The design and development of a multicentric protocol to investigate the impact of adjunctive doxycycline on the management of peripheral lymphoedema caused by lymphatic filariasis and podoconiosis.

BACKGROUND: As new lymphatic filariasis infections are eliminated through mass chemotherapy, previously affected individuals are left with the sequellae, especially chronic progressive lymphoedema. Currently this is managed by careful attention to limb hygiene to prevent infection. Studies over the past 15 years have suggested that the incorporation of doxycycline treatment may arrest or even reverse progression of lymphoedema. Most of this work has been observational or based on small studies, and if this intervention is effective, studies need to be conducted on a larger scale and under diverse geographical and social conditions before it can be incorporated into treatment policy. METHODS/DESIGN: The double-blind, placebo-controlled study was designed to investigate the impact of six weeks treatment with doxycycline added to standard limb hygiene on early stage filarial lymphoedema in five sites in Africa and the Indian subcontinent. One site in Cameroon is selected for studying lymphoedema in podoconiosis. Each site was individually powered with the potential to undertake a meta-analysis on completion. Evaluation methods followed those used in Ghana in 2012 with additions resulting from advances in technology. The details of the core protocol and how it was varied to take account of differing situations at each of the sites are provided. The study will enrol up to 1800 patients and will complete in mid-2021. CONCLUSIONS: This paper provides details of what challenges were faced during its development and discusses the issues and how they were resolved. In particular, the reasons for inclusion of new technology and the problems encountered with the supply of drugs for the studies are described in detail. By making these details available, it is hoped that the study protocol will help others interested in improving treatment for filarial lymphoedema in the design of future studies. Trial registration India: Clintrials.gov. NCT02929121 registered 10 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT02929121 Mali: Clintrials.gov. NCT02927496 registered 7 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT0292749 Sri Lanka: Clintrials.gov. NCT02929134 registered 10 Oct 2016: https://clinicaltrials.gov/ct2/show/NCT02929134 Ghana: ISRCTN. 14042737 registered 10 July 2017: https://doi.org/10.1186/ISRCTN14042737 Tanzania: ISRCTN. 65756724 registered 21 July 2017: https://doi.org/10.1186/ISRCTN65756724 Cameroon: ISRCTN. 1181662 registered 25 July 2017: https://doi.org/10.1186/ISRCTN11881662.

Portable infrared imaging for longitudinal limb volume monitoring in patients with lymphatic filariasis.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (LF) emphasizes hygiene, exercise, and other measures to reduce morbidity and disability related to LF. We recently reported that a portable, three-dimensional, infrared imaging system (3DIS) provides accurate limb volume measurements in patients with filarial lymphedema. To assess the practical utility of repeated 3DIS measurements for longitudinal lymphedema management, we examined intraday and day-to-day leg volume changes in adults with filarial lymphedema in southern Sri Lanka. METHODOLOGY AND PRINCIPAL FINDINGS: We assessed 41 participants with lower extremity lymphedema (stages 1-6) in their homes in the mornings (6:00-9:00 AM) and afternoons (2:00-6:00 PM) of three days within one calendar week. Two examiners performed replicate 3DIS volume measurements at each visit. Median coefficient of variation among replicate volume measurements was 1.7% (IQR 1.1% - 2.3%) for left legs and 2.2% (IQR 1.6% - 2.8%) for right legs. Median intraday volume increase was 3.0%. Range among daily volume measurements tended to be lower for afternoon measurements (median 2.25%, IQR 1.4%- 5.4%) than for morning measurements (median 3.0%, IQR 1.4% - 8.4%). CONCLUSIONS AND SIGNIFICANCE: Limb volume measurements by 3DIS are accurate and reproducible, and this technique is feasible for use in patients' homes. We have developed practical suggestions for optimal outcomes with 3DIS. Duplicate measurements should be performed and repeat assessments should be done at approximately the same time of day to minimize bias. Duplicate measures that vary by more than 8% should prompt review of scanning technique with a repeat measurement. With proper training and attention to technique, 3DIS can be a valuable tool for healthcare workers who work with lymphedema patients.

Reassessment of the prevalence of soil-transmitted helminth infections in Sri Lanka to enable a more focused control programme: a cross-sectional national school survey with spatial modelling.

