Detecting the unseen: covert tissue changes in lymphatic filariasis and implications for the future of morbidity management

Douglass, Janet (2017) Detecting the unseen: covert tissue changes in lymphatic filariasis and implications for the future of morbidity management. PhD thesis, James Cook University.

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Introduction: Lymphoedema is a disfiguring and debilitating disease that cannot be cured. It occurs when lymphatic clearance from the tissue spaces is inadequate and is characterised by enlargement of the skin and subcutaneous tissue compartment. These pathological connective tissue changes can lead to gross deformity of limbs, significant social stigma, and reduced quality-of-life.

The majority of the global burden of lymphoedema is caused by the parasitic infection lymphatic filariasis (LF) and it is estimated that 17 million people are living with filariasis-related lymphoedema (FRL). The global program to eliminate LF (GPELF) aims to: interrupt transmission of the parasite using preventive chemotherapy (PC) delivered via annual mass drug administration (MDA) campaigns, and provide existing cases with adequate education and support in FRL management. Recommendations for FRL management in the GPELF have few strategies to reverse or halt early disease and no recognition of a latent or covert stage of disease. In contrast, treatment for breast cancer-related lymphoedema (BCRL) has moved from managing later stage disease with specially made compression garments, to preventive intervention as soon as a covert oedema is detected.

Covert lymphatic dysfunction has been detected in asymptomatic people with LF, but this has been achieved using expensive and invasive imaging methods. There is limited evidence that PC may reverse these covert changes but this is usually in research cohorts where everyone receives the medication, and not in real-life situations where community level coverage of PC during MDA is rarely 100%. Tissue tonometry is frequently used to measure changes in skin and connective tissue composition and bio-impedance spectroscopy (BIS) has been shown to detect latent BCRL. These devices are inexpensive, field-friendly, and well validated in BCRL but have had negligible use in FRL.

Objectives of this thesis: To determine if covert connective tissue changes can be detected in the lower limbs of young people living in a LF endemic region in central Myanmar, and the effect of annual PC medication on any changes found at baseline. Secondary outcomes were to: establish the reliability of the devices in the lower limbs of young people in Myanmar and Australia and identify moderating factors associated with variance in device scores.

Methods: Three tissue tonometers and one BIS device were used to measure tissue compressibility and free fluid in the lower limbs of young people in an LF endemic region in Myanmar. Data were collected before and after the annual MDA of PC medication and again after further PC had been offered to infected cases not covered by the MDA.

Results: All the devices were found to have good to excellent intra-rater reliability in the young Australian and Myanmar cohorts. Significant variations in device scores were associated with age, gender, BMI, hydration, and the female menstrual cycle. At baseline, LF-positive cases in Myanmar had clinically relevant and statistically significant increases in tissue compressibility at the non-dominant calf using the Indurometer, and in free fluid in the non-dominant leg using BIS. After the annual MDA, and with further PC offered to positive cases missed by the MDA, these between-infection group differences were not evident at follow-up, but the effect of time made this result unclear and further statistical modelling is required to clarify this.

Conclusions and implications: The Indurometer was able to detect a clinically relevant and statistically significant increase in tissue compressibility at the non-dominant calf in LF-positive, asymptomatic cases in Myanmar compared to their LF-negative peers. This single large significant result is supported by trends within and between other devices. These trends suggest the Indurometer and BIS as potential measures of connective tissue change in overt FRL cases and further study in this population is warranted. Evidence for the existence of covert pathology associated with LF is increasing and these findings add another piece to that puzzle. This combined evidence supports the recognition of a stage 0 in FRL. Further recommendations for GPELF activities based on this thesis are: increased efforts to detect covert and early lymphoedema, and the instigation of enhanced morbidity management for early stage FRL.

Item ID: 53611
Item Type: Thesis (PhD)
Keywords: bio-impedance spectroscopy, body composition, electric impedance, geographic factor, lower extremity, lymphatic filariasis, lymphedema, Myanmar, neglected tropical disease, tissue tonometry, tonometry methods
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Publications arising from this thesis are available from the Related URLs field. The publications are:

Douglass, Janet, Graves, Patricia, and Gordon, Susan (2016) Self-care for management of secondary lymphedema: a systematic review. PLoS Neglected Tropical Diseases, 10 (6). pp. 1-20.

Douglass, Janet, Graves, Patricia, and Gordon, Susan (2017) Intrarater reliability of tonometry and bio-impedance spectroscopy to measure tissue compressibility and extracellular fluid in the legs of healthy young people in Australia and Myanmar. Lymphatic Research and Biology, 15 (1). pp. 57-63.

Douglass, Janet, Graves, Patricia, Lindsay, Daniel, Becker, Luke, Mason, Jesse, Aye, Ni Ni, Win, San San, Wai, Tint, Win, Yi Yi, and Gordon, Susan (2017) Lymphatic filariasis increases tissue compressibility and extracellular fluid in lower limbs of asymptomatic young people in Central Myanmar. Tropical Medicine and Infectious Disease, 2 (4).

Date Deposited: 10 May 2018 04:32
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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