Table 4.

Details  of the studies where monitoring was done post-MDA

Study no.	Region	Country	Author & year	No. of districts or villages or sites	No. of people/mosquitoes tested	Age (years)	Indicator	Findings
1	Americas	Haiti	Chu et al, 2013122	11 countries	29,169 children	6–7	Ag and Ab prevalence	This study was carried out to assess the revised TAS protocol in its ability to make decisions to stop MDA and also to be used as a post-MDA surveillance tool. While Burkino Faso, Dominican republic, Ghana, Indonesia, Malaysia and Tanzania were in to make decision on stopping MDA, rest of the countries were already in the post_MDA scenario. The diagnostic tools used were ICT for W.bancrofti regions, and PanLF for TAS 1 or BMR1 for Brugia spp endemic areas. Sample sizes for these surveys were obtained through SSB (range: 684 in Sri Lanka to 1556 in Burkino Faso). Either school based or community based surveys were adopted. The authors suggest that TAS based on communities face several challenges than the ones based on school survey main reason being poor census, definition of EA boundaries, estimation of target age group etc., Preliminary results from separate TAS studies appear to suggest there is no statistically significant difference or change in the TAS-recommended outcome for EUs with school primary enrolment rates as low as 59% instead of the current 75% (Gass et al, 2013). The results of this study supports the reliability of this strategy but because TAS is not powered to detect change or designed to identify hotspots, post-MDA surveillance would best be complemented in the short and long term with other, complementary diagnostic tests and surveillance methods. In future, if new diagnostic tools are to be used, then the thresholds and the sample sizes may need to be modified.
2	South East Asia	India	Srivastava et al, 2014123	42 primary schools in Goa	1692 children	6–7	Ag prevalence	The study from Goa, describes the first time implementation of the revised TAS in India. Goa, one of the historically LF endemic districts in India, started the MDA against LF in the year 2000. Four rounds of MDA with DEC alone and 5 with DEC+albendazole were completed. Post-treatment MF survey showed that Mf rates in sentinel and spot check sites were 0. In 2013 Mf surveys in additional 10 randomly selected sites also showed 0 Mf prevalence. These observations showed that the district was eligible for TAS. A sample of 1692 (based on the SSB tool for TAS by WHO), children aged 6–7 years were tested for Ag (ICT) of which only 16 were positive, less than the cut-off value of 20, indicating passing of TAS. MDA was stopped and the district is now in the post_MDA surveillance mode. The authors conclude that TAS is a scientific, practical and effective evaluation tool for decisions on stopping or continuing MDA.
3	Africa	Tanzania	Biritwuma et al, 2017124	98 endemic districts of Ghana	Not mentioned	All ages	Ab prevalence	The study describes the existence of persistent LF hotspots inspite of 14 rounds of MDA . The study aimed to compare the baseline Mf prevalence and anti_filariasis interventions (LLINs) among hotspots and those districts where MDA was stopped. The study population were from the 29 hotspot districts and 69 stopped-MDA districts. The data collected were the baseline Mf prevalences and data on distribution of LLINs to the population. Assessing LF status at baseline, during MDA implementation and the status in 2016 showed that by 2014 69 districts had stopped MDA and by 2016 another 12 more stopped MDA after TAS. Results show that the number of rounds of MDA required for hotspots were higher than those districts where the MDA was stopped. It was also observed that the baseline MF prevalence in these hotspot districts were 10 time higher that those districts in which MDA has been stopped. The authors indicated that these observations may have implication on programme stating the districts with high baseline MF prevalence may require more than the recommended 5–6 rounds of MDA compared those with low baseline prevalence.
4	Western Pacific	American Samoa	Shamsuzzaman et al, 2017125	34 districts (19 endemic and 15 low endemic)	136,080 children	6–7	Ag prevalence	This paper presents TAS results, highlighting the momentous geographical reduction in risk of LF and its contribution to the global elimination target of 2020. Since 2011, a total of 59 TAS have been conducted in 26 EUs across the 19 endemic MDA districts (99,148 students tested from 1,801 schools), and 22 TAS in the 15 low endemic non-MDA districts (36,932 students tested from 663 schools). All endemic MDA districts passed TAS, except in Rangpur which required two further rounds of MDA.The distribution was geographically sparse, with only two small focal areas showing potential evidence of persistent transmission. Bangladesh is now considered to have very low or no risk of LF infection after 15 years of programmatic activities, and is on track to meet elimination targets.Other positive influencing factors for Bangladesh include good administrative development and health system infrastructure, relative political stability, strong political commitment and financial support, strong program management leadership, heightened awareness of morbidity in the endemic areas, which helped to increase drug compliance and importance of disease elimination.
