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

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

Effectiveness of antenatal dexamethasone in reducing respiratory distress syndrome and mortality in preterm neonates: a nested case control study.

BACKGROUND: Respiratory distress syndrome (RDS) is a significant cause of preterm neonatal morbidity and mortality globally. Measures like the use of antenatal corticosteroids (ACS) and immediate resuscitation of the newborn after birth are taken to abate preterm related complications. Most studies that evidenced the benefit of ACS were done in high resource settings. Therefore, this study was conducted to assess the effectiveness of ACS in reducing RDS and neonatal mortality in preterm neonates in resource-limited settings. METHODS: A three months prospective nested case-control study (1:2 unmatched) was conducted at Muhimbili National Hospital and Amana regional referral hospital in Dar es salaam, Tanzania. Neonates delivered at 28 to 34 gestational weeks were enrolled and followed up until discharge. Data analysis was done using the statistical package of social sciences version 23. Logistic regression analysis was used to determine the effect of ACS on the RDS and mortality in the cohort, controlling for important maternal and neonatal variables. All tests were considered statistically significant at p < 0.05. RESULTS: Out of 330 preterm neonates enrolled, 110 were cases and 220 were controls. The median gestational age at delivery was 30 weeks and 6 days (IQR 4.68) among cases and 33 weeks (IQR 3) among controls. One-minute APGAR score of < 7 (AOR: 3.11; 95% CI 1.54-6.30), and neonatal birth weight (AOR: 0.998; 95% CI 0.997-0.999) were significantly associated with RDS. No significant association was observed between ACS exposure and RDS occurrence (AOR: 1.65; 95% CI 0.86 - 3.15). The overall mortality rate was 9 per 1000 neonates. Neonatal mortality occurred only among cases whereby, a unit increase in gestational age was associated with a 30% reduction in neonatal mortality (Adjusted hazard ratio, AHR: 0.70, 95% CI: 0.5-0.92, p = 0.011). CONCLUSION: Decrease in gestational age, one minute APGAR score of < 7 and decreasing birth weight were associated with RDS among preterm neonates. ACS was not associated with reduced RDS occurrence and neonatal mortality rates. Moreover, increase in gestation age was the only factor found to be protective against preterm neonatal mortality.

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

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

Knowledge and participation in mass drug administration against lymphatic filariasis and soil-transmitted helminth infections among the community members in Dar es Salaam, Tanzania.

BACKGROUND: Although the WHO has made an effort to ensure optimal participation of the community in mass drug administration (MDA) against lymphatic filariasis (LF) and soil-transmitted helminth infections (STHIs), studies are still reporting suboptimal coverage. This study assessed the knowledge and participation of the community in MDA against LF and SHTIs in Tanzania to provide updates on its acceptability. METHODS: A cross-sectional study was conducted in Dar es Salaam from December 2021 to February 2022 among market vendors. The information regarding demographic characteristics, knowledge and participation in MDA was collected using a questionnaire. Statistical Package for Social science version 26 was used for data analysis. RESULTS: More than half of the participants demonstrated an adequate level of knowledge of LF and STHI, 212 (50.8%) and 267 (64%), respectively. Only 286 (68.5%) reported having heard about MDA against LF and STHIs, out of which 119 (42%) had taken the medication. Of those who disagreed to participate in MDA, 20 (50%) claimed to fear the side effects of the medication. CONCLUSIONS: This study found that the community has average knowledge and poor participation in MDA against LF and STHIs. Community sensitization is recommended to increase the participation of the community.

Barriers and Facilitators of Availability of Hydroxyurea for Sickle Cell Disease in Tanzania; A Qualitative Study of Pharmaceutical Manufacturers, Importers, and Regulators.

Despite three decades of proven safety and effectiveness of hydroxyurea in modifying sickle cell disease (SCD), its accessibility is limited in Sub-Saharan Africa, which shares 75% of the world's SCD burden. Therefore, it is time to explore the barriers and facilitators for manufacturing and importation of hydroxyurea for SCD in Tanzania. This was qualitative research that employed a case study approach. Purposive sampling followed by an in-depth interview (IDI) using a semi-structured questionnaire aspired by data saturation enabled us to gather data from 10 participants. The study participants were people with more than three years of experience in pharmaceuticals importation, manufacturing, and regulation. The audio-recorded data were verbatim transcribed and analyzed using thematic analysis. Two themes were generated. The first comprised barriers for importation and manufacturing of hydroxyurea with sub-themes such as inadequate awareness of SCD and hydroxyurea, limited market, and investment viability. The second comprised opportunities for importation and manufacturing of hydroxyurea with sub-themes such as awareness of activities performed by medicines regulatory authority and basic knowledge on SCD and hydroxyurea. Inadequate understanding of SCD, hydroxyurea, and orphan drug regulation are major issues that aggravate the concern for limited market and investment viability. Existing opportunities are a starting point towards increasing the availability of hydroxyurea.

