National mass drug administration costs for lymphatic filariasis elimination

Background

Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk.

Methodology/Principal Findings

To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications.

Conclusions/Significance

MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones.     

Using community-owned resource persons to provide early diagnosis and treatment and estimate malaria burden at community level in north-eastern Tanzania

ABSTRACT: BACKGROUND: Although early diagnosis and prompt treatment is an important strategy for control of malaria, using fever to initiate presumptive treatment with expensive artemisinin combination therapy is a major challenge; particularly in areas with declining burden of malaria. This study was conducted using community-owned resource persons (CORPs) to provide early diagnosis and treatment of malaria, and collect data for estimation of malaria burden in four villages of Korogwe district, north-eastern Tanzania. METHODS: In 2006, individuals with history of fever within 24 hours or fever (axillary temperature [greater than or equal to]37.5degreesC) at presentation were presumptively treated using sulphadoxine/pyrimethamine. Between 2007 and 2010, individuals aged five years and above, with positive rapid diagnostic tests (RDTs) were treated with artemether/lumefantrine (AL) while under-fives were treated irrespective of RDT results. Reduction in anti-malarial consumption was determined by comparing the number of cases that would have been presumptively treated and those that were actually treated based on RDTs results. Trends of malaria incidence and slide positivity rates were compared between lowlands and highlands. RESULTS: Of 15,729 cases attended, slide positivity rate was 20.4% and declined by >72.0% from 2008, reaching <10.0% from 2009 onwards; and the slide positivity rates were similar in lowlands and highlands from 2009 onwards. Cases with fever at presentation declined slightly, but remained at >40.0% in under-fives and >20.0% among individuals aged five years and above. With use of RDTs, cases treated with AL decreased from <58.0% in 2007 to <11.0% in 2010 and the numbers of adult courses saved were 3,284 and 1,591 in lowlands and highlands respectively. Malaria incidence declined consistently from 2008 onwards; and the highest incidence of malaria shifted from children aged <10 years to individuals aged 10-19 years from 2009. CONCLUSIONS: With basic training, supervision and RDTs, CORPs successfully provided early diagnosis and treatment and reduced consumption of anti-malarials. Progressively declining malaria incidence and slide positivity rates suggest that all fever cases should be tested with RDTs before treatment. Data collected by CORPs was used to plan phase 1b MSP3 malaria vaccine trial and will be used for monitoring and evaluation of different health interventions. The current situation indicates that there is a remarkable changing pattern of malaria and these areas might be moving from control to pre-elimination levels.     

How to (or Not to) Integrate Vertical Programmes for the Control of Major Neglected Tropical Diseases in Sub-Saharan Africa

Combining the delivery of multiple health interventions has the potential to minimize costs and expand intervention coverage. Integration of mass drug administration is therefore being encouraged for delivery of preventive chemotherapy (PCT) to control onchocerciasis, lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma in sub-Saharan Africa, as there is considerable geographical overlap of these neglected tropical diseases (NTDs). With only a handful of countries having embarked on integrated NTD control, experience on how to develop and implement an efficient integrated programme is limited. Historically, national and global programmes were focused on the control of only one disease, usually through a comprehensive approach that involved several interventions including PCT. Overcoming the resulting disease-specific structures and thinking, and ensuring that the integrated programme is embedded within the existing health structures, pose considerable challenges to policy makers and implementers wishing to embark on integrated NTD control. By sharing experiences from Uganda, Tanzania, Southern Sudan, and Mozambique, this symposium article aims to outlines key challenges and solutions to assist countries in establishing efficient integrated NTD programmes.     

Factors Influencing Drug Uptake during Mass Drug Administration for Control of Lymphatic Filariasis in Rural and Urban Tanzania

Background

In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania.

Methods

A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years) were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control.

Findings

The overall drug uptake rate was 55.1% (range of 44.5–75.6% between districts). There was no overall major difference between children (54.8%) and adults (55.2%) or between females (54.9%) and males (55.8%), but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2%) followed by clinical contraindications to treatment (10.8%), missing household visits of drug distributors (10.6%), and households not being informed about the distribution (9.0%).

