SARS-CoV-2 Infection in School Settings, Okinawa Prefecture, Japan, 2021-2022.

During the COVID-19 pandemic, widespread school closures were implemented globally based on the assumption that transmission among children in the school environment is common. However, evidence regarding secondary infection rates by school type and level of contact is lacking. Our study estimated the frequency of SARS-CoV-2 infection in school settings by examining the positivity rate according to school type and level of contact by using data from a large-scale school-based PCR project conducted in Okinawa, Japan, during 2021-2022. Our results indicate that, despite detection of numerous positive cases, the average number of secondary infections remained relatively low at ≈0.5 cases across all types of schools. Considering the profound effects of prolonged closures on educational access, balancing public health benefits against potential long-term effects on children is crucial.

Assessment of fever screening at airports in detecting domestic passengers infected with SARS-CoV-2, 2020-2022, Okinawa prefecture, Japan.

BACKGROUND: While airport screening measures for COVID-19 infected passengers at international airports worldwide have been greatly relaxed, observational studies evaluating fever screening alone at airports remain scarce. The purpose of this study is to retrospectively assess the effectiveness of fever screening at airports in preventing the influx of COVID-19 infected persons. METHODS: We conducted a retrospective epidemiological analysis of fever screening implemented at 9 airports in Okinawa Prefecture from May 2020 to March 2022. The number of passengers covered during the same period was 9,003,616 arriving at 9 airports in Okinawa Prefecture and 5,712,983 departing passengers at Naha Airport. The capture rate was defined as the proportion of reported COVID-19 cases who would have passed through airport screening to the number of suspected cases through fever screening at the airport, and this calculation used passengers arriving at Naha Airport and surveillance data collected by Okinawa Prefecture between May 2020 and March 2021. RESULTS: From May 2020 to March 2021, 4.09 million people were reported to pass through airports in Okinawa. During the same period, at least 122 people with COVID-19 infection arrived at the airports in Okinawa, but only a 10 suspected cases were detected; therefore, the capture rate is estimated to be up to 8.2% (95% CI: 4.00-14.56%). Our result of a fever screening rate is 0.0002% (95%CI: 0.0003-0.0006%) (10 suspected cases /2,971,198 arriving passengers). The refusal rate of passengers detected by thermography who did not respond to temperature measurements was 0.70% (95% CI: 0.19-1.78%) (4 passengers/572 passengers). CONCLUSIONS: This study revealed that airport screening based on thermography alone missed over 90% of COVID-19 infected cases, indicating that thermography screening may be ineffective as a border control measure. The fact that only 10 febrile cases were detected after screening approximately 3 million passengers suggests the need to introduce measures targeting asymptomatic infections, especially with long incubation periods. Therefore, other countermeasures, e.g. preboarding RT-PCR testing, are highly recommended during an epidemic satisfying World Health Organization (WHO) Public Health Emergency of International Concern (PHEIC) criteria with pathogen characteristics similar or exceeding SARS-CoV-2, especially when traveling to rural cities with limited medical resources.

Informing a target product profile for rapid tests to identify HBV-infected pregnant women with high viral loads: a discrete choice experiment with African healthcare workers.

BACKGROUND: Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. METHODS: Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. RESULTS: A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (ß = 3.749), cost (ß = -2.550), specificity (ß = 1.134), and time-to-result (ß = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. CONCLUSIONS: African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.

Hepatitis B in Africa Collaborative Network: cohort profile and analysis of baseline data.

Approximately 80 million people live with chronic hepatitis B virus (HBV) infection in the WHO Africa Region. The natural history of HBV infection in this population is poorly characterised, and may differ from patterns observed elsewhere due to differences in prevailing genotypes, environmental exposures, co-infections, and host genetics. Existing research is largely drawn from small, single-centre cohorts, with limited follow-up time. The Hepatitis B in Africa Collaborative Network (HEPSANET) was established in 2022 to harmonise the process of ongoing data collection, analysis, and dissemination from 13 collaborating HBV cohorts in eight African countries. Research priorities for the next 5 years were agreed upon through a modified Delphi survey prior to baseline data analysis being conducted. Baseline data on 4,173 participants with chronic HBV mono-infection were collected, of whom 38.3% were women and the median age was 34 years (interquartile range 28-42). In total, 81.3% of cases were identified through testing of asymptomatic individuals. HBeAg-positivity was seen in 9.6% of participants. Follow-up of HEPSANET participants will generate evidence to improve the diagnosis and management of HBV in this region.

