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Background Chronic Hepatitis B Virus (HBV) infection is characterised by the persistence of hepatitis B surface antigen (HBsAg). Expanding HBV diagnosis and treatment programmes into low resource settings will require high quality but inexpensive rapid diagnostic tests (RDTs) in addition to laboratory-based enzyme immunoassays (EIAs) to detect HBsAg. The purpose of this review is to assess the clinical accuracy of available diagnostic tests to detect HBsAg to inform recommendations on testing strategies in 2017 WHO hepatitis testing guidelines. Methods The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using 9 databases. Two reviewers independently extracted data according to a pre-specified plan and evaluated study quality. Meta-analysis was performed. HBsAg diagnostic accuracy of rapid diagnostic tests (RDTs) was compared to enzyme immunoassay (EIA) and nucleic-acid test (NAT) reference standards. Subanalyses were performed to determine accuracy among brands, HIV-status and specimen type. Results Of the 40 studies that met the inclusion criteria, 33 compared RDTs and/or EIAs against EIAs and 7 against NATs as reference standards. Thirty studies assessed diagnostic accuracy of 33 brands of RDTs in 23,716 individuals from 23 countries using EIA as the reference standard. The pooled sensitivity and specificity were 90.0% (95% CI: 89.1, 90.8) and 99.5% (95% CI: 99.4, 99.5) respectively, but accuracy varied widely among brands. Accuracy did not differ significantly whether serum, plasma, venous or capillary whole blood was used. Pooled sensitivity of RDTs in 5 studies of HIV-positive persons was lower at 72.3% (95% CI: 67.9, 76.4) compared to that in HIV-negative persons, but specificity remained high. Five studies evaluated 8 EIAs against a chemiluminescence immunoassay reference standard with a pooled sensitivity and specificity of 88.9% (95% CI: 87.0, 90.6) and 98.4% (95% CI: 97.8, 98.8), respectively. Accuracy of both RDTs and EIAs using a NAT reference were generally lower, especially amongst HIV-positive cohorts. Conclusions HBsAg RDTs have good sensitivity and excellent specificity compared to laboratory immunoassays as a reference standard. Sensitivity of HBsAg RDTs may be lower in HIV infected individuals.

Background The detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples. Methods We searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias. Results In the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83–99) and 99% (95% CI: 53–100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) – one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95–99) and 98% (95% CI:95–99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity. Conclusions These findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.

Background Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV. Methods We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias. Results For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews. Conclusion HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

Background There have been few reports on programmatic experience of viral hepatitis testing and treatment in resource-limited settings. To inform the development of the 2017 World Health Organization (WHO) viral hepatitis testing guidance and in particular the feasibility of proposed recommendations, we undertook a survey across a range of organisations engaged with hepatitis testing in low- and middle-income countries (LMICs). Our objective was to describe current hepatitis B and C testing practices across a range of settings in different countries, as well as key barriers or challenges encountered and proposed solutions to promote testing scale-up. Methods Hepatitis testing programmes in predominantly LMICs were identified from the WHO Global Hepatitis Programme contacts database and through WHO regional offices, and invited to participate. The survey comprised a six-part structured questionnaire: general programme information, description of hepatitis testing, treatment and care services, budget and funding, data on programme outcomes, and perceptions on key barriers encountered and strategies to address these. Results We interviewed 22 viral hepatitis testing programmes from 19 different countries. Nine were from the African region; 6 from the Western Pacific; 4 from South-East Asia; and 3 from Eastern Europe. All but four of the programmes were based in LMICs, and 10 (45.5%) were supported by non-governmental or international organizations. All but two programmes undertook targeted testing of specific affected populations such as people living with HIV, people who inject drugs, sex workers, health care workers, and pregnant women. Only two programmes focussed on routine testing in the general population. The majority of programmes were testing in hospital-based or other health facilities, particularly HIV clinics, and community-based testing was limited. Nucleic acid testing (NAT) for confirmation of HCV and HBV viraemia was available in only 30% and 18% of programmes, respectively. Around a third of programmes required some patient co-payment for diagnosis. The most commonly identified challenges in scale-up of hepatitis testing were: limited community awareness about viral hepatitis; lack of facilities or services for hepatitis testing; no access to low cost treatment, particularly for HCV; absence of national guidance and policies; no dedicated budget for hepatitis; and lack of trained health care and laboratory workers. Conclusions At this early stage in the global scale-up of testing for viral hepatitis, there is a wide variation in testing practices and approaches across different programmes. There remains limited access to NAT to confirm viraemia, and patient self-payment for testing and treatment is common. There was consensus from implementing organizations that scale-up of testing will require increased community awareness, health care worker training, development of national strategies and guidelines, and improved access to low cost NAT virological testing.

