Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Core principles of Malakit intervention for transferability in other contexts.

To eliminate malaria, all populations must be included. For those who are not reached by the health care system, specific interventions must be tailor-made. An innovative Malakit strategy, based on the distribution of self-diagnosis and self-treatment kits, has been evaluated in the Suriname-French Guiana- Amapá (Brazil) region. The results showed effectiveness and good acceptability. The Malakit intervention is complex and has many components. Its transferability requires adaptation to other populations and regions, while retaining the main features of the intervention. This article provides the keys to adapting, implementing and evaluating it in other contexts facing residual malaria in hard-to-reach and/or mobile populations. The process of transferring this intervention includes: diagnosis of the situation (malaria epidemiology, characteristics of the population affected) to define the relevance of the strategy; determination of the stakeholders and the framework of the intervention (research project or public health intervention); adaptation modalities (adaptation of the kit, training, distribution strategy); the role of community health workers and their need for training and supervision. Finally, evaluation needs are specified in relation to prospects for geographical or temporal extension. Malaria elimination is likely to increasingly involve marginalized people due to climate change and displacement of populations. Evaluation of the transferability and effectiveness of the Malakit strategy in new contexts will be essential to increase and refine the evidence of its value, and to decide whether it could be an additional tool in the arsenal recommended in future WHO guidelines.

[Malaria vaccines: a new tool for elimination?] / Vaccins contre le paludisme : un nouvel outil pour l'élimination ?

A malaria vaccine represents an essential complementary tool to curb the stagnation, or even increase, in malaria cases observed over the last decade due to the emergence of resistance to insecticides impregnated on mosquito nets, wars and internal conflicts, as well as global warming. In October 2021, WHO recommended the use of the RTS,S/ASO1 vaccine for children aged 5-17 months in areas of moderate to high transmission. In October 2023, a second vaccine received WHO approval for deployment in the same population, following demonstration of around 70 % efficacy in protecting young children against malaria for one year. Given their partial efficacy, however, these vaccines are not generally recommended for travelers to endemic countries.

Un vaccin contre le paludisme représente une mesure complémentaire essentielle pour juguler la stagnation, voire l'augmentation des cas de paludisme observée durant cette dernière décade en raison de l'émergence de la résistance aux insecticides imprégnés sur les moustiquaires, des guerres et conflits internes ainsi que du réchauffement climatique. En octobre 2021, l'OMS a recommandé l'emploi du vaccin RTS,S/ASO1 pour les enfants de 5 à 17 mois dans les zones de transmission modérée à forte. En octobre 2023, un second vaccin a reçu l'aval de l'OMS pour son déploiement dans la même population, suite à la démonstration d'une efficacité d'environ 70 % pour protéger les jeunes enfants contre le paludisme pendant une année. Vu leur efficacité partielle, ces vaccins ne sont cependant généralement pas recommandés pour les voyageurs se rendant dans les pays d'endémie.

Progress Toward Measles Elimination - African Region, 2017-2021.

Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member states established a goal of regional measles elimination by 2020; this report describes progress during 2017-2021. Regional coverage with a first dose of measles-containing vaccine (MCV) decreased from 70% in 2017 to 68% in 2021, and the number of countries with ≥95% coverage decreased from six (13%) to two (4%). The number of countries providing a second MCV dose increased from 27 (57%) to 38 (81%), and second-dose coverage increased from 25% to 41%. Approximately 341 million persons were vaccinated in supplementary immunization activities, and an estimated 4.5 million deaths were averted by vaccination. However, the number of countries meeting measles surveillance performance indicators declined from 26 (62%) to nine (22%). Measles incidence increased from 69.2 per 1 million population in 2017 to 81.9 in 2021. The number of estimated annual measles cases and deaths increased 22% and 8%, respectively. By December 2021, no country in AFR had received verification of measles elimination. To achieve a renewed regional goal of measles elimination in at least 80% of countries by 2030, intensified efforts are needed to recover and surpass levels of surveillance performance and coverage with 2 MCV doses achieved before the COVID-19 pandemic.

Cervical screening among LGBTQ people: how affirming services may aid in achieving cervical cancer elimination targets.

