Reducing the Antigen Prevalence Target Threshold for Stopping and Restarting Mass Drug Administration for Lymphatic Filariasis Elimination: A Model-Based Cost-effectiveness Simulation in Tanzania, India and Haiti.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) aims to reduce and maintain infection levels through mass drug administration (MDA), but there is evidence of ongoing transmission after MDA in areas where Culex mosquitoes are the main transmission vector, suggesting that a more stringent criterion is required for MDA decision making in these settings. METHODS: We use a transmission model to investigate how a lower prevalence threshold (<1% antigenemia [Ag] prevalence compared with <2% Ag prevalence) for MDA decision making would affect the probability of local elimination, health outcomes, the number of MDA rounds, including restarts, and program costs associated with MDA and surveys across different scenarios. To determine the cost-effectiveness of switching to a lower threshold, we simulated 65% and 80% MDA coverage of the total population for different willingness to pay per disability-adjusted life-year averted for India ($446.07), Tanzania ($389.83), and Haiti ($219.84). RESULTS: Our results suggest that with a lower Ag threshold, there is a small proportion of simulations where extra rounds are required to reach the target, but this also reduces the need to restart MDA later in the program. For 80% coverage, the lower threshold is cost-effective across all baseline prevalences for India, Tanzania, and Haiti. For 65% MDA coverage, the lower threshold is not cost-effective due to additional MDA rounds, although it increases the probability of local elimination. Valuing the benefits of elimination to align with the GPELF goals, we find that a willingness to pay per capita government expenditure of approximately $1000-$4000 for 1% increase in the probability of local elimination would be required to make a lower threshold cost-effective. CONCLUSIONS: Lower Ag thresholds for stopping MDAs generally mean a higher probability of local elimination, reducing long-term costs and health impacts. However, they may also lead to an increased number of MDA rounds required to reach the lower threshold and, therefore, increased short-term costs. Collectively, our analyses highlight that lower target Ag thresholds have the potential to assist programs in achieving lymphatic filariasis goals.

A multicenter, community-based, mixed methods assessment of the acceptability of a triple drug regimen for elimination of lymphatic filariasis.

BACKGROUND: Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA). METHODOLOGY/PRINCIPAL FINDINGS: To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9-36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1-34.3); Papua New Guinea 32.9 (95% CI: 31.9-33.8); Indonesia 30.6 (95% CI: 29.8-31.3); Haiti 28.6 (95% CI: 27.8-29.4); India 26.8 (95% CI: 25.6-28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed. CONCLUSIONS/SIGNIFICANCE: IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.

Risk factors associated with failing pre-transmission assessment surveys (pre-TAS) in lymphatic filariasis elimination programs: Results of a multi-country analysis.

Achieving elimination of lymphatic filariasis (LF) as a public health problem requires a minimum of five effective rounds of mass drug administration (MDA) and demonstrating low prevalence in subsequent assessments. The first assessments recommended by the World Health Organization (WHO) are sentinel and spot-check sites-referred to as pre-transmission assessment surveys (pre-TAS)-in each implementation unit after MDA. If pre-TAS shows that prevalence in each site has been lowered to less than 1% microfilaremia or less than 2% antigenemia, the implementation unit conducts a TAS to determine whether MDA can be stopped. Failure to pass pre-TAS means that further rounds of MDA are required. This study aims to understand factors influencing pre-TAS results using existing programmatic data from 554 implementation units, of which 74 (13%) failed, in 13 countries. Secondary data analysis was completed using existing data from Bangladesh, Benin, Burkina Faso, Cameroon, Ghana, Haiti, Indonesia, Mali, Nepal, Niger, Sierra Leone, Tanzania, and Uganda. Additional covariate data were obtained from spatial raster data sets. Bivariate analysis and multilinear regression were performed to establish potential relationships between variables and the pre-TAS result. Higher baseline prevalence and lower elevation were significant in the regression model. Variables statistically significantly associated with failure (p-value ≤0.05) in the bivariate analyses included baseline prevalence at or above 5% or 10%, use of Filariasis Test Strips (FTS), primary vector of Culex, treatment with diethylcarbamazine-albendazole, higher elevation, higher population density, higher enhanced vegetation index (EVI), higher annual rainfall, and 6 or more rounds of MDA. This paper reports for the first time factors associated with pre-TAS results from a multi-country analysis. This information can help countries more effectively forecast program activities, such as the potential need for more rounds of MDA, and prioritize resources to ensure adequate coverage of all persons in areas at highest risk of failing pre-TAS.

