RESUMEN

Lymphatic filariasis is endemic in a few states of India and is one of the most common public health concerns. Wuchereria bancrofti (W. bancrofti) is the most common parasite that causes lymphatic filariasis in India. Microfilariae have been commonly found in the peripheral blood and body fluid, as well as demonstrated in fine needle aspirates (FNA) and bronchial cytology. They have been rarely reported in bone marrow aspirates. Due to the nocturnal periodicity of W. bancrofti, it may be missed in peripheral blood during the day. Though peripheral eosinophilia is a presenting feature of filariasis, it may be absent in the majority of cases, as in this case. We report an incidental finding of W. bancrofti in the bone marrow aspirate of a 72-year-old male who had chronic kidney disease.

RESUMEN

Lymphatic Filariasis (LF) affects over 120 million people in 72 countries, with sub-periodic filariasis common in the Pacific. Wuchereria bancrofti has three physiological races, each with a unique microfilarial periodicity, and each race is isolated to a specific geographical region. Sub-periodic W. bancrofti is transmitted by various Aedes mosquito species, with Aedes polynesiensis and Aedes samoanus being the primary vectors in Samoa. The Aedes scutellaris and Aedes kochi groups are also important vectors in the South Pacific Islands. Anopheles species are important vectors of filariasis in rural areas of Asia and Africa. The Anopheles gambiae complex, Anopheles funestus, and the Anopheles punctulatus group are the most important vectors of W. bancrofti. These vectors exhibit indoor nocturnal biting behaviour and breed in a variety of habitats, including freshwater, saltwater, and temporary water bodies. Effective vector surveillance is central to LF control and elimination programs. However, the traditional Human Landing Collection (HLC) method, while valuable, poses ethical concerns and risks to collectors. Therefore, this review critically analyses alternative trapping tools for Aedes and Anopheles vectors in LF-endemic regions. We looked at 14 research publications that discussed W. bancrofti vector trapping methods. Pyrethrum Spray Catches (PSC), one of the seven traps studied for Anopheles LF vectors, was revealed to be the second most effective strategy after HLC, successfully catching Anopheles vectors in Nigeria, Ghana, Togo, and Burkina Faso. The PSC method has several drawbacks, such as the likelihood of overlooking exophilic mosquitoes or underestimating Anopheles populations. However, exit traps offered hope for capturing exophilic mosquitoes. Anopheles populations could also be sampled using the Anopheles Gravid Trap (AGT). In contrast, the effectiveness of the Double Net Traps (DNT) and the CDC Light Trap (CDC LT) varied. Gravid mosquito traps like the OviArt Gravid Trap (AGT) were shown to be useful tools for identifying endophilic and exophilic vectors during the exploration of novel collection techniques. The Stealth trap (ST) was suggested for sampling Anopheles mosquitoes, although specimen damage may make it difficult to identify the species. Although it needs more confirmation, the Ifakara Tent Trap C design (ITT-C) showed potential for outdoor mosquito sampling in Tanzania. Furvela tent traps successfully captured a variety of Anopheles species and are appropriate for use in a variety of eco-epidemiological settings. By contrast, for Aedes LF vectors, no specific sampling tool was identified for Aedes niveus, necessitating further research and development. However, traps like the Duplex cone trap, Resting Bucket Trap (RB), and Sticky Resting Bucket trap (SRB) proved effective for sampling Aedes albopictus, offering potential alternatives to HLC. This review emphasises the value of looking into alternative trapping methods for Aedes and Anopheles vectors in the LF-endemic region. Further research is required to determine the efficacy of novel collection techniques in various contexts, even if PSC and AGT show promise for sampling Anopheles vectors. The identified traps, along with ongoing research, provide valuable contributions to vector surveillance efforts in LF-endemic regions, enabling LF control and elimination strategies to advance.

