Elimination of Viral Hepatitis in Low and Middle-Income Countries: Epidemiological Research Gaps

PURPOSE OF REVIEW: The purpose of our review was to summarize current recommendations on testing strategies, antiviral therapy eligibility and monitoring, and prevention of mother-to-child transmission of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and to highlight major research gaps in low and middle-income countries (LMIC), with a particular focus on sub-Saharan Africa (SSA). RECENT FINDINGS: While data on the prevalence of HBV and HCV infections in LMIC are increasing, current knowledge on liver-related complications as well as on treatment outcomes remains limited. Furthermore, very little information is available on the feasibility and cost-effectiveness of large-scale testing and management strategies in high-prevalence settings. The availability of policy-relevant data is particularly scarce in SSA, which accounts for a significant part of the global burden of chronic viral hepatitis. SUMMARY: Current recommendations on the management and monitoring of chronic viral hepatitis rely mainly on data from high-income settings. The global elimination of viral hepatitis will only be achieved if prevention, testing, and treatment strategies tailored to specific LMIC are implemented. In order to inform scalable and cost-effective interventions, dedicated research initiatives have to be undertaken. Future studies will have to include the evaluation of innovative testing strategies, the validation of simplified methods to diagnose liver cirrhosis and hepatocellular carcinoma, and the monitoring of long-term treatment outcomes and toxicity. In addition, national plans to achieve the elimination of HBV mother-to-child transmission are urgently needed, including effective ways to test pregnant women, treat those who are eligible, and ensure birth dose vaccination is given to all newborns

Multiplexed gene control reveals rapid mRNA turnover

The rates of mRNA synthesis and decay determine the mRNA expression level. The two processes are under coordinated control, which makes the measurements of these rates challenging, as evidenced by the low correlation among the methods of measurement of RNA half-lives. We developed a minimally invasive method, multiplexed gene control, to shut off expression of genes with controllable synthetic promoters. The method was validated by measuring the ratios of the nascent to mature mRNA molecules and by measuring the half-life with endogenous promoters that can be controlled naturally or through inserting short sequences that impart repressibility. The measured mRNA half-lives correlated highly with those obtained with the metabolic pulse-labeling method in yeast. However, mRNA degradation was considerably faster in comparison to previous estimates, with a median half-life of around 2 min. The half-life permits the estimation of promoter-dependent and promoter-independent transcription rates. The dynamical range of the promoter-independent transcription rates was larger than that of the mRNA half-lives. The rapid mRNA turnover and the broad adjustability of promoter-independent transcription rates are expected to have a major impact on stochastic gene expression and gene network behavior

Progressive signaling changes in the olfactory nerve of patients with Alzheimer’s disease

Olfaction declines with aging and appears to be a prodromal sign of cognitive decline in progressive neurodegenerative diseases. Nevertheless, very little is known about the pathophysiological changes underlying smell loss that may reflect early network dysfunction. A cross-sectional histoanatomical study was conducted on postmortem olfactory nerves of patients with increasing severity of dementia from mild cognitive impairment (MCI) to moderate and severe Alzheimer's disease. The olfactory bulbs and tracts show a prominent and progressive tauopathy in contrast to a weaker amyloid pathology localized to the glomerular region. Topological analysis of Notch signaling components reveals a transient increase in Jagged1 expression in mitral cells of the olfactory bulb of patients with MCI and a gradual decline onwards. Analysis of the olfactory tract reveals an abundance of corpora amylacea, which declines starting from the MCI stage. With the increasing severity of dementia, corpora amylacea are characterized by a gradual shift in cytoskeletal proteins, tau, MAP2 and glial fibrillary acid protein, as well as by a decrease in their Reelin and Jagged1 content. Our research indicates that the olfactory nerve undergoes early and sequential morphological and signaling alterations that correlate with the development of dementia suggesting that this structure may capture and propagate neuronal network imbalances to connected higher brain centers of the entorhinal cortex and hippocampus

Challenges in integrating cervical cancer screening in HIV care clinics in West Africa: a pilot study in Abidjan, Côte d’Ivoire

International audiencen.

