Do Health Workers' Preferences Influence their Practices? Assessment of Providers' Attitude and Personal use of new Treatment Recommendations for Management of Uncomplicated Malaria, Tanzania.

\ud \ud Due to growing antimalarial drug resistance, Tanzania changed malaria treatment policies twice within a decade. First in 2001 chloroquine (CQ) was replaced by sulfadoxine-pyrimethamine (SP) for management of uncomplicated malaria and by late 2006, SP was replaced by artemether-lumefantrine (AL). We assessed health workers' attitudes and personal practices following the first treatment policy change, at six months post-change and two years later. Two cross-sectional surveys were conducted in 2002 and 2004 among healthcare workers in three districts in South-East Tanzania using semi-structured questionnaires. Attitudes were assessed by enquiring which antimalarial was considered most suitable for the management of uncomplicated malaria for the three patient categories: i) children below 5; ii) older children and adults; and iii) pregnant women. Practice was ascertained by asking which antimalarial was used in the last malaria episode by the health worker him/herself and/or dependants. Univariate and multivariate logistic regression was used to identify factors associated with reported attitudes and practices towards the new treatment recommendations. A total of 400 health workers were interviewed; 254 and 146 in the first and second surveys, respectively. SP was less preferred antimalarial in hospitals and private health facilities (p<0.01) in the first round, and the preference worsened in the second round. In the first round, clinicians did not prefer SP for children below age of 5 and pregnant women (p<0.01), but two years later, they did not prefer it for all patient scenarios. SP was the most commonly used antimalarial for management of the last malaria episode for health workers and their dependants in both rounds, in the public sector (p<0.01). Health workers in the dispensaries had the highest odds of using SP for their own treatment [adjusted OR- first round: 6.7 (95%CI: 1.9-23.4); crude OR- second round: 4.5 (1.5-13.3)]. Following changes in malaria treatment recommendations, most health workers did not prefer the new antimalarial drug, and their preferences worsened over time. However, many of them still used the newly recommended drug for management of their own or family members' malaria episode. This indicates that, other factors than providers' attitude may have more influence in their personal treatment practices

Implementing ideal health policy in a fragile health system: the example of expanding the use of malaria rapid diagnostic tests in mainland Tanzania

Malaria confirmation before treatment provides an opportunity for improving the quality of malaria case management in endemic regions. However, increased coverage of this strategy is facing many organizational, logistical and technical challenges that threaten its success. Introducing an intervention with system-wide effect, such as the use of malaria rapid diagnostic tests in areas where malaria is still a public health problem, should be accompanied by system strengthening measures to better attain the goal of improving quality of care

Evaluation of Two Malaria Rapid Diagnostic Tests Quality Assurance (mRDT’s QA) Methods in Peripheral Health Facilities, Rural Tanzania.

