Lessons from integrating mental health as part of lymphatic filariasis morbidity management and disability prevention services in Jigawa State, Nigeria.

Lymphatic filariasis (LF) is a neglected tropical disease affecting >120 million people worldwide. LF has debilitating effects on humans and leads to morbidity and sometimes irreversible disability. A significant proportion of persons affected by LF morbidity also suffer from ill health, such as depression, anxiety, pain, stigma and social isolation due to disfigurement, as well as loss of mobility, livelihood and income. Mental health is often overlooked as a component of morbidity management and disability prevention (MMDP) services, despite the high prevalence of depression and anxiety among people affected by LF. To address this gap, Christian Blind Mission (CBM) piloted a comprehensive approach providing morbidity management and disability prevention by integrating mental health as part of the MMDP care package. The participatory evaluation of the project reviewed the project documents and a review meeting, small group discussions and in-depth interviews with project stakeholders. Findings suggest that project training and service delivery targets were exceeded in most cases. In addition, the disability and gender disaggregated data highlights the interplay of gender and disability in accessing care and the existence of unmet mental health needs. The financial cost of transportation to utilise referrals or access other MMDP services, such as replenishing treatment supplies, was a major constraint in accessing services for LF morbidity patients and low levels of awareness, fear of hydrocoele surgery and social stigmatisation were reported. The project outcomes demonstrate the feasibility and effectiveness of integrating mental health as part of a comprehensive MMDP package of care. Integration strategies should target training of MMDP providers in basic mental health skills, screening for mental health issues and the provision of mental health services and other MMDP services within the same facilities. Integration is an important step towards comprehensive care for people affected by LF and other NTD morbidities and disabilities.

Elimination of lymphatic filariasis as a public health problem in Malawi.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO. METHODOLOGY/PRINCIPAL FINDINGS: The Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1-2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools. CONCLUSIONS: Malawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success. SUMMARY: Lymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease.

The development and roll-out of a new hydrocoele surgery facility assessment tool for the elimination of lymphatic filariasis.

A hydrocoele surgery facility assessment tool (HSFAT) was developed to assess the readiness of hydrocoele surgery services in health facilities prior to implementation of hydrocoele surgical campaigns for the elimination of lymphatic filariasis (LF). A first version of the tool was piloted in Bangladesh, Malawi and Nepal in 2019, then, following feedback from country programme managers, a second version of the tool was rolled out across countries implementing hydrocoele surgery in the Accelerating the Control of Neglected Tropical Diseases (Ascend) West and Central Africa Programme, including Benin, Burkina Faso, Ghana, Guinea, Niger and Nigeria. The HSFAT assessed facilities across 10 domains: background information, essential amenities, emergency patient transfer, laboratory capacity, surgical procedures and trained staff, infection prevention, non-disposable basic equipment, disposable basic equipment, essential medicines and current hydrocoele practices. The HSFAT results highlight key areas for improvement in different countries and can be used to develop a quality improvement plan, which may include actions with agreed deadlines to improve the readiness and quality of hydrocoele surgery services provided by the health facility, prior to implementation of surgical campaigns and assist country programmes to achieve the dossier requirements set out by the World Health Organization for the elimination of LF.

Unlocking Trust in Community Health Systems: Lessons From the Lymphatic Filariasis Morbidity Management and Disability Prevention Pilot Project in Luangwa District, Zambia.

BACKGROUND: Surgery for hydrocele is commonly promoted as part of morbidity management and disability prevention (MMDP) services for lymphatic filariasis (LF). However, uptake of these surgeries has been suboptimal owing to several community level barriers that have triggered mistrust in such services. This study aimed at documenting mechanisms of unlocking trust in community health systems (CHSs) in the context of a LF hydrocele management project that was implemented in Luangwa District, Zambia. METHODS: Qualitative data was collected through in-depth interviews (IDIs) and focus group discussions (FGDs) (n=45) in February 2020 in Luangwa District. Thirty-one IDIs were conducted with hydrocele patients, community health workers (CHWs), health workers, traditional leaders and traditional healers. Two FGDs were also conducted with CHWs who had been involved in project implementation with seven participants per group. Data was analyzed using a thematic analysis approach. RESULTS: The use of locally appropriate communication strategies, development of community driven referral systems, working with credible community intermediaries as well as strengthening health systems capacity through providing technical and logistical support enhanced trust in surgery for hydrocele and uptake of the surgeries. CONCLUSION: Implementation of community led communication and referral systems as well as strengthening health services are vital in unlocking trust in health systems as such mechanisms trigger authentic partnerships, including mutual respect and recognition in the CHS. The mechanisms also enhance confidence in health services among community members.

