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The Effect of Hygiene-Based Lymphedema Management in Lymphatic Filariasis-Endemic Areas: A Systematic Review and Meta-analysis

  • Meredith E. Stocks,

    Affiliations Children Without Worms, Task Force for Global Health, Decatur, Georgia, United States of America, Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America

  • Matthew C. Freeman,

    Affiliation Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States of America

  • David G. Addiss

    Affiliation Children Without Worms, Task Force for Global Health, Decatur, Georgia, United States of America

The Effect of Hygiene-Based Lymphedema Management in Lymphatic Filariasis-Endemic Areas: A Systematic Review and Meta-analysis

  • Meredith E. Stocks, 
  • Matthew C. Freeman, 
  • David G. Addiss



Lymphedema of the leg and its advanced form, known as elephantiasis, are significant causes of disability and morbidity in areas endemic for lymphatic filariasis (LF), with an estimated 14 million persons affected worldwide. The twin goals of the World Health Organization’s Global Program to Eliminate Lymphatic Filariasis include interrupting transmission of the parasitic worms that cause LF and providing care to persons who suffer from its clinical manifestations, including lymphedema—so-called morbidity management and disability prevention (MMDP). Scaling up of MMDP has been slow, in part because of a lack of consensus about the effectiveness of recommended hygiene-based interventions for clinical lymphedema.

Methods and Findings

We conducted a systemic review and meta-analyses to estimate the effectiveness of hygiene-based interventions on LF-related lymphedema. We systematically searched PubMed, Embase, ISI Web of Knowledge, MedCarib, Lilacs, REPIDISCA, DESASTRES, and African Index Medicus databases through March 23, 2015 with no restriction on year of publication. Studies were eligible for inclusion if they (1) were conducted in an area endemic for LF, (2) involved hygiene-based interventions to manage lymphedema, and (3) assessed lymphedema-related morbidity. For clinical outcomes for which three or more studies assessed comparable interventions for lymphedema, we conducted random-effects meta-analyses. Twenty-two studies met the inclusion criteria and two meta-analyses were possible. To evaluate study quality, we developed a set of criteria derived from the GRADE methodology. Publication bias was assessed using funnel plots. Participation in hygiene-based lymphedema management was associated with a lower incidence of acute dermatolymphagioadenitis (ADLA), (Odds Ratio 0.32, 95% CI 0.25–0.40), as well as with a decreased percentage of patients reporting at least one episode of ADLA during follow-up (OR 0.29, 95% CI 0.12–0.47). Limitations included high heterogeneity across studies and variation in components of lymphedema management.


Available evidence strongly supports the effectiveness of hygiene-based lymphedema management in LF-endemic areas. Despite the aforementioned limitations, these findings highlight the potential to significantly reduce LF-associated morbidity and disability as well as the need to develop standardized approaches to MMDP in LF-endemic areas.

Author Summary

The tropical disease lymphatic filariasis (LF) causes chronic swelling of the leg—lymphedema—in 14 million people worldwide. To stop the spread of LF, a program led by the World Health Organization (WHO) offers annual preventive drug treatment to affected communities. For people who already have lymphedema, WHO recommends simple hygiene-based measures that include skin care and limb movement. Yet only a small proportion of those with LF-related lymphedema have been trained in these measures. To determine the effectiveness of hygiene-based lymphedema management, we reviewed the scientific literature. Twenty-two studies were found that 1) used hygiene-based interventions to manage lymphedema; 2) measured the effect of these interventions; and 3) were done in an area where LF occurs. Overall, use of hygiene-based measures was associated with 60% lower odds of inflammatory episodes, known as “acute attacks,” in the affected limb. Acute attacks cause severe pain, fever, and disability, and they make lymphedema worse. Hygiene and sanitation are necessary for control of many tropical diseases. Hygiene is also effective for managing LF-related lymphedema and reducing suffering caused by acute attacks. Training people with lymphedema in hygiene-based interventions should be a priority for LF programs everywhere.


