Filarial Disease Research Articles

Updated annotation and meta-analysis of Brugia malayi transcriptomics data reveals consistent transcriptional profiles across time and space with some study-specific differences in adult female worm transcriptional profiles.

Genomics, transcriptomics, and proteomics have significantly advanced our understanding of obligately host-associated microbes, where interrogation of the biology is often limited by the complexity of the biological system and limited tools. This includes the causative agents of many neglected tropical diseases, including filarial nematodes. Therefore, numerous transcriptomics studies have been undertaken on filarial nematodes. Most of these transcriptomics studies focus on Brugia malayi, which causes lymphatic filariasis and is a laboratory model for human filarial disease. Here, we undertook a meta-analysis of the publicly available B. malayi transcriptomics data enabling the direct cross comparison of samples from almost a dozen studies. This reanalysis highlights the consistency of transcriptomics results across many different studies and experimental designs from across the globe for over a decade of research, across many different generations of a sequencing technology, library preparation protocols, and differential expression tools. Males and microfilariae across samples had similar expression profiles. However, female samples were clustered into two differential expression patterns that were significantly different from one another. Largely, we confirm previous results for all studies reanalyzed including tissue-specific gene expression and anti-Wolbachia doxycycline treatment of microfilaria. However, we did not detect previously reported differential expression upon in vitro or in vivo treatment with ivermectin, albendazole, and DEC, instead identifying a consistent lack of transcriptomic change upon exposure to these anthelminthic drugs. Updated annotation has been provided that denotes poorly supported genes including those overlapping rRNAs.

Three decades of research in lymphatic filariasis-lessons learned.

Lymphatic filariasis (LF), one of the 21 Neglected Tropical Diseases (NTD) which is the second leading cause for disability globally. Wuchereria Bancrofti, Brugia malayi and Brugia timori are the parasites causing this infection. World Health Assembly in 1997 declared LF to be eliminated and the Global Program to eliminate LF (GPELF) was launched by WHO in 2000 with the two strategies viz, 1) stop transmission of infection through Mass Drug Administration (MDA) and 2) to alleviate the suffering of the people affected with the disease through Morbidity Management and Disability Prevention (MMDP. The 'Filariasis research unit' recommended by WHO TDR and ICMR was established in Alappuzha, Kerala in 1989 for research studies related to LF. Over the last three decades 23 studies have been completed, which included different trials to find out the dose, effectiveness and safety of the various drugs used in preventive chemotherapy as single drug or combinations, for treatment of microfilaraemia,, various studies related to morbidity management in filarial disease, socio-economic aspects of filarial disability, Pharmacokinetic study of antifilarial drugs, Study on lymphatic filariasis in children, Studies on dignostics of LF, efficacy of drugs in management of lymphedema etc. In this article an attempt is made to explain the lessons learned from these studies and its importance in development of policy decision making for GPELF.

Molecular detection of Wuchereria bancrofti, Loa loa and Mansonella perstans from dried blood spots taken from pregnant women in rural Burkina Faso

Introduction: Human filariasis causes high morbidity and severe illness. There is a link between helminth infection and anemia. The objective of this study was to estimate the prevalence of blood-dwelling microfilariae among pregnant women in Burkina Faso using a molecular technique and attempt to find an association between anemia and filarial infection. Methods: A total of 1018 dried blood spot samples (DBS) were collected from pregnant women at the Health District of Nanoro. The DNA was isolated from DBS samples using a rapid and simple method. Afterward, the isolated DNA was assayed using the Filaria real-time PCR (F-RT-PCR) method. Results: Ten F-RT-PCR-positive samples were obtained as follows: two W. bancrofti (0.2%), four L. loa (0.39%), and four M. perstans (0.39%). No concomitant filarial infections were detected, as well as no coinfections between filarial disease and malaria. There was no link between the presence of W. bancrofti, L. loa, or M. perstans and anemia in pregnant women. Conclusions: The prevalence and intensity of human filariasis in this study were low for all of the samples in which microfilariae were detected. The F-RT-PCR can be a confirmatory test for diagnosis in remote areas due to its effectiveness in detecting and differentiating, both sensitively and specifically, a wide range of filarial parasites.

