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.

Radioprotective effect of diethylcarbamazine on radiation-induced acute lung injury and oxidative stress in mice.

The present study was designed to evaluate the radioprotective effect of diethylcarbamazine (DEC) against oxidative stress and acute lung injury induced by total body radiation (TBI) in mice. For study the optimum dose for radiation protection of DEC, mice were administrated with three dose of DEC (10, 50 and 100 mg/kg), once daily for eight consecutive days. Animals were exposed whole body to 5 Gy X-radiation on the 9 day. The radioprotective potential of DEC in lung tissues was assessed using oxidative stress examinations at 24 h after TBI and histopathological assay also was analyzed one week after TBI. Results from biochemical analyses demonstrated increased malonyldialdehyde (MDA), nitric oxide (NO) and protein carbonyl (PC) levels of lung tissues in only irradiated group. Histopathologic findings also showed an increase in the number of inflammatory cells and the acute lung injury in this group. DEC pretreatment significantly mitigated the oxidative stress biomarkers as well as histological damages in irradiated mice. The favorable radioprotective effect against lungs injury was observed at a dose of 10 mg/kg of DEC in mice as compared with two other doses (50 and 100 mg/kg). The data of this study showed that DEC at a dose of 10 mg/kg with having antioxidant and anti-inflammatory properties can be used as a therapeutic candidate for protecting the lung from radiation-induced damage.

Isolated Epitrochlear Filarial Lymphadenopathy: Cytomorphological Diagnosis of an Unusual Presentation.

Filariasis is a major public health problem in tropical countries like India. Despite the large number of people at risk, detection of eggs with or without larva (microfilaria) on fine-needle aspiration cytology is very unusual, especially in an uncommon site or incidentally detected in clinically unsuspected cases of filariasis with the absence of microfilariae in the peripheral blood. A 19-year-old male presented with swelling over medial aspect of left arm (just above the elbow), with no other specific signs and symptoms. Fine needle aspiration cytology revealed an adult gravid female filarial worm in a background of reactive lymphoid cells and lymphohistiocytic clusters. We report a case with elaborate fine needle aspiration cytology findings of filarial worm infestation with unusual presentation of isolated epitrochlear lymph node involvement in a clinically unsuspected case and recommend clinicians and pathologists to consider a high index of suspicion for such infections at uncommon sites especially in endemic territories, as early diagnosis and treatment prevent the more severe manifestations of disease.

Are census data accurate for estimating coverage of a lymphatic filariasis MDA campaign? Results of a survey in Sierra Leone.

BACKGROUND: Preventive chemotherapy was administered to 3.2 million Sierra Leoneans in 13 health districts for lymphatic filariasis, onchocerciasis, and soil transmitted helminthes from October 2008 to February 2009. This paper aims to report the findings of a coverage survey conducted in 2009, compare the coverage survey findings with two reported rates for lymphatic filariasis coverage obtained using pre-mass drug administration (MDA) registration and national census projections, and use the comparison to understand the best source of population estimates in calculating coverage for NTD programming in Sierra Leone. METHODOLOGY/PRINCIPAL FINDINGS: Community drug distributors (CDDs) conducted a pre- MDA registration of the population. Two coverage rates for MDA for lymphatic filariasis were subsequently calculated using the reported number treated divided by the total population from: 1) the pre-MDA register and 2) national census projections. A survey was conducted to validate reported coverage data. 11,602 persons participated (response rate of 76.8%). Overall, reported coverage data aggregated to the national level were not significantly different from surveyed coverage (z-test >0.05). However, estimates based on pre-MDA registration have higher agreement with surveyed coverage (mean Kendall's W = 0.68) than coverage calculated with census data (mean Kendall's = 0.59), especially in districts with known large-scale migration, except in a highly urban district where it was more challenging to conduct a pre-MDA registration appropriately. There was no significant difference between coverage among males versus females when the analyses were performed excluding those women who were pregnant at the time of MDA. The surveyed coverage estimate was near or below the minimum 65% epidemiological coverage target for lymphatic filariasis MDA in all districts. CONCLUSION/SIGNIFICANCE: These results from Sierra Leone illustrate the importance of choosing the right denominator for calculating treatment coverage for NTD programs. While routinely reported coverage results using national census data are often good enough for programmatic decision making, census projections can quickly become outdated where there is substantial migration, e.g. due to the impact of civil war, with changing economic opportunities, in urban settings, and where there are large migratory populations. In districts where this is known to be the case, well implemented pre-MDA registration can provide better population estimates. Pre-MDA registration should, however, be implemented correctly to reduce the risk of missing pockets of the population, especially in urban settings.