This study aimed to elucidate the 12-month durability of neutralizing antibodies (NAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients infected during the 2020 workplace outbreaks of coronavirus disease 2019 (COVID-19) in Japan. We followed 33 Japanese patients infected with SARS-CoV-2 in April 2020 for 12 months (12M). Patients were tested for NAbs and for antibodies against the SARS-CoV-2 nucleocapsid (anti-NC-Ab) and antibodies against the spike receptor-binding domain (anti-RBD-Ab). Tests were performed at 2M, 6M, and 12M after the primary infection ( api ) with commercially available test kits. In 90.9% (30/33) of patients, NAbs persisted for 12M api , though the median titers significantly declined from 78.7% (interquartile range [IQR]: 73.0–85.0%) at 2M, to 59.8% (IQR: 51.2–77.9) at 6M ( P = 0.008), and to 56.2% (IQR: 39.6–74.4) at 12M ( P <0.001). An exponential decay model showed that the NAb level reached undetectable concentrations at 35.5 months api (95% confidence interval: 26.5–48.0 months). Additionally, NAb titers were significantly related to anti-RBD-Ab titers (rho = 0.736, P <0.001), but not to anti-NC-Ab titers. In most patients convalescing from COVID-19, NAbs persisted for 12M api . This result suggested that patients need a booster vaccination within one year api , even though NAbs could be detected for over two years api . Anti-RBD-Ab titers could be used as a surrogate marker for predicting residual NAb levels.

We investigated the impact of human immunodeficiency virus (HIV) infection and anti-retroviral therapy (ART) on the gut microbiota of children. This cross-sectional study investigated the gut microbiota of children with and without HIV. We collected fecal samples from 59 children with HIV (29 treated with ART [ART(+)] and 30 without ART [HIV(+)]) and 20 children without HIV [HIV(-)] in Vietnam. We performed quantitative RT-PCR to detect 14 representative intestinal bacteria targeting 16S/23S rRNA molecules. We also collected the blood samples for immunological analyses. In spearman's correlation analyses, no significant correlation between the number of dominant bacteria and age was found among children in the HIV(-) group. However, the number of sub-dominant bacteria, including Streptococcus, Enterococcus, and Enterobacteriaceae, positively correlated with age in the HIV(-) group, but not in the HIV(+) group. In the HIV(+) group, Clostridium coccoides group positively associated with the CD4.sup.+ cell count and its subsets. In the ART(+) group, Staphylococcus and C. perfringens positively correlated with CD4.sup.+ cells and their subsets and negatively with activated CD8.sup.+ cells. C. coccoides group and Bacteroides fragilis group were associated with regulatory T-cell counts. In multiple linear regression analyses, ART duration was independently associated with the number of C. perfringens, and Th17 cell count with the number of Staphylococcus in the ART(+) group. HIV infection and ART may influence sub-dominant gut bacteria, directly or indirectly, in association with immune status in children with HIV.

Background Human papillomavirus (HPV) causes cancers in men, including penile, anal, and oropharyngeal cancers. This cross-sectional study aimed to investigate the prevalence, the genotypes, and the risk factors of HPV infections in the oral cavity, compared to those in the genitals, among males diagnosed with sexually transmitted infections (STIs) in Vietnam. Methods Oral, urinary, penile, and urethral samples were collected from 198 male Vietnamese patients with STIs (median age 31.0 years, range 17–68). HPV DNA was isolated and amplified with PCR, with modified and/or original GP5 + /GP6 + primers. Samples were genotyped with a gene array assay and/or population sequencing. Results HPV DNA was detected in 69 (34.8%) of 198 patients. Of these, 16 patients (8.1%) had infections in the oral cavity and 58 (29.3%) had infections in the genitals (4.5% in the urine, 25.8% in the penis, and 8.1% in the urethra). The concordance of HPV infections between the oral cavity and the genitals was poor (kappa = 0.01). Of the 16 patients with oral HPV DNA, 11 (68.8%) had no HPV DNA in the genitals. In the remaining five patients, HPV DNA was found at both sites, but only one showed similar strains at both sites. In the other four patients, the HPV genotypes were completely discordant between these sites. HPV18 was the most common high-risk HPV genotype in both oral (9/16, 56.3%) and genital (10/58, 17.2%) sites. Multivariable analyses showed that older age (OR 1.05), higher education (OR 2.17), and no knowledge of STIs (OR 4.21) were independent risk factors for genital HPV infections; in contrast, only older age (OR 1.05) was an independent risk factor for oral HPV infections. Conclusions The low concordance of HPV genotypes between oral and genital infection sites suggested that the acquisition, persistence, and/or clearance of HPV infections were different between these sites. Although HPV DNA was detected significantly less frequently in oral samples than in genital samples, oral samples should also be used for HPV screening in men.