The story of Lymphatic Filariasis elimination as a public health problem from Yemen.

In 2000, Yemen joined the WHO global efforts to eliminate lymphatic filariasis (LF) as a public health problem by initiating a National LF Elimination Programme (NLFEP), that was fully integrated with the National Leprosy Elimination Programme (NLEP), the Ministry of Public Health and Population. This article reviews the NLFEP extensive efforts and interventions to eliminate LF in Yemen. LF mapping was started in 2000, followed by five annual rounds of mass drug administration (MDA) with ivermectin and albendazole in 8 implementation units (IUs) during 2002-2006. The epidemiological coverage for all MDA rounds was ≥80%. Based on WHO guidelines of 2005, MDA was stopped in 7 IUs, additional MDA rounds were continued in one IU until 2011. Microfilaremia monitoring and evaluation, and MDA stopping surveys were conducted based on WHO guidelines of 2005 and 2011. Information about the presence of patients suffering from lymphoedema/elephantiasis and hydrocele was collected, and basic care provided to all chronic cases by NLEP coordinators, trained on LF morbidity management and disability prevention (MMDP). As of 2017, a total of 610 lymphoedema patients were trained on self-management, and 31 hydrocele patients were referred to local General Hospitals for surgery. The NLFEP made excellent progress due to integration with NLEP, strong collaboration with national and international bodies, intensive training and supervision, and the use of robust advocacy for mobilization of endemic communities. Transmission assessment surveys (TAS), conducted in 2013 and 2016, indicated 0% antigenemia levels in schoolchildren in the 8 IUs. Thus, after almost two decades of sustained effort, Yemen met the WHO criteria for successful elimination of LF as a public health problem. In 2019, WHO validated Yemen as the second country in the WHO' Eastern Mediterranean Region to successfully eliminate LF as a public health problem.

Are census data accurate for estimating coverage of a lymphatic filariasis MDA campaign? Results of a survey in Sierra Leone.

BACKGROUND: Preventive chemotherapy was administered to 3.2 million Sierra Leoneans in 13 health districts for lymphatic filariasis, onchocerciasis, and soil transmitted helminthes from October 2008 to February 2009. This paper aims to report the findings of a coverage survey conducted in 2009, compare the coverage survey findings with two reported rates for lymphatic filariasis coverage obtained using pre-mass drug administration (MDA) registration and national census projections, and use the comparison to understand the best source of population estimates in calculating coverage for NTD programming in Sierra Leone. METHODOLOGY/PRINCIPAL FINDINGS: Community drug distributors (CDDs) conducted a pre- MDA registration of the population. Two coverage rates for MDA for lymphatic filariasis were subsequently calculated using the reported number treated divided by the total population from: 1) the pre-MDA register and 2) national census projections. A survey was conducted to validate reported coverage data. 11,602 persons participated (response rate of 76.8%). Overall, reported coverage data aggregated to the national level were not significantly different from surveyed coverage (z-test >0.05). However, estimates based on pre-MDA registration have higher agreement with surveyed coverage (mean Kendall's W = 0.68) than coverage calculated with census data (mean Kendall's = 0.59), especially in districts with known large-scale migration, except in a highly urban district where it was more challenging to conduct a pre-MDA registration appropriately. There was no significant difference between coverage among males versus females when the analyses were performed excluding those women who were pregnant at the time of MDA. The surveyed coverage estimate was near or below the minimum 65% epidemiological coverage target for lymphatic filariasis MDA in all districts. CONCLUSION/SIGNIFICANCE: These results from Sierra Leone illustrate the importance of choosing the right denominator for calculating treatment coverage for NTD programs. While routinely reported coverage results using national census data are often good enough for programmatic decision making, census projections can quickly become outdated where there is substantial migration, e.g. due to the impact of civil war, with changing economic opportunities, in urban settings, and where there are large migratory populations. In districts where this is known to be the case, well implemented pre-MDA registration can provide better population estimates. Pre-MDA registration should, however, be implemented correctly to reduce the risk of missing pockets of the population, especially in urban settings.

