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.

Adherence to Antiretroviral Therapy Among HIV-Infected Clients Attending Opioid Treatment Program Clinics in Dar es Salaam, Tanzania.

Background Adherence to antiretroviral therapy (ART) among key populations like human immunodeficiency virus (HIV)-positive People Who Inject Drugs (PWID) could be challenging, especially in low and middle-income countries (LMICs). Therefore we conducted this study to assess the adherence to ART among HIV-positive PWID attending three methadone clinics in Dar es Salaam, Tanzania. Methods A cross-sectional study was conducted at three methadone clinics in Dar es Salaam, Tanzania. Adherence to ART was measured by using pharmacy refill and patient self-report methods. Bivariate and multivariable logistic regression was performed to determine the association between dependent and independent variables. A p-value of less than 0.05 was considered to be statistically significant. Results Of the 180 participants, 97.2% recorded good adherence to ART as per the pharmacy refill method. However, only 66.1% of the PWID were found to adhere to ART based on the patient self-report method. Upon associating the self-report method with a viral load of >1000 copies/mL, participants were 3.37 times more likely to have missed their ART dose at least once in the last three days before their refill visit compared to those with a viral load of <1000 copies/mL [Adjusted Odds ratio; 3.37, 95% Confidence Interval (95% CI); 1.35 - 8.45, p = 0.009]. Conclusion The adherence to ART among HIV-infected PWID attending methadone clinics was high based on the pharmacy refill method but relatively much lower based on the patient self-report method. There was a strong correlation between viral load and the level of adherence measured by the patient self-report method.

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.

Premarital genetic screening and care of Tanzanian children with sickle cell disease: a qualitative study on parents' views and experiences.

Genetic testing and counselling is one of the approaches to reduce the high birth rate of individuals with sickle cell disease (SCD). A descriptive phenomenological approach was used to explore parents' views on premarital genetic screening for sickle cell trait and their experiences in the care of Tanzanian children with SCD using a face-to-face in-depth interview. The study was conducted at sickle cell clinic at tertiary hospital in Dar es Salaam region between June and August 2020. The study found that most of the parents with SCD children knew about genetic testing and counselling after the diagnosis of their children's SCD status. Major approaches employed in managing SCD crises were supportive, preventive, and symptomatic. Parents expressed a heavy burden related to caretaking due to the lack of financial support and stigmatization. These affected their children's quality of care and management. In conclusion, participants expressed a preference for premarital genetic testing, where others insisted it becomes compulsory. In addition, there should be an adequate clinic for early screening, accessible therapeutic support and long-term follow up for children with SCD. Support to poor families with individual with SCD through national health assurance scheme and free provision of preventive medications such as hydroxyurea, is recommended.

Electrolytes supplementation can decrease the risk of nephrotoxicity in patients with solid tumors undergoing chemotherapy with cisplatin.

BACKGROUND: Cisplatin is an important drug in the treatment of various Cancers. However, this drug causes nephrotoxicity that is linked to electrolyte derangement. The aim of this study was to evaluate the effect of electrolyte supplementation in reducing kidney injury in patients receiving cisplatin-based regimen. METHODS: This was non-randomized interventional study conducted at Ocean Road Cancer Institute (ORCI) among patients with confirmed solid tumors. Patients who received cisplatin-based chemotherapy at a dose of ≥50 mg with intravenous normal saline supplemented with Magnesium, Calcium and Potassium (triple electrolyte supplementation) were compared with those who received cisplatin-based chemotherapy with normal saline alone. The patients were followed up for 4 weeks and serum creatinine was measured at every visit. Nephrotoxicity was defined as serum creatinine elevation > 1.5 times that at baseline. RESULTS: A total of 99 patients were recruited, whereby 49 patients (49.5%) received electrolyte supplementation (treatment group) and 50 patients (51.5%) did not receive electrolyte supplementation (control group). The incidence risk of nephrotoxicity was 20.41% (n = 10) in the treatment group and 54% (n = 27) in the control group. Patients in the control group were 2.6 times more likely to experience nephrotoxicity as compared to treatment group [Relative Risks (RR); 2.6, 95%CI; 1.5-4.9, P < 0.0001]. The most common malignancy was cervical cancer, n = 43 (87.8%) in treatment group and n = 45 (90.0%) in the control group (P = 0.590). The Kaplan-Meier analysis and the log-rank test revealed that electrolytes supplementation was associated with extended survival with less nephrotoxicity incidences [P = 0.0004; Hazard ratio (HR) 0.3149; 95% CI 0.165 to 0.6011]. CONCLUSIONS: Electrolytes supplementation decreases the risk of nephrotoxicity after chemotherapy with cisplatin. A randomized controlled trial with a larger sample size is recommended to evaluate the robustness of these findings.

