Fig 1 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Map of Samoa with administrative region boundaries and selected villages. https://doi.org/10.1371/journal.pntd.0008854.g001
Source publication
The Global Programme to Eliminate Lymphatic Filariasis has made considerable progress but is experiencing challenges in meeting targets in some countries. Recent World Health Organization guidelines have recommended two rounds of triple-drug therapy with ivermectin, diethylcarbamazine (DEC), and albendazole (IDA), in areas where mass drug administr...
Contexts in source publication
Context 1
... were sampled from 35 primary sampling units (PSUs) located throughout Upolu, Savai'i, and Manono Islands (Fig 1). Five PSUs were purposively sampled (three in NWU, one in ROU, and one in SAV) in consultation with the Samoa MOH, as they were suspected to be transmission 'hotspots' based on local knowledge and results of previous surveys. ...
Context 2
... performed descriptive analyses to estimate reported MDA program awareness, reach, coverage, and compliance, as well as reported adverse events. S1 Fig and S5 Table show the flowchart and formulae for deriving each of the metrics. We used Chi-squared tests to compare proportions between population sub-groups and Clopper-Pearson binomial exact methods to estimate 95% confidence intervals (CI). ...
Citations
... 30 , 31 A study in Samoa found higher antigen prevalence (5.8%) among participants who reported never taking MDA compared with those who reported taking MDA at least once (4.9%), but the difference was not statistically significant. 32 In Myanmar, significantly higher infection rates among the never treated in a univariate analysis did not hold when other factors were controlled for in a multiple regression analysis. 37 ...
As neglected tropical disease programs rely on participation in rounds of mass drug administration (MDA), there is concern that individuals who have never been treated could contribute to ongoing transmission, posing a barrier to elimination. Previous research has suggested that the size and characteristics of the never-treated population may be important but have not been sufficiently explored. To address this critical knowledge gap, four meetings were held from December 2020 to May 2021 to compile expert knowledge on never treatment in lymphatic filariasis (LF) MDA programs. The meetings explored four questions: the number and proportion of people never treated, their sociodemographic characteristics, their infection status and the reasons why they were not treated. Meeting discussions noted key issues requiring further exploration, including how to standardize measurement of the never treated, adapt and use existing tools to capture never-treated data and ensure representation of never-treated people in data collection. Recognizing that patterns of never treatment are situation specific, participants noted measurement should be quick, inexpensive and focused on local solutions. Furthermore, programs should use existing data to generate mathematical models to understand what levels of never treatment may compromise LF elimination goals or trigger programmatic action.
... Available literature reveals that several studies reported coverage estimates (on DA) using different methodologies making it difficult to compare the estimates [19][20][21][22][23]. The present study is one of the few studies which assessed coverage using the WHO-CSB tool following inclusion of ivermectin in MDA in India [19][20][21][22][23][24]. One of the limitations was that the responses were self-reported and depend on the recall memory of participants. ...
Background
Triple drug regimen (IDA; Ivermectin, Diethylcarbamazine, Albendazole) recommended for accelerating elimination of lymphatic filariasis was launched in India in December 2018. Nagpur district in Maharashtra was one of the first five districts where this strategy was introduced. The National Vector Borne Disease Control Programme (NVBDCP) at the district reported ~85.0% treatment coverage in the first round of mass drug administration (MDA) with IDA implemented in EU-2 in Nagpur district in January 2019. As per the national guideline, a coverage evaluation survey was carried out and both quantitative and qualitative data were collected to assess the treatment coverage, the level of community preparation and identify the gaps, if any, for improvement.
Methodology
A Coverage Evaluation Survey (CES) following the WHO recommended protocol was conducted in one of the two evaluation units (EU-2) in Nagpur district in March 2019. Coverage Sample Builder (CSB) V2.9 tool was used to calculate the sample size, select sites and estimate drug coverage. The CSB tool followed a two-stage cluster sampling procedure to select 30 primary sampling units (ward/village as a cluster) and a list of random numbers for selecting households (HHs) in each cluster. The results were analyzed for operational indicators. Stata ver. 14.0 software was used to construct the 95% confidence limits accounting for clustering.
Results
A total of 1601 individuals aged 5–85 years of both gender from 328 HHs were surveyed from the 30 randomly selected clusters in EU-2. The mean age was 33.8±17.6 years. Among the surveyed population, 78.0% received the drugs (programme reach) and 66.1% consumed the drugs (survey coverage). Survey coverage was significantly higher in rural (82.6%) than in urban (59.4%) and peri-urban (58.6%) areas (P<0.001). Directly observed treatment (DOT) among the surveyed population was 51.6%. Adverse events were reported among 6.9% respondents who reported to have consumed the drugs.