FRI517 BIUX2X2

Abstract Disclosure: K. Dash: None. U. Ayyagari: None. A Rare Presentation of Solitary Thyroid Nodule - Microfilaria: Case reportDash Kalpana,* Ayyagari Usha***Department of Endocrinology & Metabolism, Apollo Hospitals, Bilaspur. Chhattisgarh, India.** Smriti Speciality Klinics, Chennai, IndiaTel: +919827143474, Email: drkdash@rediffmail.com. Introduction: Filariasis is a debilitating public health problem in the tropics most commonly presenting with asymptomatic microfilaremia. Clinical manifestations include lymphangitis/lymphadenitis in lower limbs(elephantiasis), peritoneum, scrotum(hydrocele), and rarely in breast (breast lump), pleural effusion, bone marrow, and thyroid (painless nodule or thyroiditis). Diagnosis is by demonstrating microfilaria in peripheral blood or tissue biopsy or detection of filarial antigen/antibody in blood. Adult worms are found in lymphatics, subcutaneous tissue, peritoneal and pleural fluid, heart, brain, scrotum, breast, and rarely, thyroid. Filariasis may rarely present as superficial swellings at unusual sites. We present a case of filarial thyroid nodule, a rare manifestation of filarial disease. Clinical Case: Female, 72, presented with painless swelling over the thyroid for 6 months. She had no significant past medical history, was otherwise asymptomatic, clinically and biochemically euthyroid, with normal hemogram, RFT, and LFT. Clinical examination revealed a firm, non-tender nodule measuring 35x45mm, moves with deglutition. On USG of neck, a nodular hypoechoic lesion of 41x45mm was seen over right lobe of thyroid with calcification. FNAC was done for suspected carcinoma & showed histiocytes, hurthle cells, giant cells and a single viable Microfilarial form of Wuchereria bancrofti. She was treated with Diethylcarbamazine citrate & made a full recovery with resolution of the nodule. Discussion: We report a rare manifestation of filarial disease as a painless thyroid nodule. Circulating microfilaria reach the thyroid tissue, followed by rupture of vasculature causing local inflammatory reaction and subsequent nodular transformation. Diagnosis presents challenges as the endemic species in India exhibit nocturnal periodicity and it is difficult to find microfilariae in blood and fine-needle aspirates during the day. Case reports of microfilaria in thyroid aspirates from nodules or thyroiditis are rare. Clinical Lesson: The differential diagnosis for a painless thyroid nodule includes possible malignant disease, with the associated stress of further investigation and treatment. However, accurate diagnosis of filarial disease, rare as it may be, even in endemic areas, obviates the need for surgery as evidenced by the resolution of the nodule with medical treatment in our case. Presentation: Friday, June 16, 2023

Unraveling cross-reactivity of anti-glycan IgG responses in filarial nematode infections.

Parasitic nematodes responsible for filarial diseases cause chronic disablement in humans worldwide. Elimination programs have substantially reduced the rate of infection in certain areas, but limitations of current diagnostics for population surveillance have been pointed out and improved assays are needed to reach the elimination targets. While serological tests detecting antibodies to parasite antigens are convenient tools, those currently available are compromised by the occurrence of antibodies cross-reactive between nematodes, as well as by the presence of residual antibodies in sera years after treatment and clearance of the infection. We recently characterized the N-linked and glycosphingolipid derived glycans of the parasitic nematode Brugia malayi and revealed the presence of various antigenic structures that triggered immunoglobulin G (IgG) responses in infected individuals. To address the specificity of IgG binding to these glycan antigens, we screened microarrays containing Brugia malayi glycans with plasma from uninfected individuals and from individuals infected with Loa loa, Onchocerca volvulus, Mansonella perstans and Wuchereria bancrofti, four closely related filarial nematodes. IgG to a restricted subset of cross-reactive glycans was observed in infection plasmas from all four species. In plasma from Onchocerca volvulus and Mansonella perstans infected individuals, IgG binding to many more glycans was additionally detected, resulting in total IgG responses similar to the ones of Brugia malayi infected individuals. For these infection groups, Brugia malayi, Onchocerca volvulus and Mansonella perstans, we further studied the different IgG subclasses to Brugia malayi glycans. In all three infections, IgG1 and IgG2 appeared to be the major subclasses involved in response to glycan antigens. Interestingly, in Brugia malayi infected individuals, we observed a marked reduction in particular in IgG2 to parasite glycans post-treatment with anthelminthic, suggesting a promising potential for diagnostic applications. Thus, we compared the IgG response to a broad repertoire of Brugia malayi glycans in individuals infected with various filarial nematodes. We identified broadly cross-reactive and more specific glycan targets, extending the currently scarce knowledge of filarial nematode glycosylation and host anti-glycan antibody response. We believe that our initial findings could be further exploited to develop disease-specific diagnostics as part of an integrated approach for filarial disease control.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