Elimination of lymphatic filariasis as a public health problem from the Arab Republic of Egypt.

Lymphatic filariasis (LF) has been known in Egypt since ancient times. By 1930s it was recognized to be a major public health problem in the Nile Delta, and to be caused by Wuchereria bancrofti and transmitted by Culex pipiens. Remarkably, as a result of widespread DEC treatment and intensive vector control by the Ministry of Health and Population (MoHP), the infection rate of LF declined in the 1960s. However, relaxation of these efforts resulted in resurgence of filariasis in the 1980s and 1990s. In 2000, Egypt was among the first countries to join the WHO global efforts to eliminate LF as a public health problem by initiating a national LF elimination programme (NLFEP). This article reviews the history of LF control activities and summarizes the NLFEP extensive interventions to eliminate LF in Egypt. Based on MoHP data, mass drug administration (MDA) with DEC and ALB was started in 2000 in 161 implementation units (IUs). Additional IUs were included in subsequent MDA rounds, with the last IU included in 2007. MDA stopping surveys were conducted based on WHO guidelines (2005; 2011). Information about the presence of those suffering from lymphoedema/elephantiasis and hydrocele patients was collected, and care provided to those needing care in five rural health units (RHU) by primary health care system providers who were given training on LF morbidity management and disability prevention (MMDP). The NLFEP made excellent progress due to strong collaboration between different ministries, through intensive training and supervision, and the use of advocacy for mobilization of endemic communities. The epidemiological coverage for all MDA rounds was effectively ≥80%. Antigenemia levels found in schoolchildren during transmission assessment surveys (TAS) in 166 IUs approximately 10 years after stopping MDA was 0%. In 2017, TAS conducted in additional 29 IUs indicated 0.1% antigenemia and 0% microfilaremia. In 2015, the registration of chronic LF patients was updated to 1472 lymphoedema and 18 hydrocele patients. Lymphoedema patients were trained on self-management, and hydrocele patients were referred to local General Hospitals for surgery. Thus, after over a decade of sustained effort, Egypt met the WHO criteria for successful elimination of LF as a public health problem. In December 2017, WHO validated Egypt as the first country in the Eastern Mediterranean Region to successfully achieve elimination.

Crystal structure of Brugia malayi venom allergen-like protein-1 (BmVAL-1), a vaccine candidate for lymphatic filariasis.

Brugia malayi is a causative agent of lymphatic filariasis, a major tropical disease. The infective L3 parasite stage releases immunomodulatory proteins including the venom allergen-like proteins (VALs), which are members of the SCP/TAPS (Sperm-coating protein/Tpx/antigen 5/pathogenesis related-1/Sc7) superfamily. BmVAL-1 is a major target of host immunity with >90% of infected B. malayi microfilaraemic cases being seropositive for antibodies to BmVAL-1. This study is part of ongoing efforts to characterize the structures and functions of important B. malayi proteins. Recombinant BmVAL-1 was produced using a plant expression system, crystallized and the structure was solved by molecular replacement and refined to 2.1 Å, revealing the characteristic alpha/beta/alpha sandwich topology of eukaryotic SCP/TAPS proteins. The protein has more than 45% loop regions and these flexible loops connect the helices and strands, which are longer than predicted based on other parasite SCP/TAPS protein structures. The large central cavity of BmVAL-1 is a prototypical CRISP cavity with two histidines required to bind divalent cations. The caveolin-binding motif (CBM) that mediates sterol binding in SCP/TAPS proteins is large and open in BmVAL-1 and is N-glycosylated. N-glycosylation of the CBM does not affect the ability of BmVAL-1 to bind sterol in vitro. BmVAL-1 complements the in vivo sterol export phenotype of yeast mutants lacking their endogenous SCP/TAPS proteins. The in vitro sterol-binding affinity of BmVAL-1 is comparable with Pry1, a yeast sterol transporting SCP/TAPS protein. Sterol binding of BmVAL-1 is dependent on divalent cations. BmVAL-1 also has a large open palmitate-binding cavity, which binds palmitate comparably to tablysin-15, a lipid-binding SCP/TAPS protein. The central cavity, CBM and palmitate-binding cavity of BmVAL-1 are interconnected within the monomer with channels that can serve as pathways for water molecules, cations and small molecules.

