The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites

Michael Delves and colleagues compare the activity of 50 current and experimental antimalarials against liver, sexual blood, and mosquito stages of selected human and nonhuman parasite species, including Plasmodium falciparum, Plasmodium berghei, and Plasmodium yoelii

What motivates antibiotic dispensing in accredited drug dispensing outlets in Tanzania? A qualitative study

Background: Tanzania introduced the accredited drug dispensing outlet (ADDO) program more than a decade ago. Previous evaluations have generally shown that ADDOs meet defined standards of practice better than non-accredited outlets. However, ADDOs still face challenges with overuse of antibiotics for acute respiratory infections (ARI) and simple diarrhea, which contributes to the emergence of drug resistance. This study aimed to explore the attitudes of ADDO owners and dispensers toward antibiotic dispensing and to learn how accreditation has influenced their dispensing behavior. Methods: The study used a qualitative approach. We conducted in-depth interviews with ADDO owners and dispensers in Ruvuma and Tanga regions where the government implemented the ADDO program under centralized and decentralized approaches, respectively; a secondary aim was to compare differences between the two regions. Results: Findings indicate that the ADDO program has brought about positive changes in knowledge of dispensing practices. Respondents were able to correctly explain treatment guidelines for ARI and diarrhea. Almost all dispensers and owners indicated that unnecessary use of antibiotics contributed to antimicrobial resistance. Despite this knowledge, translating it to appropriate dispensing practice is still low. Dispensers’ behavior is driven by customer demand, habit (“mazoea”), following inappropriate health facility prescriptions, and the need to make a profit. Although the majority of dispensers reported that they had intervened in situations where customers asked for antibiotics unnecessarily, they tended to give in to clients’ requests. Small variations were noted between the two study regions; for example, some dispensers in Ruvuma reported sending clients with incorrect prescriptions back to the health facility, a practice that may reflect regional differences in ADDO implementation and in Integrated Management of Childhood Illness training. Dispensers in rural settings reported more challenges in managing ARI and diarrhea than their urban counterparts did. Conclusion: To reduce inappropriate antibiotic use, integrated interventions must include communities, health facilities, and ADDOs. Periodic refresher training with an emphasis on communication skills is crucial in helping dispensers deal with customers who demand antibiotics. Responsible authorities should ensure that ADDOs always have the necessary tools and resources available

Increasing Access to Subsidized Artemisinin-based Combination Therapy through Accredited Drug Dispensing Outlets in Tanzania

Abstract Background In Tanzania, many people seek malaria treatment from retail drug sellers. The National Malaria Control Program identified the accredited drug dispensing outlet (ADDO) program as a private sector mechanism to supplement the distribution of subsidized artemisinin-based combination therapies (ACTs) from public facilities and increase access to the first-line antimalarial in rural and underserved areas. The ADDO program strengthens private sector pharmaceutical services by improving regulatory and supervisory support, dispenser training, and record keeping practices. Methods The government's pilot program made subsidized ACTs available through ADDOs in 10 districts in the Morogoro and Ruvuma regions, covering about 2.9 million people. The program established a supply of subsidized ACTs, created a price system with a cost recovery plan, developed a plan to distribute the subsidized products to the ADDOs, trained dispensers, and strengthened the adverse drug reactions reporting system. As part of the evaluation, 448 ADDO dispensers brought their records to central locations for analysis, representing nearly 70% of ADDOs operating in the two regions. ADDO drug register data were available from July 2007-June 2008 for Morogoro and from July 2007-September 2008 for Ruvuma. This intervention was implemented from 2007-2008. Results During the pilot, over 300,000 people received treatment for malaria at the 448 ADDOs. The percentage of ADDOs that dispensed at least one course of ACT rose from 26.2% during July-September 2007 to 72.6% during April-June 2008. The number of malaria patients treated with ACTs gradually increased after the start of the pilot, while the use of non-ACT antimalarials declined; ACTs went from 3% of all antimalarials sold in July 2007 to 26% in June 2008. District-specific data showed substantial variation among the districts in ACT uptake through ADDOs, ranging from ACTs representing 10% of all antimalarial sales in Kilombero to 47% in Morogoro Rural. Conclusions The intervention increased access to affordable ACTs for underserved populations. Indications are that antimalarial monotherapies are being "crowded out" of the market. Importantly, the transition to ACTs has been accomplished in an environment where the safety and efficacy of the drugs and the quality of services are being monitored and regulated. This paper presents a description of the pilot program implementation, results of the program evaluation, and a discussion of the challenges and recommendations that will be used to guide rollout of subsidized ACT in ADDOs in the rest of Tanzania and possibly in other countries.</p

Development and validation of a global positioning system-based "map book" system for categorizing cluster residency status of community members living in high-density urban slums in Blantyre, Malawi.