Prevalence and Clinical Significance of Occult Hepatitis B Infection in The Gambia, West Africa.

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.

Maternal Age at First Childbirth and Geographical Variation in Hepatitis B Virus Prevalence in Cameroon: Important Role of Mother-to-Child Transmission.

BACKGROUND: The prevalence of hepatitis B virus (HBV) infection varies geographically around the world. Yet, its underlying mechanisms are unknown. Using a nationally representative population-based sample from all 58 administrative divisions in Cameroon, we examined the association between median maternal age at first childbirth in a preceding generation, a proxy for the frequency of mother-to-child transmission (MTCT) of HBV in a region, and the risk of chronic HBV infection, defined as positive surface antigen (HBsAg), in the index generation. METHODS: We estimated a division-specific median maternal age at first childbirth using Demographic Health Surveys (DHSs) conducted in 1991, 1998, 2004, and 2011. We tested HBsAg in 2011 DHS participants. We used maps to display spatial variation. RESULTS: In 14 150 participants (median age, 27 years; 51% females), the overall weighted prevalence of HBsAg was 11.9% (95% confidence interval [CI], 11.0 to 12.8), with a wide geographical variation across the divisions (range, 6.3%-23.7%). After adjusting for confounders and spatial dependency, lower maternal age at first childbirth was significantly associated with positive HBsAg at the division level (ß, 1.89; 95% CI, 1.26 to 2.52) and at the individual level (odds ratio, 1.20; 95% CI, 1.04 to 1.39). A similar ecological correlation was observed across other African countries. CONCLUSIONS: The significant association between the maternal age at first childbirth and HBsAg positivity suggests a crucial role of MTCT in maintaining high HBV endemicity in some areas in Cameroon. This underlines an urgent need to effectively prevent MTCT in sub-Saharan Africa.

Screening for Hepatitis B in partners and children of women positive for surface antigen, Burkina Faso.

Objective: To evaluate the implementation of a screening strategy for the partners and children of pregnant women with hepatitis B virus (HBV) attending antenatal care. Methods: We identified pregnant women positive for HBV surface antigen (HBsAg) at antenatal consultation in Ouagadougou, Burkina Faso. At post-test counselling, women were advised to disclose their HBV status to partners and to encourage their partner and children to be screened for HBsAg. We used multivariable logistic regression to explore factors associated with uptake of screening and HBsAg positivity among family members. Findings: Of 1000 HBsAg-positive women, 436/1000 partners and 215/1281 children were screened. HBsAg was detected in 55 (12.6%) partners and 24 (11.2%) children. After adjusting for confounders, uptake of screening was higher in partners who were married, who attended the woman's first post-test consultation and to whom the woman had disclosed her HBV status. In children, HBsAg positivity was associated with being born before the introduction of infant hepatitis B vaccination in Burkina Faso (not significant in the multivariable analysis), having a mother positive for HBV e-antigen (adjusted OR: 8.57; 95% CI: 2.49-29.48) or having a mother with HBV DNA level ≥ 200 000 IU/mL (OR: 6.83; 95% CI: 1.61-29.00). Conclusion: In low-income countries, the antenatal consultation provides a cost-effective opportunity to identify HBV-infected household contacts and link them to care. Children born before the introduction of infant hepatitis B vaccination and whose mother has higher viral load or infectivity should be a priority for testing and linkage to care.

Assessment and Simplification of Treatment Eligibility Among Patients With Chronic Hepatitis B Infection in Vietnam.

