Search

Objectives: To investigate the cellular and molecular pathophysiology involved in the development of fibrotic skin of grade-3 lymphoedema patients with a focus on collagen types.Methods: Fibrotic and normal skin biopsy samples obtained from grade-3 lymphoedema patients and normal individuals, respectively, were analysed by histopathology, quantitative real-time PCR and immunohistochemistry to examine collagen gene expression.Results: Histopathologic analysis revealed epidermal changes such as orthokeratosis, hypergranulosis and irregular acanthosis in the skin biopsies. The thickened dermis contained nodules of haphazardly arranged thick collagen bundles. Real-time PCR data showed significant (P-value 0.0003) up-regulation of Collagen type I and type III gene transcripts in the fibrotic skin of patients resulting in 38.94-fold higher transcription of Collagen type III alpha-1 gene than of Collagen type I alpha-1 gene. Semi-quantification of the per cent of haematoxylin-DAB-stained area of immunohistochemistry images also showed significant (P < 0.0001) enhancement of both collagen proteins in the fibrotic skin of patients vs. normal human skin.Conclusions: Gene transcript analysis revealed significant up-regulation of Collagen type III vs. Collagen type I in fibrotic skin of limb nodules from patient biopsies. Histopathological and immunohistochemical analysis also revealed enhancement of Collagen types I and III in fibrotic vs. normal skin. The findings of this preliminary study indicate the potentially significant involvement of Collagen type III in the development of the fibrotic skin of grade-3 lymphoedema patients. [ABSTRACT FROM AUTHOR]

Objectives: This longitudinal comparative study investigated the effect of preventive chemotherapy (PC) on covert tissue changes associated with lymphatic filariasis (LF) among young people living in an LF-endemic area in Myanmar.Methods: Tissue compressibility and extracellular free fluid in the lower limbs of people aged 10-21 years were measured using indurometry and bioimpedance spectroscopy (BIS). Baseline measures were taken in October 2014, annual mass drug administration (MDA) of PC was delivered in December, and in March 2015 further PC was offered to LF-positive cases who had missed MDA. Follow-up measures were taken in February and June 2015.Results: A total of 50 antigen-positive cases and 46 antigen-negative controls were included. Self-reported PC consumption was 60.1% during 2014 MDA and 66.2% overall. At second follow-up, 24 of 34 cases and 27 of 43 controls had consumed PC. Significant and clinically relevant between-group differences at baseline were not found post-PC. Bayesian linear mixed models showed a significant change in indurometer scores at both calves for antigen-positive cases who consumed any PC (dominant calf: -0.30 [95% CI -0.52, -0.07], P < 0.05 and non-dominant calf: -0.35 [95% CI -0.58, -0.12], P < 0.01). Changes in antigen-negative participants or those not consuming PC were not significant.Conclusion: This study is the first attempt to use simple field-friendly tools to track fluid and tissue changes after treatment of asymptomatic people infected with LF. Results suggested that PC alone is sufficient to reverse covert lymphatic disturbance. Longer follow-up of larger cohorts is required to confirm these improvements and whether they persist over time. These findings should prompt increased efforts to overcome low PC coverage, which misses many infected young people, particularly males, who are unaware of their infection status, unmotivated to take PC and at risk of developing lymphoedema. Indurometry and BIS should be considered in assessment of lymphatic filariasis-related lymphedema. [ABSTRACT FROM AUTHOR]

Objective: The underlying problem in lymphatic filariasis is irreversible swelling of the limbs (lymphoedema), which is a unique feature of lymphatic insufficiency. It is still unclear whether the natural ability of lymphatics to form functional lymphatic vasculature is achieved or attenuated in the lymphoedemal pathology. Clinical studies have clearly shown that circulating lymphatic progenitors (CLPs), a subset of bone marrow-derived mononuclear cells (PBMCs), contribute to post-natal lymph vasculogenesis. CLP-based revascularisation could be a promising strategy to bypass the endothelial disruption and damage incurred by the filarial parasites. Thus our aim was to compare and characterise the functional prowess of PBMCs in physiological and lymphoedemal pathology.Methods: PBMCs were isolated from venous blood sample from drug-naive endemic normals (EN) and drug-deprived filarial lymphoedema (FL) individuals using density gradient centrifugation. Adhesion, transwell migration and in vitro matrigel assays were employed to characterise the lymphvasculogenic potential of PBMCs. CLPs were phenotypically characterised using flow cytometry; expression levels of lymphatic markers and inflammatory cytokines were quantified using qRT-PCR and ELISA, respectively.Results: PBMCs from FL group display poor adherence to fibronectin (P = 0.040), reduced migration towards SDF-1α (P = 0.035), impaired tubular network (P = 0.004) and branching point (P = 0.048) formation. The PBMC mRNA expression of VEGFR3 (P = 0.039) and podoplanin (P = 0.050) was elevated, whereas integrin α9 (P = 0.046) was inhibited in FL individuals; additionally, the surface expression of CD34 (P = 0.048) was significantly reduced in the FL group compared to the EN group.Conclusion: PBMCs from filarial lymphoedema show defective and dysregulated lymphvasculogenic function compared to endemic normals. [ABSTRACT FROM AUTHOR]

