Establishment of clinical pharmacy services: evidence-based information from stakeholders.

High morbidity and mortality related to the use of drugs resulted in demand for clinical pharmacy services (CPS) globally. In developed countries, the evolution of pharmacists' role in direct patient care started in the 1960s. The participation of pharmacists in CPS has resulted in positive clinical, economic, and humanistic outcomes. In developing countries, efforts have started to ensure pharmacists are engaged in the provision of CPS. However, the efforts are hampered by poorly defined pharmacist career paths, financial constraints, and a lack of political willingness. In Tanzania, efforts started in 2008, in which CPS was introduced into the Bachelor of Pharmacy curriculum, followed by the initiation of a postgraduate program on hospital and clinical pharmacy in 2013. A regulation was released by the Tanzania Ministry of Health in 2020 to enforce pharmacists' engagement in providing CPS. In 2021, a project was launched in the country, aiming to strengthen the provision of CPS in public and faith-based hospitals by training on-job pharmacists. The project was implemented in phases, including stakeholders' engagement, baseline survey, training, and supportive supervision of the trained pharmacists. Therefore, this commentary aims to share what we experienced during project implementation, the achievements, challenges, and key lessons learned.

Barriers and facilitators of integration of pharmacists in the provision of clinical pharmacy services in Tanzania.

BACKGROUND: Collaboration between medical doctors and nurses in the provision of healthcare services has been there for decades. The concept of clinical pharmacy services as a main goal for pharmacy practice is relatively new and is yielding more positive results for healthcare providers (HCPs), patients, and the health system. This study assessed barriers and facilitators toward the integration of pharmacists in the provision of CPS in Tanzania. METHODS: A qualitative study was conducted in five tertiary hospitals representing Tanzania mainland. Ten (10) focus group discussions (FGDs) with 83 HCPs and 14 in-depth interviews (IDIs) with hospital administrators in referral hospitals were conducted between August and September 2021. The experienced qualitative researchers moderated the IDIs and FGDs, and all discussions were audio-recorded. Finally, the audios were transcribed verbatim, and analysis was done using a thematic approach. RESULTS: Limited skills, lack of confidence, poor communication, inferiority, and superiority behaviors among HCPs were among the mentioned barriers. Shortage of pharmacists, lack of in-job training, standard operating procedures (SOPs), and guidelines were also mentioned. The study noted the high acceptability of CPS by other HCPs, the positive perception of pharmacists, and the recognition of CPS by the Tanzania Pharmacy Act and regulation. CONCLUSION: The facilitators and barriers to the integration of pharmacists in the provision of CPS lie at the individual, health facility, and health system levels. Therefore, the study recommends in-job pharmacists training, fostering teamwork among HCPs, and development of CPS SoPs, and guidelines.

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.

Cost effectiveness of simplified HCV screening-and-treatment interventions for people who inject drugs in Dar-es-Salaam, Tanzania.

BACKGROUND: Compared to other countries in sub-Saharan Africa, Tanzania has a relatively progressive illicit drug harm reduction (HR) policy, through a predominantly opioid substitution therapy-based programme. However, access to hepatitis C virus (HCV) diagnosis and curative direct acting antiviral therapy remains elusive. We developed a cost-effectiveness model to evaluate a simplified HCV screening-and-treatment intervention amongst PWID in Dar-es-Salaam, Tanzania. METHODS: A decision tree and Markov state transition model compared existing practice (no access to HCV viral confirmation and treatment) with the integration of point-of-care HCV screening and treatment within (1) existing HR services and (2) expansion to include PWID not currently engaged in HR. Outcome measures were screening, treatment, HR and disease-related costs per PWID, quality-adjusted life years (QALY) and disability adjusted life years (DALY). Cost-effectiveness was evaluated from a healthcare payer's perspective over a 30-year time horizon over a range of willingness-to-pay thresholds (USD$273 to USD$1,050). Both deterministic and probabilistic sensitivity analyses have been conducted. RESULTS: Assuming a chronic HCV prevalence of 18.8%, screening-and-treatment in existing HR settings resulted in an ICER per QALY-gained and DALY averted of USD$633 and USD$1,161, respectively. Expanding to include an outreach programme for unengaged PWID yielded an ICER per QALY-gained and DALY-averted of USD$4,091 and USD$10,288. Factors affecting the sensitivity of the ICER value included the cost of HR and the health utility of non-cirrhotic disease states. CONCLUSION: Simplified HCV screening and treatment of PWID has the potential to be cost-effective in Dar-es-Salaam, Tanzania. In practice, synergism of human and financial resources with established health programmes may offer a pragmatic solution to minimise operational costs.

