1. Introduction
Lymphedema is a chronic swelling of the skin and underlying tissue and a major cause of disability globally. It can occur from multiple etiologies including lymphatic filariasis (LF), a vector-borne parasite endemic to many tropical countries [
1] and podoconiosis is lymphedema caused by long-term bare-foot exposure to irritant soils [
2]. It is estimated that between these two diseases, more than 20 million people live with the daily burden of lymphedema, predominately affecting the lower limbs [
2,
3]. This burden extends to families and communities and is a major contributor to poverty in many developing countries [
4]. The Global Programme to Eliminate Lymphatic Filariasis (GPELF) as a public health problem is a World Health Organization (WHO) mandated agreement between endemic countries. Member states are required to deliver preventive chemotherapy via mass drug administration campaigns to all people at risk of infection, and to provide a basic package of care for people with existing morbidity (lymphedema and hydrocele) [
5]. This basic package is referred to as morbidity management and disability prevention (MMDP) and should be integrated into the national health system, with lymphedema services delivered through community health centers [
6]. Whilst there is no mandated elimination program for podoconiosis, it is none-the-less a public health problem in endemic countries and the WHO recommends that podoconiosis should be managed within LF MMDP programs [
2].
The lymphatic system works alongside the venous system to return fluid from the periphery to the heart. The majority of lymph is formed at the initial lymph plexus, a network of fine vessels under the skin where it plays an important role in barrier defenses. The formed lymph passes into collecting vessels which actively pump the lymph towards lymph nodes where it is processed by immune cells. Lymphedema forms when lymphatic clearance fails and can occur in any body part. Untreated lymphedema progresses through identifiable stages and there are several staging systems in common use [
7]. In the ‘mild’ stages of lymphedema distal swelling which may have initially reversed on elevation or overnight can become more persistent and progress proximally. In the middle or ‘moderate’ stages there is an overgrowth of fibrous tissue and fatty deposits which can increase tissue stiffness. In the advanced or ‘severe’ stages the skin becomes thickened and forms into deep folds.
In LF, mosquitoes transmit microfilariae between human hosts where they are picked up by the initial lymph plexus under the skin. Mature worms form ‘nests’ in the lymph vessels close to lymph nodes and reproduce. A cascade of host responses to worm products and their symbiotic bacteria dilate the lymph vessels and inhibit lymphatic pumping, eventually leading to lymphatic failure [
8,
9]. Although the disturbance is usually in vessels located near the groin, the swelling appears first at the ankles and feet. Podoconiosis also results in lymphatic failure when irritant minerals in soils of volcanic origin [
10,
11] are absorbed into the lymph plexus underlying the skin of the foot. Over time the chronic inflammatory reactions that occur damage the vessels and lymphatic failure follows. As in LF, the swelling appears first in the feet and ankles but due to the site exposure of the irritant, skin changes on the feet can occur much earlier in podoconiosis than in LF-related lymphedema.
In both diseases a major portion of the burden to patients and their communities is due to the frequency, intensity, and duration of secondary bacterial and fungal infections also known as ‘acute attacks’ [
12,
13,
14]. These debilitating and painful episodes reduce the person’s capacity to contribute to family resources and may affect other family members who are kept from work or school to attend the sick patient [
15,
16]. Wounds and ulcers (entry lesions) and skin breakdown between the toes (interdigital lesions), are a major source of these infections. A daily home-based hygiene protocol is effective in reducing acute attacks and central to lymphedema management in resource poor settings [
17]. This involves daily washing and drying of affected body parts, passive range of motion exercises and calf pump exercises, and elevation of the affected limbs overnight and whenever possible during the day [
6].
Two systematic reviews on home-based self-care for lymphedema [
17,
18] demonstrated that a hygiene-centered self-care protocol can reduce the frequency and duration of acute episodes at all stages of disease. In mild stages, swelling may also reverse, but people affected by moderate or severe lymphedema are less likely to experience any reversal of limb size or lymphedema stage. One review compared self-care for people affected by lymphedema from LF with self-care for people affected by lymphedema after cancer therapy [
18]. Simple measures such as deep breathing, self-massage, and progressive exercises were shown to benefit women with breast cancer-related lymphedema of the arm [
19,
20]. These activities aim to stimulate lymph flow from the affected area and are emphasized equally to recommendations for meticulous skin care. In contrast, MMDP guidelines for LF- and podoconiosis-related lymphedema offer minimal stimulation to the lymph vessels themselves [
6,
21].
To determine if the activities proven in cancer-related lymphedema can improve outcomes for people affected by LF- or podoconiosis-related lymphedema, an enhanced self-care protocol for lower limb lymphedema was developed and trialed in Nilphamari District in Bangladesh and Simada Woreda (district) in Ethiopia. Enhanced self-care activities were chosen on the basis of previous evidence [
9,
10] and expert opinion [
22] and with the criterion that they not add any financial burden to the local health services, patients, or their families. The additional activities were designed to stimulate lymph flow, support immune function, and improve skin integrity, and included deep breathing exercises, leg exercises, self-lymphatic-massage, and recommendations to drink clean water and eat fresh fruits and vegetables.