To reach cervical cancer elimination targets it is necessary to increase screening rates among underserved populations such as LGBTQ communities. This paper examines rates of attendance and associated factors of cervical screening in LGBTQ communities. Data from 2,424 people aged 25 to 74 years and assigned female at birth were drawn from an online national Australian survey of LGBTQ adults. Over half of the sample had accessed cervical screening in the past 2 years. Using a multivariable logistic regression analysis, significant associations were found between screening, sociodemographic traits and health-care access. Trans men were least likely to access cervical screening, while bisexual, pansexual and queer identified participants were most likely to access screening. People who lived outside inner-suburban areas and those who had a disability were less likely to have had screening. Evidence of trusting relationships with a general practitioner (having a regular GP and GP's knowledge of the individual's LGBTQ identity) increased the likelihood that participants had screened, as did recent access to a medical service that was LGBTQ-inclusive or catered specifically to LGBTQ communities. The findings suggest the importance of training health providers, as well as targeted public health messaging for increasing uptake of cervical screening among LGBTQ people.

Progress Toward Achieving and Sustaining Maternal and Neonatal Tetanus Elimination - Worldwide, 2000-2020.

Maternal and neonatal tetanus (MNT)* remains a major cause of neonatal mortality with an 80%-100% case-fatality rate among insufficiently vaccinated mothers after unhygienic deliveries, especially in low-income countries (1). In 1989, the World Health Assembly endorsed elimination† of neonatal tetanus; the activity was relaunched in 1999 as the MNT elimination (MNTE)§ initiative, targeting 59¶ priority countries. MNTE strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV2+)** among women of reproductive age through routine and supplementary immunization activities (SIAs)†† in high-risk districts,§§ 2) achieving ≥70% of deliveries by a skilled birth attendant,¶¶ and 3) implementing neonatal tetanus case-based surveillance (2). This report summarizes progress toward achieving and sustaining MNTE during 2000-2020 and updates a previous report (3). By December 2020, 52 (88%) of 59 priority countries had conducted TTCV SIAs. Globally, infants protected at birth*** against tetanus increased from 74% (2000) to 86% (2020), and deliveries assisted by a skilled birth attendant increased from 64% (2000-2006) to 83% (2014-2020). Reported neonatal tetanus cases worldwide decreased by 88%, from 17,935 (2000) to 2,229 (2020), and estimated deaths decreased by 92%, from 170,829 (2000) to 14,230 (2019).††† By December 2020, 47 (80%) of 59 priority countries were validated to have achieved MNTE, five of which conducted postvalidation assessments.§§§ To achieve elimination in the 12 remaining countries and sustain elimination, innovation is needed, including integrating SIAs to cover multiple vaccine preventable diseases and implementing TTCV life course vaccination.

Receptivity to malaria: meaning and measurement.

"Receptivity" to malaria is a construct developed during the Global Malaria Eradication Programme (GMEP) era. It has been defined in varied ways and no consistent, quantitative definition has emerged over the intervening decades. Despite the lack of consistency in defining this construct, the idea that some areas are more likely to sustain malaria transmission than others has remained important in decision-making in malaria control, planning for malaria elimination and guiding activities during the prevention of re-establishment (POR) period. This manuscript examines current advances in methods of measurement. In the context of a decades long decline in global malaria transmission and an increasing number of countries seeking to eliminate malaria, understanding and measuring malaria receptivity has acquired new relevance.

High hepatitis C treatment uptake among people with recent drug dependence in New South Wales, Australia.