5	Western Pacific	Papua New Guinea	Khieu et al, 2018126	Four sites (two sentinel and two spot check)	Not mentioned	≥5	Ab prevalence	In this study, as a first step towards LF elimination, mapping exercise was carried out in all provinces and districts, based on Ag surveys during 2000–2002. Any province with even one Ag positive as endemic. Two provinces and four districts in two other provinces classified as endemic due to the focal nature of LF. MDA with DEC and albendazole was initiated in 2005 through 2009 completing five rounds with effective coverage of 65%. In sentinel sites, Mf surveys were conducted during baseline and 2nd, 3rd and 4th years and also after the final round of MDA in 2009. In spot-check sites, mf surveys were carried out during 2nd, 3rd and 4th round of MDA. It was observed that Mf prevalence became 0% from third survey onwards and in sentinel sites it was 0% in all surveys. Hence TAS was conducted following the WHO norms and it was found that the Ag prevalence in six IUs (two provinces and four districts) ranged between 0.1 and 0.7%, much below the 1% level indicating interruption of transmission. MDA was stopped in these provinces and districts. Post MDA surveillance surveys TAS 2 on grade 1 children (after 2–3 eaof stopping MDA) and TAS 3 (after 46 years of stopping MDA) were conducted in 2013 and 2015 respectively. In both, there were no Ag positive child in both TAS2 and TAS3 surveys suggesting total transmission interruption in the IUs. To ensure this, TAS 3 with an antibody survey of children in one of the historically known LF endemic district was carried out and only one child was positive substantiating the earlier finding tha that transmission has been interrupted. Having passed TAS3, as the final stage of declaring elimination of LF, in 2015 the MoH prepared the dossier documenting elimination of LF as a public health problem and submitted to WHO which was validated by the Regional Dossier Review Group of WHO Western Pacific Regional office. In 2016, WHO headquarters officially acknowledged that LF elimination was achieved in Combodia.
6	South East Asia	Nepal	Ojha et al, 2017127	Five districts	9495 children	6–9	Ag prevalence	This study in Nepal provides findings of the Pre-TAS, TAS and drug coverage surveys conducted after 6 rounds of MDA to assess if the LF transmission has been interrupted or not. The Study was conducted in 7 of the 10 endemic districts (selected purposively) prior implementing MDA. From each districts, 2 sentinel sites were selected (Based on migration, population size and LF prevalence). All sentinel and spot check sites in districts in five districts and one spot check site of another district reported <2% Ag prevalence. Remaining 4 districts reported >2% Ag in the pre-TAS surveys. None of these four districts at achieve epidemiological coverage of ≥65% MDA coverage. TAS was conducted in all these five districts and a part of the 6th district (it was split into two EUs) and all passed TAS (number of Ag positive children less the cut-off value). The results suggest that the LF transmission was interrupted in the 5th and partly in 6th district and that MDA may be stopped in these. However in the remaining four, additional rounds of MDA may be necessary. out of the 10 district. Though the MDA coverage varied between the districts (50%-84%) they still passed TAS suggesting that a MDA coverage of around 50% may be sufficient to interrupt LF transmission in urban populations. However, in sptie of high coverage, four rural districts failed to pass TAS and these had the high baseline LF prevalence. These findings corroborate with the finding of Shamsuzzaman et al, 2017 described earlier.
7	South East Asia	Myanmar	Aye et al, 2018128	19 districts	In 206 schools in 5 districts	>2	Ag prevalence	This study also, like the previous one summarizes the programmatic activities right from mapping endemic districts to post-MDA surveillance of LF, the progress and impact of the those activities and highlights the first evidence that prevalence has been lowered to a level when transmission is not sustainable. Data for this study was from 15 administrative units of Myanmar, consisting of 65 districts. Mapping exercise in 19 districts and historical data showed that 45 districts were endemic for LF. Starting MDA in only two districts in 2001, it was upscaled to all 45 endemic districts by 2014 so the number of MDAs completed ranged between 2 and 12 in different districts. Seven years after the start of MDA, the first TAS wasconducted in three districts and subsequently in other districts too. TAS passed in 5 districts and MDA was stopped, but monitoring continued in these IUs for next 5 years. The results of this study highlights that Myanmar NPELF has moved forward towards elimination of LF and significant reduction in Mf prevalence and with evidence for interruption of transmission.
8	South East Asia	India	Swaminathan et al, 2012129	Two Primary Health Centres	35,582 persons	All ages	Ag prevalence	This study was undertaken to develop sampling strategies to decide on stopping or continuing MDA in an implementation unit. Both Mf and Ag(Og4C3) prevalence were assessed by covering all individuals in the 92 villages to see the impact of 8 rounds of MDA (upto 2007). It was found that prevalence of Mf and Ag were 0.2% and 2.3%. In these 92 villages there were 7 residual (with Mf prevalence ≥1%) and 17 transmission (atleast one Ag-positive child born during MDA period) hotspots. It was also seen that inspite of eight rounds of MDA, there was spatial clustering of infection both at household and village level. The study highlights the need for identifying factors responsible for the emergence of ‘‘transmission hotspots’’ and adoption of appropriate sampling strategies for the development of evidence-based programmatic decision-making tools.
