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.

A new approach to prevent, diagnose, and treat hepatitis B in Africa.

There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB.

Early surgery determines prognosis in patients with infective endocarditis: outcome in patients managed by an Endocarditis Team-a prospective cohort study.

Background: Infective endocarditis (IE) in South Africa is associated with significant morbidity and mortality, despite occurring in younger patients with fewer co-morbidities. Possible contributors include the high rates of blood culture negative endocarditis, high rates of mechanical valve replacement and the lack of inter-disciplinary coordination during management. Methods: The Tygerberg Endocarditis Cohort (TEC) study prospectively enrolled patients with IE between November 2019 and April 2021. All patients were managed by an Endocarditis Team with a set protocol for organism detection and a strategy of early surgery limiting the use of prosthetic material. Results: Seventy-two consecutive patients with IE were included, with a causative organism identified in 86.1% of patients. The majority of patients had a guideline indication for surgery (n=58; 80.6%). The in-hospital mortality rate was 18%, with a 6-month mortality rate of 25.7%. Surgery was performed in 42 patients (58.3%), with prosthetic valve (PVE) replacement in 32 (76.2%), conventional repair surgery in 8 (19.1%) and mitral valve reconstruction in 2 (4.8%) of patients. Patients who underwent surgery had a significantly lower in-hospital (4.8% vs. 56.3%; P<0.01) and 6-month (4.9% vs. 75.0%; P<0.01) mortality rate as compared with patients with an indication for surgery who did not undergo surgery. Conclusions: We have observed a reduction in the 6-month mortality rate in patients with IE following the establishment of an Endocarditis Team, adhering to a set protocol for organism detection and favouring early repair or reconstruction surgery. Patients who underwent surgery had a significantly lower mortality rate than patients with an indication for surgery who did not undergo surgery. Preventable residual mortality was driven by surgical delay.

Bartonella species as a cause of culture-negative endocarditis in South Africa.

Previous reports have highlighted the high prevalence of blood culture negative endocarditis (BCNE) in South Africa. The Tygerberg Endocarditis Cohort (TEC) study is an ongoing prospective cohort study of patients with confirmed or suspected IE presenting to Tygerberg Academic Hospital, Cape Town, South Africa. Current analysis includes patients that presented between November 2019 and August 2020. Forty four (44) patients have been included in this ongoing study. Fourteen of the 44 patients (31.8%) had BCNE. Further analysis of the patients with BCNE identified Bartonella species as the most common causative organism (n=6; 43%). Other causes included Mycoplasma species (n=2). No cause could be identified in 4 of the 44 patients (9%). Bartonella quintana was identified with PCR of valvular tissue as the causative organism in 4 of the 5 patients that underwent urgent surgery. The patients with Bartonella IE (n=6) had an average age of 39 years with equal gender distribution. The common clinical features were clubbing (n=5; 83%), anemia (n=4; 66.6%), haematuria (n=3; 50%), acute on chronic severe regurgitant lesion (n=3; 50%) and acute severe regurgitant lesion (n=2; 33.3%).The aortic valve was involved in 5 of 6 patients. During a mean follow-up period of 251 days after diagnosis, no major adverse events occurred. Bartonella-associated IE is an important cause of BCNE in the Western Cape of South Africa. Imaging findings (in patients with BCNE) of significant valvular destruction with large vegetations on the aortic valve not affected by congenital or rheumatic valve disease should raise the suspicion of Bartonella-associated IE.

Treatment advantage in HBV/HIV coinfection compared to HBV monoinfection in a South African cohort.