Improved assessment of mass drug administration and health district management performance to eliminate lymphatic filariasis.

Lymphatic filariasis (LF) elimination as a public health problem requires the interruption of transmission by administration of preventive mass drug administration (MDA) to the eligible population living in endemic districts. Suboptimal MDA coverage leads to persistent parasite transmission with consequential infection, disease and disability, and the need for continuing MDA rounds, requiring considerable investment. Routine coverage reports must be verified in each MDA implementation unit (IU) due to incorrect denominators and numerators used to calculate coverage estimates with administrative data. IU are usually the health districts. Coverage is verified so IU teams can evaluate their outreach and take appropriate action to improve performance. Mozambique and the Democratic Republic of Congo (DRC) have conducted MDA campaigns for LF since 2009 and 2014, respectively. To verify district reports and assess the declared achievement using administrative data of the minimum 80% coverage of eligible people (or 65% of the total population), both countries conducted rapid probability surveys using Lot Quality Assurance Sampling (LQAS)(n = 1102) in 2015 and 2016 in 58 IU in 49 districts. The surveys identified IU with suboptimal coverage, reasons residents did not take the medication, place where the medication was received, information sources, and knowledge about diseases prevented by the MDA. LQAS identified four inadequately covered IU triggering district team performance reviews with provincial and national teams and district retreatment. Provincial estimates using probability samples (weighted by populations sizes) were 10 and 17 percentage points lower than reported coverage in DRC and Mozambique. The surveys identified: absence from home during annual MDA rounds as the main reason for low performance and provided valuable information about pre-campaign and campaign activities resulting in improved strategies and continued progress towards elimination of LF and co-endemic Neglected Tropical Diseases.

Economic performance and cost-effectiveness of using a DEC-salt social enterprise for eliminating the major neglected tropical disease, lymphatic filariasis.

BACKGROUND: Salt fortified with the drug, diethylcarbamazine (DEC), and introduced into a competitive market has the potential to overcome the obstacles associated with tablet-based Lymphatic Filariasis (LF) elimination programs. Questions remain, however, regarding the economic viability, production capacity, and effectiveness of this strategy as a sustainable means to bring about LF elimination in resource poor settings. METHODOLOGY AND PRINCIPAL FINDINGS: We evaluated the performance and effectiveness of a novel social enterprise-based approach developed and tested in Léogâne, Haiti, as a strategy to sustainably and cost-efficiently distribute DEC-medicated salt into a competitive market at quantities sufficient to bring about the elimination of LF. We undertook a cost-revenue analysis to evaluate the production capability and financial feasibility of the developed DEC salt social enterprise, and a modeling study centered on applying a dynamic mathematical model localized to reflect local LF transmission dynamics to evaluate the cost-effectiveness of using this intervention versus standard annual Mass Drug Administration (MDA) for eliminating LF in Léogâne. We show that the salt enterprise because of its mixed product business strategy may have already reached the production capacity for delivering sufficient quantities of edible DEC-medicated salt to bring about LF transmission in the Léogâne study setting. Due to increasing revenues obtained from the sale of DEC salt over time, expansion of its delivery in the population, and greater cumulative impact on the survival of worms leading to shorter timelines to extinction, this strategy could also represent a significantly more cost-effective option than annual DEC tablet-based MDA for accomplishing LF elimination. SIGNIFICANCE: A social enterprise approach can offer an innovative market-based strategy by which edible salt fortified with DEC could be distributed to communities both on a financially sustainable basis and at sufficient quantity to eliminate LF. Deployment of similarly fashioned intervention strategies would improve current efforts to successfully accomplish the goal of LF elimination, particularly in difficult-to-control settings.