Conclusion

Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent) are likely to have considerable potential for increasing drug uptake, in support of successful LF transmission elimination.     

Lymphatic Filariasis Control in Tanzania: Effect of Repeated Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission

Background

In most countries of sub-Saharan Africa the control of lymphatic filariasis (LF) is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. Here we present the first detailed study on the effect of 3 repeated MDAs with this drug combination, as implemented by the Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP).

Methodology/Principal Findings

Infection and transmission was monitored during a five-year period (one pre-intervention and four post-intervention years) in a highly endemic community (Kirare village) in north-eastern Tanzania. The vectors were Anopheles gambiae, An. funestus and Cx. quinquefasciatus. After start of intervention, human microfilaraemia initially decreased rapidly and statistically significant (prevalence by 21.2% and 40.4%, and mean intensity by 48.4% and 73.7%, compared to pre-treatment values after the first and second MDA, respectively), but thereafter the effect levelled off. The initial decrease in microfilaraemia led to significant decreases in vector infection and vector infectivity rates and thus to a considerable reduction in transmission (by 74.3% and 91.3% compared to pre-treatment level after first and second MDA, respectively). However, the decrease in infection and infectivity rates subsequently also levelled off, and low-level transmission was still noted after the third MDA. The MDAs had limited effect on circulating filarial antigens and antibody response to Bm14.

Conclusion/Significance

Critical issues that may potentially explain the observed waning effect of the MDAs in the later study period include the long intervals between MDAs and a lower than optimal treatment coverage. The findings highlight the importance of ongoing surveillance for monitoring the progress of LF control programmes, and it calls for more research into the long-term effect of repeated ivermectin/albendazole MDAs (including the significance of treatment intervals and compliance), in order to optimize efforts to control LF in sub-Saharan Africa.     

Diagnostic testing holds the key to NTD elimination

“Fit-for-purpose” diagnostic tests have emerged as a prerequisite to achieving global targets for the prevention, control, elimination, and eradication of neglected tropical diseases (NTDs), as highlighted by the World Health Organization’s (WHO) new roadmap. There is an urgent need for the development of new tools for those diseases for which no diagnostics currently exist and for improvement of existing diagnostics for the remaining diseases. Yet, efforts to achieve this, and other crosscutting ambitions, are fragmented, and the burden of these 20 debilitating diseases immense. Compounded by the Coronavirus Disease 2019 (COVID-19) pandemic, programmatic interruptions, systemic weaknesses, limited investment, and poor commercial viability undermine global efforts—with a lack of coordination between partners, leading to the duplication and potential waste of scant resources. Recognizing the pivotal role of diagnostic testing and the ambition of WHO, to move forward, we must create an ecosystem that prioritizes country-level action, collaboration, creativity, and commitment to new levels of visibility. Only then can we start to accelerate progress and make new gains that move the world closer to the end of NTDs.