Treatment of Lymphatic Filariasis with Wolbachia Targets

Nematodes are the cause of filariasis. Tissue nematodes as the cause of lymphatic filariasis are 3 species, namely Wuchereria bancrofti, Brugia malayi, Brugia timori.1 Lymphatic filariasis is the second largest cause of long-term disability, namely lymphedema of the extremities (elephantiasis) and hydrocele, especially in the tropics.2 Wolbachia bacteria are found in Onchocercidae, the family of filarial nematodes, including species that cause filarial disease in humans such as lymphatic filariasis and onchocerciasis. The symbiosis of Wolbachia and Onchocercidae shows that Wolbachia bacteria play a role in the treatment of filarial parasitic infections by using antibiotics such as tetracycline, doxycycline or rifampicin causing growth retardation and embryogenesis. 4 The long term use of antibiotics is feared to cause resistance to bacteria. Therefore, it is necessary to use antibiotics with a shorter time.

Filariasis in dogs brought to the Veterinary Teaching Hospital, University of Peradeniya, Sri Lanka.

Dirofilariasis is the predominant emerging zoonotic filariasis in the world. The two most frequent filarial worms that infect dogs are Dirofilaria repens and Dirofilaria immitis. This study reports filariasis among dogs brought to the Veterinary Teaching Hospital (VTH) at the University of Peradeniya and signifies the first molecular characterization of D. repens, responsible for an emerging zoonotic filarial disease in Sri Lanka. Blood samples were collected and were morphologically analyzed using Modified Knott's Technique, followed by molecular analyses. The difference in filariasis prevalence among gender, breed, and age categories was analyzed using a chi-square test. Infection intensities were analyzed using the Mann-Whitney U test and the Kruskal Wallis test. The dogs were brought to the clinic for either vaccination and/or for a regular checkup, and most were sick having non-specific clinical signs. Among the 87 dogs tested, 27.6% were positive for Dirofilaria. Conventional PCR and bi-directional sequencing of genomic DNA of microscopically tested positive samples revealed that the species in Sri Lanka was D. repens. The infection was significantly higher in males (39.1%) than in females (14.6%; χ2 = 0.447, p = 0.011), thoughit is not significant between puppies (age < 1year) and adult dogs. More crossbred dogs were infected compared to older and purebred dogs. There was no difference in intensity of infection based on their gender, age, or breed. Sequences obtained from the current study were unique and were only 63% identical to those of D. repens reported from South India. The high number of Dirofilaria infections in domestic dogs indicates a potential reservoir for emerging human dirofilariasis cases in Sri Lanka. Thus, morphological and molecular diagnosis, along with epidemiological assessment of these zoonoses, is critical for the formulation of effective public health programs and control mechanisms.

The filarial and the antibiotics: Single or combination therapy using antibiotics for filariasis.

Filarial infections caused by nematodes are one of the major neglected tropical diseases with public health concern. Although there is significant decrease in microfilariae (mf) prevalence following mass drug administration (IVM/DEC/ALB administration), this is transient, in that there is reported microfilaria repopulation 6-12 months after treatment. Wolbachia bacteria have been recommended as a novel target presenting antibiotic-based treatment for filarial disease. Potency of antibiotics against filarial diseases is undoubtful, however, the duration for treatment remains a hurdle yet to be overcome in filarial disease treatment.

