3) ml (95% CI 10,400-19,000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies x 10(3) ml (95% CI 150-910) (P < 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6-33.9) and that of HIV-2 was 4.0% (95% CI 1.9-7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2-7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1-5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1-7.8) were risk factors for transmission that applied equally to both viruses., Conclusion: Low maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.