RESUMEN

BACKGROUND: Sixty-three out of 77 districts reported lymphatic filariasis (LF) endemic in Nepal. Mass drug administration (MDA) with diethylcarbamazine (DEC) and albendazole (ALB) treatment program was continued for 6 to 11 rounds in these districts. Nepal government has stopped the MDA program based on the transmission assessment survey (TAS) report of 2014 and 2018 indicating Wuchereria bancrofti antigenemia prevalence < 2%. But the persistence of low levels of the circulating filarial antigen (CFA) in some foci of four endemic districts of Central Nepal, i.e., 0.4% in Dhading, 0.7% in Mahottari, 0.21% in Lalitpur and 1.2% in Bara district could responsible for enhancing the risk of infection resurgence. Hence the present study was designed to assess antigenic prevalence using Filariasis Test Strip (Alere, Scarborough ME) in children born after MDA in hotspot areas of four endemic districts of Central Nepal. RESULTS: The present study covers 70% children of the eligible population. The result revealed significantly high CFA prevalence in hotspots of Mahottari district belonging to the Terai region and Dhading district belonging to the hilly region, i.e., 13% and 10%, respectively, compared to baseline prevalence and TAS report. While in Lalitpur district and Bara district CFA prevalence was still found to be less than 2%. A higher number of MDA rounds covered in hotspots were found significantly associated with the low antigenic prevalence of W. bancrofti. Whereas median treatment coverage and inter-quartile range (IQR) in study districts were not found significantly associated with CFA prevalence. Although the clinical manifestation of hydrocele (1%) was found in all four study districts, it was not due to the W. bancrofti infection. CONCLUSIONS: Two hotspot regions, one each from the Terai (Mahottari) and hilly (Dhading) districts were found highly prevalent with CFA and significantly associated with the number of MDA rounds but were not associated with treatment coverage and IQR. Higher CFA prevalence was observed in hotspots where baseline prevalence was high together indicating that rounds of MDA program need to be extended further in these hotspot regions of endemic districts.

RESUMEN

Lymphatic filariasis (LF) is one of the major health problems for the human kind in developing countries including India. LF is caused by three major nematodes namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. The recent statistics of World Health Organization (WHO) showed that 51 million people were affected and 863 million people from 47 countries around worldwide remain threatened by LF. Among them, 90% of the filarial infection was caused by the nematode W. bancrofti. Approved drugs were available for the treatment of LF but many of them developed drug resistance and no longer effective in all stages of the infection. In the current research work, we explored the Glutathione S-transferase (GST) of W. bancrofti, the key enzyme responsible for detoxification that catalyzes the conjugation of reduced GSH (glutathione) to xenobiotic compounds. Initially, we analyzed the stability of the WbGST through 200 ns MD simulation and further structure-based virtual screening approach was applied by targeting the substrate binding site to identify the potential leads from small molecule collection. The in silico ADMET profiles for the top-ranked hits were predicted and the predicted non-toxic lead molecules showed the highest docking score in the range of - 12.72 kcal/mol to - 11.97 kcal/mol. The cross docking of the identified hits with human GST revealed the potential binding specificity of the hits toward WbGST. Through WbGST-lead complex simulation, the lead molecules were observed to be stable and also intactly bound within the binding site of WbGST. Based on the computational results, the five predicted non-toxic molecules were selected for the in vitro assay. The molecules showed significant percentage of inhibition against the filarial worm Setaria digitata which is the commonly used model organism to evaluate the filarial activity. In addition, the molecules also showed better IC50 than the standard drug ivermectin. The identified lead molecules will lay a significant insight for the development of new drugs with higher specificity and lesser toxicity to control and treat filarial infections.

RESUMEN

Lymphatic filariasis (LF) is a neglected mosquito-borne parasitic disease, widely caused by Wuchereria bancrofti (Wb) in tropical and sub-tropical countries. During a blood meal, the filarial nematodes are transmitted to humans by the infected mosquito. To counter attack the invaded nematodes, the human immune system produces reactive oxygen species. However, the anti-oxidant enzymes of nematodes counteract the host oxidative cytotoxicity. Cu/Zn Superoxide dismutase (SOD1), a member of antioxidant enzymes and are widely used by the nematodes to sustain the host oxidative stress across its lifecycle, hence targeting SOD1 to develop suitable drug molecules would help to overcome the problems related to efficacy and activity of drugs upon different stages of nematodes. In order to find the potent inhibitors, a three-dimensional structure of Cu/Zn WbSOD1 was modelled and the structural stability was analysed through simulation studies. The structure-guided virtual screening approach has been used to identify lead molecules from the ChemBridge based on the docking score, ADMET properties and protein-ligand complex stability analysis. The identified compounds were observed to interact with the copper, metal binding residues (His48, His63, His80 and His120) and catalytically important residue Arg146, which play a crucial role in the disproportionation of incoming superoxide radicals of Cu/Zn WbSOD1. Further, in vitro validation of the selected leads in the filarial worm Setaria digitata exhibited higher inhibition and better IC50 compared to the standard drug ivermectin. Thus, the identified leads could potentially inhibit enzyme activity, which could subsequently act as drug candidates to control LF.Communicated by Ramaswamy H. Sarma.

