Implementation of artemether-lumefantrine treatment policy for malaria at health facilities in Tanzania

V Mugoyela1, O Minzi21Department of Medicinal Chemistry, 2Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, TanzaniaBackground: The purpose of this study was to compare knowledge on the part of health workers in public and private health facilities about prescribing and dispensing of an artemether-lumefantrine combination, 3 years after moving from sulfadoxine-pyrimethamine to artemether-lumefantrine as a first-line treatment for nonsevere malaria in Tanzania.Methods: A cross-sectional survey of a convenience sample of 306 dispensaries and pharmacies was conducted in Dar Es Salaam and the Coast region of Tanzania. Of these, 122 were community pharmacies, 143 were private dispensaries, and 41 were public dispensaries. Specific outcome measures were health workers’ knowledge of the new malaria treatment guidelines, recommended doses of artemether-lumefantrine, and food requirements.Results: A total of 489 health workers were included in the study. The respondents were prescribers in private dispensaries, public dispensaries, and community pharmacies. Participants included medical officers (3.7%), clinical officers (38%), pharmacists (5.7%), and pharmaceutical technicians (3.9%). Nearly all workers in the public dispensaries and about 50% of workers in private dispensaries and community pharmacies were aware of recommended first-line malaria treatment. The difference in the proportion of health workers with adequate knowledge about the new recommended antimalarial medicine in public and private dispensaries was statistically significant (P < 0.0001). There was a higher proportion of workers in public dispensaries who had adequate knowledge about doses of artemether-lumefantrine for adults compared with workers in private dispensaries (P = 0.001). Only 58.0% of respondents were able to state correctly the recommended doses in private dispensaries as compared with 77.0% in public dispensaries. Knowledge about the requirement for a concomitant fatty meal was not significantly different between workers in public and private dispensaries (P = 0.280) or between those working in public dispensaries and pharmacies (P = 0.622).Conclusion: Knowledge about the use of artemether-lumefantrine was higher among health workers in public dispensaries than in their counterparts from private health care settings. The training organized by the Ministry of Health for workers in public health facilities in Tanzania contributed to such differences.Keywords: knowledge, public dispensaries, private dispensaries, pharmacie

Nonmedical Prescription Drug Users in Private vs. Public Substance Abuse Treatment: A Cross Sectional Comparison of Demographic and HIV Risk Behavior Profiles

Background: Little is known regarding the demographic and behavioral characteristics of nonmedical prescription drug users (NMPDUs) entering substance abuse treatment settings, and information on the HIV-related risk profiles of NMPDUs is especially lacking. Participation in substance abuse treatment provides a critical opportunity for HIV prevention and intervention, but successful initiatives will require services appropriately tailored for the needs of NMPDUs. Methods: This paper compares the HIV risk profiles of NMPDUs in public (n = 246) and private (n = 249) treatment facilities. Participants included in the analysis reported five or more recent episodes of nonmedical prescription drug use, a prior HIV negative test result, and current enrollment in a substance abuse treatment facility. A standardized questionnaire was administered by trained interviewers with questions about demographics, HIV risk, and substance use. Results: Private treatment clients were more likely to be non-Hispanic White, younger, and opioid and heroin users. Injection drug use was higher among private treatment clients, whereas public clients reported higher likelihood of trading or selling sex. Public treatment clients reported higher rates of HIV testing and availability at their treatment facilities compared to private clients. Conclusions: Findings suggest differing demographics, substance use patterns, profiles of HIV risk and access to HIV testing between the two treatment samples. Population tailored HIV interventions, and increased access to HIV testing in both public and private substance treatment centers, appear to be warranted

Medication Adherence Challenges Among HIV Positive Substance Abusers: The Role of Food and Housing Insecurity

This study examines the prevalence of food/housing insecurity and its association with psychological, behavioral, and environmental factors impacting antiretroviral (ARV) medication adherence and diversion among substance using HIV+ patients in South Florida. Five hundred and three HIV+ substance abusers were recruited through targeted sampling. Participants completed a standardized instrument assessing demographics, mental health status, sex risk behaviors, HIV diagnosis, treatment history and access, ARV adherence and diversion, and attitudes toward health-care providers. Chi-square and t-tests were used to examine differences by food/housing status and a multivariate linear regression model examined food/housing insecurity and its associations to ARV adherence. Food/housing insecurity was reported by 43.3% of the sample and was associated with higher likelihood of severe psychological distress and substance dependence. Nearly 60% reported recent ARV diversion; only 47.2% achieved 95% medication adherence over one week. Food/housing insecure participants had deficits in their HIV care, including less time in consistent care, lower access to medical care, and less favorable attitudes toward care providers. Multivariate linear regression showed food/housing insecurity demonstrated significant main effects on adherence, including lower past week adherence. Medication diversion was also associated with reduced adherence. Our findings suggest that food/housing insecurity operates as a significant driver of ARV non-adherence and diversion in this population. In the pursuit of better long-term health outcomes for vulnerable HIV+ individuals, it is essential for providers to understand the role of food and housing insecurity as a stressor that negatively impacts ARV adherence and treatment access, while also significantly contributing to higher levels of distress and substance dependence