Nasopharyngeal Carriage and Antibiogram of Pneumococcal and Other Bacterial Pathogens from Children with Sickle Cell Disease in Tanzania.

Background: Bacterial infections contribute significantly to morbidity and mortality in sickle cell disease (SCD) patients, particularly children under five years of age. In Tanzania, prophylaxis against pneumococcal infection among children with SCD advocates the use of both oral penicillin V (PV) and pneumococcal vaccines (PNV). Therefore, this study aimed to investigate nasopharyngeal carriage and antibiogram of Streptococcal pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) in children with SCD in Tanzania. Methods: This cross-sectional study was undertaken at the two Sickle Pan-African Research Consortium (SPARCO) study sites in Dar es salaam, Tanzania. The study was conducted for six months and enrolled children with SCD between the ages of 6 to 59-months. A semi-structured questionnaire was used to collect patient data. Nasopharyngeal swabs were collected from all participants and cultured for Streptococcal pneumoniae and other bacterial isolates. Antimicrobial susceptibility tests of the isolates were done using the disc diffusion method. Results: Out of 204 participants, the overall prevalence of bacterial carriage was 53.4%, with S. aureus (23.5%), coagulase-negative Staphylococci (CoNS) (23%) and S. pneumoniae (7.8%) being commonly isolated. In antibiotic susceptibility testing, S. aureus isolates were most resistant to penicillin (81.8%), whereas 81.3% of S. pneumoniae isolates were resistant to co-trimoxazole. The least antimicrobial resistance was observed for chloramphenicol for both S. aureus and S. pneumoniae isolates (6.3% versus 0%). The proportion of multi-drug resistance (MDR) was 66.7% for S. aureus isolates and 25% for S. pneumoniae isolates. Conclusion: There are substantially high nasopharyngeal carriage pathogenic bacteria in children with SCD in Dar es Salaam, Tanzania. The presence of MDR strains to the commonly used antibiotics suggests the need to reconsider optimizing antimicrobial prophylaxis in children with SCD and advocacy on pneumococcal vaccines.

Adherence, Effectiveness and Safety of Dolutegravir Based Antiretroviral Regimens among HIV Infected Children and Adolescents in Tanzania.

Objectives:This study aimed at assessing adherence, effectiveness, and safety of DTG-based HAART regimens among HIV-infected children and adolescents in Tanzania. Methods: This was a single-center prospective cohort study, conducted at the pediatric HIV Clinic in Mbeya, Tanzania. A binary logistic regression model was used to determine predictors of undetectable viral load at week 24. The results were significant when P-value was <0.05. Results: A total of 200 patients were enrolled with the majority (85.5%) being treatment experienced. High adherence levels (71%) were observed using the pharmacy refill method. At week 24, the overall proportion of patients with undetectable viral load was 70.2%. The predictors of undetectable viral load were age, World Health Organization (WHO) clinical stage, baseline VL and adherence to pharmacy refill. Conclusion: The majority of patients attained undetectable viral load 6 months after using DTG based regimen. DTG-based regimens were generally safe with few ADEs reported.

The Effects of Sickle Cell Disease on the Quality of Life: A Focus on the Untold Experiences of Parents in Tanzania.

Tanzania is among the top five countries with a high burden of sickle cell disease (SCD) in the world. Even though the effects of SCD on quality of life have been documented in other countries including Nigeria and the United States of America, few are known from Tanzania. Therefore, this study focused on evaluating the effects of SCD on the quality of life among children living with SCD and their parents. The study employed a qualitative approach to interview purposively selected parents of children who have lived with SCD and have used hydroxyurea (HU) for more than 3 years. The in-depth interviews were conducted with 11 parents of children with SCD at the Muhimbili University of Health and Allied Sciences (MUHAS) in Dar-es-salaam, Tanzania. A semi-structured interview guide was used. Interviews were audio-recorded, transcribed, and thematically analyzed. Three themes were generated including psycho-social effects: family conflicts and divorce, limited access to education, stress and fear; financial effects: Employment limitation, reduced efficiency and productivity, loss of job and lack of self-keeping expenses; and physical effects: physical disability and dependence, and burden of the frequent crisis. Children living with SCD and their parents suffer psycho-social, financial, and physical impacts of the disease. Appropriate interventions should be introduced to minimize the observed effects as ways of improving the quality of life of the individuals living with SCD and their caregivers.