Objective: Mass drug administration (MDA) for the control of lymphatic filariasis (LF), in Ghana, started in the year 2000. While this had great success in many implementation units, there remain areas with persistent transmission, after more than 10 years of treatment. A closer examination of the parasite populations could help understand the reasons for persistent infections and formulate appropriate strategies to control LF in these areas of persistent transmission.Materials and Methods: In a longitudinal study, we assessed the prevalence of microfilaraemia (mf) in two communities with 12 years of MDA in Ghana. In baseline surveys 6 months after the National MDA in 2014, 370 consenting individuals were tested for antigenaemia using immunochromatographic test (ICT) cards and had their mf count determined through night blood surveys. 48 ICT positives, of whom, 17 were positive for mf, were treated with 400 μg/kg ivermectin + 400 mg albendazole and subsequently followed for parasitological assessment at 3-month intervals for 1 year. This overlapped with the National MDA in 2015.Results: There was a 68% parasite clearance 3 months after treatment. The pre-treatment mf count differed significantly from the post-treatment mf counts at 3 months (P = 0.0023), 6 months (P = 0.0051), 9 months (P = 0.0113) and 12 months (P = 0.0008).Conclusion: In these settings with persistent LF transmission, twice-yearly treatment may help accelerate LF elimination. Further large-scale evaluations are required to ascertain these findings. [ABSTRACT FROM AUTHOR]

Objectives: Situational analysis of lymphatic filariasis (LF) morbidity and its management in Ahanta West, Ghana, to identify potential barrier to healthcare for LF patients.Methods: Lymphoedema and hydrocoele patients were identified by community health workers from a subset of villages, and were interviewed and participated in focus group discussions to determine their attitudes and practices towards managing their morbidity, and their perceived barriers to accessing care. Local health professionals were also interviewed to obtain their views on the availability of morbidity management services in the district.Results: Sixty-two patients (34 lymphoedema and 28 hydrocoeles) and 13 local health professionals were included in the study. Lymphoedema patients predominantly self-managed their conditions, which included washing with soap and water (61.8%), and exercising the affected area (52.9%). Almost 65% of patients had sought medical assistance at some stage, but support was generally limited to receiving tablets (91%). Local health professionals reported rarely seeing lymphoedema patients, citing stigma and lack of provisions to assist patients as a reason for this. Almost half of hydrocoele patients (44%) chose not to seek medical assistance despite the negative impact it had on their lives. Whilst surgery itself is free with national health insurance, 63% those who had not sought treatment stated that indirect costs of surgery (travel costs, loss of earnings, etc.) were the most prohibitive factor to seeking treatment.Conclusions: The information obtained from this study should now be used to guide future morbidity strategies in building a stronger relationship between the local health services and LF patients, to ultimately improve patients' physical, psychological and economic wellbeing. [ABSTRACT FROM AUTHOR]

Objective Several cases of lymphatic filariasis (LF) have been reported in non-endemic countries due to travellers, military personnel and expatriates spending time in and returning from endemic areas, as well as immigrants coming from these regions. These cases are reviewed to assess the scale and context of non-endemic presentations and to consider the biological factors underlying their relative paucity. Methods Cases reported in the English, French, Spanish and Portuguese literature during the last 30 years were examined through a search of the PubMed, ProMED-mail and TropNet resources. Results The literature research revealed 11 cases of lymphatic filariasis being reported in non-endemic areas. The extent of further infections in recent migrants to non-endemic countries was also revealed through the published literature. Conclusions The life-cycle requirements of Wuchereria and Brugia species limit the extent of transmission of LF outside of tropical regions. However, until elimination, programmes are successful in managing the disease, there remains a possibility of low rates of infection being reported in non-endemic areas, and increased international travel can only contribute to this phenomenon. Physicians need to be aware of the signs and symptoms of lymphatic filariasis, and infection should be considered in the differential diagnosis of people with a relevant travel history. [ABSTRACT FROM AUTHOR]

