Diagnostic performance evaluation of hepatitis B e antigen rapid diagnostic tests in Malawi

Abstract Background The World Health Organization (WHO) has targeted a reduction in viral hepatitis-related mortality by 65% and incidence by 90% by 2030, necessitating enhanced hepatitis B treatment and prevention programmes in low- and middle-income countries. Hepatitis B e antigen (HBeAg) status is used in the assessment of eligibility for antiviral treatment and for prevention of mother-to-child transmission (PMTCT). Accordingly, the WHO has classified HBeAg rapid diagnostic tests (RDTs) as essential medical devices. Methods We assessed the performance characteristics of three commercially available HBeAg RDTs (SD Bioline, Alere, South Africa; Creative Diagnostics, USA; and Biopanda Reagents, UK) in two hepatitis B surface antigen-positive cohorts in Blantyre, Malawi: participants of a community study (n = 100) and hospitalised patients with cirrhosis or hepatocellular carcinoma (n = 94). Two investigators, blinded to the reference test result, independently assessed each assay. We used an enzyme-linked immunoassay (Monolisa HBeAg, Bio-Rad, France) as a reference test and quantified HBeAg concentration using dilutions of the WHO HBeAg standard. We related the findings to HBV DNA levels, and evaluated treatment eligibility using the TREAT-B score. Results Among 194 HBsAg positive patients, median age was 37 years, 42% were femaleand 26% were HIV co-infected. HBeAg prevalence was 47/194 (24%). The three RDTs showed diagnostic sensitivity of 28% (95% CI 16–43), 53% (38–68) and 72% (57–84) and specificity of 96–100% for detection of HBeAg. Overall inter-rater agreement κ statistic was high at 0.9–1.0. Sensitivity for identifying patients at the threshold where antiviral treatment is recommended for PMTCT, with HBV DNA > 200,000 IU/ml (39/194; 20%), was 22, 49 and 54% respectively. Using the RDTs in place of the reference HBeAg assay resulted in 3/43 (9%), 5/43 (12%) and 8/43 (19%) of patients meeting the TREAT-B treatment criteria being misclassified as ineligible for treatment. A relationship between HBeAg concentration and HBeAg detection by RDT was observed. A minimum HBeAg concentration of 2.2–3.1 log10IU/ml was required to yield a reactive RDT. Conclusions Commercially available HBeAg RDTs lack sufficient sensitivity to accurately classify hepatitis B patients in Malawi. This has implications for hepatitis B public health programs in sub-Saharan Africa. Alternative diagnostic assays are recommended.

Download Full-text

Poor Sensitivity of Commercial Rapid Diagnostic Tests for Hepatitis B e Antigen in Senegal, West Africa

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.18-0116 ◽

2018 ◽

Vol 99 (2) ◽

pp. 428-434 ◽

Cited By ~ 8

Author(s):

Abdoulaye Seck ◽

Sarah Maylin ◽

Sheikh Mohammad Fazle Akbar ◽

Anna L. Funk ◽

Raymond Bercion ◽

...

Keyword(s):

Hepatitis B ◽

West Africa ◽

Diagnostic Tests ◽

Rapid Diagnostic Tests ◽

Hepatitis B E Antigen

Download Full-text

Hepatitis B virus activity in untreated hepatitis B e antigen–negative human immunodeficiency virus–hepatitis B virus co-infected patients from sub-Saharan Africa

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/trz021 ◽

2019 ◽

Vol 113 (8) ◽

pp. 437-445

Author(s):

Anders Boyd ◽

Menan Gerard Kouamé ◽

Laura Houghtaling ◽

Raoul Moh ◽

Delphine Gabillard ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hbv Dna ◽

