Implementation research for promoting access and rational use of antibiotics for children: lessons learnt from Tanzania.

Implementation research (IR) has proved to be a potential catalyst in facilitating the uptake of evidence-based innovations into routine practices and thereby maximizing public health outcomes. IR not only focuses on the effectiveness of the innovations but also identifies and addresses the barriers and facilitators to maximize their uptake into routine practices. This article describes the processes undertaken to implement a research project aimed at promoting access and rational use of antibiotics for children (PARAC). It also provides an overview of the lessons learnt during its implementation in Tanzanian hospital and community settings.

Assessing the relationship between operationally defined zero-dose communities and access to selected primary healthcare services for children and pregnant women in emergency settings.

In this study the authors examine the relationship between "zero-dose" communities and access to healthcare services. This was done by first ensuring the first dose of the Diphtheria Tetanus and Pertussis vaccine was a better measure of zero-dose communities than the measles-containing vaccine. Once ensured, it was used to examine the association with access to primary healthcare services for children and pregnant women in the Democratic Republic of Congo, Afghanistan, and Bangladesh. These services were divided into: a) unscheduled healthcare services such as birth assistance as well as seeking care and treatment for diarrheal diseases and cough/fever episodes and b) other scheduled health services such as antenatal care visits and vitamin A supplementation. Using recent Demographic Health Survey data (2014: Democratic Republic of Congo, 2015: Afghanistan, 2018: Bangladesh), data was analyzed via Chi Squared analysis or Fischer's Exact Test. If significant, a linear regression analysis was performed to examine if the association was linear. While the linear relationship observed between children who had received the first dose of the Diphtheria Tetanus and Pertussis vaccine (the reverse to zero-dose communities) and coverage of other vaccines was expected, the results of the regression analysis depicted an unexpected split in behavior. For scheduled and birth assistance health services, a linear relationship was generally observed. For unscheduled services associated with illness treatments, this was not the case. While it does not appear that the first dose of the Diphtheria Tetanus and Pertussis vaccine can be used to predict (at least in a linear manner) access to some primary (particularly illness treatment) healthcare services in emergency/ humanitarian settings, it can serve as an indirect measure of health services not associated with the treatment of childhood infections such as antenatal care, skilled birth assistance, and to a lesser degree even vitamin A supplementation.

Profiling of antimicrobial dispensing practices in accredited drug dispensing outlets in Tanzania: a mixed-method cross-sectional study focusing on pediatric patients.

BACKGROUND: The emergency of antimicrobial resistance due to irrational antimicrobial use has put public health under threat. Accredited Drug Dispensing Outlets (ADDOs) play an important role in enhancing availability and accessibility of antimicrobials, however, there is a scarcity of studies assessing antimicrobial dispensing practices in these outlets, focusing on children in Tanzania. OBJECTIVE: This study was conducted to assess the antimicrobial dispensing practices among ADDO dispensers and explore the factors influencing the use of antimicrobials for children in Tanzania. METHODS: A community-based cross-sectional study utilizing both qualitative (interviews) and quantitative (simulated clients) methods was conducted between June and September 2020 in seven zones and 14 regions in Tanzania. RESULTS: The study found inappropriate dispensing and use of antimicrobials for children, influenced by multiple factors such as patient's and dispenser's knowledge and attitude, financial constraints, and product-related factors. Only 8% (62/773) of dispensers asked for prescriptions, while the majority (90%) were willing to dispense without prescriptions. Most dispensers, 83% (426/513), supplied incomplete doses of antimicrobials and only 60.5% (345/570) of the dispensers gave proper instructions for antimicrobial use to clients. Over 75% of ADDO dispensers displayed poor practice in taking patient history. CONCLUSION: ADDO dispensers demonstrated poor practices in dispensing and promoting rational antimicrobial use for children. Training, support, and regulatory interventions are required to improve antimicrobial dispensing practices in community drug outlets.

