Mapping and modelling the impact of mass drug adminstration on filariasis prevalencein Myanmar

Mapping and modelling the impact of mass drug adminstration on filariasis prevalencein Myanmar Background: Lymphatic filariasis (LF) is endemic in Myanmar and targeted for elimination. To highlight the National Programme to Eliminate Lymphatic Filariasis (NPELF) progress between 2000 and 2014, this paper describes the geographical distribution of LF, the scale-up and impact of mass drug administration (MDA) implementation, and the first evidence of the decline in transmission in five districts. Methods: The LF distribution was determined by mapping historical and baseline prevalence data collected by NPELF. Data on the MDA implementation, reported coverage rates and sentinel site surveillance were summarized. A statistical model was developed from the available prevalence data to predict prevalence at township level by year of measurement. Transmission assessment survey (TAS) methods, measuring antigenemia (Ag) prevalence in children, were used to determine whether prevalence was below a level where recrudescence is unlikely to occur. Results: The highest baseline LF prevalence was found in the Central Valley region. The MDA implementation activities scaled up to cover 45 districts, representing the majority of the endemic population, with drug coverage rates ranging from 60.0% to 98.5%. Challenges related to drug supply and local conflict were reported, and interrupted MDA in some districts. Overall, significant reductions in LF prevalence were found, especially after the first 2 to 3 rounds of MDA, which was supported by the corresponding model. The TAS activities in five districts found only two Ag positive children, resulting in all districts passing the critical threshold. Conclusion: Overall, the Myanmar NPELF has made positive steps forward in the elimination of LF despite several challenges, however, it needs to maintain momentum, drawing on international stakeholder support, to aim towards the national and global goals of elimination. Keywords: Lymphatic filariasis, Elephantiasis, Wuchereria bancrofti, Neglected tropical diseases, Mass drug administration, Transmission assessment surveys, Surveillance, Myanmar Multilingual abstracts Background Please see Additional file 1 for translations of the Lymphatic filariasis (LF) is a major public health prob- abstract into the five official working languages of the lem in tropical and sub-tropical countries due to the United Nations. painful, disabling and disfiguring clinical conditions as- sociated with chronic infection [1, 2]. The disease is caused by infection with filarial worms and transmitted by a range of mosquito species. In humans, the infective filarial larvae target the lymphatic system, grow to be- * Correspondence: zawlinmcp@gmail.com; Louise.Kelly-Hope@lstmed.ac.uk Ni NI Aye and Zaw Lin contributed equally to this work. come adult worms and reproduce causing conditions Ministry of Health and Sports, Department of Public Health, Nay Pyi Taw, such as lymphoedema (swelling of arms, legs or breasts), Myanmar and hydrocoele (scrotal swelling) in men [3, 4]. The Department of Parasitology, Centre for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, Liverpool, UK South-East Asia region accounts for the highest burden Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 2 of 11 of disease in the world [5–7], and many countries capital NayPyiTaw Union Territory established in 2005 adopted the strategy of the Global Program to Eliminate (Fig. 1a). These 15 administrative areas are further orga- Lymphatic Filariasis (GPELF) which comprises the main nized into districts, townships, towns, cities, wards, goals of i) interrupting transmission through at least five village-tracts (groups of adjacent villages) and villages. annual rounds of mass drug administration (MDA) with The latest census data in 2014 indicated that Myanmar 65% coverage of total population, and ii) alleviating suf- has a population of 51.5 million, with a population dens- fering through morbidity management and disability ity of 75 per square kilometre, and more than one third prevention (MMDP) through the provision of a package of the population living in urban areas [15]. Topograph- of care to manage lymphedema and hydrocoele within ically, there are three distinct regions, which include the primary health care systems [8]. Western Hill Region, Eastern Hill Region and the Cen- Myanmar, formerly known as Burma, is one of the tral Valley Region dominated by the Ayeyarwady basin most endemic countries in South-East Asia, with a high with low elevation levels. LF prevalence, where the disease is caused by the para- The NPELF is part of the Ministry of Health and site Wuchereria bancrofti and transmitted by the mos- Sports (MoHS) and responsible for the MDA imple- quito Culex quinquefasciatus [9, 10]. Like many other mentation and MMDP activities across the country countries in the region, Myanmar has a long history of [16]. In 2000, Myanmar had a total of 65 districts, filarial endemicity, with high infection prevalence levels which the NPELF continues to use for programmatic in several foci [7, 9, 10]. The Myanmar government purposes, despite the recent changes in administrative therefore responded to the new GPELF programme, and boundaries to form 74 districts in 2014. The MoHS developed the National Programme to Eliminate Lymph- delivers the preventive and curative health services at atic Filariasis (NPELF) in 2000. The Myanmar NPELF all levels, including the LF Programme. Each sub- drew on the historical evidence, national data and map- rural health centre provides health-care services to a ping studies conducted in the late 1990s to demarcate cluster of five to ten villages, which have health vol- the endemic districts of the country [11]. The peninsular unteers and who also assist with the LF MDA activ- and central inland areas were found to be most endemic ities as community drug distributors. with an estimated 41 million people (~ 80% of total population) to be at risk of infection in 45 districts. The initial primary focus of Myanmar NPELF was to Geographical distribution of LF interrupt transmission by reducing prevalence rates The endemicity status of each of the 65 districts in through MDA using two anti-filarial drugs; diethylcar- Myanmar in 2000, was based on collated historical data, bamazine (DEC) and albendazole. Over the past 15 year, national reports and rapid prevalence mapping surveys the NPELF has been up-scaling and down-scaling pro- conducted in 19 districts as part of a WHO multi- grammatic activities, including developing a National LF country study [11]. Based on this, 45 districts out of the elimination plan for the WHO in 2000, starting MDA 65 districts were defined as endemic. The most extensive implementation in 2001 and reaching 43 districts in mapping survey conducted by the WHO included a total 2013, conducting ongoing sentinel site surveillance since of 70 randomly selected townships in the 19 districts. 2000, and implementing the first surveys to show evi- The prevalence of antigenaemia (Ag) was determined dence of impact and reductions in prevalence in 2008 using the immuno-chromatographic test (ICT) card and 2014 using standard World Health Organization (BinaxNOW Filariasis, Alere Inc., Scarborough, ME) (WHO) guidelines [12–14]. Overall, key steps forward antigen detection kits from 100 voluntary participants have been made, despite several challenges related to the from randomly selected wards and households, which availability of funding, and ready access to the drug included everyone in each household except the very ill DEC. To highlight the programmatic activities in and those people who were not present at the time of Myanmar, this paper describes and maps the geograph- survey. ical distribution of LF, outlines the progress and impact To highlight the endemic distribution across the of programmatic activities, models the decline in preva- country before the scale up of MDA related activities, lence, and highlights the first evidence that prevalence the WHO prevalence point data were re-mapped has been lowered to an extent where transmission is across the 45 endemic districts by importing the ori- likely to be no longer sustainable in five districts. ginal map and digitizing the points using a standard point feature tool in the geographical information sys- Methods tem software ArcGIS 10 (ESRI, Redlands, CA). The Study area Global Digital Elevation Model (ETOPO2) was used Myanmar is a lower middle income tropical country, as a base map, which was available from ESRI, and divided into seven states, and seven regions with a Redlands, CA. Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 3 of 11 Fig. 1 Map of administrative units and distribution of LF endemicity before intervention. Note: (a). State and Region abbreviations: Kachin (KC); Sagaing (SA), Chin (CH), Shan (SH), Mandalay (ML), Magway (MG), Rakhine (RA), Ayeyarwady (AY), Yangon (YA), Bago (BA), Kayah (KH), Kayin (KN), Mon (MO), Tanintharyi (TN), (b) Endemic districts, (c) Prevalence based on antigenaemia (Ag) determined using the immuno-chromatographic test (ICT) card (BinaxNOW Filariasis, Alere Inc.,) kits. d Prevalence based on microfilaria (Mf) survey data MDA implementation and sentinel sites the directly observed treatment practice via a door-to- To describe the progress and impact of activities related door or booth distribution by community volunteers, to the decline in transmission, data on the MDA imple- once a year over the period of a week. The main social mentation, reported coverage and sentinel site surveil- mobilization activities implemented in communities be- lance (including randomly selected spot check sites) fore MDA included televised media, radio broadcasting, were summarised. The MDA implementation activities health talks in the community by programme staff and were conducted in accordance with the GPELF strategy basic health staff (i.e. health assistants, midwives, trained where each district, also known as the implementation nurses), and the distribution of pamphlets with the as- unit (IU), is required to conduct at least five rounds of sistance from civil society organizations and local au- MDA, with > 65% coverage rate of the entire population thorities. A protocol was developed on how to report [13]. MDA is community-based and implemented using and respond to a range of adverse reactions before the Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 4 of 11 start of the MDA advocacy, with the basic health staff Model (GLM, function ‘glm’)withinthe R statistical trained on the