\ud WHO recommends confirming suspected malaria cases before initiation of treatment. Due to the imited availability of quality microscopy services, this recommendation has been followed with increased use of antigen-detecting malaria rapid diagnostic tests (mRDTs) in many malaria endemic countries. With the increased use of mRDTs, the need for a thorough mRDT quality assurance (RDT QA) method has become more apparent. One of the WHO recommendations for RDT QA is to monitor the tests in field use monthly, by comparing mRDT results to reference microscopy. This study was carried out to monitor mRDT performance in selected health facilities using two quality assurance methods; first based on ference microscopy and second based on detection of parasite DNA by real time quantitative PCR (qPCR) on dried blood spots (DBS); as well as assessing the cost and timeliness of the two QA methods. Blood samples were collected from patients undergoing a rapid test for malaria for two to three consecutive days per month, for five months, in 12 health facilities in Iringa rural and Mufindi districts. The health workers were instructed to label RDT cassettes, blood smear slides, and filter papers for DBS with matching unique ID stickers. A sticker was also placed in the log book where RDT results were recorded. Blood smears (BS) were first read at the district hospital (BS1) and then transported to Bagamoyo for a reference reading at the IHI- Bagamoyo laboratory (BS2). A third BS reader (BS3) was consulted from Muhimbili University of Health and Allied Sciences (MUHAS) in case of discordant results between BS1 and BS2. Molecular analysis involved extraction of parasite DNA from DBS samples using a QIAamp DNA Mini Kit. Sample DNA aliquots were compared against standard solutions with parasite DNA diluted 10-fold to give a parasitemia ranging from 200,000/μL to 20/μL. About 20% of the study DNA aliquots were sent to the CDC laboratory in Atlanta in order to validate qPCR results performed at the Bagamoyo laboratory. Data were entered in Microsoft Access (Microsoft Corporation, 2006) and analyzed in STATA 10 (StataCorp, Texas USA). Because of the known limitations of mRDTs to detect parasitemia below 200 parasites/μL, BS and PCR results greater than or equal to 5 parasites/200 WBC or 200 parasites/μL were considered positive in comparisons with mRDT performance. In the univariate analysis, proportions of positive tests were compared among the three types of tests: mRDT, microscopy and qPCR. Microscopy readings were categorized into 3 groups; BS1, BS2 and /or BS summary which is an average of BS1 and BS2. In case of discordant results between BS1 and BS2, a third reader- BS3 was consulted. Chi-squared test was done to assess differences in proportion of positive tests per district; whereas McNemar’s test was Malaria RDT QA Final Report, March 2012 5 used to assess the difference in test positivity by type of test. Kappa statistic was used to quantify the strength of the agreement between tests results. In addition, we examined health workers performance of the testing procedure when attending patients at a health facility, using a predefined checklist. Towards the end of the study, an evaluation of health worker acceptability was carried out to assess preferences between the two RDT QA methods. We received 2369 samples and 2324 (98%) had complete information. mRDTs had the highest positivity rate (6.5%). The proportion of positive tests by all types of tests was slightly higher in Iringa DC, but only qPCR and BS2 showed statistically significant differences in positivity rate between the two districts, where Iringa DC had more positive tests than Mufindi DC (p<0.05). When qPCR was a gold standard, mRDTs had higher sensitivity (68.6%, 95%CI: 55.0-79.7) than microscopy (53.7%, 95%CI: 38.7- 68.0) but highest mRDT sensitivity was achieved with comparison to microscopy (85.3%, 95%CI: 70.0- 93.6). All tests had higher inter-observer agreement than would be expected by chance. Substantial high inter-observer agreement (kappa =0.75; p<0.001) was seen amongst the microscopists i.e. district’s quality assurance officers and the reference microscopy readings. Assessment of the time needed to process BS at the district level revealed that, smears at district level took on average 8 days (min 2 to max 33) to be processed and provide feedback; but up to an average of 44 days (min 19 to max 98) to get a second reading. Many health workers were aware that the use of mRDTs was due to changes in treatment policy (11/30), and patients who qualify for the test are those suspected to have malaria. Majority (16/30) related assessment of control line as a measure of test accuracy and suggested the use of microscopy for quality control of mRDT results (15/30). Their major concerns were mRDTs’ inability to give parasite count, stock-out of the tests kits in their working areas and the frequency of negative results. This evaluation encountered several challenges, among them were 1. Poor quality of blood smears made at health facilities, especially dispensaries, which do not have laboratory services. 2. About 3.5% of BS1 slides could not be processed for BS2 because they were damaged during transportation and/or poor quality of smears. This accounts for the small difference in the numbers of BS assessed between two readers. 3. We were not able to prepare standard concentration solutions for qPCR analysis in the country. 4. Problems with PCR machine and inability to repair it that necessitated shipment of the machine, to and from, the manufacturers in Europe (Germany). Malaria RDT QA Final Report, March 2012 6 Due to these challenges, qPCR results were not available until after specimen collection had ended. In this study malaria positivity was higher with mRDTs than microscopy and qPCR for the 200 parasites/μL lower boundary of positivity threshold. This could either be due to the strict lower cut-off point for microscopy and qPCR parasite density or higher false positivity of mRDTs due to persistent antigen in blood, errors in mRDTs performance or other patient’s characteristics. When qPCR was taken as gold standard, mRDTs showed better sensitivity than microscopy, but when microscopy was regarded as a gold standard, mRDTs showed higher sensitivity than with qPCR. However, results of qPCR demonstrated a better correlation (inter-observer agreement) with those of microscopy than with mRDTs. The challenges of performing qPCR, as observed in this evaluation, make it unsuitable for quality assurance of mRDTs in routine care, Tanzania. The high inter-observer agreement between districts’ and reference microscopists (K=0.75) and higher tests performances of BS1 when BS2 was a comparator, demonstrates the competence shown by district’s technicians/ technologists to suffice their involvement as reference microscopists for quality assurance of mRDTs in their respective districts. This is also complimented by a fact that, both BS1 and BS2 had more similar performance when qPCR was taken as a gold standard. In this setting, a microscopy-based quality assurance system to assess mRDT performance in routine use may be a practical and suitable method. However, long distance transportation of smears should be avoided.\u

Health System Factors Associated With Correct use of Artemether-Lumefantrine for Management of Uncomplicated Malaria in Rural Tanzania

