Diagnostics to support elimination of lymphatic filariasis—Development of two target product profiles

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools.

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African regional progress and status of the programme to eliminate lymphatic filariasis: 2000–2020

International Health ◽

10.1093/inthealth/ihaa058 ◽

2020 ◽

Vol 13 (Supplement_1) ◽

pp. S22-S27

Author(s):

Kebede Deribe ◽

Didier K Bakajika ◽

Honorat Marie-Gustave Zoure ◽

John O Gyapong ◽

David H Molyneux ◽

...

Keyword(s):

Vector Control ◽

Lymphatic Filariasis ◽

Neglected Tropical Diseases ◽

Public Health Problem ◽

World Health ◽

Malaria Vector Control ◽

Tropical Diseases ◽

Significant Progress ◽

African Region ◽

Preventive Chemotherapy

Abstract To eliminate lymphatic filariasis (LF) by 2020, the World Health Organization (WHO) has launched a campaign against the disease. Since the launch in 2000, significant progress has been made to achieve this ambitious goal. In this article we review the progress and status of the LF programme in Africa through the WHO neglected tropical diseases preventive chemotherapy databank, the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN) portal and other publications. In the African Region there are 35 countries endemic for LF. The Gambia was reclassified as not requiring preventive chemotherapy in 2015, while Togo and Malawi eliminated LF as a public health problem in 2017 and 2020, respectively. Cameroon discontinued mass drug administration (MDA) and transitioned to post-MDA surveillance to validate elimination. The trajectory of coverage continues to accelerate; treatment coverage increased from 0.1% in 2000 to 62.1% in 2018. Geographical coverage has also significantly increased, from 62.7% in 2015 to 78.5% in 2018. In 2019, 23 of 31 countries requiring MDA achieved 100% geographic coverage. Although much remains to be done, morbidity management and disability prevention services have steadily increased in recent years. Vector control interventions conducted by other programmes, particularly malaria vector control, have had a profound effect in stopping transmission in some endemic countries in the region. In conclusion, significant progress has been made in the LF programme in the region while we identify the key remaining challenges in achieving an Africa free of LF.

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The roadmap towards elimination of lymphatic filariasis by 2030: insights from quantitative and mathematical modelling

Gates Open Research ◽

10.12688/gatesopenres.13065.1 ◽

2019 ◽

Vol 3 ◽

pp. 1538 ◽

Cited By ~ 1

Author(s):

Keyword(s):

Public Health ◽

Lymphatic Filariasis ◽

Health Problem ◽

Neglected Tropical Diseases ◽

Public Health Problem ◽

World Health ◽

Basic Care ◽

The World ◽

Health Organization ◽

Initial Target

The Global Programme to Eliminate Lymphatic Filariasis was launched in 2000 to eliminate lymphatic filariasis (LF) as a public health problem by 1) interrupting transmission through mass drug administration (MDA) and 2) offering basic care to those suffering from lymphoedema or hydrocele due to the infection. Although impressive progress has been made, the initial target year of 2020 will not be met everywhere. The World Health Organization recently proposed 2030 as the new target year for elimination of lymphatic filariasis (LF) as a public health problem. In this letter, LF modelers of the Neglected Tropical Diseases (NTDs) Modelling Consortium reflect on the proposed targets for 2030 from a quantitative perspective. While elimination as a public health problem seems technically and operationally feasible, it is uncertain whether this will eventually also lead to complete elimination of transmission. The risk of resurgence needs to be mitigated by strong surveillance after stopping interventions and sometimes perhaps additional interventions.

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Novel tools and strategies for breaking schistosomiasis transmission: study protocol for an intervention study

BMC Infectious Diseases ◽

10.1186/s12879-021-06620-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lydia Trippler ◽

Jan Hattendorf ◽

Said Mohammed Ali ◽

Shaali Makame Ame ◽

Saleh Juma ◽

...

Keyword(s):