Prevalence and determinants of non-communicable diseases including depression among HIV patients on antiretroviral therapy in Dar es Salaam, Tanzania.

OBJECTIVE: People living with HIV/AIDS (PLHA) are experiencing growing co-morbidities due to an increase in life expectancy and the use of long-term antiretroviral therapy (ART). The lack of integrated non-communicable diseases (NCDs) screening and management at the HIV care and treatment centres (CTCs) make it difficult to determine the trends of NCD co-morbidity among patients with HIV. This study aimed to assess the burden and determinants of common NCDs, including depression among patients with HIV. METHODS: Analytical cross-sectional study of 1318 HIV patients enrolled using systematic random sampling conducted from April to November 2020. Five large CTCs in district referral hospitals were selected representing the five districts of Dar es Salaam including Mwananyamala, Temeke, and Amana regional referral hospitals and Sinza and Vijibweni hospitals. The study population consisted of adult PLHA aged 18 years and above. The primary outcome measure was the prevalence of NCDs among HIV patients. Observation of actual NCD medications or their purchase receipts or booked NCD clinic appointments that PLHA had during the study period was used to verify the reported presence of NCDs. The secondary outcome measure was the prevalence of probable depression among PLHA. The locally validated Swahili Patient Health Questionnaire (PHQ-9) was used to screen for depressive symptom severity. A logistic regression model was used to identify factors associated with common NCDs and those associated with probable depression. Potential risk factors that were statistically significant at a P-value of 0.2 or less in univariable analysis were included as potential confounders in multivariable models. RESULTS: The median age of participants was 42 (IQR 35-49) years, with 32.7% in the 36-45 years age group. The majority of patients were women (69%). Most (80.5%) had achieved HIV viral (VL) suppression (a serum HIV VL of <1000 copies/ml). Overall, 14.3% of self-reported an NCD with evidence of their current medication for the NCD from receipts for medication purchased and appointments from NCD clinics they attended. In the multivariable analyses, higher odds of NCDs were in older patients (>45 years) and those with a weight above 75 kg (P < 0.05). Male patients had 51% reduced odds of NCDs (aOR 0.49; 95% CI: 0.32-0.74) than females (P < 0.001). Probable depression prevalence was 11.8%, and depressed patients had more than twice the odds of having NCDs than those without depression (aOR 2.26; 95% CI: 1.45-3.51; P < 0.001). CONCLUSION: This study determined co-existing previously diagnosed NCDs among PLHA accessing care and high levels of depressive symptom severity. We recommend additional research on the feasibility, acceptability, and cost implications of screening and treating NCDs on HIV care platforms to provide evidence for Tanzania's integrated HIV/NCD care model.

Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review.

BACKGROUND: A wide spread of chloroquine resistance prompted its discontinued use for treatment of uncomplicated malaria in several African countries. However, disappearances of chloroquine-resistant parasites have been reported in areas with restricted use of chloroquine. This review reports the current prevalence of chloroquine-resistant Plasmodium falciparum using Pfcrt K76T and Pfmdr1 N86Y genotypes. METHODS: A PROSPERO registered systematic review searched evidence from PubMed/MEDLINE, Science Direct and Google Scholar. The search included studies on chloroquine-resistant/ susceptible P. falciparum in humans between January 1st, 2000 and May 15th, 2020. The search was conducted on 15th of May, 2020. RESULTS: Out of 519 searched records, 15 studies qualified for final analysis with 8040 samples genotyped for Pfcrt K76T. Of 8040, 43.6% (837/1572; 95%CI: -0.9 to 88.1%) carried resistant genotypes versus 23.0% (1477/6468; 95%CI: 15.7-30.2%) while for 4698 samples analyzed for Pfmdr1 N86Y, 52.4% (592/1090; 95%CI: 42.3-62.5%) had resistant genotypes versus 25.9% (1314/3608; 95%CI: 5.8-46.0%), before and after chloroquine withdrawal, respectively. The median time since chloroquine withdrawal to data collection was 7.0 (interquartile range: 4.5-13.5) years. Low prevalence of resistant genotypes (Pfcrt K76T) was reported in Zambia (0%) in 2013, Malawi (0.1%) in 2009, Tanzania (0.2%) in 2018 and Madagascar (0.3%) in 2007 with significant variations in the included studies. CONCLUSIONS: Chloroquine-resistant P. falciparum continues to disappear in countries with withdrawal of chloroquine. Areas with significant susceptible parasites, reintroduction of chloroquine can be considered, preferably in combination with other safe and affordable antimalarials.

