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.     

Achievements and challenges of lymphatic filariasis elimination in Sierra Leone

BackgroundLymphatic filariasis (LF) is targeted for elimination in Sierra Leone. Epidemiological coverage of mass drug administration (MDA) with ivermectin and albendazole had been reported >65% in all 12 districts annually. Eight districts qualified to implement transmission assessment survey (TAS) in 2013 but were deferred until 2017 due to the Ebola outbreak (2014–2016). In 2017, four districts qualified for conducting a repeat pre-TAS after completing three more rounds of MDA and the final two districts were also eligible to implement a pre-TAS.Methodology/Principal findingsFor TAS, eight districts were surveyed as four evaluation units (EU). A school-based survey was conducted in children aged 6–7 years from 30 clusters per EU. For pre-TAS, one sentinel and one spot check site per district (with 2 spot check sites in Bombali) were selected and 300–350 persons aged 5 years and above were selected. For both surveys, finger prick blood samples were tested using the Filariasis Test Strips (FTS).For TAS, 7,143 children aged 6–7 years were surveyed across four EUs, and positives were found in three EUs, all below the critical cut-off value for each EU. For the repeat pre-TAS/pre-TAS, 3,994 persons over five years of age were surveyed. The Western Area Urban had FTS prevalence of 0.7% in two sites and qualified for TAS, while other five districts had sites with antigenemia prevalence >2%: 9.1–25.9% in Bombali, 7.5–19.4% in Koinadugu, 6.1–2.9% in Kailahun, 1.3–2.3% in Kenema and 1.7% - 3.7% in Western Area Rural.Conclusions/SignificanceEight districts in Sierra Leone have successfully passed TAS1 and stopped MDA, with one more district qualified for conducting TAS1, a significant progress towards LF elimination. However, great challenges exist in eliminating LF from the whole country with repeated failure of pre-TAS in border districts. Effort needs to be intensified to achieve LF elimination.     

A Community-Based Study of Factors Associated with Continuing Transmission of Lymphatic Filariasis in Leogane,Haiti

Seven rounds of mass drug administration (MDA) have been administered in Leogane, Haiti, an area hyperendemic for lymphatic filariasis (LF). Sentinel site surveys showed that the prevalence of microfilaremia was reduced to <1% from levels as high as 15.5%, suggesting that transmission had been reduced. A separate 30-cluster survey of 2- to 4-year-old children was conducted to determine if MDA interrupted transmission. Antigen and antifilarial antibody prevalence were 14.3% and 19.7%, respectively. Follow-up surveys were done in 6 villages, including those selected for the cluster survey, to assess risk factors related to continued LF transmission and to pinpoint hotspots of transmission. One hundred houses were mapped in each village using GPS-enabled PDAs, and then 30 houses and 10 alternates were chosen for testing. All individuals in selected houses were asked to participate in a short survey about participation in MDA, history of residence in Leogane and general knowledge of LF. Survey teams returned to the houses at night to collect blood for antigen testing, microfilaremia and Bm14 antibody testing and collected mosquitoes from these communities in parallel. Antigen prevalence was highly variable among the 6 villages, with the highest being 38.2% (Dampus) and the lowest being 2.9% (Corail Lemaire); overall antigen prevalence was 18.5%. Initial cluster surveys of 2- to 4-year-old children were not related to community antigen prevalence. Nearest neighbor analysis found evidence of clustering of infection suggesting that LF infection was focal in distribution. Antigen prevalence among individuals who were systematically noncompliant with the MDAs, i.e. they had never participated, was significantly higher than among compliant individuals (p<0.05). A logistic regression model found that of the factors examined for association with infection, only noncompliance was significantly associated with infection. Thus, continuing transmission of LF seems to be linked to rates of systematic noncompliance.     