Conclusion
The IDA based MDA strategy could achieve just the required level of treatment coverage (~65%) in EU-2, Nagpur district, which had previously undergone several rounds of DA-MDAs (Diethylcarbamazine, Albendazole). Having achieved an effective treatment coverage of >80% in rural areas, the coverage in urban and peri-urban areas need to be improved in order to attain the impact of IDA-MDA. It is imperative to strengthen drug delivery and community preparation activities along with improved DOT especially in urban and peri-urban areas to achieve the required level of treatment coverage. Addition of ivermectin did not have any additional perceived adverse events.
... The key epidemiological parameters often used to monitor and evaluate the success of control programmes can be divided into three key decision points of individual MDA behaviour as recorded in Fig 1, defining the interaction between a community drug distributor (CDD) and participant [8]. Similar decision trees have been published to help clearly define these parameters [9,10]. In this review (and in keeping with the terminology previously employed [8,11]), the term coverage is used to refer to the proportion of the eligible population contacted by the CDD, who received the offered drugs. ...
Repeated distribution of preventative chemotherapy (PC) by mass drug administration forms the mainstay of transmission control for five of the 20 recognised neglected tropical diseases (NTDs); soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. The efficiency of such programmes is reliant upon participants swallowing the offered treatment consistently at each round. This is measured by compliance, defined as the proportion of eligible participants swallowing treatment. Individually linked longitudinal compliance data is important for assessing the potential impact of MDA-based control programmes, yet this accurate monitoring is rarely implemented in those for NTDs. Longitudinal compliance data reported by control programmes globally for the five (PC)-NTDs since 2016 is examined, focusing on key associations of compliance with age and gender. PubMed and Web of Science was searched in January 2022 for articles written in English and Spanish, and the subsequent extraction adhered to PRISMA guidelines. Study title screening was aided by Rayyan, a machine learning software package. Studies were considered for inclusion if primary compliance data was recorded for more than one time point, in a population larger than 100 participants. All data analysis was conducted in R. A total of 89 studies were identified containing compliance data, 57 were longitudinal studies, of which 25 reported individually linked data reported by varying methods. The association of increasing age with the degree of systematic treatment was commonly reported. The review is limited by the paucity of data published on this topic. The varying and overlapping terminologies used to describe coverage (receiving treatment) and compliance (swallowing treatment) is reviewed. Consequently, it is recommended that WHO considers clearly defining the terms for coverage, compliance, and longitudinal compliance which are currently contradictory across their NTD treatment guidelines. This review is registered with PROSPERO (number: CRD42022301991).
... Population coverage was sub-optimal in the early campaigns but was over 65% in the five most recent rounds of MDA [11]. Programmatic coverage for the 2018 triple-drug MDA was 83.9% of the eligible population [12]. However, programmatic surveys in 2013 and 2017 [11] and research projects in 2018 [13] showed ongoing transmission. ...
... However, programmatic surveys in 2013 and 2017 [11] and research projects in 2018 [13] showed ongoing transmission. In 2018, Samoa was the first country to distribute nationwide triple-drug MDA (ivermectin, albendazole and diethylcarbamazine) [12]. Evaluating the effectiveness of this intervention is therefore of interest globally, but a key challenge is the ability to detect reductions in human infection prevalence post-MDA. ...
Molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), is a potentially useful surveillance strategy for lymphatic filariasis (LF) elimination programs. Delay in filarial antigen (Ag) clearance post-treatment is a limitation of using human surveys to provide an early indicator of the impact of mass drug administration (MDA), and MX may be more useful in this setting. We compared prevalence of infected mosquitoes pre- and post-MDA (2018 and 2019) in 35 primary sampling units (PSUs) in Samoa, and investigated associations between the presence of PCR-positive mosquitoes and Ag-positive humans. We observed a statistically significant decline in estimated mosquito infection prevalence post-MDA at the national level (from 0.9% to 0.3%, OR 0.4) but no change in human Ag prevalence during this time. Ag prevalence in 2019 was higher in randomly selected PSUs where PCR-positive pools were detected (1.4% in ages 5–9; 4.8% in ages ≥10), compared to those where PCR-positive pools were not detected (0.2% in ages 5–9; 3.2% in ages ≥10). Our study provides promising evidence for MX as a complement to human surveys in post-MDA surveillance.
... According to the WHO's 2021 report, 859 million people in 50 countries are at risk of lymphatic filariasis, which requires preventive treatment. As a result, the WHO revised the target date to 2030, using a triple-drug MDA combination of IVM, DEC citrate, and ALB (IDA-MDA), which may result in patient non-compliance [65][66][67][68]. This evidence demands the development of effective vaccines and novel therapeutics. ...
