Lessons from integrating mental health as part of lymphatic filariasis morbidity management and disability prevention services in Jigawa State, Nigeria.

Lymphatic filariasis (LF) is a neglected tropical disease affecting >120 million people worldwide. LF has debilitating effects on humans and leads to morbidity and sometimes irreversible disability. A significant proportion of persons affected by LF morbidity also suffer from ill health, such as depression, anxiety, pain, stigma and social isolation due to disfigurement, as well as loss of mobility, livelihood and income. Mental health is often overlooked as a component of morbidity management and disability prevention (MMDP) services, despite the high prevalence of depression and anxiety among people affected by LF. To address this gap, Christian Blind Mission (CBM) piloted a comprehensive approach providing morbidity management and disability prevention by integrating mental health as part of the MMDP care package. The participatory evaluation of the project reviewed the project documents and a review meeting, small group discussions and in-depth interviews with project stakeholders. Findings suggest that project training and service delivery targets were exceeded in most cases. In addition, the disability and gender disaggregated data highlights the interplay of gender and disability in accessing care and the existence of unmet mental health needs. The financial cost of transportation to utilise referrals or access other MMDP services, such as replenishing treatment supplies, was a major constraint in accessing services for LF morbidity patients and low levels of awareness, fear of hydrocoele surgery and social stigmatisation were reported. The project outcomes demonstrate the feasibility and effectiveness of integrating mental health as part of a comprehensive MMDP package of care. Integration strategies should target training of MMDP providers in basic mental health skills, screening for mental health issues and the provision of mental health services and other MMDP services within the same facilities. Integration is an important step towards comprehensive care for people affected by LF and other NTD morbidities and disabilities.

Elimination of lymphatic filariasis as a public health problem in Malawi.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO. METHODOLOGY/PRINCIPAL FINDINGS: The Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1-2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools. CONCLUSIONS: Malawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success. SUMMARY: Lymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease.

Implementation and Outcomes of a Pilot Collaborative Surgical Hydrocele Training in Côte d'Ivoire.

Lymphatic filariasis (LF) is a neglected tropical disease that can cause hydrocele and its associated stigma, loss of economic productivity, and depression. Hydrocele surgery is an essential part of LF morbidity management but can be difficult for national programs to implement. To improve access to hydrocele surgeries in Côte d'Ivoire, we provided a WHO-certified surgical training for six surgical teams from five health districts in Côte d'Ivoire. We then evaluated the surgical outcomes and assessed the impact of hydrocele surgery on quality of life of hydrocelectomy patients. Preoperative and operative records were reviewed to describe baseline hydrocele characteristics and operative details. Postoperative interviews were conducted 4 to 6 months after surgical correction using a standardized questionnaire. Seventeen men underwent surgery during the training and were available for an interview at the 6-month visit. At the time of 6-month follow-up, 11/17 (64.7%) reported improvement in activities of daily living and reduction in difficulties with work, 8/17 (47.1%) reported an improved economic situation, 15/17 (88.2%) reported improved social interactions, and 15/16 (93.8%) reported improved sex life after surgical correction. Three patients (17.6%) had minor postoperative complications, but none required hospitalization. All 17 patients who were available for an interview were satisfied with their surgery. Surgical hydrocelectomy training in Côte d'Ivoire was well received and provided life-altering health improvements for participating patients across multiple domains of life. Support to scale up surgical capacity for this neglected problem is needed.

Potential mitigating role of ivermectin on the spread of Chlamydia trachomatis by Musca sorbens.

Trachoma is the world's most frequent cause of blindness from an infectious agent. The disease caused by infection is associated with lack of access to sanitation and low hygiene standards. Trachoma is controlled through the Surgery, Antibiotics, Facial cleanliness, and Environmental improvement (SAFE) strategy, which delivers azithromycin (AZM) mass drug administration (MDA) in endemic areas. The putative vector Musca sorbens principally reproduce in human faecal matter left in the environment due to open defecation. Ivermectin (IVM) is on the WHO's essential medicines list and is administered as preventative chemotherapy against two neglected tropical diseases (NTDs)-onchocerciasis, as an annual or bi-annual treatment, and lymphatic filariasis, as an annual treatment in combination with albendazole. Ivermectin has a known inhibitive effect on insects that reproduce in dung. To assess if IVM could be a viable vector control tool against M. sorbens, this study evaluates existing data from trachoma, onchocerciasis and lymphatic filariasis mass drug administration (MDA) operations in Ethiopia. Persistent and recrudescent trachoma in evaluation units (EUs) were examined for whether AZM MDA in EUs was accompanied by IVM MDA, and whether co-administration was associated with greater likelihood of trachoma control. Results show an association suggesting that EUs that received both IVM and AZM MDA benefit from improved control of trachoma in persistent or recrudescent areas, when compared to EUs that received AZM MDA. This initial investigation supports the potential for ivermectin's use to support SAFE. Findings warrant further work to validate ivermectin's impact on M. sorbens reproduction through controlled lab and field-based studies.