Health-care provision and policy for non-alcoholic fatty liver disease in sub-Saharan Africa.

Sub-Saharan Africa, which has a population of more than 1 billion people, carries 24% of the global burden of disease and spends the least on health care of any region, relying heavily on international development assistance to deliver health care for HIV, tuberculosis, and malaria. The demographic and epidemiological transitions occurring in sub-Saharan Africa, with rising prevalences of obesity and diabetes, enhance the risk of non-alcoholic fatty liver disease (NAFLD), yet this remains an unrecognised complication of metabolic syndrome. There are no guidance documents on NAFLD from sub-Saharan Africa, and non-communicable disease (NCD) guidance documents do not include the associated burden of fatty liver disease. Combating the health and socioeconomic burden of NAFLD requires an integrated liver health approach, with task-shifting to primary health care. Using clear guidance documents to link education and management of HIV, viral hepatitis, NAFLD, and associated NCDs is also crucial to an integrated approach to infectious diseases and NCDs, which requires targeted funding from both governments and international development agencies.

Upscaling prevention, testing and treatment to control hepatitis C as a public health threat in Dar es Salaam, Tanzania: A cost-effectiveness model.

BACKGROUND: Hepatitis C (HCV) elimination strategies are required for low and middle-income countries (LMICs), because although treatment access is currently limited, this is unlikely to remain the case forever. We estimate and compare the impact, cost and cost-effectiveness of a variety of prevent, test and treat strategies for HCV in Dar es Salaam, Tanzania. METHODS: A mathematical model. RESULTS: Without intervention, the HCV epidemic in Dar es Salaam was estimated to result in US$29.1 million in disease costs between 2018 and 2030. Maintaining existing harm reduction coverage (4% needle and syringe program, 42% opioid substitution therapy) over this period was estimated to prevent 22% of injecting drug use-acquired HCV infections compared to a zero coverage scenario. Implementing antibody/RNA, serum-based HCV core antigen (HCVcAg) and dry blood spot (DBS) HCVcAg test/treat programs among PWID increased the total cost by US$0.7 million, US$3.1 million and US$6.5 million respectively by 2030; however this expenditure led to 57%, 61% and 73% reductions in annual incidence among PWID, 25%, 27% and 33% reductions overall annual incidence (PWID+non-PWID), and reduced HCV prevalence among PWID from 27% to 9%, 8% and 5%, respectively. The Ab/RNA, serum-based and DBS HCVcAg test/treat programs cost US$689, US$2857 and US$5400 per disability-adjusted life year averted, respectively, compared to no test/treat program. CONCLUSION: Primary prevention among PWID can provide important reductions in HCV transmission in the absence of treatment availability. HCV Ab/RNA or serum-based HCVcAg test/treat programs among PWID are likely to be cost-effective in Dar es Salaam, with serum-based HCVcAg test/treat achieving greater impact due to a simpler diagnostic process and better retention in care. If used for regular testing of PWID, the additional coverage benefits of non-laboratory-based DBS HCVcAg tests in LMICs would outweigh their reduced sensitivity.

In-field evaluation of Xpert® HCV viral load Fingerstick assay in people who inject drugs in Tanzania.

BACKGROUND: Although novel hepatitis C virus (HCV) RNA point-of-care technology has the potential to enhance the diagnosis in resource-limited settings, very little real-world validation of their utility exists. We evaluate the performance of HCV RNA quantification using the Xpert® HCV viral load Fingerstick assay (Xpert® HCV VL Fingerstick assay) as compared to the World Health Organisation pre-qualified plasma Xpert® HCV VL assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar-es-Salaam, Tanzania. METHODS: Between December 2018 and February 2019, consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and Fingerstick samples for HCV RNA quantification. These were processed onsite using the GeneXpert® platform located at the Central tuberculosis reference laboratory. RESULTS: A total of 208 out of 220 anti-HCV-positive participants recruited (94.5%) had a valid Xpert® HCV VL result available; 126 (61%; 95% CI 53.8-67.0) had detectable and quantifiable HCV RNA. About 188 (85%) participants had paired plasma and Fingerstick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R2  = .95) and concordance (mean difference 0.13 IU/mL, (95% CI -0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and Fingerstick samples. CONCLUSION: This study found excellent performance of the Xpert® HCV VL Fingerstick assay for HCV RNA detection and quantification in an African-field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa.