Primary Schools ◽

Intervention Study ◽

Neglected Tropical Diseases ◽

Public Health Problem ◽

World Health ◽

Diagnostic Tools ◽

Urogenital Schistosomiasis ◽

Cross Sectional ◽

Adaptive Intervention ◽

Snail Control

Abstract Background Global elimination of schistosomiasis as a public health problem is set as target in the new World Health Organization’s Neglected Tropical Diseases Roadmap for 2030. Due to a long history of interventions, the Zanzibar islands of Tanzania have reached this goal since 2017. However, challenges occur on the last mile towards interruption of transmission. Our study will investigate new tools and strategies for breaking schistosomiasis transmission. Methods The study is designed as an intervention study, documented through repeated cross-sectional surveys (2020–2024). The primary endpoint will be the sensitivity of a surveillance-response approach to detect and react to outbreaks of urogenital schistosomiasis over three years of implementation. The surveys and multi-disciplinary interventions will be implemented in 20 communities in the north of Pemba island. In low-prevalence areas, surveillance-response will consist of active, passive and reactive case detection, treatment of positive individuals, and focal snail control. In hotspot areas, mass drug administration, snail control and behaviour change interventions will be implemented. Parasitological cross-sectional surveys in 20 communities and their main primary schools will serve to adapt the intervention approach annually and to monitor the performance of the surveillance-response approach and impact of interventions. Schistosoma haematobium infections will be diagnosed using reagent strips and urine filtration microscopy, and by exploring novel point-of-care diagnostic tests. Discussion Our study will shed light on the field applicability and performance of novel adaptive intervention strategies, and standard and new diagnostic tools for schistosomiasis elimination. The evidence and experiences generated by micro-mapping of S. haematobium infections at community level, micro-targeting of new adaptive intervention approaches, and application of novel diagnostic tools can guide future strategic plans for schistosomiasis elimination in Zanzibar and inform other countries aiming for interruption of transmission. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493

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LAMP in Neglected Tropical Diseases: A Focus on Parasites

Diagnostics ◽

10.3390/diagnostics11030521 ◽

2021 ◽

Vol 11 (3) ◽

pp. 521

Author(s):

Juan García-Bernalt Diego ◽

Pedro Fernández-Soto ◽

Antonio Muro

Keyword(s):

Neglected Tropical Diseases ◽

Treatment Success ◽

Public Health Problem ◽

Nucleic Acid Amplification ◽

Molecular Diagnostic ◽

Diagnostic Tools ◽

World Population ◽

Major Public Health Problem ◽

Tropical Diseases ◽

Early 21St Century

Neglected Tropical Diseases (NTDs), particularly those caused by parasites, remain a major Public Health problem in tropical and subtropical regions, with 10% of the world population being infected. Their management and control have been traditionally hampered, among other factors, by the difficulty to deploy rapid, specific, and affordable diagnostic tools in low resource settings. This is especially true for complex PCR-based methods. Isothermal nucleic acid amplification techniques, particularly loop-mediated isothermal amplification (LAMP), appeared in the early 21st century as an alternative to PCR, allowing for a much more affordable molecular diagnostic. Here, we present the status of LAMP assays development in parasite-caused NTDs. We address the progress made in different research applications of the technique: xenomonitoring, epidemiological studies, work in animal models and clinical application both for diagnosis and evaluation of treatment success. Finally, we try to shed a light on the improvements needed to achieve a true point-of-care test and the future perspectives in this field.

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The contribution of mass drug administration to global health: past, present and future

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0434 ◽

2014 ◽

Vol 369 (1645) ◽

pp. 20130434 ◽

Cited By ~ 114

Author(s):

Joanne P. Webster ◽

David H. Molyneux ◽

Peter J. Hotez ◽

Alan Fenwick

Keyword(s):

Global Health ◽

Drug Administration ◽

Mass Drug Administration ◽

Neglected Tropical Diseases ◽

World Health Organisation ◽

Essential Medicines ◽

World Health ◽

Diagnostic Tools ◽

Preventive Chemotherapy ◽

High Coverage

Mass drug administration (MDA) is a means of delivering safe and inexpensive essential medicines based on the principles of preventive chemotherapy, where populations or sub-populations are offered treatment without individual diagnosis. High-coverage MDA in endemic areas aims to prevent and alleviate symptoms and morbidity on the one hand and can reduce transmission on the other, together improving global health. MDA is the recommended strategy of the World Health Organisation to control or eliminate several neglected tropical diseases (NTDs). More than 700 million people now receive these essential NTD medicines annually. The combined cost of integrated NTD MDA has been calculated to be in the order of $0.50 per person per year. Activities have recently been expanded due, in part, to the proposed attempt to eliminate certain NTDs in the coming two decades. More than 1.9 billion people need to receive MDA annually across several years if these targets are to be met. Such extensive coverage will require additional avenues of financial support, expanded monitoring and evaluation focusing on impact and drug efficacy, as well as new diagnostic tools and social science strategies to encourage adherence. MDA is a means to help reduce the burden of disease, and hence poverty, among the poorest sector of populations. It has already made significant improvements to global health and productivity and has the potential for further successes, particularly where incorporated into sanitation and education programmes. However logistical, financial and biological challenges remain.

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A systematic literature review of schistosomiasis in urban and peri-urban settings

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0008995 ◽

2021 ◽

Vol 15 (2) ◽

pp. e0008995

Author(s):

Katharina Klohe ◽

Benjamin G. Koudou ◽

Alan Fenwick ◽

Fiona Fleming ◽

Amadou Garba ◽

...

