Economic evaluations of onchocerciasis interventions: a systematic review and research needs.

OBJECTIVE: To provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps. METHOD: A systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. No date or language stipulations were applied to the searches. RESULTS: We identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost-effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis-associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost-effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability-adjusted life year (DALY) averted of annual MDA varies between US$3 and US$30 (cost year variable). CONCLUSIONS: The cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond.

OBJECTIF: Fournir une analyse systématique des évaluations économiques réalisées pour les interventions contre l'onchocercose, résumer les principales connaissances actuelles et identifier les lacunes de la recherche. MÉTHODE: Une revue systématique de la littérature a été menée le 8 août 2018 en utilisant les bases de données électroniques PubMed (Medline) et ISI Web of Science. Aucune indication de date ou de langue n'a été appliquée aux recherches. RÉSULTATS: Nous avons identifié 14 études principales rapportant sur les résultats d'évaluations économiques d'interventions contre l'onchocercose, dont 7 étaient des analyses coût-efficacité. Les études identifiées ont utilisé diverses approches pour estimer les coûts des interventions/programmes étudiés. A l'origine, les études ne mesuraient que les avantages associés à la prévention de la cécité. Progressivement, les méthodes se sont améliorées et ont également capturé les maladies de la peau associées à l'onchocercose. Les études ont montré que l'élimination de l'onchocercose générerait des milliards de bénéfices économiques. La majorité des analyses coût-efficacité ont évalué l'administration annuelle en masse de médicaments (AMD). Le coût estimé par année de vie ajustée par rapport à l'incapacité (DALY) corrigé pour l'AMD annuelle varie entre 3 et 30 USD (variable de l'année de coût). ConclusionsLe rapport coût-efficacité et la rentabilité des interventions contre l'onchocercose se sont toujours avérés très favorables. Cette constatation fournit un solide appui probant aux efforts en cours pour éliminer l'onchocercose des zones d'endémie. Bien que ces résultats soient très prometteurs, plusieurs lacunes importantes en matière de recherche doivent être comblées à mesure que nous nous approchons des étapes clés pour 2020 et au-delà.

A systematic review of scabies transmission models and data to evaluate the cost-effectiveness of scabies interventions.

BACKGROUND: Scabies is a common dermatological condition, affecting more than 130 million people at any time. To evaluate and/or predict the effectiveness and cost-effectiveness of scabies interventions, disease transmission modelling can be used. OBJECTIVE: To review published scabies models and data to inform the design of a comprehensive scabies transmission modelling framework to evaluate the cost-effectiveness of scabies interventions. METHODS: Systematic literature search in PubMed, Medline, Embase, CINAHL, and the Cochrane Library identified scabies studies published since the year 2000. Selected papers included modelling studies and studies on the life cycle of scabies mites, patient quality of life and resource use. Reference lists of reviews were used to identify any papers missed through the search strategy. Strengths and limitations of identified scabies models were evaluated and used to design a modelling framework. Potential model inputs were identified and discussed. FINDINGS: Four scabies models were published: a Markov decision tree, two compartmental models, and an agent-based, network-dependent Monte Carlo model. None of the models specifically addressed crusted scabies, which is associated with high morbidity, mortality, and increased transmission. There is a lack of reliable, comprehensive information about scabies biology and the impact this disease has on patients and society. DISCUSSION: Clinicians and health economists working in the field of scabies are encouraged to use the current review to inform disease transmission modelling and economic evaluations on interventions against scabies.

Design and Solidification of Fast-Releasing Clofazimine Nanoparticles for Treatment of Cryptosporidiosis.

Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable. In this work, clofazimine nanoparticles were prepared with three surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, using the flash nanoprecipitation (FNP) process. Drug encapsulation efficiencies of over 92% were achieved. Lyophilization and spray-drying were applied and optimized to produce redispersible nanoparticle powders. The release kinetics of these clofazimine nanoparticle powders in biorelevant media were measured and compared with those of crystalline clofazimine and the currently marketed formulation Lamprene. Remarkably improved dissolution rates and clofazimine supersaturation levels up to 90 times equilibrium solubility were observed with all clofazimine nanoparticles tested. Differential scanning calorimetry indicated a reduction of crystallinity of clofazimine in nanoparticles. These results strongly suggest that the new clofazimine nanoparticles prepared with affordable materials in this low-cost nanoparticle formulation process can be used as viable cryptosporidiosis therapeutics.

Reflections on the Nobel Prize for Medicine 2015--The Public Health Legacy and Impact of Avermectin and Artemisinin.