Ecological and Socioeconomic Predictors of Transmission Assessment Survey Failure for Lymphatic Filariasis.

The transmission assessment survey (TAS) is recommended to determine whether cessation of mass drug administration (MDA) for lymphatic filariasis (LF) is warranted. Ministries of health typically implement TASs in evaluation units (EUs) that have had more than five rounds of annual MDA. Under TAS guidelines, sample size calculations determine a decision value: if the number of individuals testing positive exceeds this threshold, then MDA continues in the EU. The objective of this study was to determine whether fine scale geospatial covariates could be used to identify predictors of TAS failure. We geo-referenced 746 TAS EUs, of which 65 failed and extracted geospatial covariates using R to estimate odds of failure. We implemented stepwise backward elimination to select covariates for inclusion in a logistic regression to estimate the odds of TAS failure. Covariates included environmental predictors (aridity, distance to fresh water, elevation, and enhanced vegetation index), cumulative rounds of MDA, measures of urbanicity and access, LF species, and baseline prevalence. Presence of Brugia was significantly associated with TAS failure (odds ratio [OR]: 4.79, 95% CI: 2.52-9.07), as was population density (OR: 2.91, 95% CI: 1.06-7.98). The presence of nighttime lights was highly protective against failure (OR: 0.22, 95% CI: 0.10-0.50), as was an increase in elevation (OR: 0.36, 95% CI: 0.18-0.732). This work identifies predictors associated with TAS failure at the EU areal level, given the data presently available, and also identifies the need for more granular data to conduct a more robust assessment of these predictors.

Bridging the gap in outreach and compliance with mass drug administration for lymphatic filariasis elimination in an endemic district in Kerala, India: an intervention research approach.

Lymphatic filariasis (LF), a neglected tropical disease is targeted for elimination globally by 2020. National Health Policy of India set the goal by 2017 and annual single-dose mass drug administration (MDA) with anti-filarial drugs is in operation in endemic districts since 2004. Performance and effectiveness of MDA was diverse across the nation and prevalence of infection continues above threshold level in 50% of endemic districts which requires alternative strategies. National programme aims at achieving >65% consumption for transmission control. Post 10 rounds of MDA in an endemic district of Kerala state, a three-arm study identified determinants in gap in outreach and consumption, based on which context-dependent intervention using social group work and networking (SGWN) was implemented and impact assessed. A spill over effect with overall increase in coverage and consumption rates irrespective of arms apparently is due to inclusive improvement in MDA programme whereas, significant relative improvement in intervention arm reflects effectiveness of SGWN strategy. Though reduction in microfilaria prevalence in all arms was observed, it was significant between intervention and comparison arm. This study highlights need for context-dependent communication strategy to improve MDA for accelerating LF elimination by the targeted 2020.

Continuous and pulsed epidemiological models for onchocerciasis with implications for eradication strategy.

Onchocerciasis is an endemic disease in parts of sub-Saharan Africa. Complex mathematical models are being used to assess the likely efficacy of efforts to eradicate the disease; however, their predictions have not always been borne out in practice. In this paper, we represent the immunological aspects of the disease with a single empirical parameter in order to reduce the model complexity. Asymptotic approximation allows us to reduce the vector-borne epidemiological model to a model of an infectious disease with nonlinear incidence. We then consider two versions, one with continuous treatment and a more realistic one where treatment occurs only at intervals. Thorough mathematical analysis of these models yields equilibrium solutions for the continuous case, periodic solutions for the pulsed case, and conditions for the existence of endemic disease equilibria in both cases, thereby leading to simple model criteria for eradication. The analytical results and numerical experiments show that the continuous treatment version is an excellent approximation for the pulsed version and that the current onchocerciasis eradication strategy is inadequate for regions where the incidence is highest and unacceptably slow even when the long-term behavior is the disease-free state.