High prevalence and poor linkage to care of transfusion-transmitted infections among blood donors in Dar-es-Salaam, Tanzania.

Blood transfusion is one of the most commonly relied upon therapies in sub-Saharan Africa. Existing safeguards recommended include systematic screening for transfusion-transmitted infections and restricted voluntary nonremunerated blood donor selection. We report the transfusion-transmitted infection screening and notification practice at a large urban blood transfusion centre in Dar-es-Salaam, Tanzania. Between October 2016 and March 2017 anonymized records of all donors registered at the blood transfusion unit were accessed to retrospectively note demographic information, donor status, first-time status, transfusion-transmitted infection result and notification. 6402 consecutive donors were screened for transfusion-transmitted infections; the majority were family/replacement blood donors (88.0%) and male (83.8%). Overall transfusion-transmitted infections prevalence was 8.4% (95% CI 7.8-9.1), with hepatitis B being the most prevalent infection (4.1% (95% CI 3.6-4.6)). Transfusion-transmitted infections were more common in family/replacement blood donors (9.0% (95% CI 8.3-9.8)) as compared to voluntary nonremunerated blood donor (4.1% (95% CI 2.8-5.7)). A minority of infected-donors were notified of a positive result (8.5% (95% CI 6.3-11.2)). Although transfusion-transmitted infections are more prevalent among family/replacement blood donors, overall risk of transfusion-transmitted infections across all groups is considerable. In addition, existing efforts to notify donors of a positive transfusion-transmitted infection are poor. Future policies must focus on improving linkage to care for newly diagnosed patients with transfusion-transmitted infections.

Performance of a new rapid diagnostic test for the detection of antibodies to hepatitis C virus.

Rapid diagnostic tests (RDTs) represent an attractive alternative to conventional diagnostic methods for hepatitis C virus (HCV) infection. The aim of the present study was to assess the clinical performance of the new CE-marked Advanced Quality™ Rapid Anti-HCV Test for the detection of HCV antibodies in various patient populations. A total of 396 individuals, including 178 patients with chronic HCV infection, 26 patients with resolved HCV infection, and 192 subjects not infected with HCV, were studied. The clinical sensitivity and specificity in serum samples of the Advanced Quality™ Rapid Anti-HCV Test were both 99%. The new CE-marked RDT Advanced Quality™ Rapid Anti-HCV Test fulfills the World Health Organization recommendations acceptance criteria for serological assays in terms of sensitivity and specificity and can thus be confidently used for the screening of HCV antibodies.

The hepatitis C cascade of care in people who inject drugs in Dar es Salaam, Tanzania.

The World Health Organisation has recently called for hepatitis C virus (HCV) elimination and has identified people who inject drugs (PWID) as a key population to scale-up screening and linkage to care. This study reports the cascade of care for HCV in PWID attending the largest opioid substitution treatment (OST) clinic in Dar-es-Salaam, Tanzania. Between February 2011 and March 2016, HCV serology for all PWID registered at the Muhimbili National Hospital OST clinic, Dar-es-Salaam were obtained from records. In 2015, consecutive HCV-seropositive PWID were invited to undergo a clinical evaluation including epidemiological questionnaire, liver stiffness measurement (Fibroscan) and virological analysis (HCV RNA viral load and genotyping). During the study period, 1350 persons registered at the OST clinic: all had a HCV serology including 409 (30%) positive results. Among the HCV-seropositive individuals, 207 (51%) were active attenders and 153 (37%) were enrolled for clinical assessment: 141 (92%) were male, median age: 38 years (IQR 34-41), and 65 (44%) were co-infected with HIV; 116 patients (76%) had detectable HCV RNA, with genotypes 1a (68%) and 4a (32%); 21 (17%) had clinically significant fibrosis (≥F2) and 6 (5%) had cirrhosis (F4). None were offered HCV treatment. Chronic hepatitis C among PWID enrolled in the OST centre in Dar-es-Salaam is frequent, but its continuum of care is insufficient; integration of HCV diagnosis and treatment should form a part of OST intervention in PWID in Tanzania.

Hepatitis B vaccination coverage among healthcare workers at national hospital in Tanzania: how much, who and why?

