Use cases for genetic epidemiology in malaria elimination.

BACKGROUND: While traditional epidemiological approaches have supported significant reductions in malaria incidence across many countries, higher resolution information about local and regional malaria epidemiology will be needed to efficiently target interventions for elimination. The application of genetic epidemiological methods for the analysis of parasite genetics has, thus far, primarily been confined to research settings. To illustrate how these technical methods can be used to advance programmatic and operational needs of National Malaria Control Programmes (NMCPs), and accelerate global progress to eradication, this manuscript presents seven use cases for which genetic epidemiology approaches to parasite genetic data are informative to the decision-making of NMCPs. METHODS: The use cases were developed through a highly iterative process that included an extensive review of the literature and global guidance documents, including the 2017 World Health Organization's Framework for Malaria Elimination, and collection of stakeholder input. Semi-structured interviews were conducted with programmatic and technical experts about the needs and opportunities for genetic epidemiology methods in malaria elimination. RESULTS: Seven use cases were developed: Detect resistance, Assess drug resistance gene flow, Assess transmission intensity, Identify foci, Determine connectivity of parasite populations, Identify imported cases, and Characterize local transmission chains. The method currently used to provide the information sought, population unit for implementation, the pre-conditions for using these approaches, and post-conditions intended as a product of the use case were identified for each use case. DISCUSSION: This framework of use cases will prioritize research and development of genetic epidemiology methods that best achieve the goals of NMCPs, and ultimately, inform the establishment of normative policy guidance for their uses. With significant engagement of stakeholders from malaria endemic countries and collaboration with local programme experts to ensure strategic implementation, genetic epidemiological approaches have tremendous potential to accelerate global malaria elimination efforts.

The Micro-Elimination Approach to Eliminating Hepatitis C: Strategic and Operational Considerations.

The introduction of efficacious new hepatitis C virus (HCV) treatments galvanized the World Health Organization to define ambitious targets for eliminating HCV as a public health threat by 2030. Formidable obstacles to reaching this goal can best be overcome through a micro-elimination approach, which entails pursuing elimination goals in discrete populations through multi-stakeholder initiatives that tailor interventions to the needs of these populations. Micro-elimination is less daunting, less complex, and less costly than full-scale, country-level initiatives to eliminate HCV, and it can build momentum by producing small victories that inspire more ambitious efforts. The micro-elimination approach encourages stakeholders who are most knowledgeable about specific populations to engage with each other and also promotes the uptake of new models of care. Examples of micro-elimination target populations include medical patients, people who inject drugs, migrants, and prisoners, although candidate populations can be expected to vary greatly in different countries and subnational areas.

Models of Trachoma Transmission and Their Policy Implications: From Control to Elimination.

Despite great progress in eliminating trachoma from the majority of worldwide districts, trachoma control seems to have stalled in some endemic districts. Can mathematical models help suggest the way forward? We review specific achievements of models in trachoma control in the past. Models showed that, even with incomplete coverage, mass drug administration could eliminate disease through a spillover effect, somewhat analogous to how incomplete vaccine campaigns can eliminate disease through herd protection. Models also suggest that elimination can always be achieved if enough people are treated often enough with an effective enough drug. Other models supported the idea that targeting ages at highest risk or continued improvements in hygiene and sanitation can contribute meaningfully to trachoma control. Models of intensive targeting of a core group may point the way to final eradication even in areas with substantial transmission and within-community heterogeneity.

Policy Recommendations From Transmission Modeling for the Elimination of Visceral Leishmaniasis in the Indian Subcontinent.

Background: Visceral leishmaniasis (VL) has been targeted by the World Health Organization (WHO) and 5 countries in the Indian subcontinent for elimination as a public health problem. To achieve this target, the WHO has developed guidelines consisting of 4 phases of different levels of interventions, based on vector control through indoor residual spraying of insecticide (IRS) and active case detection (ACD). Mathematical transmission models of VL are increasingly used for planning and assessing the efficacy of interventions and evaluating the intensity and timescale required to achieve the elimination target. Methods: This paper draws together the key policy-relevant conclusions from recent transmission modeling of VL, and presents new predictions for VL incidence under the interventions recommended by the WHO using the latest transmission models. Results: The model predictions suggest that the current WHO guidelines should be sufficient to reach the elimination target in areas that had medium VL endemicities (up to 5 VL cases per 10000 population per year) prior to the start of interventions. However, additional interventions, such as extending the WHO attack phase (intensive IRS and ACD), may be required to bring forward elimination in regions with high precontrol endemicities, depending on the relative infectiousness of different disease stages. Conclusions: The potential hurdle that asymptomatic and, in particular, post-kala-azar dermal leishmaniasis cases may pose to reaching and sustaining the target needs to be addressed. As VL incidence decreases, the pool of immunologically naive individuals will grow, creating the potential for new outbreaks.