Poor adherence to and inappropriate use of antimalarials leads to ineffective cure and promote development of drug resistance. We assessed quality of malaria case management in two areas with health and demographic surveillance systems in rural Tanzania to ascertain health worker and facility factors that influence correct prescription and correct dosing of an artemisinin based combination therapy (ACT); Artemether-Lumefantrine (ALu). Exit interviews were conducted to all patients attending for initial illness consultation at health facilities. We collected information about health worker’s training, supervision visits and inventoried facility capacity and availability of medical products related to care of malaria patients. Data were double entered in EPI data and analyzed in STATA version 10 We used logistic regression to assess association of different health system factors to correct use of ALu. The outcomes variables were correct treatment, correct dosing and receiving counselling messages, and the predictors were a range of health worker, health facility and patient factors. Total of 1471 patients were included in this analysis. Majority of patients were seen in dispensaries 70.5 %; (95% confidence interval (95%CI): 57.6-80.8) and in public health facilities 80.2% (95%CI: 72.4-86.1). Work experience seems to be a significant predictor of health workers’ compliance to treatment recommendation. Availability of medical products at health facility and patient characteristics are shown to influence correct use of treatment recommendations. The need to develop targeted interventions to address health system bottlenecks that affect quality of care; such as in-availability of medical products is becoming more apparent

Health Worker Factors Associated with Prescribing of Artemisinin Combination Therapy for Uncomplicated Malaria in Rural Tanzania.

Improving malaria case management is partially dependent on health worker compliance with clinical guidelines. This study assessed health worker factors associated with correct anti-malarial prescribing practices at two sites in rural Tanzania. Repeated cross-sectional health facility surveys were conducted during high and low malaria transmission seasons in 2010 and collected information on patient consultations and health worker characteristics. Using logistic regression, the study assessed health worker factors associated with correct prescription for uncomplicated malaria defined as prescription of artemisinin-based combination therapy (ACT) for patients with fever and Plasmodium falciparum asexual infection based on blood slide or malaria rapid diagnostic test (RDT) according to national treatment guidelines. The analysis included 685 patients with uncomplicated malaria who were seen in a health facility with ACT in stock, and 71 health workers practicing in 30 health facilities. Overall, 58% of malaria patients were correctly treated with ACT. Health workers with three or more years' work experience were significantly more likely than others to prescribe correctly (adjusted odds ratio (aOR) 2.9; 95% confidence interval (CI) 1.2-7.1; p = 0.019). Clinical officers (aOR 2.2; 95% CI 1.1-4.5; p = 0.037), and nurse aide or lower cadre (aOR 3.1; 95% CI 1.3-7.1; p = 0.009) were more likely to correctly prescribe ACT than medical officers. Training on ACT use, supervision visits, and availability of job aids were not significantly associated with correct prescription. Years of working experience and health worker cadre were associated with correct ACT prescription for uncomplicated malaria. Targeted interventions to improve health worker performance are needed to improve overall malaria case management

Field Evaluation of the Photo-induced Electron Transfer Fluorogenic Primers (PET) Real-time PCR for the Detection of Plasmodium falciparum in Tanzania.

Accurate diagnosis of malaria infections remains challenging, especially in the identification of submicroscopic infections. New molecular diagnostic tools that are inexpensive, sensitive enough to detect low-level infections and suitable in laboratory settings of resource-limited countries are required for malaria control and elimination programmes. Here the diagnostic potential of a recently developed photo-induced electron transfer fluorogenic primer (PET) real-time polymerase chain reaction (PCR) called PET-PCR was investigated. This study aimed to (i) evaluate the use of this assay as a method for the detection of both Plasmodium falciparum and other Plasmodium species infections in a developing country's diagnostic laboratory; and, (ii) determine the assay's sensitivity and specificity compared to a nested 18S rRNA PCR. Samples used in this study were obtained from a previous study conducted in the region of Iringa, Tanzania. A total of 303 samples from eight health facilities in Tanzania were utilized for this evaluation. All samples were screened using the multiplex PET-PCR assay designed to detect Plasmodium genus and P. falciparum initially in laboratory in Tanzania and then repeated at a reference laboratory at the CDC in the USA. Microscopy data was available for all the 303 samples. A subset of the samples were tested in a blinded fashion to find the sensitivity and specificity of the PET-PCR compared to the nested 18S rRNA PCR. Compared to microscopy, the PET-PCR assay was 59% more sensitive in detecting P. falciparum infections. The observed sensitivity and specificity were 100% (95% confidence interval (CI0.95) = 94-100%) and (CI0.95 = 96-100%), respectively, for the PET-PCR assay when compared to nested 18S rRNA PCR. When compared to 18S rRNA PCR, microscopy had a low sensitivity of 40% (CI0.95 = 23-61%) and specificity of 100% (CI0.95 = 96-100%). The PET-PCR results performed in the field laboratory in Tanzania were in 100% concordance with the results obtained at the reference laboratory in the USA. The PET-PCR is a new molecular diagnostic tool with similar performance characteristics as commonly used PCR methods that is less expensive, easy to use, and amiable to large scale-surveillance studies in developing country settings