Implementation of antibiotic stewardship programmes in paediatric patients in regional referral hospitals in Tanzania: experience from prescribers and dispensers.

Background: In 2017, Tanzania launched the National Action Plan for Antimicrobial Resistance (NAPAR), 2017-2022 and implementation of antibiotic stewardship programmes (ASPs) was one of the agendas. Since the launch of the National Action Plan, no study has been done to assess its implementation. Objectives: To explore the experiences of prescribers and dispensers on implementing ASPs among paediatric patients attending Regional Referral Hospitals (RRHs) in Tanzania. Methods: An exploratory qualitative study was conducted among key informants, in 14 RRHs in Tanzania between July and August 2020. A total of 28 key informants, 14 dispensers in charge of pharmacies and 14 medical doctors in charge of paediatric departments (prescribers), were interviewed. A hybrid thematic analysis was conducted on the gathered information. Results: Most of the study participants were not conversant with the term 'antibiotic stewardship'. Some had heard about the programmes but were not aware of the activities involved in the programme. Those who were knowledgeable on ASPs mentioned the lack of existence of such programmes in their settings. They further added that absence or limited knowledge of the stewardship concepts may have influenced the current poor practices. Barriers to the implementation of ASPs mentioned were lack of laboratory facilities to support culture and susceptibility tests, lack of materials and reagents, management pressure to prevent loss or to generate income, patients' influence and limited training opportunities. Conclusions: Despite launching the NAPAR in 2017, we found limited implementation of ASPs in the management of paediatric patients. This study highlighted some barriers and identified possible intervention points.

Drivers of irrational use of antibiotics among children: a mixed-method study among prescribers and dispensers in Tanzania.

BACKGROUND: Misuse of antibiotics has been associated with poor knowledge, attitude and practice (KAP). Therefore, this study aimed to assess if KAP of prescribers and dispensers could drive irrational use of antibiotics among children in Tanzania. METHODS: A convergent parallel mixed-methods study design that employed quantitative and qualitative approaches was conducted in 14 regional referral hospitals (RRHs). A total of 108 participants, prescribers [54] and dispensers [54] working with the pediatric population in the respective regions participated in a quantitative survey, by filling the standard questionnaire while 28 key informant interviews were conducted with in-charges of units from the pharmacy and pediatric departments. Two key informants (prescriber and dispenser) were selected from each RRH. RESULTS: Overall, among prescribers and dispensers, there was adequate knowledge; 81.5% and 79.6%, p = 0.53, those with positive attitudes were 31.5% and 81.5%, p < 0.001 and poor practices were among 70.4% and 48% p = 0.0312 respectively. Among prescribers, 14.8% agreed and strongly agreed that prescribing antibiotics that a patient did not need does not contribute to resistance. Moreover 19% disagreed to prescribe antibiotics according to local guidelines. Among dispensers, a-quarter of the dispensers thought individual efforts to implement antibiotic stewardship would not make a difference, 17% agreed and strongly agreed that antibiotics can treat viral infection and 7% agreed and strongly agreed antibiotics can be stopped upon resolution of symptoms. From qualitative interviews, both participants displayed an adequate understanding of multi-contributors of antibiotic resistance (AR) including polypharmacy, community self-medication, among others. Regardless, both professions declared to prescribed and dispensed antibiotics according to the antibiotics available in stock at the facility. Furthermore, prescribers perceived laboratory investigation took a long time, hence wasting their time. On the other hand, Dispensers reported not to provide adequate instruction to the patients, after dispensing antibiotics. CONCLUSIONS: Both prescribers and dispensers had adequate knowledge, few prescribers had positive attitudes and the majority had poor practices. Few dispensers had poor attitude and practice. These findings highlight the need to provide adequate training on antimicrobial stewardship and enforce regulation that foster appropriate medical practice.

Determinants of misuse of antibiotics among parents of children attending clinics in regional referral hospitals in Tanzania.