How elimination of lymphatic filariasis as a public health problem in the Kingdom of Cambodia was achieved.

BACKGROUND: Endemicity of lymphatic filariasis (LF) in Cambodia was proven in 1956 when microfilariae were detected in mosquitos in the Kratié province. In 2001, an extensive study confirmed the presence of both Brugia malayi and Wuchereria bancrofti microfilariae. In 2003, the Ministry of Health established a national task force to develop policies and strategies for controlling and eliminating neglected tropical diseases (NTDs), with the goal of eliminating LF by 2015. This article summarizes the work accomplished to eliminate LF as a public health problem in Cambodia. METHODS: The National Program to Eliminate Lymphatic Filariasis made excellent progress in the goal towards elimination due to strong collaboration between ministries, intensive supervision by national staff, and advocacy for mobilization of internal and external resources. Mass drug administration (MDA) with diethylcarbamazine citrate and albendazole was conducted in six implementation units, achieving > 70% epidemiological coverage for five consecutive rounds, from 2005 to 2009. In 2006, in 14 provinces, healthcare workers developed a line list of lymphedema and hydrocele patients, many of whom were > 40 years old and had been affected by LF for many years. The national program also trained healthcare workers and provincial and district staff in morbidity management and disability prevention, and designated health centers to provide care for lymphedema and acute attack. Two reference hospitals were designated to administer hydrocele surgery. RESULTS: Effectiveness of MDA was proven with transmission assessment surveys. These found that less than 1% of school children had antigenemia in 2010, which fell to 0% in both 2013 and 2015. A separate survey in one province in 2015 using Brugia Rapid tests to test for LF antibody found one child positive among 1677 children. The list of chronic LF patients was most recently updated and confirmed in 2011-2012, with 32 lymphoedema patients and 17 hydrocele patients listed. All lymphedema patients had been trained on self-management and all hydrocele patients had been offered free surgery. CONCLUSIONS: Due to the success of the MDA and the development of health center capacity for patient care, along with benefits gained from socioeconomic improvements and other interventions against vector-borne diseases and NTDs, Cambodia was validated by the World Health Organization as achieving LF elimination as a public health problem in 2016.

The National Programme to Eliminate Lymphatic Filariasis from Ethiopia.

Lymphatic filariasis (LF) is one of the most debilitating and disfiguring diseases common in Ethiopia and is caused by Wuchereria bancrofti. Mapping for LF has shown that 70 woredas (districts) are endemic and 5.9 million people are estimated to be at risk. The national government's LF elimination programme commenced in 2009 in 5 districts integrated with the onchocerciasis programme. The programme developed gradually and has shown significant progress over the past 6 years, reaching 100% geographical coverage for mass drug administration (MDA) by 2016. To comply with the global LF elimination goals an integrated morbidity management and disability prevention (MMDP) guideline and a burden assessment programme has also been developed; MMDP protocols and a hydrocoele surgical handbook produced for country-wide use. In Ethiopia, almost all LF endemic districts are co-endemic with malaria and vector control aspects of the activities are conducted in the context of malaria programme as the vectors for both diseases are mosquitoes. In order to monitor the elimination, 11 sentinel and spot-check sites have been established and baseline information has been collected. Although significant achievements have been achieved in the scale up of the LF elimination programme, there is still a need to strengthen operational research to generate programme-relevant evidence, to increase access to morbidity management services, and to improve monitoring and evaluation of the LF programme. However, the current status of implementation of the LF national programme indicates that Ethiopia is poised to achieve the 2020 goal of elimination of LF. Nevertheless, to achieve this goal, high and sustained treatment coverage and strong monitoring and evaluation of the programme are essential.