BACKGROUND: Hepatitis B vaccination for healthcare workers (HCWs) is a key component of the WHO Hepatitis B Elimination Strategy 2016-2021. Data on current hepatitis B vaccine coverage among health care workers in Sub-Saharan Africa are scarce, but these data are vital for effective programming. We assessed the proportion of HCWs vaccinated for hepatitis B and the factors associated with adequate vaccination coverage at a national hospital in Tanzania. METHODS: A descriptive cross-sectional study was conducted among consenting healthcare workers between 30th July and 30th September 2015. Vaccination histories were obtained through self-administered questionnaires. Means and proportions were used to summarize the data. Student's t and chi-squared tests were used as appropriate. Logistic regression was used to determine the factors associated with vaccination. RESULTS: A total of 348 HCWs were interviewed, of whom 198 (56.9%) had received at least one dose of hepatitis B vaccination, while only 117 (33.6%) were fully vaccinated. About half of the 81 HCWs with partial vaccination (49.4%) had missed their subsequent vaccination appointments. Among unvaccinated HCWs, 14 (9.3%) had either HBV infection or antibodies against HBV infection upon pre-vaccination screening. However, the remaining participants were not vaccinated and did not know their immune status against HBV. Nearly all respondents (347, 99.3%) had heard about the hepatitis B viral vaccine. The following reasons for non-vaccination were given: 98 (65.3%) reported that they had not been offered the vaccine; 70 (46.7%) observed standard precautions to ensure infection prevention and 60 (41.3%) blamed a low level of awareness regarding the availability of the hepatitis B vaccine. CONCLUSION: The current vaccination coverage among practicing healthcare workers at Muhimbili National Hospital is low, despite a high level of awareness and the acceptance of the vaccine. Expedited and concerted efforts to scale vaccine uptake should include improved access to the vaccine, especially for newly recruited HCWs. The extension of the study to private healthcare settings and lower-level facilities would be useful.

Hepatitis B in sub-Saharan Africa: strategies to achieve the 2030 elimination targets.

The WHO global health sector strategy on viral hepatitis, created in May, 2016, aims to achieve a 90% reduction in new cases of chronic hepatitis B and C and a 65% reduction in mortality due to hepatitis B and C by 2030. Hepatitis B virus (HBV) is endemic in sub-Saharan Africa, and despite the introduction of universal hepatitis B vaccination and effective antiviral therapy, the estimated overall seroprevalence of hepatitis B surface antigen remains high at 6·1% (95% uncertainty interval 4·6-8·5). In this Series paper, we have reviewed the literature to examine the epidemiology, burden of liver disease, and elimination strategies of hepatitis B in sub-Saharan Africa. This paper reflects a supranational perspective of sub-Saharan Africa, and recommends several priority elimination strategies that address the need both to prevent new infections and to diagnose and treat chronic infections. The key to achieving these elimination goals in sub-Saharan Africa is the effective prevention of new infections via universal implementation of the HBV birth-dose vaccine, full vaccine coverage, access to affordable diagnostics to identify HBV-infected individuals, and to enable linkage to care and antiviral therapy.

Hepatitis C in sub-Saharan Africa: the current status and recommendations for achieving elimination by 2030.

In 2016, WHO adopted a strategy for the elimination of viral hepatitis by 2030. Africa, and more specifically, sub-Saharan Africa, carries a substantial portion of the global burden of viral hepatitis, especially chronic hepatitis B and hepatitis C virus infections. The task that lies ahead for sub-Saharan Africa to achieve elimination is substantial, but not insurmountable. Major developments in the management of hepatitis C have put elimination within reach, but several difficulties will need to be navigated on the path to elimination. Many of the challenges faced are unique to sub-Saharan Africa and the development of strategies is complicated by a scarcity of good data from countries and regions within sub-Saharan Africa. However, this hindrance should not act as a barrier to delay interventions in screening, detection, and linkage to care. Moreover, by sharing experiences from across sub-Saharan Africa, countries can create supranational synergies to develop their programmes and work together in a more cohesive manner to tackle the burden of hepatitis C in sub-Saharan Africa. In this Series paper, several issues related to hepatitis C in sub-Saharan Africa are addressed, including prevalence, risk factors, and fibrosis assessment, and recommendations are given by experts from across the region. Simplified diagnostic algorithms and treatment regimens for both HIV co-infected and hepatitis C mono-infected patients are suggested. The recommendations are consensus based and provided to guide the development of programmes in sub-Saharan Africa. Political will and appropriate funding will be required to provide impetus to implement these recommendations.