Leishmaniasis: current challenges and prospects for elimination with special focus on the South Asian region.

Leishmania donovani, the most virulent species of Leishmania, is found in the South Asian region that harbours the majority of visceral leishmaniasis (VL) cases in the world. The traditionally accepted relationships between the causative species of Leishmania and the resultant disease phenotype have been challenged during recent years and have underscored the importance of revisiting the previously established taxonomy with revisions to its classification. The weak voice of the afflicted with decades of neglect by scientists and policy makers have led to the miserably inadequate and slow advancements in product development in the fields of diagnostics, chemotherapeutics and vector control that continue to hinder the effective management and control of this infection. Limitations notwithstanding, the regional drive for the elimination of VL initiated over a decade ago that focused on India, Nepal and Bangladesh, the three main afflicted countries in the Indian subcontinent is therefore, commendable, with the subsequent status reviews and restructuring of strategies possibly even more so. However, the renewed efforts would need to be combined with plans to combat new challenges in the South-Asian region that includes the emergence of atypical parasite variants, in order to realistically achieve the set goal of regional elimination of VL.

Regulatory Aspects of Sabin Type 2 Withdrawal From Trivalent Oral Poliovirus Vaccine: Process and Lessons Learned.

Withdrawal of type 2 oral poliovirus vaccine (OPV) in OPV-using countries required regulatory approval for use of inactivated poliovirus vaccine and bivalent OPV in routine immunization. Worldwide, a variety of mechanisms were used by member states, with some differences in approach observed between inactivated poliovirus vaccine and bivalent OPV. These included acceptance for use of World Health Organization (WHO) prequalified vaccines, registration and licensure pathways, participation in WHO-convened joint reviews of licensing dossiers, as well as pragmatic application of alternatively available mechanisms, when appropriate. Simple but effective tools were used to monitor progress and to record, authenticate, and share information. Essential to achievement of regulatory targets was ongoing communication with key stakeholders, including switch-country national regulatory authorities, vaccine manufacturers, partner organizations, and relevant units within WHO. Understanding of the regulatory environment gained through the OPV switch can be helpful in supporting further stages of the polio end game and other time-sensitive vaccine introduction programs.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges.

BACKGROUND.: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a "90-90-90" target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether countries have reached this target are not standardized, hindering comparisons. METHODS.: Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that ever initiated ART; and (4) proportion of stage 3 who became virally suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. RESULTS.: In 2013, 674500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%-0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. CONCLUSIONS.: European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.

Social and cultural complexities of anti-malarial drug circulation: an ethnographic investigation in three rural remote communes of Cambodia.

BACKGROUND: Anti-malarial medicine has a central role in malaria case management in Cambodia. It is, therefore, essential to study how anti-malarial drugs are distributed and consumed. This study aims to understand the socio-cultural complexity of anti-malarial drugs provision and usage practices. METHODS: Semi-structured interviews and observation were conducted in Cambodia at the communal, provincial, and national levels from January 2014 to January 2015. Health ministers, non-governmental officers, anti-malarial medicines distributors, village malaria volunteers and malaria patients were interviewed. FINDINGS: The findings show that artemisinin-based combination therapy (ACT) flows into unregulated outlets, and was sold without any diagnostic tests. Affordable Medicines Facility for malaria scheme (AMFm) cannot drive ineffective anti-malarial medicines out of the market because ACT is still more expensive due to price absortion by private and public providers. Malaria patients might not consume ACT because of patients' notions of 'Korp', and pharmaceutical and parasitic familiarity. The findings reflect that neither public nor private institutions have the capacity and resources to control the flow of ACT from going into the unlicensed sector. They do not have the ability to ensure that ACT is consumed after a positive rapid diagnostic test. CONCLUSIONS: With a weak regulation system and ailing public health infrastructure, pharmaceutical-neoliberal mechanism like AMFm is not an effective means to eradicate any forms of malaria. Therefore, horizontal programmes, such as public health infrastructure improvement, and population participation must be implemented. Ethnical responsibilities of medical practitioners must be enforced and be included into the national curriculum. The awareness of drug resistance must be implemented at all levels.

An appraisal of the neglected tropical diseases control program in Cameroon: the case of the national program against onchocerciasis.