Lymphedema of the leg and its advanced form, known as elephantiasis, are significant causes of disability and morbidity in areas endemic for lymphatic filariasis (LF), with an estimated 14 million persons affected worldwide [1]. In 1998, the World Health Organization (WHO) launched its Global Program to Eliminate Lymphatic Filariasis (GPELF) with the twin goals of (a) interrupting transmission of the parasitic worms that cause LF and (b) providing care to persons who suffer from lymphedema and other clinical manifestations of LF [2, 3]. Although mass treatment with antiparasitic drugs has led to significant reductions in transmission worldwide [4], scaling up of LF morbidity management and disability prevention (MMDP) activities has lagged behind [5, 6]. Consequently, countries that have successfully interrupted transmission may have sizeable numbers of people who continue to suffer from the disabling and stigmatizing effects of lymphedema and elephantiasis [7].

Although the factors associated with progression of lymphedema in filariasis-endemic areas are complex, the importance of repeated episodes of acute bacterial dermatolymphangioadenitis (ADLA) has been demonstrated in several studies [811]. These inflammatory episodes, which are characterized by pain, fever, and swelling of the affected limb [12], further erode lymphatic function, stimulate fibrosis, and increase the risk of further ADLA episodes. Clinical studies suggest that a simple intervention to reduce ALDA risk, based on hygiene and skin care, can halt and even reverse this progression [1318]. The intervention package goes by different names, e.g., “foot care” or basic lymphedema management, and includes various components based on resources (e.g., compressive bandaging) and local healing practices (e.g., yogic breathing), but hygiene (regular, careful washing with soap and water) is the central component in all of these packages. The importance of water, sanitation, and hygiene (WASH) is increasingly recognized as essential for the control and elimination of several neglected tropical diseases (NTDs), and systematic reviews have been recently published on the effect of WASH interventions on trachoma, soil-transmitted helminth infection, and schistosomiasis [1921].

The reasons for the lagging promotion of MMDP are complex [6, 7] and include a lack of funding, inadequate integration of LF elimination into national health services, and the fact that relatively few LF program managers have been clinically trained. In addition, lack of consensus about the degree of effectiveness of WASH interventions on LF-related lymphedema is a contributing factor. To address this gap, we conducted a systematic review and meta-analysis of the literature to assess the evidence base and quantify the relationship between lymphedema management programs involving a hygiene component and health-related outcomes.


Search strategy

We performed a systematic review and meta-analysis of the literature to address the effects of hygiene-based interventions on morbidity and quality of life related to lymphedema in filariasis-endemic areas. We systematically searched PubMed, Embase, ISI Web of Knowledge, MedCarib, Lilacs, REPIDISCA, DESASTRES, and African Index Medicus databases with no restrictions on language or year of publication. Our search was performed through March 23, 2015 with no restriction of start date. We employed a broad set of search terms, pairing the terms [lymphedema] and [lymphoedema] with the following keywords: [water], [hygiene], [hand wash*], [foot wash*], [soap], [morbidity management], [morbidity control], [disability prevention]. In addition, we hand-searched the bibliographies of relevant publications. Any additional articles found to be pertinent during this process were included.

Studies were included in the systematic review if they 1) were conducted in an area endemic for lymphatic filariasis as determined by WHO (5); 2) involved lymphedema management that included hygiene; and 3) assessed lymphedema-related morbidity (e.g. incidence of ADLA, change in limb circumference) or quality of life. All studies were eligible if they met these inclusion criteria; however, because prophylactic antibiotics have been shown to reduce incidence of ADLA, any study arms that included prophylactic antibiotics were excluded from the meta-analysis. If an article was considered relevant but data were not available in the format needed for our meta-analysis, the corresponding authors were contacted by e-mail and asked to supply the relevant data. We conducted meta-analyses for specific exposure-outcome relationships based on available data. Meta-analyses were conducted in adherence to the PRISMA statement (S1 Text). Our complete protocol is available in the supplemental materials (S2 Text).

Search strategy, selection criteria and data extraction

Articles were selected for inclusion using a two-step review process. First, the titles and abstracts of all identified studies were examined, and studies that failed to meet the inclusion criteria after this step were excluded. Second, two reviewers (M.E.S. and M.P.) independently examined the full text of potentially relevant articles using a standard protocol developed by M.E.S. and M.C.F. In the event of disagreement regarding the eligibility of a study during this phase, the opinion of a third reviewer (D.G.A.) was sought, and the parameters of the study’s inclusion were discussed until consensus was reached.

