44th Myanmar Health Research Congress

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1 44th Myanmar Health Research Congress Early Detection of Lymphatic Disturbance in Adolescent Infected with Lymphatic Filariasis Jan Douglass 1, Susan Gordon 1, Patricia Graves 1, Ben Dickson 1, Dr Ni Ni Aye 2, Dr Khin Nan Lon 2, Dr Khin Saw Aye 2 Dr San San Win 3, Dr Yi Yi Win 2, Dr Tint Wai 2 1 James Cook University, Australia 2 Ministry of Health, Myanmar 3 World Health Organization, Myanmar

2 Lymphatic Filariasis Infection with nematode worms Wuchereria bancrofti Brugia malayi, Brugia timori Microfilaria transmitted by mosquitoes Culex Aedes, Anopheles, Mansoni spp

3 Clinical Manifestations

4 Lymphatic Filariasis Major cause of disability globally 73 endemic countries 1.39 billion people at risk 60% SE Asia 30% Africa 120 million infected 40 million have chronic disease 25 million hydrocele 15 million lymphoedema

5 Global Program to Eliminate LF Mass Drug Administration Annual single dose of preventive chemotherapy 5 6 consecutive years Morbidity Management and Disability Prevention Daily hygiene protocol Treat acute attacks

6 LF in Myanmar Highly endemic in low-lying areas Elimination program commenced in 2001 but inconsistent coverage Only Magwe Region has received adequate MDA coverage Very limited prevalence data No formal morbidity management program

7 Breast Cancer Related Lymphedema

8 Filariasis Related Lymphedema Treatment Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Stage 6 Stage 7 Hygiene (washing & drying) Yes (ideally at night) Yes (ideally at night) Yes (ideally at night) Yes (ideally at night) Yes (twice a day if possible) Yes (twice a day if possible) Yes (twice a day if possible) Care of entry lesions If present If present If present If present If present If present If present Exercise Yes Yes Yes Yes If possible If possible If possible Elevation Compression bandaging Usually not Day and night Day and night Day and night Day and night Day and night necessary Stage 0?? if possible Only when Only when Not advised in Optional Optional Optional advised advised most cases Day and night if possible Not advised in most cases Prophylactic creams No No No When necessary Usually necessary Always necessary Always necessary Prophylactic Ab (send to doctor) No No No Usually not necessary Usually necessary Always necessary Always necessary Plastic surgery No No No If medically indicated If medically indicated If medically indicated If medically indicated

9 Study - Aims 1. Determine if latent lymphedema can be detected in young people infected with LF 2. Identify the optimal point and form of intervention to prevent progression to chronic disease

10 Study Design LF endemic Townships in Central Myanmar identified during MDA, September 2013 Morbidity Survey; Prevalence of Lymphoedema and Hydrocele - Ben Dickson Cross Sectional Survey; Screening for LF infection by ICT Age and Gender matched positive and negative adolescents Physical Measures of lower limbs Blood samples for dried filter paper and plasma Longitudinal Study; Interventional Study; Repeat measures and blood samples collected after the annual MDA, December 2014 and again after treatment of positive cases, March 2015 RCT of prevention strategies in young people at risk of developing chronic disease

11 Study Site Selection LF endemic Townships in Central Myanmar identified during MDA, September 2013

12

13 Data Collection LF endemic Townships in Central Myanmar identified during MDA, September 2013 Morbidity Survey; Prevalence of Lymphoedema and Hydrocele - Ben Dickson Cross Sectional Survey; Screening for LF infection by ICT Age and Gender matched positive and negative adolescents Physical Measures of lower limbs Blood samples for dried filter paper and plasma Longitudinal Study; Interventional Study; Repeat measures and blood samples collected after the annual MDA, December 2014 and again after treatment of positive cases, March 2015 RCT of prevention strategies in young people at risk of developing chronic disease

14 Sampling 4 Townships Amarapura Patheingyi Tada-U Wundwin 24 randomly selected villages 20 randomly selected households from each village 460 Households 1014 Participants

15 Household Interview

16 Testing For Infection

17 Clinical Assessment

18 Data Collection LF endemic Townships in Central Myanmar identified during MDA, September 2013 Morbidity Survey; Prevalence of Lymphoedema and Hydrocele - Ben Dickson Cross Sectional Survey; Screening for LF infection by ICT Age and Gender matched positive and negative adolescents Physical Measures of lower limbs Blood samples for dried filter paper and plasma Longitudinal Study; Interventional Study; Repeat measures and blood samples collected after the annual MDA, December 2014 and again after treatment of positive cases, March 2015 RCT of prevention strategies in young people at risk of developing chronic disease

19 Screening and Participant Selection

20 Immuno Chromatographic Test Card

21 Data Collection LF endemic Townships in Central Myanmar identified during MDA, September 2013 Morbidity Survey; Prevalence of Lymphoedema and Hydrocele - Ben Dickson Cross Sectional Survey; Screening for LF infection by ICT Age and Gender matched positive and negative adolescents Physical Measures of lower limbs Blood samples for dried filter paper and plasma Longitudinal Study; Interventional Study; Repeat measures and blood samples collected after the annual MDA, December 2014 and again after treatment of positive cases, March 2015 RCT of prevention strategies in young people at risk of developing chronic disease

