Strengthening Pharmacovigilance System to Capture Safety Data from HIV Clients on ART in Tanzania: Identification of Gaps in Safety Reporting System

In Tanzania, pharmacovigilance system is implemented by Tanzania Food and Drugs Authority (TFDA) that monitors drug use countrywide. TFDA is the main national custodian for recording, analyzing and disseminating safety information that is generated through conventional health care facilities. Since the introduction of Care and Treatment Centre (CTC) in the health care system, little has been achieved on translating safety information from these facilities to the TFDA. Since the inception of national pharmacovigilance framework in 2003 there has been no systematic operational research to map the gaps in the existing pharmacovigilance system. Furthermore, it is not clear if there is adequate training and supervision. It is, therefore, important to strengthen antiretroviral therapy (ART) related adverse drug reactions (ADRs) reporting by mapping gaps in implementation of pharmacovigilance (PV) system. Information obtained will assist in addressing training needs to ensure effective reporting of ADRs through coordinated approach involving TFDA and National AIDS Control Program (NACP) in Tanzania. A cross-sectional study was conducted in four regions (Tanga, Singida, Dodoma and Mtwara) in two PV zones. Qualitative and quantitative data collection techniques with triangulation design were used. These included; desk document review of PV recording and reporting of drug safety information; in-depth interviews with various implementation stakeholders, exit interviews with patients, in-interviews with care takers and community based organizations (CBOs) involved in the provision of care and treatment of HIV/AIDS. A total of 801 respondents participated in the quantitative data component which included; 545 exit interviews to CTC clients, 177 health service providers, 62 in-depth interviews to CTC in-charges and 17 regional and district pharmacists. Ownership of these CTCs included 83.9% government, 12.9% faith based organizations and 3.2% co-owned by the government and faith based organizations. High proportions (97.2%) of the CTC health care providers had wide knowledge on ART related ADRs. However, more than half (53.4%) of the CTC service providers had not attended any training on ART related ADRs. Among the service providers, majority (67.8%) mentioned there was no guideline in place for reporting ART related ADRs. Only, 32.1% of health care providers indicated to be aware of the tool used for collection of ART related ADRs events. Of those, 37.5% mentioned that the forms were mainly obtained from district or regional pharmacists. The ADR reports were submitted to district and regional pharmacists 48.3%, TFDA 7.0%, and NACP 7.0%. Of those who indicated to have filled and submitted ADR form, only 7.4% received feedback. The proportion of ART clients who provided information was significantly different between urban and rural in Dodoma region (p=0.002). There was variation in proportions of ART clients who had mentioned seen/heard of ART related ADR by regions and difference was significant between rural and urban for all regions except Tanga (p<0.05). Majority (47.9%) of the ART clients reported ART related ADRs to the health provider for duration ranging from 3-7 days. The qualitative results revealed that that most of the guidelines from TFDA were not known and unavailable according to most of the respondents at national level (NACP), regional, district, and at health facility level. It was surprising that one of the district pharmacists interviewed was unaware of existence of guidelines in place for ADR and PV for use in the districts. It was also found that Sometimes even when available at health facilities, there was inadequate knowledge on how to fill the ADR forms according to Key Informant at national level. Moreover, several health workers admitted that that they were not reporting ADR due to a lack of forms according to some CTC in-charges interviewed. This study has shown that despite the established PV system in Tanzania, the frequency of reporting of ART related ADRs to TFDA is low. This is due to inadequate training of health care providers on ADR reporting, shortage of staff, unavailability of TFDA ADR reporting forms and lack of regular supportive supervision. Based on these results therefore we recommend TFDA should ensure that ADR reporting forms as well as guidelines are adequately supplied and utilized at CTC level NACP should ensure sharing of safety information with TFDA and recommend dedicated focal person liable for documenting and reporting ART related ADRs recorded in CTC II patient file. Regular training, supportive supervision and feedback on ART related ADR reporting system for health care providers is needed. The financial support was provided by the Global Fund Round 8. The total budget for the project was Tsh. 69,993,000/-

Molecular methods for tracking residual Plasmodium falciparum transmission in a close-to-elimination setting in Zanzibar

Molecular detection of low-density Plasmodium falciparum infections is essential for surveillance studies conducted to inform malaria control strategies in close-to-elimination settings. Molecular monitoring of residual malaria infections usually requires a large study size, therefore sampling and diagnostic processes need to be economical and optimized for high-throughput. A method comparison was undertaken to identify the most efficient diagnostic procedure for processing large collections of community samples with optimal test sensitivity, simplicity, and minimal costs.; In a reactive case detection study conducted on Zanzibar, parasitaemia of 4590 individuals of all ages was investigated by a highly sensitive quantitative (q) PCR that targets multiple var gene copies per parasite genome. To reduce cost, a first round of positivity screening was performed on pools of dried blood spots from five individuals. Ten cycles of a pre-PCR were performed directly on the filter paper punches, followed by qPCR. In a second round, samples of positive pools were individually analysed by pre-PCR and qPCR.; Prevalence in household members and neighbors of index cases was 1.7% (78/4590) with a geometric mean parasite density of 58 parasites/µl blood. Using qPCR as gold standard, diagnostic sensitivity of rapid diagnostic tests (RDTs) was 37% (29/78). Infections positive by qPCR but negative by RDT had mean densities of 15 parasites/µl blood.; The approach of pre-screening reactive case detection samples in pools of five was ideal for a low prevalence setting such as in Zanzibar. Performing direct PCR on filter paper punches saves substantial time and justifies the higher cost for a polymerase suitable for amplifying DNA directly from whole blood. Molecular monitoring in community samples provided a more accurate picture of infection prevalence, as it identified a potential reservoir of infection that was largely missed by RDT. The developed qPCR-based methodology for screening large sample sets represents primarily a research tool that should inform the design of malaria elimination strategies. It may also prove beneficial for diagnostic tasks in surveillance-response activities

