Molecular xenomonitoring as an indicator of microfilaraemia prevalence for lymphatic filariasis in Samoa in 2019.

BACKGROUND: Lymphatic filariasis (LF) is a globally significant, vector-borne, neglected tropical disease that can result in severe morbidity and disability. As the World Health Organization (WHO) Global Programme to Eliminate Lymphatic Filariasis makes progress towards LF elimination, there is greater need to develop sensitive strategies for post-intervention surveillance. Molecular xenomonitoring (MX), the detection of pathogen DNA in vectors, may provide a sensitive complement to traditional human-based surveillance techniques, including detection of circulating filarial antigen and microfilaraemia (Mf). This study aims to explore the relationship between human Mf prevalence and the prevalence of polymerase chain reaction (PCR)-positive mosquitoes using MX. METHODS: This study compared Mf and MX results from a 2019 community-based survey conducted in 35 primary sampling units (PSUs) in Samoa. This study also investigated concordance between presence and absence of PCR-positive mosquitoes and Mf-positive participants at the PSU level, and calculated sensitivity and negative predictive values for each indicator using presence of any Mf-positive infection in humans or PCR-positive mosquitoes as a reference. Correlation between prevalence of filarial DNA in mosquitoes and Mf in humans was estimated at the PSU and household/trap level using mixed-effect Bayesian multilevel regression analysis. RESULTS: Mf-positive individuals were identified in less than half of PSUs in which PCR-positive mosquito pools were present (13 of 28 PSUs). Prevalence of PCR-positive mosquitoes (each species separately) was positively correlated with Mf prevalence in humans at the PSU level. Analysed at the species level, only Aedes polynesiensis demonstrated strong evidence of positive correlation (r) with human Mf prevalence at both PSU (r: 0.5, 95% CrI 0.1-0.8) and trap/household levels (r: 0.6, 95% CrI 0.2-0.9). CONCLUSIONS: Findings from this study demonstrate that MX can be a sensitive surveillance method for identifying residual infection in low Mf prevalence settings. MX identified more locations with signals of transmission than Mf-testing. Strong correlation between estimated PCR-positive mosquitoes in the primary vector species and Mf in humans at small spatial scales demonstrates the utility of MX as an indicator for LF prevalence in Samoa and similar settings. Further investigation is needed to develop MX guidelines to strengthen the ability of MX to inform operational decisions.

Lymphatic filariasis in soldiers exposed in INDOPACOM.

Some military organizations in the U.S. Indo-Pacific Command (INDOPACOM) give returning soldiers presumptive treatment for filariasis. As there have been few clinical cases in recent decades, the historical basis for this chemotherapy was reviewed. During the Second World War, U.S. Marines stationed on Polynesian islands such as Tonga, Samoa, and Fiji experienced clinical lymphatic filariasis. Although thousands of both U.S. and Australian soldiers served in New Guinea, few, if any, cases of lymphatic filariasis were ascribed to Melanesia. While the French Army reported dozens of cases of filariasis among its service members during the 1950s Vietnam conflict, the U.S. military experienced only a few cases among the nearly 2 million service members who served in Vietnam in the 1960s. Australian soldiers deployed to Timor Leste in the 21st century showed rare seroconversions to filaria but no clinical disease. Following mass drug administration to eliminate lymphatic filaria in the INDOPACOM region, exposure in deployed soldiers rarely occurs and preventive chemotherapy should cease.

Current Status of the Diagnosis of Brugia spp. Infections.

Filarial nematodes of the genus Brugia include parasites that are significant to both human and veterinary medicine. Accurate diagnosis is essential for managing infections by these parasites and supporting elimination programs. Traditional diagnostic methods, such as microscopy and serology, remain vital, especially in resource-limited settings. However, advancements in molecular diagnostics, including nucleic acid amplification tests, offer enhanced sensitivity and specificity. These techniques are becoming increasingly field-friendly, expanding their applications in diagnostics. By refining existing methods, developing novel biomarkers, and understanding the zoonotic potential of various Brugia species, it is possible to improve control measures and better support elimination efforts.