Integrated Schistosomiasis and Soil-Transmitted Helminthiasis Control over Five Years on Kome Island,Tanzania

Integrated control strategies are important for sustainable control of schistosomiasis and soil-transmitted helminthiasis, despite their challenges for their effective implementation. With the support of Good Neighbors International in collaboration with National Institute of Medical Research, Mwanza, Tanzania, integrated control applying mass drug administration (MDA), health education using PHAST, and improved safe water supply has been implemented on Kome Island over 5 years for controlling schistosomiasis and soil-transmitted helminths (STHs). Baseline surveys for schistosomiasis and STHs was conducted before implementation of any integrated control strategies, followed by 4 cross-sectional follow-up surveys on randomly selected samples of schoolchildren and adults in 10 primary schools and 8 villages, respectively, on Kome islands. Those follow-up surveys were conducted for impact evaluation after introduction of control strategies interventions in the study area. Five rounds of MDA have been implemented from 2009 along with PHAST and improved water supply with pumped wells as other control strategies for complementing MDA. A remarkable steady decline of schistosomiasis and STHs was observed from 2009 to 2012 with significant trends in their prevalence decline, and thereafter infection rate has remained at a low sustainable control. By the third follow-up survey in 2012, Schistosoma mansoni infection prevalence was reduced by 90.5% and hookworm by 93.3% among schoolchildren while in adults the corresponding reduction was 83.2% and 56.9%, respectively. Integrated control strategies have successfully reduced S. mansoni and STH infection status to a lower level. This study further suggests that monitoring and evaluation is a crucial component of any large-scale STH and schistosomiasis intervention.     

Prevalence of Trachoma at Sub-District Level in Ethiopia: Determining When to Stop Mass Azithromycin Distribution

Background

To eliminate blinding trachoma, the World Health Organization emphasizes implementing the SAFE strategy, which includes annual mass drug administration (MDA) with azithromycin to the whole population of endemic districts. Prevalence surveys to assess impact at the district level are recommended after at least 3 years of intervention. The decision to stop MDA is based on a prevalence of trachomatous inflammation follicular (TF) among children aged 1–9 years below 5% at the sub-district level, as determined by an additional round of surveys limited within districts where TF prevalence is below 10%. We conducted impact surveys powered to estimate prevalence simultaneously at the sub-district and district in two zones of Amhara, Ethiopia to determine whether MDA could be stopped.

Methodology

Seventy-two separate population-based, sub-district surveys were conducted in 25 districts. In each survey all residents from 10 randomly selected clusters were screened for clinical signs of trachoma. Data were weighted according to selection probabilities and adjusted for correlation due to clustering.

Principal Findings

Overall, 89,735 residents were registered from 21,327 households of whom 72,452 people (80.7%) were examined. The prevalence of TF in children aged 1–9 years was below 5% in six sub-districts and two districts. Sub-district level prevalence of TF in children aged 1–9 years ranged from 0.9–76.9% and district-level from 0.9–67.0%. In only one district was the prevalence of trichiasis below 0.1%.

Conclusions/Significance

The experience from these zones in Ethiopia demonstrates that impact assessments designed to give a prevalence estimate of TF at sub-district level are possible, although the scale of the work was challenging. Given the assessed district-level prevalence of TF, sub-district-level surveys would have been warranted in only five districts. Interpretation was not as simple as stopping MDA in sub-districts below 5% given programmatic challenges of exempting sub-districts from a highly regarded program and the proximity of hyper-endemic sub-districts.     

Pilot Assessment of Soil-Transmitted Helminthiasis in the Context of Transmission Assessment Surveys for Lymphatic Filariasis in Benin and Tonga

Background

Mass drug administration (MDA) for lymphatic filariasis (LF) programs has delivered more than 2 billion treatments of albendazole, in combination with either ivermectin or diethylcarbamazine, to communities co-endemic for soil-transmitted helminthiasis (STH), reducing the prevalence of both diseases. A transmission assessment survey (TAS) is recommended to determine if MDA for LF can be stopped within an evaluation unit (EU) after at least five rounds of annual treatment. The TAS also provides an opportunity to simultaneously assess the impact of these MDAs on STH and to determine the frequency of school-based MDA for STH after community-wide MDA is no longer needed for LF.

Methodology/Principal Findings

Pilot studies conducted in Benin and Tonga assessed the feasibility of a coordinated approach. Of the schools (clusters) selected for a TAS in each EU, a subset of 5 schools per STH ecological zone was randomly selected, according to World Health Organization (WHO) guidelines, for the coordinated survey. In Benin, 519 children were sampled in 5 schools and 22 (4.2%) had STH infection (A. lumbricoides, T. trichiura, or hookworm) detected using the Kato-Katz method. All infections were classified as light intensity under WHO criteria. In Tonga, 10 schools were chosen for the coordinated TAS and STH survey covering two ecological zones; 32 of 232 (13.8%) children were infected in Tongatapu and 82 of 320 (25.6%) in Vava''u and Ha''apai. All infections were light-intensity with the exception of one with moderate-intensity T. trichiura.