The Status of Maternal and Newborn Health Care Services in Zanzibar.

It is estimated that 287,000 women worldwide die annually from pregnancy and childbirth-related conditions, and 6.9 million under-five children die each year, of which about 3 million are newborns. Most of these deaths occur in sub-Saharan Africa. The maternal health situation in Tanzania mainland and Zanzibar is similar to other sub-Saharan countries. This study assessed the availability, accessibility and quality of emergency obstetric care services and essential resources available for maternal and child health services in Zanzibar. From October and November 2012, a cross-sectional health facility survey was conducted in 79 health facilities in Zanzibar. The health facility tools developed by the Averting Maternal Death and Disability program were adapted for local use. Only 7.6 % of the health facilities qualified as functioning basic EmONC (Emergency Obstetric and Neonatal Care) facilities and 9 % were comprehensive EmONC facilities. Twenty-eight percent were partially performing basic EmONC and the remaining 55.7 % were not providing EmONC. Neonatal resuscitation was performed in 80 % of the hospitals and only 17.4 % of the other health facilities that were surveyed. Based on World Health Organisation (WHO) criteria, the study revealed a gap of 20 % for minimum provision of EmONC facilities per 500,000 population. The met need at national level (proportion of women with major direct obstetric complications treated in a health facility providing EmONC) was only 33.1 % in the 12 months preceding the survey. The study found that there was limited availability of human resources in all visited health facilities, particularly for the higher cadres, as per Zanzibar minimum staff requirements. There is a need to strengthen human resource capacity at primary health facilities through training of health care providers to improve EmONC services, as well as provision of necessary equipment and supplies to reduce workload at the higher referral health facilities and increase geographic access

Operational coverage and timeliness of reactive case detection for malaria elimination in Zanzibar, Tanzania

Since 2012, the Zanzibar Malaria Elimination Program has been implementing reactive case detection (RACD). Health facility (HF) staff send individual malaria case notifications by using mobile phones, triggering a review of HF records and malaria testing and treatment at the household level by a district malaria surveillance officer. We assessed the completeness and timeliness of this system, from case notification to household-level response. We reviewed two years (2015-2016) of primary register information in 40 randomly selected HFs on Zanzibar's two islands Unguja and Pemba and database records of case notifications from all registered HFs for the period 2013-16. The operational coverage of the system was calculated as proportion of HF-registered cases that were successfully reviewed and followed up at their household. Timeliness was defined as completion of each step within 1 day. Public HFs notified almost all registered cases (91% in Unguja and 87% in Pemba), and 74% of cases registered at public HFs were successfully followed up at their household in Unguja and 79% in Pemba. Timely operational coverage (defined as each step, diagnosis to notification, notification to review, and review to household-level response, completed within 1 day) was achieved for only 25% of registered cases in Unguja and 30% in Pemba. Records and data from private HFs on Unguja indicated poor notification performance in the private sector. Although the RACD system in Zanzibar achieved high operational coverage, timeliness was suboptimal. Patients diagnosed with malaria at private HFs and hospitals appeared to be largely missed by the RACD system

Understanding sexual and reproductive health needs of adolescents: Evidence from a formative study in three districts of lake regions in Tanzania

Background: Teenage marriage and adolescent pregnancy present a significant health challenge in the Tanzania. About 36% of women aged 15-49 are married before the age of 18, and 32% of rural adolescents (10-19 years) gave birth, compared with 19% of urban. In Mwanza region, one third of currently married adolescent and women aged 15-49 experienced unmet need for family planning and had low use of modern contraceptives. Here we present a study that explored the gaps in accessing and utilization of quality adolescent sexual and reproductive health services (ASRH). Methods: This was a descriptive and exploratory cross-sectional formative study utilizing multiple qualitative research methods. Purposive sampling was used to select an urban district (Nyamagana), rural district (Magu) and an island (Ukerewe). Sixty-seven IDI and 30 focus group discussions (FGDs) stratified by gender (12 out-of-school, 12 in-school), and (3 male, 3 female adults) were purposefully sampled. Vignettes were done with 15-19 years old in-school and out-of-schools boys and girls. An experienced moderator, along with a note-taker, led the discussions while taking notes. The FGDs were recorded using an MP3 voice recorder. Thematic analysis approach was undertaken and data was analysed using NVivo 12, a qualitative software. Results: Adolescent girls needed special service such as counselling on menstrual health, sexual consent, HIV/AIDS, and prevention of pregnancies. Sanitary pads during the menstrual period were a very important pressing need of adolelescent girls. Adolescents both girls and boys preferred to receive friendly health care services in a respectful manner. Girls mentioned that they would like to receive SRH support from nurses in health facilities, mothers, sisters,aunties and friends. With regards to the boys, they preferred to receive the the SRH from health care providers followed by their peer\u27s friends.Several obstacles were reported to hinder access to SRHS predominantly among adolescent girls as compared to boys. Poor infrastructure tended to impair the privacy at the health facilities, and rarely there were specific buildings to provide friendly adolescent sexual and reproductive health services. Conclusions: The strategies to guide the delivery of ASRH should involve the inclusion of duty bearers, promotion of friendly health care services where health workers provide services in friendly- manner, and provision of ASRH education for awareness creation to adolescents and supportive parents/caretakers