Objectives To assess the performance of an educational campaign to increase adherence to a mass-administered DEC regimen against lymphatic filariasis (LF) in Orissa, and to identify factors that could enhance future campaigns. Method Randomized cluster survey, comparing areas that did and did not receive the educational campaign, using a household coverage survey and knowledge, attitudes and practices (KAP) survey. Results LF MDA coverage for the entire population ( n = 3449) was 56% (95% CI: 50.0–61.9). There was no statistical difference between the areas that did and did not receive the educational campaign. The most common barriers to adherence were fear of medication side effects (47.4%) and lack of recognition of one’s risk for LF (15.8%). Modifiable, statistically significant, multivariable predictors of adherence were knowing that DEC prevents LF (aOR = 2.6, 95% CI: 1.4–5.1), knowing that mosquitoes transmit LF (aOR = 1.9, 95% CI: 1.1–3.2), and knowing both about the mass drug administration (MDA) in advance and that mosquitoes transmit LF (aOR = 5.4, 95% CI: 2.8–10.4). Conclusions India needs to increase compliance with MDA programmes to reach its goal of interrupting LF transmission. Promoting a simple public health message before MDA distribution, which takes into account barriers to and predictors of adherence, could raise compliance with the LF MDA programme. [ABSTRACT FROM AUTHOR]

A diethylcarbamazine (DEC)-fortified salt intervention programme was implemented between 1982 and 1986 in Karaikal district, Union territory of Pondicherry, south India, to control Culex transmitted bancroftian filariasis. The intervention reduced the microfilaria (Mf) rate from 4.49% to 0.08%. To eliminate the residual microfilaraemia, the health department detected and treated Mf carriers from 1987 to 2005 and mass-administered drugs in 2004 and 2005. Surveillance from 1987 to 2005 revealed persistent microfilaraemia in 0.03–0.42% of the population. In 2006, we conducted a more detailed Mf survey and a child antigenaemia (Ag) survey in 15 urban wards and 17 rural villages. These surveys showed an overall Mf rate of 0.46% in the high-risk urban areas and 0.18% in the rural areas; none of the sampled children was positive for Ag. All detected Mf carriers were >20 years old. The age of the youngest Mf carrier was 30 years in urban and 21 years in rural areas, which suggests that transmission was interrupted and there was no incidence of new Mf case after cessation of DEC salt programme. Eleven of 15 urban and 15 of 17 villages were totally free from microfilaraemia. Nevertheless, three of 15 surveyed urban localities and two of 17 villages showed >1% Mf rate. Thus, it seems that (i) post-intervention very low levels of microfilaraemia can continue as long as 20 years; (ii) 0.60–0.70% Mf rate is a safe level and at this level recrudescence of infection may not occur; (iii) there can be isolated localities with >1% Mf rate and their detection for further intervention measures could be challenging in larger control/elimination programmes and (iv) the residual infection mostly gets concentrated in the adult population, in underdeveloped urban areas and in historically highly endemic or large endemic rural areas. These groups and areas should be targeted with rigorous intervention measures such as mass drug administration to eliminate the residual infection. [ABSTRACT FROM AUTHOR]

Objective To describe the spatial distribution of lymphatic filariasis and its relationship with the socioenvironmental risk indicator, thus identifying priority localities for interventions in endemic urban areas. Methods The study area was the municipality of Jaboatão dos Guararapes, State of Pernambuco, Brazil. The data sources were a parasitological survey and the 2000 demographic census. From these data, a socioenvironmental composite risk indicator was constructed using the 484 census tracts (CT) as the analysis units, based on the score-formation technique. Census tracts with higher indicator values presented higher risk of occurrences of filariasis. Results Six thousand five hundred and seven households were surveyed and 23 673 individuals were examined, among whom 323 cases of microfilaremia were identified. The mean prevalence rate for the municipality was 1.4%. The indicator showed that 73% (237/323) of the cases of microfilaremia were in high-risk areas (third and fourth quartiles) with worse socioenvironmental conditions (RR = 4.86, CI = 3.09–7.73, P < 0.05). Conclusions The socioenvironmental composite risk indicator demonstrated sensitivity, since it was able to identify the localities with greater occurrence of infection. Because it can stratify spaces by using official and available data, it constitutes an important tool for use in the worldwide program for eliminating lymphatic filariasis. [ABSTRACT FROM AUTHOR]