Distinct loiasis infection states and associated clinical and hematological manifestations in patients from Gabon.

BackgroundLoiasis–a filarial disease endemic in Central and West Africa–is increasingly recognized as significant individual and public health concern. While the understanding of the disease characteristics remains limited, significant morbidity and excess mortality have been demonstrated. Here, we characterize clinical and hematological findings in a large cohort from Gabon.MethodsLoiasis-related clinical manifestations and microfilaremia, hemoglobin and differential blood counts were recorded prospectively during a cross-sectional survey. For analysis, participants were categorized into distinct infection states by the diagnostic criteria of eye worm history and microfilaremia.ResultsAnalysis of data from 1,232 individuals showed that occurrence of clinical and hematological findings differed significantly between the infection states. Eye worm positivity was associated with a wide range of clinical manifestations while microfilaremia by itself was not. Loa loa infection was associated with presence of eosinophilia and absolute eosinophil counts were associated with extent of microfilaremia (p-adj. = 0.012, ß-estimate:0.17[0.04–0.31]).ConclusionsLoiasis is a complex disease, causing different disease manifestations in patients from endemic regions. The consequences for the affected individuals or populations as well as the pathophysiological consequences of correlating eosinophilia are largely unknown. High-quality research on loiasis should be fostered to improve patient care and understanding of the disease.

Geospatial modeling of pre-intervention nodule prevalence of Onchocerca volvulus in Ethiopia as an aid to onchocerciasis elimination.

BackgroundOnchocerciasis is a neglected tropical filarial disease transmitted by the bites of blackflies, causing blindness and severe skin lesions. The change in focus for onchocerciasis management from control to elimination requires thorough mapping of pre-control endemicity to identify areas requiring interventions and to monitor progress. Onchocerca volvulus nodule prevalence in sub-Saharan Africa is spatially continuous and heterogeneous, and highly endemic areas may contribute to transmission in areas of low endemicity or vice-versa. Ethiopia is one such onchocerciasis-endemic country with heterogeneous O. volvulus nodule prevalence, and many districts are still unmapped despite their potential for onchocerciasis transmission.Methodology/Principle findingsA Bayesian geostatistical model was fitted for retrospective pre-intervention nodule prevalence data collected from 916 unique sites and 35,077 people across Ethiopia. We used multiple environmental, socio-demographic, and climate variables to estimate the pre-intervention prevalence of O. volvulus nodules across Ethiopia and to explore their relationship with prevalence. Prevalence was high in southern and northwestern Ethiopia and low in Ethiopia’s central and eastern parts. Distance to the nearest river (RR: 0.9850, 95% BCI: 0.9751–0.995), precipitation seasonality (RR: 0.9837, 95% BCI: 0.9681–0.9995), and flow accumulation (RR: 0.9586, 95% BCI: 0.9321–0.9816) were negatively associated with O. volvulus nodule prevalence, while soil moisture (RR: 1.0218, 95% BCI: 1.0135–1.0302) was positively associated. The model estimated the number of pre-intervention cases of O. volvulus nodules in Ethiopia to be around 6.48 million (95% BCI: 3.53–13.04 million).Conclusions/SignificanceNodule prevalence distribution was correlated with habitat suitability for vector breeding and associated biting behavior. The modeled pre-intervention prevalence can be used as a guide for determining priorities for elimination mapping in regions of Ethiopia that are currently unmapped, most of which have comparatively low infection prevalence.

Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses.

