Concurrence of dermatological and ophthalmological morbidity in onchocerciasis

Prevalence of skin and eye disorders in African onchocerciasis (river blindness) is well documented. However, less is known about their joint occurrence. Information on concurrence may improve our understanding of disease pathogenesis and is required to estimate the disease burden of onchocerciasis. We analysed data from 765 individuals from forest villages in the Kumba and Ngambe Health districts, Cameroon. These data were collected in 1998, as baseline data for the evaluation of the African Programme for Onchocerciasis Control. Concurrence of symptoms was assessed using logistic regression. Onchocerciasis was highly endemic in the study population (63% nodule prevalence among males aged ≥20). Considerable overall prevalences of onchocercal visual impairment (low vision or blindness: 4%), troublesome itch (15%), reactive skin disease (19%), and skin depigmentation (25%) were observed. The association between onchocercal visual impairment and skin depigmentation (OR 9.0, 95% CI 3.9-20.8) was partly explained by age and exposure to infection (OR 3.0, 95% CI 1.2-7.7). The association between troublesome itch and reactive skin disease was hardly affected by adjustment (adjusted OR 6.9, 95% CI 4.2-11.1). Concluding, there is significant concurrence of morbidities within onchocerciasis. Our results suggest a possible role of host characteristics in the pathogenesis of depigmentation and visual impairment. Further, we propose a method to deal with concurrence when estimating the burden of disease.     

Stability Studies of Gabapentin in Aqueous Solutions

Gabapentin is a -aminobutyric acid analogue, which has been shown to be an effective antiepileptic. The solution stability of gabapentin in buffered systems was studied in order to facilitate the formulation of a liquid product. The degradation of the drug was followed as a function of pH, buffer concentration, ionic strength, and temperature. The results indicated that the rate of degradation was proportional to the buffer concentration and temperature. The pH–rate profile of gabapentin degradation showed that the rate of degradation was minimum at an approximate pH of 6.0. Further, the data suggested a slower solvent-catalyzed degradation rate for the zwitterionic species compared to the cationic or anionic species in the pH range of 4.5 to 7.0. There was no influence of ionic strength on the rate of degradation. Arrhenius plots of the data indicated that a shelf life of 2 years or more at room temperature may be obtained in an aqueous solution at a pH value of 6.0.     

Short-term virological efficacy, immune reconstitution, tolerance, and adherence of once-daily dosing of didanosine, lamivudine, and efavirenz in HIV-1-infected African children: ANRS 12103 Burkiname

Access to antiretroviral therapy (ART) and routine laboratory monitoring are limited for HIV-1-infected children from sub-Saharan Africa. This trial conducted in Bobo-Dioulasso, Burkina Faso, aimed to describe the biological efficacy, tolerance, and adherence of the combination of didanosine, lamivudine, efavirenz in once-daily administration among eligible HIV-1-infected children. From February 2006 to November 2007, 51 HIV-1-infected children aged from 30 months to 15 years and eligible for ART were enrolled in a phase II open clinical trial with follow-up visits every 3 months. HIV-1 genotype testing was performed in children with plasma viral load (PVL) >1000 copies per milliliter after ART initiation. Children were followed for a median of 13.4 months [interquartile range (IQR) 12.8-14.2]. At enrollment, median CD4 count was 8% (IQR = 4.5-12). PVL was 341,032 (IQR = 127,838-761,539) copies per milliliter. At 12 months, median CD4 increased significantly by +15% (P < 10(-3)), and median PVL decreases significantly by -290,500 copies per milliliter (P < 10(-4)). Hemoglobin and platelets counts increased significantly by +1.05 g/dL (P < 10(-5)) and 108,500 cells per milliliter (P < 10(-3)), respectively. Based on pill count, mean yearly adherence was 97.3%, and 48% of the children had an adherence rate ≥ 95% at the four quarterly visits. Adherence was better for girls than for boys independently of other sociodemographic variables or markers of HIV disease progression. Drug-resistant mutations were found in 11 children (21.6%). This once-daily drug combination is associated with excellent virological efficacy, immune reconstitution, and good adherence. However, the high prevalence of drug resistance mutations is a matter of concern.     

A model for evaluating the sustainability of community-directed treatment with ivermectin in the African Program for Onchocerciasis Control

Onchocerciasis is controlled by mass treatment of at‐risk populations with ivermectin. Ivermectin is delivered through community‐directed treatment (CDTI) approach. A model has been developed to evaluate the sustainability of the approach and has been tested at 35 projects in 10 countries of the African Program for Onchocerciasis Control (APOC). It incorporates quantitative and qualitative data collection and analysis, taking account of two factors identified as crucial to project sustainability. These are (i) the provision of project performance information to partners, and (ii) evidence‐based support for project implementation. The model is designed to provide critical indicators of project performance of the model to implementing, coordinating, and funding partners. The model's participatory and flexible nature makes it culturally sensitive and usable by project management. This model is able to analyze the different levels involved in project implementation and arrive at a judgment for the whole project. It has inbuilt mechanisms for ensuring data reliability and validity. The model addresses the complex issue of sustainability with a cross‐sectional design focusing on how and at which operational level of implementation to strengthen a CDTI project. The unique attributes and limitations of the model for evaluating the sustainability of projects were described. Copyright © 2012 John Wiley & Sons, Ltd.     

Performance of predictors: evaluating sustainability in community-directed treatment projects of the African programme for onchocerciasis control

The predictors of sustainability of community-directed treatment with ivermectin (CDTI) at four implementation levels were evaluated in 41 African Programme for Onchocerciasis Control (APOC) projects, encompassing 492 communities in 10 countries. A model protocol provided information on indicators corresponding to nine aspects of a project that is likely to be sustainable at community level after the cessation of external support. Six of the nine aspects had components of community ownership as predictors of project sustainability. Quantitative and qualitative assessments were used to obtain individual community scores and an overall sustainability score for each project graded on a scale of 0-4. Of the 41 projects evaluated, 70% scored "satisfactorily" to "highly sustainable" at the community level. We found variations among countries and that health system weaknesses could hamper community efforts in sustaining a project, such as when ivermectin was delivered late. Community ownership was of primary importance to the community score, and the community-level scores correlated with overall project sustainability. The therapeutic coverage achieved in each project correlated with the ratio of volunteer ivermectin distributors per population served. Surprisingly, the performance of these distributors was not affected by the direct incentives offered, and coverage appeared to be highest when cash or in-kind compensation was not given at all. Although further research is required, anecdotal evidence pointed to diverse indirect benefits for distributors-political goodwill, personal satisfaction and altruistic fulfillment. The results demonstrate that community ownership is among the important determining factors of sustainability of community-based programmes.     

Dissolution studies of microencapsulated indomethacin; effect of method and medium on dissolution

In vitro dissolution studies of microencapsulated indomethacin showed that the USP paddle method was superior to the USP basket method in that the drug release was higher and more uniform with the paddle. Simulated intestinal fluid (pH 7.2) was an appropriate medium to use for dissolution studies on prolonged-release microcapsules.     

Risk Management in the Pharmaceutical Product Development Process

“The manufacture and use of a drug product, including its components, necessarily entail some degree of risk.”—International Conference for Harmonization (ICH) Q9. This paper examines the role of risk management in pharmaceutical product development in the context of patient safety and drug efficacy. Its objective is to contribute to building a common understanding of this quality risk management among the various functional groups involved in developing, testing, manufacturing, and approving of drug products within pharmaceutical companies and regulatory agencies. Selected aspects of drug substance and drug product development are used to demonstrate principles of risk management in action and presented as case studies.