3. Study Design and Participants
3.1. Study Design
Cluster randomization was used to select 20 community clinics (CC) in Nilphamari District and 20 health posts (HP) in Simada Woreda and to allocate each to either the intervention or control group (
Figure 1). Adults aged 18 or over were eligible to participate if they had lymphedema in at least one leg at Stage 3 or higher according to the Dreyer stage criterion which describe the identifying features of seven stages [
25].
3.2. Outcomes
Participants were interviewed at baseline and on exit to elicit demographic information, medical and lymphedema history, and lymphedema knowledge, attitudes, and practice (KAP). Objective measures and quality of life (QOL) questionnaires were collected at baseline and repeated at four weeks, 12 weeks, and 24 weeks. Primary outcome measures included the change in lymphedema stage, midcalf circumference, midcalf tissue compressibility (an indication of the degree of fibrotic induration), number of entry lesions and interdigital lesions, and frequency and duration of acute attacks. Secondary outcome measures were perceived function, lymphedema KAP, QOL, and adherence to the self-care protocols. All questionnaire responses and biometric measurements were recorded via the Open Data Kit Collect (ODK Collect) application [
26] loaded to an electronic tablet (Samsung Galaxy Tab A 10.1).
3.3. Participants at Baseline
In Bangladesh baseline data were collected on 146 patients who were mostly female (n = 107, 73.3 %) with a mean age of 54 years (SD 11.3, range 27–88). Lymphoedema was found in 177 legs (60.6% of all legs) and the median stage was Stage 3 (n = 103 legs (58.2% of affected legs)) and there were 32 legs at Stage 6 (18.1% of affected legs). No-one was affected by leg lymphoedema at Stage 7. Thirty-nine percent of participants had unilateral right leg lymphoedema, 40.4% had unilateral left leg lymphoedema, and 20.6% had bilateral leg lymphoedema. Of the 140 participants who said they had ever had an acute attack, 130 had suffered at least one attack in the previous 6 months. The mean frequency was 4.76 episodes (SD 4.75, median 3 attacks, range 0–24), and the mean duration of each attack was 4.66 days (SD 3.18, median 4 days, range 0–20).
In Ethiopia baseline data were collected on 129 patients who were relatively evenly distributed by sex (males; n = 70, 54.3%) with a mean age of 58 years (SD 11.467, range 25–84). Lymphoedema was found in 227 legs (88% of all legs) and the median stage was Stage 6 (n = 149 legs (65.6% of affected legs)) and there were 51 legs at Stage 3 (22.5% of affected legs). One person was affected by leg lymphoedema at Stage 7. Unilateral lymphedema was present on the right leg of 16.3% of participants, 7.8% had unilateral left leg lymphoedema, and 75.9% had bilateral leg lymphoedema. Of the 103 participants who said they ever had an acute attack 92 people had suffered at least one attack in the previous 6 months. The mean frequency was 3.31 episodes (SD 3.96, median 3 attacks, range 0–34), and the mean duration of each attack was 4.64 days (SD 5.133, median 3 days, range 0–29).
5. Participant Training
Lymphedema management in resource poor settings usually relies on community-based home-care. Typically, patients will be identified by local health authorities or non-governmental agencies and shown how to perform the hygiene routine and other self-care recommendations including advice on management of acute attacks. How this information is distributed, and what local resources are available to patients, may vary from country to country and region to region. In this study, training in the standard-care activities followed usual implementation of MMDP in each country. Education in locally relevant risk factors was given, and risk reduction behaviors were encouraged. This included advice such as the use of bed nets in LF endemic areas, and wearing shoes and covering dirt floors in podoconiosis endemic areas. In centers allocated to the enhanced-care intervention, trainers included the additional activities within the self-care training session.
Each activity was carefully explained and demonstrated by the trainer(s), including information about the purpose of each component and suggestions for integrating self-care activates into normal daily routines. A time frame for performing daily self-care was not specified to the participants, rather the formation of habits was encouraged. Participants in both groups were instructed not to cause pain with any of the limb care activities, but to do things as gently as needed to remain comfortable. At the end of the study participants who had been allocated to the standard-care group were offered training in the additional enhanced-care activities.
Material and Resources
Participants were provided with materials in keeping with what would usually be supplied to patients affected by lymphedema in each country, therefore there were some small variations between countries in what was supplied. In Bangladesh the Filariasis Elimination Program offers a kit box of materials which includes wash cloths, towels, medicated creams and gauze bandages. This was modified slightly to add nail clippers (both groups) and coconut oil for the massage (enhanced-care group only). The kit box was supplied at the beginning of the study and again at 12 weeks In Ethiopia patients were supplied with a wash bowl, wash cloths, towels, medicated creams, nail clippers and vegetable oil (enhanced-care group only) at the beginning of study. The soaps and medicated creams were replenished at every follow-up. A list of materials supplied in each country is given in
Table 3. A color brochure with pictures of the allocated self-care activities was provided to participants in local language and examples for each group are provided in
Supplementary materials Figure S1: Standard-care brochure Bangladesh, and
Figure S2: Enhanced-care brochure Ethiopia. Participants were advised on what services could be accessed locally during acute attacks and when materials for the study would be replenished.