OBJECTIVES: Prompted by international targets for elimination of hepatitis B virus (HBV), we set out to characterise individuals with HBV monoinfection vs. those coinfected with HBV/HIV, to evaluate the impact of therapy and to guide improvements in clinical care. METHODS: We report observational data from a real world cross-sectional cohort of 115 adults with chronic hepatitis B infection (CHB), at a university hospital in Cape Town, South Africa. HIV coinfection was present in 39 (34%) subjects. We recorded cross-sectional demographic, clinical and laboratory data. RESULTS: Compared to those with HIV coinfection, HBV monoinfected adults were less likely to be HBeAg-positive (p=0.01), less likely to have had assessment with elastography (p<0.0001), and less likely to be on antiviral treatment (p<0.0001); they were more likely to have detectable HBV viraemia (p=0.04), and more likely to have features of liver disease including moderate/severe thrombocytopaenia (p=0.007), elevated bilirubin (p=0.004), and elevated APRI score (p=0.02). Three cases of hepatocellular carcinoma all arose in HBV monoinfection. CONCLUSIONS: Our data demonstrate that individuals with HBV monoinfection may be disadvantaged compared to those with HIV coinfection, highlighting potential systematic inequities in referral, monitoring and treatment.

HBV and HIV viral load but not microbial translocation or immune activation are associated with liver fibrosis among patients in South Africa.

BACKGROUND: Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection. METHODS: We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa. All HIV-infected patients were on antiretroviral therapy for ≥3 months. Liver stiffness measurements were assessed using the Fibroscan (Fibroscan 402, Echosens). Cell-based immunomarkers were measured by flow cytometry. Soluble serum/plasma immunomarkers were measured by Luminex technology and enzyme immunoassays. HIV (COBAS/Ampliprep TaqMan HIV-1) and HBV viral loads (in-house assay) were also performed. RESULTS: HBV/HIV co-infected patients showed significantly higher levels of immune activation %CD8+/HLA-DR+/CD38+ (median 30%, interquartile range: 17-53) and %CD8+/PD-1 (median 22%, interquartile range: 15-33), p ≤ 0.01 compared to all other study groups. Despite this, the HBV-mono-infected group had the highest proportion of patients with advanced liver fibrosis (≥13 kPa) as measured by Fibroscan (18%). HBV mono-infected patients showed highest expression of most cytokines including IL-17 and basic fibroblastic growth factor. There was significant positive correlation between detectable HIV and HBV viral replication and liver fibrosis but not immune activation or gut translocation. DISCUSSION: Highly-active antiretroviral therapy, including tenofovir, is effective against both HIV and HBV. Earlier therapy in the co-infected patients may therefore have controlled viral replication leading to better fibrosis scores when compared to HBV mono-infection in this study. On-going HBV and HIV viraemia, rather than microbial translocation or immune activation, appear to be the drivers of liver fibrosis. Moderate to advanced liver fibrosis in HBV-mono-infection may well indicate poor access to screening and treatment of HBV infection.

AIDS-Related Endemic Mycoses in Western Cape, South Africa, and Clinical Mimics: A Cross-Sectional Study of Adults With Advanced HIV and Recent-Onset, Widespread Skin Lesions.

BACKGROUND: Skin lesions are common in advanced HIV infection and are sometimes caused by serious diseases like systemic mycoses (SM). AIDS-related SM endemic to Western Cape, South Africa, include emergomycosis (formerly disseminated emmonsiosis), histoplasmosis, and sporotrichosis. We previously reported that 95% of patients with AIDS-related emergomycosis had skin lesions, although these were frequently overlooked or misdiagnosed clinically. Prospective studies are needed to characterize skin lesions of SM in South Africa and to help distinguish these from common HIV-related dermatoses. METHODS: We prospectively enrolled HIV-infected adult patients living in Western Cape, South Africa, with CD4 counts ≤100 cells/µL and widespread skin lesions present ≤6 months that were deemed clinically compatible with SM. We obtained skin biopsies for histopathology and fungal culture and collected epidemiological and clinical data. RESULTS: Of 34 patients enrolled and in whom a diagnosis could be made, 25 had proven SM: 14 had emergomycosis, and 3 each had histoplasmosis and sporotrichosis; for 5 additional patients, the fungal species could not be identified. Antiretroviral therapy (ART) had been initiated in the preceding 4 weeks for 11/25 (44%) patients with SM (vs no patients without SM). Plaques and scale crust occurred more frequently in patients with SM (96% vs 25%, P = .0002; and 67% vs 13%, P = .01, respectively). CONCLUSIONS: Recent ART initiation and presence of plaques or scale crust should make clinicians consider SM in patients with advanced HIV infection in this geographic area. Clinical overlap between SM and other dermatoses makes early skin biopsy critical for timely diagnosis and treatment.