Addressing the Syndemic Relationship between Lymphatic Filariasis and Mental Distress in Malawi: The Potential of Enhanced Self-Care.

Lymphatic filariasis (LF) causes disfiguring and disabling lymphoedema, which can lead to mental distress and requires life-long self-care treatment. This study applies syndemic theory to understand the biosocial relationship between LF and mental distress in Malawi. Using in-depth qualitative methods, we critically evaluate experiences of mental distress and LF through 21 life-history interviews, to narrate experiences from the perspective of persons affected by LF, and to understand how enhanced self-care (ESC) for lymphoedema management disrupts the syndemic relationship. Complementary key informant interviews with Ministry of Health LF programme staff were conducted to further understand intervention and health system delivery. All interviews were recorded, transcribed, and translated, and then subject to thematic analysis. Our findings suggest that for persons affected by LF in Malawi, before being trained in ESC, absent referral pathways, inequalities in healthcare provision or available treatment, and limited knowledge of the condition (LF) drove the syndemic of LF and mental distress. Distress was often exacerbated by stigma and social exclusion, and shaped by intersections of gender, generation, poverty, and extreme climate conditions. We argue that addressing the syndemic suffering associated with LF and mental distress through interventions which center the needs of persons affected is critical in effective and equitable LF care delivery.

Mitragyna parvifolia as apotential therapeutic agent for lymphatic filariasis.

This study investigates the medicinal potential of Mitragyna parvifolia (M. parvifolia) leaves for the management of Lymphatic filariasis (LF). Phytochemical screening of the methanolic leaf extract revealed the presence of alkaloids, terpenoids, phenols, tannins, and flavonoids. The GC-MS analysis identified 24 phytoconstituents, including the major alkaloid "mitraphylline." Infrared spectroscopy confirmed the presence of various functional groups corresponding to the identified compounds. The extract exhibited significant antibacterial activity against Staphylococcus epidermidis, Bacillus cereus, and Salmonella typhi. In vitro macrofilaricidal screening demonstrated dose-dependent inhibition of worm motility and MTT reduction, indicating its potential as a macrofilaricidal agent. The larvicidal bioassay showed notable effectiveness against Culex quinquifasciatus larvae, with 1% concentration displaying the highest larvicidal activity. Concentration-dependent antioxidant activity was observed using the DPPH assay, with 100 µg/ml showing the highest antioxidant potential. The findings suggest the potential of M. parvifolia leaves for LF management, supporting further research to identify active compounds and elucidate their mechanisms of action. The study highlights the plant's diverse bioactive compounds, antibacterial and macrofilaricidal activities, larvicidal efficacy, and significant antioxidant properties. Future investigations, including in vivo experiments and clinical trials, are warranted to validate the safety and efficacy of M. parvifolia as a potential therapeutic agent for LF.

The long and winding road towards new treatments against lymphatic filariasis and onchocerciasis.

Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing.

Anti-filarial antibodies are sensitive indicators of lymphatic filariasis transmission and enable identification of high-risk populations and hotspots.

OBJECTIVES: Circulating filarial antigen (Ag) is used by elimination programs to monitor lymphatic filariasis (LF) transmission; however, antifilarial antibodies (Ab) may be more sensitive than Ag for detecting LF. Our objectives were to describe Ab seroprevalence, identify risk factors for Ab seropositivity, investigate age-specific associations between Ag and Ab, and evaluate geographic clustering of seropositivity. METHODS: Community-based serosurveys of participants aged ≥5 years were conducted in 35 primary sampling units (PSUs). Ag-positivity was detected using Alere™ Filariasis Test Strips and Ab-seropositivity using multiplex bead assays. Seroprevalence was adjusted for study design. RESULTS: Of 3795 participants (range:5-90 years), adjusted prevalence for Ag, Bm14 Ab, Wb123 Ab, and Bm33 Ab were 3.7% (n=117), 20.3% (n=583), 32.2% (n=987), and 51.0% (n=1659), respectively. Male sex, older age, and residents of suspected hotspots had higher odds of seropositivity to all seromarkers. Seroprevalence was lower in 5-9-year-olds vs ≥10-year-olds (P<0.001). Clustering was significantly higher in households (intra-cluster correlation for Ag:0.45; Bm14 Ab:0.32; Bm33 Ab:0.31; Wb123 Ab:0.29) compared to PSUs or region. CONCLUSIONS: Abs enabled identification of risk factors for seropositivity and geographical clustering to inform targeted interventions for LF programmes. Further research is needed to define Ab thresholds for active versus past infection and elimination targets.