9	South East Asia	India	Ramaiah et al, 2007130	Ten communites	7% of Households, adults and 20–40 children	≥15 & 1–10	Mf prevalence	Ten rounds of mass drug administration was done in 10 communities (5 each for DEC alone and Ivermectin alone) and 49—84% of the eligible population received treatment in different villages. Out of five villages in each treatment arm, the mf rate declined to ≤1% in four villages in the DEC arm and two villages in the ivermectin arm. No mosquitoes with infectivestage larvae were found in three of five villages in the DEC arm and two of five villages in the ivermectin arm. None of the children (n=130) were found to be positive for mf in either treatment arm. None of the 40 sampled children were found to be positive for circulating filarial antigenaemia in villages with lower endemicity in the DEC arm. The results suggest that ten rounds of DEC mass administration have the potential to interrupt transmission of infection in the majority of communities. The outcome was relatively less remarkable with ivermectin.
10	South East Asia	India	Ramaiah et al, 2013131	Five villages	700 persons and 10842 mosquitoes	>2	Mf, Ag and Vector infection prevalence	Robust monitoring and evaluation of MDA is necessary to assess its impact and to stop MDA when the indicators of impact – Mf prevalence in the population or vector infection rate or antigenemia (Ag) prevalence in the children born during the MDA period – fall below the threshold level. The impact of 10 rounds of MDA (using DEC alone) on LF infection and transmission in 5 endemic communities of south India, were monitored and evaluated for 6 years after the overall Mf rate of the study communities was brought down to,1.0%, considered to be the safe and threshold level to stop MDA. Overall Mf prevalence (n=700) and vector infection rates (n=803–3520) showed a declining trend. Both Mf status in humans and infection in vectors were zero from 3rd year after stopping MDA. In only one village, community Mf rate was at 1.0% and Ag prevalence among 1–7 -year old children was 4.6% (n = 44) and vector infectivity rate during the sixth year was 0.1% (n = 852).
11	South East Asia	India	Ramaiah et al, 2002132	10 villages	588 persons	individuals with ≥15 kg weight	Mf prevalence	This placebo-controlled study examined the potential of six rounds of mass treatment with DEC or IVM to eliminate Wuchereria bancroftiinfection in humans in rural areas in south India. The results indicate that DEC is as effective as or slightly better than IVM against microfilaraemia. Results from this and other recent operational studies proved that single-dose treatment with antifilarials is very effective at community level, feasible, logistically easier and cheap and hence a highly appropriate strategy to control or eliminate LF. Higher treatment coverage than that observed in this study and a few more than six cycles of treatment and more effective treatment tools/strategies may be necessary to reduce microfilaraemia to zero level in all communities, which may lead to elimination of LF.
12	South East Asia	India	Subramanian et al, 2015133	33 villages/wards in Tanjavur district	20,049 mosquitoes	Not relevant	Parasite DNA rate	The monitoring and evaluation of lymphatic filariasis (LF) has largely relied on the detection of antigenemia and antibodies in human populations. Molecular xenomonitoring (MX), the detection of parasite DNA/RNA in mosquitoes, may be an effective complementary method, particularly for detecting signals in low-level prevalence areas where Culex is the primary mosquito vector. This article investigated the application of a household-based sampling method for MX in Tamil Nadu, India. Households were systematically selected using a sampling interval proportional to the number of households in the EU. Mosquito pools were collected and analyzed by real-time polymerase chain reaction (qPCR).The household-based sampling strategy for MX led to mostly reproducible results and supported the observed LF infection trends found in humans. MX has the potential to be a costeffective, non-invasive monitoring and evaluation tool with sensitive detection of infection signals in low prevalence settings
13	Western Pacific	American Samoa	Lau et al, 2016134	32 villages of American Samoa	376 persons	All ages	Ag and Vector infection prevalence (MX)	The study evaluated xeno-monitoring as a surveillance tool by linking village level results of published human and vector studies. A total of 32 villages were included in the study. While a 34.4% were positive for Ag (by Og4C3), 56.3% positive for Wb123 Ab and 84.4% were positive for Bm14 Ab. Parasite DNA in vectors was detected in 15 of the 32 villages. Particularly in those villages which recorded Ag positive and Wb 123 positive persons, parasite DNA was found in 91% and 72% of the vectors. In those villages that had no positive persons (for Ag or Wb123), PCR positivity for vector infection were absent.