RESUMEN

Lymphatic filariasis (LF) is a leading cause of permanent disability worldwide that has been listed as a neglected tropical disease by the World Health Organization. Significant progress made by the Global Program to Eliminate Lymphatic Filariasis (GPELF) has led to a substantial decline in the population of the worm that causes LF infection. Diagnostic assays capable of detecting low levels of parasite presence are needed to diagnose LF. There is also a need for new tools that can be used in areas where multiple filarial species are coendemic and for mass screening or for use in a point-of-care setting. In the present study, we applied our previously developed semi-automated microfluidic device in combination with our recently developed mini polymerase chain reaction (miniPCR) with a duplex lateral flow dipstick (DLFD) (miniPCR-DLFD) for rapid mass screening and visual species identification of lymphatic filariae in human blood. The study samples comprised 20 Brugia malayi microfilariae (mf) positive human blood samples, 14 Wuchereria bancrofti mf positive human blood samples and 100 mf negative human blood samples. Microfilariae detection and visual species identification was performed using the microfluidic device. To identify the species of the mf trapped in the microfluidic chips, DNA of the trapped mf was extracted for miniPCR amplification of W. bancrofti and B. malayi DNA followed by DLFD. Thick blood smear staining for microfilariae detection was used as the gold standard technique. Microfilariae screening and visual species identification using our microfluidic device plus miniPCR-DLFD platform yielded results concordant with those of the gold standard thick blood smear technique. The microfluidic device, the miniPCR and the DLFD are all portable and do not require additional equipment. Use of this screening and visual species identification platform will facilitate reliable, cost-effective, and rapid surveillance for the presence of LF infection in resource-poor settings.

RESUMEN

Lymphatic filariasis (LF), a mosquito-borne parasitic disease caused by nematode Wuchereria bancrofti in tropical and sub-tropical countries. These nematodes are transferred into the human host when the infected mosquito carrying L3 larvae is released into the bloodstream during the blood ingestion process. The host immune system produces ROS (Reactive Oxygen Species) as a primary defence mechanism to remove the invading filarial worms. However, well-defined antioxidant enzymes of the nematodes scavenge the host-produced ROS to escape from oxidative stress. The enzyme peroxiredoxin 6 (Prx6) belongs to the peroxiredoxin family, catalyses hydrogen peroxide (H2O2) into water (H2O). In order to find the inhibitors that inhibit the activity of peroxiredoxin 6 of W. bancrofti. We performed the homology modelling to predict the WbPrx6 three-dimensional structure using the Schrödinger-Prime and the dynamic stability of the modelled WbPrx6 was analyzed by carrying out the molecular dynamic (MD) simulation for the time scale of 200ns. Further, the structure-based virtual screening shortlisted the hit molecules from the ChemBridge database based on the glide score. The potential lead molecules (ID: 10239274, 11112883, 79879205, 58160895, and 42133744) that have better binding and satisfied the ADMET properties were selected for further complex simulation and DFT calculations. The identified compounds interact with the N-terminal region of the thioredoxin domain, which plays a key role in reducing phospholipase A2 activity. Interestingly, upon binding the lead molecule, the fluctuation of the loop region that connects α-IV with the ß-VI plays a vital role in affecting the geometry of the active site, which in turn affects the activity WbPrx6. The outcomes of the present computational studies could help in future drug development and designing of the effective candidate to control Lymphatic filariasis.

Asunto(s)

RESUMEN

Filariasis is a common parasitic infection in India. It is rare to find neglected cases of Filariasis nowadays. We reported the presence of microfilaria species in the follicular fluid of an egg donor undergoing an ovum pick up procedure. She was a 23-year-old egg donor who underwent stimulation using the GnRH antagonist protocol. Antagonist protocol is one of the standard protocols used for controlled ovarian hyperstimulation as a part of the IVF/ICSI(in-vitro fertilization / intracytoplasmic sperm injection) procedure where GnRH antagonist (cetrorelix) is used to suppress the endogenous LH surge. Her baseline investigations were normal, with no significant history suggestive of any worm infestations. During the ovum pickup procedure, follicular fluid revealed the presence of worm-like structures suggestive of larvae of some parasites. The follicular fluid was sent to the microbiology department along with the blood sample to confirm the parasite species. The parasite was found to be the larvae of W. Bancroft. The oocytes were of poor quality and were discarded. The patient was treated with Diethylcarbamazine citrate. There are so many reports about scrotal Filariasis, but rare literature quotes ovarian Filariasis.

Asunto(s)

RESUMEN

Lymphatic filariasis (LF) is a major public health problem globally and in the Pacific Region. The Global Programme to Eliminate LF has made great progress but LF is persistent and resurgent in some Pacific countries and territories. Samoa remains endemic for LF despite elimination efforts through multiple two-drug mass drug administrations (MDA) since 1965, including renewed elimination efforts started in 1999 under the Pacific Programme for Elimination of LF (PacELF). Despite eight rounds of national and two rounds of subnational MDA under PacELF, Samoa failed transmission assessment surveys (TAS) in all three evaluation units in 2017. In 2018, Samoa was the first to distribute countrywide triple-drug MDA using ivermectin, diethylcarbamazine (DEC), and albendazole. This paper provides a review of MDAs and historical survey results from 1998 to 2017 in Samoa and highlights lessons learnt from LF elimination efforts, including challenges and potential ways to overcome them to successfully achieve elimination.