procedures. environment (R Development Core Team, 2012) was The monitoring and evaluation of the programme was then used to predict the average Mf values for each conducted through regular sentinel and spot check site township in a year. surveillance at township level. These field data were ana- The parsimony protocol outlined by Crawley [17]was lysed to help assess the impact before- during- after used to simplify the model by removing any redundant MDA implementation activities. Standard surveillance variables and producing the Minimum Adequate Model involved selecting two sites (villages) per IU, with be- (MAM), i.e. non-significant values and interaction terms tween 300 to 500 people (including all ages ≥2 years of were removed sequentially from the highest order inter- age), selected for assessment of infection by examining actions downwards. At each step, the significance of de- night bloods slides for microfilaria (Mf) as per standard leted items was assessed using analysis of variance using guidelines [13]. The blood smears were processed and the AIC statistic. examined in each IU (district) headquarters. The data were then sent to the central level, where all the data Interruption of transmission were maintained in registers and examined at township The transmission assessment survey (TAS) is a standar- level. All baseline sentinel site prevalence data were dised decision-making tool developed and recommended mapped by Township geographical boundary using the by the WHO [13], and was used to determine the de- software ArcGIS 10 (ESRI, Redland, CA). cline in transmission in 2014 in five districts from three regions, including the Magway Region (Minbu District), Modelling the impact of MDA on prevalence Sagaing Region (Kathur, Kalay, Tamu Districts), and To better understand the reductions in prevalence asso- Mandalay Region (Pyin Oolwin District). Prior to stop- ciated with MDA, a statistical model was developed to ping MDA, each district had at least five effective rounds predict the change in Mf prevalence in a township since of MDA, showed evidence of > 65% coverage rates, and the most recent assessment of prevalence, which varied demonstrated significant reduction in Ag (< 2%) and Mf by site. This most recent Mf value was therefore referred (< 1%) prevalence rates in all sites. to below as the “most recent Mf value”. Data were fil- The Kathur, Kalay and Tamu Districts stopped MDA tered to include only townships for which both a base- in late 2007, and were assessed for the decline in trans- line Mf value (i.e. measurement taken prior to any mission using cluster surveys in 2008 according to MDA), and at least one later sentinel and/or spot check WHO guidelines at the time. Therefore, the TAS surveys Mf value were available. Where there were multiple Mf conducted in 2014 were considered to be the second values recorded at the same township in the same a year, TAS or “TAS 2” for these three districts. The results of a mean value was taken and used. Variables considered the first cluster surveys or “TAS 1” from the 2008 sur- for the model included the baseline Mf prevalence value, veys, and the results from TAS 2 in 2014 were presented the most recent Mf value (this may have been either a for these three districts. baseline Mf prevalence value or the results of a post- The TAS survey design was dependent upon factors baseline programmatic survey), the number of MDA such as the net primary school rate in each evaluation rounds undertaken since the beginning of the MDA unit (EU), the target population size, school enrolment, programme, and the number of MDA rounds and years number of schools, mosquito vector type and parasite since the most recent Mf value was collected. Also con- species. The TAS Survey Sample Builder was used to sidered were calculated variables that attempted to automate the calculations of the sample design, size, in- quantify the fragmented nature of the MDA programme; tervals and critical cut-off values. The rapid ICT Binax for example, the number of MDAs since the most recent NOW Filariasis (Alere Inc., Scarborough, ME) was used Mf value divided by the number of years over which these to detect circulating filarial antigen (CFA) in the chil- MDAs has been administered. Also, the total number dren, and validated with a positive control prior to the of MDAs since the beginning of the MDA commencement of the survey. programme divided by the number of years over, which the programme was administered. Finally, the Results maximum and mean number of years between MDAs, Distribution of LF both since the start of the programme and since the The WHO LF prevalence survey found filarial antigen most recent Mf value. ranged from 0% to > 25%. These data were analysed First, all Mf values were transformed using log10(x + 1) spatially to provide an estimated prevalence of filarial due to asymmetry observed in qq plot when untrans- antigen for each district, which highlighted the major fil- formed data was modelled. A number of other transfor- arial focus in the central region of the country. Based on mations were also considered. A Generalized Linear this national reports and historical data, the NPELF Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 5 of 11 defined the 45 endemic IUs (districts) that required (Fig. 2). MDA was extended to 10 IUs across the Mag- MDA, which were predominately in the lowland areas in way and Sagaing Regions in 2002, and then to 22 IUs in the Central Valley Region (Fig. 1b and c). 2004, representing approximately 48% geographical The baseline Mf sentinel site prevalence for each IU coverage. The majority of these MDA IUs had a rela- was conducted prior to MDA implementation. Sentinel tively higher burden of LF. The NPELF aimed to imple- sites were conducted in a step-wise manner over a ment MDA uninterruptedly, however, no MDA took 13 year period between 2001 and 2013. Table 1 summa- place in the years 2005 and 2008 due to delays in DEC rises the MDA and Mf sentinel site information for en- supplies from the donors. Further, in the Mandalay Re- demic IUs in each region. All baseline sentinel site gion, seven IUs had MDA interrupted twice over the prevalence data were mapped by township geographical study period; in 2006 due to incidence of serious adverse boundary, which highlighted similar endemicity patterns reactions during the preceding MDAs, and in 2010 due in the Central Valley Region (Fig. 1d). to DEC supply constraints. The adverse reactions ob- The Mf baseline average rates were highest in Sagaing served during 2001–2004 after the initial MDAs were (7.9%), Mandalay (5.2%) and Magway (3.6%) Regions conducted in Magway Region included giddiness, head- with the highest rates recorded in the districts of Shwe aches, nausea, rashes, fever, urticaria and vomiting. This Bo (15.1%), Kyauk Se (14.7%) and Pakokku (9.1%) in is the only data on adverse reactions available to present, 2002, 2003 and 2002, respectively. Overall the Mf base- and it is recognized the reporting system needs to be line average rates were lowest in the districts of Ayeya- strengthened. waddy (0.5%), Kayin (0.002%) and Tanintharyi (0.5%) The expansion of MDA activities did not take place Regions with the highest Mf rates recorded in Pathein until 2013. Considerable efforts were made to extend the (2.4%), Myawaddy (0.1%) and Dawei (1.8%) in 2004, MDA programme to cover all endemic IUs in 2011 and 2012 and 2008, respectively. See Additional file 2 for 2012. However, the NPELF could not scale up due to the baseline sentinel site prevalence data. lack of funding, need for many resources (e.g. training of basic health staff, advocacy materials), continued prob- MDA implementation lems in procuring adequate quantities of DEC, as well as The first MDA was implemented in two IUs viz., Mag- security related issues in the two endemic districts of way and Theyet Districts in the Magway Region in 2001 Kachin State. No MDA was conducted in 2012. Table 1 Summary of regional/provincial endemic districts, MDA start dates and sentinel site prevalence a b b Region/ Endemic Districts Year of MDA Year of Mf Baseline Mf Mf 3–5 MDA Mf > 5 MDA Province (Implementation Unit – IUs) Start Baseline Average Baseline Round Average Round Average Sentinel Site (no. sites) Range (no. sites) (no. sites) Magway Magway, Thayet, Minbu, Pakoku, 2001–2002 2001–2002 3.2 (n = 9) 0.2–9.1 2.3 (n = 21) 1.2 (n = 29) Sagaing Sagaing, Shwe Bo, Monywa, Kathur, 2002 2002 4.7 (n = 11) 0–15.1 2.8 (n = 12) 1.2 (n = 43) Kalay, Tamu, Chin Paletwa 2004 2003 1.5 (n = 2) 1.4–1.6 0.2 (n =2) - Mandalay Mandalay, Pyin Oo Lwin, Kyauk Se, 2004 2003 5.2 (n = 14) 0.2–14.7 - 2.3 (n = 20) Yamethin, Myin Gyan, Meikhtilar, Nyaung Oo Nay pyi taw Nay pyi taw 2013 2011 1.9 (n = 1) 1.9 - - Rakhine Sittwe, Maungdaw, Kyauk Phyu, 2004 2003–2004 3.0 (n =6) 0–12.6 0.6 (n = 13) Thandwe Ayeyarwaddy Pathein, Hantada, Myaungmya, 2013 2002–2013 0.5 (n = 12) 0–2.4 - - Phyarpone. Maubin Bago Bago, Thanung Ngu, Tharyawaddy, 2013 2005–2013 0.7 (n = 10) 0–2.8 - - Pyay Kayin Hpaan, Kawkareik, Myawaddy 2013 2013 0.002 (n =5) 0–0.1 - - Mon Mawlamying, Thaton 2013 2004–2013 1.8 (n = 4) 0.8–3.2 - - Tanintharyi Dawei, Myeik, Kawthaung 2013 2004–2013 0.5 (n =8) 0–1.8 - - Yangon Yangon North, Yangon South, 2013 2004–2013 0.1 (n =8) 0–0.4 - - Yangon East, Yangon West Mf average based on the total number of sites (in brackets) across the endemic districts. At each site between 300 and 500 people tested. Some sites were tested multiple years before MDA started Mf based on both sentinel sites and spot check sites based on number of sites (in brackets). At each site between 300 and 500 people tested Mf: microfilaria Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 6 of 11 Fig. 2 Programme MDA up scale and down scale between 2001 and 2014 However, in 2013, a major increase in coverage was fi- temporarily stopping MDA due to security related issues. nally reached with support from Sanofi Pasteur, WHO Additional file 3 summarises the scale up and scale down and the Global Network for NTDs for supply of DEC of MDA related activities between 2001 and 2014. and operational costs. This up scaling of MDA resulted Overall, the reported treatment coverage i.e. the cover- in a further 21 IUs receiving treatment in 2013, which co- age calculated for each IU on the basis of reports sent incided with the down scaling of MDA in 2 IUs (Minbu from lower level units (townships, villages) was high, and Pyin Oo Lwin Districts) as they reached the require- ranging from 68.7% to 98.5% of the IU’s entire popula- ments for TAS, and a further 4 IUs from Rakhine State tion (Table 2). A cross-sectional evaluation of the