BACKGROUND: Treatment eligibility and the accuracy of its simplified criteria have been poorly documented in patients with chronic hepatitis B virus (HBV) infection worldwide, especially in low- and middle-income countries. METHODS: From a cohort of HBV-infected patients in Vietnam, we assessed the proportion of patients eligible for treatment using the national guidelines based on reference tests (HBV DNA quantification and FibroScan); and the accuracy of simplified treatment criteria free from HBV DNA and FibroScan (Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score and simplified World Health Organization [WHO] criteria) to select patients for antiviral therapy using the national guidelines as a reference. RESULTS: We analyzed 400 consecutive treatment-naïve HBV-monoinfected patients: 49% males, median age 38 years (range, 18-86), 32% hepatitis B e antigen-positive, median HBV DNA 4.8 log10 IU/mL (undetectable -8.4), median FibroScan 5.3 kPa (3.0-67.8), and 25% having significant liver fibrosis including 12% with cirrhosis. Of these, 167 (42%) fulfilled treatment criteria according to national guidelines. Using the national criteria as a reference, the performance of TREAT-B to select patients for treatment was high (area under the receiver operating characteristic [AUROC], 0.89 [95% confidence interval 0.87-0.92]) with a sensitivity of 74.3% and a specificity of 88.4%. In a subset of patients with 2 alanine aminotransferase measurements over a 6-month period (n = 89), the AUROC of TREAT-B was significantly higher than that of the simplified WHO criteria (P < .001). CONCLUSIONS: Our study suggests that a large proportion of patients with chronic HBV infection require antiviral therapy in Vietnam. Compared with the simplified WHO criteria free from HBV DNA quantification, TREAT-B is a better alternative to easily indicate treatment eligibility and might help scale up treatment intervention in Vietnam.

Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants.

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. METHODS: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. RESULTS: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83-0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94-0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. CONCLUSIONS: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.

Analytical validation of hepatitis B core-related antigen (HBcrAg) using dried blood spots (DBS).

Limited access to nucleic acid testing (NAT) to quantify HBV DNA levels, an essential tool to determine anti-HBV treatment eligibility, represents a significant barrier to scale up HBV diagnostic services in resource-limited countries. Hepatitis B core-related antigen (HBcrAg) has the potential to become an affordable alternative because of its low cost (US$ <15/assay) and strong correlation with HBV DNA levels in treatment-naïve patients. However, the current assay requires plasma or serum. To further facilitate its application to decentralized settings, we developed and evaluated a standardized procedure to quantify HBcrAg using dried blood spots as a tool to diagnose HBV-infected people with high viraemia. We evaluated the following elution method optimized to quantify HBcrAg: suspension of a punched blood-soaked disc (11 mm) of Whatman 903 Protein Saver Card in 450 µL of PBS 0.05% Tween 20, followed by an incubation for 4 h at room temperature and a centrifugation at 10,000 g for 10 minutes. 150 µL of DBS eluate was used to quantify HBcrAg using chemiluminescent enzyme immunoassay (LUMIPULSE® G600II, Fujirebio). The limit of detection of dried blood spot HBcrAg in relation with HBV DNA levels was 19,115 IU/mL across the five major HBV genotypes (A/B/C/D/E). A strong linear correlation was confirmed between dried blood spot HBcrAg and HBV DNA levels (r = 0.94, p < 0.0001) in samples with high viral loads (range: 3.7-7.0 log IU/mL). The coefficient of variation ranged between 4.0-11.2% for repeatability and 3.9-12.2% for reproducibility. Analytical specificity was 100% (95% CI: 83.9-100%) in HBV-negative samples. Using our elution method, it may be possible to identify HBV-infected patients with high viraemia who need antiviral therapy using dried blood spot and HBcrAg. A large-scale clinical validation is warranted in resource-limited countries.

Clinical utility of quantifying hepatitis B surface antigen in African patients with chronic hepatitis B.

