ONLINE VISIBILITY OF PHARMACY RESEARCH IN TANZANIA: A SCIENTOMETRIC STUDY

Objective: This scientometric analysis was carried out to map the online visibility of pharmacy research at Muhimbili University of Health and Allied Sciences (MUHAS) from 1981 to 2016.Methods: Publish or Perish software was used to collect data for 33 scientists from the School of Pharmacy at MUHAS. We retrieved data on scholars' publications, citation counts, the number of authors per publication, average citations per paper, average citations per year, h-index, g-index, contemporary H-index (Hc index) and the HI-norm index.Results: A total of 499 publications were recorded for all scholars and the most (61; 12.2%) productive was 2013. The whole study period recorded the mean relative growth rate (RGR) and doubling time (Dt) of 1.62 and 0.46 respectively. A great majority (484; 97%) of the publications were multiple-authored with nearly one third (157; 31.5%) of these being jointly contributed by six or more authors. The maximum number of citations received in a single publication was 241. The degree of collaboration among scientists was as high as 0.97. The top ranked pharmacy researchers showed variation in various metrics.Conclusion: The study findings indicate a continuous growth of pharmacy publications at MUHAS since 1981. There is a high level of collaboration among scholars and many publications have made a great impact through citations.Â

the interplay of two wicked problems

Funding Information: This work was funded by VLIR-UOS, grant numbers TZ2019SIN263 and TZ2020JOI032A101. Publisher Copyright: ©Concern is justified observing the link between the AIDS and COVID-19 pandemics. COVID-19 outcomes are significantly worse in many people living with HIV (PLHIV), even when vaccinated, because of their impaired immune system. Moreover, CD4 T-cells are affected by both HIV and SARS-CoV-2.1-3 SARS-CoV-2 variants can evolve in immunosuppressed patients due to prolonged viral replication in the context of an inadequate immune response.4 Accelerated intrahost evolution of SARS-CoV-2 was reported in a South African HIV patient with antiretroviral therapy (ART) failure.5 6 With 25 million HIV patients in sub-Saharan Africa (SSA) of whom an estimated 8 million are not virologically suppressed, this potentially creates a reservoir for future variants. Such variants, arising in PLHIV anywhere in the world, can spread to other continents, as has been reported for variants of concern (VoCs) (Beta, Omicron) and variants of interest (B.1.6.20, B.1.640.2) that arose in Africa.7-9 Conversely, the COVID-19 pandemic impacts HIV treatment programmes, due to supply chain issues, overburdening of healthcare systems, limiting access to testing, treatment and prevention programmes and further increasing inequalities.10 Modelled COVID-19 disruptions of HIV programmes in SSA included decreased functionality of HIV prevention programmes, HIV testing and treatment, healthcare services such as viral load testing, adherence counselling, drug regimen switches and ART interruptions, which may lead to selection of drug-resistant HIV.11 A 6-month interruption affecting 50% of the population would lead to a median number of excess deaths of 296 000, during 1 year. Scientists advocate for the AIDS and COVID-19 pandemics in Africa to be addressed simultaneously, by increasing African access to COVID-19 vaccines, prioritising research on the interaction between HIV care and COVID-19, maintaining high-quality HIV services and integrating health services for both viruses.7 Both the COVID-19 and the AIDS pandemic, more specifically the issue of HIV drug resistance (HIVDR), have previously been described as wicked problems which are best studied as complex adaptive systems (CASs).12-15Wicked problems consist of diverse interconnected factors and require complexity-informed and locally adapted solutions rather than one solution that fits all. We recently designed a qualitative model of all known factors influencing HIVDR in SSA and analysed its complexity.13 Our detailed systems map featured three main feedback loops driving HIVDR, representing (1) the alternation between adherence and non-adherence, (2) the impact of an overburdened healthcare system and (3) the importance of sustaining global efforts of tackling HIVDR even when new antiretroviral drugs with high genetic barriers become available. These HIV-related feedback loops are interconnected with COVID-19 pandemic impact (in yellow, figure 1). The loop starts from PLHIV with an unsuppressed viral load, which weakens the immune system and may in turn slow down immune clearance of SARS-CoV-2, allowing prolonged replication and mutation of the virus in the context of an inadequate immune response. Prolonged viral clearance facilitates the selection of immune escape SARS-CoV-2 variants. Variants may emerge that have a selective advantage and therefore may spread through populations due to increased transmissibility (with possibly increased virulence), thereby creating an additional burden on the healthcare system, putting the overall healthcare system and the HIV care at risk. These stressors on the healthcare system lead to a higher risk of unsuppressed viral load in PLHIV, increasing the risk of HIVDR. Figure 1 shows the need to address both wicked problems simultaneously and to do so in a complexity-informed manner as they are inevitably linked and influence each other. Evidently, the exact interconnections between both pandemics need to be locally assessed. For instance, a study in South Africa showed that while lockdown severely impacted HIV testing and ART initiation, ART provision was largely maintained, indicating that the strength of the connection between the virological suppression-related loop and the pandemic, indicated in figure 1, are context-dependent.16publishersversionpublishe