Conclusions

Synchronous assessment of STH with TAS is feasible and provides a well-timed evaluation of infection prevalence to guide ongoing treatment decisions at a time when MDA for LF may be stopped. The coordinated field experiences in both countries also suggest potential time and cost savings. Refinement of a coordinated TAS and STH sampling methodology should be pursued, along with further validation of alternative quantitative diagnostic tests for STH that can be used with preserved stool specimens.     

Lymphatic filariasis epidemiology in Samoa in 2018: Geographic clustering and higher antigen prevalence in older age groups

BackgroundSamoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5–9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years.MethodsA community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5–9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5–9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households.ResultsA total of 3940 persons were included (1942 children aged 5–9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8–5.6%) and 10.0% (95% CI 7.4–13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5–9 years (1.3%, 95% CI 0.8–2.1%) than ≥10 years (4.7%, 95% CI 3.1–7.0%), and poorly correlated at the PSU level (R-square = 0.1459). Adjusted Ag prevalence in PSUs ranged from 0% to 10.3% (95% CI 5.9–17.6%) in randomly selected and 3.8% (95% CI 1.3–10.8%) to 20.0% (95% CI 15.3–25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01).ConclusionsOur study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5–9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots.     

Serology,infection, and clinical trachoma as tools in prevalence surveys for re-emergence of trachoma in a formerly hyperendemic district

BackgroundTo eliminate trachoma as a public health problem, countries must achieve a district-level prevalence of trachomatous inflammation—follicular (TF) <5% in children ages 1–9 years. Re-emergence of TF could trigger additional rounds of mass drug/antibiotic administration (MDA), so accurate tools for use in surveys assessing trachoma prevalence are essential.Methodology & principal findingsWe surveyed 2401 children ages 1–9 years from 50 villages in Kongwa, Tanzania, 2 years post-MDA and 1.5 years after an impact survey found TF <5% in the same villages. Our survey included multiple tools: clinical determination of TF, Cepheid testing for Chlamydia trachomatis infection, and testing for anti-pgp3 antibodies via multiplex bead array. Photographs of the upper tarsal conjunctiva were taken in a subset of children to corroborate the field grades.Overall TF prevalence in 1–9 year olds was 7.1% (95% CI: 5.6%-8.9%), which decreased with age (p = <0.0001). TF prevalence by village was heterogeneous, with 19 villages having TF <5% and 16 villages having TF >10%. There was a strong correlation between field and photo grading of TF (kappa = 0.69; 95% CI: 0.60–0.78) and between TF and infection, with 21.5% of TF-positive children also testing positive for infection, as compared to only 1.6% of TF-negative children (p = 0.0010). Overall seroprevalence was 18.2% (95% CI: 14.8%-22.1%), which increased with age (p = <0.0001). Notably, 1–2 year olds, who were born after the cessation of MDA and theoretically should not have had exposure to C. trachomatis in the absence of transmission, had an average seroprevalence of 6.7%.Conclusions & significanceField TF prevalence, supported by photographic review and infection data, suggested re-emergence of trachoma in Kongwa. Moreover, seropositivity in the children born after cessation of MDA indicated exposure to C. trachomatis despite a previous survey finding of TF <5%. Examining seropositivity in specific age groups expected to have limited exposure to C. trachomatis can be used to detect re-emergence.     

Maternal Infection Is a Risk Factor for Early Childhood Infection in Filariasis

Background

Global Program to Eliminate Lymphatic Filariasis (GPELF) launched by WHO aims to eliminate the disease by 2020. To achieve the goal annual mass drug administration (MDA) with diethylcarbamazine (DEC) plus albendazole (ABZ) has been introduced in all endemic countries. The current policy however excludes pregnant mothers and children below two years of age from MDA. Since pregnancy and early childhood are critical periods in determining the disease outcome in older age, the present study was undertaken to find out the influence of maternal filarial infection at the time of pregnancy on the susceptibility outcome of children born in a community after implementation of MDA for the first time.