Keyword(s):

Literature Review ◽

Systematic Literature Review ◽

Urban Areas ◽

Neglected Tropical Diseases ◽

Public Health Problem ◽

World Health ◽

World Population ◽

Rapid Urbanization ◽

Urban Settings ◽

The World

Background Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and belongs to the neglected tropical diseases. The disease has been reported in 78 countries, with around 290.8 million people in need of treatment in 2018. Schistosomiasis is predominantly considered a rural disease with a subsequent focus of research and control activities in rural settings. Over the past decades, occurrence and even expansion of schistosomiasis foci in peri-urban and urban settings have increasingly been observed. Rural–urban migration in low- and middle-income countries and subsequent rapid and unplanned urbanization are thought to explain these observations. Fifty-five percent (55%) of the world population is already estimated to live in urban areas, with a projected increase to 68% by 2050. In light of rapid urbanization and the efforts to control morbidity and ultimately achieve elimination of schistosomiasis, it is important to deepen our understanding of the occurrence, prevalence, and transmission of schistosomiasis in urban and peri-urban settings. A systematic literature review looking at urban and peri-urban schistosomiasis was therefore carried out as a first step to address the research and mapping gap. Methodology Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic computer-aided literature review was carried out using PubMed, ScienceDirect, and the World Health Organization Database in November 2019, which was updated in March 2020. Only papers for which at least the abstract was available in English were used. Relevant publications were screened, duplicates were removed, guidelines for eligibility were applied, and eligible studies were reviewed. Studies looking at human Schistosoma infections, prevalence, and intensity of infection in urban and peri-urban settings were included as well as those focusing on the intermediate host snails. Principal findings A total of 248 publications met the inclusion criteria. The selected studies confirm that schistosomiasis is prevalent in peri-urban and urban areas in the countries assessed. Earlier studies report higher prevalence levels in urban settings compared to data extracted from more recent publications, yet the challenge of migration, rapid uncontrolled urbanization, and resulting poor living conditions highlight the potential for continuous or even newly established transmission to take place. Conclusions The review indicates that schistosomiasis has long existed in urban and peri-urban areas and remains a public health problem. There is, however, a challenge of comparability of settings due to the lack of a clear definition of what constitutes urban and peri-urban. There is a pressing need for improved monitoring of schistosomiasis in urban communities and consideration of treatment strategies.

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Improving data use for decision making by neglected tropical disease program teams: eight use cases

Gates Open Research ◽

10.12688/gatesopenres.13407.1 ◽

2021 ◽

Vol 5 ◽

pp. 153

Author(s):

Liz Grubin ◽

Lakshmi Balachandran ◽

Sarah Bartlett ◽

Nana-Kwadwo Biritwum ◽

Simon Brooker ◽

...

Keyword(s):

Decision Making ◽

Neglected Tropical Diseases ◽

National Level ◽

Data Use ◽

Routine Data ◽

Population Data ◽

Use Cases ◽

Use Case ◽

Global Trends ◽

National Programs

Background: The achievement of neglected tropical diseases (NTDs) program goals depends on numerous factors, including the ability of national programs to use high-quality, timely data to inform their decision-making and program delivery. This paper presents a use case analysis of the routine data used by national NTD programs targeting lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma. Methods: The use cases were developed through a combination of secondary and primary research focused on both global trends and deep dives into Burkina Faso, Ethiopia, and Tanzania. Results were refined through a stakeholder convening and the final eight use cases were determined through iteration and prioritization with stakeholders. Results: Eight use cases were developed: improve treatment register data quality, strengthen supervision of drug distributors during mass drug administration (MDA), generate accurate community-level population data for MDAs, create and manage an accurate inventory of drugs, meet district coverage targets during MDA campaigns, feedback and performance to sub-district teams, feedback on performance to sub-national teams, and national-level program use of data for evaluation and decision making. Each use case identifies key actors and their data-related needs and critical challenges, defines the current and desired state, and articulates the profile of a solution (digital and non-digital) needed to complete the use case. Conclusion: The systematic strengthening of data use for decision-making in NTD programs is key for reaching the 2030 Roadmap goals. Integrated together, the presented use cases, when translated into action using appropriate and innovative solutions, can help to ensure that accurate and timely data are present at every step of a program and empower countries to use these data to make program decisions.

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Comparative protein composition and biological effects caused by Bothrops jararacussu and B. moojeni crude venoms.

Venoms and Toxins ◽

10.2174/2666121701999200618102634 ◽

2020 ◽

Vol 01 ◽

Author(s):

Otacílio B. Paixão-Júnior ◽

Diana P. Silva ◽

Sarah S. Ferreira ◽

Ayrton R. Barbosa ◽

Pedro G. N. dos Santos ◽

...