Crystal structure of dihydrofolate reductase from the filarial nematode W. bancrofti in complex with NADPH and folate.

Lymphatic filariasis is a debilitating illness with an estimated 50 million cases as of 2018. The majority of cases are caused by the parasitic worm W. bancrofti and additional cases by the worms B. malayi and B. timori. Dihydrofolate reductase (DHFR) is an established target in the treatment of cancer, bacterial, and protozoal infections and may be a potential target for drugs targeting parasitic worm infections, including filariasis. Recent studies have shown that known antifolate compounds, including methotrexate, inhibit the activity of W. bancrofti DHFR (WbDHFR). However, the absence of structural information for filarial DHFRs has limited the study of more in-depth structure-function relationships. We report the structure of WbDHFR complexed with NADPH and folate using X-ray diffraction data measured to 2.47 Å resolution. The structure of WbDHFR reveals the usual DHFR fold and is currently only the second nematode DHFR structure in the Protein Data Bank. The equilibrium dissociation constants for NADPH (90 ± 29 nM) and folate (23 ± 4 nM) were determined by equilibrium titrations. The interactions of known antifolates with WbDHFR were analyzed using molecular docking programs and molecular dynamics simulations. Antifolates with a hydrophobic core and extended linker formed favorable interactions with WbDHFR. These combined data should now facilitate the rational design of filarial DHFR inhibitors, which in turn can be used to determine whether DHFR is a viable drug target for filariasis and whether existing antifolates may be repurposed for its treatment.

Atividade locomotora de Culex quinquefasciatus (Diptera: Culicidae) em condições de laboratório / Locomotor activity of Culex quinquefasciatus (Diptera: Culicidae) under laboratory conditions

Ritmos biológicos de insetos vetores têm sido estudados com o objetivo de melhor compreender seus comportamentos e traçar estratégias de controle mais eficientes para reduzir a disseminação de patógenos. Culex quinquefasciatus possui competência vetorial para diversos patógenos de importância médica, como a filária causadora da Filariose Bancroftiana e o arbovírus West Nile (WNV). O presente trabalho tem como objetivo estudar a atividade locomotora de Cx. quinquefasciatus em diferentes condições fisiológicas, comparando machos, fêmeas virgens, fêmeas inseminadas, fêmeas alimentadas com sangue e fêmeas inseminadas e alimentadas com sangue. Além disso, comparamos a atividade locomotora de fêmeas inseminadas por cópula com machos com a de fêmeas inseminadas a partir da inoculação intratorácica de extrato de glândulas acessórias de seus machos coespecíficos. Nossos resultados mostraram que a atividade locomotora de machos e fêmeas de Cx. quinquefasciatus é noturna, com pico pronunciado no apagar das luzes. Observamos que tanto as fêmeas virgens quanto as inseminadas, após alimentação sanguínea, apresentam redução da atividade locomotora durante a escotofase em comparação com os demais grupos, especialmente as inseminadas e alimentadas com sangue. Em contrapartida, as fêmeas inseminadas e não alimentadas apresentaram aumento significativo na atividade locomotora durante a escotofase em comparação aos demais grupos. Ao compararmos os grupos de fêmeas não injetadas - virgens e inseminadas - com os grupos das fêmeas injetadas, observamos que estas apresentaram menor atividade locomotora do que aquelas. Entre as não injetadas, fêmeas inseminadas apresentaram maior atividade locomotora do que as virgens, enquanto, entre os grupos das injetadas, as fêmeas virgens inoculadas com glândulas acessórias de machos coespecíficos apresentaram maior atividade do que as inseminadas injetadas com solução salina. Esse estudo fornece importantes informações acerca da atividade locomotora dessa espécie, que podem ajudar na compreensão da dinâmica de transmissão de patógenos, direcionar novas pesquisas, além de auxiliar na elaboração de estratégias de vigilância e controles.