Here, we investigated the effects of the probiotic strain Lactobacillus casei Shirota (LcS) on immune profiles and intestinal microbial translocation among children infected with human immunodeficiency virus (HIV). This prospective study included 60 HIV-infected children—including 31 without antiretroviral therapy (ART) (HIV(+)) and 29 who received ART for a median of 3.5 years (ART(+)) and 20 children without HIV infection (HIV(−)). Participants were recruited in Vietnam. All children were given fermented milk containing LcS (6.5 × 109 cfu) daily for 8 weeks. Before and after LcS ingestion, blood samples were collected for virological, immunological, and bacteriological analyses. After LcS ingestion, peripheral CD4+ T-cell and Th2 (CXCR3−CCR6−CD4+) counts significantly increased in both HIV-infected groups; Th17 (CXCR3−CCR6+CD4+) counts increased in all three groups; regulatory T-cell (CD25highCD4+) counts decreased in the ART(+) and HIV(−) groups; activated CD8+ cells (CD38+HLA-DR+CD8+) decreased from 27.5% to 13.2% (p < 0.001) in HIV(+) children; and plasma HIV load decreased slightly but significantly among HIV(+) children. No group showed a significantly altered frequency of bacterial 16S/23S rRNA gene detection in the plasma. No serious adverse events occurred. These findings suggest that short-term LcS ingestion is a safe supportive approach with immunological and virological benefits in HIV-infected children.

Enterovirus-A71 (EV-A71) is a common cause of hand-foot-and-mouth disease (HFMD) and, rarely, causes severe neurological disease. This study aimed to elucidate the epidemiological and genetic characteristics and virulence of EV-A71 strains isolated from children diagnosed with HFMD. Rectal and throat swabs were collected from 488 children with HFMD in Hanoi, Vietnam, in 2015–2016. From 391 EV-positive patients, 15 EVs, including coxsackievirus A6 (CV-A6; 47.1%) and EV-A71 (32.5%, n = 127), were identified. Of the 127 EV-A71 strains, 117 (92.1%) were the B5 subgenotype and 10 (7.9%) were the C4 subgenotype. A whole-genome analysis of EV-A71 strains showed that seven of the eight C4a strains isolated in 2016 formed a new lineage, including two possible recombinants between EV-A71 C4 and CV-A8. The proportion of inpatients among C4-infected children was higher than among B5-infected children (80.0% vs. 27.4%; P = 0.002). The virulence of EV-A71 strains was examined in human scavenger receptor class B2 (hSCARB2)-transgenic mice, and EV-A71 C4 strains exhibited higher mortality than B5 strains (80.0% vs. 30.0%, P = 0.0001). Thus, a new EV-A71 C4a-lineage, including two possible recombinants between EV-A71 C4 and CV-A8, appeared in 2016 in Vietnam. The EV-A71 C4 subgenotype may be more virulent than the B5 subgenotype.

We previously reported a significant reduction in the prevalence of human immunodeficiency virus type 1 (HIV) from 2007 to 2012 in people who inject drugs (PWID; 35.9% to 18.5%, p < 0.001) and female sex workers (FSW; 23.1% to 9.8%, p < 0.05), but not in blood donors (BD) or pregnant women, in Haiphong, Vietnam. Our aim in the present study was to assess trends in the prevalence of infection with hepatitis B and C viruses (HBV and HCV, respectively). We also investigated the coinfection rates of HBV and HCV with HIV in the same groups. Between 2007 and 2012, HBV prevalence was significantly decreased in BD (18.1% vs. 9.0%, p = 0.007) and slightly decreased in FSW (11.0% vs. 3.9%, p = 0.21), but not in PWID (10.7% vs. 11.1%, p = 0.84). HCV prevalence was significantly decreased in PWID (62.1% in 2007 vs. 42.7% in 2008, p < 0.0001), but it had rebounded to 58.4% in 2012 (2008 vs. 2012, p < 0.0001). HCV prevalence also increased in FSW: 28.6% in 2007 and 2009 vs. 35.3% in 2012; however, this difference was not significant (2007 vs. 2012, p = 0.41). Rates of coinfection with HBV and HCV among HIV-infected PWID and FSW did not change significantly during the study period. Our findings suggest that the current harm reduction programs designed to prevent HIV transmission in PWID and FSW may be insufficient to prevent the transmission of hepatitis viruses, particularly HCV, in Haiphong, Vietnam. New approaches, such as the introduction of catch-up HBV vaccination to vulnerable adult populations and the introduction of HCV treatment as prevention, should be considered to reduce morbidity and mortality due to HIV and hepatitis virus coinfection in Vietnam.