Elimination of lymphatic filariasis as a public health problem from the Arab Republic of Egypt.

Lymphatic filariasis (LF) has been known in Egypt since ancient times. By 1930s it was recognized to be a major public health problem in the Nile Delta, and to be caused by Wuchereria bancrofti and transmitted by Culex pipiens. Remarkably, as a result of widespread DEC treatment and intensive vector control by the Ministry of Health and Population (MoHP), the infection rate of LF declined in the 1960s. However, relaxation of these efforts resulted in resurgence of filariasis in the 1980s and 1990s. In 2000, Egypt was among the first countries to join the WHO global efforts to eliminate LF as a public health problem by initiating a national LF elimination programme (NLFEP). This article reviews the history of LF control activities and summarizes the NLFEP extensive interventions to eliminate LF in Egypt. Based on MoHP data, mass drug administration (MDA) with DEC and ALB was started in 2000 in 161 implementation units (IUs). Additional IUs were included in subsequent MDA rounds, with the last IU included in 2007. MDA stopping surveys were conducted based on WHO guidelines (2005; 2011). Information about the presence of those suffering from lymphoedema/elephantiasis and hydrocele patients was collected, and care provided to those needing care in five rural health units (RHU) by primary health care system providers who were given training on LF morbidity management and disability prevention (MMDP). The NLFEP made excellent progress due to strong collaboration between different ministries, through intensive training and supervision, and the use of advocacy for mobilization of endemic communities. The epidemiological coverage for all MDA rounds was effectively ≥80%. Antigenemia levels found in schoolchildren during transmission assessment surveys (TAS) in 166 IUs approximately 10 years after stopping MDA was 0%. In 2017, TAS conducted in additional 29 IUs indicated 0.1% antigenemia and 0% microfilaremia. In 2015, the registration of chronic LF patients was updated to 1472 lymphoedema and 18 hydrocele patients. Lymphoedema patients were trained on self-management, and hydrocele patients were referred to local General Hospitals for surgery. Thus, after over a decade of sustained effort, Egypt met the WHO criteria for successful elimination of LF as a public health problem. In December 2017, WHO validated Egypt as the first country in the Eastern Mediterranean Region to successfully achieve elimination.

Effect of sildenafil and pimobendan on intracardiac heartworm infections in four dogs.

Four dogs, referred for management of heartworm (HW) disease, were found to have HWs entangled in their tricuspid valve apparatus. None of the dogs were actively hemolyzing or showed signs of acute cardiovascular collapse that would have necessitated emergency transvenous HW extraction, and surgery was not performed at time of presentation. The dogs received pimobendan and sildenafil within 24 h of identifying HW in the tricuspid valve apparatus, and the HW moved to the pulmonary arteries within 2 days in most cases (median 2 days, range 1-14 days). All dogs survived to discharge from the original hospital admission and were subsequently treated with adulticide (melarsomine) without complication. All dogs were HW antigen negative 6 months after their last melarsomine injection. Four dogs appeared to respond positively to medical management aimed at decreasing pulmonary arterial pressure and improving the right ventricular function, but movement of HW out of the heart for other reasons cannot be excluded. This therapeutic option is not advised when dogs with HW disease are presented for acute collapse, ongoing hemolysis, and hypotension as surgical extraction is still considered the best option in these cases. It remains unknown if medical management is a safe option for all dogs with intracardiac HW without clinical signs of caval syndrome. Controlled prospective studies are required to determine the efficacy and safety of this treatment regimen in comparison with surgical extraction.

Preventive chemotherapy reverses covert, lymphatic-associated tissue change in young people with lymphatic filariasis in Myanmar.