Short-term risk of anaemia following initiation of combination antiretroviral treatment in HIV-infected patients in countries in sub-Saharan Africa, Asia-Pacific, and central and South America

BACKGROUND:The objective was to examine the short-term risk and predictors of anaemia following initiation of combination antiretroviral therapy (cART) in HIV-infected patients from the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) collaboration. METHODS: Anaemia was defined as haemoglobin of = 10 g/dL, and had one or more follow-up haemoglobin tests. Factors associated with anaemia up to 12 months were examined using Cox proportional hazards models and stratified by IeDEA region. RESULTS: Between 1998 and 2008, 19,947 patients initiated cART with baseline and follow-up haemoglobin tests (7358, 7289, 2853, 471, 1550 and 426 in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian-Pacific, and Caribbean and Central and South America regions, respectively). At initiation, anaemia was found in 45% of Western Africa patients, 29% of Eastern Africa patients, 21% of Southern Africa patients, 36% of Central Africa patients, 15% of patients in Asian-Pacific and 14% of patients in Caribbean and Central and South America. Among patients with haemoglobin of > = 10 g/dL at baseline (13,445), the risks of anaemia were 18.2, 6.6, 9.7, 22.9, 11.8 and 19.5 per 100 person-years in the Western Africa, Eastern Africa, Southern Africa, Central Africa, Asian, and Caribbean and Central and South America regions, respectively. Factors associated with anaemia were female sex, low baseline haemoglobin level, low baseline CD4 count, more advanced disease stage, and initial cART containing zidovudine. CONCLUSIONS: In data from 34 cohorts of HIV-infected patients from sub-Saharan Africa, Central and South America, and Asia, the risk of anaemia within 12 months of initiating cART was moderate. Routine haemoglobin monitoring was recommended in patients at risk of developing anaemia following cART initiation

Barriers and facilitators in cervical cancer screening uptake in Abidjan, Cote d'Ivoire in 2018: a cross-sectional study

BACKGROUNDS: Cervical cancer (CC) incidence remains unacceptably high in Côte d'Ivoire. In an effort to prevent this malignant condition, a national CC screening program has been scaled up in the country. This study aimed at assessing CC screening uptake and its associated factors in Abidjan in 2018. METHODS: A cross-sectional survey was conducted from July to September 2018 in the main healthcare facilities of three randomly selected out of the eight health districts of Abidjan. During the study period, a standardized questionnaire was administrated by research assistants to all women aged 25 to 55 years old, attending the three participating facilities. Demographics, knowledge on CC, personal history of CC screening and reasons for not attending CC screening were collected. A logistic regression model was computed to document factors associated with reported CC screening uptake. RESULTS: A total of 1158 women with a median age of 32 years (IQR [27-36]), including 364 (31.4%) with no formal education were included. Of those participants, 786 (67.9%) had ever heard about CC. CC screening uptake at least once was reported by 7.5% [95% CI: 6.0-9.0] participants. In multivariable analysis, being ≥45 years (aOR: 6.2 [2.3-17.2]), having a university level (aOR: 2.8 [1.2-6.6]) (versus non formal education) and access to mass campaign information (aOR: 18.2 [8.5-39.1]) were associated with a reported CC screening uptake. The main reported barriers to CC screening were unawareness towards CC screening (75.5%), negligence (20.5%), fear of CC detection (3.9%) and fear of additional costs (3.3%). CONCLUSION: CC screening uptake remains low despite current initiatives to support awareness and prevention in Abidjan. Awareness campaigns need to be massively increased with the adjunction of tailored messages based on the level of women's education to enhance the CC screening coverage and reach the WHO goal of CC elimination by 2030

Updating vital status by tracking in the community among patients with epidemic Kaposi sarcoma who are lost to follow-up in sub-Saharan Africa.