BACKGROUND & AIMS: High HCV treatment uptake among people at most risk of transmission is essential to achieve elimination. We aimed to characterise subpopulations of people with HCV based on drug dependence, to estimate direct-acting antiviral (DAA) uptake in an unrestricted treatment era, and to evaluate factors associated with treatment uptake among people with recent drug dependence. METHODS: HCV notifications in New South Wales, Australia (1995-2017) were linked to opioid agonist therapy (OAT), hospitalisations, incarcerations, HIV notifications, deaths, and prescription databases. Drug dependence was defined as hospitalisation due to injectable drugs or receipt of OAT, with indicators in 2016-2018 considered recent. Records were weighted to account for spontaneous clearance. Logistic regression was used to analyse factors associated with treatment uptake among those with recent drug dependence. RESULTS: 57,467 people were estimated to have chronic HCV throughout the DAA era. Treatment uptake was highest among those with recent (47%), compared to those with distant (38%), and no (33%) drug dependence. Among those with recent drug dependence, treatment was more likely among those with HIV (adjusted odds ratio [aOR] 1.71; 95% CI 1.24-2.36), recent incarceration (aOR 1.10; 95% CI 1.01-1.19), and history of alcohol use disorder (aOR 1.22; 95% CI 1.13-1.31). Treatment was less likely among women (aOR 0.78; 95% CI 0.72-0.84), patients of Indigenous ethnicity (aOR 0.75; 95% CI 0.69-0.81), foreign-born individuals (aOR 0.86; 95% CI 0.78-0.96), those with outer-metropolitan notifications (aOR 0.90; 95% CI 0.82-0.98), HBV coinfection (aOR 0.69; 95% CI 0.59-0.80), and >1 recent hospitalisation (aOR: 0.91; 95% CI 0.84-0.98). CONCLUSIONS: These data provide evidence of high DAA uptake among people with recent drug dependence, including those who are incarcerated. Enhancing this encouraging initial uptake among high-risk populations will be essential to achieve HCV elimination. LAY SUMMARY: To facilitate HCV elimination, those at highest risk of infection and transmission are a treatment priority. This study shows the successes of Australia's universal provision of DAA therapy in reducing the barriers to treatment which have historically persisted among people who inject drugs. Despite higher DAA therapy uptake among those with recent drug dependence, gaps remain. Strategies which aim to reduce marginalisation and increase treatment uptake to ensure equitable HCV elimination must be advanced.

Opinions of key stakeholders on alternative interventions for malaria control and elimination in Tanzania.

BACKGROUND: Malaria control in Tanzania currently relies primarily on long-lasting insecticidal nets and indoor residual spraying, alongside effective case management and behaviour change communication. This study explored opinions of key stakeholders on the national progress towards malaria elimination, the potential of currently available vector control interventions in helping achieve elimination by 2030, and the need for alternative interventions that could be used to supplement malaria elimination efforts in Tanzania. METHODS: In this exploratory qualitative study, Focus group discussions were held with policy-makers, regulators, research scientists and community members. Malaria control interventions discussed were: (a) improved housing, (b) larval source management, (c) mass drug administration (MDA) with ivermectin to reduce vector densities, (d) release of modified mosquitoes, including genetically modified or irradiated mosquitoes, (e) targeted spraying of mosquito swarms, and (f) spatial repellents. RESULTS: Larval source management and spatial repellents were widely supported across all stakeholder groups, while insecticide-spraying of mosquito swarms was the least preferred. Support for MDA with ivermectin was high among policy makers, regulators and research scientists, but encountered opposition among community members, who instead expressed strong support for programmes to improve housing for poor people in high transmission areas. Policy makers, however, challenged the idea of government-supported housing improvement due to its perceived high costs. Techniques of mosquito modification, specifically those involving gene drives, were viewed positively by community members, policy makers and regulators, but encountered a high degree of scepticism among scientists. Overall, policy-makers, regulators and community members trusted scientists to provide appropriate advice for decision-making. CONCLUSION: Stakeholder opinions regarding alternative malaria interventions were divergent except for larval source management and spatial repellents, for which there was universal support. MDA with ivermectin, housing improvement and modified mosquitoes were also widely supported, though each faced concerns from at least one stakeholder group. While policy-makers, regulators and community members all noted their reliance on scientists to make informed decisions, their reasoning on the benefits and disadvantages of specific interventions included factors beyond technical efficiency. This study suggests the need to encourage and strengthen dialogue between research scientists, policy makers, regulators and communities regarding new interventions.

History of malaria control in Rwanda: implications for future elimination in Rwanda and other malaria-endemic countries.