Asunto(s)

RESUMEN

Filariasis is a major public health concern in tropical and subtropical countries including India. There have been very few case reports of incidental filariasis in the bone marrow aspirate smears in patients with hematological malignancies. We present a case of blastic phase of chronic myeloid leukemia (CML) with associated filariasis with monocytosis. Such an association, to the best of our knowledge, is hitherto unreported. Moreover, eosinophilia was not a feature in our case. A 37-year-old male, diagnosed case of CML, presented with low grade fever, weight loss and abdominal distension for one month. Physical examination revealed massive splenomegaly and hepatomegaly. However, there was no lymphadenopathy. His hemoglobin was 10.5 g/dl, total leukocyte count was 52.31x 109 / L with platelet count of 30x 109/L .Differential leukocyte count on peripheral smear showed 21% blasts, 30% polymorphs, 16% lymphocytes, 1% myelocyte, 1%metamyelocyte, 30%monocytoid cells and 1% eosinophils. Bone marrow aspirate smears were diluted with peripheral blood and showed blasts and monocytoid cells constituting 25% and 15% of marrow nucleated cells respectively. In addition, occasional microfilaria of Wuchereria bancrofti were also seen both in the peripheral blood and aspirate smears. Based on the above findings, a diagnosis of blastic phase of CML with monocytosis with microfilaria of W.bancrofti. Hence this was an unusual case of CML blastic phase which was associated with filariasis. Moreover, inspite of having filariasis and CML, patient lacked eosinophilia and instead showed monocytosis, which is hitherto unreported.

RESUMEN

The chromadorea abundant larval transcript (ALT) family of proteins contains ALT one of the most studied putative vaccine candidate in experimental filariasis. This study reports the characterization of Wuchereria bancrofti 20/22 (Wb20/22) as a member of chromadorea, the ALT family of proteins from the L3 stage of W. bancrofti. The high reactivity with serum from the endemic normal (EN) population suggests that Wb20/22 could be a target of elicit protective immunity. The glutamic acid-rich region of Wb20/22 was predicted to harbour the longest linear B-cell epitope by insilico prediction tools. The significance of this region was revealed by studying the mutant form of Wb20/22, without acidic domain (WOAD) which was cloned, and the immune response was compared with Wb20/22. The signal sequence of Wb20/22 was also an immunodominant region, and mutant construct without signal sequence (WOSS) was cloned and characterized. The peak antibody titre elicited by WOAD was higher than Wb20/22 or WOSS, which pointed to the immunomodulatory role of glutamic acid-rich region. Wb20/22 elicited very high levels of IL-10 and diminished levels of IL-4 and IL-5 which could be the reason for low antibody titre. The prophylactic efficacy of WOAD conferred protection (62·26%) which was higher than Wb20/22 (49·82%) and WOSS (54·78%).

Asunto(s)

RESUMEN

Filarial infections in humans are chronic infections that cause significant morbidity. The chronic nature of these infections with continuous antigen release is associated with a parasite-specific T cell hypo-responsiveness that may over time also affect the immune responses to bystander antigens. Previous studies have shown the filarial parasite antigen-specific T cells hypo-responsiveness is mediated by regulatory cytokines - IL-10 and TGF-ß in particular. Recent studies have suggested that the modulated/regulated T cell responses associated with patent filarial infection may reflect an expansion of regulatory T cells (Tregs) that include both Tregs induced in peripheral circulation or pTregs and the thymus-derived Tregs or tTregs. Although much is known about the phenotype of these regulatory populations, the mechanisms underlying their expansion and their mode of action in filarial and other infections remain unclear. Nevertheless there are data to suggest that while many of these regulatory cells are activated in an antigen-specific manner the ensuing effectors of this activation are relatively non-specific and may affect a broad range of immune cells. This review will focus on the subsets and function of regulatory T cells in filarial infection.

RESUMEN

Lymphatic filariasis caused byWuchereria bancrofti is a major health problem next only to malaria. A study had been conducted to estimate the prevalence of microfilaraemia in a rural endemic community near Raipur. The incidence of microfilaramia in the community was found to be about 14% when studied by night finger prick method. The incidence appears to be more in males as compared to females. The infection rate in vector population i.e.,Culex quinquefasciatus was recorded at a rate of 10%. No relationship could be drawn between the rates of vector and human filarial infections or between the density of vector population and the rate of vector/human infection(s). Prior health education is essential before taking up control and preventive measures in given endemic zone.