Biological rhythms of insect vectors have been studied for better understanding their behavior and designing more efficient control strategies to reduce the spread of pathogens. Culex quinquefasciatus has vector competence for several pathogens of medical importance, such as the filaria that causes Bancroftian Filariasis and the West Nile arbovirus (WNV). The present study aims to evaluate the locomotor activity of Cx. quinquefasciatus in different physiological conditions, comparing males, virgin females, inseminated females, blood-fed females and inseminated and blood-fed females. In addition, we compared the locomotor activity of females inseminated by mating with males with that of females inseminated by intrathoracic inoculation of accessory gland extract from their conspecific males. Our results showed that the locomotor activity of males and females of Cx. quinquefasciatus is nocturnal, with a pronounced peak at the lights-off. We observed that both virgin and inseminated females, after blood feeding, showed reduced locomotor activity during scotophase compared to the other groups, especially inseminated and blood fed females. In contrast, inseminated and unfed females showed a significant increase in locomotor activity during scotophase compared to the other groups. When comparing the groups of non-injected females - virgin and inseminated - with the groups of injected females, we observed that the latter showed lower locomotor activity than the former. Among non-injected females, inseminated females showed greater locomotor activity than virgin ones, whereas, among injected groups, virgin females inoculated with accessory glands from conspecific males showed greater activity than inseminated females injected with saline solution. This study provides important information about the locomotor activity of this species, which can help in understanding the dynamics of pathogen transmission, direct new research, and help in the development of surveillance and control strategies.

The development and roll-out of a new hydrocoele surgery facility assessment tool for the elimination of lymphatic filariasis.

A hydrocoele surgery facility assessment tool (HSFAT) was developed to assess the readiness of hydrocoele surgery services in health facilities prior to implementation of hydrocoele surgical campaigns for the elimination of lymphatic filariasis (LF). A first version of the tool was piloted in Bangladesh, Malawi and Nepal in 2019, then, following feedback from country programme managers, a second version of the tool was rolled out across countries implementing hydrocoele surgery in the Accelerating the Control of Neglected Tropical Diseases (Ascend) West and Central Africa Programme, including Benin, Burkina Faso, Ghana, Guinea, Niger and Nigeria. The HSFAT assessed facilities across 10 domains: background information, essential amenities, emergency patient transfer, laboratory capacity, surgical procedures and trained staff, infection prevention, non-disposable basic equipment, disposable basic equipment, essential medicines and current hydrocoele practices. The HSFAT results highlight key areas for improvement in different countries and can be used to develop a quality improvement plan, which may include actions with agreed deadlines to improve the readiness and quality of hydrocoele surgery services provided by the health facility, prior to implementation of surgical campaigns and assist country programmes to achieve the dossier requirements set out by the World Health Organization for the elimination of LF.

Adverse drug effects among students following mass de-worming exercise involving administration of Praziquantel and Albendazole in KEEA Municipality, Ghana.

BACKGROUND: To manage the deleterious effects of parasitic infections such as lymphatic filariasis (LF) and schistosomiasis among school children, most countries including Ghana make use of mass drug administration (MDA). Although MDA has proven effective in reducing worm burden, unfortunately adverse drug effects (ADEs) post-MDA are derailing the gains and also remain poorly monitored. The study assessed incidence and factors associated with ADEs among students following a school-based mass de-worming exercise involving administration of Praziquantel (PZQT) and Albendazole (ADZ) against LF and SCH at Komenda-Edina-Eguafo-Abirem (KEEA) Municipal. METHODOLOGY: After fulfilling all ethical obligations, a total of 598 students aged 5-20 years who received PZQT or ADZ monotherapy or a combination of the two (PZQT + ADZ) as part of the mass de-worming exercise were recruited through quota and random sampling. Bodyweight and height of students were measured and body mass index (BMI) calculated. Students were orally interviewed to obtain information such as age, sex, intake of diet before taking drugs. Subsequently, students were monitored over 24 hours post-MDA for cases of ADEs. Descriptive statistics and logistic regression analysis using SPSS version 26 was used to describe data collected and to determine associations between incidence of ADEs and predictor variables. PRINCIPAL FINDINGS: Out of the 598 students, 243 (40.64%) represented by 124 males (51.03%) and 119 females (48.97%) with mean (SD) age of 13.43 (2.74) years experienced one or more forms of ADE. In decreasing order, the detected ADEs included headache (64.6%), Abdominal pain (48.6%), fever (30.0%), diarrhea (21.4%) and itching (12.8%). Multivariable statistical analysis showed that age 5-9 years (OR: 2.01, p = 0.041) and underweight (OR: 2.02, p = 0.038) were associated with incidence of ADEs. Compared with students who received combination therapy, students who received ADZ only (OR: 0.05, p < 0.001) and PZQT only (OR: 0.26, p < 0.001) had low cases of ADEs. Gender and diet intake before MDA were not associated with ADE incidence. CONCLUSION: ADE incidence was common among students in the KEEA municipality. Age, underweight, and double dosing were associated with increase in ADE incidence, while gender and food intake were not associated with increase in ADE incidence. The Disease Control Unit of the Ghana Health Service should incorporate stringent ADE monitoring in post-MDA surveillance in the National MDA program in order to be able to detect, manage and report ADEs to inform planning for future MDA programs. Such initiatives will help not only in improving effectiveness of MDA programs but also identify high risk groups and exact strategies to reduce negative influence of ADE on MDA coverage and anthelminthic drug compliance.