Sub Saharan Africa ◽

Hepatitis B E Antigen ◽

Hiv Rna ◽

B Virus ◽

Immunodeficiency Virus ◽

Sub Saharan

Abstract Background In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients from sub-Saharan Africa with hepatitis B e antigen (HBeAg)-negative status, data are limited on the evolution of HBV activity when antiretroviral treatment (ART) is absent. Methods A total of 43 HBeAg-negative co-infected patients not indicated for ART (per concomitant World Health Organization recommendations) were followed during participation in a randomized controlled trial in Côte d’Ivoire. Chronic HBeAg-negative phases were classified at yearly visits and defined as ‘infection’ (HBV DNA ≤10 000 copies/mL and normal alanine aminotransferase [ALT]) or ‘hepatitis’ (HBV DNA >10 000 copies/mL and/or above normal ALT). Dispersion in HBV DNA and ALT levels during follow-up was assessed using interquartile range (IQR) regression. Results During a median 25 months (IQR 19–31), 17 (40%) patients consistently had ‘infection’, 5 (12%) consistently had ‘hepatitis’ and 21 (48%) fluctuated between phases. Wider dispersion in HBV DNA over time was associated with higher baseline HIV RNA (p=0.02) and higher baseline HBV DNA levels (p=0.008), while wider dispersion in ALT was associated with higher baseline HIV RNA (p<0.001), higher baseline ALT levels (p=0.02) and baseline hepatitis surface antigen >4.0 log10 IU/mL (p=0.02). Conclusions HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication. Fluctuations in disease phase make it difficult to assess the risk of morbidity and mortality after ART initiation.

Download Full-text

Prevalence of sero-markers and non-invasive assessment of liver cirrhosis in patients with Hepatitis B virus infection in Freetown, Sierra Leone: a cross-sectional study

BMC Gastroenterology ◽

10.1186/s12876-021-01892-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sulaiman Lakoh ◽

Emmanuel Firima ◽

Darlinda F. Jiba ◽

Matilda N. Kamara ◽

Wadzani Gashau ◽

...

Keyword(s):

Liver Cirrhosis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Sierra Leone ◽

Treatment Guidelines ◽

Antiviral Treatment ◽

Sub Saharan Africa ◽

World Health ◽

Non Invasive ◽

B Virus

Abstract Background Hepatitis B virus (HBV) is a major global health problem. Although sub-Saharan Africa has a high proportion of the global burden of HBV, the epidemiology and clinical features of HBV in this region are poorly characterized, and access to diagnostic and treatment services remain limited. Methods We conducted a retrospective study of HBV-infected children and adults of all age groups who were evaluated at public and private health facilities in Freetown, Sierra Leone between January 2017 and January 2019. We assessed their clinical presentation, HBV sero-markers, stages of liver disease, prevalence of cirrhosis by non-invasive tools, and the proportion of treatment eligible patients using the criteria recommended by the World Health Organization’s 2015 treatment guidelines for HBV. Logistic regression was used to identify predictors of liver cirrhosis. Results 163 HBV patients included in the study, with mean age 32.6 years and 65.0% (106) being males. Most (84.0%) were asymptomatic at presentation. The majority (69.9%) were classified as having HBeAg-negative chronic infection (or inactive HBsAg carrier phase), 24.5% were in the HBeAg-negative immune active phase, 3.1% had HBeAg positive hepatitis, and 2.5% were HBsAg negative. The median Aspartate aminotransferase to Platelet Ratio (APRI) and Fibrosis-4 (FIB-4) scores were 0.37 and 0.80, respectively. The prevalence of cirrhosis was 7.6% and 6.2%, estimated by the APRI and FIB-4 scores, respectively. About 20.0% of patients were eligible for treatment with antiviral agents. Based on APRI scores, the presence of any symptom [adjusted odds ratio (aOR) 20.0, 95% confidence interval (CI) (4.1–85.9); p < 0.001], elevated direct bilirubin [aOR 12.1, 95% CI (1.9–63.0); p = 0.003], and elevated total bilirubin [aOR 16.1, 95% CI (3.2–80.8); p = 0.001] were independent predictors of cirrhosis. Conclusion Although most patients with HBV infection were asymptomatic, the prevalence of liver cirrhosis and proportion of patients requiring antiviral treatment were substantial. This small study from a hyperendemic setting in Sierra Leone suggests that routine population-based screening may increase early detection and linkage of HBV patients to care before development of complications. Larger studies are needed to confirm our findings.