A Nationwide Survey of the Quality of Antimalarials in Retail Outlets in Tanzania

INTRODUCTION\ud \ud Retail pharmaceutical products are commonly used to treat fever and malaria in sub-Saharan African countries. Small scale studies have suggested that poor quality antimalarials are widespread throughout the region, but nationwide data are not available that could lead to generalizable conclusions about the extent to which poor quality drugs are available in African communities. This study aimed to assess the quality of antimalarials available from retail outlets across mainland Tanzania.\ud \ud METHODS AND FINDINGS\ud \ud We systematically purchased samples of oral antimalarial tablets from retail outlets across 21 districts in mainland Tanzania in 2005. A total of 1080 antimalarial formulations were collected including 679 antifol antimalarial samples (394 sulfadoxine/pyrimethamine and 285 sulfamethoxypyrazine/pyrimethamine), 260 amodiaquine samples, 63 quinine samples, and 51 artemisinin derivative samples. A systematic subsample of 304 products was assessed for quality by laboratory based analysis to determine the amount of the active ingredient and dissolution profile by following the published United States Pharmacopoeia (USP) monogram for the particular tablet being tested. Products for which a published analytical monogram did not exist were assessed on amount of active ingredient alone. Overall 38 or 12.2% of the samples were found to be of poor quality. Of the antifolate antimalarial drugs tested 13.4% were found to be of poor quality by dissolution and content analysis using high-performance liquid chromatography (HPLC). Nearly one quarter (23.8%) of quinine tablets did not comply within the tolerance limits of the dissolution and quantification analysis. Quality of amodiaquine drugs was relatively better but still unacceptable as 7.5% did not comply within the tolerance limits of the dissolution analysis. Formulations of the artemisinin derivatives all contained the stated amount of active ingredient when analysed using HPLC alone.\ud \ud CONCLUSIONS\ud \ud Substandard antimalarial formulations were widely available in Tanzania at the time of this study. No products were detected that did not contain any amount of the stated active ingredient. Quinine and sulfadoxine/pyrimethamine products were the most widely available and also the most likely to be of poor quality. Substandard products were identified in all parts of the country and were labeled as made by both domestic and international manufacturers. With the expansion of the retail pharmaceutical sector as a delivery channel for antimalarial formulations the need for regular nationwide monitoring of their quality will become increasingly important

Predictors of Antibiotics Co-prescription with Antimalarials for Patients Presenting with Fever in Rural Tanzania.

Successful implementation of malaria treatment policy depends on the prescription practices for patients with malaria. This paper describes prescription patterns and assesses factors associated with co-prescription of antibiotics and artemether-lumefantrine (AL) for patients presenting with fever in rural Tanzania. From June 2009 to September 2011, a cohort event monitoring program was conducted among all patients treated at 8 selected health facilities in Ifakara and Rufiji Health and Demographic Surveillance System (HDSS).It included all patients presenting with fever and prescribed with AL. Logistic regression was used to model the predictors on the outcome variable which is co-prescription of AL and antibiotics on a single clinical visit. A cohort of 11,648 was recruited and followed up with 92% presenting with fever. Presumptive treatment was used in 56% of patients treated with AL. On average 2.4 (1 -- 7) drugs was prescribed per encounter, indicating co-prescription of AL with other drugs. Children under five had higher odds of AL and antibiotics co-prescription (OR = 0.63, 95% CI: 0.46 -- 0.85) than those aged more than five years. Patients testing negative had higher odds (OR = 2.22, 95%CI: 1.65 -- 2.97) of AL and antibiotics co-prescription. Patients receiving treatment from dispensaries had higher odds (OR = 1.45, 95% CI: 0.84 -- 2.30) of AL and antibiotics co-prescription than those from served in health centres even though the deference was not statistically significant. Regardless the fact that Malaria is declining but due to lack of laboratories and mRDT in most health facilities in the rural areas, clinicians are still treating malaria presumptively. This leads them to prescribe more drugs to treat all possibilities

Increased use of malaria rapid diagnostic tests improves targeting of anti-malarial treatment in rural Tanzania: implications for nationwide rollout of malaria rapid diagnostic tests.