Investment Success in Public Health: An Analysis of the Cost-Effectiveness and Cost-Benefit of the Global Programme to Eliminate Lymphatic Filariasis.

Background: It has been estimated that $154 million per year will be required during 2015-2020 to continue the Global Programme to Eliminate Lymphatic Filariasis (GPELF). In light of this, it is important to understand the program's current value. Here, we evaluate the cost-effectiveness and cost-benefit of the preventive chemotherapy that was provided under the GPELF between 2000 and 2014. In addition, we also investigate the potential cost-effectiveness of hydrocele surgery. Methods: Our economic evaluation of preventive chemotherapy was based on previously published health and economic impact estimates (between 2000 and 2014). The delivery costs of treatment were estimated using a model developed by the World Health Organization. We also developed a model to investigate the number of disability-adjusted life years (DALYs) averted by a hydrocelectomy and identified the cost threshold under which it would be considered cost-effective. Results: The projected cost-effectiveness and cost-benefit of preventive chemotherapy were very promising, and this was robust over a wide range of costs and assumptions. When the economic value of the donated drugs was not included, the GPELF would be classed as highly cost-effective. We projected that a typical hydrocelectomy would be classed as highly cost-effective if the surgery cost less than $66 and cost-effective if less than $398 (based on the World Bank's cost-effectiveness thresholds for low income countries). Conclusions: Both the preventive chemotherapy and hydrocele surgeries provided under the GPELF are incredibly cost-effective and offer a very good investment in public health.

Knowledge, attitudes and perceptions regarding lymphatic filariasis: study on systematic noncompliance with mass drug administration

ABSTRACT The aim of this study was to investigate the epidemiological characteristics, antigenic profile, perceptions, attitudes and practices of individuals who have been systematically non-compliant in mass drug administration (MDA) campaigns targeting lymphatic filariasis, in the municipality of Olinda, State of Pernambuco, Northeastern Brazil. A pretested questionnaire was used to obtain information on socioenvironmental demographics, perceptions of lymphatic filariasis and MDA, and reasons for systematic noncompliance with treatment. A rapid immunochromatographic test (ICT) was performed during the survey to screen for filariasis. It was found that the survey subjects knew about filariasis and MDA. Filariasis was identified as a disease (86.2%) and 74.4% associated it with the presence of swelling in the legs. About 80% knew about MDA, and the main source of information was healthcare workers (68.3%). For men the main reasons for systematic noncompliance with MDA were that “the individual had not received the medication” (p=0.03) and for women “the individual either feared experiencing adverse reactions”. According to the ICT, the prevalence of lymphatic filariasis was 2%. The most important causes of systematic noncompliance were not receiving the drug and fear of side-effects. For successful implementation of MDA programs, good planning, educational campaigns promoting the benefits of MDA, adoption of measures to minimize the impact of adverse effects and improvement of drug distribution logistics are needed.

The Impact of Lymphatic Filariasis Mass Drug Administration Scaling Down on Soil-Transmitted Helminth Control in School-Age Children. Present Situation and Expected Impact from 2016 to 2020.