Deciphering the pH-dependent oligomerization of aspartate semialdehyde dehydrogenase from Wolbachia endosymbiont of Brugia malayi: An in vitro and in silico approaches.

The enzyme aspartate semialdehyde dehydrogenase (ASDH) plays a pivotal role in the amino acid biosynthesis pathway, making it an attractive target for the development of new antimicrobial drugs due to its absence in humans. This study aims to investigate the presence of ASDH in the filarial parasite Wolbachia endosymbiont of Brugia malayi (WBm) using both in vitro and in silico approaches. The size exclusion chromatography (SEC) and Native-PAGE analysis demonstrate that WBm-ASDH undergoes pH-dependent oligomerization and dimerization. To gain a deeper understanding of this phenomenon, the modelled monomer and dimer structures were subjected to pH-dependent dynamics simulations in various conditions. The results reveal that residues Val240, Gln161, Thr159, Tyr160, and Trp316 form strong hydrogen bond contacts in the intersurface area to maintain the structure in the dimeric form. Furthermore, the binding of NADP+ induces conformational changes, leading to an open or closed conformation in the structure. Importantly, the binding of NADP+ does not disturb either the dimerization or oligomerization of the protein, a finding confirmed through both in vitro and in silico analysis. These findings shed light on the structural characteristics of WBm-ASDH and offer valuable insights for the development of new inhibitors specific to WBm, thereby contributing to the development of potential therapies for filarial parasitic infections.

Evaluation of Mass Drug Administration Coverage for Lymphatic Filariasis in the Lukonga Health Zone in 2022.

(1) Background and rationale: To validate the reported therapeutic coverage, a lymphatic filariasis post-mass drug administration (MDA) campaign survey was conducted in the Lukonga health zone from 10 June to 15 July 2023. (2) Materials and methods: This was a descriptive, cross-sectional study conducted at the community level in 30 villages in the Lukonga health zone from 10 June to 15 July 2023. The study population included all individuals from the visited communities. The study variables included age, sex, drug use (ivermectin + albendazole), adverse events, and adherence to MDA guidelines for supervised drug use. Questionnaires were administered on Android phones using the SurveyCTO platform. Stata version 17 was used for data analysis. (3) Results: Of the 1092 respondents, 54.8% were female and one-third were between the ages of 5 and 14. Two-thirds of the households surveyed, or 64%, had more than six people living in them, and 1031 individuals, or 94%, reported being present during the community mass drug distribution. Notably, 678 individuals, or 66%, reported taking the drugs offered, and 66.4% of those who took the drugs reported doing so in the presence of drug distributors. Thus, the survey coverage was 65.7% [95% CI: 62.9-68.7]. The results of this study show that the survey coverage was above the 65% threshold recommended by the WHO but below the 82.3% reported by the Lukonga health zone. The main reason for non-compliance was a fear of ivermectin-related side effects (47%). Supervised or directly observed treatment was not adhered to (66.4%). (4) Discussion and conclusions: Key challenges to further increase treatment coverage include assessing data quality, building capacity, motivating drug distributors, improving data reporting tools, proper recording by drug distributors, and accurate reporting on non-residents who take the drugs during the MDA. In addition, harmonization of the numerator for calculating drug coverage in the health zone is critical. It is imperative to provide the public with explicit information regarding the objective of drug distribution and the probable adverse effects.

Assessment of mass drug administration for lymphatic filariasis elimination in the Armori and Chamorshi blocks of Gadchiroli District, Maharashtra: A cross-sectional study.