Evaluation of Treatment Coverage and Enhanced Mass Drug Administration for Onchocerciasis and Lymphatic Filariasis in Five Local Government Areas Treating Twice Per Year in Edo State, Nigeria.

The western region of Edo state in southern Nigeria is highly endemic for onchocerciasis. Despite years of mass drug administration (MDA) with ivermectin (IVM), reports suggest persistently high prevalence of onchocerciasis, presumably because of poor coverage. In 2016, twice-per-year treatment with IVM (combined with albendazole for lymphatic filariasis in the first round where needed) began in five local government areas (LGAs) of Edo state. We undertook a multistage cluster survey within 3 months after each round of MDA to assess coverage. First-round coverage was poor: among 4,942 people of all ages interviewed from 145 clusters, coverage was 31.1% (95% confidence intervals [CI]: 24.1-38.0%). Most respondents were not offered medicines. To improve coverage in the second round, three LGAs were randomized to receive MDA through a "modified campaign" approach focused on improved supervision and monitoring. The other two LGAs continued with standard MDA as before. A similar survey was conducted after the second round, interviewing 3,362 people in 87 clusters across the five LGAs. Coverage was not statistically different from the first round (40.0% [95% CI: 31.0-49.0%]) and there was no significant difference between the groups (P = 0.7), although the standard MDA group showed improvement over round 1 (P < 0.01). The additional cost per treatment in the modified MDA was 1.6 times that of standard MDA. Compliance was excellent among those offered treatment. We concluded that poor mobilization, medicine distribution, and program penetration led to low coverage. These must be addressed to improve treatment coverage in Edo state.

First evidence of lymphatic filariasis transmission interruption in Cameroon: Progress towards elimination.

BACKGROUND: Lymphatic filariasis (LF) is among the 10 neglected tropical diseases targeted for control or elimination by 2020. For LF elimination, the World Health Organization (WHO) has proposed a comprehensive strategy including (i) interruption of LF transmission through large-scale annual treatment (or mass drug administration (MDA)) of all eligible individuals in endemic areas, and (ii) alleviation of LF-associated suffering through morbidity management and disability prevention. In Cameroon, once-yearly mass administration of ivermectin and albendazole has been implemented since 2008. The aim of this study was to assess progress towards the elimination goal, looking specifically at the impact of six rounds of MDA on LF transmission in northern Cameroon. METHODOLOGY: The study was conducted in the North and Far North Regions of Cameroon. Five health districts that successfully completed six rounds of MDA (defined as achieving a treatment coverage ≥ 65% each year) and reported no positive results for Wuchereria bancrofti microfilariaemia during routine surveys following the fifth MDA were grouped into three evaluation units (EU) according to WHO criteria. LF transmission was assessed through a community-based transmission assessment survey (TAS) using an immunochromatographic test (ICT) for the detection of circulating filarial antigen (CFA) in children aged 5-8 years old. PRINCIPAL FINDINGS: A total of 5292 children (male/female ratio 1.04) aged 5-8 years old were examined in 97 communities. Positive CFA results were observed in 2, 8 and 11 cases, with a CFA prevalence of 0.13% (95% CI: 0.04-0.46) in EU#1, 0.57% (95% CI: 0.32-1.02) in EU#2, and 0.45% (95% CI: 0.23-0.89) in EU#3. CONCLUSION/SIGNIFICANCE: The positive CFA cases were below WHO defined critical cut-off thresholds for stopping treatment and suggest that transmission can no longer be sustained. Post-MDA surveillance activities should be organized to evaluate whether recrudescence can occur.

Assessment of parasitological findings in heartworm-infected beagles treated with Advantage Multi® for dogs (10% imidacloprid + 2.5% moxidectin) and doxycycline.