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.

Knowledge of use of antibiotics among consumers in Tanzania.

BACKGROUND: Studies assessing consumers' knowledge of the rational use of antibiotics are essential to understand the knowledge gap before intervention strategies are instituted. OBJECTIVES: To assess the knowledge of rational use of antibiotics among consumers in Dar es Salaam, Tanzania. METHODS: A cross-sectional study assessing knowledge of rational use of antibiotics among 960 consumers was conducted in Dar es salaam in March 2021. Participants were consecutively enrolled from outpatient pharmacies in selected public and private hospitals and marketplaces in Ilala Municipality. Data were collected using the WHO-validated questions on knowledge of consumers of antibiotic uses. RESULTS: Overall, 196 (20.4%) and 503 (52.4%) participants demonstrated good knowledge of rational antibiotic use and conditions that can be treated with antibiotics, respectively. However, 678 (70.6%) responded that they stopped using antibiotics after dose completion, 515 (53.6%) would request the same antibiotic if it had helped to treat a similar condition in the past and 406 (42.3%) are willing to use the same antibiotic if a friend or family member used the medication previously to treat similar signs and symptoms. Besides, the following conditions were mentioned as being treatable with antibiotics: influenza (50.7%), sore throat (61.4%) and urinary tract infection (60.5%). CONCLUSIONS: The majority of the consumers had poor knowledge of the rational uses of antibiotics and a moderate proportion had good knowledge of the conditions that are treatable with antibiotics. Those with a high level of education and with health insurance had good knowledge of rational uses of antibiotics.

The Existence of High Bacterial Resistance to Some Reserved Antibiotics in Tertiary Hospitals in Tanzania: A Call to Revisit Their Use.

BACKGROUND: Antibiotic resistance poses burden to the community and health-care services. Efforts are being made at local, national and global level to combat the rise of antibiotic resistance including antibiotic stewardship. Surveillance to antibiotic resistance is of importance to aid in planning and implementing infection prevention and control measures. The study was conducted to assess the resistance pattern to cefepime, clindamycin and meropenem, which are reserved antibiotics for use at tertiary hospitals in Tanzania. METHODS: A hospital-based antibiotic resistance surveillance was conducted between July and November 2019 at Muhimbili National Hospital and Bugando Medical Center, Tanzania. All organisms isolated were identified based on colony morphology, Gram staining and relevant biochemical tests. Antibiotic susceptibility testing was performed on Muller-Hinton agar using Kirby-Bauer disc diffusion method. Antibiotic susceptibility was performed according to the protocol by National Committee for Clinical Laboratory Standards. RESULTS: A total of 201 clinical samples were tested in this study. Urine (39.8%, n=80) and blood (35.3%, n=71) accounted for most of the collected samples followed by pus (16.9%, n=34). The bacterial resistance to clindamycin, cefepime and meropenem was 68.9%, 73.2% and 8.5%, respectively. About 68.4% Staphylococcus aureus isolates were resistant to clindamycin whereby 56.3%, 75.6%, 93.8% and 100% of the tested Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa and Enterobacter cloacae, respectively, were cefepime resistant. About 8.5% of isolated Klebsiella spp were resistant and 6.4% had intermediate susceptibility to meropenem. Also, Pseudomonas aeruginosa was resistant by 31.2% and 25% had intermediate susceptibility to meropenem. CONCLUSION: The bacterial resistance to clindamycin and cefepime is high and low in meropenem. Henceforth, culture and susceptibility results should be used to guide the use of these antibiotics. Antibiotics with low resistance rate should be introduced to the reserve category and continuous antibiotic surveillance is warranted.

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.

