Socio-economic and environmental factors associated with high lymphatic filariasis morbidity prevalence distribution in Bangladesh.

BACKGROUND: Lymphatic filariasis (LF) is a vector-borne parasitic disease which affects 70 million people worldwide and causes life-long disabilities. In Bangladesh, there are an estimated 44,000 people suffering from clinical conditions such as lymphoedema and hydrocoele, with the greatest burden in the northern Rangpur division. To better understand the factors associated with this distribution, this study examined socio-economic and environmental factors at division, district, and sub-district levels. METHODOLOGY: A retrospective ecological study was conducted using key socio-economic (nutrition, poverty, employment, education, house infrastructure) and environmental (temperature, precipitation, elevation, waterway) factors. Characteristics at division level were summarised. Bivariate analysis using Spearman's rank correlation coefficient was conducted at district and sub-district levels, and negative binomial regression analyses were conducted across high endemic sub-districts (n = 132). Maps were produced of high endemic sub-districts to visually illustrate the socio-economic and environmental factors found to be significant. RESULTS: The highest proportion of rural population (86.8%), poverty (42.0%), tube well water (85.4%), and primary employment in agriculture (67.7%) was found in Rangpur division. Spearman's rank correlation coefficient at district and sub-district level show that LF morbidity prevalence was significantly (p<0.05) positively correlated with households without electricity (district rs = 0.818; sub-district rs = 0.559), households with tube well water (sub-district rs = 0.291), households without toilet (district rs = 0.504; sub-district rs = 0.40), mean annual precipitation (district rs = 0.695; sub-district rs = 0.503), mean precipitation of wettest quarter (district rs = 0.707; sub-district rs = 0.528), and significantly negatively correlated with severely stunted children (district rs = -0.723; sub-district rs = -0.370), mean annual temperature (district rs = -0.633.; sub-district rs = 0.353) and mean temperature (wettest quarter) ((district rs = -0.598; sub-district rs = 0.316) Negative binomial regression analyses at sub-district level found severely stunted children (p = <0.001), rural population (p = 0.002), poverty headcount (p = 0.001), primary employment in agriculture (p = 0.018), households without toilet (p = <0.001), households without electricity (p = 0.002) and mean temperature (wettest quarter) (p = 0.045) to be significant. CONCLUSIONS: This study highlights the value of using available data to identify key drivers associated with high LF morbidity prevalence, which may help national LF programmes better identify populations at risk and implement timely and targeted public health messages and intervention strategies.

Implementation of test-and-treat with doxycycline and temephos ground larviciding as alternative strategies for accelerating onchocerciasis elimination in an area of loiasis co-endemicity: the COUNTDOWN consortium multi-disciplinary study protocol.

BACKGROUND: Onchocerciasis is a priority neglected tropical disease targeted for elimination by 2025. The standard strategy to combat onchocerciasis is annual Community-Directed Treatment with ivermectin (CDTi). Yet, high prevalence rates and transmission persist following > 12 rounds in South-West Cameroon. Challenges include programme coverage, adherence to, and acceptability of ivermectin in an area of Loa loa co-endemicity. Loiasis patients harbouring heavy infections are at risk of potentially fatal serious adverse events following CDTi. Alternative strategies are therefore needed to achieve onchocerciasis elimination where CDTi effectiveness is suboptimal. METHODS/DESIGN: We designed an implementation study to evaluate integrating World Health Organisation-endorsed alternative strategies for the elimination of onchocerciasis, namely test-and-treat with the macrofilaricide, doxycycline (TTd), and ground larviciding for suppression of blackfly vectors with the organophosphate temephos. A community-based controlled before-after intervention study will be conducted among > 2000 participants in 20 intervention (Meme River Basin) and 10 control (Indian River Basin) communities. The primary outcome measure is O. volvulus prevalence at follow-up 18-months post-treatment. The study involves four inter-disciplinary components: parasitology, entomology, applied social sciences and health economics. Onchocerciasis skin infection will be diagnosed by skin biopsy and Loa loa infection will be diagnosed by parasitological examination of finger-prick blood samples. A simultaneous clinical skin disease assessment will be made. Eligible skin-snip-positive individuals will be offered directly-observed treatment for 5 weeks with 100 mg/day doxycycline. Transmission assessments of onchocerciasis in the communities will be collected post-human landing catch of the local biting blackfly vector prior to ground larviciding with temephos every week (0.3 l/m3) until biting rate falls below 5/person/day. Qualitative research, including in-depth interviews and focus-group discussions will be used to assess acceptability and feasibility of the implemented alternative strategies among intervention recipients and providers. Health economics will assess the cost-effectiveness of the implemented interventions. CONCLUSIONS: Using a multidisciplinary approach, we aim to assess the effectiveness of TTd, alone or in combination with ground larviciding, following a single intervention round and scrutinise the acceptability and feasibility of implementing at scale in similar hotspots of onchocerciasis infection, to accelerate onchocerciasis elimination.