BACKGROUND: Throughout most of sub-Saharan Africa (and, indeed, most resource-limited areas), lack of death registries prohibits linkage of cancer diagnoses and precludes the most expeditious approach to determining cancer survival. Instead, estimation of cancer survival often uses clinical records, which have some mortality data but are replete with patients who are lost to follow-up (LTFU), some of which may be caused by undocumented death. The end result is that accurate estimation of cancer survival is rarely performed. A prominent example of a common cancer in Africa for which survival data are needed but for which frequent LTFU has precluded accurate estimation is Kaposi sarcoma (KS). METHODS: Using electronic records, we identified all newly diagnosed KS among HIV-infected adults at 33 primary care clinics in Kenya, Uganda, Nigeria, and Malawi from 2009 to 2012. We determined those patients who were apparently LTFU, defined as absent from clinic for ≥90 days at database closure and unknown to be dead or transferred. Using standardized protocols which included manual chart review, telephone calls, and physical tracking in the community, we attempted to update vital status amongst patients who were LTFU. RESULTS: We identified 1222 patients with KS, of whom 440 were LTFU according to electronic records. Manual chart review revealed that 18 (4.1%) were classified as LFTU due to clerical error, leaving 422 as truly LTFU. Of these 422, we updated vital status in 78%; manual chart review was responsible for updating in 5.7%, telephone calls in 26%, and physical tracking in 46%. Among 378 patients who consented at clinic enrollment to be tracked if they became LTFU and who had sufficient geographic contact/locator information, we updated vital status in 88%. Duration of LTFU was not associated with success of tracking, but tracking success was better in Kenya than the other sites. CONCLUSION: It is feasible to update vital status in a large fraction of patients with HIV-associated KS in sub-Saharan Africa who have become LTFU from clinical care. This finding likely applies to other cancers as well. Updating vital status amongst lost patients paves the way towards accurate determination of cancer survival

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

INTRODUCTION Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. RESULTS Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). CONCLUSIONS Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings

An Insight Into Cervical Cancer Screening and Treatment Capacity in Sub Saharan Africa.

OBJECTIVE Approximately 85% of cervical cancer cases and deaths occur in resource-constrained countries where best practices for prevention, particularly for women with HIV infection, still need to be developed. The aim of this study was to assess cervical cancer prevention capacity in select HIV clinics located in resource-constrained countries. MATERIALS AND METHODS A cross-sectional survey of sub-Saharan African sites of 4 National Institutes of Health-funded HIV/AIDS networks was conducted. Sites were surveyed on the availability of cervical cancer screening and treatment among women with HIV infection and without HIV infection. Descriptive statistics and χ or Fisher exact test were used as appropriate. RESULTS Fifty-one (65%) of 78 sites responded. Access to cervical cancer screening was reported by 49 sites (96%). Of these sites, 39 (80%) performed screening on-site. Central African sites were less likely to have screening on-site (p = .02) versus other areas. Visual inspection with acetic acid and Pap testing were the most commonly available on-site screening methods at 31 (79%) and 26 (67%) sites, respectively. High-risk HPV testing was available at 29% of sites with visual inspection with acetic acid and 50% of sites with Pap testing. Cryotherapy and radical hysterectomy were the most commonly available on-site treatment methods for premalignant and malignant lesions at 29 (74%) and 18 (46%) sites, respectively. CONCLUSIONS Despite limited resources, most sites surveyed had the capacity to perform cervical cancer screening and treatment. The existing infrastructure of HIV clinical and research sites may provide the ideal framework for scale-up of cervical cancer prevention in resource-constrained countries with a high burden of cervical dysplasia

BMJ Open

OBJECTIVES: The aim of this study was to estimate alcohol and tobacco use prevalence and their correlates among female sex workers (FSW), men who have sex with men (MSM) and drug users (DU) in Togo. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional bio-behavioural study was conducted among 2115 MSM, FSW and DU in 2017 using a respondent-driven sampling method, in the eight biggest towns of Togo. Selection criteria for the MSM were being male and having had oral or anal intercourse with a man in the previous 12 months; for FSW, being a female and having exchanged sex for money in the previous 12 months; and for DU, consuming heroin, cocaine or hashish for MSM, FSW and DU, respectively. All participants had to be at least 18 years old and residing in the territory for the past 3 months. RESULTS: The prevalence of alcohol consumption, hazardous/harmful consumption and binge drinking was 64.8%, 38.4% and 45.5%, respectively. Current tobacco use was reported by 30.6% of participants and HIV prevalence was estimated at 12.5%. DU were more likely to engage in binge drinking compared with other key populations (adjusted odds ratio (aOR)=2.0; 95% CI 1.4 to 2.8; p=0.001). Participants who were identified as having hazardous/harmful alcohol consumption had almost three times the odds of tobacco consumption than those with no risky consumption (aOR=2.6; 95% CI 2.0 to 3.4; p=0.001). Hazardous/harmful alcohol consumption was three times more likely among participants with severe psychological distress compared with those with no psychological distress (aOR=3.3, 95% CI 2.2 to 5.1; p=0.001). CONCLUSION: Findings from this study demonstrate the need for the integration of mental health and substance abuse reduction interventions into HIV prevention programme, particularly those geared towards key populations