The magnitude of prescribing medicines by brand names at Muhimbili National Hospital, Tanzania.

Background: Tanzania National Treatment Guidelines and National Therapeutic Committee circular of 2012 requires prescribers to prescribe medicines using their generic names as recommended by the World Health Organization. The implementation of the aforementioned recommendations by prescribers is not well documented in our settings. Therefore, this study aimed to explore the compliance on the use of generic names by prescribers at Muhimbili National Hospital. Methods: A descriptive cross-sectional study was conducted at Muhimbili National Hospital from January to May 2019 in both inpatient and outpatient pharmacy units. Data were analyzed using SPSS, version 23. Chi-square test was used to analyze proportions between the different variables of the study. A p-value for significance was <0.05. Results: Of 1001 prescriptions analyzed, 71.6% contained medicines prescribed using brand names. The mean (±standard deviation (SD)) number of medicines per prescription was 2.98 (±1.5). The most frequently prescribed medicines by brand names were a combination of vitamin and mineral supplements (34.4%) followed by antibiotics (26.7%). Medical doctors (25.6%) and medical specialists (21.6%) prescribed ⩾2 medicines using brand names per prescription compared to interns (15.0%) and residents (6.9%) (p < 0.001). Conclusion: Prescribing medicines using brand names was highly observed in this study. Supplements and antibiotics were among the products that were highly prescribed using their brand names. Qualitative studies to explore reasons for brand name prescribing practices are recommended.

Utilization patterns of malaria chemoprophylaxis among Tanzanian children attending sickle cell clinic in Dar es Salaam tertiary hospitals.

BACKGROUND: Malaria is among the leading cause of infection in individuals with sickle cell disease (SCD) living in sub-Saharan Africa, including Tanzania. However, after 2005 the standard treatment guidelines (STGs) on malaria chemoprevention for SCD patients were non-existent, and at present no medicine is recommended for SCD patients. Since several anti-malarials have been approved for the treatment of malaria in Tanzania, it is important to establish if there is a continued use of chemoprevention against malaria among SCD children. METHODS: A cross-sectional, hospital-based study was conducted between January and June 2019 at tertiary hospitals in Dar es Salaam. Data were collected using a semi-questionnaire and analysed using SPSS software version 25. The descriptive statistics were summarized using proportions, while factors associated with the use of chemoprophylaxis were analysed using multivariate logistic regression. Statistical significance of p < 0.05 was accepted. RESULTS: A total of 270 SCD children were involved. The median age of SCD children was 6 years (interquartile range (IQR): 3-11 years). Of 270 SCD children, 77% (number (n) = 218) of children with SCD had not been diagnosed with malaria in the previous year, whereas 12.6% (n = 34) of children were admitted because of malaria in the previous year. Regarding the use of chemoprophylaxis in SCD children, 32.6% (n = 88) of parents were aware that, chemoprophylaxis against malaria is recommended in SCD children. Of the 270 participants, 17% (n = 46) were using malaria chemoprophylaxis. A majority used artemisinin combination therapy (ACT), 56.8% (n = 26). Of 223 parents who did not give chemoprophylaxis, the majority (n = 142, 63.7%) indicated unavailability at clinics as the reason. Children whose parents were primary level educated were 9.9 times more likely to not use chemoprophylaxis (adjusted odds ratio (AOR); 9.9, 95% CI 1.8-56.5, P = 0.01) compared to those whose parents had tertiary education. CONCLUSION: Despite the lack of STGs, a small proportion of children with SCD were using malaria chemoprophylaxis where the majority used ACT, i.e., dihydroartemisinin-piperaquine.