Keyword(s):

Erythrocyte Membrane ◽

Rural Areas ◽

Neglected Tropical Diseases ◽

Biological Effects ◽

Public Health Problem ◽

World Health ◽

Protein Profiles ◽

Important Public Health Problem ◽

Priority List ◽

Bothrops Jararacussu

: The World Health Organization added snakebite envenoming to its priority list of neglected tropical diseases. Snakebite envenoming is a particularly important public health problem in rural areas of tropical and sub-tropical countries. In 2017, more than 30 thousand cases of snakebites were reported in Brazil, with the North and Northeast regions being the most affected and Bothrops sp snakes causing most of these cases. The objective of this study was to evaluate, in vitro, the coagulating, cytotoxic, oxidizing and antioxidant effects caused by the Bothrops jararacussu and B. moojeni crude venoms. The crude venoms protein profiles were characterized, and the biological effects were evaluated and compared between the species. The crude venoms composition showed similar protein profiles. The B. jararacussu and B. moojeni crude venoms showed coagulant activity and were capable of causing indirect hemolysis on the erythrocyte membrane, but did not protect the erythrocyte membrane from damage against hypotonic solutions. The B. jararacussu crude venom promoted hemagglutination. The crude venoms were not able to promote an oxidizing effect on hemoglobin and could not prevent the phenylhydrazine oxidizing effect; however, the crude venoms presence caused increase in the methemoglobin formation by phenylhydrazine oxidation.

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Diagnosis of Lymphatic Filariasis Using Immunochromatography and Microscopy in Three Local Government Areas of Cross River State, Nigeria

Nigerian Journal of Parasitology ◽

10.4314/njpar.v41i2.8 ◽

2020 ◽

Vol 41 (2) ◽

Author(s):

M Maurice ◽

E.U Sode ◽

I.B Otu-Bassey

Keyword(s):

Local Government ◽

Lymphatic Filariasis ◽

Neglected Tropical Diseases ◽

Age Groups ◽

Public Health Problem ◽

Diagnostic Methods ◽

Blood Samples ◽

Cross River ◽

Cross River State ◽

Significant Difference

Human Lymphatic filariasis (LF) caused by three types of filarial worms; Wuchereria bancrofti, Brugia malayi and Brugiatimori is one of the neglected tropical diseases and spread by bites of infected Anopheles, Culex, Aedes, Ochleratus andMansoni mosquitoes. The study evaluated diagnostic methods using blood samples from 420 consented participants in threeLocal Government Areas of Cross River State. Blood samples were examined following one hour of administration ofDiethylcarbamazine citrate for LF microfilaria microscopy (Knott’s concentration) and for LF antigen usingimmunochromatographic (ICT) method (Alere filariasis test strip). Of the 420 samples examined, 1.7% was found to bepositive using microscopy while 4.8% were positive using ICT. There was no significant difference in the diagnosis oflymphatic filariasis using microscopy and ICT among participants in the local government areas (χ2= 21.84, p>0.05). Of the214 males and 206 females examined, 4.2% males and 5.3% females tested positive using ICT while 1.4% males and 1.9%females were found positive using microscopy. The difference in the infection between gender was statistically significant(χ2=0.298, p<0.05). Participants aged 21-24 years had the highest prevalence of 19.4% while the least prevalence of 1.5%was observed among age group 9-12years using ICT. Also, no significant difference was observed in the diagnosis of LFamong the age groups (χ2= 19.88, p>0.05). The study showed that LF still remains a public health problem in Cross RiverState. Mass drug administration should be scaled up in the state so as to reduce and finally eradicate the disease. Keywords: Diagnosis, Lymphatic filariasis, Immunochromatography, Microscopy

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Drug Resistance in Visceral Leishmaniasis

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/617521 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 97

Author(s):

Helena C. Maltezou

Keyword(s):

Visceral Leishmaniasis ◽

Neglected Tropical Diseases ◽

Public Health Problem ◽

New Drugs ◽

World Health ◽

Oral Agent ◽

Molecular Surveillance ◽

Health Organization ◽

Combination Regimens ◽

Emergence Of Resistance

Visceral leishmaniasis remains a public health problem worldwide. This illness was included by the World Health Organization in the list of neglected tropical diseases targeted for elimination by 2015. The widespread emergence of resistance to pentavalent antimonials in India where half cases occur globally and the unavailability of a vaccine in clinical use constitute major obstacles in achieving this goal. The last decade new antileishmanials became available, including the oral agent miltefosine. However, in poor endemic countries their wide use was curtailed because of the high costs, and also due to concerns of toxicity and emergence of resistance. Various mechanisms of antileishmanial resistance were identified recently in field isolates. Their elucidation will boost the design of new drugs and the molecular surveillance of resistance. Combination regimens should be evaluated in large trials. Overall, the development of antileishmanials has been generally slow; new drugs are needed. In order to control visceral leishmaniasis worldwide, treatment advances should become affordable in the poorest countries, where they are needed most.

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