The clinical utility of quantifying hepatitis B surface antigen (qHBsAg) levels in African subjects with chronic hepatitis B virus (HBV) infection has been poorly documented. From a multicentre cohort of 944 HBV-infected African patients, we aimed to assess whether qHBsAg alone can accurately identify i) those in a HBeAg-negative chronic HBV infection phase at low risk of liver disease progression and ii) those in need of antiviral therapy according to the 2017 EASL guidelines. We analysed 770 HBV mono-infected treatment-naïve patients, mainly males (61%) from West Africa (92%), median age 35 years (IQR: 30-44), median HBV DNA: 95.6 IU/ml (10.0-1,300.0), median qHBsAg 5,498 IU/ml (1,171-13,000) and HBeAg-pos 38 (5%). A total of 464/770 (60.2%) patients were classified as HBeAg-negative chronic infection (median age 36 years (31-46), median ALT 23 IU/l (18-28), median HBV-DNA 33.5 IU/ml (3.8-154.1), median LSM 4.8 kPa (4.1-5.8)) and qHBsAg levels had poor accuracy to identify these subjects with an AUROC at 0.58 (95%CI: 0.54-0.62), sensitivity 55.0% and specificity 55.6%; 118/770 (15.3%) patients were eligible for treatment according to the 2017 EASL criteria. qHBsAg correlated poorly with HBV DNA and had poor accuracy to select patients for antiviral therapy with an AUROC at 0.54 (0.49-0.60), sensitivity 46.6% and specificity 46.9%. In African treatment-naïve HBV-infected subjects, the clinical utility of qHBsAg to identify subjects in HBeAg-negative infection phase or subjects eligible for antiviral therapy seems futile. Whether qHBsAg levels can be used as a predictor of long-term liver complications in Africa needs to be further investigated.

Improving care of migrants is key for viral hepatitis elimination in Europe.

By 2040, deaths from chronic viral hepatitis worldwide are projected to exceed those from human immunodeficiency virus infection, tuberculosis and malaria combined. The burden of this disease is predominantly carried by low-resource countries in Africa and Asia. In resource-rich countries, the epidemiological spread of viral hepatitis is partially driven by migrant movements from areas of high endemicity. In the last decade, Member States of the European Union and the European Economic Area have experienced an unprecedented influx of migrants, which has resulted in the polarization of political views about migration. In addition, the coronavirus disease 2019 pandemic has worsened the economic and health conditions of migrants and contributed to hostility to ensuring their health rights. Moreover, the implementation of hostile laws in some host nations has increased the vulnerability of marginalized migrant subgroups, such as asylum seekers and undocumented individuals. These developments have complicated the historical challenge of identifying high-risk migrant groups for screening and treatment. However, if European countries can apply the simplified assessment tools and diagnostic tests for viral hepatitis that have been used for decentralized screening and monitoring in resource-poor countries, the uptake of care by migrants could be dramatically increased. Given the global calls for the elimination of viral hepatitis, European nations should recognize the importance of treating this vulnerable migrant population. Political and health strategies need to be adapted to meet this challenge and help eliminate viral hepatitis globally.

D'ici 2040, les décès causés par l'hépatite virale chronique dans le monde devraient dépasser ceux dus à trois grandes maladies réunies: l'infection au virus de l'immunodéficience humaine, la tuberculose et la malaria. Le fardeau que représente cette affection repose surtout sur les pays disposant de ressources limitées en Afrique et en Asie. Dans les pays riches en ressources, la propagation épidémiologique de l'hépatite virale est en partie liée aux mouvements migratoires depuis les zones à endémicité élevée. Au cours de la dernière décennie, les États membres de l'Union européenne et l'Espace économique européen ont connu un afflux de migrants sans précédent qui a polarisé les opinions politiques concernant la migration. En outre, la pandémie de maladie à coronavirus 2019 a aggravé la situation économique et sanitaire des migrants, contribuant à l'animosité ambiante à l'égard du respect de leurs droits en matière de santé. L'adoption de lois hostiles dans certains pays d'accueil a également accru la vulnérabilité des sous-groupes de migrants marginalisés, tels que les demandeurs d'asile et les sans-papiers. Des conditions qui compliquent la tâche d'identification des groupes de migrants à haut risque pour le dépistage et le traitement. Néanmoins, si les pays européens pouvaient appliquer les outils d'évaluation simplifiés et les tests de diagnostic de l'hépatite virale, qui ont été employés pour la surveillance et le dépistage décentralisé dans les pays disposant de ressources limitées, la prise en charge des migrants pourrait nettement s'améliorer. Compte tenu des nombreux appels internationaux à éliminer l'hépatite virale, les nations européennes devraient reconnaître l'importance de soigner ces populations de migrants vulnérables. Les stratégies politiques et sanitaires doivent être adaptées afin de relever ce défi et de contribuer à éradiquer l'hépatite virale dans le monde.