BACKGROUND: Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles. METHODS: This study utilized 16 dogs, 8 dogs in each of non-treated control and treated groups. A total of 16 adult Dirofilaria immitis (Missouri strain) were surgically transplanted into the jugular vein of each study dog. The treatment regimen of monthly IMD + MOX topically (per labeled dosage and administration) for 10 months and 10 mg/kg doxycycline BID orally for 30 days was initiated 30 days post-surgical transplant. Echocardiograms, radiographs, complete blood counts, clinical chemistry profiles, heartworm antigenemia and microfilaremia were evaluated every 4 weeks. Serum samples were assayed for heartworm antigen using the DiroCHEK® heartworm antigen test. The DiroCHEK® was performed according to the manufacturer's recommendations and read using a spectrophotometer at 490 nm. RESULTS: All dogs tested positive for the presence of heartworm antigen post-surgical transplant and prior to treatment. Heartworm antigen levels began declining in treated dogs 3 months post-treatment. Non-treated control dogs remained antigen-positive. No microfilariae were detected in treated dogs after 21 days post-treatment. At necropsy, adult heartworms were recovered from all non-treated control dogs with a range of 10-12 adult worms/dog for an average recovery of 10.6 adult heartworms/dog. In the IMD + MOX- and doxycycline-treated dogs, the range of adult heartworms recovered was 0-2 adult worms/dog, with five dogs having no adult heartworms present. The average adult heartworm recovery was 0.6/dog in the treated group. This treatment regimen demonstrated a 95.9% efficacy in eliminating adult heartworms (P < 0.0001). CONCLUSIONS: This study demonstrated that this treatment regimen successfully eliminated D. immitis microfilariae by 21 days post-treatment, reduced heartworm antigen concentration over time, and had a 95.9% efficacy in the elimination of mature adult heartworms. Based on this study, we conclude that this treatment regimen is a relatively quick, reliable and safe option to treat canine heartworm infection as compared to other treatment regimens involving macrocyclic lactones, when the approved drug melarsomine dihydrochloride is unavailable, contraindicated or declined by an owner unable to afford the more costly treatment or concerned about the potential side effects.

Molecular xenomonitoring (MX) and transmission assessment survey (TAS) of lymphatic filariasis elimination in two villages, Menoufyia Governorate, Egypt.

Lymphatic filariasis (LF) is focally endemic in Egypt where the female mosquito, Culex pipiens, is responsible for its transmission. The aim of the study was to investigate the impact of implementation of the 13th round of MDA in two Egyptian villages in the Menoufyia Governorate area after failing the transmission assessment survey (TAS) in 2005 using two methods, and to decide whether it is safe to stop MDA in these, as well as in similar implementation units (IUs). To achieve this aim, both the immunochromatographic card test (ICT) and molecular xenomonitoring (MX) techniques were employed. A cross-sectional study was carried out in the villages in 2014 with two sections: Section (1): a school-based survey where all the primary school entrants (6-7) years of age were tested by ICT. Section (2): a mosquito-based survey where a total of 152 mosquito pools collected from Samalay and 167 from Kafr El-Tarainah were tested for the presence of the gDNA of Wuchereria bancrofti microfilaria by real-time PCR assays. The results revealed that all primary school children in both villages were 100% negative for antigenemia. Also, all mosquito pools were 100% negative for the microfilarial gDNA.

Can community-based integrated vector control hasten the process of LF elimination?

Community-based integrated vector control (IVC) using polystyrene beads (EPS) and pyrethroid impregnated curtains (PIC) as an adjunct to mass drug administration (MDA) was implemented for lymphatic filariasis elimination, in the filaria endemic villages of Tirukoilur, south India. In all the villages, MDA was carried out by the state health machinery, as part of the national filariasis elimination programme. Thirty-six difficult-to-control villages were grouped as, viz, MDA alone, MDA + EPS and MDA + EPS + PIC arms. Implementation and monitoring of IVC was carried out by the community. After 3 years of IVC, higher reductions in filariometric indices were observed in both the community and vector population. Decline in antigenaemia prevalence was higher in MDA + IVC as compared to MDA alone arm. Vector density dropped significantly (P < 0.05) in both the IVC arms, and nil transmission was observed during post-IVC period. Almost 53.8 and 75.8 % of the cesspits in MDA + EPS and MDA + EPS + PIC arms were closed by the householders, due to the enhanced awareness on vector breeding. The paper presents the key elements of IVC implementation through social mobilization in a LF prevalent area. Thus, community-based IVC strategy can hasten LF elimination, as it reduced the transmission and filariometric indices significantly. Indices were maintained at low level with nil transmission, by the community through IVC tools.