ABSTRACT: BACKGROUND: The World Health Organization recommends parasitological confirmation of all malaria cases. Tanzania is implementing a phased rollout of malaria rapid diagnostic tests (RDTs) for routine use in all levels of care as one strategy to increase parasitological confirmation of malaria diagnosis. This study was carried out to evaluated artemisinin combination therapy (ACT) prescribing patterns in febrile patients with and without uncomplicated malaria in one pre-RDT implementation and one post-RDT implementation area. METHODS: A cross-sectional health facility surveys was conducted during high and low malaria transmission seasons in 2010 in both areas. Clinical information and a reference blood film on all patients presenting for an initial illness consultation were collected. Malaria was defined as a history of fever in the past 48 hours and microscopically confirmed parasitaemia. Routine diagnostic testing was defined as RDT or microscopy ordered by the health worker and performed at the health facility as part of the health worker-patient consultation. Correct diagnostic testing was defined as febrile patient tested with RDT or microscopy. Over-testing was defined as a febrile patient tested with RDT or microscopy. Correct treatment was defined as patient with malaria prescribed ACT. Over-treatment was defined as patient without malaria prescribed ACT. RESULTS: A total of 1,247 febrile patients (627 from pre-implementation area and 620 from post-implementation area) were included in the analysis. In the post-RDT implementation area, 80.9% (95% CI, 68.2-89.3) of patients with malaria received recommended treatment with ACT compared to 70.3% (95% CI, 54.7-82.2) of patients in the pre-RDT implementation area. Correct treatment was significantly higher in the post-implementation area during high transmission season (85.9% (95%CI, 72.0-93.6) compared to 58.3% (95%CI, 39.4-75.1) in pre-implementation area (p=0.01). Over-treatment with ACT of patients without malaria was less common in the post-RDT implementation area (20.9%; 95% CI, 14.7-28.8) compared to the pre-RDT implementation area (45.8%; 95% CI, 37.2-54.6) (p<0.01) in high transmission. The odds of overtreatment was significantly lower in post- RDT area (adjusted Odds Ratio (OR: 95%CI) 0.57(0.36-0.89); and much higher with clinical diagnosis adjusted OR (95%CI) 2.24(1.37-3.67) CONCLUSION: Implementation of RDTs increased use of RDTs for parasitological confirmation and reduced over-treatment with ACT during high malaria transmission season in one area in Tanzania. Continued monitoring of the national RDT rollout will be needed to assess whether these changes in case management practices will be replicated in other areas and sustained over time. Additional measures (such as refresher trainings, closer supervisions, etc) may be needed to improve ACT targeting during low transmission seasons

Correct Dosing of Artemether-Lumefantrine for Management of Uncomplicated Malaria in Rural Tanzania: Do facility and Patient Characteristics Matter?

Use of artemisinin-based combination therapy (ACT), such as artemether-lumefantrine (AL), requires a strict dosing schedule that follows the drugs' pharmacokinetic properties. The quality of malaria case management was assessed in two areas in rural Tanzania, to ascertain patient characteristics and facility-specific factors that influence correct dosing of AL for management of uncomplicated malaria. Exit interviews were conducted with patients attending health facilities for initial illness consultation. Information about health workers' training and supervision visits was collected. Health facilities were inventoried for capacity and availability of medical products related to care of malaria patients. The outcome was correct dosing of AL based on age and weight. Logistic regression was used to assess health facility factors and patient characteristics associated with correct dosing of AL by age and weight. A total of 1,531 patients were interviewed, but 60 pregnant women were excluded from the analysis. Only 503 (34.2%) patients who received AL were assessed for correct dosing. Most patients who received AL (85.3%) were seen in public health facilities, 75.7% in a dispensary and 91.1% in a facility that had AL in stock on the survey day. Overall, 92.1% (463) of AL prescriptions were correct by age or weight; but 85.7% of patients received correct dosing by weight alone and 78.5% received correct dosing by age alone. In multivariate analysis, patients in the middle dosing bands in terms of age or weight, had statistically significant lower odds of correct AL dosing (p < 0.05) compared to those in the lowest age or weight group. Other factors such as health worker supervision and training on ACT did not improve the odds of correct AL dosing. Although malaria treatment guidelines indicate AL dosing can be prescribed based on age or weight of the patient, findings from this study show that patients within the middle age and weight dosing bands were least likely to receive a correct dose by either measure. Clinicians should be made aware of AL dosing errors for patients aged three to 12 years and advised to use weight-based prescriptions whenever possible