Lymphedema resulting from filariasis successfully treated by surgery

Filariasis is an infectious disease caused by a filarial worm infection transmitted by mosquito bites. The disease can result in reduced work productivity, disability and social stigma. This disease transmission process begins when a mosquito bite and suck the blood containing the microfilaria. Filarial infections have been grouped into three categories based on their location diseases of the disease: (1) lymphatics, (2) skin, and (3) body cavities. Morbidity is almost entirely due to the species that cause lymphatic diseases, and skin diseases to a lesser degree. A 28-year-old male came with a chief complaint of swollen right leg since four years ago which worsened in the last three months. Upon physical examination, edema, fibrosis, and hyper-pigmented plaques were present on the right lower extremity. The blood microfilariae examination was positive for Wuchereria bancrofti. The lymphedema did not resolve despite of antifilarial treatment and surgery was eventually performed to resect the fibrous tissue and subcutaneous edema. The patient responded well to the treatment with a significant reduction in the edema. No complication was present until two years after surgery.

Advances in Antiwolbachial Drug Discovery for Treatment of Parasitic Filarial Worm Infections

The intracellular bacteria now known as Wolbachia were first described in filarial worms in the 1970s, but the idea of Wolbachia being used as a macrofilaricidal target did not gain wide attention until the early 2000s, with research in filariae suggesting the requirement of worms for the endosymbiont. This new-found interest prompted the eventual organization of the Anti-Wolbachia Consortium (A-WOL) at the Liverpool School of Tropical Medicine, who, among others have been active in the field of antiwolbachial drug discovery to treat filarial infections. Clinical proof of concept studies using doxycycline demonstrated the utility of the antiwolbachial therapy, but efficacious treatments were of long duration and not safe for all infected. With the advance of robotics, automation, and high-speed computing, the search for superior antiwolbachials shifted away from smaller studies with a select number of antibiotics to high-throughput screening approaches, centered largely around cell-based phenotypic screens due to the rather limited knowledge about, and tools available to manipulate, this bacterium. A concomitant effort was put towards developing validation approaches and in vivo models supporting drug discovery efforts. In this review, we summarize the strategies behind and outcomes of recent large phenotypic screens published within the last 5 years, hit compound validation approaches and promising candidates with profiles superior to doxycycline, including ones positioned to advance into clinical trials for treatment of filarial worm infections.

Ragam Spesies dan Karakteristik Habitat Nyamuk di Kecamatan Juai, Kabupaten Balangan, Provinsi Kalimantan Selatan

Filariasis is a mosquito borne disease which caused by filarial worm. In addition, beside causing ahigh morbidity rate and socioeconomic losses, the disease may also decrease the human productivity. Thecontrol efforts have been done by vector control program, yet still not effective. This is due to a lack ofunderstanding of the biology of mosquito vector. The aim of this research was to determine diversity ofmosquitoes, density, behavior, characteristic habitat and their role of filariasis transmission. The researchwas conducted from Januari to April 2015 in Hamarung and Hukai Villages, Juai Subdistrict, BalanganDistrict, South Kalimantan Province. Collection of mosquitoes was done by bare leg bait indoor collectionmethod and outdoor collection method from 06.00 pm–06.00 am. In additon, larvae were collected in theirpotencial habitats. There were 15 species mosquitoes comprising of 5 genera i.e. genus of Culex, Mansonia,Anopheles, Armigeres, and Aedes. There were 5 dominant species of mosquitoes i.e. Cx. tritaeniorhynchus(36.80%), Cx. quinquefasciatus (29.60%), Ma. dives (11.73%), Ma. annulata (10.04%) dan Ma. uniformis(4.62%). The peak activity of Cx. tritaeniorhynchus and Cx. quinquefasciatus in both villages occurred at21.00–00.45. Based on the habitat of mosquitoes, genus of Culex, Mansonia and Anopheles were found inswamps. Mosquitoes dissection did not show any microfilaria stages (L1, L2, L3).

Kepatuhan Masyarakat Minum Obat Pencegah Massal Filariasis (Kaki Gajah): Studi Kasus Desa Bilas, Kabupaten Tabalong