Methodology and Principal Findings

The participants in this cohort consists of pregnant mothers and their subsequently born children living in eight adjacent villages endemic for filarial infections, in Khurda District, Odisha, India, where MDA has reduced microfilariae (Mf) rate from 12% to 0.34%. Infection status of mother and their children were assessed by detection of Mf as well as circulating filarial antigen (CFA) assay. The present study reveals a high rate of acquiring filarial infection by the children born to infected mother than uninfected mothers even though Mf rate has come down to < 1% after implementation of ten rounds of MDA.

Significance

To attain the target of eliminating lymphatic filariasis the current MDA programme should give emphasis on covering the women of child bearing age. Our study recommends incorporating supervised MDA to Adolescent Reproductive and Sexual Health Programme (ARSH) to make the adolescent girls free from infection by the time of pregnancy so as to achieve the goal.     

Dynamics of spread of HIV-I infection in a rural district of Uganda.

OBJECTIVE--To define the geographical distribution of HIV infection and the community characteristics associated with HIV prevalence in a rural population of Uganda. DESIGN--Seroprevalence survey and interviews of the population aged 13 years and older in 21 randomly selected clusters. SETTING--Rural population of Rakai district, south west Uganda. SUBJECTS--1292 adults, of whom 594 men and 698 women gave a blood sample and answered the questionnaire. MAIN OUTCOME MEASURES--HIV status determined by ELISA and western blotting in relation to community characteristics. RESULTS--The weighted seroprevalence of HIV for the district was 12.6% with prevalence by cluster varying from 1.2% to 52.8%. Seroprevalence was highest in main road trading centres (men 26%, women 47%), intermediate in rural trading villages on secondary roads (men 22%, women 29%), and lowest in rural agricultural villages (men 8%, women 9%). For both men and women, multiple regression showed a strong negative association between cluster seroprevalence and the proportion of the population employed in agriculture (beta = -0.677 for men, -0.807 for women). Among women, cluster seroprevalence increased with a higher proportion of the population reporting multiple sex partners (beta = 0.814), external travel (beta = 0.579), and injections (beta = 0.483). CONCLUSIONS--Community characteristics, particularly the proportion of the population in agriculture, are associated with HIV prevalence and can be used for targeting interventions. The seroprevalences of HIV suggest spread of infection from main road trading centres, through intermediate trading villages, to rural agricultural villages.     

The impact of a filariasis control program on Lihir Island, Papua New Guinea

Background

Annual mass drug administration (MDA) over five years is the WHO''s recommended strategy to eliminate lymphatic filariasis (LF). Some experts, however, consider that longer periods of treatment might be necessary in certain high prevalence and transmission environments based upon past unsuccessful field experience and modelling.

Methodology/Principal Findings

To evaluate predictors of success in a LF control program we conducted an ecological study during a pre-existing MDA program. We studied 27 villages in Lihir Island, Papua New Guinea, from two areas with different infection rates before MDA. We undertook surveys to collect information on variables potentially having an influence on the outcome of the program, including epidemiological (baseline prevalence of infection, immigration rate), entomological (vector density) and operational (treatment coverage, vector control strategies) variables. The success in a village was defined using variables related to the infection (circulating filarial antigenemia prevalence <1%) and transmission (antigenemia prevalence <1 in 1000 children born since start of MDA). 8709 people were involved in the MDA program and average coverage rates were around 70%. The overall prevalence of filariasis fell from an initial 17.91% to 3.76% at round 5 (p<0.001). Viewed on a village by village basis, 12/27 (44%) villages achieved success. In multivariate analysis, low baseline prevalence was the only factor predicting both success in reducing infection rates (OR 19,26; CI 95% 1,12 to 331,82) and success in preventing new infections (OR 27,44; CI 95% 1,05 to 719,6). Low vector density and the use of an optimal vector control strategy were also associated with success in reducing infection rates, but this did not reach statistical significance.

Conclusions/Significance

Our results provide the data that supports the recommendation that high endemic areas may require longer duration MDA programs, or alternative control strategies.     