Outcomes of a Behavioral Intervention to Reduce HIV Risk among Drug-Involved Female Sex Workers

Although street-based female sex workers (FSWs) are highly vulnerable to HIV, they often lack access to needed health services and medical care. This paper reports the results of a recently completed randomized intervention trial for FSWs in Miami, Florida, which tested the relative efficacy of two case management interventions that aimed to link underserved FSWs with health services and to reduce risk behaviors for HIV. Participants were recruited using targeted sampling strategies and were randomly assigned to: a Strengths-Based/Professional Only (PO) or a Strengths-Based/Professional-Peer condition (PP). Follow-up data were collected 3 and 6 months post-baseline. Outcome analyses indicated that both intervention groups displayed significant reductions in HIV risk behaviors and significant increases in services utilization; the Professional-Peer condition provided no added benefit. HIV seropositive FSWs responded particularly well to the interventions, suggesting the utility of brief strengths-based case management interventions for this population in future initiatives

HIV Testing and Engagement in Care Among Highly Vulnerable Female Sex Workers: Implications for Treatment as Prevention Models

Background: Although emerging Treatment as Prevention models can be effective in reducing HIV incidence among high-risk populations, many HIV infected individuals remain undiagnosed or fail to engage in HIV care. Methods: This study examined the factors associated with HIV testing and care among a population of substance using female sex workers. Results: Recent HIV testing was associated with higher education level, having a regular health care provider or clinic, recent crack use, and higher sexual risk behaviors; HIV treatment utilization was associated with higher levels of social support, having a regular health care provider or clinic, housing stability and insurance coverage. Qualitative data revealed HIV-related stigma, denial, social isolation, and substance use as barriers to HIV testing and treatment; social support and accessibility of services were key enablers. Conclusions: Improving HIV testing and linkage to treatment among female sex workers will require structural initiatives to reduce stigma and increase service seeking support

Antiretroviral Medication Diversion Among HIV-Positive Substance Abusers in South Florida

The high cost of life-saving antiretroviral (ARV) therapy for HIV represents an expense that impedes accessibility and affordability by patients. This price structure also appears to motivate the diversion of ARVs and the targeting of HIV-positive patients by pill brokers in the illicit market. Our field research with indigent, HIV-positive substance abusers links ARV diversion to high levels of competing needs, including psychiatric disorders, HIV stigma, and homelessness. Interventions to reduce diversion must address the needs of highly vulnerable patients

A simple cost-effective high performance liquid chromatographic assay of sulphadoxine in whole blood spotted on filter paper for field studies

<p>Abstract</p> <p>Background</p> <p>Artesunate plus sulphadoxine-pyrimethamine is one of the four artemisinin-based combination therapies currently recommended by WHO as first-line treatment for falciparum malaria. Sulphadoxine-pyrimethamine is also used for intermittent preventive treatment for malaria in pregnancy. Drug use patterns and drug pharmacokinetics are important factors impacting the spread of drug resistant parasites hence it is imperative to monitor the effect of pharmacokinetic variability on therapeutic efficacy. Unfortunately, information on the pharmacokinetics of sulphadoxine in children and pregnant women with malaria is very limited. Methods for the assay of sulphadoxine-pyrimethamine have been previously reported, but they are not cost-effective and practicable in analytical laboratories in low resource areas where malaria is endemic. Efforts in this study were thus devoted to development and evaluation of a simple, cost-effective and sensitive method for quantification of sulphadoxine in small capillary samples of whole blood dried on filter paper.</p> <p>Methods</p> <p>Sulphadoxine was determined in whole blood by reversed-phase high performance liquid chromatography with UV detection at 340 nm. Sulisoxazole (SLX) was used as internal standard. Chromatographic separation was achieved using a Beckman Coulter ODS C₁₈and a mobile phase consisting of 0.05 M phosphate buffer-methanol-acetonitrile (70:17:13 V/V/V) containing 1% triethylamine solution.</p> <p>Results</p> <p>Standard curves from sulphadoxine-spiked blood added to filter paper were linear over the concentration range studied. Linear regression analysis yielded correlation coefficient r²> 0.99 (n = 6). Extraction recoveries were about 82-85%. The limit of quantification was 120 ng/ml while the within and between assay coefficient of variations were < 10%. The inter-day precision was < 5.8% and inter-day accuracy ranged from 4.1 to 5.3%. There was no interference from endogenous compounds or any of the commonly used anti-malarial, analgesic and anti-infective drugs with the peaks of SDX or the internal standard.</p> <p>Conclusion</p> <p>The recovery and accuracy of determination of SDX from whole blood filter paper samples using the method described in this study is satisfactory, thus making the method a valuable tool in epidemiological studies and therapeutic drug monitoring in developing endemic countries. Furthermore, the applicability of the method in studying the pharmacokinetic disposition of SDX in a patient suggests that the method is suitable in malaria endemic areas.</p

Comparison of Bioavailability Between the Most Available Generic Tablet Formulation Containing Artemether and Lumefantrine on the Tanzanian Market and the Innovator's Product.

Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa has raised a concern on patients achieving therapeutic concentrations after intake of these products. This work compared bioavailability of one generic tablet formulation with innovator's product. Both were fixed dose combination tablet formulations containing artemether and lumefantrine.MethodologyThe study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most widely available generic (Artefan(R), Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability comparison with Coartem(R) (Novartis Pharma, Basel, Switzerland) - the innovator's product. A randomized, two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer received Artefan(R) (test) and Coartem(R) (as reference) formulation separated by 42 days of drug-free washout period. Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines. The most widely available generic in pharmacies was Artefan(R) from India. All eighteen enrolled volunteers completed the study and both test and reference tablet formulations were well tolerated. It was possible to quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The geometric mean ratios for Cmax, AUC0-t and AUC0-[infinity] were 84% in all cases and within FDA recommended bioequivalence limits of 80% -- 125%, but the 90% confidence intervals were outside FDA recommended limits (CI 49--143%, 53 - 137%, 52 - 135% respectively). There were no statistical significant differences between the two formulations with regard to PK parameters (P > 0.05). Although the ratios of AUCs and Cmax were within the acceptable FDA range, bioequivalence between Artefan(R) and Coartem(R) tablet formulations was not demonstrated due to failure to comply with the FDA 90 % confidence interval criteria. Based on the observed total drug exposure (AUCs), Artefan(R) is likely to produce a similar therapeutic response as Coartem(R)

Improved protein arrays for quantitative systems analysis of the dynamics of signaling pathway interactions

An improved version of quantitative protein array platform utilizing linear Quantum dot signaling for systematically measuring protein levels and phosphorylation states is presented. The signals are amplified linearly by a confocal laser Quantum dot scanner resulting in ~1000-fold more sensitivity than traditional Western blots, but are not linear by the enzyme-based amplification. Software is developed to facilitate the quantitative readouts of signaling network activities. Kinetics of EGFRvIII mutant signaling was analyzed to quantify cross-talks between EGFR and other signaling pathways

Adherence to Antiretroviral Therapy among HIV Infected Children Measured by Caretaker Report, Medication Return, and Drug Level in Dar Es Salaam, Tanzania.

Adherence to antiretroviral drugs in the treatment of paediatric HIV infection is complicated because of many factors including stigma and drug intake logistics. It is therefore important to identify children with non-adherence in order to intervene before they become at risk of developing treatment failure or drug resistance. The aim of this study was to determine the level of adherence to antiretroviral therapy (ART), measured by caretaker report, medication return and nevirapine plasma concentration. In addition, the association between level of adherence and patient's immune status was compared across the three methods of measuring adherence. This was a descriptive cross-sectional study involving HIV infected children aged 2-14 years, on nevirapine- based antiretroviral treatment for at least six months, attending care and treatment clinic in three municipal hospitals in Dar- Es- Salaam City. Eligible patients and their accompanying caretakers were consecutively enrolled after obtaining written informed consent. Structured questionnaires were administered to caretakers to assess patient's adherence by caretaker report and medication return whereas a single blood sample for CD4 cell count/percent and determination of nevirapine plasma concentration was taken from patients on the day of assessment. A total of 300 patients and accompanying caretakers were enrolled and the mean patient age (SD) was 8 (3) years. Caretakers' report and medication return showed good adherence (98% and 97%) respectively. However, the level of adherence assessed by nevirapine plasma concentration (85%) was significantly lower than caretaker report and medication return (p < 0.001). The agreement between nevirapine plasma concentration and medication return and between nevirapine plasma concentration and caretaker report was weak (k = 0. 131) (k = 0. 09) respectively. Nevirapine plasma concentration below 3 μg/ml was associated with immunosuppression (p = 0. 021) whereas medication return (>5% of prescribed doses) and caretaker reported missing more than one dose within 72 hours prior to interview were not associated with immunosuppression (p = 0. 474), (p = 0. 569) respectively. Lower adherence level observed using nevirapine plasma concentration and its association with immunological response supports the validity of the method and indicates that adherence data obtained from caretaker report and medication return may overestimate the true adherence in paediatric antiretroviral therapy