Once a set of eligible studies was agreed upon, relevant data were extracted from each study by M.E.S. using a standard protocol. To ensure extraction reliability, M.P. also extracted data from a subset of 10% of identified studies, and no discrepancies were found. Data extracted included a brief description of the study (e.g., study design, setting, year, and sample size), details of the study population, a description of the components of lymphedema management, details about how morbidity was measured, and study results. Measures of lymphedema-related morbidity included incidence of acute attacks (ADLA), limb volume or circumference, days of work missed due to disability, and other variables. Clinical signs of morbidity were measured by researchers through physical examination and interviews. Physical examinations commonly focused on staging of the limbs for lymphedema severity and the presence of skin lesions that could serve as entry points for infection, usually on the feet and between the toes. Quality of life was assessed by questionnaire.

Quality issues

To determine the quality of identified studies, we developed a set of criteria derived from the GRADE methodology. Our criteria took into account diagnostic features, characteristics of the lymphedema management programs, study design, and overall strengths and limitations of the studies. Studies were awarded 1 point for meeting each individual criterion listed in Table 1 and could obtain an overall score ranging between 0 and 10 points for each meta-analysis. M.E.S. performed the quality assessment independently and documented the results (S3 Text). All relevant studies were included in the review regardless of their overall quality rating. Quality ratings did not affect the summary of effect measures, but they help to demonstrate the overall quality of individual studies and to identify research gaps.

Table 1. Criteria for which studies received +1 point for GRADE score.


We conducted meta-analyses when three or more studies reported the same measure of effect on morbidity (e.g., ADLA incidence). For studies with multiple arms that included prophylactic antibiotics, only the arm that did not include prophylactic antibiotics was used in the analysis. Observation periods for ADLA varied among studies. In the meta-analysis of ADLA incidence, the observation period was standardized to person-year. For the analysis of change in the proportion of patients with one or more ADLA episodes in a given observation period (both before and after lymphedema management was initiated) it was not possible to standardize the observation period. Findings of studies included in the systematic review, but not meeting the criteria for a meta-analysis were summarized and examined for patterns, as recommended by the Cochrane Review [22].

We used Microsoft Excel (Microsoft Corporation, Redmond, WA, United States of America) to conduct meta-analyses and to develop forest plots [23]. Funnel plots were utilized to investigate the existence of publication bias [24]. Heterogeneity between studies was determined using Higgins’ I2 and Cochran’s Q-tests [22]. Random effects models were used throughout to enhance generalizability of results [25], and pooled estimates for the effect of lymphedema management on measures of morbidity were employed [22].


Characteristics of identified studies

Our initial search yielded 1,666 publications (Fig 1). One hundred seven publications were deemed relevant after review of titles and, when available, abstracts. These articles were fully screened by M.E.S. and M.P. Following this screening, 22 articles were determined to meet systematic review inclusion criteria (Table 2) [13, 14, 1618, 2642]. We conducted two meta-analyses. One included eight studies reporting ADLA incidence ratios (Fig 2). The other included eight studies comparing the percentage of patients reporting at least one ADLA episode in a given time period before and after implementation of lymphedema management (Fig 3). Twenty of the included publications were intervention studies that involved a hygiene education component; the two remaining studies were cross-sectional studies comparing patients who had and had not participated in a hygiene-based intervention program. In three studies, antibiotics were administered in response to acute attacks. Five additional studies had study arms in which antibiotics were administered prophylactically at the time of health education; as noted earlier, these study arms were not included in the meta-analyses. Seven studies (32%) were conducted in Africa, 12 studies (55%) were conducted in Asia (primarily India and Sri Lanka) and three studies (14%) were conducted in the Americas. The quality scores of studies included in the meta-analyses were generally moderate to high (S3 Text).

Table 2. Summary of studies reporting on lymphedema morbidity management program.

Fig 1. Flow chart of publications identified and excluded for this review.

Fig 2. Meta-analysis examining the association between hygiene-based lymphedema management and the incidence of acute dermatolymphangioadenitis ADLA).

Fig 3. Meta-analysis examining the association between hygiene-based lymphedema management and the percentage of patients reporting at least one episode of ADLA during a specific time interval.