BACKGROUND: Onchocerciasis is a severe parasitic infestation which causes disabling skin and subcutaneous tissue changes. Current global estimates suggest that it accounts for 1135.7 disability adjusted life years (DALYs) per 100,000 population. The disease is endemic in many African countries including Cameroon, probably suggesting that the current health policies are inadequate to achieve eradication of the disease. We aimed to appraise the current Onchocerciasis control program in Cameroon in the context of existing literature. METHODS: We carried out a MEDLINE search via PubMed to source for articles on Onchocerciasis in Cameroon. RESULTS: Our appraisal of the literature suggests that Onchocerciasis poses a significant health and economic burden in Cameroon. A composite of factors contribute to the challenge of containing and eradicating Onchocerciasis in Cameroon and include: continuous transmission of the disease; non-compliance to mass drug administration; inability of health care providers (HCPs) to adequately diagnose the disease; limited access of most individuals in endemic zones to annual preventive chemotherapy and inadequate population education on simple and practical measures to prevent the disease. More robust population-based epidemiologic studies are needed to better quantify the current disease burden and consequently guide intervention strategies for complete disease eradication. CONCLUSION: Onchocerciasis is still a neglected tropical disease (NTD) in Cameroon and urgently demands a need for intensification and probably modification of some strategies in the current onchocerciasis elimination program. Control of the disease will contribute to achievement of the corresponding Sustainable Development Goals (SDGs) quota.

[Chikungunya and urban sprawl on Reunion Island]. / Le chikungunya et l'habitat informel a La Réunion.

The proportion of unsanitary housing in French overseas departments is much higher than in mainland France. Reunion Island is no exception to this fact. Between 80 and 90% of housing in Reunion Island was built by squatters with no legal claim or deed to the property. This has resulted in uncontrolled urban sprawl with living conditions reminiscent of those in developing countries. The absence of adequate drainage systems for sewage and rain water and the lack of properly organized garbage disposal that characterizes these sprawl areas constitutes a particularly favorable breeding ground for vector-borne diseases, especially chikungunya. Thus, implementing measures to control this type of settlement and to relocate of people out of existing sprawl areas constitutes a significant tool to control this epidemiological risk. Up to now, public officials have shown a clear reluctance to intervene in sprawl areas despite good knowledge of their location. On June 26th of this year, a law containing provisions relative to the control of urban sprawl and unsanitary housing in overseas departments and territories will come into effect. This law should provide public officials with the legal basis that has up until now been lacking to take action. Persistence in the "wait-and-see" attitude could lead to condemnation by French or European courts.

Do the most heavily burdened countries have the right policies to eliminate viral hepatitis B and C?

In 2019, a Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis reported on the status of 11 viral hepatitis policy indicators in 66 countries and territories with the heaviest burden by global region. Policies were reported as being either in place, in development, or not in place. This study uses the Commission findings to estimate hepatitis B virus (HBV) and hepatitis C virus (HCV) policy scores and rankings for these 66 countries and territories. We applied a multiple correspondence analysis technique to reduce data on policy indicators into a weighted summary for the HBV and HCV policies. We calculated HBV and HCV policy scores for each country. Countries and territories that received higher scores had more policies in place and in development than did countries with lower scores. The highest scoring country for HBV was Australia, whereas Somalia had the lowest score. For the HCV policy score, Australia and New Zealand had perfect scores, whereas Somalia, Sudan, and Yemen had the lowest scores, all having no policy indicators in place.

Epidemiological situation of yaws in the Americas: A systematic review in the context of a regional elimination goal.

BACKGROUND: Yaws is targeted for eradication by 2020 in the WHA66.12 resolution of the World Health Assembly. The objective of this study was to describe the occurrence of yaws in the Americas and to contribute to the compilation of evidence based on published data to undertake the certification of yaws eradication. METHODOLOGY: A systematic review of the epidemiological situation of yaws in the Americas was performed by searching in MEDLINE, Embase, LILACS, SCOPUS, Web of Science, DARE and Cochrane Database of Systematic Reviews. Experts on the topic were consulted, and institutional WHO/PAHO library databases were reviewed. PRINCIPAL FINDINGS: Seventy-five full-text articles published between 1839 and 2012 met the inclusion criteria. Haiti and Jamaica were the two countries with the highest number of papers (14.7% and 12.0%, respectively). Three-quarters of the studies were conducted before 1970. Thirty-three countries reported yaws case count or prevalence data. The largest foci in the history were described in Brazil and Haiti. The most recent cases reported were recorded in eight countries: Suriname, Guyana, Colombia, Haiti, Martinique, Dominica, Trinidad and Tobago, and Brazil. Gaps in information and heterogeneity were detected in the methodologies used and outcome reporting, making cross-national and chronological comparisons difficult. CONCLUSIONS: The lack of recent yaws publications may reflect, in the best-case scenario, the interruption of yaws transmission. It should be possible to reach the eradication goal in the region of the Americas, but it is necessary to collect more information. We suggest updating the epidemiological status of yaws, especially in two countries that need to assess ongoing transmission. Twenty-four countries need to demonstrate the interruption of transmission and declare its status of yaws endemicity, and sixteen countries should declare if they are yaws-free. It is necessary to formally verify the achievement of this goal in Ecuador.