The Costs of Implementing Vaccination With the RTS,S Malaria Vaccine in Five Sub-Saharan African Countries

Background. The World Health Organization has recommended pilot implementation of a candidate vaccine against malaria (RTS,S/AS01) in selected sub-Saharan African countries. This exploratory study aimed to estimate the costs of implementing RTS,S in Burkina Faso, Ghana, Kenya, Mozambique, and Tanzania. Methods. Key informants of the expanded program on immunization at all levels in each country were interviewed on the resources required for implementing RTS,S for routine vaccination. Unit prices were derived from the same sources or from international price lists. Incremental costs in 2015 US dollars were aggregated per fully vaccinated child (FVC). It was assumed the four vaccine doses were either all delivered at health facilities or the fourth dose was delivered in an outreach setting. Results. The costs per FVC ranged from US$25 (Burkina Faso) to US$37 (Kenya) assuming a vaccine price of US$5 per dose. Across countries, recurrent costs represented the largest share dominated by vaccines (including wastage) and supply costs. Non-recurrent costs varied substantially across countries, mainly because of differences in needs for hiring personnel, in wages, in cold-room space, and equipment. Recent vaccine introductions in the countries may have had an impact on resource availability for a new vaccine implementation. Delivering the fourth dose in outreach settings raised the costs, mostly fuel, per FVC by less than US$1 regardless of the country. Conclusions. This study provides relevant information for donors and decision makers about the cost of implementing RTS,S. Variations within and across countries are important and the unknown future price per dose and wastage rate for this candidate vaccine adds substantially to the uncertainty about the actual costs of implementation

Multiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania

Abstract Zanzibar has made significant progress toward malaria elimination, but recent stagnation requires novel approaches. We developed a highly multiplexed droplet digital PCR (ddPCR)-based amplicon sequencing method targeting 35 microhaplotypes and drug-resistance loci, and successfully sequenced 290 samples from five districts covering both main islands. Here, we elucidate fine-scale Plasmodium falciparum population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. Despite high genetic diversity, we observe pronounced fine-scale spatial and temporal parasite genetic structure. Clusters of near-clonal infections on Pemba indicate persistent local transmission with limited parasite importation, presenting an opportunity for local elimination efforts. Furthermore, we observe an admixed parasite population on Unguja and detect a substantial fraction (2.9%) of significantly related infection pairs between Zanzibar and the mainland, suggesting recent importation. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and provides actionable insights for prioritizing malaria elimination efforts

Malaria infection prevalence and sensitivity of reactive case detection in Zanzibar

Reactive case detection (RCD) is a commonly used strategy for malaria surveillance and response in elimination settings. Many approaches to RCD assume detectable infections are clustered within and around homes of passively detected cases (index households), which has been evaluated in a number of settings with disparate results.; Household questionnaires and diagnostic testing were conducted following RCD investigations in Zanzibar, Tanzania, including the index household and up to 9 additional neighboring households.; Of 12,487 participants tested by malaria rapid diagnostic test (RDT), 3·2% of those residing in index households and 0·4% of those residing in non-index households tested positive (OR = 8·4; 95%CI: 5·7, 12·5). Of 6,281 participants tested by quantitative polymerase chain reaction (qPCR), 8·4% of those residing in index households and 1·3% of those residing in non-index households tested positive (OR = 7·1; 95%CI: 6·1, 10·9). Within households of index cases defined as imported, odds of qPCR-positivity amongst members reporting recent travel were 1·4 times higher than among those without travel history (95%CI: 0·2, 4·4). Amongst non-index households, odds of qPCR-detectable infection were no different between households located within 50 m of the index household as compared with those located farther away (OR = 0·8, 95%CI: 0·5, 1·4). Sensitivity of RDT to detect qPCR-detectable infections was 34% (95%CI: 26·4, 42·3).; Malaria prevalence in index households in Zanzibar is much higher than in non-index households, in which prevalence is very low. Travelers represent a high-risk population. Low sensitivity of RDTs due to a high prevalence of low-density infections results in an RCD system missing a large proportion of the parasite reservoir