Table 2 Summary of population and reported treatment coverage rates 2001–2014 Year No. of No. of Total population Population which Reported Treatment coverage regions districts covered ingested drugs Overall Range among districts 2001 1 2 1 939 964 1 803 306 93 - 2002 2 10 8 634 179 7 474 094 95.7 93.2–98.5 2004 5 22 17 929 178 15 838 896 82.6 80.1–94.3 2005 - - No MDA No MDA - - 2006 4 15 11 868 901 10 761 777 90.7 79.5–94.1 2007 5 22 20 000 250 18 397 240 91.9 83.4–93.9 2008 - - No MDA No MDA - - 2009 5 19 17 702 845 15 790 286 89.2 85.5–96.4 2010 4 12 10 035 458 9 002 092 89.7 82.7–95.4 2011 5 19 1 7031 636 15 429 100 90.5 85.8–93.4 2012 - - No MDA No MDA - - 2013 7 36 35 488 298 30 313 249 85.4 68.7–93.8 2014 7 37 36 407 716 31 121 035 85.5 74.8–93.7 Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 7 of 11 treatment coverage conducted by a team within the De- The most significant coefficient, was an interaction term partment of Health in randomly selected townships in consisting of two predictor variables (the most recently 2013, found that coverage rates ranged from 60% to collected Mf prevalence (log + 1) and the number of 97.4% across 19 IUs, and reflected reported coverage MDAs administered since that Mf prevalence data were rates in each corresponding IU. Of those people who collected (log + 1). The second most significant coeffi- were eligible, but did not take the drug, the main rea- cient was the baseline prevalence (log + 1). Together, sons were that they were absent at the time of MDA, this demonstrates that whilst the number of rounds of or had refused to take the drugs related to negative MDA is the most important predictor, the underlying rumours regarding MDA. conditions reflected by the baseline figure also affects the results, i.e. two rounds of MDA in a high baseline area will not reduce prevalence as much as two rounds Impact of MDA on field collected prevalence data of MDA in a low baselines area, even if the most recent (baseline and sentinel/spot check sites) Mf value in the two areas is the same. Surprisingly, the The field collected baseline data varied significantly be- covariates that described the fragmented nature of the tween 15.1% to zero in 46 townships across the country. MDA (i.e. the number of missed MDA years) did not Figure 3a highlights the prevalence trends by the num- feature in the MAM. That is, they did not significantly ber of MDA rounds. All but two townships displayed a improve the fit of the model. This may be due to the significant reduction in prevalence over the 13 years for small number of data points available. which data was available, especially after two to three The model unexpectedly predicted an increase in MDA rounds where the prevalence ranged from 0 to prevalence if there were more rounds of MDA between 8.8%. The two townships, Amapura and Pakokku, measurements of prevalence. However, this appears to which reported a rise in prevalence at spot check sites be an artifact of the MDA administration; prevalence (outliers) were removed so that general trends could bet- data were usually collected after every two MDA rounds ter be examined. This resulted in 138 individual Mf site but were collected after 3 rounds of MDA in Mandalay. values included in further analysis, and showed that the The model shows that three rounds of MDA in Manda- prevalence after two to three MDA rounds was signifi- lay had less effect on prevalence than two rounds of cantly reduced, and ranged from 0 to 5.9%. MDA elsewhere; therefore suggesting that in Mandalay specifically, the MDAs were less effective. Modelling the impact of MDA on prevalence The modelled data shown in Fig. 3b clearly reflects the The townships for which sentinel site and spot check same prevalence trend as the field collected data. The prevalence data were available received between 0 and initial two MDA rounds produced a significant reduc- 12 rounds of MDA. A model predicting the Mf preva- tion in prevalence which was followed by a much lence in a township in a year from the most recent as- smaller reduction in subsequent MDA rounds, with sessment of Mf prevalence at the same township was prevalence levelling out. The models suggest a similar produced. After the removal of redundant terms, the trend, for example an area with 30% baseline prevalence, model consisted of two coefficients (Fig. 3b; Table 3). drops to 6.5% after the first two MDA rounds indicating Fig. 3 Sentinel and spot check data and modelled distributions by number of MDA rounds. (a) Township data (b) Modelled data. Note. Township data includes all points from all sentinel sites and modelled data include selected sites Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 8 of 11 Table 3 Minimal Adequate Model (MAM) predicting prevalence at Township level from prevalence previously measured and number rounds MDAs Coefficients: Estimate Std. Error t value Pr(>|t|) (Intercept) - 0.05012 0.03641 - 1.377 0.172 logBaselineMf 0.27098 0.05263 5.149 1.77e - 06 logPreviousMf: logMDAsSincePreviousMf 0.73239 0.11677 6.272 1.59e - 08 Residual standard error: 0.1507 on 82 degrees of freedom Multiple R-squared: 0.6162, Adjusted R-squared: 0.6069 F-statistic: 65.84 on 2 and 82 DF, P-value < 2.2e - 16 a reduction of 78%. The next two MDA rounds reduce critical cut-off of 18 positive children calculated for all further, but less dramatically, to 3.5%, and two further EUs (Table 4). MDA rounds reduce prevalence to 2.8%. For sites with a The field activities involved 5 to 7 teams consisting of baseline of 15%, the effect of the first two MDA rounds three people each: supervisor, data collector and a tech- is a 73% reduction to 3.9% prevalence (next two MDA nician. All team members were trained per the TAS rounds reduce prevalence to 2.3%, with little further ef- guidelines by a Central and Regional Team leader. The fect after four MDA rounds). For areas with a baseline Township Medical Officer was responsible for informing of 7%, the effect of the first two rounds of MDA is a and coordinating activities with the Township Education 69% reduction to a prevalence of 2.2% (next two MDA Department, and Headmasters of the selected school be- rounds reduce to 1.4% prevalence, with little effect after fore the survey. The Headmaster of each school pro- four MDA rounds). vided an official class register and all eligible children were identified for selection. For each selected child, their name, sex, age, and grade was recorded and 100 μl Decline in transmission of blood collected for ICT. No child refused to partici- In 2008, the first cluster surveys or “TAS 1” for the pate in the survey. Kalay, Kathar and Tamu Districts found no ICT positive The TAS 1 results for Minbu and Pyin Oo Lwin EUs children among the 2269, 3003, and 3085 tested across found 1 positive child, and the TAS 2 results for Kalay, 16, 31, and 25 schools respectively. Further details of the Kathar and Tamu EUs found 1 positive child (Table 4). schools surveyed are in Additional files 4, 5, and 6. These results resulted in all EUs being under the critical In 2014, the pre-TAS assessments indicated that all cut-off and passing TAS. The two positive children were five IUs had sufficient number of MDA rounds, and high treated and the parents and relative Township Medical reported treatment coverage rates of > 85%. Based on Officer informed for further monitoring as required. the population size and school enrolment rates of > 90%, school-based surveys were conducted in each IUs, which Discussion were evaluated as EUs, with sample sizes of between Overall good programmatic progress has been made by the 1556 to 1548 children across 30 to 52 schools, and Myanmar NPELF with the successful scale up of MDA Table 4 Summary of IU populations, MDA and TAS characteristics Population and MDA TAS Districts Total Pop. MDA Rounds MDA Coverage No. 6–7 aged No. Total Sample No. Schools Children No. ICT & Years Range Children Schools Size Tested Absent % Positive Minbu TAS 1 689 965 10 MDAs 86–94% 27 252 759 1556 52 2.3% 1 2002–2014 Pyin Oolwin 851 945 6 MDAs 85–99% 32 529 634 1556 36 0.2% 0 TAS 1 2004–2014 Kalay TAS 2 487 762 5 MDAs 85–98% 24 461 387 1556 30 0.7% 0 2002–2007 Kathar TAS 2 819 281 5 MDAs 92–100% 34 090 1077 1556 58 0.4% 1 2002–2007 Tamu TAS 2 105 100 5 MDA 92–100% 17 155 77 1548 30 0% 0 2002–2007 Note. Details of MDA years available in Additional file 3 IU: Implementation Unit MDA: Mass drug administration TAS: Transmission assessment survey Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 9 of 11 implementation, widespread significant reductions in the Culex spp. vectors [28]. Thus, information on the prevalence, and the initiation of post-MDA surveillance ac- vector biting rates may be key for better insights into the tivities in five districts. This national overview extends transmission dynamics and elimination in a geographic the findings from four endemic states/regions by Win et al., region, especially in the endgame phase where there is and highlights that progress has been achieved despite the risk of recrudescence, as highlighted in recent math- some challenges in obtaining regular funding and support ematical models [29, 30]. from international partners and stakeholders, reports of The NPELF may also consider the possibility and side-effects during MDA, internal security issues, and diffi- feasibility of triple drug therapy, including ivermectin, culties in obtaining the drug DEC. The progress to-date DEC and albendazole (IDA) and the protocols have may be attributed to several factors identified as determi- recently been released for field use [31, 32]. The high nants of LF programme success as noted in other countries effectiveness of this therapy, may shorten the duration [18, 19] including the i) general low transmission levels and cost of MDAs, especially in potential ‘hotspot’ found at baseline with the majority of Mf rates < 15%; areas, or where MDA coverage has been repeatedly ii) MDA regime of albendazole and DEC which is consid- interrupted such as Mandalay, which had only three ered a highly effective combination against the MDAs over a 8 year period and showed areas of per- parasite W. bancrofti; and iii) good health system infra- sistent infection [33]. The IDA may also be useful for structure, administration and training. It is also likely that areas with low, or lowered prevalence where trans- this widespread MDA coverage with albendazole for LF mission appears difficult to ultimately interrupt [28]. has impacted on soil transmitted helminths (STH) infec- However, measuring and modelling the impact of IDA tion rates, which will be beneficial to the STH MDA on filariasis prevalence will