Components of lymphedema management programs

Lymphedema management programs all included a hygiene element, usually in the form of education about the importance of daily washing the affected limbs with soap and water. The health education intervention varied from study to study (Table 1), but generally involved training by a nurse or other healthcare provider. In 10 (45%) studies, soap was provided to the patients to ensure its availability when washing limbs. Eight studies also emphasized yoga or other movement or exercises, two studies included manual lymph drainage of the affected limb(s), and three studies used compression bandaging. Only seven (32%) studies explicitly stated that they checked for compliance with limb care (through soap checks or questionnaires), while 12 (55%) studies provided antiseptic or antibiotic foot creams to supplement foot washing with soap and water.

Measures of morbidity and quality of life

The most commonly reported outcome measures are summarized in Table 3; they included various measures of ADLA (n = 18); perceived quality of life, disability, or depression (n = 5); limb circumference and/or volume (n = 3); stage or grade of affected limb (n = 4); days of work lost due to disability (n = 1); and changes in histologic features in the affected limb(s) (n = 1).

Table 3. Studies reporting on various measures of lymphedema-related morbidity.

ADLA incidence and duration

Of the 18 studies reporting some measure of ADLA, 8 (42%) provided enough data to calculate ADLA incidence ratios and were included in a random-effects meta-analysis, which provided a pooled estimated IRR of 0.32 (a mean of 2.39 and 0.69 episodes per person-year before and after intervention, respectively), with a 95% confidence interval 0.25–0.40 (Fig 2). Heterogeneity was fairly high (I2 = 75%).

Eight publications (including one report from the World Health Organization with data for three separate pilot projects [36]) compared the percentage of study participants reporting at least one ADLA in an equivalent time period before and at some time after implementation of the lymphedema management intervention. The periods of observation or recall were 1 month [29, 31, 36], 3 months [33], 1 year [13, 28, 37], and unspecified [34]. These were included in a random-effects meta-analysis. The proportion of lymphedema patients experiencing at least one ADLA episode in a given time period decreased from 49.6% at baseline to 16.2% after implementation of lymphedema management, with a pooled estimated ratio of 0.29 and a 95% confidence interval of 0.12–0.47 (Fig 3). Heterogeneity was high (I2 = 96%).

Change in duration of acute attacks was reported in two studies. Akogun and colleagues found that duration of acute attacks declined with consistent foot care in all intervention arms, but most noticeably between the first and twelfth months [28]. Wijesinghe et al. found that the mean duration of acute attacks was slightly shorter after implementation of lymphedema management than at baseline (5.70 days vs. 5.84 days, p>0.05) [37].

Quality of life, depression, and perceived disability

Five studies reported on some measure of quality of life or emotional wellbeing. No meta-analysis was conducted because the tools and methods used to quantify quality of life varied across studies.

Quality of life.

Aggithaya and colleagues used an LF-specific quality of life questionnaire (LFSQQ) to assess perceived quality of life of patients before and after participation in basic lymphedema management and found that overall quality of life increased significantly [38]. Narahari et al., also found statistically significant improvements in quality of life scores on LFSQQ among patients who attended an LF training “camp” [33].


Budge et al. administered the WHO Disability Assessment Schedule II at regular intervals to 370 lymphedema patients in order to assess perceived disability due to lymphedema. Disability scores decreased significantly (p<0.0001) in patients enrolled in a community-based lymphedema management program, particularly among patients with moderate to advanced lymphedema [39]. Additionally, patients reported losing an average of 2.5 fewer work days per month (p<0.001) after the implementation of a community-based lymphedema management program [39]. A study from Togo found significant decreases in depression, based on the Duke Anxiety-Depression (DUKE-AD) scale, after the implementation of a National Lymphoedema Management Program [40]. After hygiene training and antifungal cream were provided to patients in Guyana, McPherson and colleagues found a significant mean improvement of 6.8 points (p<0.0001) on the Dermatology Life Quality Index (DLQI) scale, which is a dermatology-specific quality of life questionnaire [14].