OBJECTIVES: This longitudinal comparative study investigated the effect of preventive chemotherapy (PC) on covert tissue changes associated with lymphatic filariasis (LF) among young people living in an LF-endemic area in Myanmar. METHODS: Tissue compressibility and extracellular free fluid in the lower limbs of people aged 10-21 years were measured using indurometry and bioimpedance spectroscopy (BIS). Baseline measures were taken in October 2014, annual mass drug administration (MDA) of PC was delivered in December, and in March 2015 further PC was offered to LF-positive cases who had missed MDA. Follow-up measures were taken in February and June 2015. RESULTS: A total of 50 antigen-positive cases and 46 antigen-negative controls were included. Self-reported PC consumption was 60.1% during 2014 MDA and 66.2% overall. At second follow-up, 24 of 34 cases and 27 of 43 controls had consumed PC. Significant and clinically relevant between-group differences at baseline were not found post-PC. Bayesian linear mixed models showed a significant change in indurometer scores at both calves for antigen-positive cases who consumed any PC (dominant calf: -0.30 [95% CI -0.52, -0.07], P < 0.05 and non-dominant calf: -0.35 [95% CI -0.58, -0.12], P < 0.01). Changes in antigen-negative participants or those not consuming PC were not significant. CONCLUSION: This study is the first attempt to use simple field-friendly tools to track fluid and tissue changes after treatment of asymptomatic people infected with LF. Results suggested that PC alone is sufficient to reverse covert lymphatic disturbance. Longer follow-up of larger cohorts is required to confirm these improvements and whether they persist over time. These findings should prompt increased efforts to overcome low PC coverage, which misses many infected young people, particularly males, who are unaware of their infection status, unmotivated to take PC and at risk of developing lymphoedema. Indurometry and BIS should be considered in assessment of lymphatic filariasis-related lymphedema.

OBJECTIFS: Cette étude comparative longitudinale a investigué l'effet de la chimiothérapie préventive (CP) sur les modifications tissulaires cachées associées à la filariose lymphatique (FL) chez les jeunes vivant dans une zone d'endémie pour la FL au Myanmar. MÉTHODES: La compressibilité des tissus et le liquide libre extracellulaire dans les membres inférieurs des personnes âgées de 10 à 21 ans ont été mesurés par indurométrie et spectroscopie de bioimpédance (BIS). Les mesures de base ont été prises en octobre 2014, la distribution en masse de médicament (DMM) annuelle a été administrée en décembre et en mars 2015, et une CP additionnelle a été offerte aux cas positifs pour la FL qui avaient manqué la DMM. Des mesures de suivi ont été prises en février et juin 2015. RÉSULTATS: 50 cas positifs pour l'antigène et 46 témoins négatifs ont été inclus. L'administration de CP auto-déclarée était de 60,1% durant la DMM de 2014 et de 66,2% au total. Au deuxième suivi, 24 des 34 cas et 27 des 43 témoins avaient pris la CP. Des différences significatives et cliniquement pertinentes entre les groupes au départ n'ont pas été trouvées après la CP. Les modèles mixtes linéaires bayésiens ont montré un changement significatif des scores d'indurometrie aux deux mollets pour les cas positifs pour l'antigène qui prenaient une CP (mollet dominant: -0,30 [IC95%: -0,52, -0,07], p <0,05, mollet non dominant: - 0,35 [IC95%: -0,58, -0,12], p <0,01). Les changements chez les participants négatifs pour l'antigène ou ceux qui ne prenaient pas de CP n'étaient pas significatifs. CONCLUSION: Cette étude est la première tentative d'utilisation d'outils simples, conviviaux sur le terrain, pour suivre les modifications du tissu conjonctif après le traitement de personnes asymptomatiques infectées par la FL. Les résultats suggèrent que la CP seule est suffisante pour inverser les modifications lymphatiques cachées. Un suivi plus long de plus grandes cohortes est nécessaire pour confirmer ces améliorations et déterminer si elles persistent ou non. Ces résultats devraient inciter à redoubler d'efforts pour surmonter la faible couverture en CP, qui rate beaucoup de jeunes infectés, en particulier les hommes, qui ne sont pas au courant de leur statut d'infection, qui ne sont pas motivés pour prendre une CP et risquent de développer un lymphœdème. L'indurométrie et la BIS devraient être considérées dans l'évaluation du lymphoedème associé à la filariose lymphatique.