Challenges for monitoring HIV-1 therapy response in resource-limited settings

The advent of the potent combination antiretroviral therapy (cART) in 1996, often called HAART (highly active antiretroviral therapy) changed the impact of HIV both for an individual and the population. These cocktails of three or more antiretroviral (ARV) drugs significantly improved life expectancy in patients who have access to it and thus restored hope for fighting the disease epidemic.Recently, ART is being scaled up in resource limited-settings (RLS), giving access to treatment in geographic areas where the majority of HIV infected patients reside. The main concern of scaling up ART in RLS is whether these expensive treatment programs translate to an effective reduction in morbidity and mortality among HIV and AIDS patients. Factors such as lack of potency of ARV combinations, insufficient drug adherence and transmission of drug resistant virus strains may lead to treatment failure. Therefore, HAART requires high levels of adherence, typically above 95%, in order to prevent the development of HIV drug resistance (HIVDR) mutations, which ultimately lead to poor treatment response.In developed countries, the standard of care includes virological monitoring: measuring the amount of circulating virus in the blood and determining the genotypic susceptibility of patient isolates. In this way, a rational selection and use of ARVs can bring a successful treatment response. In RLS, virological monitoring is hampered by high costs. Following reports of both acquired and transmitted resistance in sub-Saharan Africa, it is imperative to devise more robust methods for monitoring of therapy response. These reports call for cheaper and simpler viral load and resistance-testing platforms to identify virologically failing patients and measure the presence of key drug resistance mutations. Most often this is not possible and alternatives are needed for identifying therapy failure and emerging HIVDR at both population and individual levels. In RLS, ART adherence monitoring is a potential surrogate that could be incorporated into clinical care. Alternatively, a model for predicting drug resistance based on limited genotyping combined with past treatment history from large databases could be useful in RLS.Chapter one provides a general overview of the problem of HIV and AIDS epidemic, while, chapter 2 outlines the rationale and the objective of this research. In chapter 3 we studied adherence measurements in an adult cohort in Dar es Salaam, Tanzania. The first method to probe adherence was self-reports by using the visual analog scale (VAS) and the Swiss HIV cohort study-adherence questionnaire (SHCS-AQ). Additionally, pill count, appointment keeping and pharmacy prescription refill methods were used. We revealed good adherence to ART in between 50 to 86% of this population, using the different adherence measurements. Comparable adherence levels reported in other sub-Saharan Africa countries were at proportions of 96%, 82% and 78% among respondents in Ethiopia, Kenya and Cote d'Ivoire, respectively. We identified forgetfulness as a major reason for skipping medications. Older age, less alcohol consumption, being at more advanced WHO staging and having less body mass index were significant predictors of good adherence in multivariate analysis. Further, in chapter 4 we validated the different measurement outcomes of adherence against the virological outcome after one year of follow-up among for 162 patients having both baseline and follow-up viral load. The patients were followed for a period of one year median (interquartile range) 13 (11-13) months. Of these patients 34% and 10.5% had detectable viral load and immunological failure, respectively at one year after recruitment. The pharmacy refill estimate was the only adherence measurement associated to virological outcome. Further, the prediction of virological outcome was improved by combining pharmacy refill with immunological status.Information on levels of HIVDR among HIV patients on therapy is not available in Tanzania. The ultimate objective of this research was to determine genotypic HIVDR in both treatment naïve and experienced patients. Furthermore, the research intended to find cheap predictors for treatment failure and resistance development, such as adherence and treatment history. In chapter 5, genotyping was performed from virologically failing patients plasma samples in order to determine subtype diversity of HIV isolates and the mutation patterns at various stages of ART in Tanzania. The study revealed wide subtype diversity among isolates in these patients. The isolates belonged mostly to subtypes A followed by subtypes C and D; and their recombinant forms. The study did not uncover any transmitted drug resistance mutations in naïve patients initiating ART. However, a high prevalence of resistance was evident among virologically failing patients on therapy for more than four months. The major nucleoside reverse transcriptase inhibitor (NRTI) mutation M184V was found in 70% of patient failing virologically, threatening the utility of lamivudine and emtricitabine, which are the main NRTIs recommended in the Tanzanian national guidelines for management of ART. Resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) NNRTIs was found in 86% of virologically failing patients, with K103N being the most abundant mutation. All potential second line regimens were already compromised in 86% of patients. These high prevalence of HIVDR in virologically failing patients warrant appropriate interventions to prevent further transmission of multi-HIVDR in Tanzania.Chapter 6 approached our objectives from a different angle. Genetic fitness landscapes (FL) can be used to derive the genetic barrier to resistance given a baseline genotype. This in turn, can be used to predict the response to therapy. Such FLs are built in two steps, first mapping epistatic interactions among the amino acids in the targeted proteins using Bayesian Network Learning, and then scaling the FL by modelling evolution during treatment selective pressure using sequences from untreated versus treated patients. In chapter 6, we evaluated a new approach to building a FL by using longitudinal sequence pairs, instead of cross-sectional data only, using the drug indinavir as a model drug. We compared four FLs estimated from different HIV sequence populations. One was built using for both steps only cross-sectional data from drug-naïve and indinavir experienced patients. Three FLs were built by using for the first step three different cross-sectional Bayesian Networks, trained with indinavir, all protease inhibitors (PIs) and all PIs except indinavir sequence data respectively, followed by the second scaling step using longitudinal viral sequence pairs from patients failing a combination including the drug indinavir. We derived parameters of viral fitness and genetic barrier to resistance by simulating sequences over the FLs. These parameters successfully predicted the short and long term virological response at 12 and 48 weeks, respectively. The predictive power was comparable to that of standard rule based interpretation systems such as the Rega algorithm and HIVdb. Additionally, the FLs could predict a failing genotype in longitudinal sequence pairs before and after treatment with indinavir.This research investigated adherence measurements that are feasible in RLS and identified predictors of good adherence. We also found adherence in combination with immune response to be good predictors of virological response. We found no transmitted drug resistance among treatment-naïve patients, but rather high levels of HIVDR among patients failing cART in Tanzania. This signals Tanzania and other countries in sub-Saharan Africa to consider scaling resistance testing where feasible. Adherence was an independent predictor of virological failure, therefore, it can be a surrogate marker to earmark patients in need for virological and HIVDR testing. Moreover, a computational modelling approach could offer an added value by combining sparse genotypic information with other factors such as treatment history to predict therapy response.These research findings provide additional information and valuable insights for policy decisions on ART interventions that will reduce the risk of emergence of HIVDR among patients on treatment in RLS. In general, the baseline data provided by these studies collectively suggest that regular surveillance of HIVDR needs to be implemented in this setting.status: publishe