Transformation in the pharmaceutical industry--a systematic analysis of operational evidence.

Through systematic collection and trending of pharmaceutical data, operational evidence to verify existence of 14 factors affecting the ongoing pharmaceutical transformation has been compiled. These 14 factors are termed transformation triggers. The theoretical evidence in support of these triggers is carried forward from a systematic review of the literature that was conducted previously. Trends in operational evidence and the associated theoretical evidence were compared to identify areas of similarity and contrast. Areas of strong correlation between theoretical evidence and operational evidence included four transformation triggers: a fully integrated pharma network, personalized medicine, translational research, and pervasive computing. Key areas of contrast included three transformation triggers-namely, healthcare management focus, adaptive trials, and regulatory enforcement-for which the operational evidence was stronger than the theoretical evidence. LAY ABSTRACT: The intent of this paper is to provide proof to demonstrate if there is any operational evidence that supports the 14 transformation triggers previously identified during the theoretical part of this research. The theoretical evidence for these triggers was carried forward to this paper for study from an operational perspective. The practical evidence established in this paper was compared with the corresponding theoretical evidence to identify areas of similarity and difference. This resulted in four triggers that had strong relationship between operational and theoretical evidence; they are a fully integrated pharma network, personalized medicine, translational research, and pervasive computing. The areas of difference included three transformation triggers for which the operational evidence was stronger than the theoretical evidence. These were healthcare management focus, adaptive trials, and regulatory enforcement.

Characterization of the evolution of the pharmaceutical regulatory environment.

This paper is part of a research study that is intended to identify pharmaceutical quality risks induced by the ongoing transformation in the industry. This study establishes the current regulatory context by characterizing the development of the pharmaceutical regulatory environment. The regulatory environment is one of the most important external factors that affects a company's organization, processes, and technological strategy. This is especially the case with the pharmaceutical industry, where its products affect the quality of life of the consumers. The quantitative analysis of regulatory events since 1813 and review of the associated literature resulted in identification of six factors influencing the regulatory environment, namely public health protection, public health promotion, crisis management, harmonization, innovation, and modernization. From 1813 to the 1970s the focus of regulators was centered on crisis management and public health protection-a basic mission that has remained consistent over the years. Since the 1980s a gradual move in the regulatory environment towards a greater focus on public health promotion, international harmonization, innovation, and agency modernization may be seen. LAY ABSTRACT: The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities. The impact of these changes on the approaches to quality risk management requires more understanding. The authors are engaged in research to identify elements of the changes that influence pharmaceutical quality. As quality requirements are an integral part of the pharmaceutical regulations, a comprehensive understanding of these regulations is seen as the first step. The results of this study show that (i) public health protection, public health promotion, crisis management, harmonization, innovation, and modernization are factors that affect regulations in the pharmaceutical industry; (ii) the regulators' main mission of public health protection has remained a constant feature over the years; and (iii) since the 1970s other factors such as public health promotion, international harmonization, innovation, and agency modernization are playing more important role in regulatory agency thinking and actions.

Transformation in the pharmaceutical industry: transformation-induced quality risks--a survey.

This paper is the fourth in a series that explores ongoing transformation in the pharmaceutical industry and its impact on pharmaceutical quality from the perspective of risk identification. The aim of this paper is to validate proposed quality risks through elicitation of expert opinion and define the resultant quality risk model. Expert opinion was obtained using a questionnaire-based survey with participants with recognized expertise in pharmaceutical regulation, product lifecycle, or technology. The results of the survey validate the theoretical and operational evidence in support of the four main pharmaceutical transformation triggers previously identified. The quality risk model resulting from the survey indicated a firm relationship between the pharmaceutical quality risks and regulatory compliance outcomes during the marketing approval and post-marketing phases of the product lifecycle and a weaker relationship during the pre-market evaluation phase. LAY ABSTRACT: In this paper through conduct of an expert opinion survey the proposed quality risks carried forward from an earlier part of the research are validated and resultant quality risk model is defined. The survey results validate the theoretical and operational evidence previously identified. The quality risk model indicates that transformation-related risks have a larger regulatory compliance impact during product approval, manufacturing, distribution, and commercial use than during the development phase.

Transformation in the pharmaceutical industry--a systematic review of the literature.

The evolutionary development of pharmaceutical transformation was studied through systematic review of the literature. Fourteen triggers were identified that will affect the pharmaceutical business, regulatory science, and enabling technologies in future years. The relative importance ranking of the transformation triggers was computed based on their prevalence within the articles studied. The four main triggers with the strongest literature evidence were Fully Integrated Pharma Network, Personalized Medicine, Translational Research, and Pervasive Computing. The theoretical quality risks for each of the four main transformation triggers are examined, and the remaining ten triggers are described. LAY ABSTRACT: The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities (this is termed pharmaceutical transformation). The impact of these changes on the approaches to quality risk management requires more understanding. In this paper, a comprehensive review of the academic, regulatory, and industry literature were used to identify 14 triggers that influence pharmaceutical transformation. The four main triggers, namely Fully Integrated Pharma Network, Personalized Medicine, Translational Research, and Pervasive Computing, were selected as the most important based on the strength of the evidence found during the literature review activity described in this paper. Theoretical quality risks for each of the four main transformation triggers are examined, and the remaining ten triggers are described.