Human lymphatic filariae have evolved numerous immune evasion strategies to secure their long-term survival in a host. These strategies include regulation of pattern recognition receptors , mimicry with host glycans and immune molecules, manipulation of innate and adaptive immune cells, induction of apoptosis in effector immune cells, and neutralization of free radicals. This creates an anti-inflammatory and immunoregulatory milieu in the host: a modified Th2 immune response. Therefore, targeting filarial immunomodulators and manipulating the filariae-driven immune system against the filariae can be a potential therapeutic and prophylactic strategy. Filariae-derived immunosuppression can also be exploited to treat other inflammatory diseases and im-munopathologic states of parasitic diseases, such as cerebral malaria, and to prevent leishmaniasis. This paper reviews immunomodulatory mechanisms acquired by these filariae for their own survival and their potential application in the development of novel therapeutic approaches against parasitic and inflammatory diseases. Insight into the intricate network of host immune-parasite interactions would aid in the development of effective immune-therapeutic options for both infectious and immune-pathological diseases.
... So, eradication of this disease, which is endemic in over 50 countries, is crucial. (6,18,(40)(41)(42)29,(33)(34)(35)(36)(37)(38)(39) In this systematic review and meta-analysis, we assessed the efficacy and safety of IDA in microfilariae filtration and so on the elimination of LF. ...
Objective
Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis.
Methods
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple to dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724).
Results
We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; P= 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; P= 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared to the dual therapy group.
Conclusion
Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.
... Population coverage was not optimal in the early campaigns but was over 65% in the five most recent rounds of MDA [12]. Programmatic coverage for the 2018 tripledrug MDA was 83.9% of the eligible population [13]. However, programmatic surveys in 2013 and 2017 [12] and research projects in 2018 [14] showed ongoing transmission. ...
... However, programmatic surveys in 2013 and 2017 [12] and research projects in 2018 [14] showed ongoing transmission. In 2018, Samoa was the first country to distribute nation-wide triple-drug MDA (ivermectin, albendazole and diethylcarbamazine) [13]. Evaluating the effectiveness of this intervention is therefore of interest globally, but a key challenge is the ability to detect reductions in infection prevalence post-MDA. ...
Molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), is a potentially useful surveillance strategy for lymphatic filariasis (LF) elimination programs. Delay in filarial antigen (Ag) clearance post-treatment limits the usefulness of human surveys as an early indicator of the effectiveness of mass drug administration (MDA), and MX may be more sensitive in this setting. We compared prevalence of infected mosquitoes pre- and post-MDA (2018 and 2019) in Samoa, and investigated associations between presence of PCR-positive mosquitoes and Ag-positive humans. We observed a statistically significant decline in mosquito infection prevalence post-MDA, but no change in human Ag prevalence during this time. Presence of PCR-positive pools of ‘all species’ was most sensitive (78.6%) for detecting villages with Ag-positive humans, while Ae. polynesiensis provided the highest positive predictive value (81.8%). Our study provides promising evidence for MX as a complement to human surveys in post-MDA surveillance.
... Population coverage was not optimal in the early campaigns but was over 65% in the five most recent rounds of MDA [12]. Programmatic coverage for the 2018 tripledrug MDA was 83.9% of the eligible population [13]. However, programmatic surveys in 2013 and 2017 [12] and research projects in 2018 [14] showed ongoing transmission. ...
... However, programmatic surveys in 2013 and 2017 [12] and research projects in 2018 [14] showed ongoing transmission. In 2018, Samoa was the first country to distribute nation-wide triple-drug MDA (ivermectin, albendazole and diethylcarbamazine) [13]. Evaluating the effectiveness of this intervention is therefore of interest globally, but a key challenge is the ability to detect reductions in infection prevalence post-MDA. ...
Molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), is a potentially useful surveillance strategy for lymphatic filariasis (LF) elimination programs. Delay in filarial antigen (Ag) clearance post-treatment is a limitation of using human surveys to provide an early indicator of the impact of mass drug administration (MDA), and MX may be more useful in this setting. We compared prevalence of infected mosquitoes pre- and post-MDA (2018 and 2019) in 35 primary sampling units (PSUs) in Samoa, and investigated associations between presence of PCR-positive mosquitoes and Ag-positive humans. We observed a statistically significant decline in mosquito infection prevalence post-MDA at the National Level (from 0.9% to 0.3%, OR 0.4) but no change in human Ag prevalence during this time. Antigen prevalence was higher in randomly selected PSUs where PCR-positive pools were detected (1.4% in ages 5-9; 4.8% in ages ³10), compared to those where PCR-positive pools were not detected (0.2% in ages 5-9; 3.2% in ages ³10). Presence of PCR-positive pools of ‘all species’ was most sensitive (78.6%) for detecting villages with Ag-positive humans, while Ae. polynesiensis provided the highest positive predictive value (81.8%). Our study provides promising evidence for MX as a complement to human surveys in post-MDA surveillance.
