A cost analysis of a simplified model for HCV screening and treatment at a tertiary hospital in Zimbabwe.

BACKGROUND: The treatment of chronic hepatitis C virus (HCV) infection using directly acting antivirals was recently adopted in the treatment guidelines of Zimbabwe. The objectives of this study were to design a simplified model of HCV care and estimate the cost of screening and treatment of hepatitis C infection at a tertiary hospital in Zimbabwe. METHODS: We developed a model of care for HCV using WHO 2018 guidelines for the treatment of HCV infection and expert opinion. We then performed a micro-costing to estimate the costs of implementing the model of care from the healthcare sector perspective. Deterministic and probabilistic sensitivity analyses were performed to explore the impact of uncertainty in input parameters on the estimated total cost of care. RESULTS: The total cost of screening and treatment was estimated to be US$2448 (SD=$290) per patient over a 12-week treatment duration using sofosbuvir/velpatasvir. The cost of directly acting antivirals contributed 57.5% to the total cost of care. The second largest cost driver was the cost of diagnosis, US$819, contributing 34.6% to the total cost of care. CONCLUSION: Screening and treatment of HCV-infected individuals using directly acting antivirals at a tertiary hospital in Zimbabwe may require substantial financial resources.

Clinical characteristics and outcomes of patients admitted with COVID-19 at a public-sector hospital over the first two waves of SARS-CoV-2 infection in Harare, Zimbabwe: A prospective cohort study.

BACKGROUND: We investigated the clinical profile, complications, and outcomes of inpatients with COVID-19 at Parirenyatwa Hospital, Harare, across the first two waves of SARS-CoV-2 infection, and factors associated with mortality. METHODS: We conducted a prospective cohort study on all patients admitted to the COVID-19 unit. Data were extracted from medical records and negative binomial regression with robust standard errors was used to assess the association between sociodemographic and clinical characteristics and mortality. Cox Regression was used for sensitivity analysis. RESULTS: Of 563 people admitted with COVID-19 between 2 July 2020 and 19 March 2021, 214 (38.0%) died, 340 were discharged and 9 transferred. The median age was 56 (IQR 44-68) years and 53.8% were male. Overall, 38.8% experienced a complication, the most common being acute kidney injury (17.9%) and hyperglycaemia (13.1%). The most common comorbidity was hypertension (41.3%) followed by diabetes (28.6%), HIV (12.1%), cardiovascular disease (10.9%) and chronic kidney disease (7.8%). Among participants who stayed in the ward for more than 1 night, mortality was higher in patients with comorbidity compared to those without any comorbidity (38.7% vs 25.5%, risk ratio (RR) = 1.52 (95% CI 1.11, 2.07), p = 0.008). After adjusting for oxygen saturation, comorbidities, sex and pregnancy, mortality was higher in the second wave than in the first (adjusted RR 1.23, 95% CI 1.00-1.51, p = 0.05). In the second wave 57/161 (35.4%) deaths were attributed to lack of resources, mainly human resources. CONCLUSION: The mortality rate was high and clinical COVID-19 care needs to pay careful attention to patient monitoring for complications and management of comorbidities. This will require addressing the critical health workforce shortage issues. Prevention of COVID-19 including vaccination particularly among individuals with comorbidities remains a high priority.

Managing cirrhosis with limited resources: perspectives from sub-Saharan Africa.

Cirrhosis represents the end stage of chronic liver disease. Sub-Saharan Africa, a resource-constrained region, has a high burden of chronic liver disease, with causes including chronic viral hepatitis, excessive alcohol use, and metabolic dysfunction-associated steatotic liver disease (MASLD), the risk of which is burgeoning. The development of liver cirrhosis predicts for morbidity and mortality, driven by both liver dysfunction and the consequences of portal hypertension. Compensated cirrhosis portends a better prognosis than decompensated cirrhosis, highlighting the need for the early diagnosis of cirrhosis and its causes. With resource challenges, the diagnosis and management of cirrhosis is demanding, but less costly and less invasive interventions with substantial benefits, ranging from simple blood tests to transient elastography, are feasible in such settings. Simple interventions are also available to manage the complex manifestations of decompensation, such as ß blockers in variceal bleeding prophylaxis, salt restriction and appropriate diuretic use in ascites, and lactulose and generic rifaximin in hepatic encephalopathy. Ultimately, managing the underlying causative factors of liver disease is key in improving prognosis. Management demands expanded policy interventions to increase screening and treatment for hepatitis B and C and reduce alcohol use and the metabolic factors driving MASLD. Furthermore, the skills needed for more specialised interventions, such as transjugular intrahepatic portosystemic shunt procedures and even liver transplantation, warrant planning, increased capacity, and support for regional centres of excellence. Such centres are already being developed in sub-Saharan Africa, demonstrating what can be achieved with dedicated initiatives and individuals.

Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance.

Introduction: Combination antiretroviral therapy (cART) effectively controls HIV; however, chronic low-level viremia and gut microbiota dysbiosis remain significant drivers of gut and systemic inflammation. In this study, we explored the relationship between gut microbiota composition, intestinal inflammation, microbial translocation, and systemic inflammation in women on cART in Sub-Saharan Africa. Methods: We conducted a study in HIV-infected and HIV-uninfected lactating women followed up at 6 weeks and 6 months postpartum in Harare, Zimbabwe. We used 16S ribosomal Ribonucleic Acid (rRNA) sequencing and MesoScale Discovery V-Plex assays to examine the gut microbiome and to quantify plasma inflammatory biomarkers, respectively. In addition, we measured fecal calprotectin, plasma lipopolysaccharide-binding protein (LBP), and soluble cluster of differentiation 14 (sCD14) by enzyme-linked immunosorbent assay to assess gut inflammation, microbial translocation, and monocyte/macrophage activation. Results: A group of 77 lactating women were studied, of which 35% were HIV-infected. Fecal calprotectin levels were similar by HIV status at both follow-up time points. In the HIV-infected group at 6 weeks postpartum, fecal calprotectin was elevated: median (interquartile range) [158.1 µg/g (75.3-230.2)] in women who had CD4+ T-lymphocyte counts <350 cells/µL compared with those with ≥350 cells/µL [21.1 µg/g (0-58.4)], p = 0.032. Plasma sCD14 levels were significantly higher in the HIV-infected group at both 6 weeks and 6 months postpartum, p < 0.001. Plasma LBP levels were similar, but higher levels were observed in HIV-infected women with elevated fecal calprotectin. We found significant correlations between fecal calprotectin, LBP, and sCD14 with proinflammatory cytokines. Gut microbial alpha diversity was not affected by HIV status and was not affected by use of antibiotic prophylaxis. HIV significantly affected microbial beta diversity, and significant differences in microbial composition were noted. The genera Slackia and Collinsella were relatively more abundant in the HIV-infected group, whereas a lower relative abundance of Clostriduim sensu_stricto_1 was observed. Our study also found correlations between gut microbial taxa abundance and systemic inflammatory biomarkers. Discussion and conclusion: HIV-infected lactating women had increased immune activation and increased microbial translocation associated with increased gut inflammation. We identified correlations between the gut inflammation and microbial composition, microbial translocation, and systemic inflammation. The interplay of these parameters might affect the health of this vulnerable population.

Challenges in the diagnosis and management of IBD: a sub-Saharan African perspective.

With the exception of South Africa, inflammatory bowel disease (IBD) has long been considered uncommon in sub-Saharan Africa (SSA) with a dearth of peer-reviewed publications from the subcontinent. This most likely reflects underreporting as some cases may be missed due to the high burden of infectious diseases which may closely mimic IBD. In addition, many countries in SSA have limited endoscopic capacity, inadequate access to diagnostic imaging and a notable scarcity of histopathologists, radiologists and gastroenterologists. Beyond these obstacles, which significantly impact patient care, there are many other challenges in SSA, particularly the unavailability of key IBD therapies. In this review, we discuss barriers in diagnosing and managing IBD in SSA, as well as some of the initiatives currently in place to address these short comings.

Immunogenicity and Safety of Hepatitis B Virus (HBV) Vaccine With a Toll-Like Receptor 9 Agonist Adjuvant in HBV Vaccine-Naïve People With Human Immunodeficiency Virus.