Context: Medical colleges regularly examine mass drug administration (MDA) programs to determine their effectiveness and pinpoint areas for development. These analyses frequently show a discrepancy between the program's coverage and actual drug use. This study was conducted in the Chamorshi and Armori blocks of the Gadchiroli District in Maharashtra. Aim: This study aimed to find out the coverage and compliance of MDA in the Chamorshi and Armori blocks of Gadchiroli, Maharashtra. Settings and Design: This study was a cross-sectional study. Materials and Methods: Thirty houses from each of the three randomly chosen villages and a ward were surveyed in each implementing unit. Thus, a total of 120 households' worth of data were gathered and examined. Information was gathered from each individual in the chosen home at the individual level. Statistical Analysis Used: Data were collected and duly filled out on questionnaire forms, which were then entered in Microsoft (MS) Excel. Statistical Package for the Social Sciences (SPSS) version 16.0 (Chicago) was used as a statistical tool in the analysis. Results: Consumption rates in rural areas were much higher than in urban areas. A minimum consumption rate was found in the 2- to 5-year-old age range. Conclusions: In this study, the percentage of coverage and compliance rates was 89.5% and 99.4% and 90.81% and 99.2% for the Armori and Chamorshi blocks, respectively. In comparison, coverage was better in rural areas than in urban areas. The MDA program must therefore be significantly strengthened in urban areas, particularly by guaranteeing improved compliance through monitored drug consumption.

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti-Wolbachia Candidate Macrofilaricide.

AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first-in-human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double-blind, placebo-controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700-mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.

Efficacy of ivermectin and albendazole combination in suppressing transmission of lymphatic filariasis following mass administration in Tanzania: a prospective cohort study.

BACKGROUND: Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA. METHODS: This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA. RESULTS: Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA. CONCLUSIONS: Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030.

Wuchereria bancrofti Lymphatic Filariasis, Barrancabermeja, Colombia, 2023.

We describe a recent case of lymphatic filariasis in Colombia caused by Wuchereria bancrofti nematodes. Our study combines clinical-epidemiologic findings with phylogenetic data. Resurgence of lymphatic filariasis may be linked to increasing urbanization trends and migration from previously endemic regions. Fieldwork can be a beneficial tool for screening and containing transmission.

Enhancing encapsulation of filarial antigen Brugia malayi thioredoxin in nano-liposomes: The role of lecithin composition.

Background and purpose: Lymphatic filariasis is a debilitating infectious disease prevalent in endemic areas, necessitating the development of an effective vaccine for eradication. Although recombinant vaccine candidates have been deemed safe, they often fail to provide sufficient protection, which can be overcome by encapsulating them in nano-liposomes. In this study, we have optimised the liposomal composition for enhanced stability and encapsulation of filarial antigen Brugia malayi thioredoxin (Bm-TRX). Experimental approach: Nano-liposomes were prepared using egg phosphatidylcholine (EPC) and cholesterol via thin-film hydration, followed by sonication and characterizing. Encapsulation efficiency was optimised using different weight ratios of EPC to cholesterol (8:2, 7:3, and 6:4) and total lipid (EPC+Cholesterol) concentration to antigen Bm-TRX (10:1, 10:2, and 10:3) followed by release kinetics study. Key results: Optimised parameters yielded spherical liposomes measuring 209 nm in diameter with narrow polydispersity. Our findings demonstrated the highest encapsulation efficiency of 70.685 % and stability of 10 hours for an EPC to cholesterol weight ratio of 7:3. The in silico study proved the antigenic nature of TRX. Conclusion: The liposomal formulations loaded with TRX, as optimized in this study, hold promise for improving antigen efficiency by enhancing stability, bioavailability, and prophylactic effects by acting as immune potentiators.

Ghana's path towards eliminating lymphatic filariasis.