Current practices in the management of lymphatic filariasis.

Lymphatic filariasis is a major cause of acute and chronic morbidity in 81 countries. The availability of safe treatment regimens along with rapid diagnostic tools resulted in a global program to eliminate the disease. The two main objectives of the global elimination program are to interrupt transmission of the parasites and to provide care for those with the disease. The strategy for transmission interruption is preventive chemotherapy through mass drug administration. This article reviews the current treatment regimens for lymphatic filariasis and discusses the challenges posed by co-endemicity with other diseases. The role of integrated vector management as a supplementary strategy for mass drug administration and new strategies for treatment and morbidity control through antibiotic targeting of the Wolbachia endosymbionts are also discussed.

Quantitative risk modelling for new pharmaceutical compounds.

The process of discovering and developing new drugs is long, costly and risk-laden. Faced with a wealth of newly discovered compounds, industrial scientists need to target resources carefully to discern the key attributes of a drug candidate and to make informed decisions. Here, we describe a quantitative approach to modelling the risk associated with drug development as a tool for scenario analysis concerning the probability of success of a compound as a potential pharmaceutical agent. We bring together the three strands of manufacture, clinical effectiveness and financial returns. This approach involves the application of a Bayesian Network. A simulation model is demonstrated with an implementation in MS Excel using the modelling engine Crystal Ball.

Combined Utilisation of Rapid Assessment Procedures for Loiasis (RAPLOA) and Onchocerciasis (REA) in Rain forest Villages of Cameroon.

BACKGROUND: Individuals with high microfilarial loads of Loa loa are at increased risk of neurologic serious adverse (SAE) events following ivermectin treatment against onchocerciasis. RAPLOA (Rapid Assessment Procedure for loiasis), a newly developed rapid assessment procedure for loiasis that relates the prevalence of key clinical manifestation of loiasis (history of eye worm) to the level of endemicity of the infection (prevalence of high intensity), is a very useful tool to identify areas at potential risk of L. loa post ivermectin treatment encephalopathy. In a perspective of treatment decision making in areas of co-endemicity of loiasis/onchocerciasis, it would be advantageous (both in time and cost savings) for national onchocerciasis control programmes to use RAPLOA and the Rapid epidemiologic assessment for onchocerciasis (REA), in combination in given surveys. Since each of the two rapid assessment tools have their own specificities, the workability of combining the two methods needed to be tested. METHODS: We worked in 10 communities of a forest area presumed co-endemic for loiasis and onchocerciasis in the North-West Province of Cameroon where the mass-treatment with ivermectin had not been carried out. A four-step approach was used and comprised: (i) generating data on the prevalence and intensity of loiasis and onchocerciasis in an area where such information is scarce; (ii) testing the relationship between the L. loa microfilaraemia prevalence and the RAPLOA prevalence, (iii) testing the relationship between the O. volvulus microfiladermia prevalence and the REA prevalence, (iv) testing the workability of combining RAPLOA/REA by study teams in which a single individual can perform the interview for RAPLOA and the nodule palpation for REA. RESULTS: The microfilaraemia prevalence of loiasis in communities ranged from 3.6% to 14.3%. 6 (0.61%) individuals had L. loa microfilarial loads above 8000 mf/ml but none of them attained 30,000 mf/ml, the threshold value above which the risk of developing neurologic SAE after ivermectin treatment is very high. None of the communities surveyed had RAPLOA prevalence above 40%. All the communities had microfiladermia prevalence above 60%. The microfiladermia results could be confirmed by the rapid epidemiologic method (nodule palpation), with all the 10 communities having REA prevalence above 20%. For the first time, this study has demonstrated that the two rapid assessment procedures for loiasis and onchocerciasis can be carried out simultaneously by a survey team, in which a single individual can administer the questionnaire for RAPLOA and perform the nodule palpation for REA. CONCLUSION: This study has: (i) Revealed that the Momo valley of the North West province of Cameroon is hyperendemic for onchocerciasis, but is of lower level of endemicity for L. loa. (ii) Confirmed the previous relationships established between RAPLOA and the L. loa microfilaraemia prevalence in one hand and between the REA and the O. volvulus microfiladermia prevalence in another hand (iii) Shown that RAPLOA and REA could be used simultaneously for the evaluation of loiasis and onchocerciasis endemicity in areas targeted by the African Programme for onchocerciasis Control for community-directed treatment with ivermectin (CDTI).