Download Full-text

European Recommendations for the Management of Healthcare Workers Occupationally Exposed to Hepatitis

European Journal of Medicine and Natural Sciences ◽

10.26417/ejmn.v2i1.p49-49 ◽

2018 ◽

Vol 2 (1) ◽

pp. 49

Author(s):

Enis Uruci

Keyword(s):

Occupational Exposure ◽

Hepatitis B ◽

Healthcare Workers ◽

Antiviral Treatment ◽

World Health ◽

Antibody Concentration ◽

Post Exposure Prophylaxis ◽

Transferase Activity ◽

Mediterranean Countries

Exposure prevention is the primary strategy to reduce the risk of occupational bloodborne pathogen infections in healthcare workers (HCW). HCWs should be made aware of the medicolegal and clinical relevance of reporting an exposure, and have ready access to expert consultants to receive appropriate counselling, treatment and follow-up. Vaccination against hepatitis B virus (HBV), and demonstration of immunisation before employment are strongly recommended. HCWs with postvaccinal anti-HBs levels, 1-2 months after vaccine completion, .or=10 mIU/mL are considered as responders. Responders are protected against HBV infection: booster doses of vaccine or periodic antibody concentration testing are not recommended. Alternative strategies to overcome non-response should be adopted. Isolated anti-HBc positive HCWs should be tested for anti-HBcIgM and HBV-DNA: if negative, anti-HBs response to vaccination can distinguish between infection (anti-HBs .or=50 mIU/ml 30 days after 1st vaccination: anamnestic response) and false positive results(anti-HBs .or=10 mUI/ml 30 days after 3rd vaccination: primary response); true positive subjects have resistance to re-infection. and do not need vaccination The management of an occupational exposure to HBV differs according to the susceptibility of the exposed HCW and the serostatus of the source. When indicated, post-exposure prophylaxis with HBV vaccine, hepatitis B immunoglobulin or both must be started as soon as possible (within 1-7 days). In the absence of prophylaxis against hepatitis C virus (HCV) infection, follow-up management of HCV exposures depends on whether antiviral treatment during the acute phase is chosen. Test the HCW for HCV-Ab at baseline and after 6 months; up to 12 for HIV-HCV co-infected sources. If treatment is recommended, perform ALT (amino alanine transferase) activity at baseline and monthly for 4 months after exposure, and qualitative HCV-RNA when an increase is detected. Introduction Bloodborne pathogens such as hepatitis B (HBV) and C virus (HCV) represent an important hazard for healthcare workers (HCWs) (1). In the general population, HCV prevalence varies geographically from about 0.5% in northern countries to 2% in Mediterranean countries, with some 5 million chronic carriers estimated in Europe; while HBV prevalence ranges from 0.3% to 3%. The World Health Organization (WHO) estimates that each year in Europe 304 000 HCWs are exposed to at least one percutaneous injury with a sharp object contaminated with HBV, 149 000 are exposed to HCV and 22 000 to HIV. The probability of acquiring a bloodborne infection following an occupational exposure has been estimated to be on average.

Download Full-text

Hepatitis B Vaccination in Senegalese Children: Coverage, Timeliness, and Sociodemographic Determinants of Non-Adherence to Immunisation Schedules (ANRS 12356 AmBASS Survey)

Vaccines ◽

10.3390/vaccines9050510 ◽

2021 ◽

Vol 9 (5) ◽

pp. 510

Author(s):

Lauren Périères ◽

Fabienne Marcellin ◽

Gora Lo ◽

Camelia Protopopescu ◽

El Ba ◽

...

Keyword(s):

Hepatitis B ◽

Dose Schedule ◽

World Health Organisation ◽

Sub Saharan Africa ◽

World Health ◽

Hepatitis B Vaccination ◽

Detailed Knowledge ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Hbv Vaccination

Detailed knowledge about hepatitis B virus (HBV) vaccination coverage and timeliness for sub-Saharan Africa is scarce. We used data from a community-based cross-sectional survey conducted in 2018–2019 in the area of Niakhar, Senegal, to estimate coverage, timeliness, and factors associated with non-adherence to the World Health Organisation-recommended vaccination schedules in children born in 2016 (year of the birth dose (BD) introduction in Senegal) and 2017–2018. Vaccination status was assessed from vaccination cards, surveillance data, and healthcare post vaccination records. Among 241 children with available data, for 2016 and 2017–2018, respectively, 31.0% and 66.8% received the BD within 24 h of birth (BD schedule), and 24.3% and 53.7% received the BD plus at least two pentavalent vaccine doses within the recommended timeframes (three-dose schedule). In logistic regression models, home birth, dry season birth, and birth in 2016 were all associated with non-adherence to the recommended BD and three-dose schedules. Living over three kilometres from the nearest healthcare post, being the firstborn, and living in an agriculturally poorer household were only associated with non-adherence to the three-dose schedule. The substantial proportion of children not vaccinated according to recommended schedules highlights the importance of considering vaccination timeliness when evaluating vaccination programme effectiveness. Outreach vaccination activities and incentives to bring children born at home to healthcare facilities within 24 h of birth, must be strengthened to improve timely HBV vaccination.