Parents are the important implementers on appropriate/inappropriate use of antibiotics, especially in the pediatric population. Limited studies have associated poor knowledge, attitude, and practice (KAP) among parents with antibiotics misuse. Therefore, this study was conducted to determine the parents' KAP and factors associated with inappropriate use of antibiotics among Tanzanian children. A hospital-based cross-sectional study was conducted in 14 regional referral hospitals (RRHs) in Tanzania between June and September 2020. KAP was estimated using a Likert scale, whereas KAP factors were determined using logistic regression models. A total of 2802 parents were enrolled in the study. The median age (interquartile range) of parents was 30.0 (25-36) years where 82.4% (n = 2305) were female parents. The majority of the parents had primary education, 56.1% (n = 1567). Of 2802 parents, only 10.9% (n = 298) had good knowledge about antibiotics, 16.4% (n = 455) had positive attitude whereas 82.0% (n = 2275) had poor practice on the appropriate use of antibiotics. Parents' education level, i.e., having a university degree (aOR: 3.27 95% CI 1.62-6.63, p = 0.001), good knowledge (aOR: 1.70, 95% CI 1.19-2.23, p = 0.003) and positive attitudes (aOR: 5.56, 95% CI 4.09-7.56, p < 0.001) were significantly associated with the appropriate use of antibiotics in children. Most parents had poor knowledge, negative attitude, and poor practice towards antibiotics use in children. Parents' education level, employment status, knowledge on antibiotic use, and good attitude contributed to the appropriate use of antibiotics in children attending clinics at RRHs.

Closing the know-do gap for child health: UNICEF's experiences from embedding implementation research in child health and nutrition programming.

UNICEF operates in 190 countries and territories, where it advocates for the protection of children's rights and helps meet children's basic needs to reach their full potential. Embedded implementation research (IR) is an approach to health systems strengthening in which (a) generation and use of research is led by decision-makers and implementers; (b) local context, priorities, and system complexity are taken into account; and (c) research is an integrated and systematic part of decision-making and implementation. By addressing research questions of direct relevance to programs, embedded IR increases the likelihood of evidence-informed policies and programs, with the ultimate goal of improving child health and nutrition.This paper presents UNICEF's embedded IR approach, describes its application to challenges and lessons learned, and considers implications for future work.From 2015, UNICEF has collaborated with global development partners (e.g. WHO, USAID), governments and research institutions to conduct embedded IR studies in over 25 high burden countries. These studies focused on a variety of programs, including immunization, prevention of mother-to-child transmission of HIV, birth registration, nutrition, and newborn and child health services in emergency settings. The studies also used a variety of methods, including quantitative, qualitative and mixed-methods.UNICEF has found that this systematically embedding research in programs to identify implementation barriers can address concerns of implementers in country programs and support action to improve implementation. In addition, it can be used to test innovations, in particular applicability of approaches for introduction and scaling of programs across different contexts (e.g., geographic, political, physical environment, social, economic, etc.). UNICEF aims to generate evidence as to what implementation strategies will lead to more effective programs and better outcomes for children, accounting for local context and complexity, and as prioritized by local service providers. The adaptation of implementation research theory and practice within a large, multi-sectoral program has shown positive results in UNICEF-supported programs for children and taking them to scale.

Correction: Effective maternal, newborn and child health programming among Rohingya refugees in Cox's Bazar, Bangladesh: Implementation challenges and potential solutions.

[This corrects the article DOI: 10.1371/journal.pone.0230732.].

Effective maternal, newborn and child health programming among Rohingya refugees in Cox's Bazar, Bangladesh: Implementation challenges and potential solutions.