A significant methodological challenge in implementing community-based cluster-randomized trials is how to accurately categorize cluster residency when data are collected at a site distant from households. This study set out to validate a map book system for use in urban slums with no municipal address systems, where classification has been shown to be inaccurate when address descriptions were used. Between April and July 2011, 28 noncontiguous clusters were demarcated in Blantyre, Malawi. In December 2011, antiretroviral therapy initiators were asked to identify themselves as cluster residents (yes/no and which cluster) by using map books. A random sample of antiretroviral therapy initiators was used to validate map book categorization against Global Positioning System coordinates taken from participants' households. Of the 202 antiretroviral therapy initiators, 48 (23.8%) were categorized with the map book system as in-cluster residents and 147 (72.8%) as out-of-cluster residents, and 7 (3.4%) were unsure. Agreement between map books and the Global Positioning System was 100% in the 20 adults selected for validation and was 95.0% (κ = 0.96, 95% confidence interval: 0.84, 1.00) in an additional 20 in-cluster residents (overall κ = 0.97, 95% confidence interval: 0.90, 1.00). With map books, cluster residents were classified rapidly and accurately. If validated elsewhere, this approach could be of widespread value in that it would enable accurate categorization without home visits

What roles do accredited drug dispensing outlets in Tanzania play in facilitating access to antimicrobials? Results of a multi-method analysis

Background: People in low-income countries purchase a high proportion of antimicrobials from retail drug shops, both with and without a prescription. Tanzania’s accredited drug dispensing outlet (ADDO) program includes dispenser training, enforcement of standards, and the legal right to sell selected antimicrobials. We assessed the role of ADDOs in facilitating access to antimicrobials. Methods: We purposively chose four regions, randomly selected three districts and five wards per district. Study methods included interviews at 1200 households regarding care-seeking for acute illness and knowledge about antimicrobials; mystery shoppers visiting 306 ADDOs posing as a caregiver of a child with 1) pneumonia, 2) mild acute respiratory infection (ARI), or 3) a runny nose and request for co-trimoxazole; and audits of antimicrobial availability and prices at 84 public health facilities (PHFs) and 96 ADDOs. Results: Four hundred sixty seven (76 %) members from 367 (77 %) households had recently sought care outside the home for acute illness; 128 had purchased antimicrobials, of which 61 % had been recommended by a doctor or nurse and 32 % by an ADDO dispenser. Only 29 % obtained the antimicrobial at a PHF, whereas, 48 % purchased them at an ADDO. Most thought that ADDOs are convenient place for care, usually have needed medicines, and have high quality services and products, contrasting with 66 % who reported dissatisfaction with PHF waiting times and 56 % with medicine availability. One-third (34 %) of mystery shoppers presenting the mild ARI scenario were inappropriately sold an antimicrobial and 85 % were sold one on request; encouragingly, 99 % presenting a case of pneumonia received either an antimicrobial, referral to a trained provider, or request to bring the child for examination. Overall, 63 and 60 % of the 15 tracer antimicrobials were in stock in ADDOs and PHFs, respectively; ADDOs had significantly more antimicrobial formulations for children available (83 vs. 51 %). Of 369 records of antimicrobial sales in 47 ADDOs, 63 % were dispensed on prescription. Conclusion: ADDOs have increased access to antimicrobials in Tanzania. Community members see them as integral to the health system. Antimicrobials are overused due to poor ADDO dispensing, poor PHF prescribing, and inappropriate public demand. Multi-pronged interventions are needed to address all determinants. Electronic supplementary material The online version of this article (doi:10.1186/s13756-015-0075-2) contains supplementary material, which is available to authorized users

Understanding the Role of Accredited Drug Dispensing Outlets in Tanzania’s Health System

Introduction: People in many low-income countries access medicines from retail drug shops. In Tanzania, a public-private partnership launched in 2003 used an accreditation approach to improve access to quality medicines and pharmaceutical services in underserved areas. The government scaled up the accredited drug dispensing outlet (ADDO) program nationally, with over 9,000 shops now accredited. This study assessed the relationships between community members and their sources of health care and medicines, particularly antimicrobials, with a specific focus on the role ADDOs play in the health care system. Methods: Using mixed methods, we collected data in four regions. We surveyed 1,185 households and audited 96 ADDOs and 84 public/nongovernmental health facilities using a list of 17 tracer drugs. To determine practices in health facilities, we interviewed 1,365 exiting patients. To assess dispensing practices, mystery shoppers visited 306 ADDOs presenting one of three scenarios (102 each) about a child’s respiratory symptoms. Results and Discussion Of 614 household members with a recent acute illness, 73% sought outside care—30% at a public facility and 31% at an ADDO. However, people bought medicines more often at ADDOs no matter who recommended the treatment; of the 581 medicines that people had received, 49% came from an ADDO. Although health facilities and ADDOs had similar availability of antimicrobials, ADDOs had more pediatric formulations available (p<0.001). The common perception was that drugs from ADDOs are more expensive, but the difference in the median cost to treat pneumonia was relatively minimal (US$0.26 in a public facility and US$0.30 in an ADDO). Over 20% of households said they had someone with a chronic condition, with 93% taking medication, but ADDOs are allowed to sell very few chronic care-related medicines. ADDO dispensers are trained to refer complicated cases to a health facility, and notably, 99% of mystery shoppers presenting a pneumonia scenario received an antimicrobial (54%), a referral (90%), or both (45%), which are recommended practices for managing pediatric pneumonia. However, one-third of the dispensers needlessly sold antibiotics for cold symptoms, and 85% sold an antibiotic on request. In addition, the pneumonia scenario elicited more advice on handling the illness than the cold symptoms scenario (61% vs. 15%; p<0.0001), but overall, only 44% of the dispensers asked any of the shoppers about danger signs potentially associated with pneumonia in a child. Conclusion: ADDOs are the principal source of medicines in Tanzania and an important part of a multi-faceted health care system. Poor prescribing in health facilities, poor dispensing at ADDOs, and inappropriate patient demand continue to contribute to inappropriate medicines use. Therefore, while accreditation has attempted to address the quality of pharmaceutical services in private sector drug outlets, efforts to improve access to and use of medicines in Tanzania need to target ADDOs, public/nongovernmental health facilities, and the public to be effective

Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial

BACKGROUND: Artemisinin-combination therapy (ACT) is recommended as first-line treatment of falciparum malaria throughout the world, and fixed-dose combinations are preferred by WHO; whether a single gametocytocidal dose of primaquine should be added is unknown. We aimed to compare effectiveness of four fixed-dose ACTs and a loose tablet combination of artesunate and mefloquine, and assess the addition of a single gametocytocidal dose of primaquine. METHODS: In an open-label randomised trial in clinics in Rakhine state, Kachin state, and Shan state in Myanmar (Burma) between Dec 30, 2008, and March 20, 2009, we compared the effectiveness of all four WHO-recommended fixed-dose ACTs (artesunate-mefloquine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, artemether-lumefantrine) and loose artesunate-mefloquine in Burmese adults and children. Eligible patients were those who presented to the clinics with acute uncomplicated Plasmodium falciparum malaria or mixed infection, who were older than 6 months, and who weighed more than 5 kg. Treatments were randomised in equal numbers within blocks of 50 and allocation was in sealed envelopes. All patients were also randomly assigned to receive either a single dose of primaquine 0·75 mg base/kg or not. Patients were followed up for 63 days. Treatment groups were compared by analysis of variance and multiple logistic regression. The primary outcome was the 63 day recrudescence rate. This study is registered with clinicaltrials.gov, number NCT00902811. FINDINGS: 155 patients received artesunate-amodiaquine, 162 artemether-lumefantrine, 169 artesunate-mefloquine, 161 loose artesunate-mefloquine, and 161 dihydroartemisinin-piperaquine. By day 63 of follow-up, 14 patients (9·4%; 95% CI 5·7-15·3%) on artesunate-amodiaquine had recrudescent P falciparum infections, a rate significantly higher than for artemether-lumefantrine (two patients; 1·4%; 0·3-5·3; p=0·0013), fixed-dose artesunate-mefloquine (0 patients; 0-2·3; p<0·0001), loose artesunate-mefloquine (two patients; 1·3%; 0·3-5·3; p=0·0018), and dihydroartemisinin-piperaquine (two patients 1·3%; 0·3-5·2%; p=0·0012). Hazard ratios for re-infection (95% CI) after artesunate-amodiaquine were 3·2 (1·3-8·0) compared with the two artesunate-mefloquine groups (p=0·01), 2·6 (1·0-6-0) compared with artemether-lumefantrine (p=0·04), and 2·3 (0·9-6·0) compared with dihydroartemisinin-piperaquine (p=0·08). Mixed falciparum and vivax infections were common: 129 (16%) had a mixed infection at presentation and 330 (41%) patients had one or more episodes of Plasmodium vivax infection during follow-up. The addition of a single dose of primaquine (0·75 mg/kg) reduced P falciparum gametocyte carriage substantially: rate ratio 11·9 (95% CI 7·4-20·5). All regimens were well tolerated. Adverse events were reported by 599 patients, most commonly vomiting and dizziness. Other side-effects were less common and were not related to a specific treatment. INTERPRETATION: Artesunate-amodiaquine should not be used in Myanmar, because the other ACTs are substantially more effective. Artesunate-mefloquine provided the greatest post-treatment suppression of malaria. Adding a single dose of primaquine would substantially reduce transmission potential. Vivax malaria, not recurrent falciparum malaria, is the main complication after treatment of P falciparum infections in this region. FUNDING: Médecins sans Frontières (Holland) and the Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme

Additional file 1: of What roles do accredited drug dispensing outlets in Tanzania play in facilitating access to antimicrobials? Results of a multi-method analysis

Annex 1. Household survey respondent opinions about health services and medicines. Annex 2. Predictors of summary factor scores of respondent opinions about health services from univariate logistic regressions. (DOCX 45 kb

Percent Availability and Median Price Ratios of Tracer Medicines by Facility Type.

<p>Percent Availability and Median Price Ratios of Tracer Medicines by Facility Type.</p