An open label,block randomized,community study of the safety and efficacy of co-administered ivermectin,diethylcarbamazine plus albendazole vs. diethylcarbamazine plus albendazole for lymphatic filariasis in India

BackgroundBetter drug regimens for mass drug administration (MDA) could accelerate the Global Programme to Eliminate Lymphatic Filariasis (LF). This community study was designed to compare the safety and efficacy of MDA with IDA (ivermectin, diethylcarbamazine and albendazole) or DA (diethylcarbamazine and albendazole) in India.Methodology/Principal findingsThis two-armed, open-labelled, block randomised, community study was conducted in LF endemic villages in Yadgir district, Karnataka, India. Consenting participants ≥5 years of age were tested for circulating filarial antigenemia (CFA) and microfilaremia (Mf) before treatment with a single oral dose of IDA or DA. Adverse events (AEs) were monitored actively for two days and passively for five more days. Persons with positive CFA or Mf tests at baseline were retested 12-months post-treatment to assess treatment efficacy.Baseline CFA and Mf-rates were 26.4% and 6.9% in IDA and 24.5% and 6.4% in DA villages respectively. 4758 and 4160 participants received IDA and DA. Most AEs were mild after both treatments; fewer than 0.1% of participants experienced AEs with severity > grade 1. No serious AEs were observed. Fever, headache and dizziness were the most common AEs. AE rates were slightly higher after IDA than DA (8.3% vs. 6.4%, P<0.01). AEs were more frequent in females and Mf-positives after either treatment, but significantly more frequent after IDA (40.5% vs 20.2%, P < 0.001).IDA was more effective for clearing Mf than DA (84% vs. 61.8%, P < 0.001). Geometric mean Mf counts per 60μl in retested Mf-positives decreased by 96.4% from 11.8 after IDA and by 90.0% from 9.5 after DA. Neither treatment was effective for clearing CFA.Conclusions/SignificanceIDA had an acceptable safety profile and was more effective for clearing Mf than DA. With adequate compliance and medical support to manage AEs, IDA has the potential to accelerate LF elimination in India.Trial registrationClinical Trial Registry of India (CTRI No/2016/10/007399)     

A survey of Brugia malayi infection on the Heugsan Islands,Korea

Lymphatic filariasis due to Brugia malayi infection was endemic in several areas of South Korea. The infection was controlled, or disappeared, in most areas, with the exception of the remote southwestern islands of Jeonranam-do, including the Heugsan Islands. To discover its current situation, a small-scale survey was performed on the Heugsan Islands in September 2000. A total of 378 people, 151 male and 227 female, living in 8 villages (6 on Daeheugsan-do, 1 on Daejang-do, and 1 on Yeongsan-do) were subjected to a night blood survey for microfilaremia, and physical examination for elephantiasis on the extremities. There were 6 (1.6%) microfilaria positive cases, all in females aged 57-72 years, and from only two villages of the Daeheugsan-do area. There were 4 patients with lower leg elephantiasis, but they showed no microfilaremia. The results show that a low-grade endemicity of filariasis remains on the Daeheugsan-do.     

Schistosomiasis in Indonesia: past and present

Schistosomiasis is endemic in Indonesia in two isolated areas, Lindu valley and Napu valley, both located in the Province of Central Sulawesi. In 1940, a prevalence survey was initiated in Lake Lindu, which indicated a Schistosoma japonicum infection prevalence of 56% among the population of Anca, Tomado and Langko villages. Another survey was conducted in 1973 in Napu valley and very high infection prevalences of up to 72% were found among the population in Winowanga village. Since then, comprehensive studies on the epidemiology and the effects of control have been carried out in 24 endemic villages in both areas. Over the past six decades, schistosomiasis control has been implemented and the average prevalence is now much lower than before the control programme was launched. In 2006, it was 0.49% in 7 villages in Lindu valley. In Napu valley, the average infection prevalence among the population of 17 villages was 1.08% in the same year. Again in 2006, the prevalence of infection in snails ranged from 0 to 13.4% and from 0 to 9.1% in Napu and Lindu valleys, respectively. The highest prevalence among snails was found in Dodolo village. The prevalence of S. japonicum in the reservoir host Rattus spp. ranged from 0 to 20% and the highest prevalence was again found in Dodolo village. Contemporary data suggest that transmission of schistosomiasis is still ongoing in Indonesia despite regular surveillance and control activities covering the whole endemic area.     