Clinical utility of HCV core antigen detection and quantification using serum samples and dried blood spots in people who inject drugs in Dar-es-Salaam, Tanzania.

INTRODUCTION: A lack of access to hepatitis C virus (HCV) diagnostics is a significant barrier to achieving the World Health Organization 2030 global elimination goal. HCV core antigen (HCVcAg) quantification and dried blood spot (DBS) are appealing alternatives to conventional HCV serology and nucleic acid testing (NAT) for resource-constraint settings, particularly in difficult-to-reach populations. We assessed the accuracy of serum and DBS HCVcAg testing in people who inject drugs in Tanzania using HCV NAT as a reference. METHOD: Between May and July 2015, consecutive HCV-seropositive patients enrolled in the local opioid substitution treatment centre were invited to participate in the study. All had HCV RNA detection (Roche Molecular Systems, Pleasanton, CA, USA), genotyping (NS5B gene phylogenetic analysis) and HCVcAg on blood samples and DBS (Architect assay; Abbott Diagnostics, Chicago, IL, USA). RESULTS: Out of 153 HCV-seropositive individuals, 65 (42.5%) and 15 (9.8%) were co-infected with HIV (41 (63%) were on anti-retroviral therapy (ARVs)) and hepatitis B respectively. In total, 116 were viraemic, median viral load of 5.7 (Interquartile range (IQR); 4.0-6.3) log iU/ml (75 (68.2%) were genotype 1a, 35 (31.8%) genotype 4a). The median alanine transaminase (ALT) (iU/l), aspartate transaminase (AST) (iU/l) and gamma-glutamyl transferase (GGT) (iU/l) were 35 (IQR; 23-51), 46 (32-57) and 69 (35-151) respectively. For the quantification of HCV RNA, serum HCVcAg had a sensitivity at 99.1% and a specificity at 94.1%, with an area under the receiver operating curve (AUROC) at 0.99 (95% CI 0.98-1.00). DBS HCVcAg had a sensitivity of 76.1% and a specificity of 97.3%, with an AUROC of 0.87 (95% CI 0.83-0.92). HCVcAg performance did not differ by HIV co-infection or HCV genotype. Conclusions Our study suggests that HCVcAg testing in serum is an excellent alternative to HCV polymerase chain reaction in Africa. Although HCVcAg detection and quantification in DBS has a reduced sensitivity, its specificity and accuracy are good and it could therefore be used for scaling up HCV testing and care in resource-limited African settings.

Prevalence and predictors of HCV among a cohort of opioid treatment patients in Dar es Salaam, Tanzania.

BACKGROUND: The government of Tanzania launched an opioid treatment program (OTP), using methadone, in Dar es Salaam in February of 2011. Hepatitis C virus (HCV) is a leading cause of morbidity and mortality globally, especially among people who inject drugs (PWID). We conducted a cross-sectional study among PWID engaged in OTP in Dar es Salaam to describe the prevalence and predictors of HCV antibody serostatus. METHODS: Routine programmatic data on patients enrolled in Muhimbili National Hospital's OTP clinic from February 2011 to January 2013 were utilized. Multivariable Poisson regression was used to examine factors associated with HCV antibody serostatus. RESULTS: A total of 630 PWID enrolled into the OTP clinic during the study period, seven percent of which were women. The overall seroprevalence of HCV antibody was 57% (95% Confidence interval: 53-61%). In adjusted analysis, methadone patients who used heroin for 5-10 years (adjusted prevalence ratio; aPR=1.41; 95% CI: 1.10-1.81) and >10years (aPR=1.48; 95% CI: 1.17-1.88) were more likely to be HCV antibody positive, compared to patients who used heroin for <5years. Patients who reported sharing needles or other equipment at their last injection (aPR=1.20; 95% CI: 1.01-1.41; p=0.022), being arrested (aPR=1.20; 95% CI: 1.04-1.40; p=0.012) and who were HIV-positive (aPR=1.84; 95% CI: 1.56-2.16; p<0.001) were also more likely to be HCV antibody positive than their counterparts. CONCLUSION: Our observed HCV antibody prevalence among PWID engaged in OTP is higher than previously reported estimates in Dar es Salaam. Predictors of HCV antibody serostatus in this sample were similar to those found among PWID in many other settings. Integrating HCV care and treatment into OTP clinics should be considered, leveraging lessons learned from the integration of HIV services into OTP. Global efforts to develop HCV care and treatment programs in low and middle-income countries are critical, especially among PWID who have a high burden of HCV.