Para 2040, se prevé que las muertes por hepatitis vírica crónica en todo el mundo superen a las causadas por la infección del virus de la inmunodeficiencia humana, la tuberculosis y la malaria juntas. La carga de esta enfermedad recae sobre todo en los países con recursos limitados de África y Asia. En los países ricos en recursos, la propagación epidemiológica de las hepatitis víricas se debe en parte a los movimientos migratorios desde las zonas altamente endémicas. En la última década, los Estados miembros de la Unión Europea y del Espacio Económico Europeo han experimentado una afluencia de inmigrantes sin precedentes, lo que ha polarizado las opiniones políticas sobre la inmigración. Además, la pandemia de la enfermedad del coronavirus de 2019 ha empeorado las condiciones económicas y sanitarias de los inmigrantes y ha contribuido a la hostilidad para garantizar sus derechos sanitarios. Además, la aplicación de leyes hostiles en algunas naciones de acogida ha aumentado la vulnerabilidad de subgrupos de inmigrantes marginados, como los solicitantes de asilo y los indocumentados. Estos acontecimientos han complicado el reto histórico de identificar a los grupos de inmigrantes de alto riesgo para su detección y tratamiento. Sin embargo, si los países europeos pueden aplicar las herramientas de evaluación y las pruebas de diagnóstico simplificadas para la hepatitis vírica que se han utilizado para el cribado y el seguimiento descentralizados en los países con pocos recursos, la aceptación de la atención por parte de los inmigrantes podría aumentar drásticamente. Dados los llamamientos mundiales para la eliminación de la hepatitis vírica, las naciones europeas deberían reconocer la importancia de tratar a esta población inmigrante vulnerable. Es necesario adaptar las estrategias políticas y sanitarias para hacer frente a este reto y ayudar a eliminar la hepatitis vírica a nivel mundial.

Epidemiological projections of viral-induced hepatocellular carcinoma in the perspective of WHO global hepatitis elimination.

Hepatitis B is an eminent risk factor for hepatocellular carcinoma (HCC) in Southeast Asia and sub-Saharan Africa, whereas hepatitis C is a key risk factor for HCC in Western Europe and North America. Increased awareness of the global burden of viral hepatitis resulted, in May 2016, in the adoption of the first global health sector strategy on viral hepatitis by the World Health Assembly, which calls for the elimination of viral hepatitis as a public health threat by 2030. Although the incidence of liver cancer resulting from viral infections has increased since the 1990s, the implementation of public health interventions, such as hepatitis B vaccination and antiviral therapies might have reduced the global burdens of HCC. Hepatitis B immunization in infancy has been associated with a reduction in the risk of infant fulminant hepatitis, chronic liver disease, and HCC in Taiwan. Achieving viral hepatitis elimination by 2030 can be accelerated by improving the access to HCC screening programs. HCC surveillance programs in developed countries must be refined to increase an access to personalized surveillance program, whereas the limited access to surveillance and treatment of HCC in developing countries remains a significant public health issue.

Hepatitis B Core-related Antigen: An Alternative to Hepatitis B Virus DNA to Assess Treatment Eligibility in Africa.

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.

Mother-to-child transmission of hepatitis B: What more needs to be done to eliminate it around the world?

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a key component of the hepatitis B burden worldwide. Despite its efficacy to prevent HBV transmission, infant vaccination is not enough to control HBV MTCT. Additional efforts are urgently needed to evaluate and scale-up preventive strategies especially in endemic countries, which are most affected. This review highlights the efficacy and barriers of the currently validated measures for the prevention of HBV MTCT and proposes alternatives adapted to resource-limited settings to eventually achieve HBV elimination worldwide.