Pharmaceuticals imports in Tanzania: Overview of private sector market size, share, growth and projected trends to 2021.

BackgroundTo assess the extent to which foreign pharmaceutical imports vary from year to year and identifying leading generic and branded formulations, key countries and key importers of pharmaceuticals in private sector supply chain.MethodologyA systematic analysis of data for pharmaceutical imports from the Ministry of Health.Data from 2013 to 2016 fiscal years and relevant documents were accessed from the Tanzania Food and Drugs Authority (TFDA). Data cleaning was carried out to remove duplicate entries and to exclude pharmaceutical imports for individual uses, promotion purpose, donations, raw material, medical devices, government institutions and veterinary products.ResultsA total of 397 different suppliers imported pharmaceutical in Tanzania mainland from 2013 to 2016 fiscal years. In the 2013-2014 fiscal year, the private sector suppliers imported pharmaceutical worth 216 U.S million dollars. India ranked as the first country for exporting highest value of pharmaceutical into the country. It displays a 54% cumulative market share of total imports from 2013-2016, followed by Egypt (11.7%), Switzerland and the USA hold 4.1% of cumulative market share. By 2020-2021 fiscal years, we forecast for imported pharmaceuticals to reach a total value of 906 U.S million dollars for the private sector supply chain. All analysis in this study and the forecasted figures are limited to private sector pharmaceutical supply chain only and does not include data for government pharmaceutical supply chain.ConclusionsOur result shows that the vast majority of pharmaceutical imports in the private sector supply chain are dominated by imports from India. India is competing with other countries such as Egypt, Switzerland, USA and South Africa among the top importing countries. There was almost an equal distribution of pharmaceutical for both communicable and non-communicable diseases. Data presented shows a growing trend for the market segment for medicines required for the management of non-communicable diseases. Generally, the private sector pharmaceutical market is keeping on rising at a rapid pace. By the year 2021, the growth is forecasted to increase by 28% compared to the current market value. The projected growth rate could be good news for foreign pharmaceutical companies seeking new sources of growth in international pharmaceutical trading. It is also good news to the poor patients if the availability of drugs previously unavailable in the country is significantly increased