Filariasis (elephantiasis), huntut or tubab people lived in South Kalimantan often mentioned is an annual infectious disease and categorized as neglected tropical disease (NTD) caused by filarial worm. Filariasis is an endemic diseases in Tabalong District, especially Bilas Village. The selective and Mass Drug Treatment have been conduct in Bilas village but the village still decided as a filariasis endemic area, so it is necessary to study the compliance of the filariasis Mass Drug Assessment (MDA) consumption in the community to against filariasis incidences in Bilas Village. Study was held by Finger Blood Survey (SDJ) and interview using questionnaire about people’s obedience of filariasis MDA drug consumption. 341 responden have been interviewed and held by SDJ, 11 responden were positive filariasis B. malayi in Bilas village. The compliance of people consumed POPM drugs routinely of filariasis patients was only 20% and non patient were 21,64%. It was necessary to conduct a simultaneous MDA with district coverage area accompanied by medical illumination and socialization to the community. Medication supervisors placed at POPM posts or home-to-home visits was needed to ensure medication is actually consumed by the community, it will be better if the MDA was consumed immediately in front of cadres/health officers. Abstrak Filariasis atau kaki gajah atau sering disebut dengan huntut atau tubab oleh masyarakat Kalimantan Selatan adalah penyakit menular menahun yang merupakan penyakit tropis terabaikan disebabkan oleh cacing filaria. Filariasis endemis di Kabupaten Tabalong, khususnya Desa Bilas. Pengobatan selektif dan pengobatan massal telah dilakukan namun desa tersebut masih dinyatakan sebagai desa endemis sehingga perlu dilakukan penelitian terhadap kepatuhan masyarakat minum obat pencegah massal terhadap kejadian filariasis di Desa Bilas. Kegiatan yang dilakukan yaitu Survei Darah Jari (SDJ) dan kegiatan wawancara menggunakan kuesioner tentang kepatuhan meminum obat pencegah massal filariasis. Sebanyak 341 responden yang berhasil diwawancara dan dilakukan pemeriksaan darah jari, 11 orang diantaranya positif filariasis jenis parasit B. malayi di Desa Bilas. Kepatuhan masyarakat yang minum obat POPM secara rutin pada penderita hanya 20%, sedangkan pada non penderita sebanyak 21,64%. Perlu dilakukan pengobatan massal serentak sekabupaten disertai dengan sosialisasi dan penyuluhan tentang pengobatan massal kepada masyarakat. Kader pengawas minum obat yang ditempatkan di pos-pos pelaksanaan POPM atau kunjungan dari rumah ke rumah diperlukan untuk memastikan obat benar-benar diminum, akan lebih baik jika obat diminum langsung didepan kader/ petugas kesehatan.

Microfilaria Detection on Giemsa Blood Smears using Real-Time PCR

Filariasis is an infectious disease caused by filarial worms, which found in many tropical and subtropical regions. In 2017, 12,677 cases of chronic filariasis were found in Indonesia, which 132 cases of them were from Central Kalimantan province. Data of Kapuas District Health Office shows 17 cases filariasis in 2015. Frequently, filariasis patients did not show any diseases symptoms, especially when the level of microfilariae in the blood is deficient. On the other hand, microscopic assay with Giemsa blood smears is still the gold standard to define filariasis. Thus, a false negative result may occur due to a low level of microfilariae in the blood. In this study, we develop a real-time PCR method, targeting the HhaI gene of filaria, to detect filarial worm from stored Giemsa blood taken from filariasis patients, in both dry and wet scraping methods. Our result shows that real-time PCR can detect Brugia malayi in all scraping samples, with Ct value from wet scraping sample tends to be higher than dry scraping. In conclusion, the real-time PCR method can be further used to define filariasis, especially in the condition when Giemsa smear blood cannot determine patient filariasis status.

Preclinical development of an oral anti-Wolbachia macrolide drug for the treatment of lymphatic filariasis and onchocerciasis

There is an urgent global need for a safe macrofilaricide drug to accelerate elimination of the neglected tropical diseases onchocerciasis and lymphatic filariasis. From an anti-infective compound library, the macrolide veterinary antibiotic, tylosin A, was identified as a hit against Wolbachia. This bacterial endosymbiont is required for filarial worm viability and fertility and is a validated target for macrofilaricidal drugs. Medicinal chemistry was undertaken to develop tylosin A analogs with improved oral bioavailability. Two analogs, A-1535469 and A-1574083, were selected. Their efficacy was tested against the gold-standard second-generation tetracycline antibiotics, doxycycline and minocycline, in mouse and gerbil infection models of lymphatic filariasis (Brugia malayi and Litomosoides sigmodontis) and onchocerciasis (Onchocerca ochengi). A 1- or 2-week course of oral A-1535469 or A-1574083 provided >90% Wolbachia depletion from nematodes in infected animals, resulting in a block in embryogenesis and depletion of microfilarial worm loads. The two analogs delivered comparative or superior efficacy compared to a 3- to 4-week course of doxycycline or minocycline. A-1574083 (now called ABBV-4083) was selected for further preclinical testing. Cardiovascular studies in dogs and toxicology studies in rats and dogs revealed no adverse effects at doses (50 mg/kg) that achieved plasma concentrations >10-fold above the efficacious concentration. A-1574083 (ABBV-4083) shows potential as an anti-Wolbachia macrolide with an efficacy, pharmacology, and safety profile that is compatible with a short-term oral drug course for treating lymphatic filariasis and onchocerciasis.

An perspective: Potential medicinal plant resources for filariasis disease.

Filariasis is one of the oldest and most debilitating neglected tropical diseases, which is caused by parasitic filarial worm that are transmitted to humans by mosquitoes. In the lymphatics system filarial worm become adult worm that cause damage to lymphatics resulting in dilatation of lymph vessels. An estimated approximately 120 million people in 83 countries. An estimated approximately one and half billion live in areas where filariasis is endemic and are at risk of infection with Wuchereria bancrofti, Brugia timori and Brugia malayi. Presently diethylcarbamazine and Ivermectin and a single-dose treatment are currently employing in an attempt to control the infection but these drugs cannot treat properly and have lots of side effects. Recently limited plant products were reported to be beneficial in the treatment or control of these parasitic infections like filariasis but they could not be developed into viable drugs for a variety of reasons. This review focuses on searching medicinal plants for filariasis diseases. In this review, we explored medicinal plant that show the anti-filarial activities on filarial worm. These medical plants will help for further development the potation drug development for the treatment