Despite long-term mass drug administration programmes, approximately 220 million people are still infected with filariae in endemic regions. Several research studies have characterized host immune responses but a major obstacle for research on human filariae has been the inability to obtain adult worms which in turn has hindered analysis on infection kinetics and immune signalling. Although the Litomosoides sigmodontis filarial mouse model is well-established, the complex immunological mechanisms associated with filarial control and disease progression remain unclear and translation to human infections is difficult, especially since human filarial infections in rodents are limited. To overcome these obstacles, we performed adoptive immune cell transfer experiments into RAG2IL-2Rγ-deficient C57BL/6 mice. These mice lack T, B and natural killer cells and are susceptible to infection with the human filaria Loa loa. In this study, we revealed a long-term release of L. sigmodontis offspring (microfilariae) in RAG2IL-2Rγ-deficient C57BL/6 mice, which contrasts to C57BL/6 mice which normally eliminate the parasites before patency. We further showed that CD4+ T cells isolated from acute L. sigmodontis-infected C57BL/6 donor mice or mice that already cleared the infection were able to eliminate the parasite and prevent inflammation at the site of infection. In addition, the clearance of the parasites was associated with Th17 polarization of the CD4+ T cells. Consequently, adoptive transfer of immune cell subsets into RAG2IL-2Rγ-deficient C57BL/6 mice will provide an optimal platform to decipher characteristics of distinct immune cells that are crucial for the immunity against rodent and human filarial infections and moreover, might be useful for preclinical research, especially about the efficacy of macrofilaricidal drugs.

Developing Strategies for Onchocerciasis Elimination Mapping and Surveillance Through The Diagnostic Network Optimization Approach

BackgroundOnchocerciasis (river blindness) is a filarial disease targeted for elimination of transmission. However, challenges exist to the implementation of effective diagnostic and surveillance strategies at various stages of elimination programs. To address these challenges, we used a network data analytics approach to identify optimal diagnostic scenarios for onchocerciasis elimination mapping (OEM).MethodsThe diagnostic network optimization (DNO) method was used to model the implementation of the old Ov16 rapid diagnostic test (RDT) and of new RDTs in development for OEM under different testing strategy scenarios with varying testing locations, test performance and disease prevalence. Environmental suitability scores (ESS) based on machine learning algorithms were developed to identify areas at risk of transmission and used to select sites for OEM in Bandundu region in the Democratic Republic of Congo (DRC) and Uige province in Angola. Test sensitivity and specificity ranges were obtained from the literature for the existing RDT, and from characteristics defined in the target product profile for the new RDTs. Sourcing and transportation policies were defined, and costing information was obtained from onchocerciasis programs. Various scenarios were created to test various state configurations. The actual demand scenarios represented the disease prevalence at IUs according to the ESS, while the counterfactual scenarios (conducted only in the DRC) are based on adapted prevalence estimates to generate prevalence close to the statistical decision thresholds (5% and 2%), to account for variability in field observations. The number of correctly classified implementation units (IUs) per scenario were estimated and key cost drivers were identified.ResultsIn both Bandundu and Uige, the sites selected based on ESS had high predicted onchocerciasis prevalence &amp;gt;10%. Thus, in the actual demand scenarios in both Bandundu and Uige, the old Ov16 RDT correctly classified all 13 and 11 IUs, respectively, as requiring CDTi. In the counterfactual scenarios in Bandundu, the new RDTs with higher specificity correctly classified IUs more cost effectively. The new RDT with highest specificity (99.8%) correctly classified all 13 IUs. However, very high specificity (e.g., 99.8%) when coupled with imperfect sensitivity, can result in many false negative results (missing decisions to start MDA) at the 5% statistical decision threshold (the decision rule to start MDA). This effect can be negated by reducing the statistical decision threshold to 2%. Across all scenarios, the need for second stage sampling significantly drove program costs upwards. The best performing testing strategies with new RDTs were more expensive than testing with existing tests due to need for second stage sampling, but this was offset by the cost of incorrect classification of IUs.ConclusionThe new RDTs modelled added most value in areas with variable disease prevalence, with most benefit in IUs that are near the statistical decision thresholds. Based on the evaluations in this study, DNO could be used to guide the development of new RDTs based on defined sensitivities and specificities. While test sensitivity is a minor driver of whether an IU is identified as positive, higher specificities are essential. Further, these models could be used to explore the development and optimization of new tools for other neglected tropical diseases.

Evaluation of macrofilaricidal and microfilaricidal activities against Onchocerca ochengi and cytotoxicity of some synthesized azo compounds containing thiophene backbone.