Polyphenol enriched ethanolic extract of Cajanus scarabaeoides (L.) Thouars exerts potential antifilarial activity by inducing oxidative stress and programmed cell death.

Development of antifilarial drug from the natural sources is considered as one of the most efficacious, safe, and affordable approaches. In this study, we report the antifilarial activity of a leguminous plant Cajanus scarabaeoides (L.) Thouars. The polyphenol-rich ethanolic extract obtained from the stem part of the plant C. scarabaeoides (EECs) was found to be efficient in killing the filarial nematode Setaria cervi in all the three developmental stages viz. oocytes, microfilariae (Mf) and adults with LD50 values of 2.5, 10 and 35 µg/ml, respectively. While studying the molecular mechanism of action, we found that induction of oxidative stress plays the key role in inducing the mortality in S. cervi. The redox imbalance finally results in activation of the nematode CED pathway that executes the death of the parasite. Intriguingly, EECs was found to be selectively active against the worm and absolutely non-toxic to the mammalian cells and tissues. Taken together, our experimental data demonstrate that C. scarabaeoides can be chosen as an affordable natural therapeutic for treating filarial infection in the future with high efficacy and less toxicity.

Atypical cases of filariasis from a non-endemic area.

Filariasis can present in many different ways and pose significant dilemma to the clinician. We report four atypical cases of filariasis which presented as abdominal mass, cervical lymph node enlargement, fever in pregnancy and nosocomial febrile illness respectively. All the four cases were treated successfully with oral antifilarial agents. It is essential to be aware of such atypical presentations of filariasis so that prompt therapy can be initiated.

High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration.

Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); and uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm-infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats.

Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria bancrofti infection in children from Odisha, India and its reversal with DEC and albendazole treatment.

BACKGROUND: Once interruption of transmission of lymphatic filariasis is achieved, morbidity prevention and management becomes more important. A study in Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology with potential reversibility. We studied a Wuchereria bancrofti infected population, the major contributor to LF globally. METHODS: Children aged 5-18 years from Odisha, India were screened for W. bancrofti infection and disease. 102 infected children, 50 with filarial disease and 52 without symptoms were investigated by lymphoscintigraphy and then randomized to receive a supervised single oral dose of DEC and albendazole which was repeated either annually or semi-annually. The lymphatic pathology was evaluated six monthly for two years. FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics in 80% of symptomatic (40/50) and 63·5% (33/52) of asymptomatic children. Progressive improvement in baseline pathology was seen in 70·8, 87·3, 98·6, and 98·6% of cases at 6, 12, 18, and 24 months follow up, while in 4·2, 22·5, 47·9 and 64·8%, pathology reverted to normal. This was independent of age (p = 0·27), symptomatic status (p = 0·57) and semi-annual/bi-annual dosing (p = 0·46). Six of eleven cases showed clinical reduction in lymphedema of legs. INTERPRETATION: A significant proportion of a young W. bancrofti infected population exhibited lymphatic pathology which was reversible with annual dosage of DEC and albendazole. This provides evidence for morbidity prevention & treatment of early lymphedema. It can also be used as a tool to improve community compliance during mass drug administration. TRIAL REGISTRATION: ClinicalTrials.gov No CTRI/2013/10/004121.

Filarial breast lump.

Lymphatic filariasis is one of the most debilitating and disfiguring scourges among all diseases. This report presents a case of a woman with recurrent breast nodularity after being previously operated for a suspected breast neoplasm. We would like to highlight the issue of similar clinical presentation of a filarial breast lump and other breast lesions leading to inappropriate therapy.

New developments in chyluria after global programs to eliminate lymphatic filariasis.

Chyluria, commonly seen in south Asian countries, is mainly a manifestation of lymphatic filariasis as a result of infestation with Wuchereria bancrofti, although many other causes can contribute. Many patients can be effectively treated with dietary modifications and drug therapy. The most widely used drug is diethyl carbamazine. The recurrences are common after such treatment. Such patients would benefit from sclerotherapy to obliterate the lympatico-renal fistulae located mainly in the renal pelvicalyceal system. The commonly used sclerosing agent is a combination of 5% povidone-iodine and 50% dextrose instilled through a ureteric catheter. A small percentage of patients who recur after sclerotherapy and those with systemic complications, such as hypoproteinemia and edema, might require surgery in the form of renal hilar lymphatic disconnection. Although it is a major operation, the success rates are >90%. Laparoscopic and robotic techniques have minimized the morbidity related to such surgery. With the advent of the global program for eradication of filariasis initiated by the World Health Organization, the incidence of the disease is decreasing. Mass chemotherapy with diethyl carbamazine is the mainstay of this global program. Many years after eliminating filariasis, chyluria continue to occur in such populations, though in dwindling numbers. Future research should aim at finding more efficacious sclerosing agents with minimal recurrences.