Limb circumference and volume

Three studies measured morbidity through limb circumference and/or volume. No meta-analysis was conducted because the methods used to measure leg circumference and/or volume varied across studies. Addiss et al. assessed leg volume using water displacement and found that 78.3% of patients experienced a reduction in leg volume after the implementation of basic lymphedema management emphasizing hygiene and self-care, especially among those with legs with more advanced lymphedema [26]. Narahari and colleagues found a statistically significant 1% reduction in thigh volume among patients who attended LF training “camps” [33], and in another study, found that both circumference and volume of affected limbs decreased significantly after implementation of a comprehensive lymphedema management program [34].

Stage or grade of affected limb

Four studies reported on change in the stage or grade of the affected limb. No meta-analysis was conducted because the standardized staging systems used on affected limbs varied across studies. Budge et al. conducted independent staging of leg(s) using the 7-stage Dreyer system [43], and found that patients with moderate (stage 3) or advanced (stages 4–7) lymphedema in affected limbs experienced significantly greater improvement after implementing a community-based treatment program for lymphedema, which employed a network of village volunteers trained to provide home-based care and education in lymphedema management [39]. Wijesinghe et al. found that, after the intervention period, a significant number of patients had reductions from grade II to grade I lymphedema, according to the WHO-recommended lymphedema staging system [37, 44]. In another study using the WHO-recommended lymphedema staging system, Wilson et al. found no significant change in the stage of affected limbs [41].

Other measures of morbidity

Wilson et al. examined changes in histologic features from skin-punch biopsies before and after training in lymphedema self-care, with an emphasis on hygiene, basic skin care, range of motion exercises, and limb elevation. Several histologic improvements were noted in the follow-up biopsies of the leg, most notably reductions in fibrosis [41].


The physical, social, and psychological suffering caused by lymphatic filariasis is enormous [45]. Our understanding of the nature and magnitude of this suffering is still incomplete, although several studies in LF-endemic areas have documented significant adverse impacts of lymphedema on physical and mental health, as well as on quality of life. Lymphedema patients frequently report depression, embarrassment, and increased social isolation [46, 47], even in the early stages of the disease [48]. The stigma of lymphedema creates barriers both to health-seeking and to adherence to recommended treatment [49]. Stigma also leads to social disconnectedness, which, in turn contributes to depression and other negative health outcomes [50]. In the absence of appropriate MMDP programs, misdiagnosis and improper treatment is not uncommon, and patients seek out cures and treatments that may be ineffective and expensive [51]. Additionally, increased frequency of ADLA may negatively impact socio-economic status through decreased ability to work and perhaps even reduced cognition [52].

Given these far-ranging consequences, providing treatment to the 14 million people who suffer from lymphedema in LF-endemic areas is an urgent matter, both for health and human dignity. Much of this suffering is related to ADLA [52]; thus, measures to reduce ADLA are especially important. The pioneering studies of Dreyer and colleagues in Brazil and Shenoy and colleagues in India provided the first convincing evidence of salutary effects of hygiene-based measures on ADLA [10, 12, 35] and established them as the cornerstone of the MMDP “pillar” of the GPELF [3, 6]. Despite this evidence and the development of WHO training modules on hygiene-based lymphedema management, uptake has been particularly slow. Although there are undoubtedly many factors involved, one of these has been a lack of recognition as to the degree to which these simple measures reduce ADLA and other morbidity.

Our meta-analyses revealed a significant association between hygiene-based interventions and decreased ADLA. Although meta-analyses for other physical measures of morbidity (e.g. stage of affected limb, limb circumference/volume) were not feasible, several studies documented that participation in lymphedema management programs was associated with improved health and well-being, including self-reported quality of life, lower levels of perceived disability and depression, and increased capacity to work.

Improved hygiene and basic skin care were core features of all the intervention packages that were assessed in the studies we reviewed. However, the components of lymphedema management are not fully standardized across LF-endemic areas. This represents not only a limitation of our study but also a challenge to MMDP as key element of the global LF elimination programs. Investigators included movement, leg elevation, and local (e.g., Ayruvedic) practices to varying degrees. Further, lymphedema management programs in filariasis-endemic areas typically have not emphasized the use of emollients to maintain skin hydration and barrier function, although this is recommended by lymphologists and dermatologists in other settings [53].