Control and treatment of onchocerciasis, a devastating tropical filarial disease caused by Onchocerca volvulus, rely solely on the community directed treatment with ivermectin. However, ivermectin is only microfilaricidal with evidence of resistance of the parasite among other limitations, which necessitate the search for new efficacious and safe filaricides. Ten synthetic thienylazoryl dyes were screened in vitro against adult and microfilariae worm stages of Onchocerca ochengi based on worm motility and MTT formazan assay. Cytotoxicity of active compounds was assessed on monkey kidney epithelial cells (LLC-MK2) using the MTT formazan assay. Seven (7) compounds showed both macrofilaricidal activity against adult male worms and microfilaricidal activity among which three 4a, 4c and 4e recorded the highest activity (IC50 = 4.2 to 8.8μM) against adult male worms, comparable to some standard anthelmintics. Five compounds showed rapid activity against microfilariae with 100% inhibition after 24-h incubation. The active compounds were nontoxic on monkey kidney cells (CC50> 4μg/mL), but their selectivity index values were relatively low (≤ 3). The thienylazoarylswith both macrofilaricidal and microfilaricidal activities may yield molecules which could be used for eradication of onchocerciasis following further medicinal chemistry modification of their structures to enhance their selectivity.

“CLINICO-PATHOLOGICAL STUDY OF SURGICAL LESIONS OF FILARIASIS”

Background: Lymphatic lariasis, transmitted by mosquitoes is the commonest cause of lymphedema in endemic countries. Among 120 million infected people in 83 countries, up to 16 million have lymphedema. Microlariae ingested by mosquitoes grow into infective larvae. These larvae entering humans after infected mosquito bites grow in the lymphatics to adult worms that cause damage to lymphatics resulting in dilatation of lymph vessels. This earliest pathology is demonstrated in adults as well as in children, by ultrasonography, lymphoscintigraphy and histopathology studies. Once established, this damage was thought to be irreversible. This lymphatic damage predisposes to bacterial infection that causes recurrent acute attacks of dermato-lymphangio-adenitis in the affected limbs. Bacteria, mainly streptococci gain entry into the lymphatics through 'entry lesions' in skin, like interdigital fungal infections, injuries, eczema or similar causes that disrupt integrity of skin. Methods-This study was conducted among 124 patients who attended SOPD and Filaria clinic (103) and admitted in Surgical wards (21) of S.G.M Hospital Rewa. All incidence, surgical manifestations and clinical diagnosed of lariasis in surgical patients include the study. Children with &lt;6 years of age, critically ill patients and cases where calcication has been established for the exclusion criteria. Follow up of the patients was done on 7th, 14th and 21th day and the treatment effects were recorded every time. Complications, progression / regression and over all effects were recorded. Results- Filarial disease was diagnosed in 124 patients. The majority of the patients with Filarial disease 28.22% and Microlaria positive 80% were in the age group of 21-30 years . Youngest patient was 7 years male with right thigh lymphedema and oldest patient was 74 years old male with bilateral hydrocele. male : female ratio with Filarial disease is 2.86:1. Regional lymphadenopathy was noted in 17.74%, overlying skin was inamed and oedematous in 12.9%, hypertrophic or thick skin 4.03%, ulceration and nodularity was present in 2.41% each .Maculopapular eruption and blisters was present in 1.61 % cases each. The commonest manifestation constituted 54.03% of cases. Epididymoorchitis was present in 25%, lymphangitis in 13.71%, lymphadenitis in 11.29%, hydrocele in 7.26%, and cellulitis in 4.84% cases. Funiculitis and elephantiasis in 4.84% and 4.03% respectively. Conclusion- Reducing the suffering caused by LF through morbidity management and disability prevention. The general population should be well educated and informed about the disease and prevention from mosquito bite. Patients who are already suffering from the disease should be made aware of the treatment modalities available and benets of promoting self-hygiene and self-help regimens. From the current study we can conclude that prevalence of laria in Vindhya Region is 0.11% which is less than 1% which was target under NPELF.