In this international, multicenter open-label study (ACTG A5379) of HepB-CpG vaccine in people with human immunodeficiency virus (HIV) without prior hepatitis B virus (HBV) vaccination, all 68 participants achieved HBV seroprotective titers after the 3-dose series in the primary analysis. No unexpected safety issues were observed.

Investigating point-of-care diagnostics for sexually transmitted infections and antimicrobial resistance in antenatal care in Zimbabwe (IPSAZ): protocol for a mixed-methods study.

INTRODUCTION: Sexually transmitted infections (STIs) can cause serious morbidity, including pelvic inflammatory disease, and adverse pregnancy outcomes. In low/middle-income countries, limited laboratory infrastructure has resulted in a syndrome-based approach being used for management of STIs, which has poor sensitivity and specificity, leading to considerable underdiagnosis and overtreatment. The WHO has called for development and evaluation of strategies to inform replacement of syndromic management by diagnostic testing.The aim of this project is to evaluate a strategy of point-of-care testing for six STIs in antenatal care (ANC) in Zimbabwe. METHODS AND ANALYSIS: A prospective interventional study will be conducted in ANC clinics in Harare province, Zimbabwe. One thousand pregnant women will be recruited when registering for routine ANC. Alongside routine HIV and syphilis testing, participants will be offered an integrated screening package including testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and hepatitis B. All individuals with STIs will receive treatment, partner notification services, risk reduction counselling and referral if needed according to national guidelines. Gonorrhoea samples will be cultured and tested for antimicrobial resistance as per WHO enhanced gonococcal antimicrobial surveillance programme guidelines.The primary outcome measure is the composite prevalence of CT, NG, TV, syphilis and hepatitis B. A mixed-methods process evaluation and economic evaluation will be conducted to understand the acceptability, feasibility and cost-effectiveness of integrated STI testing, compared with standard of care (syndromic management). ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Research Council of Zimbabwe, the Biomedical Research and Training Institute Institutional Review Board, and the London School of Hygiene & Tropical Medicine Research Ethics Committee. Results will be submitted to open-access peer-reviewed journals, presented at academic meetings and shared with participating communities and with national and international policymaking bodies. TRIAL REGISTRATION NUMBER: NCT05541081.

Inflammatory bowel disease in sub-Saharan Africa: epidemiology, risk factors, and challenges in diagnosis.

Over the past century, the incidence of inflammatory bowel disease (IBD) in high-income countries has shown a sharp rise that then plateaued, and a similar trend has been observed in newly industrialised countries. IBD has long been considered uncommon in sub-Saharan Africa, possibly reflecting low exposure to environmental risk factors described in high-income populations. Alternatively, individuals living in sub-Saharan Africa might have a different genetic disposition. However, some cases of IBD might remain undetected in sub-Saharan Africa because of a lack of awareness, deficiencies in diagnostic and clinical capacity, and a substantial rate of misdiagnosis due to the high burden of infectious diseases. There are few published data describing the natural history of IBD in sub-Saharan Africa, and the true burden of the disease remains largely unknown, although there is some evidence that the incidence of IBD is rising in this region. This Series paper summarises the present understanding of IBD and challenges facing clinicians when diagnosing this disease in sub-Saharan Africa.

Challenges in the management of inflammatory bowel disease in sub-Saharan Africa.

Inflammatory bowel disease (IBD) is generally considered a disease of high-income countries and is regarded as rare in sub-Saharan Africa. However, this assumption is almost certainly an underestimate, and the high burden of communicable diseases makes IBD in sub-Saharan Africa difficult to detect. Furthermore, some gastrointestinal infections can closely mimic IBD, contributing to delays in diagnosis and complicating therapeutic decision making. Constraints in endoscopic capacity alongside a scarcity of qualified diagnostic pathologists add to the difficulties. Implementing evidence-based guidelines recommended by international societies is challenging, mostly due to high costs and unavailability of medication. However, cost-effective approaches can still be implemented to manage IBD in sub-Saharan Africa as the predominant disease phenotype is mild-to-moderate ulcerative colitis, which often responds to treatment with basic medication. In this Series paper, we summarise the current management of IBD in sub-Saharan Africa and propose how it can be tailored to suit the epidemiological and socioeconomic specificities of the region. We also discuss measures required to address existing challenges, such as educating health-care workers about the diagnosis and management of IBD or improving endoscopic capacity.