Ahead of the second-ever World Neglected Tropical Disease (NTD) Day in January 2021, and amid the global Coronavirus Disease 2019 (COVID-19) crisis, the World Health Organization (WHO) launched a new roadmap for the prevention, control, elimination, and eradication of NTDs—a group of 20 diseases affecting more than one billion people worldwide [1]. Diagnostic testing is central to safeguarding decades of progress in NTDs and must be strategically leveraged to reach the goals laid out in the new NTD roadmap.Stepping back, we recognize the massive progress that has been made to combat NTDs. Today, 500 million fewer people need treatment for these debilitating diseases than in 2010, and 40 countries or areas have eliminated at least one of the 20 [1]. Yet, despite these gains, NTDs continue to impose a devastating human, social, and economic toll on the world’s poorest and most vulnerable communities [2–6]. COVID-19 is compounding the situation by wreaking havoc on health systems, which impacts progress on NTDs: this includes interruptions to mass treatment campaigns for diseases controlled through preventive chemotherapy (PCT) or individual case management interventions, as well as rerouting the already sparse available funding and resources [7].Diagnostic testing has been central to the COVID-19 response even with the introduction of vaccines. The rapid ramp up of research and development (R&D), the scaling up of low-cost and decentralized testing, and country-led approaches to tailored testing strategies for COVID-19, as well as lessons learned, can also provide new thinking around testing for NTDs. The new NTD roadmap offers a series of multisectoral actions and intensified, cross-cutting approaches to get us back on track—with diagnostics central to unlocking and accelerating this progress [1].However, the NTD roadmap shows that, of all 20 diseases or disease groups, just 2 (yaws and snakebite envenoming) are supported by adequate and accessible diagnostic tools. Six have no diagnostic tests available at all, with tools for each of the remaining conditions in urgent need of adaptation, modification, and/or improved accessibility (likely a more cost-effective option than the development of new diagnostics for these NTDs) [1]. This has to change. NTDs cannot continue to be neglected in favor of other competing priorities, or we risk losing the progress made to date.Until the COVID-19 pandemic thrust testing into the spotlight, diagnostics have been a “silent partner” in healthcare, receiving little by way of international attention and funding, specific country strategies, and dedicated budget lines. NTDs are no exception. Just 5% of the (limited) funding made available to NTDs has been invested in new diagnostics, compared with 44% and 39% on basic research and medicines and vaccines, respectively [1]. For most NTDs, diagnostics are a market failure situation, and as such, are not commercially viable enough to attract private investment. Consequently, very few diagnostic developers engage in this area—contrary, for example, to COVID-19, where developers are in the hundreds. Furthermore, as some diseases approach the last mile of elimination, falling infection rates precipitate the need for increasingly sensitive tests [1]. But progress in R&D is slow and fragmented, with a lack of engagement and coordination between governments, industry, donors, and development actors, leading to the duplication—and potential waste—of scant resources. While serial testing using multiple diagnostic tools or techniques can compensate for low sensitivity [8], such approaches are associated with increased costs of testing, sample collection, and transportation.Closing the diagnostic gap then, is a prerequisite to achieving the global ambition for NTDs, with the new NTD roadmap giving a blueprint for action. It is for this reason that we call on governments, industry, donors, and development actors to

• Prioritize country-level diagnostic action: As we enter a new era in NTD management and control, we need to shift from traditional, donor-led models to country-driven initiatives. Government ministries must engage with, and advocate on behalf of, their poorest and most vulnerable populations so that no one is left behind. Political frameworks should prioritize diagnostics for NTDs in line with local disease burdens, and as part of fully funded, national health action plans that include a commitment to seeing the process through. Capacity building for diagnostics is also essential at country, sub-regional, and regional levels, including the establishment of laboratory networks, so that testing can be implemented in field settings.
• Collaborate and create: There is never going to be a one-size-fits-all for NTD diagnostics. If targets are to be achieved, we need global frameworks that enable industry, manufacturers, and pharmaceutical companies to engage in the whole process, from R&D to supply chain logistics. Companies need to share knowledge, learnings, and innovation across multiple diseases. This will mean breaking silos and finding new ways to harness the power of existing products, technologies, and infrastructures. Further, it will mean creating economies of scale through regional manufacturing hubs and finding new, cross-cutting approaches to drive systemic change. To obtain the maximum access to technology and relevant intellectual property rights for NTD diagnostics, it is important to ensure that such rights are broadly available (non-exclusively) in NTD-endemic countries and are affordable (e.g., zero royalty rights).
• Commit to new levels of visibility: The resources needed to realize that this ambition is limited, with a lack of visibility around the diagnostic landscape undermining progress in NTD management and control. Creating an ecosystem with visibility, transparency, and integration at its core will help streamline programmatic action, reduce the risk of duplication, and leverage the full potential from this limited pool. To do this, industry, donors, and other development actors must provide the information needed to map both funding and product landscapes. Using this information to create a virtual product pipeline will bring an unprecedented level of transparency to diagnostic developments—harmonizing multisectoral efforts and creating a robust information platform from which new collaborations, synergies, and innovation can grow. Developing an online open-access diagnostic pipeline for WHO NTD roadmap priority pathogens would serve multiple purposes: (i) drive advocacy to address critical product and funding gaps; and (ii) reduce the likelihood of duplication of efforts. Together, this would strengthen partnerships across all stakeholders, from donors to industry partners, to accelerate development, evaluation, and adoption of diagnostic solutions for NTDs. The newly established NTD Diagnostic Technical Advisory Group (DTAG) to WHO NTD department has already identified the priority diagnostic needs for NTD programs not only in terms of developing new tools, but also the accessibility of existing tools [9]. Several sub-groups that focus more narrowly on single diseases or specific topics (i.e., skin NTDs or cross-cutting) have been established and have been tasked to develop tool and biomarker agnostic target product profiles (TPPs), which are now available (for the most part) on WHO website for use by any diagnostic manufacturer to support development of their specific technology. Alignment with these diagnostic priorities by all stakeholders is strongly recommended to facilitate attainment of WHO 2030 NTD roadmap goals.