be crucial. Understanding programme and should be taken into account [20]. the barriers to high MDA coverage will also be im- Notwithstanding these positive steps forward, the portant, and more in-depth studies in problem areas NPELF will face some challenges to complete all pro- should be undertaken [34, 35]. Further, it will be im- grammatic activities by the GPELF elimination goal of portant for the NPELF to strengthen its response to 2020 [21, 22]. It will require pro-active interaction with and recording of adverse reactions as this has been a drug donors to ensure steady DEC supply. International programme weakness to date. collaboration and support may be more achievable now The TAS in five districts confirms that transmission has with the changed political situation in country [23]. This declined significantly in some areas of the country. How- may help to address any challenges that arise and main- ever, as standard post-MDA surveillance activities scale up tain the momentum of the programme. The NPELF is at over the next 5 years, the NPELF could be further crucial stage now in terms of undertaking multiple activ- strengthened by training more personnel and increasing ities in as many as 45 districts. Hence, more technical the number of teams to support the activities on a more and financial support from international partners and full-time basis as other countries have done [7, 19]. Inte- stakeholders is key to its future success. grating alternative methods of monitoring and evaluation Importantly, MDA implementation was initially fo- into the existing health system structure will also be cused in high transmission areas, and the programme important to ensure that surveillance is sustainable long- was able to demonstrate that the most significant reduc- term, and sufficiently sensitive and targeted to find poten- tions occurred after 2 to 3 rounds of MDA. This trans- tial problem areas or hotspots of transmission [36, 37]. In mission reduction pattern is consistent with other parallel, MMDP mapping and related activities, and add- studies in the South-East Asian Region and elsewhere itional integrated post-TAS activities need be initiated and [19, 24–27], and is in agreement with the predicted could be conducted using new tools and field scenar- model presented in this paper. The model confirms that ios [7, 38]. The districts with high burden of chronic dis- LF prevalence reduces with number of MDAs. However, ease and high baseline infection should be prioritized, and the effect of each subsequent MDA is less than the one the key activities integrated with health system. before, and also dependent on the initial prevalence rate. Notably, after a number of MDAs, the prevalence Conclusions reaches an asymptote i.e. levels out to a point, that was This study highlights that the Myanmar NPELF has proportional to the initial prevalence rate. This suggests made positive steps forward in the elimination of LF that, whilst in low endemic areas MDA may be sufficient with significant reductions in prevalence and the first to reach elimination, in higher endemic areas, reducing evidence of interrupting transmission. It will be im- the transmission levels to zero may prove difficult and portant for the NPELF to maintain this momentum, the current MDA strategy would potentially benefit aim to maximize its capacity and draw on inter- from supplementary interventions such as vector con- national stakeholder support to help meet the na- trol, and environmental management to better control tional and global goals of elimination. Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 10 of 11 Additional files Centre for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, Liverpool, UK. Additional file 1: Multilingual abstracts in the five official working Received: 31 July 2017 Accepted: 5 April 2018 languages of the United Nations. (PDF 250 kb) Additional file 2: Baseline Mf prevalence in district sentinel sites. (DOCX 35 kb) Additional file 3: Matrix of MDA in endemic districts from 2001 to References 2014. (DOCX 37 kb) 1. World Health Organization. Global programme to eliminate lymphatic filariasis: progress report, 2015. Wkly. Epidemiol. Rec. 2016;91:73–88. Additional file 4: ICT Survey in school children in Tamu Township Available from: http://www.who.int/lymphatic_filariasis/resources/who_ District in 2008. (DOCX 23 kb) wer9139/en/. Accessed 16 Mar 2018. Additional file 5: ICT Survey in school children in Katha District in 2008. 2. Ramaiah KD, Ottesen E a. Progress and impact of 13 years of the global (DOCX 25 kb) Programme to eliminate lymphatic Filariasis on reducing the burden of Additional file 6: ICT Survey in infant and school children from Kalay filarial disease. PLoS Negl Trop Dis 2014;8:e3319. Available from: http://dx. District in 2008. (DOCX 22 kb) plos.org/10.1371/journal.pntd.0003319. Accessed 16 Mar 2018. 3. Dreyer G, Norões J, Figueredo-Silva J, Piessens WF. Pathogenesis of lymphatic disease in bancroftian filariasis: a clinical perspective. Parasitol Abbreviations Today. 2000;16:544–8. Ag: Antigenaemia; DEC: Diethylcarbamazine; EU: Evaluation unit; 4. World Health Organization. Lymphatic filariasis: Managing morbidity and ICT: Immuno-chromatographic test; IU: Implementation unit; preventing disability. Geneva; 2013. Available from: http://www.who.int/ GIS: Geographical information system; GPELF: Global program to eliminate lymphatic_filariasis/resources/9789241505291/en/. Accessed 16 Mar 2018. lymphatic filariasis; LF: Lymphatic filariasis; MDA: Mass drug administration; 5. Michael E, Bundy DAP, Grenfell BT. Re-assessing the global prevalence and Mf: Microfilaria; MAM: Minimum adequate model; MoHS: Ministry of Health distribution of lymphatic filariasis. Parasitology. 1996;112:409–28. and Sports; MMDP: Morbidity management and disability prevention; 6. Cano J, Rebollo MP, Golding N, Pullan RL, Crellen T, Soler A, et al. The global NPELF: National Programme to Eliminate Lymphatic Filariasis; distribution and transmission limits of lymphatic filariasis: past and present. TAS: Transmission assessment survey; WHO: World Health Organization Parasit Vectors. 2014;7:466. 7. Dickson B, Graves P, McBride W. Lymphatic Filariasis in mainland Southeast Acknowledgements Asia: a systematic review and meta-analysis of prevalence and disease We are grateful to the children, parents, Head Masters, teachers, basic Health burden. Trop Med Infect Dis. 2017;2:32. Staff working in the relative Health Centers in the study communities, and to 8. World Health Organization. Regional Strategic Plan for Integrated Neglected the individuals, personnel from Central, State a/ Regional, District and Tropical Diseases Control in South-East Asia Region, 2012-2016. New Delhi, Township Vector Borne Disease Control teams, and the field research India, 9–10 August 2011; 2012 Available from: http://appssearowhoint/pds_ assistants who helped in undertaking the programmatic work. docs/B4867pdf?ua=1. Accessed 16 Mar 2018. 9. de Meillon B, Grab B, Sebastian A. Evaluation of Wuchereria bancrofti Funding infection in Culex pipiens fatigans in Rangoon, Burma. Bull World Health The LF programme activities were supported by the Ministry of Health and Organ. 1967;36:91–100. Sports, and funds from the Centre for Neglected Tropical Diseases (CNTD), 10. Sasa M. Human filariasis – a global survey of epidemiology and control. Liverpool, UK through a grant from the Department for International Baltimore: University Park Press; 1976. Development (DFID) and GlaxoSmithKline (GSK) for the elimination of 11. Research and Training in Tropical Diseases (TDR). Research on Rapid lymphatic filariasis. Geographical Assessment of Bancrofti Filariasis. 1997. Report No.: Document TDR/TDF/ComCT/98.2. Available from: http://apps.who.int/iris/handle/10665/ Availability of data and materials 63960. Accessed 16 Mar 2018. Please contact author for additional data requests. 12. World Health Organization. Report on the mid-term assessment of microfilaraemia reduction in sentinel sites of 13 countries of the Global Authors’ contributions Programme to Eliminate Lymphatic Filariasis. Wkly. Epidemiol. Rec. 2004;79: NNA and LAKH conceived the idea for the study. LAKH, KR and HB 358–367. Available from: http://www.who.int/neglected_diseases/resources/ conducted the formal data analysis and visualization. NNA, ZL, TWN and who_wer7940/en/. Accessed 16 Mar 2018. KMM curated and organized the data. LAKH, KR, and NNA wrote the first 13. World Health Organization. Global Programme to Eliminate Lymphatic version of the manuscript. All authors contributed equally to the critical Filariasis: A Manual for National Elimination Programmes (Monitoring and review and editing of the final manuscript. All authors read and approved Epidemiological Assessment of Mass Drug Administration). Geneva; 2011. the final manuscript. Available from: http://www.who.int/lymphatic_filariasis/resources/ 9789241501484/en/ Accessed 16 Mar 2018. Ethics approval and consent to participate 14. World Health Organization (WHO). Transmission Assessment Workshops. The LF programmatic MDA implementation, and surveillance surveys Available from: http://apps.searo.who.int/PDS_DOCS/B4925.pdf and http:// conducted by the Ministry of Health, Myanmar are part of routine activities www.wpro.who.int/mvp/meetings/docs/en/ Accessed 16 Mar 2018. and permit the use of oral consent. For TAS, additional approval from the 15. MIMU. Myanmar Information Management Unit. The 2014 Myanmar Ministry of Education, local authorities, and Headmasters of the selected population and housing census. 2014. Available from: http://themimu.info/ schools was obtained prior to the commencement of the surveys. All census-data. Accessed 16 Mar 2018. parents were informed of the TAS activity and provided consent, and the 16. Vector Borne Disease Control Program. VBDC Annual Report. The Republic selected children were verbally informed of the procedures on the day of of the Union of Myanmar, Ministry of Health and Sports. 2014. Available the survey. Those who did not want to participate were excluded. Approval from: http://www.moh.gov.mm/. Accessed 16 Mar 2018. was obtained from the Liverpool School of Tropical Medicine Research Ethics 17. Crawley M. The R Book. Chichester: Wiley; 2007. Committee (Research Protocol 11.89R). 18. Kyelem D, Biswas G, Bockarie MJ, Bradley MH, El-Setouhy M, Fischer PU, et al. Determinants of success in national programs to eliminate lymphatic Competing interests filariasis: a perspective identifying essential elements and research needs. The authors declare that they have no competing interests. Am J Trop Med Hyg. 2008;79:480–4. 