Bakary Sanneh

Validation of Rapid Point-of-Care (POC) Tests for Detection of Hepatitis B Surface Antigen in Field and Laboratory Settings in the Gambia, Western Africa

ABSTRACT 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.

Seroprevalence of Pertussis in The Gambia Evidence for Continued Circulation of Bordetella pertussis Despite High Vaccination Rates

Background: Bordetella pertussis can cause severe respiratory disease and death in children. In recent years, large outbreaks have occurred in high-income countries; however, little is known about pertussis incidence in sub-Saharan Africa. Methods: We evaluated antibody responses to pertussis toxin (Ptx) from individuals aged between 2 and 90 years in rural Gambia. IgG-Ptx was measured using luminex xMAP technology. IgG-Ptx geometric mean concentrations (GMC) and their 95% confidence intervals were calculated. The proportion seropositive (>20 EU/mL or ≥62.5 EU/mL) and GMCs were compared by age, sex, ethnic group, vaccination status, birth order and number of siblings per household using logistic and linear regression. Results: 76.3% had anti-Ptx levels <20 EU/mL, 17.5% had concentrations between 20 and 62.5 EU/mL, 4.4% had concentrations between 62.5 and 125 EU/mL and 1.8% had concentrations ≥125 EU/mL. The overall Ptx antibody GMC was 6.4 EU/mL (95% confidence interval: 5.8–6.9). Higher antibody concentrations were observed in older populations with evidence for an increase in infection risk with increasing age (1.9% yearly increase, 95% confidence interval: 1.3–2.5). No child under 6 years of age had GMC above 62.5 EU/mL but 29.5% had concentrations between 20 and 62.5 EU/mL. Conclusions: These data provide evidence that B. pertussis is being transmitted within this population despite high vaccination coverage. Re-infection may occur implying that immunity from childhood vaccination may not be lifelong. In the absence of data on actual clinical cases of pertussis, seroprevalence studies remain valuable tools to assess the transmission dynamics of B. pertussis.

48 COMMUNITY-BASED SCREENING FOR HEPATITIS B VIRUS INFECTION IN THE GAMBIA, WEST AFRICA: PREVALENCE OF INFECTION AND FACTORS AFFECTING THE SCREENING ATTENDANCE

47 TESTING FOR HEPATITIS B VIRUS (HBV) ALONE DOES NOT INCREASE VACCINE COVERAGE IN NON-IMMUNIZED PERSONS J. Bottero, A. Boyd, J. Gozlan, M. Lemoine, A. Collignon, N. Boo, P. Dhotte, B. Varsat, C. Charlois, O. Cha, O. Picard, M.-D. Pauti, P. Campa, B. Silbermann, M. Bary, H. Rougier, P.-M. Girard, K. Lacombe. INSERM U 707, Universite Pierre et Marie Curie, Infectious Diseases, Virology Department, Hepatology Department, Hopital Saint Antoine, Laboratoire St Marcel, Direction de l’Action Sociale, de l’Enfance et de la Sante, CDAG du Figuier, Mairie de Paris, CPAM-CNAMTS, CDAG de Belleville, Mairie de Paris, Policlinique Baudelaire, Hopital Saint Antoine, Centre d’Accueil, de Soins et d’Orientation, Medecin du Monde, Unite de Consultation et de Soins Ambulatoires, Maison d’Arret de la Sante, Centre Croix Rouge du Moulin Joly, Paris, France E-mail: julie.bottero@sat.aphp.fr

Impact of pentavalent rotavirus vaccine against severe rotavirus diarrhoea in The Gambia

INTRODUCTION Rotavirus vaccines protect against the leading cause of severe childhood diarrhoea, and have been introduced in many low-income African countries. The Gambia introducedRotateq® (RV5) into their national immunization program in 2013. We revieweddata from an active rotavirus sentinel surveillancesitefor early evidence of vaccine impact. METHODS We compared rotavirus prevalence in diarrhoeal stool in children< 5 years of age admittedat the Edward Francis Small Teaching Hospital sentinel surveillance site before (2013) andafterRV5 introduction (2015-2016) in the Gambia. The rotavirus-percent positive was separately compared for all diarrhoealhospitalizations and for hospitalizations with severe symptoms. Rotavirus prevalence was compared annually for the pre-vaccine year of 2013 with post-vaccine years of 2015 and 2016 using chi-square or Fishers exact tests and the p-value to establish significant relationship was set at p < 0.05. All analyses were completed in SAS 9.3 (SAS Analytics, North Carolina). RESULTS Rotavirus prevalence among all diarrhoeahospitalizations decreased from 22% in 2013 to 11% in 2015 (p = 0.04), while remaining unchanged in 2016 (18%, p = 0.56). For hospitalizations that were clinically severe and/or treated with intravenous fluids (mean of 46 per year), the rotavirus prevalence decreased from 33% in 2013 to 8% in 2015 (p = 0.04), and to 15% in 2016 (p = 0.08). The children with age <1 year accounted for 45% the population infected with rotavirus in both pre and post rotavirus vaccination periods. CONCLUSIONS Rotavirus vaccine introduction in the Gambia could be among factors resulting in decreased diarrhea hospitalizations among children at the Edward Francis Small Teaching Hospital, particularly those with severe disease. These results support the continuation of rotavirus vaccine and additional monitoring of rotavirus hospitalization trends in the country.