Clinical Characteristics, Diagnosis, Management, and Outcomes of Disseminated Emmonsiosis: A Retrospective Case Series.

BACKGROUND: We describe the geographic distribution, clinical characteristics, and management of patients with disease caused by Emmonsia sp., a novel dimorphic fungal pathogen recently described in South Africa. METHODS: We performed a multicenter, retrospective chart review of laboratory-confirmed cases of emmonsiosis diagnosed across South Africa from January 2008 through February 2015. RESULTS: Fifty-four patients were diagnosed in 5/9 provinces. Fifty-one patients (94%) were human immunodeficiency virus coinfected (median CD4 count 16 cells/µL [interquartile range, 6-40]). In 12 (24%) of these, antiretroviral therapy had been initiated in the preceding 2 months. All patients had disseminated disease, most commonly involving skin (n = 50/52, 96%) and lung (n = 42/48, 88%). Yeasts were visualized on histopathologic examination of skin (n = 34/37), respiratory tissue (n = 2/4), brain (n = 1/1), liver (n = 1/2), and bone marrow (n = 1/15). Emmonsia sp. was cultured from skin biopsy (n = 20/28), mycobacterial/fungal and aerobic blood culture (n = 15/25 and n = 9/37, respectively), bone marrow (n = 12/14), lung (n = 1/1), lymph node (n = 1/1), and brain (n = 1/1). Twenty-four of 34 patients (71%) treated with amphotericin B deoxycholate, 4/12 (33%) treated with a triazole alone, and none of 8 (0%) who received no antifungals survived. Twenty-six patients (48%) died, half undiagnosed. CONCLUSIONS: Disseminated emmonsiosis is more widespread in South Africa and carries a higher case fatality rate than previously appreciated. Cutaneous involvement is near universal, and skin biopsy can be used to diagnose the majority of patients.

Electronic decision protocols for ART patient triaging to expand access to HIV treatment in South Africa: a cross sectional study for development and validation.

BACKGROUND: The shortage of doctors and nurses, along with future expansion into rural clinics, will require that the majority of clinic visits by HIV infected patients on antiretroviral therapy (ART) are managed by non-doctors. The goal of this study was to develop and evaluate a screening protocol to determine which patients needed a full clinical assessment and which patients were stable enough to receive their medications without a doctor's consultation. For this study, we developed an electronic, handheld tool to guide non-physician counselors through screening questions. METHODS: Patients visiting two ART clinics in South Africa for routine follow-up visits between March 2007 and April 2008 were included in our study. Each patient was screened by non-physician counselors using the handheld device and then received a full clinical assessment. Clinicians' report on whether full clinical assessment had been necessary was used as the gold standard for determining "required referral". Observations were randomly divided into two datasets--989 for developing a referral protocol and 200 for validating protocol performance. RESULTS: A third of patients had at least one physical complaint, and 16% had five or more physical complaints. 38% of patients required referral for full clinical assessment. We identify a subset of questions which are 87% sensitive and 47% specific for recommended patient referral. CONCLUSIONS: The final screening protocol is highly sensitive and could reduce burden on ART clinicians by 30%. The uptake and acceptance of the handheld tool to support implementation of the protocol was high. Further examination of the data reveals several important questions to include in future referral algorithms to improve sensitivity and specificity. Based on these results, we identify a refined algorithm to explore in future evaluations.