A Comparative Review of Prevention of Rabies Incursion between Japan and Other Rabies-Free Countries or Regions.

Although rabies still kills many people, the global eradication of human rabies is considered to be feasible. Progress towards eradication may differ among regions with differing socio-economic statuses; therefore, states that successfully eradicate this disease must be vigilant for rabies re-emergence. Here, we discuss challenges that remain concerning current rabies prevention measures and risk assessment results concerning possible rabies introduction and spread in rabies-free Japan. We summarize the preventative measures undertaken by representative rabies-free countries and regions. Our risk assessment results show that the risk of rabies reintroduction under current circumstances is very low, and that subsequent spread of the disease would be minimal because of quite low value of basic reproduction number. Similar assessments conducted in other rabies-free areas also showed limited risks of introduction. The majority of rabies-free countries maintain their rabies-free status through strict import quarantine of carnivorous animals, efficient surveillance of animal rabies including wildlife, quick emergency responses, and raising public awareness of the disease. To maintain the current rabies-free status in Japan, we strongly recommend maintaining the current quarantine system and reinforcing stakeholder compliance for those involved in international movement of dogs. Moreover, sustainable surveillance systems targeting wildlife are indispensable.

Regional reports for the subnational monitoring of measles elimination in Italy and the identification of local barriers to the attainment of the elimination goal.

Although most countries in the WHO European Region were verified in 2017 as having interrupted endemic measles transmission, nine countries were still endemic. Among these, Italy accounted for the second highest number of measles cases reported in Europe in 2017. The elimination of measles is verified at national level by each country's National Verification Committee (NVC) through the production of an Annual Status Update (ASU). Since in Italy decentralization has led to an inhomogeneous implementation of immunization strategies among the 21 administrative Regions, the Italian NVC proposed that measles elimination should also be documented at the subnational level through regional ASUs and Synthetic Regional Reports (SRRs). The regional ASUs and the SRRs for 2014, 2015 and 2016 were produced and appraised by the NVC to evaluate the Regions' performances in each individual year as well as over the whole period. A specific analysis of vaccination coverage, including official immunization data for 2017, was performed. Moreover, the measles epidemic of 2017 was examined. Firstly, in the period 2014-2016, low immunization rates were registered in most Regions. Sixty-three per cent of southern Regions reported rates below the national mean and an overall low-quality performance. The approval of Italy's mandatory vaccination law in 2017 resulted in a marked increase in vaccination coverage; however, this increase was not homogeneous among Regions. Secondly, more than 50% of Regions did not report any supplemental immunization activity (SIA) for the period 2014-2016. Thirdly, from 2014 to 2016, fewer than one-third of Regions improved their reporting of outbreaks. Finally, over the study period, only two Regions reached the target required by the WHO for measles laboratory investigations. In countries with decentralized health policies, subnational monitoring can help identify local barriers to measles elimination. In Italy it has highlighted the need for further SIAs and a stronger surveillance system.

Localized US Efforts to Eliminate Hepatitis C.

The United States has national plans for the elimination of hepatitis C virus but much of US health care is organized on the state level and requires local solutions. This article describes the plans developed by New York, Massachusetts, and the city/county of San Francisco for hepatitis C virus elimination. Coalitions capitalize on existing resources and advocate for new resources to address barriers in hepatitis C virus care. Although each coalition has distinct plans, all share a commitment to groups that are disproportionately affected and are at risk for being excluded from advances in hepatitis C virus treatment and cure.

Five Questions Concerning Managing Hepatitis C in the Justice System: Finding Practical Solutions for Hepatitis C Virus Elimination.

An estimated 30% of Americans with hepatitis C virus (HCV) pass through a jail or prison annually. One in 7 incarcerated persons is viremic. Screening and treatment is cost-effective and beneficial to society as a whole. Yet at current (2018) levels of funding for HCV management, prisons are not aggressively seeking cases; few incarcerated persons with HCV actually receive treatment. This article explores barriers to screening for and treating hepatitis C in state prisons, and ways that states may overcome these barriers, such as nominal pricing. While high prices for direct-acting antivirals discourage treatment, potential strategies exist to lower prices.

Elimination of Hepatitis C Virus in Australia: Laying the Foundation.

Australia is on-track to achieve World Health Organization hepatitis C virus (HCV) elimination targets. An active HCV screening program led to 82% of HCV-infected population being diagnosed. An unrestricted direct-acting antiviral (DAA) program, launched in March 2016 resulted in an estimated 58,500 individuals (26% of total HCV-infected population, including 70% of those with cirrhosis) initiating treatment through 2017. Treatment uptake was high among sub-populations at greater HCV transmission risk with 22% of people injecting drugs and >60% of those with HIV/HCV coinfection initiating DAA treatment in 2016. A monitoring and evaluation program will inform strategies required to achieve HCV elimination targets.