Identification of anti-Caenorhabditis and anti-Onchocerca constituents from leaves of Annona senegalensis Pers. (Annonaceae)

Onchocerciasis is a filarial disease caused by Onchocerca volvulus and transmitted through the bite of a blackfly of the genus Simulium. The microfilaricidal drug ivermectin has long been relied on to treat onchocerciasis. Nowadays, the focus is on the complete elimination of the disease through the development of macro-filaricidal drugs. In this study, a hydro-alcoholic extract from Annona senegalensis leaves was screened for micro- and macrofilaricidal activities against the cattle parasitic nematode Onchocerca ochengi and the free-living nematode Caenorhabditis elegans, both model organisms. Worms were assessed by in vitro motility/mortality assay studies and incubated with the various natural products and their effects on mortality were monitored after 48 h. The crude extract showed high activity with LC50 = 1450.2 µg/mL on the young adult of C. elegans wild type and 19.63 µg/mL on adult males of O. ochengi after 48 h post-exposure. The compounds, Quercetin-3-O-glucoside, (+)-Catechin, (-)-Epicatechin, Rutin and AS14.5, displayed LC50 of 179.3, 840.5, 1270.3, 118.2 and 129.7 µg/mL on C. elegans wild type (young adult), respectively, and 7.3, 17.5, 12.6, 6.6 and 11.5 µg/mL on O. ochengi (adult males), respectively, after 48 h. These data support the use of Annona senegalensis for the treatment of infections caused by Onchocerca volvulus.

Collateral Impact of Community-Directed Treatment with Ivermectin (CDTI) for Onchocerciasis on Parasitological Indicators of Loa loa Infection.

Ivermectin (IVM) is a broad spectrum endectocide whose initial indication was onchocerciasis. Although loiasis is not among its indications, IVM also exhibits antiparasitic activity against Loa loa. IVM-based preventive chemotherapies (PCs), so-called community-directed treatment with ivermectin (CDTI), have led to the interruption of transmission of onchocerciasis in some foci. A cross-sectional study was conducted in the Yabassi Health District where CDTI have been implemented since 20 years to fight onchocerciasis. All volunteers aged ≥ 5 years underwent daytime calibrated thick blood smears to search for L. loa microfilariae (mf). The prevalence of loiasis was 3.7% (95% CI: 2.2–6.2), significantly lower than its baseline prevalence (12.4%; 95% CI: 10.1–15.2; Chi-Square = 21.4; df = 1; p < 0.0001). Similarly, the microfilarial density was significantly low (mean = 1.8 mf/mL; SD = 13.6; max = 73,600) compared to baseline microfilarial density (mean = 839.3 mf/mL; SD = 6447.1; max = 130,840; Wilcoxon W = 179,904.5; p < 0.0001). This study revealed that the endemicity level of loiasis was significantly low compared to its baseline value, indicating a significant impact of IVM-based PC on this filarial disease. However, transmission is still ongoing, and heavily infected individuals are still found in communities, supporting why some individuals are still experiencing severe adverse events despite > 2 decades of CDTI in this Health District.

Slithering Through the Bone Marrow: Loiasis in a Patient With Human T-Cell Leukemia Virus-1-Associated Adult T-Cell Lymphoma.

Loiasis is a filarial disease endemic to areas of Central and West Africa. We present a case of Loa loa microfilaremia in a patient with HTLV-1-related adult T-cell lymphoma. This case may suggest the possible role of cellular immunity in controlling microfilaria burden.

Influence of nature in controlling filarial transmission: A study in slums of Burdwan

Purpose: Lymphatic filariasis is a crippling disease which affects the health status as well as economic condition of a person and also the society. Many attempts are made by scientists all over the world to control the filarial worm as well as vector. But nature plays important role in controlling the filariasis. Methods: To have some clear picture on how nature helps to control transmission of filarial disease, four slums of Burdwan (Hatgobindapur, Pandaveswar, Jamuria and Memari) were sampled for Daily survival rate (DSR), Daily Mortality Rate (DMR), Presumptive Mortality Rate (PMR) and Ovariolar dilatatations. Results: Lack of synchronization between the highest vector density and transmission disease, fall in parasitic load, mortality between two successive gonotrophic cycles, rise and fall in temperature and humidity is noticed in all the four slums which help to keep the check on transmission level of filaria by nature itself. Conclusions: Factors behind the natural phenomena of control is reflected in this article which perhaps helps to adopt strategies for effective control.

Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania.

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1–6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.