Control of lymphatic filariasis by annual single-dose diethylcarbamazine treatments

It has long been stressed that diethylcarbamazine citrate must be given at a total dosage of 72 mg per kilogram of body weight in 12 divided doses of 6 mg kg(-1) to obtain maximum effect against Wuchereria bancrofti. However, recent studies revealed that only a single dose at 6 mg kg(-1) could reduce microfilaria (Mf) counts by 90%, and that the effect would persist for 12-18 months. The annual repeat of the single-dose mass treatment was shown to be effective in reducing Mf prevalence and density in large-scale, long-term field trials. The scheme is simple and economic, and could be sustainable in many endemic areas, where health manpower and resources are often not sufficient. Annual single-dose mass treatments can be an effective weapon against human lymphatic filariasis, as discussed here by Eisaku Kimura and Jona Mataika.     

The Impact of Repeated Rounds of Mass Drug Administration with Diethylcarbamazine Plus Albendazole on Bancroftian Filariasis in Papua New Guinea

Background

This study employed various monitoring methods to assess the impact of repeated rounds of mass drug administration (MDA) on bancroftian filariasis in Papua New Guinea, which has the largest filariasis problem in the Pacific region.

Methodology/Principal Findings

Residents of rural villages near Madang were studied prior to and one year after each of three rounds of MDA with diethylcarbamazine plus albendazole administered per World Health Organization (WHO) guidelines. The mean MDA compliance rate was 72.9%. Three rounds of MDA decreased microfilaremia rates (Mf, 1 ml night blood by filter) from 18.6% pre-MDA to 1.3% after the third MDA (a 94% decrease). Mf clearance rates in infected persons were 71%, 90.7%, and 98.1% after 1, 2, and 3 rounds of MDA. Rates of filarial antigenemia assessed by card test (a marker for adult worm infection) decreased from 47.5% to 17.1% (a 64% decrease) after 3 rounds of MDA. The filarial antibody rate (IgG₄ antibodies to Bm14, an indicator of filarial infection status and/or exposure to mosquito-borne infective larvae) decreased from 59.3% to 25.1% (a 54.6% decrease). Mf, antigen, and antibody rates decreased more rapidly in children <11 years of age (by 100%, 84.2%, and 76.8%, respectively) relative to older individuals, perhaps reflecting their lighter infections and shorter durations of exposure/infection prior to MDA. Incidence rates for microfilaremia, filarial antigenemia, and antifilarial antibodies also decreased significantly after MDA. Filarial DNA rates in Anopheles punctulatus mosquitoes that had recently taken a blood meal decreased from 15.1% to 1.0% (a 92.3% decrease).

Conclusions/Significance

MDA had dramatic effects on all filariasis parameters in the study area and also reduced incidence rates. Follow-up studies will be needed to determine whether residual infection rates in residents of these villages are sufficient to support sustained transmission by the An. punctulatus vector. Lymphatic filariasis elimination should be feasible in Papua New Guinea if MDA can be effectively delivered to endemic populations.     

Effects of 5 rounds of mass drug administration with diethylcarbamazine and albendazole on filaria-specific IgG4 titers in urine: 6-year follow-up study in Sri Lanka

ELISA for filaria-specific IgG4 in urine (urine ELISA) was applied to children in 7 schools in Sri Lanka, before and after 5 rounds of annual mass drug administration (MDA). The pre-treatment IgG4 prevalence in 2002 was 3.20%, which decreased to 0.91% in 2003 after the first MDA (P<0.001), and finally to 0.36% in 2007 after the 5th MDA. Among 5-10 year-old children, the prevalence decreased from 3.37% in 2002 to 0.51% in 2003 (P=0.009). A pattern of IgG4 titer distribution according to age and its yearly change could also provide useful information in drug efficacy analysis. In 2008, new samples from eleven 2006/07 urine ELISA-positive students and their family members (total n=56) were examined by ICT antigen test, microfilaria test, and urine ELISA. No infection was confirmed among them. Urine ELISA will be useful in monitoring elimination/resurgence in a post-MDA low endemic situation.     