BACKGROUND: The health status of Rohingya refugees or Forcibly Displaced Myanmar Nationals (FDMNs), especially women and children, is a significant challenge for humanitarian workers in Bangladesh. Though the Government of Bangladesh, in partnership with other organizations, is offering health care services to FDMNs, a comprehensive understanding of the program implementation is required for continuation in the future. This study explores the challenges and potential solutions for effective implementation of maternal, newborn, and child health (MNCH) programs for FDMNs residing in camps of Cox's Bazar, Bangladesh. METHODS: We conducted a qualitative study conducted in Cox's Bazar district, Bangladesh, which involved 34 interviews (15 key informant interviews and 19 in-depth interviews) with relevant persons working in organizations responsible for MNCH services to FDMNs. We relied on both inductive and deductive coding and applied the Consolidated Framework for Implementation Research (CFIR) as a guide to our thematic analysis and presentation of qualitative data. RESULTS: Our study identified some key challenges hindering the effective implementation of MNCH service delivery for the FDMNs. High turnover and poor retention of staff, overlapping of service, weak referral mechanism, complex health information system, and lack of security of the front line health providers were some of the key challenges identified. Motivating the health workers, task shifting, capacity building on emergency obstetric care, training CHW & TBA on danger signs, and ensuring the security of the workers are the potential solutions suggested by the respondents. Selecting a few indicators and the introduction of E-tracker can harmonize the health information system. CONCLUSION: Providing healthcare in an emergency setting has several associated challenges. Considering the CFIR as the base for identifying different challenges and their potential solutions at a different level of the program can prove to be an excellent asset for the program implementers in designing their plans. Two additional domains, context, and security should be included in the CFIR framework for any humanitarian settings.

Public sector services for the prevention of mother-to-child transmission of HIV infection: a micro-costing survey in Namibia and Rwanda.

OBJECTIVE: To assess the costs associated with the provision of services for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus in two African countries. METHODS: In 2009, the costs to health-care providers of providing comprehensive PMTCT services were assessed in 20 public health facilities in Namibia and Rwanda. Information on prices and on the total amount of each service provided was collected at the national level. The costs of maternal testing and counselling, male partner testing, CD4+ T-lymphocyte (CD4+ cell) counts, antiretroviral prophylaxis and treatment, community-based activities, contraception for 2 years postpartum and early infant diagnosis were estimated in United States dollars (US$). FINDINGS: The estimated costs to the providers of PMTCT, for each mother-infant pair, were US$202.75-1029.55 in Namibia and US$94.14-342.35 in Rwanda. These costs varied with the drug regimen employed. At 2009 coverage levels, the maximal estimates of the national costs of PMTCT were US$3.15 million in Namibia and US$7.04 million in Rwanda (or < US$0.75 per capita in both countries). Adult testing and counselling accounted for the highest proportions of the national costs (37% and 74% in Namibia and Rwanda, respectively), followed by management and supervision. Treatment and prophylaxis accounted for less than 20% of the costs of PMTCT in both study countries. CONCLUSION: The costs involved in the PMTCT of HIV varied widely between study countries and in accordance with the protocols used. However, since per-capita costs were relatively low, the scaling up of PMTCT services in Namibia and Rwanda should be possible.

HIV-free survival among nine- to 24-month-old children born to HIV-positive mothers in the Rwandan national PMTCT programme: a community-based household survey.

BACKGROUND: Operational effectiveness of large-scale national programmes for the prevention of mother to child transmission (PMTCT) of HIV in sub-Saharan Africa remains limited. We report on HIV-free survival among nine- to 24-month-old children born to HIV-positive mothers in the national PMTCT programme in Rwanda. METHODS: We conducted a national representative household survey between February and May 2009. Participants were mothers who had attended antenatal care at least once during their most recent pregnancy, and whose children were aged nine to 24 months. A two-stage stratified (geographic location of PMTCT site, maternal HIV status during pregnancy) cluster sampling was used to select mother-infant pairs to be interviewed during household visits. Alive children born from HIV-positive mothers (HIV-exposed children) were tested for HIV according to routine HIV testing protocol. We calculated HIV-free survival at nine to 24 months. We subsequently determined factors associated with mother to child transmission of HIV, child death and HIV-free survival using logistic regression. RESULTS: Out of 1448 HIV-exposed children surveyed, 44 (3.0%) were reported dead by nine months of age. Of the 1340 children alive, 53 (4.0%) tested HIV positive. HIV-free survival was estimated at 91.9% (95% confidence interval: 90.4-93.3%) at nine to 24 months. Adjusting for maternal, child and health system factors, being a member of an association of people living with HIV (adjusted odds ratio: 0.7, 95% CI: 0.1-0.995) improved by 30% HIV-free survival among children, whereas the maternal use of a highly active antiretroviral therapy (HAART) regimen for PMTCT (aOR: 0.6, 95% CI: 0.3-1.07) had a borderline effect. CONCLUSIONS: HIV-free survival among HIV-exposed children aged nine to 24 months is estimated at 91.9% in Rwanda. The national PMTCT programme could achieve greater impact on child survival by ensuring access to HAART for all HIV-positive pregnant women in need, improving the quality of the programme in rural areas, and strengthening linkages with community-based support systems, including associations of people living with HIV.