Awareness and coverage of mass drug administration for elimination of lymphatic filariasis: a community based cross sectional study in Nepal.

Lymphatic filariasis (LF) is among the major public health problems in Nepal. The disease is a major cause of morbidities primarily, lymphedema of legs and hydrocele and it impedes socio economic development in many endemic areas of the country. This study is aimed at exploring the understanding of people about mass drug administration (MDA) of the said disease and the status of compliance of MDA in Nepal. This study is a cross sectional study carried out among 894 household samples in three of the sixty LF endemic districts. The selected districts were Dhading, Kapilvastu and Kailali. The sentinel surveillance of sites in three districts constituted the sampling frame at the first stage. The peripheral health care centers in the sentinel sites constituted the sampling frame at the second stage of sampling. The coverage of MDA was 95.5 %. However, the compliance was less. Only 71.6 % of the respondents who took the drugs from health workers swallowed the diethyl carbamazine (DEC) completely, other did not swallow. In the present study, majority of respondents reported that they had heard or seen persons with side effects of DEC in their community. A total of 20 % of respondents reported that they had side effects after having DEC and only 3.9 % of these side effects were treated. The Female Community Health volunteers (FCHVs), health workers and radio/Television (TV) were the chief sources of MDA related information. This study recommends for a concerted public health action combining effective drug delivery mechanism and sound public awareness campaigns. The community people need to be made aware beforehand about the location, time of drug distribution. Also public awareness of the DEC should be conducted so that people would trust it and comply with the drug regime. Along with the health workers and radio/TV that has been used traditionally, we recommend mobilization of FCHVs in the public awareness campaigns the MDA campaigns.

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.

Rapid assessment procedures to detect hidden endemic foci in areas not subjected to mass drug administration in Sri Lanka.

For the declaration of elimination of lymphatic filariasis, reliable epidemiological data in all parts of a country are required. In Sri Lanka, due to social disturbance, there are 3 provinces whose endemicity has been declared unknown. Further, a recent report revealed an endemic pocket, which is on the border with the district that was not covered by the national elimination program. These facts indicate the necessity of more extensive studies to discover hidden endemic foci. To facilitate such studies, we evaluated 2 methods of Rapid Assessment Procedure (RAP) in Hambantota district, where the filariasis endemicity was low: (1) indirect questioning by mailing a questionnaire to each local leader (IndQ), asking about the presence of clinical cases, and (2) focus group discussion (FGD) by villagers. The information given by people was validated with clinical examination by doctors (CE) and IgG4 ELISA using urine samples. In the results: there was a strong positive correlation between CE and ELISA rates. The hydrocele rates obtained by FGD or IndQ were associated significantly with CE rates. The rates by FGD or Cluster-IndQ ('modified' IndQ) were also associated significantly with ELISA rates. The IndQ was most cost-effective. Based on these findings, we have concluded that screening by IndQ and confirmation by the ELISA would be an effective and practical way in Sri Lanka to locate endemic foci in hitherto unsurveyed districts.

African Programme For Onchocerciasis Control 1995-2015: model-estimated health impact and cost.