The award of the Nobel Prize to Dr Bill Campbell and Professor Satoshi Omura for their role in the discovery of avermectin and Professor Youyou Tu for her work on the development of artemisinin has been universally welcomed by the International Health community for what the Nobel Committee described as 'The discoveries of Avermectin and Artemisinin have revolutionized therapy for patients suffering from devastating parasitic diseases. Campbell, Omura and Tu have transformed the treatment of parasitic diseases. The global impact of their discoveries and the resulting benefit to mankind are immeasurable'.

Parasite control in Canadian companion animal shelters and a cost-comparison of anthelmintics.

Animal shelters have limited resources and must accommodate large numbers of animals at unpredictable intake rates. These dogs and cats are often parasitized, which can adversely affect the health of animals and expose shelter workers and adoptive owners to zoonoses. We analyzed survey responses from rural (n = 32) and urban (n = 50) companion animal shelters across Canada, and compared the wholesale cost of commercially available anthelmintics to identify cost-effective methods of managing parasites within shelters. Almost all shelters employed nematocides (98% to 99%), but cestocides and ectoparasiticides were used less frequently. Shelters identified cost as an important consideration in choosing to perform fecal diagnostic testing and administer anthelmintics, and this motivated many shelters to selectively perform testing (66%) or never to test (32%), and to use drugs extralabel (80%).

Contrôle des parasites dans les refuges pour animaux de compagnie du Canada et comparaison des coûts des anthelminthiques. Les refuges pour animaux possèdent des ressources limitées et doivent héberger un grand nombre d'animaux à des taux d'accueil imprévisibles. Des produits antiparasitaires sont souvent administrés à ces chiens et chats, ce qui peut influencer négativement la santé des animaux et exposer les travailleurs et les propriétaires adoptifs aux zoonoses. Nous avons analysé les réponses à un sondage provenant de refuges pour animaux de compagnie en région rurale (n = 32) et urbaine (n = 50) à l'échelle du Canada et nous avons comparé le coût de gros des anthelminthiques disponibles dans le commerce pour identifier des méthodes économiques de gérer les parasites dans les refuges. Presque tous les refuges employaient des nématicides (98 % à 99 %), mais les cestocides et les ectoparasiticides étaient utilisés moins fréquemment. Les refuges ont identifié le coût comme une considération importante lors des décisions relatives aux analyses des fèces et à l'administration des anthelminthiques et cette situation a motivé beaucoup de refuges à réaliser des analyses de manière sélective (66 %) ou de ne jamais effectuer d'analyses (32 %) et d'utiliser des médicaments en dérogation des directives de l'étiquette (80 %).(Traduit par Isabelle Vallières).

Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study.

BACKGROUND: More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire. METHODS: We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted. FINDINGS: Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities. INTERPRETATION: Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment. FUNDING: Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund.

Onchocerciasis control in the Democratic Republic of Congo (DRC): challenges in a post-war environment.

OBJECTIVE: To evaluate onchocerciasis control activities in the Democratic Republic of Congo (DRC) in the first 12 years of community-directed treatment with ivermectin (CDTI). METHODS: Data from the National Programme for Onchocerciasis (NPO) provided by the National Onchocerciasis Task Force (NOTF) through the annual reports of the 21 CDTI projects for the years 2001-2012 were reviewed retrospectively. A hypothetical-inputs-process-outputs-outcomes table was constructed. RESULTS: Community-directed treatment with ivermectin expanded from 1968 communities in 2001 to 39 100 communities by 2012 while the number of community-directed distributors (CDD) and health workers (HW) multiplied. By 2012, there were ratios of 1 CDD per 262 persons and 1 HW per 2318 persons at risk. More than 80% of the funding came from the fiduciary funds of the African Programme for Onchocerciasis Control. The cost of treatment per person treated fell from US$ 1.1 in 2001 to US$ 0.1 in 2012. The therapeutic coverage increased from 2.7% (2001) to 74.2% (2012); the geographical coverage, from 4.7% (2001) to 93.9% (2012). Geographical coverage fell in 2005 due to deaths in loiasis co-endemic areas, and the therapeutic coverage fell in 2008 due to insecurity. CONCLUSIONS: Challenges to CDTI in DRC have been serious adverse reactions to ivermectin in loiasis co-endemic areas and political conflict. Targets for personnel or therapeutic and geographical coverages were not met. Longer term funding and renewed efforts are required to achieve control and elimination of onchocerciasis in DRC.

High-cost generic drugs--implications for patients and policymakers.