Mathematical modelling of lymphatic filariasis elimination programmes in India: required duration of mass drug administration and post-treatment level of infection indicators.

BACKGROUND: India has made great progress towards the elimination of lymphatic filariasis. By 2015, most endemic districts had completed at least five annual rounds of mass drug administration (MDA). The next challenge is to determine when MDA can be stopped. We performed a simulation study with the individual-based model LYMFASIM to help clarify this. METHODS: We used a model-variant for Indian settings. We considered different hypotheses on detectability of antigenaemia (Ag) in relation to underlying adult worm burden, choosing the most likely hypothesis by comparing the model predicted association between community-level microfilaraemia (Mf) and antigenaemia (Ag) prevalence levels to observed data (collated from literature). Next, we estimated how long MDA must be continued in order to achieve elimination in different transmission settings and what Mf and Ag prevalence may still remain 1 year after the last required MDA round. The robustness of key-outcomes was assessed in a sensitivity analysis. RESULTS: Our model matched observed data qualitatively well when we assumed an Ag detection rate of 50 % for single worm infections, which increases with the number of adult worms (modelled by relating detection to the presence of female worms). The required duration of annual MDA increased with higher baseline endemicity and lower coverage (varying between 2 and 12 rounds), while the remaining residual infection 1 year after the last required treatment declined with transmission intensity. For low and high transmission settings, the median residual infection levels were 1.0 % and 0.4 % (Mf prevalence in the 5+ population), and 3.5 % and 2.0 % (Ag prevalence in 6-7 year-old children). CONCLUSION: To achieve elimination in high transmission settings, MDA must be continued longer and infection levels must be reduced to lower levels than in low-endemic communities. Although our simulations were for Indian settings, qualitatively similar patterns are also expected in other areas. This should be taken into account in decision algorithms to define whether MDA can be interrupted. Transmission assessment surveys should ideally be targeted to communities with the highest pre-control transmission levels, to minimize the risk of programme failure.

Breast filariasis or inflammatory breast carcinoma? Reaching a diagnosis.

Lymphatic filariasis is a neglected tropical disease caused by the parasite Wuchereria bancrofti. Involvement of the breast is relatively uncommon and may affect only 10% of individuals with lymphatic filariasis. We present a case of an elderly woman with breast pathology. The condition clinically appeared as a malignancy. Routine diagnostic tests including tissue histopathological studies failed to clinch a diagnosis. However, a serological test helped in identifying the pathology, which turned out to be a manifestation of breast filariasis, and aided in instituting appropriate therapy for this condition.

Case report of an epidural cervical Onchocerca lupi infection in a 13-year-old boy.

A 13-year-old boy presented with fever and neck pain and stiffness, which was initially misdiagnosed as culture-negative meningitis. Magnetic resonance images of the brain and cervical spine demonstrated what appeared to be an intradural extramedullary mass at the C1-3 level, resulting in moderate cord compression, and a Chiari Type I malformation. The patient underwent a suboccipital craniectomy and a C1-3 laminectomy with intradural exploration for excisional biopsy and resection. The lesion containing the parasite was extradural, extending laterally through the C2-3 foramina. Inflammatory tissue secondary to Onchocerca lupi infection was identified, and treatment with steroids and doxycycline was initiated. At the 6-month follow-up, the patient remained asymptomatic, with MR images demonstrating a significant reduction in lesional size. However, 10 weeks postoperatively, the infection recurred, necessitating a second operation. The patient was treated with an additional course of doxycycline and is currently maintained on ivermectin therapy. This is the second reported case of cervical O. lupi infection in a human. In the authors' experience, oral doxycycline alone was insufficient in controlling the disease, and the addition of ivermectin therapy was necessary.