In-field evaluation of Xpert® HCV viral load Fingerstick assay in people who inject drugs in Tanzania.

BACKGROUND: Although novel hepatitis C virus (HCV) RNA point-of-care technology has the potential to enhance the diagnosis in resource-limited settings, very little real-world validation of their utility exists. We evaluate the performance of HCV RNA quantification using the Xpert® HCV viral load Fingerstick assay (Xpert® HCV VL Fingerstick assay) as compared to the World Health Organisation pre-qualified plasma Xpert® HCV VL assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar-es-Salaam, Tanzania. METHODS: Between December 2018 and February 2019, consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and Fingerstick samples for HCV RNA quantification. These were processed onsite using the GeneXpert® platform located at the Central tuberculosis reference laboratory. RESULTS: A total of 208 out of 220 anti-HCV-positive participants recruited (94.5%) had a valid Xpert® HCV VL result available; 126 (61%; 95% CI 53.8-67.0) had detectable and quantifiable HCV RNA. About 188 (85%) participants had paired plasma and Fingerstick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R2  = .95) and concordance (mean difference 0.13 IU/mL, (95% CI -0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and Fingerstick samples. CONCLUSION: This study found excellent performance of the Xpert® HCV VL Fingerstick assay for HCV RNA detection and quantification in an African-field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa.

High prevalence and poor linkage to care of transfusion-transmitted infections among blood donors in Dar-es-Salaam, Tanzania.

Blood transfusion is one of the most commonly relied upon therapies in sub-Saharan Africa. Existing safeguards recommended include systematic screening for transfusion-transmitted infections and restricted voluntary nonremunerated blood donor selection. We report the transfusion-transmitted infection screening and notification practice at a large urban blood transfusion centre in Dar-es-Salaam, Tanzania. Between October 2016 and March 2017 anonymized records of all donors registered at the blood transfusion unit were accessed to retrospectively note demographic information, donor status, first-time status, transfusion-transmitted infection result and notification. 6402 consecutive donors were screened for transfusion-transmitted infections; the majority were family/replacement blood donors (88.0%) and male (83.8%). Overall transfusion-transmitted infections prevalence was 8.4% (95% CI 7.8-9.1), with hepatitis B being the most prevalent infection (4.1% (95% CI 3.6-4.6)). Transfusion-transmitted infections were more common in family/replacement blood donors (9.0% (95% CI 8.3-9.8)) as compared to voluntary nonremunerated blood donor (4.1% (95% CI 2.8-5.7)). A minority of infected-donors were notified of a positive result (8.5% (95% CI 6.3-11.2)). Although transfusion-transmitted infections are more prevalent among family/replacement blood donors, overall risk of transfusion-transmitted infections across all groups is considerable. In addition, existing efforts to notify donors of a positive transfusion-transmitted infection are poor. Future policies must focus on improving linkage to care for newly diagnosed patients with transfusion-transmitted infections.

Development and clinical validation of the Genedrive point-of-care test for qualitative detection of hepatitis C virus.

OBJECTIVE: Recently approved direct acting antivirals provide transformative therapies for chronic hepatitis C virus (HCV) infection. The major clinical challenge remains to identify the undiagnosed patients worldwide, many of whom live in low-income and middle-income countries, where access to nucleic acid testing remains limited. The aim of this study was to develop and validate a point-of-care (PoC) assay for the qualitative detection of HCV RNA. DESIGN: We developed a PoC assay for the qualitative detection of HCV RNA on the PCR Genedrive instrument. We validated the Genedrive HCV assay through a case-control study comparing results with those obtained with the Abbott RealTime HCV test. RESULTS: The PoC assay identified all major HCV genotypes, with a limit of detection of 2362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semiquantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. CONCLUSION: We report a rapid, simple, portable and accurate PoC molecular test for HCV, with sensitivity and specificity that fulfils the recent FIND/WHO Target Product Profile for HCV decentralised testing in low-income and middle-income countries. This Genedrive HCV assay may positively impact the continuum of HCV care from screening to cure by supporting real-time treatment decisions. TRIAL REGISTRATION NUMBER: NCT02992184 .

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.