Lymphatic filariasis, also known as elephantiasis, is a debilitating parasitic disease that has been prevalent in various parts of the world, including China and Ghana. This paper explores the historical context of lymphatic filariasis in Ghana and China, as well as the fights towards eliminating the disease in both countries. The review also covered the strategies employed by the Chinese government to eliminate lymphatic filariasis and the key lessons that Ghana can learn from China's success. The discussion highlights the importance of political commitment, multisectoral collaboration, tailoring control strategies to local contexts, adopting a comprehensive approach, and emphasising health education and community mobilisation. By adopting these lessons and fostering a robust national strategy, engaging diverse stakeholders, and ensuring active community involvement, Ghana can work towards achieving lymphatic filariasis elimination, improving public health, and fostering sustainable development.

Unraveling Lymphatic Filariasis in an Old Man: A Case Report.

Lymphatic filariasis, caused by filarial worms such as Wuchereria bancrofti, Brugia malayi, and Brugia timori, represents a significant public health burden in endemic regions. The disease primarily affects the lymphatic system, leading to lymphatic dysfunction and chronic morbidity. This abstract provides a comprehensive overview of lymphatic filariasis, including its transmission dynamics, pathogenesis, clinical manifestations, diagnostic approaches, and treatment options. Special attention is given to the socioeconomic impact of the disease and the challenges associated with its control and elimination. The patient in this particular case is a 58-year-old man who had lower limb swelling and pain, characteristic of chronic lymphatic obstruction. Additionally, the swelling tends to worsen during the evening hours often resulting in difficulty in walking and discomfort. Lymphatic filariasis was diagnosed based on clinical presentation.

Sero-antigen prevalence of lymphatic filariasis and risk factors of podoconiosis in Busiriba sub-county, Kamwenge district, Southwestern Uganda, August-September 2018.

OBJECTIVE: Given the neglected nature of filariasis, especially in Uganda where data are scarce, this cross-sectional study aimed to determine the sero-antigen prevalence of lymphatic filariasis and risk factors associated with non-lymphatic filariasis (podoconiosis) in Busiriba Sub-county, Kamwenge District, Uganda, during August-September 2018, to inform targeted elimination efforts. RESULTS: We enrolled 101 participants, among whom 35 (34.7%) had podoconiosis. The sero-antigen prevalence of lymphatic filariasis was 1.0%. Older age and walking barefoot were associated with increased podoconiosis risk. Specifically, individuals aged 25-49 years with had 7.38 times higher odds of podoconiosis (adjusted odds ratio [aOR] = 7.38, 95% CI: 1.36-40.13) compared to those under 25 years, while those aged ≥ 50 years had even higher odds (aOR = 8.49, 95%CI: 1.44-50.15). Additionally, individuals who reported walking barefoot had 14 times higher odds of podoconiosis (aOR = 14.08; 95% CI: 2.49-79.50).

Towards Understanding the Microepidemiology of Lymphatic Filariasis at the Community Level in Ghana.

Studies on the distribution of lymphatic filariasis (LF) have mostly focused on reporting prevalence at the community level and distribution at the district levels. Understanding the distribution patterns at community levels may help in designing surveillance strategies. This study aimed to characterize the spatial distribution of LF infections in four hotspot communities in Ghana. The research, involving 252 participants, collected demographic data, mass drug administration (MDA) information, household GPS coordinates, and antigen detection test results. The LF prevalence varied significantly among the communities, with Asemda having the highest (33.33%) and Mempeasem having the lowest (4.44%). Females had lower odds of infection than males (OR = 2.67, p = 0.003 CI: 1.39-5.13). Spatial analysis using kernel density, Anselin Local Moran's, Getis-Ord Gi models, Ordinary Least Squares, and Geographic Weighted Regression revealed mixed patterns of spatial autocorrelation. This study identified LF hotspots, indicating clusters of high or low prevalence with some areas showing disparities between MDA coverage and LF positivity rates. Despite these hotspots, the overall distribution of LF appeared random, suggesting the importance of purposeful sampling in surveillance activities. These findings contribute valuable insights into the micro-epidemiology of LF, emphasizing the need for community-specific investigations to understand the factors influencing the effectiveness of MDA programs in controlling filarial infections. The study highlights the importance of refining surveillance strategies based on community-level distribution patterns.