The Connection between Climate Change, Surgical Care and Neglected Tropical Diseases.

The surgical burden of neglected tropical diseases (NTDs) is set to rise alongside average temperatures and drought. NTDs with surgical indications, including trachoma and lymphatic filariasis, predominantly affect people in low- and middle-income countries where the gravest effects of climate change are likely to be felt. Vectors sensitive to temperature and rainfall will likely expand their reach to previously nonendemic regions, while drought may exacerbate NTD burden in already resource-strained settings. Current NTD mitigation strategies, including mass drug administrations, were interrupted by COVID-19, demonstrating the vulnerability of NTD progress to global events. Without NTD programming that meshes with surgical systems strengthening, climate change may outpace current strategies to reduce the burden of these diseases.

Las TICs aplicada a la salud mental comunitaria y enfermedades endémicas / ICTs applied to community mental health and endemic diseases

Las enfermedades tropicales desatendidas suelen presentar una evolución crónica y se caracterizan por producir discapacidad física y mental a quienes las padecen, siendo asociadas a la estigmatización social. Se realizó un estudio descriptivo en 182 pacientes con enfermedades tropicales en regiones endémicas para leishmania, enfermedad de Chagas, filariasis linfática, oncocercosis, dengue y parasitosis intestinales; con el fin de evaluar la salud mental comunitaria, aplicando las tecnologias de información y comunicación (TIC), mediante el uso de telefónos móviles y telefonía fija. Se aplicó una encuesta para valorar el conocimiento y disposición de los pacientes respecto a las TIC, se valoró la salud mental calificada y la percibida por los pacientes mediante una escala de Likert. A partir de la calificación de la salud mental comunitaria se asociaron los estigmas sobre las enfermedades endémicas y luego se aplicó una encuesta para conocer la percepción de los pacientes, respecto a la influencia de los estigmas en la salud mental comunitaria. La mayor proporción de los participantes coincidieron en ser evaluados por parte del personal de salud, mediante herramientas de TIC y manifestaron tener problemas emocionales. Asimismo, el rechazo social como las secuelas de la enfermedad resultaron ser las manifestaciones más frecuentes de los participantes. En conclusión, el empleo de las TIC, en el área de salud mental comunitaria, supone un avance importante en el intercambio de información entre terapeutas y pacientes con enfermedades tropicales desatendidas, contribuyendo a disminuir el estigma social al que se ven sometidos y reestablecer su bienestar mental(AU)

Neglected tropical diseases usually present a chronic evolution and are characterized by causing physical and mental disability to those who suffer from them, being associated with social stigmatization. A descriptive study was carried out in 182 patients with tropical diseases in endemic regions for leishmania, Chagas disease, lymphatic filariasis, onchocerciasis, dengue and intestinal parasites; in order to assess community mental health, applying information and communication technologies (ICT), through the use of mobile phones and landlines. A survey was applied to assess the knowledge and disposition of the patients regarding ICT, the qualified mental health and that perceived by the patients was assessed using a Likert scale. From the qualification of community mental health, stigmas about endemic diseases were associated and then a survey was applied to know the perception of patients regarding the influence of stigmas in community mental health. The largest proportion of the participants agreed to be evaluated by health personnel, using ICT tools, and reported having emotional problems. Likewise, social rejection as the sequelae of the disease turned out to be the most frequent manifestations of the participants. In conclusion, the use of ICTs in the area of community mental health represents an important advance in the exchange of information between therapists and patients with neglected tropical diseases, helping to reduce the social stigma to which they are subjected and reestablish their mental health(AU)

Filariasis presenting as pancytopenia in a child.