Under-two child mortality according to maternal HIV status in Rwanda: assessing outcomes within the National PMTCT Program.

INTRODUCTION: We sought to compare risk of death among children aged under-2 years born to HIV positive mother (HIV-exposed) and to HIV negative mother (HIV non-exposed), and identify determinants of under-2 mortality among the two groups in Rwanda. METHODS: In a stratified, two-stage cluster sampling design, we selected mother-child pairs using national Antenatal Care (ANC) registers. Household interview with each mother was conducted to capture socio-demographic data and information related to pregnancy, delivery and post-partum. Data were censored at the date of child death. Using Cox proportional hazard model, we compared the hazard of death among HIV-exposed children and HIV non-exposed children. RESULTS: Of 1,455 HIV-exposed children, 29 (2.0%; 95% CI: 1.3%-2.7%) died by 6 months compared to 18 children of the 1,565 HIV non-exposed children (1.2%; 95% CI: 0.6%-1.7%). By 9 months, cumulative risks of death were 3.0% (95%; CI: 2.2%-3.9%) and 1.3% (96%; CI: 0.7%-1.8%) among HIV-exposed and HIV non-exposed children, respectively. By 2 years, the hazard of death among HIV-exposed children was more than 3 times higher (aHR:3.5; 95% CI: 1.8-6.9) among HIV-exposed versus non-exposed children. Risk of death by 9-24 months of age was 50% lower among mothers who attended 4 or more antenatal care (ANC) visits (aHR: 0.5, 95% CI: 0.3-0.9), and 26% lower among families who had more assets (aHR: 0.7, 95% CI: 0.5-1.0). CONCLUSION: Infant mortality was independent of perinatal HIV exposure among children by 6 months of age. However, HIV-exposed children were 3.5 times more likely to die by 2 years. Fewer antenatal visits, lower household assets and maternal HIV seropositive status were associated with increased mortality by 9-24 months.

Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT) of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens.

BACKGROUND: Mother-to-child transmission (MTCT) of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV) regimens for the prevention of MTCT (PMTCT); but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp) to md-ARV regimens in a resource-limited setting. METHODS: Program data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy) of sites providing PMTCT as a stand-alone service (stand-alone site) versus sites providing PMTCT as well as antiretroviral therapy (ART) (full package site). CD4 cell count screening, enrollment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp) prophylaxis and highly active antiretroviral therapy (HAART) were analysed. RESULTS: From July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+) during antenatal care (ANC). CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at full package sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending stand-alone sites (relative risk (RR) = 1.3; 95% confidence interval (CI): 1.1-1.4). Enrollment of HIV+ pregnant women in ART services was almost twice as likely at full package sites than at stand-alone sites (RR = 1.9; 95% CI: 1.5-2.3). However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0). CONCLUSIONS: All sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT. Full package sites offer the most efficient model for providing immunological assessment and enrollment into care and treatment of HIV+ pregnant women. Strengthening the capacity of stand-alone PMTCT sites to achieve the same objectives is paramount.