Download Full-text

Performance of rapid diagnostic tests for detection of Hepatitis B and C markers in HIV infected patients

Journal of Virological Methods ◽

10.1016/j.jviromet.2017.08.001 ◽

2017 ◽

Vol 248 ◽

pp. 244-249 ◽

Cited By ~ 12

Author(s):

Jakeline Ribeiro Barbosa ◽

Jeová Keny Baima Colares ◽

Geane Lopes Flores ◽

Vanessa Faria Cortes ◽

Juliana Custódio Miguel ◽

...

Keyword(s):

Hepatitis B ◽

Diagnostic Tests ◽

Rapid Diagnostic Tests

Download Full-text

Real-World Experience of Telbivudine and Lamivudine as Antiviral Prophylaxis for Chemotherapy-Related Hepatitis B Reactivation

Indonesian Journal of Cancer ◽

10.33371/ijoc.v15i1.767 ◽

2021 ◽

Vol 15 (1) ◽

pp. 11

Author(s):

Lianda Siregar ◽

Imelda Maria Loho ◽

Agus Sudiro Waspodo ◽

Siti Nadliroh ◽

Rahmanandhika Swadari ◽

...

Keyword(s):

Hepatitis B ◽

Medical Records ◽

Antiviral Treatment ◽

Hbv Dna ◽

Hbv Reactivation ◽

Lamivudine Therapy ◽

Number Of Patients ◽

Group 2 ◽

Good Treatment Option ◽

Hbs Ag

Background: There is currently no data regarding the efficacy of prophylactic telbivudine in hepatitis B patients undergoing chemotherapy. This study aims to describe the results of preemptive telbivudine and lamivudine to prevent chemotherapy-related HBV reactivation.Methods: The medical records of all patients with HBsAg positive or HBs-Ag negative, anti-HBc positive, who were referred to the hepatology clinic between May 2014 and December 2016, were retrospectively reviewed. As this is a descriptive study, no statistical analysis was done.Results: A total of 52 patients with prophylactic telbivudine or lamivudine therapy were included, with 26 patients in each group. Rituximab-based treatment was given in nine and five patients in the telbivudine and lamivudine group, respectively. The number of patients who completed antiviral treatment up to six months after chemotherapy was 17 patients in each group. There was less incidence of HBV reactivation in the telbivudine group (2 of 17 patients, 11.8%) than in the lamivudine group (7 of 17 patients, 41.2%). Delayed reactivation was noticed in 1 of 2 patients in the telbivudine group and 3 of 7 patients in the lamivudine group. The median log10[HBV DNA] at reactivation was 4.52 (1.70 – 8.35) IU/mL. Severe hepatitis was observed in two patients in the lamivudine group and one patient in the telbivudine group. Of 34 patients who completed antiviral treatment, two patients died due to primary cancer. No interruption of chemotherapy or mortality due to hepatitis was noticed in both groups.Conclusions: Preemptive telbivudine or lamivudine in HBsAg positive or HBsAg negative, anti-HBc positive patients seems to be a good treatment option.

Download Full-text

Prevalence and Epidemiological Characteristics of Asymptomatic Malaria Based on Ultrasensitive Diagnostics: A Cross-sectional Study

Clinical Infectious Diseases ◽

10.1093/cid/ciy1005 ◽

2018 ◽

Vol 69 (6) ◽

pp. 1003-1010 ◽

Cited By ~ 20

Author(s):

Seble Girma ◽

James Cheaveau ◽

Abu Naser Mohon ◽

Dewdunee Marasinghe ◽

Ruth Legese ◽

...