BACKGROUND: In Sri Lanka, deworming programmes for soil-transmitted helminth infections became an integral part of school health in the 1960s, whereas routine antenatal deworming with mebendazole started in the 1980s. A 2003 national soil-transmitted helminth survey done among schoolchildren found an overall prevalence of 6·9%. In our study, we aimed to reassess the national prevalence of soil-transmitted helminth infections to enable implementation of a more focused control programme that targets smaller administrative areas at risk of continued transmission. METHODS: We did a cross-sectional, school-based, national survey using multistage stratified cluster sampling, covering all nine provinces as well as populations at high risk of soil-transmitted helminth infections living in urban slums and in plantation-sector communities. Our study population was children aged 5-7 years attending state schools. Faecal samples were collected and analysed with duplicate modified Kato-Katz smears. We modelled the risk of soil-transmitted helminth infection using generalised linear mixed-effects models, and we developed prevalence maps to enable informed decision making at the smallest health administrative level in the country. FINDINGS: Between Jan 23 and May 9, 2017, we recruited 5946 children from 130 schools; 4276 (71·9%) children provided a faecal sample for examination. National prevalence of soil-transmitted helminth infection was 0·97% (95% CI 0·63-1·48) among primary schoolchildren. Prevalence in the high-risk communities surveyed was higher than national prevalence: 2·73% (0·75-6·87) in urban slum communities and 9·02% (4·29-18·0) in plantation sector communities. Our prevalence maps showed that the lowest-level health administrative regions could be categorised into low risk (prevalence <1%), high risk (prevalence >10%), or intermediate risk (1-10%) areas. INTERPRETATION: Our survey findings indicate that the national prevalence of soil-transmitted helminth infection has continued to decline in Sri Lanka. On the basis of WHO guidelines, we recommend discontinuation of routine deworming in low-risk areas, continuation of annual deworming in high-risk areas, and deworming once every 2 years in intermediate-risk areas, for at least 4 years. FUNDING: Task Force for Global Health and WHO.

Use of a Novel Portable Three-Dimensional Imaging System to Measure Limb Volume and Circumference in Patients with Filarial Lymphedema.

The World Health Organization's Global Program to Eliminate Lymphatic Filariasis (LF) has reduced LF transmission worldwide, but millions remain affected by filarial lymphedema. Tools for clinically monitoring lymphedema in developing nations are limited. We tested a novel, portable, infrared three-dimensional imaging system (3DIS) against water displacement (WD) and tape measurement of limb circumference (TMLC) among patients with filarial leg lymphedema in Galle, Sri Lanka. Outcomes were accuracy and reproducibility of imaging system measurements. In parallel, we also tested the reproducibility of skin thickness ultrasound (STU) measurements. We examined 52 patients (104 limbs) with lymphedema of stages 0-6 (N = 28, 19, 20, 21, 2, 4, and 10, respectively). 3DIS measurements correlated nearly perfectly with WD (r2 = 0.9945) and TMLC values (r2 > 0.9801). The median time required to acquire imaging system measurements for both legs was 2.1 minutes, compared with 17, 7, and 29 minutes, respectively, for WD, TMLC, and STU. Median interexaminer coefficients of variation (CVs) for volume measurements were 1.1% (interquartile range [IQR] 0.5-2.1%) for WD and 1.7% (IQR 1.2-2.4%) for the 3DIS. CVs for circumference measurements were 1.4% (IQR 0.8-2.4%) by TMLC and 1.3% (0.8-1.9%) by 3DIS. Median interexaminer CV for STU was 13.7% (IQR 8.5-21.3%). The portable imaging system noninvasively provided accurate and reproducible limb volume and circumference measurements in approximately 2 minutes per patient. This portable technology has the potential to greatly improve assessment and monitoring of lymphedema in the clinic and in the field.

Social mobilisation, drug coverage and compliance and adverse reactions in a Mass Drug Administration (MDA) Programme for the Elimination of Lymphatic Filariasis in Sri Lanka.

BACKGROUND: In Sri Lanka filariasis is endemic in Southern, Western and North Western provinces covering eight districts designated as implementation units in the Programme for the Elimination of Lymphatic Filariasis (PELF). Despite control activities over sixty years including multidose diethylcarbamazine, 6 mg/kg treatment microfilaria rates had persisted at low levels. Following systematic social mobilisation the first MDA with DEC albendazole combination was conducted in 2002. METHODS: We investigated the extent social mobilisation had reached the people, their drug compliance and adverse reactions. Three localities were selected from each district to pick target population samples for pre-tested questionnaire. Three teams each with six people visited one district each day. One team worked from three starting points in one locality. A member applied eight part questionnaire to one family member totalling 150-160 people from one locality. Questions included social mobilisation, drug compliance and adverse reactions. RESULTS: Information was disseminated by television, radio, banners and leaflets, to a lesser extent by people. Information reached more people in the periphery than in Colombo. 35.2% from Colombo municipality were unaware of the MDA. Drug coverage was 79.6%, home delivery 71.7% and delivery centres 7.9%. 35.6% in Colombo district and 53.4% from Colombo municipality did not receive drugs. Drugs were consumed by 71.4%. 28.6% who did not comply included 20.4% who did not receive them. 91.4% showed no adverse reactions, 7.5% were mild, 1.1% recovered with home remedies. CONCLUSION: Drug compliance showed significant positive correlation with awareness of the MDA. Door to door delivery was more successful than delivery from centres. More delivery centres conveniently located would have rectified this disparity. Poor awareness and compliance in Colombo and urban areas could be rectified with separate strategy for urban areas. More time for MDA and trained adequate manpower would ensure coverage to achieve elimination.