Abstract
Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management. Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding. In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR’s were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points. This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies.
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References
Nutman TB, Kazura JWLymphatic Filariasis. In: Guerrant RL, Walker DH, Weller P F, editors. Tropical Infectious Diseases: Principles, Pathogens, and Practice. Edinburg, London, New York, Oxford, Philadelphia, St. Louis, Sydney, Toronto: Saunders Elsevier; 2011, p. 729–34.
Shenoy RK, Kumaraswami V, Suma TK, Rajan K, Radha-kuttyamma G. A double-blind, placebo-controlled study of the efficacy of oral penicillin, diethylcarbamazine or local treatment of the affected limb in preventing acute adenolymphangi-tis in lymphoedema caused by brugian filariasis. Ann Trop Med Parasitol 1999;93;367–77.
Pani S P, Yuvaraj J, Vanamail P, Dhanda V, Michael E, Grenfell BT, et al. Episodic adenolymphangitis and lymphoedema in patients with bancroftian filariasis. Trans R Soc Trop Med Hyg 1995;89;72–4.
Pani SP, Srividya A. Clinical manifestations of bancroftian filaria-sis with special reference to lymphoedema grading. Indian J Med Res 1995;102;114–8.
Shenoy RK, Suma TK, Rajan K, Kumaraswami V. Prevention of acute adenolymphangitis in brugian filariasis: comparison of the efficacy of ivermectin and diethylcarbamazine, each combined with local treatment of the affected limb. Ann Trop Med Parasitol 1998;92;587–94.
Addiss DG, Michel MC, Michelus A, Radday J, Billhimer W, Louis-Charles J, et al. Evaluation of antibacterial soap in the management of lymphoedema in Leogane, Haiti. Trans R Soc Trop Med Hyg 2011;105;58–60.
Dreyer G, Addiss D, Dreyer P, Noroes J. Basic Lymphoedema management: treatment and prevention of problems associated with lymphatic filariasis, Hollis, NH: Hollis Publishing Company; 2002.
Fox LM, Wilson SF, Addiss DG, Louis-Charles J, Beau de Rochars M V, Lammie PJ. Clinical correlates of filarial infection in Haitian children: an association with interdigital lesions. Am J Trop Med Hyg 2005;73;759–65.
McPherson T, Persaud S, Singh S, Fay MP, Addiss D, Nutman TB, et al. Interdigital lesions and frequency of acute dermatolymph-angioadenitis in lymphoedema in a filariasis-endemic area. Br J Dermatol 2006;154;933–41.
Dreyer G, Addiss D, Gadelha P, Lapa E, Williamson J, Dreyer A. Interdigital skin lesions of the lower limbs among patients with lymphoedema in an area endemic for bancroftian filariasis. Trop Med Int Health 2006;11;1475–81.
Babu BV, Nayak AN, Dhal K. Epidemiology of episodic adeno-lymphangitis: a longitudinal prospective surveillance among a rural community endemic for bancroftian filariasis in coastal Orissa, India. BMC Public Health 2005;5;50.
Suma TK, Shenoy RK, Kumaraswami V. Efficacy and sustain-ability of a footcare programme in preventing acute attacks of adenolymphangitis in Brugian filariasis. Trop Med Int Health 2002;7;763–6.
Kerketta AS, Babu BV, Rath K, Jangid PK, Nayak AN, Kar SK. A randomized clinical trial to compare the efficacy of three treatment regimens along with footcare in the morbidity management of filarial lymphoedema. Trop Med Int Health 2005;10;698–705.
Addiss DG, Louis-Charles J, Robert J, Leconte F, Wendt JM, Milord MD, et al. Feasibility and effectiveness of basic lymphedema management in Leogane, Haiti, an area endemic for bancroftian filariasis. PLoS Negl Trop Dis 2010;4;e668.
Jullien P, Some JD, Brantus P, Bougma RW, Bamba I, Kyelem D. Efficacy of home-based lymphoedema management in reducing acute attacks in subjects with lymphatic filariasis in Burkina Faso. Acta Trop 2011;120;S55–S61.
Mues KE, Deming M, Kleinbaum DG, Budge PJ, Klein M, Leon JS, et al. Impact of a community-based lymphedema management program on episodes of Adenolymphangitis (ADLA) and lymphedema progression–Odisha State, India. PLoS Negl Trop Dis 2014;8;e3140.
Dreyer G, Addiss D, Dreyer P, Noroes J. Assessment of Chronic Lymphoedema. In: Dreyer G, Addiss D, Dreyer P, Noroes J, editors. Basic Lymphoedema Management: Treatment and Prevention of Problemts Associated with Lymphatic Filariasis, Hollis NH: Hollis Publishing Company; p. 13–22.
Faires DEK, Kadziola ZA. Analysis of Longitudinal Observational Data Using Marginal Structural Models. In: Faires DEK, Leon AC, Haro JM, Obenchain RL, editors. Analysis of Observational Health Care Data Using SAS, Cary, NC: SAS Institute Cary; 2010.
Robins JM. Correction for non-compliance in equivalence trials. Stat Med 1998;17;269–302. discussion 387–9.
Robins JM, Hernan MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology 2000;11;550–60.
Baird JB, Charles JL, Streit TG, Roberts JM, Addiss DG, Lammie OJ. Reactivity to bacterial, fungal, and parasite antigens in patients with lymphedema and elephantiasis. Am J Trop Med Hyg 2002;66;163–9.
World Health Organization (WHO). Lymphatic filariasis: managing morbidity and preventing disability: an aide-memoire for national programme managers. Geneva, Switzerland; 2013.
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Mues, K.E., Klein, M., Kleinbaum, D.G. et al. The Effect of a Regimen of Antifungal Cream Use on Episodes of Acute Adenolymphangitis (ADL) among Lymphedema Patients: An Application Using Marginal Structural Models. J Epidemiol Glob Health 8, 176–182 (2018). https://doi.org/10.2991/j.jegh.2017.10.009
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DOI: https://doi.org/10.2991/j.jegh.2017.10.009