Hepatocellular carcinoma: measures to improve the outlook in sub-Saharan Africa.

Hepatocellular carcinoma is a leading public health concern in sub-Saharan Africa, and it is most prevalent in young adults (median 45 years [IQR 35-57]). Overall, outcomes are poor, with a median survival of 2·5 months after presentation. Major risk factors for hepatocellular carcinoma are hepatitis B virus (HBV), hepatitis C virus, aflatoxin B1 exposure, and alcohol consumption, with metabolic dysfunction-associated fatty liver disease slowly emerging as a risk factor over the past few years. Crucially, these risk factors are preventable and manageable with effective implementation of the HBV birth-dose vaccination, treatment of chronic viral hepatitis, provision of harm reduction services, and by decreasing aflatoxin B1 exposure and harmful alcohol consumption. Primary prevention is central to the management of hepatocellular carcinoma, especially in poorly resourced environments. Effective screening and surveillance programmes with recall policies need to be implemented, because detection and curative management of hepatocellular carcinoma is possible if it is detected at an early stage, even in countries with minimal resources, with appropriate upskilling of medical personnel. The establishment of centres of excellence with advanced diagnostic and therapeutic capabilities within countries should improve hepatocellular carcinoma outcomes and assist in driving the implementation of much needed systematic data systems focused on hepatocellular carcinoma to establish the accurate burden in sub-Saharan Africa. Such data would support the public health importance of hepatocellular carcinoma and provide a strong basis for advocacy, programme development, resource allocation, and monitoring of progress in reducing mortality.

Interactions between the environmental and human microbiota in the preservation of health and genesis of disease: symposium report.

PURPOSE OF REVIEW: The purpose of this symposium was to bring thought leaders in the microbiome from the west to Africa to share their unique experiences with African investigators in order to build the foundations for scientifically rigorous explorations into the African human and environmental microbiome that may explain why disease patterns are different in Africa where the chief killers are infectious diseases, whereas noncommunicable diseases (NCDs) are the major threat to healthcare resources in the developed world. RECENT FINDINGS: The application of new high throughput technologies to the investigation of the microbiome and its metabolome has revealed mechanisms whereby a traditional African high fiber diet can suppress NCDs which include colon cancer, inflammatory bowel diseases, obesity, type 2 diabetes and atherosclosis. There is concern that with migration and westernization, NCDs are becoming more common in Africa and that food security is becoming impaired by unbalanced obesogenic foods rather than inadequate food intake. SUMMARY: There is an urgent need for the formation of combined African-Western research programs to identify what is good and bad in the African diet-microbiome axis to develop strategies to prevent the incidence of NCDs rising to western levels in Africa, at the same time offering novel prevention strategies against the #1 healthcare threat in the developed world.

Epidemiology, risk factors, social determinants of health, and current management for non-alcoholic fatty liver disease in sub-Saharan Africa.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and is estimated to affect approximately 25% of the world's population. Data about the prevalence and incidence of NAFLD in Africa are scarce, but the prevalence is estimated to be 13·5% for the general population. This is likely to be an underestimate considering the increasing burden of non-communicable diseases, particularly the rising prevalence of obesity and type 2 diabetes, driven by the overlapping challenges of food insecurity, nutritional transition, and associated increased consumption of calorie-dense foods. Establishing the true prevalence of NAFLD, raising public awareness around the risk factors behind the increase in NAFLD, and proactively addressing all components of metabolic syndrome will be important to combat this silent epidemic, which will have long-term health-care costs and economic consequences for the region.

Progress on the elimination of viral hepatitis in Zimbabwe: A review of the policies, strategies and challenges.