BACKGROUND: Onchocerciasis causes a considerable disease burden in Africa, mainly through skin and eye disease. Since 1995, the African Programme for Onchocerciasis Control (APOC) has coordinated annual mass treatment with ivermectin in 16 countries. In this study, we estimate the health impact of APOC and the associated costs from a program perspective up to 2010 and provide expected trends up to 2015. METHODS AND FINDINGS: With data on pre-control prevalence of infection and population coverage of mass treatment, we simulated trends in infection, blindness, visual impairment, and severe itch using the micro-simulation model ONCHOSIM, and estimated disability-adjusted life years (DALYs) lost due to onchocerciasis. We assessed financial costs for APOC, beneficiary governments, and non-governmental development organizations, excluding cost of donated drugs. We estimated that between 1995 and 2010, mass treatment with ivermectin averted 8.2 million DALYs due to onchocerciasis in APOC areas, at a nominal cost of about US$257 million. We expect that APOC will avert another 9.2 million DALYs between 2011 and 2015, at a nominal cost of US$221 million. CONCLUSIONS: Our simulations suggest that APOC has had a remarkable impact on population health in Africa between 1995 and 2010. This health impact is predicted to double during the subsequent five years of the program, through to 2015. APOC is a highly cost-effective public health program. Given the anticipated elimination of onchocerciasis from some APOC areas, we expect even more health gains and a more favorable cost-effectiveness of mass treatment with ivermectin in the near future.

Modeling the impact and costs of semiannual mass drug administration for accelerated elimination of lymphatic filariasis.

The Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020.

Epidemiological assessment of eight rounds of mass drug administration for lymphatic filariasis in India: implications for monitoring and evaluation.

BACKGROUND: Monitoring and evaluation guidelines of the programme to eliminate lymphatic filariasis require impact assessments in at least one sentinel and one spot-check site in each implementation unit (IU). Transmission assessment surveys (TAS) that assess antigenaemia (Ag) in children in IUs that have completed at least five rounds of mass drug administration (MDA) each with >65% coverage and with microfilaria (Mf) levels <1% in the monitored sites form the basis for stopping the MDA. Despite its rigour, this multi-step process is likely to miss sites with transmission potential ('hotspots') and its statistical assumptions for sampling and threshold levels for decision-making have not been validated. We addressed these issues in a large-scale epidemiological study in two primary health centres in Thanjavur district, India, endemic for bancroftian filariasis that had undergone eight rounds of MDA. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence and intensity of Mf (per 60 µl blood) were 0.2% and 0.004 respectively in the survey that covered >70% of 50,363 population. The corresponding values for Ag were 2.3% and 17.3 Ag-units respectively. Ag-prevalence ranged from 0.7 to 0.9%, in children (2-10 years) and 2.7 to 3.0% in adults. Although the Mf-levels in the survey and the sentinel/spot check sites were <1% and Ag-level was <2% in children, we identified 7 "residual" (Mf-prevalence ≥ 1%, irrespective of Ag-status in children) and 17 "transmission" (at least one Ag-positive child born during the MDA period) hotspots. Antigenaemic persons were clustered both at household and site levels. We identified an Ag-prevalence of ~1% in children (equivalent to 0.4% community Mf-prevalence) as a possible threshold value for stopping MDA. CONCLUSIONS/SIGNIFICANCE: Existence of 'hotspots' and spatial clustering of infections in the study area indicate the need for developing good surveillance strategies for detecting 'hotspots', adopting evidence-based sampling strategies and evaluation unit size for TAS.

Intention to continue with ivermectin treatment for onchocerciasis control after eight years of annual distribution in Cameroon, Nigeria, and Uganda.

This study identified the socio-demographic correlates of intention to comply with ivermectin treatment, from a structured interview of 2,306 persons aged 10 years and above, grouped into high and low compliers, who took ivermectin 6-8 times and 0-2 times respectively. Simple descriptive statistics were employed in characterizing the respondents into high and low compliers, while some socio-demographic and key perceptual factors were employed in regression models constructed to explain levels of compliance among the respondents. Demographic and perceptual factors associated with intention to comply with prolonged treatment with ivermectin were identified. Intention to comply was higher among married persons (91.8%, p < 0.001); local populations (89.8%, p < 0.001); and those with history of complying with treatment (98.2%, p < 0.001). Perception of onchocerciasis and effectiveness of ivermectin influenced intention to continue. The perceptual factors that drive the intention to comply should inform plans for health education at the project and village levels.