19. Shamsuzzaman AKM, Haq R, Karim MJ, Azad MB, Mahmood ASMS, Khair A, Author details et al. The significant scale up and success of transmission assessment Ministry of Health and Sports, Department of Public Health, Nay Pyi Taw, surveys ‘TAS’ for endgame surveillance of lymphatic filariasis in Bangladesh: 2 3 Myanmar. Tagore Nagar, Pondicherry, India. Department of Parasitology, one step closer to the elimination goal of 2020. PLoS Negl Trop Dis 2017;11: Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 11 of 11 e0005340. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/ 37. Hollingsworth T, Langley I, Nokes D, Macpherson EE, McGivern G, Adams ER, PMC5302837/. Accessed 16 Mar 2018. et al. Infectious disease and health systems modelling for local decision 20. Dunn JC, Bettis AA, Wyine NY, Lwin AMM, Lwin ST, Su KK, et al. A cross- making to control neglected tropical diseases. BMC Proc. 2015;9:S6. sectional survey of soil-transmitted helminthiases in two Myanmar villages Available from: http://www.biomedcentral.com/1753-6561/9/S10/S6. receiving mass drug administration: epidemiology of infection with a focus Accessed 16 Mar 2018. on adults. Parasit Vectors. 2017;10:374. 38. Mableson H, Martindale S, Stanton MC, Mackenzie C, Kelly-Hope LA. Community-based field implementation scenarios of an SMS reporting tool 21. World Health Organization. Integrating neglected tropical diseases into for lymphatic filariasis case estimates in Africa and Asia. mHealth. 2016;3:28. global health and development: fourth WHO report on neglected tropical diseases. 2017. Available from: http://www.who.int/neglected_diseases/ resources/9789241565448/en/ Accessed 16 Mar 2018. 22. World Health Organization. Validation of elimination of lymphatic filariasis as a public health problem. Geneva; 2017. Available from: http://www.who.int/ lymphatic_filariasis/resources/9789241511957/en/. Accessed 16 Mar 2018. 23. Risso-Gill I, McKee M, Coker R, Piot P, Legido-Quigley H. Health system strengthening in Myanmar during political reforms: perspectives from international agencies. Health Policy Plan. 2014;29:466–74. 24. Ramaiah KD, Das PK, Vanamail P, Pani SP. Impact of 10 years of diethylcarbamazine and ivermectin mass administration on infection and transmission of lymphatic filariasis. Trans R Soc Trop Med Hyg 2007;101:555–63. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239120/. Accessed 16 Mar 2018. 25. Swaminathan S, Perumal V, Adinarayanan S, Kaliannagounder K, Rengachari R, Purushothaman J. 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Bayesian calibration of simulation models for supporting management of the elimination of the macroparasitic disease, lymphatic Filariasis. Parasit Vectors. 2015;8:522. 30. Michael E, Singh BK. Heterogeneous dynamics, robustness/fragility trade- offs, and the eradication of the macroparasitic disease, lymphatic filariasis. BMC Med. 2016;14:14. Available from: 31. Thomsen EK, Sanuku N, Baea M, Satofan S, Maki E, Lombore B, et al. Efficacy, safety, and pharmacokinetics of Coadministered Diethylcarbamazine, Albendazole, and Ivermectin for treatment of Bancroftian Filariasis. Clin Infect Dis. 2016;62:334–41. 32. World Health Organization. Guideline: alternative mass drug administration regimens to eliminate lymphatic filariasis. Geneva; 2017. Available from: http://apps.who.int/iris/handle/10665/259381 Accessed 16 Mar 2018. 33. Dickson B, Graves P, Aye N, Nwe T, Win S, Douglass J, et al. The prevalence of lymphatic filariasis related hydrocele, lymphedema and infection in Mandalay region, Myanmar. In: American Society of Tropical Medicine and th Hygiene. 64 annual meeting. Philadelphia; 2015. http://www.astmh.org/ annual-meeting/past-meetings. 34. Krentel A, Gyapong M, Mallya S, Boadu NY, Amuyunzu-Nyamongo M, Stephens M, et al. Review of the factors influencing the motivation of community drug distributors towards the control and elimination of neglected tropical diseases (NTDs). PLoS Negl Trop Dis. 2017;11:e0006065. 35. Krentel A, Fischer PU, Weil GJ. A review of factors that influence individual compliance with mass drug administration for elimination of lymphatic filariasis. PLoS Negl Trop Dis. 2013;7:e2447. 36. Baker MC, Mathieu E, Fleming FM, Deming M, King JD, Garba A, et al. Mapping, monitoring, and surveillance of neglected tropical diseases: towards a policy framework. 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Mapping and modelling the impact of mass drug adminstration on filariasis prevalencein Myanmar

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Abstract

Background: Lymphatic filariasis (LF) is endemic in Myanmar and targeted for elimination. To highlight the National Programme to Eliminate Lymphatic Filariasis (NPELF) progress between 2000 and 2014, this paper describes the geographical distribution of LF, the scale-up and impact of mass drug administration (MDA) implementation, and the first evidence of the decline in transmission in five districts. Methods: The LF distribution was determined by mapping historical and baseline prevalence data collected by NPELF. Data on the MDA implementation, reported coverage rates and sentinel site surveillance were summarized. A statistical model was developed from the available prevalence data to predict prevalence at township level by year of measurement. Transmission assessment survey (TAS) methods, measuring antigenemia (Ag) prevalence in children, were used to determine whether prevalence was below a level where recrudescence is unlikely to occur. Results: The highest baseline LF prevalence was found in the Central Valley region. The MDA implementation activities scaled up to cover 45 districts, representing the majority of the endemic population, with drug coverage rates ranging from 60.0% to 98.5%. Challenges related to drug supply and local conflict were reported, and interrupted MDA in some districts. Overall, significant reductions in LF prevalence were found, especially after the first 2 to 3 rounds of MDA, which was supported by the corresponding model. The TAS activities in five districts found only two Ag positive children, resulting in all districts passing the critical threshold. Conclusion: Overall, the Myanmar NPELF has made positive steps forward in the elimination of LF despite several challenges, however, it needs to maintain momentum, drawing on international stakeholder support, to aim towards the national and global goals of elimination. Keywords: Lymphatic filariasis, Elephantiasis, Wuchereria bancrofti, Neglected tropical diseases, Mass drug administration, Transmission assessment surveys, Surveillance, Myanmar Multilingual abstracts Background Please see Additional file 1 for translations of the Lymphatic filariasis (LF) is a major public health prob- abstract into the five official working languages of the lem in tropical and sub-tropical countries due to the United Nations. painful, disabling and disfiguring clinical conditions as- sociated with chronic infection [1, 2]. The disease is caused by infection with filarial worms and transmitted by a range of mosquito species. In humans, the infective filarial larvae target the lymphatic system, grow to be- * Correspondence: zawlinmcp@gmail.com; Louise.Kelly-Hope@lstmed.ac.uk Ni NI Aye and Zaw Lin contributed equally to this work. come adult worms and reproduce causing conditions Ministry of Health and Sports, Department of Public Health, Nay Pyi Taw, such as lymphoedema (swelling of arms, legs or breasts), Myanmar and hydrocoele (scrotal swelling) in men [3, 4]. The Department of Parasitology, Centre for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, Liverpool, UK South-East Asia region accounts for the highest burden Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 2 of 11 of disease in the world [5–7], and many countries capital NayPyiTaw Union Territory established in 2005 adopted the strategy of the Global Program to Eliminate (Fig. 1a). These 15 administrative areas are further orga- Lymphatic Filariasis (GPELF) which comprises the main nized into districts, townships, towns, cities, wards, goals of i) interrupting transmission through at least five village-tracts (groups of adjacent villages) and villages. annual rounds of mass drug administration (MDA) with The latest census data in 2014 indicated that Myanmar 65% coverage of total population, and ii) alleviating suf- has a population of 51.5 million, with a population dens- fering through morbidity management and disability ity of 75 per square kilometre, and more than one third prevention (MMDP) through the provision of a package of the population living in urban areas [15]. Topograph- of care to manage lymphedema and hydrocoele within ically, there are three distinct regions, which include the primary health care systems [8]. Western Hill Region, Eastern Hill Region and the Cen- Myanmar, formerly known as Burma, is one of the tral Valley Region dominated by the Ayeyarwady basin most endemic countries in South-East Asia, with a high with low elevation levels. LF prevalence, where the disease is caused by the para- The NPELF is part of the Ministry of Health and site Wuchereria bancrofti and transmitted by the mos- Sports (MoHS) and responsible for the MDA imple- quito Culex quinquefasciatus [9, 10]. Like many other mentation and MMDP activities across the country countries in the region, Myanmar has a long history of [16]. In 2000, Myanmar had a total of 65 districts, filarial endemicity, with high infection prevalence levels which the NPELF continues to use for programmatic in several foci [7, 9, 10]. The Myanmar government purposes, despite the recent changes in administrative therefore responded to the new GPELF programme, and boundaries to form 74 districts in 2014. The MoHS developed the National Programme to Eliminate Lymph- delivers the preventive and curative health services at atic Filariasis (NPELF) in 2000. The Myanmar NPELF all levels, including the LF Programme. Each sub- drew on the historical evidence, national data and map- rural health centre provides health-care services to a ping studies conducted in the late 1990s to demarcate cluster of five to ten villages, which have health vol- the endemic districts of the country [11]. The peninsular unteers and who also assist with the LF MDA activ- and central inland areas were found to be most endemic ities as community drug distributors. with an estimated 41 million people (~ 80% of total population) to be at risk of infection in 45 districts. The initial primary focus of Myanmar NPELF was to Geographical distribution of LF interrupt transmission by reducing prevalence rates The endemicity status of each of the 65 districts in through MDA using two anti-filarial drugs; diethylcar- Myanmar in 2000, was based on collated historical data, bamazine (DEC) and albendazole. Over the past 15 year, national reports and rapid prevalence mapping surveys the NPELF has been up-scaling and down-scaling pro- conducted in 19 districts as part of a WHO multi- grammatic activities, including developing a National LF country study [11]. Based on this, 45 districts out of the elimination plan for the WHO in 2000, starting MDA 65 districts were defined as endemic. The most extensive implementation in 2001 and reaching 43 districts in mapping survey conducted by the WHO included a total 2013, conducting ongoing sentinel site surveillance since of 70 randomly selected townships in the 19 districts. 