Very few low-income countries have developed national plans to achieve the viral hepatitis elimination targets set in the World Health Organization (WHO) strategy. We reviewed the policy environment, strategies and challenges on the fight against viral hepatitis in Zimbabwe. The review focussed on the Ministry of Health and Child Care (MoHCC) policy documents, strategic plans and reports. We performed key informant interviews to enhance evidence generated from the document review. Twelve documents were reviewed and interviews with 10 key informants were completed. The MoHCC established a technical working group to work towards elimination of viral hepatitis. The technical working group drafted a strategic plan for elimination of viral hepatitis; however, it is still awaiting implementation. Key strategies that are working well include screening of donated blood for transfusion, safe injection practices and hepatitis B virus (HBV) three-dose vaccination. Current challenges in the drive towards elimination of viral hepatitis include poor to non-existent surveillance systems, lack of epidemiological data, absence of the HBV vaccine birth dose and lack of systematic screening and treatment services for viral hepatitis. In conclusion, despite political will demonstrated towards achieving viral hepatitis elimination, substantial investment and work are required to implement the strategic plan and realize significant success.

Inflammatory bowel disease in sub-Saharan Africa: a protocol of a prospective registry with a nested case-control study.

INTRODUCTION: The epidemiology of inflammatory bowel disease (IBD) in sub-Saharan Africa is poorly documented. We have started a registry to determine the burden, phenotype, risk factors, disease course and outcomes of IBD in Zimbabwe. METHODS AND ANALYSIS: A prospective observational registry with a nested case-control study has been established at a tertiary hospital in Harare, Zimbabwe. The registry is recruiting confirmed IBD cases from the hospital, and other facilities throughout Zimbabwe. Demographic and clinical data are obtained at baseline, 6 months and annually. Two age and sex-matched non-IBD controls per case are recruited-a sibling or second-degree relative, and a randomly selected individual from the same neighbourhood. Cases and controls are interviewed for potential risk factors of IBD, and dietary intake using a food frequency questionnaire. Stool is collected for 16S rRNA-based microbiota profiling, and along with germline DNA from peripheral blood, is being biobanked. The estimated sample size is 86 cases and 172 controls, and the overall registry is anticipated to run for at least 5 years. Descriptive statistics will be used to describe the demographic and phenotypic characteristics of IBD, and incidence and prevalence will be estimated for Harare. Risk factors for IBD will be analysed using conditional logistic regression. For microbial analysis, alpha diversity and beta diversity will be compared between cases and controls, and between IBD phenotypes. Mann-Whitney U tests for alpha diversity and Adonis (Permutational Multivariate Analysis of Variance) for beta diversity will be computed. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Parirenyatwa Hospital's and University of Zimbabwe's research ethics committee and the Medical Research Council of Zimbabwe. Findings will be discussed with patients, and the Zimbabwean Ministry of Health. Results will be presented at scientific meetings, published in peer reviewed journals, and on social media. TRIAL REGISTRATION NUMBER: NCT04178408.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Epidemic in Zimbabwe: Quo Vadis?

The trajectory and impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in sub-Saharan Africa are unclear, but they are seemingly varied between different countries, with most reporting low numbers. We use the situation in Zimbabwe to build an argument that the epidemic is likely to be attenuated in some countries with similar socioeconomic and cultural structures. However, even an attenuated epidemic may overwhelm weak health systems, emphasizing the importance of prevention. These prevention strategies should be tailored to the unique social and cultural networks of individual countries, which may facilitate the spread of SARS-CoV-2. It is also equally important to maintain services for the major infectious diseases in the region, such as tuberculosis and malaria. A breakdown of treatment and prevention services for these conditions may even overshadow the projected morbidity and mortality from coronavirus disease 2019 (COVID-19).

Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases.