Our review was also limited by variation in the way morbidity was measured across studies, which made it impossible to conduct meta-analyses for some outcomes. Inconsistent definitions and methods may have introduced error into the meta-analyses. Study design and setting varied, and heterogeneity was high for both meta-analyses on ADLA outcomes, although funnel plots did not appear to show high publication bias (S4 Text).

If basic lymphedema care were provided to all 14 million affected persons in LF-endemic areas, as recommended by WHO [5, 6], considerable benefits would be realized in health, quality of life, and economic productivity. Our meta-analysis suggests, conservatively, that basic lymphedema care could result in at least 14 million fewer ADLA episodes annually (an average of one episode fewer per affected person), marked improvement in quality of life, and perhaps a 10% increase in the number of days worked.

Given these significant benefits and huge burden of disease, it is crucial that LF elimination programs implement lymphedema management. LF program managers have been under considerable pressure to scale up antifilarial drug distribution to interrupt transmission by 2020. In this context, MMDP was often seen as in competition with mass drug treatment. This need not be the case. In fact, providing lymphedema management to affected persons increases acceptance of mass treatment with antifilarial drugs, resulting in higher drug coverage [54]. Further, 2020 is fast approaching and significant LF-related morbidity remains, which threatens the goal of “elimination as a public health problem.” The necessity of MMDP can no longer be ignored. Recent work by WHO to highlight the importance of MMDP and to include indicators for MMDP in criteria for national verification of LF elimination represents important new developments. It is our hope that this review will serve to document the benefits that can be realized through relatively simple hygiene-based measures and thereby encourage their broader application.

During the past few years, the importance of WASH for the control and prevention of major NTDs has been increasingly recognized [55]. Recent systematic reviews highlight the impact of WASH on STH [20], schistosomiasis [21] and trachoma [19]. The current study underscores the crucial importance of WASH—particularly hygiene—in the secondary prevention of morbidity and disability for LF-related lymphedema. The basic hygiene-based interventions recommended for management of lymphedema are also effective for leprosy, Buruli ulcer, and diabetic foot, as well as other chronic conditions of the lower limbs [6, 56]. Further, essentially the same hygiene-based measures are recommended for persons with podoconiosis [57]. Thus, integrated hygiene-based interventions are increasingly recognized as critical for the management of a wide range of lower limb conditions, several of which are diseases of neglected populations, associated with poverty, and targeted for elimination as public health problems. Expansion of hygiene-based measures for morbidity management in resource-poor settings can therefore benefit many more persons than the 14 million affected by LF-associated lymphedema. Refinement of integrated intervention packages and delivery mechanisms is the subject of ongoing research and programmatic innovation. Integrated guidelines that are applicable for LF-related lymphedema, leprosy, podoconiosis, and a range of other diseases have recently been published [58].

In addition to the importance of hygiene in LF-related morbidity management, the other components of WASH—water and sanitation—have played significant roles in preventing the transmission of LF. Improved sanitation and water management can decrease the breeding habitat of mosquitoes, which are responsible for transmitting the parasitic worms that cause LF. Installation of a municipal sewer system was apparently the major factor that led to the elimination of LF transmission in Charleston, South Carolina, where some 29% percent of the population had been infected [59]. Water management, particularly the reduction of standing water, has been crucial in decreasing transmission of LF in other areas [60, 61].

In conclusion, WASH is emerging as a critical factor for the control and elimination of several major NTDs. Recent reviews highlight the importance of WASH in reducing transmission of schistosomiasis, soil-transmitted helminthiasis, and trachoma. Our review underscores the value of WASH in preventing morbidity and promoting healing among persons suffering from LF-associated lymphedema. It also indicates that massive reductions in acute suffering associated with ADLA are possible through improved hygiene-based lymphedema management, and point to significant improvements in quality of life, emotional well-being, and economic productivity. Available data strongly support WHO recommendations to fully realize the intention of the 1997 World Health Assembly resolution 50.29, which called for LF elimination as a public health problem—not only as a parasitic infection.

Supporting Information

S2 Text. Systematic Review Search Protocol Proposal.


S4 Text. Funnel Plots for Publication Bias.



The authors are grateful to Maggie Person for reviewing published studies and abstracting data.

Author Contributions

Conceived and designed the experiments: MES MCF DGA. Performed the experiments: MES. Analyzed the data: MES. Wrote the paper: MES MCF DGA.


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