2000, and implementing the first surveys to show evi- The prevalence of antigenaemia (Ag) was determined dence of impact and reductions in prevalence in 2008 using the immuno-chromatographic test (ICT) card and 2014 using standard World Health Organization (BinaxNOW Filariasis, Alere Inc., Scarborough, ME) (WHO) guidelines [12–14]. Overall, key steps forward antigen detection kits from 100 voluntary participants have been made, despite several challenges related to the from randomly selected wards and households, which availability of funding, and ready access to the drug included everyone in each household except the very ill DEC. To highlight the programmatic activities in and those people who were not present at the time of Myanmar, this paper describes and maps the geograph- survey. ical distribution of LF, outlines the progress and impact To highlight the endemic distribution across the of programmatic activities, models the decline in preva- country before the scale up of MDA related activities, lence, and highlights the first evidence that prevalence the WHO prevalence point data were re-mapped has been lowered to an extent where transmission is across the 45 endemic districts by importing the ori- likely to be no longer sustainable in five districts. ginal map and digitizing the points using a standard point feature tool in the geographical information sys- Methods tem software ArcGIS 10 (ESRI, Redlands, CA). The Study area Global Digital Elevation Model (ETOPO2) was used Myanmar is a lower middle income tropical country, as a base map, which was available from ESRI, and divided into seven states, and seven regions with a Redlands, CA. Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 3 of 11 Fig. 1 Map of administrative units and distribution of LF endemicity before intervention. Note: (a). State and Region abbreviations: Kachin (KC); Sagaing (SA), Chin (CH), Shan (SH), Mandalay (ML), Magway (MG), Rakhine (RA), Ayeyarwady (AY), Yangon (YA), Bago (BA), Kayah (KH), Kayin (KN), Mon (MO), Tanintharyi (TN), (b) Endemic districts, (c) Prevalence based on antigenaemia (Ag) determined using the immuno-chromatographic test (ICT) card (BinaxNOW Filariasis, Alere Inc.,) kits. d Prevalence based on microfilaria (Mf) survey data MDA implementation and sentinel sites the directly observed treatment practice via a door-to- To describe the progress and impact of activities related door or booth distribution by community volunteers, to the decline in transmission, data on the MDA imple- once a year over the period of a week. The main social mentation, reported coverage and sentinel site surveil- mobilization activities implemented in communities be- lance (including randomly selected spot check sites) fore MDA included televised media, radio broadcasting, were summarised. The MDA implementation activities health talks in the community by programme staff and were conducted in accordance with the GPELF strategy basic health staff (i.e. health assistants, midwives, trained where each district, also known as the implementation nurses), and the distribution of pamphlets with the as- unit (IU), is required to conduct at least five rounds of sistance from civil society organizations and local au- MDA, with > 65% coverage rate of the entire population thorities. A protocol was developed on how to report [13]. MDA is community-based and implemented using and respond to a range of adverse reactions before the Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 4 of 11 start of the MDA advocacy, with the basic health staff Model (GLM, function ‘glm’)withinthe R statistical trained on the procedures. environment (R Development Core Team, 2012) was The monitoring and evaluation of the programme was then used to predict the average Mf values for each conducted through regular sentinel and spot check site township in a year. surveillance at township level. These field data were ana- The parsimony protocol outlined by Crawley [17]was lysed to help assess the impact before- during- after used to simplify the model by removing any redundant MDA implementation activities. Standard surveillance variables and producing the Minimum Adequate Model involved selecting two sites (villages) per IU, with be- (MAM), i.e. non-significant values and interaction terms tween 300 to 500 people (including all ages ≥2 years of were removed sequentially from the highest order inter- age), selected for assessment of infection by examining actions downwards. At each step, the significance of de- night bloods slides for microfilaria (Mf) as per standard leted items was assessed using analysis of variance using guidelines [13]. The blood smears were processed and the AIC statistic. examined in each IU (district) headquarters. The data were then sent to the central level, where all the data Interruption of transmission were maintained in registers and examined at township The transmission assessment survey (TAS) is a standar- level. All baseline sentinel site prevalence data were dised decision-making tool developed and recommended mapped by Township geographical boundary using the by the WHO [13], and was used to determine the de- software ArcGIS 10 (ESRI, Redland, CA). cline in transmission in 2014 in five districts from three regions, including the Magway Region (Minbu District), Modelling the impact of MDA on prevalence Sagaing Region (Kathur, Kalay, Tamu Districts), and To better understand the reductions in prevalence asso- Mandalay Region (Pyin Oolwin District). Prior to stop- ciated with MDA, a statistical model was developed to ping MDA, each district had at least five effective rounds predict the change in Mf prevalence in a township since of MDA, showed evidence of > 65% coverage rates, and the most recent assessment of prevalence, which varied demonstrated significant reduction in Ag (< 2%) and Mf by site. This most recent Mf value was therefore referred (< 1%) prevalence rates in all sites. to below as the “most recent Mf value”. Data were fil- The Kathur, Kalay and Tamu Districts stopped MDA tered to include only townships for which both a base- in late 2007, and were assessed for the decline in trans- line Mf value (i.e. measurement taken prior to any mission using cluster surveys in 2008 according to MDA), and at least one later sentinel and/or spot check WHO guidelines at the time. Therefore, the TAS surveys Mf value were available. Where there were multiple Mf conducted in 2014 were considered to be the second values recorded at the same township in the same a year, TAS or “TAS 2” for these three districts. The results of a mean value was taken and used. Variables considered the first cluster surveys or “TAS 1” from the 2008 sur- for the model included the baseline Mf prevalence value, veys, and the results from TAS 2 in 2014 were presented the most recent Mf value (this may have been either a for these three districts. baseline Mf prevalence value or the results of a post- The TAS survey design was dependent upon factors baseline programmatic survey), the number of MDA such as the net primary school rate in each evaluation rounds undertaken since the beginning of the MDA unit (EU), the target population size, school enrolment, programme, and the number of MDA rounds and years number of schools, mosquito vector type and parasite since the most recent Mf value was collected. Also con- species. The TAS Survey Sample Builder was used to sidered were calculated variables that attempted to automate the calculations of the sample design, size, in- quantify the fragmented nature of the MDA programme; tervals and critical cut-off values. The rapid ICT Binax for example, the number of MDAs since the most recent NOW Filariasis (Alere Inc., Scarborough, ME) was used Mf value divided by the number of years over which these to detect circulating filarial antigen (CFA) in the chil- MDAs has been administered. Also, the total number dren, and validated with a positive control prior to the of MDAs since the beginning of the MDA commencement of the survey. programme divided by the number of years over, which the programme was administered. Finally, the Results maximum and mean number of years between MDAs, Distribution of LF both since the start of the programme and since the The WHO LF prevalence survey found filarial antigen most recent Mf value. ranged from 0% to > 25%. These data were analysed First, all Mf values were transformed using log10(x + 1) spatially to provide an estimated prevalence of filarial due to asymmetry observed in qq plot when untrans- antigen for each district, which highlighted the major fil- formed data was modelled. A number of other transfor- arial focus in the central region of the country. Based on mations were also considered. A Generalized Linear this national reports and historical data, the NPELF Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 5 of 11 defined the 45 endemic IUs (districts) that required (Fig. 2). MDA was extended to 10 IUs across the Mag- MDA, which were predominately in the lowland areas in way and Sagaing Regions in 2002, and then to 22 IUs in the Central Valley Region (Fig. 1b and c). 