BACKGROUND: Approximately 25% of colorectal cancer patients in sub-Saharan Africa are younger than 40 years, and hereditary factors may contribute. We investigated the frequency and patterns of inherited colorectal cancer among black Zimbabweans. METHODS: A population-based cross-sectional study of ninety individuals with a new diagnosis of colorectal cancer was carried out in Harare, Zimbabwe between November 2012 and December 2015. Phenotypic data was obtained using interviewer administered questionnaires, and reviewing clinical and pathology data. Cases were screened for mismatch repair deficiency by immunohistochemistry and/or microsatellite instability testing, and for MLH1, MSH2 and EPCAM deletions using multiplex ligation-dependent probe amplification. Next generation sequencing using a 16-gene panel was performed for cases with phenotypic features consistent with familial colorectal cancer. Variants were assessed for pathogenicity using the mean allele frequency, phenotypic features and searching online databases. RESULTS: Three Lynch syndrome cases were identified: MSH2 c.2634G>A pathogenic mutation, c.(1896+1_1897-1)_(*193_?)del , and one fulfilling the Amsterdam criteria, with MLH1 and PMS2 deficiency, but no identifiable pathogenic mutation. Two other cases had a strong family history of cancers, but the exact syndrome was not identified. The prevalence of Lynch syndrome was 3·3% (95% CI 0·7-9·4), and that of familial colorectal cancer was 5·6% (95% CI, 1·8-12·5). CONCLUSIONS: Identifying cases of inherited colorectal cancer in sub-Saharan Africa is feasible, and our findings can inform screening guidelines appropriate to this setting.

A case-control study of risk factors for colorectal cancer in an African population.

The interplay between hereditary and environmental factors in the causation of colorectal cancer in sub-Saharan Africa is poorly understood. We carried out a community based case-control study to identify the risk factors associated with colorectal cancer in Zimbabwe. We recruited 101 cases of colorectal cancer and 202 controls, matched for age, sex and domicile. Potential risk factors including family history, socioeconomic status, urbanization, diabetes mellitus and previous schistosomiasis were evaluated. Conditional logistic regression was used to estimate the odds ratios associated with the different factors. Cases were more likely to have a tertiary education (32.7 vs. 13.4%, P<0.001) and a higher income (18.8 vs. 6.9%, P=0.002). After multivariate analysis, diabetes mellitus [odds ratio (OR): 5.3; 95% confidence interval (CI): 1.4-19.9; P=0.012], previous urban domicile (OR: 2.8; 95% CI: 1.0-7.8; P=0.042), previous schistosomiasis (OR: 2.4; 95% CI: 1.4-4.2; P=0.001) and cancer in a first-degree relative (OR: 2.4; 95% CI: 1.2-4.8; P=0.018) were associated independently with colorectal cancer. Our findings suggest that family history, diabetes mellitus, previous schistosomiasis and approximation to a western lifestyle are the predominant associations with colorectal cancer in Africans. This offers opportunities for targeted prevention and hypothesis-driven research into the aetiology of colorectal cancer in this population.

Dietary patterns and colorectal cancer risk in Zimbabwe: A population based case-control study.

BACKGROUND: The rising incidence of colorectal cancer in sub-Saharan Africa may be partly caused by changing dietary patterns. We sought to establish the association between dietary patterns and colorectal cancer in Zimbabwe. METHODS: One hundred colorectal cancer cases and 200 community-based controls were recruited. Data were collected using a food frequency questionnaire, and dietary patterns derived by principal component analysis. Generalised linear and logistic regression models were used to assess the associations between dietary patterns, participant characteristics and colorectal cancer. RESULTS: Three main dietary patterns were identified: traditional African, urbanised and processed food. The traditional African diet appeared protective against colorectal cancer (Odds Ratio (OR) 0.35; 95% Confidence Interval (CI), 0.21 - 0.58), which had no association with the urban (OR 0.68; 95% CI, 0.43-1.08), or processed food (OR 0.91; 0.58-1.41) patterns. The traditional African diet was associated with rural domicile, (OR 1.26; 95% CI, 1.00-1.59), and a low income (OR1.48; 95% CI, 1.06-2.08). The urbanised diet was associated with urban domicile (OR 1.70; 95% CI, 1.38-2.10), secondary (OR 1.30; 95% CI, 1.07-1.59) or tertiary education (OR 1.48; 95% CI, 1.11-1.97), and monthly incomes of $201-500 (OR 1.30; 95% CI, 1.05-1.62), and the processed food pattern with tertiary education (OR 1.42; 95% CI, 1.05-1.92), and income >$1000/month (OR 1.48; 95% CI, 1.02-2.15). CONCLUSION: A shift away from protective, traditional African dietary patterns may partly explain the rising incidence of colorectal cancer in sub-Saharan Africa.