A female child hailing from South Asia, India presented with pallor, multiple petechiae and ecchymosis. Based on the clinical picture and demography, the differentials considered were pancytopenia of nutritional origin, acute leukaemia, autoimmune and infective aetiologies. After ruling these out by respective tests, a literature review was done which revealed the possibility of filariasis especially in a patient with eosinophilia which was present in our case. A repeat peripheral blood smear study with a nocturnally drawn sample revealed multiple microfilariae and a diagnosis of filariasis was made. The patient was treated with triple drug therapy of diethylcarbamazine (6 mg/kg), ivermectin (6 µg/kg) and albendazole (400 mg) administered as a single dose. Subsequent haemograms showed improved cell counts. This along with a previous handful of case reports emphasises filariasis as one of the differentials of pancytopenia and should be kept in mind while evaluating for the same, especially in the endemic areas.

Community-based trial assessing the impact of annual versus semiannual mass drug administration with ivermectin plus albendazole and praziquantel on helminth infections in northwestern Liberia.

We assessed the impact of three annual vs five semiannual rounds of mass drug administration (MDA) with ivermectin plus albendazole followed by praziquantel for the control or elimination of lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminth (STH) infections and schistosomiasis in Lofa County, Liberia. The study started in 2012 and was interrupted in 2014 during the Ebola virus outbreak. Repeated cross-sectional surveys were conducted in individuals 5 years and older to measure infection markers. Wuchereria bancrofti antigenemia prevalences decreased from 12.5 to 1.2% (90% reduction) and from 13.6 to 4.2% (69% reduction) one year after three rounds of annual or five rounds of semiannual MDA, respectively. Mixed effects logistic regression models showed decreases in odds of antigenemia positivity were 91 and 74% at that time in the annual and semiannual treatment zones, respectively (p < 0.001). Semiannual MDA was slightly more effective for reducing Onchocerca volvulus microfiladermia prevalence and at follow-up 3 were 74% (from 14.4 to 3.7%) and 83% (from 23.6 to 4.5%) in the annual and semiannual treatment zones, respectively. Both treatment schedules had similar beneficial effects on hookworm prevalence. Thus, annual and semiannual MDA with ivermectin and albendazole had similar beneficial impacts on LF, onchocerciasis, and STH in this setting. In contrast, MDA with praziquantel had little impact on hyperendemic Schistosoma mansoni in the study area. Results from a long-term follow-up survey showed that improvements in infection parameters were sustained by routine annual MDA provided by the Liberian Ministry of Health after our study endpoint.

Unlocking Trust in Community Health Systems: Lessons From the Lymphatic Filariasis Morbidity Management and Disability Prevention Pilot Project in Luangwa District, Zambia.

BACKGROUND: Surgery for hydrocele is commonly promoted as part of morbidity management and disability prevention (MMDP) services for lymphatic filariasis (LF). However, uptake of these surgeries has been suboptimal owing to several community level barriers that have triggered mistrust in such services. This study aimed at documenting mechanisms of unlocking trust in community health systems (CHSs) in the context of a LF hydrocele management project that was implemented in Luangwa District, Zambia. METHODS: Qualitative data was collected through in-depth interviews (IDIs) and focus group discussions (FGDs) (n=45) in February 2020 in Luangwa District. Thirty-one IDIs were conducted with hydrocele patients, community health workers (CHWs), health workers, traditional leaders and traditional healers. Two FGDs were also conducted with CHWs who had been involved in project implementation with seven participants per group. Data was analyzed using a thematic analysis approach. RESULTS: The use of locally appropriate communication strategies, development of community driven referral systems, working with credible community intermediaries as well as strengthening health systems capacity through providing technical and logistical support enhanced trust in surgery for hydrocele and uptake of the surgeries. CONCLUSION: Implementation of community led communication and referral systems as well as strengthening health services are vital in unlocking trust in health systems as such mechanisms trigger authentic partnerships, including mutual respect and recognition in the CHS. The mechanisms also enhance confidence in health services among community members.