A decade since sulfonamide-based anti-malarial medicines were limited for intermittent preventive treatment of malaria among pregnant women in Tanzania.

BACKGROUND: Despite the development of resistance to Plasmodium falciparum malaria, sulfadoxine-pyrimethamine is still effective for intermittent preventive treatment of malaria in pregnancy (IPTp). In Tanzania, more than 10 years have passed since sulfadoxine-pyrimethamine and sulfamethopyrazine-pyrimethamine (SPs) were reserved for IPTp only. However, the retail pharmaceutical outlet dispensers' knowledge and their compliance with the policies have not been recently explored. Therefore, this study was designed to investigate dispensers' knowledge about these medications together with their actual dispensing practices, a decade since they were limited for IPTp use only. METHODS: This descriptive cross-sectional study was conducted between February and July 2017 in all municipalities of Dar-es-Salaam city. Data were collected by direct interviews using a structured questionnaire to assess knowledge and a simulated client approach was used to assess the actual practice of medicine dispensers. Data analysis was done by using SPSS version 20 and Chi square test was used to test significant differences in proportions between different categorical variables. A p-value of less than 0.05 was considered to be statistically significant. RESULTS: A random sample of 422 medicine dispensers participated in this study whereby 185 (43.8%) were from community pharmacies and 237 (56.2%) from accredited drug dispensing outlets. The study revealed that SPs were available in 76% of the community pharmaceutical outlets in Dar es Salaam. In general majority of the dispensers (64%) had moderate to high knowledge about SPs and their indication. About 80% of the dispensers were aware that SP is reserved for IPTp. However, irrespective of the level of knowledge, almost all dispensers (92%) were willing to dispense the medicines for the purpose of treating malaria, contrary to the current Tanzania malaria treatment guideline. CONCLUSION: Majority of the medicine dispensers in the community pharmaceutical outlets were knowledgeable about SPs and their indications. Disappointingly, almost all dispensers irrespective of their levels of knowledge were willing to dispense SPs for treatment of malaria contrary to the available treatment guidelines.

Ready-to-use food supplement, with or without arginine and citrulline, with daily chloroquine in Tanzanian children with sickle-cell disease: a double-blind, random order crossover trial.