• Establish NTD biobanks: Biobanks are required for the clinical evaluation and validation of new diagnostic tests. Establishing local biobanks would support a country-driven approach as well as allowing for head-to-head comparisons between tests and assessments of cross-reactivity across different NTDs.
• Invest in existing diagnostics: The development of new diagnostics is a complex process, and the time from development to implementation can be lengthy. Training laboratory staff in the use of existing diagnostics and the establishment of robust quality control systems are effective approaches to achieving shorter-term improvements.

There is a long road ahead, but the past 10 years have shown us what can be achieved when governments, industry, donors, and development actors are bound by a shared, global goal. As we look forward to the next decade, we must prioritize country-level action, collaboration, creativity, and commitment to new levels of visibility, if we are to finally end the neglect of NTDs.     

Prevalence of Lymphatic Filariasis and Treatment Effectiveness of Albendazole/ Ivermectin in Individuals with HIV Co-infection in Southwest-Tanzania

BackgroundAnnual mass treatment with ivermectin and albendazole is used to treat lymphatic filariasis in many African countries, including Tanzania. In areas where both diseases occur, it is unclear whether HIV co-infection reduces treatment success.MethodologyIn a general population study in Southwest Tanzania, individuals were tested for HIV and circulating filarial antigen, an indicator of Wuchereria bancrofti adult worm burden, before the first and after 2 consecutive rounds of anti-filarial mass drug administration.Conclusion/SignificanceIn an area with a high prevalence for both diseases, no difference was found between HIV-infected and uninfected individuals regarding the initial prevalence of lymphatic filariasis. A moderate but significant reduction in lymphatic filariasis prevalence and worm burden was demonstrated after two rounds of treatment with albendazole and ivermectin. Treatment effects were more pronounced in the HIV co-infected subgroup, indicating that the effectiveness of antifilarial treatment was not reduced by concomitant HIV-infection. Studies with longer follow-up time could validate the observed differences in treatment effectiveness.     

Eliminating the Neglected Tropical Diseases: Translational Science and New Technologies

Today, the World Health Organization recognizes 17 major parasitic and related infections as the neglected tropical diseases (NTDs). Despite recent gains in the understanding of the nature and prevalence of NTDs, as well as successes in recent scaled-up preventive chemotherapy strategies and other health interventions, the NTDs continue to rank among the world’s greatest global health problems. For virtually all of the NTDs (including those slated for elimination under the auspices of a 2012 London Declaration for NTDs and a 2013 World Health Assembly resolution [WHA 66.12]), additional control mechanisms and tools are needed, including new NTD drugs, vaccines, diagnostics, and vector control agents and strategies. Elimination will not be possible without these new tools. Here we summarize some of the key challenges in translational science to develop and introduce these new technologies in order to ensure success in global NTD elimination efforts.