Pregnancy and CYP3A5 Genotype Affect Day 7 Plasma Lumefantrine Concentrations.

Pregnancy and pharmacogenetics variation alter drug disposition and treatment outcome. The objective of this study was to investigate the effect of pregnancy and pharmacogenetics variation on day 7 lumefantrine (LF) plasma concentration and therapeutic responses in malaria-infected women treated with artemether-lumefantrine (ALu) in Tanzania. A total of 277 (205 pregnant and 72 nonpregnant) women with uncomplicated Plasmodium falciparum malaria were enrolled. Patients were treated with ALu and followed up for 28 days. CYP3A4, CYP3A5, and ABCB1 genotyping were done. Day 7 plasma LF concentration and the polymerase chain reaction (PCR) - corrected adequate clinical and parasitological response (ACPR) at day 28 were determined. The mean day 7 plasma LF concentrations were significantly lower in pregnant women than nonpregnant women [geometric mean ratio = 1.40; 95% confidence interval (CI) of geometric mean ratio (1.119-1.1745), P < 0.003]. Pregnancy, low body weight, and CYP3A5*1/*1 genotype were significantly associated with low day 7 LF plasma concentration (P < 0.01). PCR-corrected ACPR was 93% (95% CI = 89.4-96.6) in pregnant women and 95.7% (95% CI = 90.7-100) in nonpregnant women. Patients with lower day 7 LF concentration had a high risk of treatment failure (mean 652 vs. 232 ng/ml, P < 0.001). In conclusion, pregnancy, low body weight, and CYP3A5*1 allele are significant predictors of low day 7 LF plasma exposure. In turn, lower day 7 LF concentration is associated with a higher risk of recrudescence. SIGNIFICANCE STATEMENT: This study reports a number of factors contributing to the lower day 7 lumefantrine (LF) concentration in women, which includes pregnancy, body weight, and CYP3A5*1/*1 genotype. It also shows that day 7 LF concentration is a main predictor of malaria treatment. These findings highlight the need to look into artemether-LF dosage adjustment in pregnant women so as to be able to maintain adequate drug concentration, which is required to reduce treatment failure rates in pregnant women.

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.

Effect of pharmacogenetics on plasma lumefantrine pharmacokinetics and malaria treatment outcome in pregnant women.

BACKGROUND: Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. METHODS: Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania. Day-7 LF plasma concentration and genotyping forCYP2B6 (c.516G>T, c.983T>C), CYP3A4*1B, CYP3A5 (*3, *6, *7) and ABCB1 c.4036A4G were determined. Blood smear for parasite quantification by microscopy, and dried blood spot for parasite screening and genotyping using qPCR and nested PCR were collected at enrolment up to day 28 to differentiate between reinfection from recrudescence. Treatment response was recorded following the WHO protocol. RESULTS: In total, 92 pregnant women in their second and third trimester were included in the study and 424 samples were screened for presence of P. falciparum. Parasites were detected during the follow up period in 11 (12%) women between day 7 and 28 after treatment and PCR genotyping confirmed recrudescent infection in 7 (63.3%) women. The remaining four (36.4%) pregnant women had reinfection: one on day 14 and three on day 28. The overall PCR-corrected treatment failure rate was 9.0% (95% CI 4.4-17.4). Day 7 LF concentration was not significantly influenced by CYP2B6, CYP3A4*1B and ABCB1 c.4036A>G genotypes. Significant associations between CYP3A5 genotype and day 7 plasma LF concentrations was found, being higher in carriers of CYP3A5 defective variant alleles than CYP3A5*1/*1 genotype. No significant influence of CYP2B6, CYP3A5 and ABCB1 c.4036A>Genotypes on malaria treatment outcome were observed. However, CYP3A4*1B did affect malaria treatment outcome in pregnant women followed up for 28 days (P = 0.018). CONCLUSIONS: Genetic variations in CYP3A4 and CYP3A5may influence LF pharmacokinetics and treatment outcome in pregnant women.

Implementation of co-trimoxazole preventive therapy policy for malaria in HIV-infected pregnant women in the public health facilities in Tanzania.