Lymphatic filariasis (LF) and soil-transmitted-helminths (STH) are co-endemic in 58 countries which are mostly in Africa and Asia. Worldwide, 486 million school-age children are considered at risk of both diseases. In 2000, the World Health Organization (WHO) established the global programme to eliminate LF by 2020. Since then, the LF elimination programme has distributed ivermectin or diethylcarbamazine citrate (DEC) in combination with albendazole, thereby also treating STH. Consequently, many school-age children have been treated for STH through the LF programme. As treatment targets towards the 2020 LF elimination goal are achieved, many countries are implementing the transmission assessment survey (TAS) and, if the LF prevalence is estimated to be less than 1%, scaling down mass drug administration (MDA). We analysed the 2014 data on preventive chemotherapy (PC) reported from LF STH co-endemic countries and projected the year and location of TAS expected to be conducted between 2016 and 2020 to assess the impact of this scaling down on STH PC. Eighty percent of all co-endemic countries that have already stopped LF MDA nationally were able to establish STH PC through schools. It is estimated that 14% of the total number of children presently covered by the LF programme is at risk of not continuing to receive PC for STH. In order to achieve and maintain the WHO 2020 goal for STH control, there is an urgent need to establish and reinforce school-based deworming programmes in countries scaling-down national LF elimination programmes.

Mathematical modelling of lymphatic filariasis elimination programmes in India: required duration of mass drug administration and post-treatment level of infection indicators.

BACKGROUND: India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation study with the individual-based model LYMFASIM to help clarify this. METHODS: We used a model-variant for Indian settings. We considered different hypotheses on detectability of antigenaemia (Ag) in relation to underlying adult worm burden, choosing the most likely hypothesis by comparing the model predicted association between community-level microfilaraemia (Mf) and antigenaemia (Ag) prevalence levels to observed data (collated from literature). Next, we estimated how long MDA must be continued in order to achieve elimination in different transmission settings and what Mf and Ag prevalence may still remain 1 year after the last required MDA round. The robustness of key-outcomes was assessed in a sensitivity analysis. RESULTS: Our model matched observed data qualitatively well when we assumed an Ag detection rate of 50 % for single worm infections, which increases with the number of adult worms (modelled by relating detection to the presence of female worms). The required duration of annual MDA increased with higher baseline endemicity and lower coverage (varying between 2 and 12 rounds), while the remaining residual infection 1 year after the last required treatment declined with transmission intensity. For low and high transmission settings, the median residual infection levels were 1.0 % and 0.4 % (Mf prevalence in the 5+ population), and 3.5 % and 2.0 % (Ag prevalence in 6-7 year-old children). CONCLUSION: To achieve elimination in high transmission settings, MDA must be continued longer and infection levels must be reduced to lower levels than in low-endemic communities. Although our simulations were for Indian settings, qualitatively similar patterns are also expected in other areas. This should be taken into account in decision algorithms to define whether MDA can be interrupted. Transmission assessment surveys should ideally be targeted to communities with the highest pre-control transmission levels, to minimize the risk of programme failure.

Larvicidal and repellent potential of Zingiber nimmonii (J. Graham) Dalzell (Zingiberaceae) essential oil: an eco-friendly tool against malaria, dengue, and lymphatic filariasis mosquito vectors?

Mosquitoes (Diptera: Culicidae) are important vectors of terms of public health relevance, especially in tropical and sub-tropical regions. The continuous and indiscriminate use of conventional pesticides for the control of mosquito vectors has resulted in the development of resistance and negative impacts on non-target organisms and the environment. Therefore, there is a need for development of effective mosquito control tools. In this study, the larvicidal and repellent activity of Zingiber nimmonii rhizome essential oil (EO) was evaluated against the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti, and the lymphatic filariasis vector Culex quinquefasciatus. The chemical composition of the EO was analyzed by gas chromatography-mass spectroscopy (GC-MS). GC-MS revealed that the Z. nimmonii EO contained at least 33 compounds. Major constituents were myrcene, ß-caryophyllene, α-humulene, and α-cadinol. In acute toxicity assays, the EO showed significant toxicity against early third-stage larvae of An. stephensi, Ae. aegypti, and Cx. quinquefasciatus, with LC50 values of 41.19, 44.46, and 48.26 µg/ml, respectively. Repellency bioassays at 1.0, 2.0, and 5.0 mg/cm(2) of Z. nimmonii EO gave 100 % protection up to 120, 150, and 180 min. against An. stephensi, followed by Ae. aegypti (90, 120, and 150 min) and Cx. quinquefasciatus (60, 90, and 120 min). Furthermore, the EO was safer towards two non-target aquatic organisms, Diplonychus indicus and Gambusia affinis, with LC50 values of 3241.53 and 9250.12 µg/ml, respectively. Overall, this research adds basic knowledge to develop newer and safer natural larvicides and repellent from Zingiberaceae plants against malaria, dengue, and filariasis mosquito vectors.