Objectives To determine the current status of lymphatic filariasis (LF) in Korea. Methods Epidemiological surveys between 2002 and 2006 in areas where LF was previously endemic: remote and coastal areas Jeollanam-do, Gyeongsangnam-do, and Jeju-do, and inland Gyeongsangbuk-do. We took night blood smears from 9426 people for microfilaria testing and assayed samples from 3049 children (10- to 13-year-olds) and 1526 adults for Brugia malayi antibodies. Results We found two cases (0.01%) with low microfilaria density in their peripheral blood (1–2/20 μl) on the remote island of Jeollanam-do in the southern part of the Korean peninsula. These patients, males over 60-years old, were treated with diethylcarbamazine (DEC). None of the 4575 people surveyed tested positive for specific B. malayi antibodies. Conclusion Lymphatic filariasis appears to have been eliminated in Korea. [ABSTRACT FROM AUTHOR]

Objective To identify possible associations between selected micronutrient status indicators (serum ferritin, retinol, β-carotene, α-tocopherol, and the acute phase reactant α-1 antichymotrypsin) and infection with human immunodeficiency virus (HIV) or Wuchereria bancrofti, and to assess the effect of the antifilarial drug diethylcarbamazine (DEC) on the micronutrient status indicators in individuals positive for one or both of the two infections. Methods Serum concentrations of ferritin, retinol, β-carotene, α-tocopherol and the acute phase reactant α-1 antichymotrypsin were examined in 59 individuals with HIV, W. bancrofti infection, or both, in Tanga Region, Tanzania, before and 12 weeks after treatment with DEC. Results HIV infection, but not W. bancrofti infection, was associated with higher serum ferritin concentrations and lower β-carotene and α-tocopherol. Neither HIV infection nor W. bancrofti infection was associated with serum retinol. The four micronutrient status indicators and α-1 antichymotrypsin were generally lower at 12 weeks after treatment both in the DEC and the placebo groups. Conclusions The negative association between HIV infection and the antioxidant vitamins β-carotene and α-tocopherol may be due to infection-induced oxidative stress, whereas W. bancrofti infection seemed not to be associated with oxidative stress. The drop in antioxidant vitamin concentrations after treatment may be due to oxidative stress induced by HIV progression (HIV infected) and inflammation around dead adult worms and microfilariae ( W. bancrofti infected) rather than to an effect of DEC. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of seven rounds of mass administration of diethylcarbamazine (DEC) and ivermectin on the prevalence of chronic lymphatic filariasis and to compare it with that observed in a placebo arm in a community-level trial. Methods Cross-sectional clinical surveys were carried out before and after seven rounds of mass drug administration (MDA). About 54–75% of the target population were treated at each round of MDA. Results After seven rounds, the hydrocele prevalence had declined from the pre-intervention level of 20.5–5.1% ( P < 0.05) in the DEC arm, from 23.9% to 10.4% ( P < 0.05) in the ivermectin arm and from 20.4% to 10.9% ( P < 0.05) in the placebo arm, equivalent to reductions of 75.3%, 56.6% and 46.6%, respectively. The lymphoedema/elephantiasis prevalence declined only marginally and without statistical significance from 3.7% to 3.2%, 4.6% to 3.9% and 2.9% to 2.3% in the DEC, ivermectin and placebo arm. After the seventh MDA, none of the sampled people in the 0–20 age group was found with hydrocele and there was a statistically significant decline in hydrocele prevalence in all other age groups in the communities treated with DEC, the drug known to have macrofilaricidal effect. The impact was relatively less in ivermectin arm. Conclusion Repeated DEC administration has the potential to prevent incidence of new hydrocele cases and may resolve the manifestation at least in a proportion of affected people. Apart from reducing the microfilaraemia prevalence and transmission of infection, MDA also results in significant public health benefits by reducing the burden of hydrocele in treated communities. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy of doxycycline as a macrofilaricidal agent against Wuchereria bancrofti. Method In the Western Region of Ghana, 18 patients infected with W. bancrofti were recruited and treated with 200 mg doxycycline per day for 4 weeks. Seven untreated patients served as controls. Four months after doxycycline treatment, all patients received 150 μg/kg ivermectin. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance sign (FDS). Results Four months after doxycycline treatment, cases had a significantly lower Wolbachia load than controls; and 24 months after treatment, microfilaraemia, antigenaemia and frequency of FDS were significantly lower in cases than controls. Most importantly, 4 weeks of doxycycline killed 80% of macrofilariae, which is comparable with the results of a 6-week regimen. Circulating filarial antigenaemia and FDS were strongly correlated. Conclusion A 4-week regimen of doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients, e.g. in outpatient clinics. [ABSTRACT FROM AUTHOR]