... After failing a TAS in one evaluation unit in 2013, two further targeted rounds of MDA were distributed in that area only in 2015 and 2017, but all three evaluation units in Samoa failed TAS-2 later in 2017. Due to apparently resurging antigen prevalence back to 1999 levels, the country initiated triple-drug MDA with the first nationwide distribution successfully completed in August 2018 [17]. ...
... A large population representative LF community survey as part of the Surveillance and Monitoring for Elimination of LF and Scabies in Samoa (SaMELFS) project was conducted in Oct-Nov 2018, 8-11 weeks after the August 2018 MDA, and showed age-and gender-standardized antigen prevalence of 4.0% (95% CI 2.8-5.6%) in 3940 participants aged 5 years and over [9]. The MDA coverage was reported to be very good with 80.2% of the total population reporting taking MDA [17]. Amongst the 122 Ag-positive participants, slides were available for 121 (99.2%) [9], and 18 (14.9%) ...
... Each person was weighed by a doctor or nurse using medical-grade scales. Treatment with ivermectin (150-200 ug/kg, Merck), DEC (6 mg/kg, Eisai), and albendazole (one 400mg tablet, GSK) was provided according to weight as per the Samoa Ministry of Health 2018 MDA schedule [17] shown in Table 1. Medications were donated for the triple drug MDA in 2018 by Merck, Eisai and GSK and provided through WHO. ...
Following the first triple-drug mass drug administration (MDA) for lymphatic filariasis in Samoa in 2018, unexpected persistence of microfilaria (Mf) positivity in 18 (15%) of 121 antigen-positive persons was observed in a nationwide household survey 1–2 months later. Of the 18 Mf positive persons, 14 reported taking the MDA, raising concerns about MDA efficacy. In 2019, 5–6 months after the 2018 survey, a monitored treatment study was done to evaluate directly observed weight-based treatment in these Mf positive individuals. Mf presence and density were assessed before and 7 days after treatment, using 1 mL membrane filtered venous blood, and 60uL thick blood films on slides prepared from venous or fingerprick blood. All 14 participants were still Mf positive on filters from venous blood pre-treatment samples, but two were negative by slide made from the same samples. Mf were cleared completely by day 7 in 12 of 13 participants followed up, and by day 30 in the remaining participant. Filtered blood using EDTA samples (to reduce clumping of Mf) is preferred over slides alone for improving the likelihood of detecting Mf and estimating their density. The triple-drug MDA strategy was effective at clearing Mf when given and taken at the correct dose.
... After failing a TAS in one evaluation unit in 2013, two further targeted rounds of MDA were distributed in that area only in 2015 and 2017, but all three evaluation units in Samoa failed TAS-2 later in 2017. Due to apparently resurging antigen prevalence back to 1999 levels, the country initiated triple-drug MDA with the first nationwide distribution successfully completed in August 2018 [17]. ...
... A large population representative LF community survey as part of the Surveillance and Monitoring for Elimination of LF and Scabies in Samoa (SaMELFS) project was conducted in Oct-Nov 2018, 8-11 weeks after the August 2018 MDA, and showed age-and genderstandardized antigen prevalence of 4.0% (95% CI 2.8-5.6%) in 3940 participants aged 5 years and over [9]. The MDA coverage was reported to be very good with 80.2% of the total population reporting taking MDA [17]. Amongst the 122 Ag-positive participants, slides were available for 121 (99.2%) [9], and 18 (14.9%) ...
... Each person was weighed by a doctor or nurse using medical-grade scales. Treatment with ivermectin (150-200 ug/kg, Merck), DEC (6 mg/kg, Eisai), and albendazole (one 400 mg tablet, GSK) was provided according to weight as per the Samoa Ministry of Health 2018 MDA schedule [17] shown in Table 1. Medications were donated for the triple drug MDA in 2018 by Merck, Eisai and GSK and provided through WHO. ...
Following the first triple-drug MDA for lymphatic filariasis in Samoa in 2018, unexpected persistence of Mf-positivity in 18 (15%) of 121 antigen-positive persons was observed in a nationwide household survey 1-2 months later, raising concerns about MDA efficacy. In 2019, a monitored treatment study was done before and 7 days after directly observed weight-based treatment. Mf presence and density were evaluated using 1 mL membrane filtered venous blood, and 60uL thick blood films on slides prepared from venous or fingerprick blood. All 14 participants were still Mf positive on filters from venous blood pre-treatment samples, but two were negative by slide made from the same samples. Mf were cleared completely by day 7 in 12 of 13 participants followed up, and by day 30 in the remaining participant. Filtered blood using EDTA samples (to reduce clumping of Mf) is preferred over slides alone for improving the likelihood of detecting Mf and estimating their density. The triple-drug MDA strategy was effective at clearing Mf by day 30 when given and taken at the correct dose.