14	South East Asia	Bangladesh	Irish et al, 2018135	30 villages in two districts	10,021 mosquitoes	Not relevant	Parasite DNA rate	In this study, MX evaluation was conducted in two areas of Bangladesh, one previously endemic district that had stopped MDA (Panchagarh), and part of a non-endemic district (Gaibandha) that borders the district where transmission was most recently recorded.The results showed that none of the mosquito pools tested were positive for W. bancrofti DNA which confirms the results of TAS conducted during 2013 and 2015. The authors suggest that MX can be used to identify missing foci of transmission with smaller geographical areas, in areas were Ag positive cases were identified in TAS
15	South East Asia	Sri Lanka	Rao et al, 2014136	30 health administrative units	28,000 mosquitoes	Not relevant	Parasite DNA rate	Galle district (population 1.1 million) was divided into two EUs. These included a coastal EU with known persistent LF and an inland EU with little persistent LF. Mosquitoes were systematically sampled from ~300 trap locations in 30 randomly selected clusters (health administrative units) per EU. Approximately 28,000 Culex quinquefasciatuswere collected with gravid traps and tested for filarial DNA by qPCR. 92/625 pools (14.7%) from the coastal EU and 8/583 pools (1.4%) from the inland EU were positive for filarial DNA. Maximum likelihood estimates (MLE) for filarial DNA rates were essentially the same when the same number of mosquito pools were collected and tested from 75, 150, or 300 trap sites (range 0.61–0.78% for the coastal EU and 0.04–0.07% for the inland EU). The ability to use a smaller number of trap sites reduces the cost and time required for mosquito sampling. These results suggest there is widespread persistence of W. bancrofti infection in the coastal Galle EU 8 years after the last round of MDA in 2006, and this is consistent with other data from the district. This study has shown that MX can be used by national programs to assess and map the persistence of W. bancrofti at the level of large EUs in areas with Culex transmission.
16	Africa	Tanzania	Rebollo et al, 2015137	Two sentinel sites (islands of Unguja and Pemba)	3,275 children	6–7	Ab prevalence	The study from Tanzania was conducted in Zanzibar where five rounds of MDA with IVM and albendazole was completed and resulted in zero prevalence of MF, Ag and vector infection in sentinel and spot check villages. MDA was stopped and TAS was performed to assess if transmission was interrupted. The study was conducted in islands Pemba and Unguja of Zanzibar. Two sentinel sites from the islands of Unguja were used for monitoring and data on Mf prevalence and coverages were collected at the baseline (prior to MDA) and repeated before each round of MDA. The Mf rates in these two sites reduced from 17.8% and 17.2% to 1.0% and 0.0% respectively. Following this, TAS was conducted in the two islands and children were examined for Ag (ICT). However the number of Ag positive children was much higher than the cut-off value in Pemba but within the cut-off value for Unguja. The low prevalence of Ag in children in Unguja is attributed vector control measures like usage of LLINs and IRS. However, earlier entomological studies in Unguja immediately after stopping MDA showed that transmission was on-going in Unguja islands. The authors indicate that 5 years of MDA may not be sufficient for interrupting LF transmission. Based on this study, the government of Zanzibar decided to resume MDA with ivermectin and albendazole in both these islands in 2013.TAS will be conducted in 2015.
17	South East Asia	Sri Lanka	Rao et al, 2016138	19 PHIs	17,479 children, 78,000 mosquitoes	All ages for MF and Ag, Ab in 6–7	Mf, Ag, Ab and Vector infection prevalence	Comprehensive surveillance was performed in 19 Public Health Inspector (PHI) areas (subdistrict health administrative units) 6 years after stopping MDA. The surveillance package included cross-sectional community surveys for microfilaremia (Mf) and circulating filarial antigenemia (CFA), school surveys for CFA and anti-filarial antibodies, and collection of Culex mosquitoes with gravid traps for detection of filarial DNA (molecular xenomonitoring, MX). Provisional target rates for interruption of LF transmission were community CFA,2%, antibody in school children,2%, and filarial DNA in mosquitoes,0.25%. Community Mf and CFA prevalence rates ranged from 0–0.9% and 0–3.4%, respectively. Infection rates were significantly higher in males and lower in people who denied prior treatment. Antibody rates in school children exceeded 2% in ten study sites; the area that had the highest community and school CFA rates also had the highest school antibody rate (6.9%). Filarial DNA rates in mosquitoes exceeded 0.25% in 10 PHI areas.

Abbreviations: LF, Lymphatic filariasis; DEC, Diethylcarbamazine; IVM, Ivermectin; Ag - Antigeneamia; Mf, Microfilaraemia; Ab, Antibody; MDA, Mass drug administration; TAS, Transmission Assessment Survey; ICT, Immunochromatographic Test; MX, Molecular Xenomontoring.