22 Data Collection

23

24 Data Collection LF endemic Townships in Central Myanmar identified during MDA, September 2013 Morbidity Survey; Prevalence of Lymphoedema and Hydrocele - Ben Dickson Cross Sectional Survey; Screening for LF infection by ICT Age and Gender matched positive and negative adolescents Physical Measures of lower limbs Blood samples for dried filter paper and plasma Longitudinal Study; Interventional Study; Repeat measures and blood samples collected after the annual MDA, December 2014 and again after treatment of positive cases, March 2015 RCT of prevention strategies in young people at risk of developing chronic disease

25 Data Collection LF endemic Townships in Central Myanmar identified during MDA, September 2013 Morbidity Survey; Prevalence of Lymphoedema and Hydrocele - Ben Dickson Cross Sectional Survey; Screening for LF infection by ICT Age and Gender matched positive and negative adolescents Physical Measures of lower limbs Blood samples for dried filter paper and plasma Longitudinal Study; Repeat measures and blood samples collected after MDA, December 2014 Treatment of positive cases, March 2015

26 Data Collection LF endemic Townships in Central Myanmar identified during MDA, September 2013 Morbidity Survey; Prevalence of Lymphoedema and Hydrocele - Ben Dickson Cross Sectional Survey; Screening for LF infection by ICT Age and Gender matched positive and negative adolescents Physical Measures of lower limbs Blood samples for dried filter paper and plasma Longitudinal Study; Interventional Study; Repeat measures and blood samples collected after the annual MDA, December 2014 and again after treatment of positive cases, March 2015 RCT of prevention strategies in young people at risk of developing chronic disease

27 Data Analysis Comparison of positive and negative cases Analysis of plasma samples, Department of Medical Research, Yangon Og4C3 and Bm14 ELISA

28 Data Analysis Analysis of plasma samples, Department of Medical Research, Yangon Og4C3 and Bm14 ELISA Confirmation of positive and negative cases Comparison of plasma and dried filter papers, NTD Lab, Cairns. Jesse Martin Validation of Bm14 ELISA from filter paper samples Physical Measures Three devices which measure tissue compressibility Extracellular fluid loads by bio impedance spectroscopy Analysis of plasma for pro-inflammatory cytokines and vascular endothelial growth factors Liverpool School of Tropical Medicine, PhD student Julio Furlong Silva Analysis of plasma for vascular endothelial growth factors DMR Yangon unfunded

29 Results Analysis of plasma samples, Department of Medical Research, Yangon Og4C3 and Bm14 ELISA Confirmation of positive and negative cases Physical Measures Three devices which measure tissue compressibility Extracellular fluid loads by bio impedance spectroscopy Comparison of plasma and dried filter papers, NTD Lab, Cairns. Jesse Martin Validation of Bm14 ELISA from filter paper samples Analysis of plasma for pro-inflammatory cytokines and vascular endothelial growth factors Morbidity Survey Lymphoedema and hydrocele cases Infection rates MDA consumption

30 Cross Sectional Survey n= % 71.11% 57.14% % 19.1% 17.89% 23.08% 26.67% 12.22% 50 0 Male Female years years Tha Le Swart Sar Kyin Wa Other* Screened October 2014 Positive by ICT Participated in Longitudinal Study

31 Baseline Characteristics, Longitudinal Study n= Age Height (cm) (lbs) Weight Positive 0 Positive Negative

32 Baseline - Tonometer

33 p = 0.04 Baseline - Indurometer

34 Non-dominant Calf after MDA and/or Deworming Treatment p = 0.04 p = 0.28 p = 0.89 p = 0.18 p = 0.77 p = 0.10

35 MDA Consumption (%) % 57% 0 Male +ve Male -ve Female +ve Female -ve Total MDA 2013 MDA 2014

36 Prevalence (%) Morbidity Survey n=1014 Infection Prevalence by ICT (%) Adjusted Infection Prevalence by Mf (%) Amarapura Patheingyi Tada-U Wundwin Total

37 MDA Participation No. Program HH Visits (n of 6)

38 Chronic Limb Morbidity

39 Prevalence (%) Chronic Scrotal Morbidity 35.0 Hydrocele Prevalence in Males 15y (%) Amarapura Patheingyi Tada-U Wundwin Total

40 Conclusions and Future Directions Morbidity Survey 4 Townships High prevalence of hydrocele cases Surgical program Low prevalence of lymphedema 3000 cases MMDP program MDA consumption Social Engagement Training volunteer drug distributors Education of quarter leaders

41 Conclusions and Future Directions Early Detection Study Uniform trend of tissue softening Infected participants Amend MMDP guidelines to Include Stage 0 Include preventative practices Further research on Identification of people at risk Proactive intervention in early stages

42 Acknowledgements - Institutions Ministry of Health, Union of the Republic of Myanmar Vector Borne Disease Control, Mandalay Public Health Laboratory, Mandalay Department of Medical Research, Yangon WHO, Myanmar Regional Office Australian Embassy, Yangon JCU WHO Collaborating Centre for the Control of Lymphatic Filariasis, Soil Transmitted Helminths and other Neglected Tropical Diseases

43 Local Research Assistants

44 Acknowledgements Impedimed Australia Delfin Technologies Finland Cellabs Australia JCU Division of Tropical Medicine Pentagon Freight Nation Advertising Aetherstudios web design Singapore Airlines

45

46 Thank You Facebook, Jan Douglass (Myanmar Project)

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