Some older generic drugs have become very expensive, owing to factors including drug shortages, supply disruptions, and consolidations in the generic-drug industry. But generics manufacturers that legally obtain a market monopoly can also unilaterally raise prices.

The cost of annual versus biannual community-directed treatment of onchocerciasis with ivermectin: Ghana as a case study.

BACKGROUND: It has been proposed that switching from annual to biannual (twice yearly) mass community-directed treatment with ivermectin (CDTI) might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana. METHODOLOGY: The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective. PRINCIPAL FINDINGS: The estimated cost of treating annually was US Dollars (USD) 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round). The cost of CDTI was approximately 50-60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable. CONCLUSIONS/SIGNIFICANCE: This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control (or eliminate) onchocerciasis in Africa.

Ethical considerations in an era of mass drug administration.

In a Plenary debate at the 51st Spring meeting of the British Society of Parasitology, Bristol, UK, April 8-11, 2013, the bioethicist James Wilson used the value of a life in the present and future to question the effectiveness of current health strategies.

Morita-Baylis-Hillman adducts: biological activities and potentialities to the discovery of new cheaper drugs.

This review aims to present by the first time the Morita-Baylis-Hillman adducts (MBHA) as a new class of bioactive compounds and highlight its potentialities to the discovery of new cheaper and efficient drugs. Now, most these compounds can be prepared fast and on a single synthetic step (one-pot reaction) in high yields and using ecofriendly synthetic protocols. We highlight here the aromatic MBHA, which have shown diverse biological activities as anti-Leishmania chagasi and Leishmania amazonensis (parasites that cause cutaneous and visceral leishmaniasis), anti-Trypanosoma cruzi (parasite that cause Chagas disease), anti-Plasmodium falciparum and Plasmodium berghei (parasites that cause malaria), lethal against Biomphalaria glabrata (the snail transmitter of schistosomiasis), antibacterial, antifungal, herbicide and actives against some human tumor cell lines. Understanding of the biological mechanisms of action of this new class of molecules is still in the infancy stage. However, we report here which has been described to date on the possibilities of biological mechanisms of action, and we present new analyzes based on literature in this area. The academic and industrial interest in selecting green and cheaper experiments to the drugs development has been the prime mover of the growth on the subject.

Research priorities for zoonoses and marginalized infections.

This report provides a review and analysis of the research landscape for zoonoses and marginalized infections which affect poor populations, and a list of research priorities to support disease control. The work is the output of the Disease Reference Group on Zoonoses and Marginalized Infectious Diseases of Poverty (DRG6), which is part of an independent think tank of international experts, established and funded by the Special Programme for Research and Training in Tropical Diseases (TDR), to identify key research priorities through review of research evidence and input from stakeholder consultations. The report covers a diverse range of diseases, including zoonotic helminth, protozoan, viral and bacterial infections considered to be neglected and associated with poverty. Disease-specific research issues are elaborated under individual disease sections and many common priorities are identified among the diseases such as the need for new and/or improved drugs and regimens, diagnostics and, where appropriate, vaccines. The disease-specific priorities are described as micro priorities compared with the macro level priorities which will drive policy-making for: improved surveillance; interaction between the health, livestock, agriculture, natural resources and wildlife sectors in tackling zoonotic diseases; and true assessment of the burden of zoonoses. This is one often disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report search on Infectious Diseases of Poverty, available at: w.who.int/tdr/stewardship/global_report/en/index.html.

A randomised controlled clinical trial on the safety of co-administration of albendazole, ivermectin and praziquantel in infected schoolchildren in Uganda.

Integrated chemotherapy of neglected tropical diseases (NTD) through mass drug administration given as a single dose would increase treatment coverage and cost-effectiveness. This study reports on the safety of a combination of albendazole, ivermectin and praziquantel in the treatment of lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminthiasis (STH) in infected children. In this randomised, controlled, single-blinded clinical trial conducted in 235 primary school children aged 5-18 years in Yumbe District in Northern Uganda, the triple combination therapy was compared with the current NTD programme regimen. Liver function testing was performed for all children who received combined therapy. The study included 48 children with LF alone, 60 children with schistosomiasis (Schistosoma mansoni), 41 children with STH, 49 children with schistosomiasis + LF and 37 children with all three types of infection. Children were closely monitored by a paediatrician for any adverse reactions for 7 days. No serious adverse events were experienced. However, 4 of 18 children in the test group and 2 of 3 children in the control group who did not report any ill conditions before treatment developed adverse drug reactions. The combined and conventional therapies were found to be equally safe. The efficacies of both therapies were comparable and satisfactory. [ClinicalTrials.gov identifier: NCT01050517].