Treatment of chronic hepatitis B virus infection in resource‐constrained settings: expert panel consensus

Most of the estimated 350 million people with chronic hepatitis B virus (HBV) infection live in resource‐constrained settings. Up to 25% of those persons will die prematurely of hepatocellular carcinoma (HCC) or cirrhosis. Universal hepatitis B immunization programmes that target infants will have an impact on HBV‐related deaths several decades after their introduction. Antiviral agents active against HBV are available; treatment of HBV infection in those who need it has been shown to reduce the risk of HCC and death. It is estimated that 20–30% of persons with HBV infection could benefit from treatment. However, drugs active against HBV are not widely available or utilized in persons infected with HBV. Currently recommended antiviral agents used for treatment of human immunodeficiency virus (HIV) infection do not adequately suppress HBV, which is of great concern for the estimated 10% of the HIV‐infected persons in Africa who are co‐infected with HBV. Progressive liver disease has been shown to occur in co‐infected persons whose HBV infection is not suppressed. In view of these concerns, an informal World Health Organization consultation of experts concluded that: chronic HBV is a major public health problem in emerging nations; all HIV‐infected persons should be screened for HBV infection; HIV/HBV co‐infected persons should be treated with therapies active against both viruses and that reduce the risk of resistance; standards for the management of chronic HBV infection should be adapted to resource‐constrained settings. In addition, a research agendum was developed focusing on issues related to prevention and treatment of chronic HBV in resource‐constrained settings.     

Involvement of mast cells in inflammation induced by Trichomonas vaginalis via crosstalk with vaginal epithelial cells

Vaginal epithelial cells (VECs) are thought to function as immune‐responsive cells in trichomoniasis, and mast cells have been detected in vaginal smears and the vaginal wall in trichomoniasis. It therefore seemed possible that the VEC‐trichomonad reaction might affect the activity of mast cells present in the lamina propria of the vaginal mucosa. In this study, we tested whether culture supernatants of VEC incubated with Trichomonas vaginalis (TCM) could stimulate mast cells. When VECs (MS74) were incubated with live trichomonads, IL‐8, IL‐6 and MCP‐1 expressions increased in the TCM, and mast cells (HMC‐1) and human neutrophils migrated more actively towards the TCM. Also, when the TCM was added to mast cells, β‐hexosaminidase and cytokines (IL‐8 and TNF‐α) expressions were increased. Moreover, the culture supernatant of mast cells incubated with TCM (M‐TCM) had more increased chemotactic activity for neutrophils than that of TCM. We conclude that inflammatory mediators made by VECs in response to activation by T. vaginalis activate and attract mast cells and then stimulate them to induce neutrophil migration. Our results indicate, for the first time, that VECs play a role in the infiltration of mast cells and neutrophils early in T. vaginalis infection.     

Cysteine proteinase 30 (CP30) and antibody response to CP30 in serum and vaginal washes of symptomatic and asymptomatic Trichomonas vaginalis-infected women

Infection with Trichomonas vaginalis may be asymptomatic or with symptoms suggestive of vaginitis. Because cysteine proteinase 30 (CP30) of T. vaginalis is known to be a virulence marker that plays a role in cytoadherence, the aim of this study was to analyse the presence of CP30 and antibody to CP30 in clinical samples of symptomatic and asymptomatic infected women. CP30 was detected in all the serum and vaginal washes (VWs) of symptomatic women and in 65% of the serum and 80% of the VWs of asymptomatic women. This suggested that the majority of asymptomatic women also exhibit CP30 in the serum and VWs. Antibody to CP30 was detected in all the serum samples of symptomatic and asymptomatic women and in the VWs of only 54.5% of the symptomatic and 35% of the asymptomatic women. Antibody to CP30 was also detected in 3/20 of the serum samples and in none of the VWs from uninfected women. Significantly higher amounts of antibody (mean OD values) were observed in serum and VWs of symptomatic as compared to asymptomatic and healthy women (P<0.001). These results indicate that besides CP30, other factors may also be playing a role in leading to symptomatic infection, because CP30 was detected in clinical samples from all the symptomatic and the majority of the asymptomatic women. Although anti-CP30 antibodies do not appear to be protective, detection of antibody to CP30 antigen in serum samples may be used as a diagnostic tool.     

Measurement of CD4+ T cells in point-of-care settings with the Sysmex pocH-100i haematological analyser

The decision to provide antiretroviral therapy to HIV-positive patients mainly depends on the CD4(+) T-cell count, with therapy indicated at a cut-off value of <350-200 CD4(+) T cells/microl blood. Monitoring patients is still a major problem in countries with limited resources where blood samples often have to be transported over long distances to regional referral centres in which the count can be performed on flow cytometers. We have evaluated a newly developed simple and inexpensive method for CD4(+) T-cell quantification. It is a variation of the Invitrogen T4 Quant kit, with manual isolation of nuclei from CD4(+) T cells and subsequent counting on the small haematology analyser pocH-100i, Sysmex. We have demonstrated that this new method is highly reproducible and gives stable and linear results over a wide range of CD4(+) T-cell concentrations. Method comparison to two different flow cytometers showed excellent correlation with concordances of about 93%. Overall, this method is rapid, easy to perform and offers a good reliable alternative to measurement by flow cytometry. The pocH-100i has the additional benefit of providing a complete blood count with a three-part white blood cell differential and software for patient data storage and handling.     