Establishing a Multi-Country Sickle Cell Disease Registry in Africa: Ethical Considerations

Sickle cell disease (SCD) is one of the most prevalent genetic conditions in sub-Saharan Africa. It is a chronic, lifelong disease often characterized by severe pain. However, SCD has received little investment terms of health research, though there is currently a growing pool of SCD data from health and research facilities in different countries. To facilitate research on SCD in Africa, the SickleInAfrica consortium has established a SickleInAfrica registry. The registry will store a systematic collection of longitudinal data from persons with SCD across sub-Saharan Africa, and currently, participants are being enrolled in Ghana, Nigeria, and Tanzania. In establishing this registry, the SickleInAfrica consortium decided to actively identify and anticipate possible ethical issues that may arise in the development and management of the registry. This was motivated, in part, by the near absence of well documented ethical issues for registry research in Africa, more-so for registries enrolling participants across multiple countries and for a genetic condition. The consortium aims to establish standards for the equitable use of data stored in the registry. This paper presents a comprehensive report on the ethical considerations that came up in setting up a genetic disease registry across multiple African countries and how they were addressed by the SickleInAfrica consortium. Major issues included: active involvement of patients in the initiation and management of the registry; questions of assent and re-consent; the importance of ensuring that fears of exploitation are not replicated in African-African research collaborations; and the importance of public engagement in the management of registries. Drawing on this experience, SickleInAfrica plans to set up an ethics helpdesk for genetic disease registries and research in Africa

National Antibiotics Utilization Trends for Human Use in Tanzania from 2010 to 2016 Inferred from Tanzania Medicines and Medical Devices Authority Importation Data

Antimicrobial use (AMU) is one of the major drivers of emerging antimicrobial resistance (AMR). The surveillance of AMU, which is a pillar of AMR stewardship (AMS), helps devise strategies to mitigate AMR. This descriptive, longitudinal retrospective study quantified the trends in human antibiotics utilization between 2010 and 2016 using data on all antibiotics imported for systemic human use into Tanzania’s mainland. Regression and time series analyses were used to establish trends in antibiotics use. A total of 12,073 records for antibiotics were retrieved, totaling 154.51 Defined Daily Doses per 1000 inhabitants per day (DID), with a mean (±standard deviation) of 22.07 (±48.85) DID. The private sector contributed 93.76% of utilized antibiotics. The top-ranking antibiotics were amoxicillin, metronidazole, tetracycline, ciprofloxacin, and cefalexin. The DIDs and percentage contribution of these antibiotics were 53.78 (34.81%), 23.86 (15.44), 20.53 (13.29), 9.27 (6.0) and 6.94 (4.49), respectively. The time series model predicted a significant increase in utilization (p-value = 0.002). The model forecasted that by 2022, the total antibiotics consumed would be 89.6 DIDs, which is a 13-fold increase compared to 2010. Government intervention to curb inappropriate antibiotics utilization and mitigate the rising threat of antibiotic resistance should focus on implementing AMS programs in pharmacies and hospitals in Tanzania

Exploring the value and acceptability of peer support in the process of improving adherence to HIV antiretroviral drugs in Tanzania, Dar-es-Salaam

Challenge: A way to understand and instruct on best practices for delivering and accepting HIV drug treatments in Africa. This transdisciplinary team focused on the problem of continuously rising levels of HIV drug resistance in Africa that as a result can lead to increased rates of mortality and morbidity. The main source of the HIV drug resistance problem is believed to be insufficient adherence to therapy. The challenge submitter suggested to explore whether improving the relationship between patient and health-care provider would be the next best step to improve adherence. However, after gathering knowledge from different sources, it was found that the burden on local doctors was already very high and would only increase in the coming years. A better relationship with the patient would be an extra burden on the time of health personnel. Instead, the team researched the feasibility of implementing peer support groups in Dar Es Salaam, Tanzania, as a possible way to increase patient adherence. With the creation of a questionnaire, a first step was taken in researching the value and acceptability of peer support groups in combating problems with adherence in regions where time constraints on skilled health workers limit possible interventions

HIV-related Peer Support in Dar es Salaam: A Pilot Questionnaire Inquiry

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