Accuracy of Coverage Survey Recall following an Integrated Mass Drug Administration for Lymphatic Filariasis, Schistosomiasis, and Soil-Transmitted Helminthiasis.

BACKGROUND: Achieving target coverage levels for mass drug administration (MDA) is essential to elimination and control efforts for several neglected tropical diseases (NTD). To ensure program goals are met, coverage reported by drug distributors may be validated through household coverage surveys that rely on respondent recall. This is the first study to assess accuracy in such surveys. METHODOLOGY/PRINCIPAL FINDINGS: Recall accuracy was tested in a series of coverage surveys conducted at 1, 6, and 12 months after an integrated MDA in Togo during which three drugs (albendazole, ivermectin, and praziquantel) were distributed. Drug distribution was observed during the MDA to ensure accurate recording of persons treated during the MDA. Information was obtained for 506, 1131, and 947 persons surveyed at 1, 6, and 12 months, respectively. Coverage (defined as the percentage of persons taking at least one of the MDA medications) within these groups was respectively 88.3%, 87.4%, and 80.0%, according to the treatment registers; it was 87.9%, 91.4% and 89.4%, according to survey responses. Concordance between respondents and registers on swallowing at least one pill was >95% at 1 month and >86% at 12 months; the lower concordance at 12 months was more likely due to difficulty matching survey respondents with the year-old treatment register rather than inaccurate responses. Respondents generally distinguished between pills similar in appearance; concordance for recall of which pills were taken was over 80% in each survey. SIGNIFICANCE: In this population, coverage surveys provided remarkably consistent coverage estimates for up to one year following an integrated MDA. It is not clear if similar consistency will be seen in other settings, however, these data suggest that in some settings coverage surveys might be conducted as much as one year following an MDA without compromising results. This might enable integration of post-MDA coverage measurement into large, multipurpose, periodic surveys, thereby conserving resources.

[Lymphatic filariasis transmission assessment survey in schools three years after stopping mass drug treatment with albendazole and ivermectin in the 7 endemic districts in Togo]. / Enquête d'évaluation de la transmission de la filariose lymphatique en milieu scolaire, 3 ans après l'arrêt du traitement de masse à l'albendazole et à l'ivermectine dans les 7 districts endémiques du Togo.

The aim of this study is to verify the level of transmission of lymphatic filariasis three years after stopping mass drug treatment in the 7 endemic districts in Togo. The survey was conducted in 2012 in Togo's 7 endemic districts grouped into four evaluation units (EU) using the WHO-recommended transmission assessment survey (TAS) protocol. Children aged 6-7 years were screened for Wuchereria bancofti antigen using the immunochromatographic card (ICT) method. A cluster sampling method was used to select eligible children in schools as the net primary-school enrolment ratio is greater than or equal to 75% in each of the four EUs. The number of children and schools to be selected in each EU, the randomization list for the selection of these children and the critical cut-off number of positive cases not to exceed were automatically generated using the Survey Sample Builder (SSB) tool, (NTD Support Center, Atlanta, Ga, USA). For confirmation, positive cases were subsequently tested for microfilaremia using nocturnal thick blood smear and for filarial antigen using Og4C3 antigen ELISA (TropBio ELISA Kit®, Townsville, Queensland, Australia). An EU is considered to have passed the test successfully (it is assumed that transmission can no longer be sustained), when the number of positive cases is below the critical cut-off number set by the SSB, which is roughly equivalent to 2% prevalence. Of the 1 706 children surveyed in Kpendjal-Tone's EU, 1 549 in Binah-Doufelgou's EU, 1 550 in Kozah's EU and the 1 575 in Amou-Haho's EU, 8 (0.46%), 1 (0.08%), 0 (0.00%) and 4 (0.25%) ICT positive cases respectively were detected. The number of positive ICT tests was well below 18, the critical cut number for each of the 4 EUs. All 13 ICT positive cases tested negative for nocturnal microfilaremia and Og4C3 ELISA. We conclude that all four EU passed the TAS with success, and the transmission of Wuchereria bancrofti is no longer likely to be sustained in the 7 endemic districts in Togo 3 years after stopping the MDA. A new TAS will be carried out in 2015, after which, if the results are still good, the country will submit a dossier to WHO for verification of the elimination of lymphatic filariasis.