BACKGROUND: Sickle-cell disease increases the risk of malnutrition. Low arginine and nitric oxide bioavailability are implicated in morbidity related to sickle-cell disease. Simple interventions are required, especially in low-income settings. We aimed to test the hypotheses that: (1) supplementary arginine, citrulline, and daily chloroquine increase bioavailable arginine and flow-mediated dilatation (FMD; maximal diameter change; FMDmax%), a measure of nitric oxide-dependent endothelial function; and (2) protein energy supplementation in the form of ready-to-use supplementary food (RUSF) improves the height-for-age and body-mass index-for-age Z-scores in children with sickle-cell disease. METHODS: We performed a double-blind, random order crossover trial with two 4-month intervention periods (each followed by 4-month washout periods) in Muhimbili National Hospital in Dar-es-Salaam, Tanzania. We enrolled 119 children from the Muhimbili Sickle Cohort who were aged 8-12 years, naive to hydroxyurea, and had documented HbSS phenotype. Two formulations of RUSF (providing 500 kcal/day) were tested: basic (RUSF-b), with which children also received weekly chloroquine (150 mg or 225 mg chloroquine base, dependent on bodyweight); and vascular (RUSF-v), which was fortified with arginine and citrulline (designed to achieve mean intakes of 0·2 g/kg per day of arginine and 0·1 g/kg per day of citrulline), and with which children received daily chloroquine (maximum 3 mg chloroquine base/kg per day). Children were randomly allocated to receive either RUSF-b first or RUSF-v first and, after a washout period, were then given the other treatment. The primary outcomes in comparing the two RUSF formulations were mean plasma arginine, arginine to ornithine ratio, and arginine to asymmetric dimethylarginine ratio, and mean FMDmax%. The primary outcomes of the combined effect of both RUSF interventions were mean height-for-age Z-score and body-mass index-for-age Z-score. Analyses were done on the eligible intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01718054; and with ISRCTN74331412. FINDINGS: Between Aug 9, 2012, and Feb 26, 2014, 145 children were randomised (71 children to RUSF-v first and 74 children to RUSF-b first) and 119 children were treated, of whom 114 children yielded complete data for all reported endpoints. The ratio of arginine to ornithine (mean of individual differences -8·67%, 95% CI -19·55 to 2·20; p=0·12) and the mean FMDmax% (1·00, -0·47 to 2·47; p=0·18) did not significantly differ between the RUSF-b and RUSF-v treatments. However, the arginine to asymmetric dimethylarginine ratio was significantly increased by RUSF-v compared with RUSF-b (56·26%, 31·13 to 81·38; p<0·0001). In planned analyses that used mixed effects models to estimate the effect of each intervention compared with the participants at baseline or during washout periods, the arginine to asymmetric dimethylarginine ratio increased following both RUSF-v treatment (86%; p<0·0001) and RUSF-b treatment (40%; p<0·0001). However, FMDmax% was higher after treatment with RUSF-v (0·92; p<0·0001) but not RUSF-b (0·39; p=0·22). Following either intervention (RUSF-b and RUSF-v, pooled) body-mass index-for-age Z-score (0·091; p=0·001) and height-for-age Z-score (0·013; p=0·081) increased compared with baseline and washout timepoints. In 83 participants in the treated population, there were 71 adverse events during the intervention, of which 21 (30%) were serious, and 81 adverse events during the washout periods, of which 26 (32%) were serious (p=0·31), including one patient who died in the second washout period. INTERPRETATION: RUSF providing 500 kcal/day results in small weight gains in children with sickle-cell disease. However, even without arginine and citrulline fortification, RUSF seems to ameliorate arginine dysregulation and might improve endothelial function. Long-term studies are required to assess whether these physiological effects translate to improved clinical outcomes and better growth and development in patients with sickle-cell disease. FUNDING: Wellcome Trust.

A pilot study of a non-invasive oral nitrate stable isotopic method suggests that arginine and citrulline supplementation increases whole-body NO production in Tanzanian children with sickle cell disease.

BACKGROUND: Low bioavailability of nitric oxide (NO) is implicated in the pathophysiology of sickle cell disease (SCD). We designed a nested pilot study to be conducted within a clinical trial testing the effects of a daily ready-to-use supplementary food (RUSF) fortified with arginine (Arg) and citrulline (Citr) vs. non-fortified RUSF in children with SCD. The pilot study evaluated 1) the feasibility of a non-invasive stable isotope method to measure whole-body NO production and 2) whether Arg+Citr supplementation was associated with increased whole-body NO production. SUBJECTS: Twenty-nine children (70% male, 9-11years, weight 16.3-31.3 kg) with SCD. METHODS: Sixteen children received RUSF+Arg/Citr (Arg, 0.2  g/kg/day; Citr, 0.1  g/kg/day) in combination with daily chloroquine (50 mg) and thirteen received the base RUSF in combination with weekly chloroquine (150 mg). Plasma amino acids were assessed using ion-exchange elution (Biochrom-30, Biochrom, UK) and whole-body NO production was measured using a non-invasive stable isotopic method. RESULTS: The RUSF+Arg/Citr intervention increased plasma arginine (P = .02) and ornithine (P = .003) and decreased the ratio of asymmetric dimethylarginine to arginine (P = .01), compared to the base RUSF. A significant increase in whole-body NO production was observed in the RUSF-Arg/Citr group compared to baseline (weight-adjusted systemic NO synthesis 3.38 ± 2.29 µmol/kg/hr vs 2.35 ± 1.13 µmol/kg/hr, P = .04). No significant changes were detected in the base RUSF group (weight-adjusted systemic NO synthesis 2.64 ± 1.14 µmol/kg/hr vs 2.53 ± 1.12 µmol/kg/hr, P = .80). CONCLUSIONS: The non-invasive stable isotopic method was acceptable and the results provided supporting evidence that Arg/Citr supplementation may increase systemic NO synthesis in children with SCD.