2004, representing approximately 48% geographical The baseline Mf sentinel site prevalence for each IU coverage. The majority of these MDA IUs had a rela- was conducted prior to MDA implementation. Sentinel tively higher burden of LF. The NPELF aimed to imple- sites were conducted in a step-wise manner over a ment MDA uninterruptedly, however, no MDA took 13 year period between 2001 and 2013. Table 1 summa- place in the years 2005 and 2008 due to delays in DEC rises the MDA and Mf sentinel site information for en- supplies from the donors. Further, in the Mandalay Re- demic IUs in each region. All baseline sentinel site gion, seven IUs had MDA interrupted twice over the prevalence data were mapped by township geographical study period; in 2006 due to incidence of serious adverse boundary, which highlighted similar endemicity patterns reactions during the preceding MDAs, and in 2010 due in the Central Valley Region (Fig. 1d). to DEC supply constraints. The adverse reactions ob- The Mf baseline average rates were highest in Sagaing served during 2001–2004 after the initial MDAs were (7.9%), Mandalay (5.2%) and Magway (3.6%) Regions conducted in Magway Region included giddiness, head- with the highest rates recorded in the districts of Shwe aches, nausea, rashes, fever, urticaria and vomiting. This Bo (15.1%), Kyauk Se (14.7%) and Pakokku (9.1%) in is the only data on adverse reactions available to present, 2002, 2003 and 2002, respectively. Overall the Mf base- and it is recognized the reporting system needs to be line average rates were lowest in the districts of Ayeya- strengthened. waddy (0.5%), Kayin (0.002%) and Tanintharyi (0.5%) The expansion of MDA activities did not take place Regions with the highest Mf rates recorded in Pathein until 2013. Considerable efforts were made to extend the (2.4%), Myawaddy (0.1%) and Dawei (1.8%) in 2004, MDA programme to cover all endemic IUs in 2011 and 2012 and 2008, respectively. See Additional file 2 for 2012. However, the NPELF could not scale up due to the baseline sentinel site prevalence data. lack of funding, need for many resources (e.g. training of basic health staff, advocacy materials), continued prob- MDA implementation lems in procuring adequate quantities of DEC, as well as The first MDA was implemented in two IUs viz., Mag- security related issues in the two endemic districts of way and Theyet Districts in the Magway Region in 2001 Kachin State. No MDA was conducted in 2012. Table 1 Summary of regional/provincial endemic districts, MDA start dates and sentinel site prevalence a b b Region/ Endemic Districts Year of MDA Year of Mf Baseline Mf Mf 3–5 MDA Mf > 5 MDA Province (Implementation Unit – IUs) Start Baseline Average Baseline Round Average Round Average Sentinel Site (no. sites) Range (no. sites) (no. sites) Magway Magway, Thayet, Minbu, Pakoku, 2001–2002 2001–2002 3.2 (n = 9) 0.2–9.1 2.3 (n = 21) 1.2 (n = 29) Sagaing Sagaing, Shwe Bo, Monywa, Kathur, 2002 2002 4.7 (n = 11) 0–15.1 2.8 (n = 12) 1.2 (n = 43) Kalay, Tamu, Chin Paletwa 2004 2003 1.5 (n = 2) 1.4–1.6 0.2 (n =2) - Mandalay Mandalay, Pyin Oo Lwin, Kyauk Se, 2004 2003 5.2 (n = 14) 0.2–14.7 - 2.3 (n = 20) Yamethin, Myin Gyan, Meikhtilar, Nyaung Oo Nay pyi taw Nay pyi taw 2013 2011 1.9 (n = 1) 1.9 - - Rakhine Sittwe, Maungdaw, Kyauk Phyu, 2004 2003–2004 3.0 (n =6) 0–12.6 0.6 (n = 13) Thandwe Ayeyarwaddy Pathein, Hantada, Myaungmya, 2013 2002–2013 0.5 (n = 12) 0–2.4 - - Phyarpone. Maubin Bago Bago, Thanung Ngu, Tharyawaddy, 2013 2005–2013 0.7 (n = 10) 0–2.8 - - Pyay Kayin Hpaan, Kawkareik, Myawaddy 2013 2013 0.002 (n =5) 0–0.1 - - Mon Mawlamying, Thaton 2013 2004–2013 1.8 (n = 4) 0.8–3.2 - - Tanintharyi Dawei, Myeik, Kawthaung 2013 2004–2013 0.5 (n =8) 0–1.8 - - Yangon Yangon North, Yangon South, 2013 2004–2013 0.1 (n =8) 0–0.4 - - Yangon East, Yangon West Mf average based on the total number of sites (in brackets) across the endemic districts. At each site between 300 and 500 people tested. Some sites were tested multiple years before MDA started Mf based on both sentinel sites and spot check sites based on number of sites (in brackets). At each site between 300 and 500 people tested Mf: microfilaria Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 6 of 11 Fig. 2 Programme MDA up scale and down scale between 2001 and 2014 However, in 2013, a major increase in coverage was fi- temporarily stopping MDA due to security related issues. nally reached with support from Sanofi Pasteur, WHO Additional file 3 summarises the scale up and scale down and the Global Network for NTDs for supply of DEC of MDA related activities between 2001 and 2014. and operational costs. This up scaling of MDA resulted Overall, the reported treatment coverage i.e. the cover- in a further 21 IUs receiving treatment in 2013, which co- age calculated for each IU on the basis of reports sent incided with the down scaling of MDA in 2 IUs (Minbu from lower level units (townships, villages) was high, and Pyin Oo Lwin Districts) as they reached the require- ranging from 68.7% to 98.5% of the IU’s entire popula- ments for TAS, and a further 4 IUs from Rakhine State tion (Table 2). A cross-sectional evaluation of the Table 2 Summary of population and reported treatment coverage rates 2001–2014 Year No. of No. of Total population Population which Reported Treatment coverage regions districts covered ingested drugs Overall Range among districts 2001 1 2 1 939 964 1 803 306 93 - 2002 2 10 8 634 179 7 474 094 95.7 93.2–98.5 2004 5 22 17 929 178 15 838 896 82.6 80.1–94.3 2005 - - No MDA No MDA - - 2006 4 15 11 868 901 10 761 777 90.7 79.5–94.1 2007 5 22 20 000 250 18 397 240 91.9 83.4–93.9 2008 - - No MDA No MDA - - 2009 5 19 17 702 845 15 790 286 89.2 85.5–96.4 2010 4 12 10 035 458 9 002 092 89.7 82.7–95.4 2011 5 19 1 7031 636 15 429 100 90.5 85.8–93.4 2012 - - No MDA No MDA - - 2013 7 36 35 488 298 30 313 249 85.4 68.7–93.8 2014 7 37 36 407 716 31 121 035 85.5 74.8–93.7 Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 7 of 11 treatment coverage conducted by a team within the De- The most significant coefficient, was an interaction term partment of Health in randomly selected townships in consisting of two predictor variables (the most recently 2013, found that coverage rates ranged from 60% to collected Mf prevalence (log + 1) and the number of 97.4% across 19 IUs, and reflected reported coverage MDAs administered since that Mf prevalence data were rates in each corresponding IU. Of those people who collected (log + 1). The second most significant coeffi- were eligible, but did not take the drug, the main rea- cient was the baseline prevalence (log + 1). Together, sons were that they were absent at the time of MDA, this demonstrates that whilst the number of rounds of or had refused to take the drugs related to negative MDA is the most important predictor, the underlying rumours regarding MDA. conditions reflected by the baseline figure also affects the results, i.e. two rounds of MDA in a high baseline area will not reduce prevalence as much as two rounds Impact of MDA on field collected prevalence data of MDA in a low baselines area, even if the most recent (baseline and sentinel/spot check sites) Mf value in the two areas is the same. Surprisingly, the The field collected baseline data varied significantly be- covariates that described the fragmented nature of the tween 15.1% to zero in 46 townships across the country. MDA (i.e. the number of missed MDA years) did not Figure 3a highlights the prevalence trends by the num- feature in the MAM. That is, they did not significantly ber of MDA rounds. All but two townships displayed a improve the fit of the model. This may be due to the significant reduction in prevalence over the 13 years for small number of data points available. which data was available, especially after two to three The model unexpectedly predicted an increase in MDA rounds where the prevalence ranged from 0 to prevalence if there were more rounds of MDA between 8.8%. The two townships, Amapura and Pakokku, measurements of prevalence. However, this appears to which reported a rise in prevalence at spot check sites be an artifact of the MDA administration; prevalence (outliers) were removed so that general trends could bet- data were usually collected after every two MDA rounds ter be examined. This resulted in 138 individual Mf site but were collected after 3 rounds of MDA in Mandalay. values included in further analysis, and showed that the The model shows that three rounds of MDA in Manda- prevalence after two to three MDA rounds was signifi- lay had less effect on prevalence than two rounds of cantly reduced, and ranged from 0 to 5.9%. MDA elsewhere; therefore suggesting that in Mandalay specifically, the MDAs were less effective. Modelling the impact of MDA on prevalence The modelled data shown in Fig. 3b clearly reflects the The townships for which sentinel site and spot check same prevalence trend as the field collected data. The prevalence data were available received between 0 and initial two MDA rounds produced a significant reduc- 12 rounds of MDA. A model predicting the Mf preva- tion in prevalence which was followed by a much lence in a township in a year from the most recent as- smaller reduction in subsequent MDA rounds, with sessment of Mf prevalence at the same township was prevalence levelling out. The models suggest a similar produced. After the removal of redundant terms, the trend, for example an area with 30% baseline prevalence, model consisted of two coefficients (Fig. 3b; Table 3). drops to 6.5% after the first two MDA rounds indicating Fig. 3 Sentinel and spot check data and modelled distributions by number of MDA rounds. (a) Township data (b) Modelled data. Note. Township data includes all points from all sentinel sites and modelled data include selected sites Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 8 of 11 Table 3 Minimal Adequate Model (MAM) predicting prevalence at Township level from prevalence previously measured and number rounds MDAs Coefficients: Estimate Std. Error t value Pr(>|t|) (Intercept) - 0.05012 0.03641 - 1.377 0.172 logBaselineMf 0.27098 0.05263 5.149 1.77e - 06 logPreviousMf: logMDAsSincePreviousMf 0.73239 0.11677 6.272 1.59e - 08 Residual standard error: 0.1507 on 82 degrees of freedom Multiple R-squared: 0.6162, Adjusted R-squared: 0.6069 F-statistic: 65.84 on 2 and 82 DF, P-value < 2.2e - 16 a reduction of 78%. The next two MDA rounds reduce critical cut-off of 18 positive children calculated for all further, but less dramatically, to 3.5%, and two further EUs (Table 4). MDA rounds reduce prevalence to 2.8%. For sites with a The field activities involved 5 to 7 teams consisting of baseline of 15%, the effect of the first two MDA rounds three people each: supervisor, data collector and a tech- is a 73% reduction to 3.9% prevalence (next two MDA nician. All team members were trained per the TAS rounds reduce prevalence to 2.3%, with little further ef- guidelines by a Central and Regional Team leader. The fect after four MDA rounds). For areas with a baseline Township Medical Officer was responsible for informing of 7%, the effect of the first two rounds of MDA is a and coordinating activities with the Township Education 69% reduction to a prevalence of 2.2% (next two MDA Department, and Headmasters of the selected school be- rounds reduce to 1.4% prevalence, with little effect after fore the survey. The Headmaster of each school pro- four MDA rounds). vided an