Progress and impact of 13 years of the global programme to eliminate lymphatic filariasis on reducing the burden of filarial disease.

BACKGROUND: A Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, with mass drug administration (MDA) as the core strategy of the programme. After completing 13 years of operations through 2012 and with MDA in place in 55 of 73 endemic countries, the impact of the MDA programme on microfilaraemia, hydrocele and lymphedema is in need of being assessed. METHODOLOGY/PRINCIPAL FINDINGS: During 2000-2012, the MDA programme made remarkable achievements - a total of 6.37 billion treatments were offered and an estimated 4.45 billion treatments were consumed by the population living in endemic areas. Using a model based on empirical observations of the effects of treatment on clinical manifestations, it is estimated that 96.71 million LF cases, including 79.20 million microfilaria carriers, 18.73 million hydrocele cases and a minimum of 5.49 million lymphedema cases have been prevented or cured during this period. Consequently, the global prevalence of LF is calculated to have fallen by 59%, from 3.55% to 1.47%. The fall was highest for microfilaraemia prevalence (68%), followed by 49% in hydrocele prevalence and 25% in lymphedema prevalence. It is estimated that, currently, i.e. after 13 years of the MDA programme, there are still an estimated 67.88 million LF cases that include 36.45 million microfilaria carriers, 19.43 million hydrocele cases and 16.68 million lymphedema cases. CONCLUSIONS/SIGNIFICANCE: The MDA programme has resulted in significant reduction of the LF burden. Extension of MDA to all at-risk countries and to all regions within those countries where MDA has not yet reached 100% geographic coverage is imperative to further reduce the number of microfilaraemia and chronic disease cases and to reach the global target of interrupting transmission of LF by 2020.

Immunogenicity of Brugia malayi Abundant Larval Transcript-2, a potential filarial vaccine candidate expressed in tobacco.

KEY MESSAGE: Transgenic tobacco plants with Bm ALT-2, a filarial vaccine candidate, were developed. The plant-produced antigen showed immunogenicity on par with the E.coli product. Transgenic tobacco plants were developed using Brugia malayi Abundant Larval Transcript-2 (Bm ALT-2), a major antigen produced from recombinant E.coli found to be experimentally successful as potential vaccine candidate against lymphatic filariasis. Results of experiments on the transformation and expression of the Bm ALT-2 in tobacco plant to produce plant-based vaccine are presented here. We have successfully transformed the tobacco plant with Bm ALT-2 and confirmed that the plants expressed the filarial protein by PCR analysis and Western blotting. The level of expression varied from 50 to 90 ng/µg of total soluble protein for ALT-2. Immunization of mice with plant-extracted protein indicated that the plant-produced protein had immunological characteristics similar to the E.coli-produced protein. Antibody titres produced by plant-produced recombinant ALT 2-immunized mice were on par with those immunized with recombinant protein produced by E.coli. Antibody isotype assay showed that plant-produced recombinant ALT-2 induced significant IgG1, whereas E.coli-produced recombinant ALT-2 induced IgG3. This result is a step forward towards the development of a model eukaryotic system for the production of recombinant filarial proteins, which can be utilized to produce therapeutic and diagnostic molecules against lymphatic filariasis, a neglected tropical infectious disease which has a negative impact on socioeconomic development. In addition, this is the first report of the immunogenicity of a plant-derived filarial antigen.