Keyword(s):

Diagnostic Tests ◽

Cross Sectional Study ◽

Rapid Diagnostic Tests ◽

World Health ◽

Asymptomatic Malaria ◽

Global Public Health ◽

Sectional Study ◽

Cross Sectional ◽

Qrt Pcr ◽

Epidemiological Characteristics

Abstract Background As the global public-health objectives for malaria evolve from malaria control towards malaria elimination, there is increasing interest in the significance of asymptomatic infections and the optimal diagnostic test to identify them. Method We conducted a cross-sectional study of asymptomatic individuals (N = 562) to determine the epidemiological characteristics associated with asymptomatic malaria. Participants were tested by rapid diagnostic tests (CareStart, Standard Diagnostics [SD] Bioline, and Alere ultrasensitive RDT [uRDT]), loop-mediated isothermal amplification (LAMP), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine malaria positivity. Hemoglobin values were recorded, and anemia was defined as a binary variable, according to World Health Organization guidelines. Results Compared to reference qRT-PCR, LAMP had the highest sensitivity (92.6%, 95% confidence interval [CI] 86.4–96.5), followed by uRDT Alere Malaria (33.9%, 95% CI 25.5–43.1), CareStart Malaria (14.1%, 95% CI 8.4–21.5), microscopy (5.0%, 95% CI 1.8–10.5), and SD Bioline (5.0%, 95% CI 1.8–10.5). For Plasmodium falciparum specimens only, the sensitivity for uRDT Alere Malaria was 50.0% (95% CI 38.8–61.3) and SD Bioline was 7.3% (95% CI 2.7–15.3). Based on multivariate regression analysis with qRT-PCR as the gold standard, for every 3.2% increase in the prevalence of asymptomatic malaria, hemoglobin decreased by 1 gram per deciliter (prevalence ratio 0.968, 95% CI 0.940–0.997; P = .032). Deletions (4.8%) in hrp2 were noted. Conclusions While uRDT Alere Malaria has superior sensitivity to rapid diagnostic tests and microscopy in detecting asymptomatic malaria, LAMP is superior still. Ultrasensitive diagnostics provide the accurate prevalence estimates of asymptomatic malaria required for elimination.

Download Full-text

Clinical overlap between malaria and pneumonia: can malaria rapid diagnostic test play a role?

The Journal of Infection in Developing Countries ◽

10.3855/jidc.945 ◽

2011 ◽

Vol 5 (03) ◽

pp. 199-203 ◽

Cited By ~ 10

Author(s):

Kingsley Nnanna Ukwaja ◽

Olufemi B Aina ◽

Ademola A Talabi

Keyword(s):

Diagnostic Test ◽

Rapid Diagnostic Test ◽

Diagnostic Tests ◽

Health Centre ◽

Rapid Diagnostic Tests ◽

Case Definition ◽

Sub Saharan Africa ◽

Malaria Rapid Diagnostic Test ◽

Chi Square ◽

Symptom Overlap

Introduction: Malaria and pneumonia account for 40% of mortality among children under five years of age in sub-Saharan Africa. Due to lack of diagnostic facilities, their management is based on the integrated management of childhood illnesses (IMCI) strategy. Symptoms of malaria and pneumonia overlap in African children, necessitating dual IMCI classifications at health centres and treatment with both antibiotics and antimalarials. This study determined the prevalence of malaria-pneumonia symptom overlap and confirmed the diagnosis of malaria in these cases using a rapid diagnostic test. Methodology: Consecutive consultations of 1,216 children (two months to five years old) were documented over a three-month period in a comprehensive health centre. Malaria rapid diagnostic tests were conducted only for children who had symptom overlap. Results: Of the 1,216 children enrolled, 1,090 (90%) reported cough or fever. Among the children fulfilling the malaria case definition, 284 (30%) also met the pneumonia case definition. Twenty-three percent (284) of all children enrolled met the criteria for both malaria and pneumonia. However, only 130 (46%) of them had a positive result for malaria using a malaria rapid diagnostic test. During a malaria-pneumonia overlap, female children (chi-square 5.9, P = 0.01) and children ≥ one year (chi-square 4.8, P = 0.003) were more likely to seek care within two days of fever. Conclusion: Dual treatment with antimalarials and antibiotics in children with malaria-pneumonia overlap may result in unnecessary over-prescription of antimalarial medications. Use of rapid diagnostic tests in their management can potentially avoid over-prescribing of malaria medications.

Download Full-text