BACKGROUND: In 2011, Tanzania adopted a policy for provision of daily co-trimoxazole prophylaxis to HIV-infected pregnant women for prevention of malaria and other opportunistic infections. As per the policy, HIV-infected pregnant women should not be given sulfadoxine-pyrimethamine (SP) for intermittent preventive therapy. The challenges associated with this policy change and the extent to which the new policy for prevention of malaria in pregnant women coinfected with HIV was implemented need to be assessed. AIM: To assess the implementation of malaria-preventive therapy policy among HIV-infected pregnant women in the public health facilities in Dar es Salaam, Tanzania. METHODOLOGY: The study was conducted in Kinondoni Municipality, Dar es Salaam, Tanzania, from January 2015 to July 2015. Three hundred and fifty-three HIV-infected pregnant women who were attending antenatal clinics (ANCs) and using co-trimoxazole for prevention of malaria were interviewed. Twenty-six health care workers working at the ANCs were also interviewed regarding provision of co-trimoxazole prophylaxis to pregnant women. A knowledge scale was used to grade the level of knowledge of health care providers. Focus group discussions were also conducted with 18 health care workers to assess the level of implementation of the policy and the challenges encountered. RESULTS: Twenty-three (6.5%) pregnant women with known HIV serostatus were using co-trimoxazole for prevention of opportunistic infections even before they became pregnant. Out of the 353 HIV-infected pregnant women, eight (2.5%) were coadministered with both SP and co-trimoxazole. Sixty (16.7%) pregnant women had poor adherence to co-trimoxazole prophylaxis. Out of the 26 interviewed health care providers, 20 had high level of knowledge regarding malaria-preventive therapy in HIV-infected pregnant women. Lack of adequate supply of co-trimoxazole in health facilities and inadequate training of health care providers were among the factors causing poor implementation of co-trimoxazole prophylaxis for prevention of malaria in HIV-infected pregnant women. CONCLUSION: There is a need to continue sensitization of pregnant women and communities about the importance of early attendance to the ANCs for testing of HIV and provision of co-trimoxazole prophylaxis. Availability of co-trimoxazole in the health facilities, regular training, and sensitization of health care providers are necessary for effective implementation of this policy.

Malaria prevalence, severity and treatment outcome in relation to day 7 lumefantrine plasma concentration in pregnant women.

BACKGROUND: Day 7 plasma concentrations of lumefantrine (LF) can serve as a marker to predict malaria treatment outcome in different study populations. Two main cut-off points (175 and 280 ng/ml) are used to indicate plasma concentrations of LF, below which treatment failure is anticipated. However, there is limited data on the cumulative risk of recurrent parasitaemia (RP) in relation to day 7 LF plasma concentrations in pregnant women. This study describes the prevalence, severity, factors influencing treatment outcome of malaria in pregnancy and day 7 LF plasma concentration therapeutic cut-off points that predicts treatment outcome in pregnant women. METHODS: This was a one-arm prospective cohort study whereby 89 pregnant women with uncomplicated Plasmodium falciparum malaria receiving artemether-lumefantrine (ALu) participated in pharmacokinetics and pharmacodynamics study. Blood samples were collected on days 0, 2, 7, 14, 21 and 28 for malaria parasite quantification. LF plasma concentrations were determined on day 7. The primary outcome measure was an adequate clinical and parasitological response (ACPR) after treatment with ALu. RESULTS: The prevalence of malaria in pregnant women was 8.1 % (95 % CI 6.85-9.35) of whom 3.4 % (95 % CI 1.49-8.51) had severe malaria. The overall PCR-uncorrected treatment failure rate was 11.7 % (95 % CI 0.54-13.46 %). Low baseline hemoglobin (<10 g/dl) and day 7 LF concentration <600 ng/ml were significant predictors of RP. The median day 7 LF concentration was significantly lower in pregnant women with RP (270 ng/ml) than those with ACPR (705 ng/ml) (p = 0.016). The relative risk of RP was 4.8 folds higher (p = 0.034) when cut-off of <280 ng/ml was compared to ≥280 ng/ml and 7.8-folds higher (p = 0.022) when cut-off of <600 ng/ml was compared to ≥600 ng/ml. The cut-off value of 175 ng/ml was not associated with the risk of RP (p = 0.399). CONCLUSIONS: Pregnant women with day 7 LF concentration <600 ng/ml are at high risk of RP than those with ≥600 ng/ml. To achieve effective therapeutic outcome, higher day 7 venous plasma LF concentration ≥600 ng/ml is required for pregnant patients than the previously suggested cut-off value of 175 or 280 ng/ml for non-pregnant adult patients.