Effectiveness of interventions for the prevention of HIV and other sexually transmitted infections in female sex workers in resource poor setting: a systematic review

Objective To systematically review the evidence for effectiveness of HIV and sexually transmitted infection (STI) prevention interventions in female sex workers in resource poor settings. Method Published and unpublished studies were identified through electronic databases (Cochrane database, Medline, Embase, and Web of Science), hand searching and contacting experts. Randomized‐controlled‐trials and quasi‐experimental studies were included if they were conducted in female sex workers from low and middle income settings; if the exposure was described; if the outcome was externally measurable, it was after the discovery of HIV, and if follow‐up was longer than 6 months. A priori criteria were used to extract data. Meta‐analysis was not performed due to the heterogeneity of studies. Results Twenty‐eight interventions were included. Despite methodological limitations, the evidence suggested that combining sexual risk reduction, condom promotion and improved access to STI treatment reduces HIV and STI acquisition in sex workers receiving the intervention. Strong evidence that regular STI screening or periodic treatment of STIs confers additional protection against HIV was lacking. It appears that structural interventions, policy change or empowerment of sex workers, reduce the prevalence of STIs and HIV. Conclusion Rigorous evaluation of HIV/STI prevention interventions in sex workers is challenging. There is some evidence for the efficacy of multi‐component interventions, and/or structural interventions. The effect of these interventions on the wider population has rarely been evaluated.     

Challenge of managing hepatitis B virus and hepatitis C virus infections in resource-limited settings

The global burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and coinfection represents a major public health concern, particularly in resource-limited settings. Elimination of HCV by 2030 has become foreseeable, with effective direct-acting antiviral oral therapies and the availability of affordable generics in low-and-middle-income countries (LMICs). However, access to oral nucleos(t)ide therapy for HBV remains critical and is limited outside the existing global HIV program platforms despite affordable prices. Prevention of mother-to-child transmission of HBV through scaling up of birth dose implementation in LMICs is essential to achieve the 2030 elimination goal. Most individuals living with HBV and/or HCV in resource-limited settings are unaware of their infection, and with improved access to medications, the most significant barrier remains access to affordable diagnostics and preventive strategies. The coronavirus disease 2019 pandemic interrupted hepatitis elimination programs, albeit offered opportunities for improved diagnostic capacities and raised political awareness of the critical need for strengthening health care services and universal health coverage. This review underpins the HBV and HCV management challenges in resource-limited settings, highlighting the current status and suggested future elimination strategies in some of these countries. Global efforts should continue to improve awareness and political commitment. Financial resources should be secured to access and implement comprehensive strategies for diagnosis and linkage to care in resource-constrained settings to fulfill the 2030 elimination goal.     

Next-generation point-of-care testing in pediatric human immunodeficiency virus infection facilitates diagnosis and monitoring of treatment

Point-of-care (PoC) testing facilitates early infant diagnosis (EID) and treatment initiation, which improves outcome. We present a field evaluation of a new PoC test (Cepheid Xpert® HIV-1 Qual XC RUO) to determine whether this test improves EID and assists the management of children living with human immunodeficiency virus (HIV) infection.We compared 2 PoC tests with the standard-of-care (SoC) test used to detect HIV infection from dry blood spots in newborn infants at high risk of in utero infection. We also evaluated the ability of the PoC tests to detect HIV total nucleic acid (TNA) in children living with HIV infection who had maintained undetectable plasma viremia following very early combination antiretroviral therapy (cART) initiation.Qualitative (Qual) detection of HIV using the Xpert® HIV-1 Qual XC RUO (“RUO”) and Xpert® HIV-1 Qual (“Qual”) PoC tests was compared in 224 infants with the SoC DBS Roche COBAS® HIV-1/HIV-2 qualitative test. The same 2 PoC tests were also evaluated in 35 older children who had initiated cART before 21 days of age and maintained undetectable plasma viremia for a mean of 25 months.No discrepancies were observed in detection of HIV infection via the 2 PoC tests or the SoC test in the 224 neonates studied, but only 95% of the SoC test results were generated compared with 100% of the PoC test results (P = .0009). The cycle threshold values for the research use only (RUO) assay were the lowest of the 3 assays (P < .0001 in each case). In 6 of the 35 early-treated aviremic children, HIV TNA was detected by RUO but not Qual.The RUO assay outperforms Qual in detecting HIV-1 infection. RUO would therefore potentially improve EID and assist in identifying cART-adherent early-treated children with the lowest HIV TNA levels and the highest HIV cure potential.     