official class register and all eligible children were identified for selection. For each selected child, their name, sex, age, and grade was recorded and 100 μl Decline in transmission of blood collected for ICT. No child refused to partici- In 2008, the first cluster surveys or “TAS 1” for the pate in the survey. Kalay, Kathar and Tamu Districts found no ICT positive The TAS 1 results for Minbu and Pyin Oo Lwin EUs children among the 2269, 3003, and 3085 tested across found 1 positive child, and the TAS 2 results for Kalay, 16, 31, and 25 schools respectively. Further details of the Kathar and Tamu EUs found 1 positive child (Table 4). schools surveyed are in Additional files 4, 5, and 6. These results resulted in all EUs being under the critical In 2014, the pre-TAS assessments indicated that all cut-off and passing TAS. The two positive children were five IUs had sufficient number of MDA rounds, and high treated and the parents and relative Township Medical reported treatment coverage rates of > 85%. Based on Officer informed for further monitoring as required. the population size and school enrolment rates of > 90%, school-based surveys were conducted in each IUs, which Discussion were evaluated as EUs, with sample sizes of between Overall good programmatic progress has been made by the 1556 to 1548 children across 30 to 52 schools, and Myanmar NPELF with the successful scale up of MDA Table 4 Summary of IU populations, MDA and TAS characteristics Population and MDA TAS Districts Total Pop. MDA Rounds MDA Coverage No. 6–7 aged No. Total Sample No. Schools Children No. ICT & Years Range Children Schools Size Tested Absent % Positive Minbu TAS 1 689 965 10 MDAs 86–94% 27 252 759 1556 52 2.3% 1 2002–2014 Pyin Oolwin 851 945 6 MDAs 85–99% 32 529 634 1556 36 0.2% 0 TAS 1 2004–2014 Kalay TAS 2 487 762 5 MDAs 85–98% 24 461 387 1556 30 0.7% 0 2002–2007 Kathar TAS 2 819 281 5 MDAs 92–100% 34 090 1077 1556 58 0.4% 1 2002–2007 Tamu TAS 2 105 100 5 MDA 92–100% 17 155 77 1548 30 0% 0 2002–2007 Note. Details of MDA years available in Additional file 3 IU: Implementation Unit MDA: Mass drug administration TAS: Transmission assessment survey Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 9 of 11 implementation, widespread significant reductions in the Culex spp. vectors [28]. Thus, information on the prevalence, and the initiation of post-MDA surveillance ac- vector biting rates may be key for better insights into the tivities in five districts. This national overview extends transmission dynamics and elimination in a geographic the findings from four endemic states/regions by Win et al., region, especially in the endgame phase where there is and highlights that progress has been achieved despite the risk of recrudescence, as highlighted in recent math- some challenges in obtaining regular funding and support ematical models [29, 30]. from international partners and stakeholders, reports of The NPELF may also consider the possibility and side-effects during MDA, internal security issues, and diffi- feasibility of triple drug therapy, including ivermectin, culties in obtaining the drug DEC. The progress to-date DEC and albendazole (IDA) and the protocols have may be attributed to several factors identified as determi- recently been released for field use [31, 32]. The high nants of LF programme success as noted in other countries effectiveness of this therapy, may shorten the duration [18, 19] including the i) general low transmission levels and cost of MDAs, especially in potential ‘hotspot’ found at baseline with the majority of Mf rates < 15%; areas, or where MDA coverage has been repeatedly ii) MDA regime of albendazole and DEC which is consid- interrupted such as Mandalay, which had only three ered a highly effective combination against the MDAs over a 8 year period and showed areas of per- parasite W. bancrofti; and iii) good health system infra- sistent infection [33]. The IDA may also be useful for structure, administration and training. It is also likely that areas with low, or lowered prevalence where trans- this widespread MDA coverage with albendazole for LF mission appears difficult to ultimately interrupt [28]. has impacted on soil transmitted helminths (STH) infec- However, measuring and modelling the impact of IDA tion rates, which will be beneficial to the STH MDA on filariasis prevalence will be crucial. Understanding programme and should be taken into account [20]. the barriers to high MDA coverage will also be im- Notwithstanding these positive steps forward, the portant, and more in-depth studies in problem areas NPELF will face some challenges to complete all pro- should be undertaken [34, 35]. Further, it will be im- grammatic activities by the GPELF elimination goal of portant for the NPELF to strengthen its response to 2020 [21, 22]. It will require pro-active interaction with and recording of adverse reactions as this has been a drug donors to ensure steady DEC supply. International programme weakness to date. collaboration and support may be more achievable now The TAS in five districts confirms that transmission has with the changed political situation in country [23]. This declined significantly in some areas of the country. How- may help to address any challenges that arise and main- ever, as standard post-MDA surveillance activities scale up tain the momentum of the programme. The NPELF is at over the next 5 years, the NPELF could be further crucial stage now in terms of undertaking multiple activ- strengthened by training more personnel and increasing ities in as many as 45 districts. Hence, more technical the number of teams to support the activities on a more and financial support from international partners and full-time basis as other countries have done [7, 19]. Inte- stakeholders is key to its future success. grating alternative methods of monitoring and evaluation Importantly, MDA implementation was initially fo- into the existing health system structure will also be cused in high transmission areas, and the programme important to ensure that surveillance is sustainable long- was able to demonstrate that the most significant reduc- term, and sufficiently sensitive and targeted to find poten- tions occurred after 2 to 3 rounds of MDA. This trans- tial problem areas or hotspots of transmission [36, 37]. In mission reduction pattern is consistent with other parallel, MMDP mapping and related activities, and add- studies in the South-East Asian Region and elsewhere itional integrated post-TAS activities need be initiated and [19, 24–27], and is in agreement with the predicted could be conducted using new tools and field scenar- model presented in this paper. The model confirms that ios [7, 38]. The districts with high burden of chronic dis- LF prevalence reduces with number of MDAs. However, ease and high baseline infection should be prioritized, and the effect of each subsequent MDA is less than the one the key activities integrated with health system. before, and also dependent on the initial prevalence rate. Notably, after a number of MDAs, the prevalence Conclusions reaches an asymptote i.e. levels out to a point, that was This study highlights that the Myanmar NPELF has proportional to the initial prevalence rate. This suggests made positive steps forward in the elimination of LF that, whilst in low endemic areas MDA may be sufficient with significant reductions in prevalence and the first to reach elimination, in higher endemic areas, reducing evidence of interrupting transmission. It will be im- the transmission levels to zero may prove difficult and portant for the NPELF to maintain this momentum, the current MDA strategy would potentially benefit aim to maximize its capacity and draw on inter- from supplementary interventions such as vector con- national stakeholder support to help meet the na- trol, and environmental management to better control tional and global goals of elimination. Aye et al. Infectious Diseases of Poverty (2018) 7:56 Page 10 of 11 Additional files Centre for Neglected Tropical Diseases, Liverpool School of Tropical Medicine, Liverpool, UK. Additional file 1: Multilingual abstracts in the five official working Received: 31 July 2017 Accepted: 5 April 2018 languages of the United Nations. (PDF 250 kb) Additional file 2: Baseline Mf prevalence in district sentinel sites. (DOCX 35 kb) Additional file 3: Matrix of MDA in endemic districts from 2001 to References 2014. (DOCX 37 kb) 1. World Health Organization. Global programme to eliminate lymphatic filariasis: progress report, 2015. Wkly. Epidemiol. Rec. 2016;91:73–88. Additional file 4: ICT Survey in school children in Tamu Township Available from: http://www.who.int/lymphatic_filariasis/resources/who_ District in 2008. (DOCX 23 kb) wer9139/en/. Accessed 16 Mar 2018. Additional file 5: ICT Survey in school children in Katha District in 2008. 2. Ramaiah KD, Ottesen E a. Progress and impact of 13 years of the global (DOCX 25 kb) Programme to eliminate lymphatic Filariasis on reducing the burden of Additional file 6: ICT Survey in infant and school children from Kalay filarial disease. PLoS Negl Trop Dis 2014;8:e3319. Available from: http://dx. District in 2008. (DOCX 22 kb) plos.org/10.1371/journal.pntd.0003319. Accessed 16 Mar 2018. 3. Dreyer G, Norões J, Figueredo-Silva J, Piessens WF. Pathogenesis of lymphatic disease in bancroftian filariasis: a clinical perspective. Parasitol Abbreviations Today. 2000;16:544–8. 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New Delhi, Township Vector Borne Disease Control teams, and the field research India, 9–10 August 2011; 2012 Available from: http://appssearowhoint/pds_ assistants who helped in undertaking the programmatic work. docs/B4867pdf?ua=1. Accessed 16 Mar 2018. 9. de Meillon B, Grab B, Sebastian A. Evaluation of Wuchereria bancrofti Funding infection in Culex pipiens fatigans in Rangoon, Burma. Bull World Health The LF programme activities were supported by the Ministry of Health and Organ. 1967;36:91–100. Sports, and funds from the Centre for Neglected Tropical Diseases (CNTD), 10. Sasa M. Human filariasis – a global survey of epidemiology and control. Liverpool, UK through a grant from the Department for International Baltimore: University Park Press; 1976. Development (DFID) and GlaxoSmithKline (GSK) for the elimination of 11. Research and Training in Tropical Diseases (TDR). Research on Rapid lymphatic filariasis. Geographical Assessment of Bancrofti Filariasis. 1997. 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Journal

Infectious Diseases of PovertySpringer Journals

Published: May 31, 2018

References

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