Evaluation of the angiogenic properties of Brugia malayi asparaginyl-tRNA synthetase and its mutants: A study on the molecular target for antifilarial drug development.

Brugia malayi asparaginyl-tRNA synthetase (BmAsnRS) has been identified as an immunodominant antigen and a physiocrine that mimics Interleukin-8 (IL-8) to induce chemotaxis and angiogenesis in endothelial cells. Computational analyses have shown that the N-terminal region of BmAsnRS has a novel fold, a lysine rich ß-hairpin α-helix, (FLIRTKKDGKQIWE) which is similar to that present in IL-8 chemokine, CXCR1. This novel fold is involved in tRNA binding and is integral for the manifestation of the disease, lymphatic filariasis (LF). Drug discovery programmes carried out so far for LF have not been successful because of the target (BmAsnRS) resistance due to the disease-associated mutation. Mutations in AARS targets have been shown to correlate with several diseases. However, no disease-associated mutational studies have been carried out for LF. BmAsnRS has been an established target for LF. It was proposed, therefore, to study the effect of single point mutations in BmAsnRS so as to elucidate the molecular target. An understanding of the molecular consequences of mutations will provide insight into how resistance develops in addition to the identification of the likely resistance-conferring mutations. Three mutants were, therefore, generated by site-directed mutagenesis using CUPSAT server and their angiogenic properties evaluated. Cytometric analysis of the mutants on endothelial cell cycle was also carried out. CUPSAT prediction of protein stability upon point mutations reveal that two mutants generated are likely resistance-conferring mutations. All the three mutants show significant reduction in their angiogenic properties and reduction in the DNA content in the cells of S and G2/M phases thus showing altered function of the gene encoding the drug target. The resistance- conferring mutants, however, show angiogenic properties nearer to the wild type protein, BmAsnRS. Future work on designing newer drugs may take into consideration these drug resistance-conferring mutations.

The implementation and impact of a pilot hydrocele surgery camp for LF-endemic communities in Ethiopia.

BACKGROUND: Ethiopia aims to eliminate lymphatic filariasis by 2020, through a dual approach of mass drug administration to interrupt transmission and morbidity control which includes making hydrocele surgery available in all endemic areas. Locating patients requiring surgery, providing high quality surgeries, and following up patients are all formidable challenges for many resource-challenged or difficult-to-reach communities. To date, hydrocele surgery in Ethiopia has only occurred when a patient has the knowledge, time and resources to travel to regional hospitals. Ethiopia tested the novel approach of using a surgical camp, defined as mobilizing, transporting, providing surgery at a static site, and following up of a large cohort of hydrocele patients within a hospital's catchment area, to address delays in seeking and receiving care. METHODOLOGY AND RESULTS: Health extension workers mobilized 252 patients with scrotal swelling from a list of 385 suspected hydrocele cases from seven endemic districts in the region of Beneshangul-Gumuz. Clinical health workers and surgeons confirmed 119 as eligible for surgery. Of 70 additional patients who self-referred, 56 were eligible for surgery. Over a two-week period at a regional hospital, 175 hydrocele excision surgeries were conducted. After discharge three days after surgery, trained clinical health workers followed up with the patients on Day 5, Day 8, Day 14 and 1st-month benchmarks with a randomized follow-up of a selection of patients conducted at 9-12 months. There were no post-operative complications upon discharge at Day 3 and 22, while minor complications occurred (12.6%) between Day 3 and one month. The 9-12 month follow-up found patients self-reported an improvement in quality of life, health and economic status. CONCLUSION: A hydrocele surgery camp was effective at providing a large number of quality surgeries in a short time. Using peripheral health workers to mobilize and follow up patients helped address delays in seeking and receiving quality care. Mainstreaming patient mobilization and follow-up into a community health system could be effective in other countries. The camp's results also influenced two regions in Ethiopia to change their policies in order to offer free hydrocele surgery (including patient transport, consultation, surgery, diagnostic tests and necessary medications).

Investigating immunological interaction between lymphatic filariasis and COVID-19 infection: a preliminary evidence.