Prevalence and risk factors for faecal carriage of Extended Spectrum β-lactamase producing Enterobacteriaceae among food handlers in lower basic schools in West Coast Region of The Gambia

Background The isolation of Extended spectrum βlactamase (ESBLs) producing Enterobacteriaceae among food handlers and their implication as sources of food borne outbreaks are a public health concern. This study seeks to investigate the prevalence of faecal carriage of these bacteria among food handlers in the West Coast Region of The Gambia. Method This study enrolled 600 participants from 60 Lower Basic Schools in West Coast Region of the country. Stool samples collected from the participants were presumptively screened for the ESBLs producing Enterobacteriaceae, using Drigalski agar, supplemented with 2mg/L cefotaxime. The bacterial colonies that grew on each Drigalski agar were tested for ESBL production by the double disk synergy test as recommended by Clinical and Laboratory Standard Institute (CLSI-2015). The confirmatory analysis for ESBL was determined as the zone of inhibition of cefotaxime and/or ceftazidime to ≥5mm from that of cefotaxime /clavulanicacid and/or ceftazidime/clavulanic acid. The presumptive screening of isolates for AmpC phenotypes was done by testing the organism against cefoxitin. The prevalence of the ESBL carriage was presented in percentages. The association of risk factors to the faecal carriage of ESBLs producing Enterobacteriaceae was performed by Pearson Chi-squared and Fishers Exact at (p ≤ 0.05). Result The prevalence of faecal carriage ESBL producing Enterobacteriaceae among food handlers was 5.0% (28/565). We found50% (14/28) and3.57% (1/28) ESBL producing bacteria were presumptive AmpC and carbapenemase resistance phenotype. Themost abundant ESBL producing Enterobacteriaceae were Klebsiella spp 32.1% (9/28) and Escherichia spp 28.6% (8/28). The use of antibiotics in the last 3 months was found to be significantly associated (P = 0.012) with the faecal carriage of ESBLs producing Enterobacteriaceae. Conclusion The prevalence of faecal carriage of ESBLs producing Enterobacteriaceae among food handlers in the Gambia is low. The history to use of the antibiotics in the last three months was found to be significantly associated with this prevalence. Therefore, the institution of a robust antimicrobial surveillance and treatment of patients with such infections are necessary to curb the spread of these multidrug resistant bacteria in the country. Rational prescription and usage of the antibiotics especially cephalosporin should be advocated both in public and private health facilities.

Development of a simple score based on HBeAg and ALT for selecting patients for HBV treatment in Africa

BACKGROUND & AIMS To eliminate hepatitis B virus (HBV) infection, it is essential to scale up antiviral treatment through decentralized services. However, access to the conventional tools to assess treatment eligibility (liver biopsy/Fibroscan®/HBV DNA) is limited and not affordable in resource-limited countries. We developed and validated a simple score to easily identify patients in need of HBV treatment in Africa. METHODS As a reference, we used treatment eligibility determined by the European Association for the Study of the Liver based on alanine aminotransferase (ALT), liver histology and/or Fibroscan and HBV DNA. We derived a score indicating treatment eligibility by a stepwise logistic regression using a cohort of chronic HBV infection in The Gambia (n = 804). We subsequently validated the score in an external cohort of HBV-infected Africans from Senegal, Burkina Faso, and Europe (n = 327). RESULTS Out of several parameters, two remained in the final model, namely HBV e antigen (HBeAg) and ALT level, constituting a simple score (treatment eligibility in Africa for the hepatitis B virus: TREAT-B). The score demonstrated a high area under the receiver operating characteristic curve (0.85, 95% CI 0.79-0.91) in the validation set. The score of 2 and above (HBeAg-positive and ALT ≥20 U/L or HBeAg-negative and ALT ≥40 U/L) had a sensitivity and specificity for treatment eligibility of 85% and 77%, respectively. The sensitivity and specificity of the World Health Organization criteria based on the aspartate aminotransferase-to-platelet ratio index (APRI) and ALT were 90% and 40%, respectively. CONCLUSIONS A simple score based on HBeAg and ALT had a high diagnostic accuracy for the selection of patients for HBV treatment. This score could be useful in African settings. LAY SUMMARY Limited access to the diagnostic tools used to assess treatment eligibility (liver biopsy/Fibroscan/hepatitis B virus DNA) has been an obstacle to the scale up of hepatitis B treatment programs in low- and middle-income countries. Using the data from African patients with chronic HBV infection, we developed and validated a new simple diagnostic score for treatment eligibility, which only consists of hepatitis B virus e antigen and alanine aminotransferase level. The diagnostic accuracy of the score for selecting patients for HBV treatment was high and could be useful in African settings.