Epidemiological and entomological evaluations after six years or more of mass drug administration for lymphatic filariasis elimination in Nigeria

The current strategy for interrupting transmission of lymphatic filariasis (LF) is annual mass drug administration (MDA), at good coverage, for 6 or more years. We describe our programmatic experience delivering the MDA combination of ivermectin and albendazole in Plateau and Nasarawa states in central Nigeria, where LF is caused by anopheline transmitted Wuchereria bancrofti. Baseline LF mapping using rapid blood antigen detection tests showed mean local government area (LGA) prevalence of 23% (range 4-62%). MDA was launched in 2000 and by 2003 had been scaled up to full geographic coverage in all 30 LGAs in the two states; over 26 million cumulative directly observed treatments were provided by community drug distributors over the intervention period. Reported treatment coverage for each round was ≥85% of the treatment eligible population of 3.7 million, although a population-based coverage survey in 2003 showed lower coverage (72.2%; 95% CI 65.5-79.0%). To determine impact on transmission, we monitored three LF infection parameters (microfilaremia, antigenemia, and mosquito infection) in 10 sentinel villages (SVs) serially. The last monitoring was done in 2009, when SVs had been treated for 7-10 years. Microfilaremia in 2009 decreased by 83% from baseline (from 4.9% to 0.8%); antigenemia by 67% (from 21.6% to 7.2%); mosquito infection rate (all larval stages) by 86% (from 3.1% to 0.4%); and mosquito infectivity rate (L3 stages) by 76% (from 1.3% to 0.3%). All changes were statistically significant. Results suggest that LF transmission has been interrupted in 5 of the 10 SVs, based on 2009 finding of microfilaremia ≥1% and/or L3 stages in mosquitoes. Four of the five SVs where transmission persists had baseline antigenemia prevalence of >25%. Longer or additional interventions (e.g., more frequent MDA treatments, insecticidal bed nets) should be considered for 'hot spots' where transmission is ongoing.     

Secondary Mapping of Lymphatic Filariasis in Haiti-Definition of Transmission Foci in Low-Prevalence Settings

To eliminate Lymphatic filariasis (LF) as a public health problem, the World Health Organization (WHO) recommends that any area with infection prevalence greater than or equal to 1% (denoted by presence of microfilaremia or antigenemia) should receive mass drug administration (MDA) of antifilarial drugs for at least five consecutive rounds. Areas of low-antigen prevalence (<1%) are thought to pose little risk for continued transmission of LF. Five low-antigen prevalence communes in Haiti, characterized as part of a national survey, were further assessed for transmission in this study. An initial evaluation of schoolchildren was performed in each commune to identify antigen-positive children who served as index cases for subsequent community surveys conducted among households neighboring the index cases. Global positioning system (GPS) coordinates and immunochromatographic tests (ICT) for filarial antigenemia were collected on approximately 1,600 persons of all ages in the five communes. The relationship between antigen-positive cases in the community and distance from index cases was evaluated using multivariate regression techniques and analyses of spatial clustering. Community surveys demonstrated higher antigen prevalence in three of the five communes than was observed in the original mapping survey; autochthonous cases were found in the same three communes. Regression techniques identified a significantly increased likelihood of being antigen-positive when living within 20 meters of index cases when controlling for age, gender, and commune. Spatial clustering of antigen-positive cases was observed in some, but not all communes. Our results suggest that localized transmission was present even in low-prevalence settings and suggest that better surveillance methods may be needed to detect microfoci of LF transmission.     

Mansonella ozzardi in the Federal Territory of Roraima, Brazil. Distribution and finding of a new vector in the area of Surumu River

A survey conducted among the Makuxi Indians from 15 settlements in the northeastern part of the Territory of Roraima, Brazil, revealed the occurrence of Mansonella ozzardi in 3,2% (21/652) of the persons examined. The absence of demonstrable infection--with one exception--in persons under 15 years of age, and the low microfilaria density in adults suggest that mansonelliasis has been acquired by the Makuxi Indians outside their villages. As many Indians from the region pan gold on the Upper Maú (Ireng) river--where black flies occur in great quantity--the mining camps are probably the sites of transmission. Experimental infection with M. ozzardi of Simulium oyapockense s.l. (or Simulium roraimense) showed that this species, at the least in the Surumu river area, is capable of supporting the full development of the microfilariae. Although S. oyapockense has a wide distribution in the extreme north of Brazil, it does not appear to be an efficient vector, since only 20,6% (19/92) of the specimens collected after a blood meal on a naturally infected Indian contained larval stages of M. ozzardi (with an average of 1-2 larvae per fly). The high prevalence rate of infection found, in a previous survey, among the Sanumá and Mayongong, two Indian groups living at the Auaris river area, on the other side of the Territory of Roraima, indicates that a more competent intermediate host should exist in that region.