The foremost concerns of COVID-19 vaccines are safety and efficacy, which becomes grave in countries with a high burden of Neglected Tropical Diseases. Studies proposed helminthic infections might alleviate the efficacy of COVID-19 vaccines. We share preliminary evidence on the association between filariasis and COVID-19 infection. We collated 2 ml of blood from 174 participants residing in filariasis endemic area. To determine filarial antigen, the Og4C3 test and for COVID-19 antibodies, tests through ELISA was performed. COVID-19 antibodies were present among 74/174 (42.5%), whereas filarial antigens were detected in 24/174 (13.8%) participants. An insignificant association [OR = 0.855 (0.36-2.034)] between two was observed. Hence, people in filarial endemic regions can continue taking vaccines without worrying about their efficacy due to the helminthic load in community.

Recombinant antigens used as diagnostic tools for lymphatic filariasis.

Lymphatic filariasis (LF) is a parasitic disease caused by the worms Wuchereria bancrofti, Brugia malayi, or Brugia timori. It is a tropical and subtropical illness that affects approximately 67 million people worldwide and that still requires better diagnostic tools to prevent its spread and enhance the effectiveness of control procedures. Traditional parasitological tests and diagnostic methods based on whole protein extracts from different worms are known for problems related to sample time collection, sensitivity, and specificity. More recently, new diagnostic tools based on immunological methods using recombinant antigens have been developed. The current review describes the several recombinant antigens used as tools for lymphatic filariasis diagnosis in antigen and antibody capture assays, highlighting their advantages and limitations as well as the main commercial tests developed based on them. The literature chronology is from 1991 to 2021. First, it describes the historical background related to the identification of relevant antigens and the generation of the recombinant polypeptides used for the LF diagnosis, also detailing features specific to each antigen. The subsequent section then discusses the use of those proteins to develop antigen and antibody capture tests to detect LF. So far, studies focusing on antibody capture assays are based on 13 different antigens with at least six commercially available tests, with five proteins further used for the development of antigen capture tests. Five antigens explored in this paper belong to the SXP/RAL-2 family (BmSXP, Bm14, WbSXP-1, Wb14, WbL), and the others are BmShp-1, Bm33, BmR1, BmVAH, WbVAH, BmALT-1, BmALT-2, and Wb123. It is expected that advances in research with these antigens will allow further development of tests combining both sensitivity and specificity with low costs, assisting the Global Program to Eliminate Lymphatic Filariasis (GPELF).

Foot care practice and associated factors among patients with lymphoedema in Boreda district, Gamo zone, southern Ethiopia, 2020. Implications for elimination of podoconiosis and lymphatic filariasis.

BACKGROUND: Lymphatic filariasis is ranked as the second leading cause of disability world-wide. The current global programme to eliminate lymphatic filariasis is based on the interruption of transmission and the alleviation of disability and suffering. OBJECTIVE: to assess foot care practice and associated factors among lymphoedema patients in Boreda district, Gamo zone Southern Ethiopia. METHODS: a community based cross sectional study was employed from December 2020 to June 2021 in Boreda district. Simple random sampling technique was used for selecting participants. Pretested structured interviewer administered questionnaire was prepared in English and translated to local language. FINDINGS: a total of 280 lymphedema patients were involved in this study. More than half 153 (54.6%) had poor practice towards foot care practice with 95% CI (48.7, 60.4%). Patients who fetched 50 l of water or below and wore shoes at the age above 20 years were negatively associated with foot care practice, (AOR = 0.383, 95%CI: 0.155, 0.945) and (AOR = 0.261, 95%CI: 0.107, 0.63), respectively. Patients who owned only one pair and two pairs were negatively associated with foot care practice (AOR = 0.04, 95%CI: 0.009, 0.182) and (AOR = 0.27, 95%CI: 0.087, 0.85), respectively. On the other hand, attending LMMDP service and frequency of adenolymphangitis once and twice or more per month were positively associated with foot care practice (AOR = 3.339, 95%CI: 1.53, 7.285) and (AOR = 8.15, 95% CI: 3.157, 21.058) and (AOR = 9.35, 95% CI: 3.118, 28.059), respectively. CONCLUSION: this study indicated foot care practice among lymphedema patients in Boreda district was poor. Number of litre of water collected per day, age at which footwear first worn, number of shoes owned, attending LMMDP and frequency of adenolymphangitis were significantly associated with foot care practice. Standard foot care practice should be emphasized to control progression of lymphedema. Foot care practices like skin care, exercise and elevation, washing legs, bandaging and massaging are important factors that influence in reduction of lymphedema volume and acute attacks among people who are suffering from the diseases.