Use of point-of-care tests and antibiotic prescribing in sore throat and lower respiratory infections by general practitioners

IntroductionThis study was aimed at assessing general practitioners’ (GP) reliance on patient history, examination findings and the influence of the utilisation of point-of-care tests (POCT) in antibiotic prescribing for sore throat and lower respiratory tract infections (LRTI).MethodsAudit-based study carried out in 2015. A group of GPs received an intervention six years earlier with provision of POCTs and another group of GPs acted as controls. Odds ratios for clinical variables predicting antibiotic prescribing were calculated by logistic regression analyses.ResultsA total of 238 GPs included 1906 patients with sore throat and 1970 LRTIs. A negative POCT result was negatively associated with antibiotic prescribing, with odds ratios ranging from 0.09 to 0.23. GPs using POCTs attached less weight to clinical criteria.ConclusionGPs using rapid tests are mainly influenced by POCT results in the decision to prescribe antibiotics. However, antibiotic prescribing is still observed with negative POCT results.     

Prevalence of vaginal infections and associated lifestyles of students in the university of Cape Coast,Ghana

Objective

To determine the prevalence of vaginal infections and associated lifestyles of students visiting the University of Cape Coast Hospital.

Methods

Fifty female students presenting with clinical symptoms of vaginitis were sampled. One hundred samples made up of 50 urine and 50 higher vaginal swabs (HVS) were obtained from patients and questionnaire administered. Samples were wet prepared, examined microscopically, and cultured on blood and chocolate agars for 24 h at (35±2) °C. Colonial morphology, Gram reactions and biochemical tests were used for the identification of isolates.

Results

There were high percentages of pus cells (64%), epithelial cells (62%) and yeast cells (56%) in all urine samples. Bacterial isolates included Staphylococcus aureus (28%) and (22%), Klebsiella spp. (6%) and (4%) in urine and HVS samples respectively; Escherichia coli in urine (18%) and Candida in HVS (16%). The overall prevalence of vaginitis was 66%, including bacterial vaginosis 28%, Candida infection 22% and co-infection of bacterial and Candida 16%. Lifestyle data showed all sampled students were sexually active, 48% used contraceptives, 54% used antimicrobial agents, and 92% prefered wearing of trousers and shorts.

Conclusions

The present study indicates prevalence of vaginal infection among female students, which strongly correlates with student lifestyle. Education on lifestyle modifications will go a long way in reducing the prevalence of vaginitis.     

Evaluation of serological tests for diagnosis of Bordetella pertussis infection in adolescents and adults

Background and objective: Bacterial agglutination antibodies against Bordetella pertussis, Yamaguchi and Tohama strains, are frequently measured for serodiagnosis of pertussis infection in Japan. To determine the serological criteria, the comparative titres of bacterial agglutination antibody and anti‐pertussis toxin (PT) antibody were evaluated. Methods: Antibody titres were analysed in 36 definitive (fourfold increase in agglutination antibody) and 137 presumptive (high titre of single‐antibody) cases of B. pertussis infection among adolescents and adults, and in a control group of 318 healthy volunteers. Results: When a single Yamaguchi agglutinin titre of ≥1:1280 (> three SD above the geometric mean for the control group) was taken as diagnostic, the sensitivity and specificity at 4–5 weeks after onset of cough were 58% and 98%, respectively. Using this criterion, the clinical findings in presumptive cases were almost identical to those in definitive cases. When the two tests were compared using 318 control sera, there was no association between the Tohama agglutinin titre and the anti‐PT antibody titre, whereas a weak association between the Yamaguchi agglutinin titre and the anti‐PT antibody titre was observed. When the numbers of pertussis cases with high antibody titres in the two tests were compared, 60% of cases with a Yamaguchi agglutinin titre of ≥1:1280 showed an anti‐PT antibody titre of ≥100 EU/mL. Conclusions: These results indicate that the bacterial agglutination test is a method with low sensitivity and specificity for the diagnosis of B. pertussis infection. Therefore, to yield an accurate diagnosis, anti‐PT antibody levels should be measured instead of bacterial agglutination antibody.     

Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: a prospective study

AIM: To prospectively analyze the impact of increased intestinal permeability(IP) on mortality and the occurrence of infections in patients with cirrhosis.METHODS: IP was quantified using the lactulose/mannitol(L/M) test in 46 hospitalized patients with cirrhosis(25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPSbinding protein, Interleukin-6(IL-6)] and enterocyte death [intestinal fatty-acid binding protein(I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol test.RESULTS: Thirty-nine(85%) patients with cirrhosis had a pathologically increased IP index(L/M ratio 0.07) compared to 4(25%) healthy controls(P 0.0001). The IP index correlated with the ChildPugh score(r = 0.484, P = 0.001) and with serum IL-6(r = 0.342, P = 0.02). Within one year, nineteen(41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis(SBP)(n = 7) had a higher IP index than patients who did not(0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free survival.CONCLUSION: Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective cohort study.