BACKGROUND: Malaria was first reported in Rwanda in the early 1900s with significant heterogeneity and volatility in transmission over subsequent decades. Here, a comprehensive literature review of malaria transmission patterns and control strategies in Rwanda between 1900 and 2018 is presented to provide insight into successes and challenges in the country and to inform the future of malaria control in Rwanda. METHODS: A systematic literature search of peer-reviewed publications (Web of Knowledge, PubMed, Google Scholar, and the World Health Organization Library (WHOLIS) and grey literature on malaria control in Rwanda between 1900 and 2019 was conducted with the following search terms: "malaria"", "Rwanda", "epidemiology", "control", "treatment", and/or "prevention." Reports and other relevant documents were also obtained from the Rwanda National Malaria Control Programme (NMCP). To inform this literature review and evidence synthesis, epidemiologic and intervention data were collated from NMCP and partner reports, the national routine surveillance system, and population surveys. RESULTS: Two hundred sixty-eight peer-reviewed publications and 56 grey literature items were reviewed, and information was extracted. The history of malaria control in Rwanda is thematically described here according to five phases: 1900 to 1954 before the launch of the Global Malaria Eradication Programme (GMEP); (2) Implementation of the GMEP from 1955 to 1969; (3) Post- GMEP to 1994 Genocide; (4) the re-establishment of malaria control from 1995 to 2005, and (5) current malaria control efforts from 2006 to 2018. The review shows that Rwanda was an early adopter of tools and approaches in the early 2000s, putting the country ahead of the curve and health systems reforms created an enabling environment for an effective malaria control programme. The last two decades have seen unprecedented investments in malaria in Rwanda, resulting in significant declines in disease burden from 2000 to 2011. However, in recent years, these gains appear to have reversed with increasing cases since 2012 although the country is starting to make progress again. CONCLUSION: The review shows the impact and fragility of gains against malaria, even in the context of sustained health system development. Also, as shown in Rwanda, country malaria control programmes should be dynamic and adaptive to respond and address changing settings.

Eradicating Measles: A Call for an Exceptional Coordinated Global Effort.

There are compelling epidemiological, economic, and ethical arguments for setting a global measles eradication goal. The 6 chairpersons of Regional Verification Commissions for Measles and Rubella elimination advocate that the time for courageously accelerating efforts to ensure a world where no child dies of measles, is NOW!

Addressing critical needs in the fight to end tuberculosis with innovative tools and strategies.

This month in PLOS Medicine we launched a Special Issue on New Tools and Strategies for Tuberculosis Diagnosis, Care, and Elimination. In this issue's Editorial, the Guest Editors Claudia Denkinger, Richard Chaisson, and Mark Hatherill highlight some of the research that will publish and how these studies focusing on discovery, clinical trials and implementation research collectively add to the prospects for reaching the EndTB targets of the WHO by 2035.

Setting targets for HIV/AIDS-What lessons can be learned from other disease control programmes?

In a Collection Review, Richard Hayes and colleagues discuss metrics for assessing progress in control of the HIV/AIDS epidemic in the context of prior disease control programmes.

Toward the elimination of hepatitis C in the United States.

The emergence of effective direct-acting antiviral (DAA) agents has reignited discussion over the potential for hepatitis C elimination in the United States. Eliminating hepatitis C will require a critical examination of technical feasibility, economic considerations, and social/political attention. Tremendous advancement has been made with the availability of sensitive diagnostic tests and highly effective DAAs capable of achieving sustained viral response (SVR) in more than 95% of patients. Eliminating hepatitis C also requires escalating existing surveillance networks to monitor for new epidemics. All preventive interventions such as clean syringe and needle exchange programs, safe injection sites, opioid substitution therapies, and mental health services need to be expanded. Although costs of DAAs have raised budget concerns for hepatitis C elimination, studies have shown that eliminating hepatitis C will produce a savings of up to 6.5 billion USD annually along with other intangible benefits such as increased work productivity and quality of life. Economic models and meta-analyses strongly suggest universal hepatitis C screening for all adults rather than just for birth cohort and high-risk populations. Social and political factors are at least as important as technical feasibility and economic considerations. Due to lack of promotion and public awareness, HCV elimination efforts continue to receive inadequate funding. Social stigma continues to impede meaningful policy changes. Eliminating hepatitis C is an attainable public health goal that will require intense collaboration and sustained public support. (Hepatology 2018;67:2449-2459).

"Remarkable solutions to impossible problems": lessons for malaria from the eradication of smallpox.

BACKGROUND: Malaria elimination and eventual eradication will require internationally coordinated approaches; sustained engagement from politicians, communities, and funders; efficient organizational structures; innovation and new tools; and well-managed programmes. As governments and the global malaria community seek to achieve these goals, their efforts should be informed by the substantial past experiences of other disease elimination and eradication programmes, including that of the only successful eradication programme of a human pathogen to date: smallpox. METHODS: A review of smallpox literature was conducted to evaluate how the smallpox programme addressed seven challenges that will likely confront malaria eradication efforts, including fostering international support for the eradication undertaking, coordinating programmes and facilitating research across the world's endemic countries, securing sufficient funding, building domestic support for malaria programmes nationally, ensuring strong community support, identifying the most effective programmatic strategies, and managing national elimination programmes efficiently. RESULTS: Review of 118 publications describing how smallpox programmes overcame these challenges suggests eradication may succeed as a collection of individual country programmes each deriving local solutions to local problems, yet with an important role for the World Health Organization and other international entities to facilitate and coordinate these efforts and encourage new innovations. Publications describing the smallpox experience suggest the importance of avoiding burdensome bureaucracy while employing flexible, problem-solving staff with both technical and operational backgrounds to overcome numerous unforeseen challenges. Smallpox's hybrid strategy of leveraging basic health services while maintaining certain separate functions to ensure visibility, clear targets, and strong management, aligns with current malaria approaches. Smallpox eradication succeeded by employing data-driven strategies that targeted resources to the places where they were most needed rather than attempting to achieve mass coverage everywhere, a potentially useful lesson for malaria programmes seeking universal coverage with available tools. Finally, lessons from smallpox programmes suggest strong engagement with the private sector and affected communities can help increase the sustainability and reach of today's malaria programmes. CONCLUSIONS: It remains unclear whether malaria eradication is feasible, but neither was it clear whether smallpox eradication was feasible until it was achieved. To increase chances of success, malaria programmes should seek to strengthen programme management, measurement, and operations, while building flexible means of sharing experiences, tools, and financing internationally.

Mass drug administration should be implemented as a tool to accelerate elimination: against.

In most malaria situations, mass drug administration (MDA) will result in a rapid reduction in the incidence and prevalence of malaria in the target population. However, due to practical reasons MDA hardly ever achieves coverage of the entire population and, therefore, will leave residual malaria infections in the population, from which malaria transmission can be resumed. Depending on the degree of access to prompt diagnosis and treatment and to effective vector control in the area, previous levels of incidence and prevalence will eventually be reached after MDA. It is, therefore, imperative that coverage with these interventions is ensured if MDA is to be implemented. Both effective vector control and access to treatment in combination will also reduce the malaria incidence and prevalence in an area, albeit more slowly than MDA. MDA's role in elimination has to be considered in relation to the following: (1) MDA is logistically difficult, ethically questionable and may evoke parasite resistance to the medicines being used, (2) MDA will only accelerate elimination by reducing the starting number of infections, but that (3) it will be of no benefit to elimination unless both effective vector control and good access to treatment are in place. All malaria elimination efforts have, and will, succeed with good access to treatment, effective vector control, and case surveillance and response systems, and most have not, and will not require MDA. The role of MDA in elimination, if any, will be limited to some very specific situations-small foci of high transmission within a larger area which has made progress towards elimination, to which the former constitutes a continuing source of parasites and, therefore, could jeopardize the elimination effort in the larger area. Elimination of malaria needs not only to be achieved but also be sustained. This is particularly challenging in tropical countries where the risk of re-introduction is high. The haste to eliminate malaria using MDA must be balanced by investment of time and effort to establish effective vector control programmes, and case surveillance and response systems based on diagnosis and treatment services, which are core requisites for achieving elimination, and the latter for sustaining it.

Are new national malaria strategic plans informed by the previous ones? A comprehensive assessment of sub-Saharan African countries from 2001 to present.

BACKGROUND: New national malaria strategic plans (NMSPs) should build upon the achievements and challenges identified during the implementation of previous plans, but there is limited research on the transition process between NMSPs. This study aims to fill this gap through an assessment of NMSPs across sub-Saharan Africa. METHODS: The study reviewed the two most recent NMSPs for selected sub-Saharan African countries. Targets for six core malaria indicators were extracted from each NMSP and compared to the coverage achieved according to corresponding population-based surveys completed near the end of the NMSP term. Implementation challenges and proposed solutions identified through the NMSP analysis were documented. The current NMSP was reviewed to determine whether proposed solutions had been integrated into the strategy. RESULTS: Twenty-two countries in sub-Saharan Africa were included in the assessment. Of the 135 verified targets, only 4 were achieved. No country reached more than one of the six targets assessed in each NMSP. Despite this low success rate, only four of the 22 countries lowered a subsequent target, with most setting the next target at an equal or greater level. Most NMSPs identified solutions to address implementation challenges faced, but the solutions were not always fully incorporated in the new strategy. CONCLUSIONS: The results show a disconnect between NMSPs. Most targets were set according to global goals rather than the individual country's previous achievements and limitations. This indicates a need to revise the NMSP development process to guide programmes in defining targets based on their country context and incorporate strategies to address challenges identified in the previous NMSP. This will allow countries to set and meet achievable targets as they work toward global goals.