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.

Filariasis presenting with bicytopenia, progressive splenomegaly and acute renal failure: An unusual case report.

Extra-lymphatic manifestation of filariasis, especially as acute renal failure, is uncommon and may be clinically unsuspected. We document the case of a 60 year old elderly male who presented with bilateral pedal oedema, fatigue and abdominal distension. Investigations revealed severe anaemia, splenomegaly and acute renal failure. Bone marrow aspiration was performed to evaluate the clinical suspicion of malignancy. Out of eight smears examined, microfilaria (Brugia malayi) were identified in two. This presentation was devoid of peripheral eosinophilia. The patient was commenced on a regimen of diethylcarbamazine, on which he made a good recovery. The incidence of extra-lymphatic filariasis is largely unknown and sparsely reported. Such a presentation should be kept in mind by both clinicians and pathologists as it is potentially treatable.

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.

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.

Elefantiasis escrotal. Presentación de un caso en Gambia / Elefantíase escrotal. Apresentação de caso na Gâmbia / Scrotal elephantiasis. Case presentation in the Gambia

Se presentó un paciente masculino con 25 años de edad, procedencia rural. Refirió en la cara lateral del hemiescroto derecho secreciones de color amarillo. En los genitales externos presentó una masa de 38 cm de largo y 35 cm de ancho, bordes irregulares, piel circundante edematosa, seca, acartonada, ulcera de 10 x 5 cm, no dolorosa y secreciones blanquecinas y serohemática escasa, pérdida de la anatomía del pene y disuria. Se confirmó el diagnóstico de elefantiasis escrotal secundaria a filariasis. Se aplicó tratamiento con dietilcarbamazina y quirúrgico. El tratamiento posibilitó la curación y la reincorpación social y sexual del paciente(AU)

A 25-year-old male patient was presented, of rural origin to the Urology office of the Royal Victoria National Hospital in the Republic of Gambia. He reported on the lateral side of the right hemiescrot yellow secretions. In the external genitalia it presented a mass of 38 cm long and 35 cm wide, irregular edges, surrounding edematous, dry, cracked skin, ulcer of 10x5 cm, non-painful and whitish secretions and serohematic scarce, loss of penile anatomy and dysuria The diagnosis of scrotal elephantiasis secondary to filariasis was confirmed. Diethylcarbamazine treatment and surgical intervention were applied. The treatment allowed the healing and social and sexual reincorpation of the patient(AU)

Um paciente do sexo masculino, 25 anos, foi apresentado, de origem rural, ao consultório de Urologia do Royal Victoria National Hospital, na República da Gâmbia. Ele relatou no lado lateral das secreções amarelas hemiescrot à direita. Na genitália externa, apresentava massa de 38 cm de comprimento e 35 cm de largura, bordas irregulares, circundando pele edematosa, seca e quebradiça, úlcera de 10x5 cm, secreções não dolorosas e esbranquiçadas e escassez seroemática, perda de anatomia peniana e disúria O diagnóstico de elefantíase escrotal secundária à filariose foi confirmado. Tratamento com dietilcarbamazina e intervenção cirúrgica foram aplicados. O tratamento permitiu a cura e a reincorpação social e sexual do paciente(AU)

Primary retroperitoneal filariasis: a common disease of tropics with uncommon presentation and review of literature.

Lymphatic filariasis is caused by nematode filariae Wuchereria bancrofti, Brugia malayi or Brugia timori. It is commonly seen in tropical and subtropical regions of the world and affects the lymphatic system of humans, who are the definitive host while mosquito is the intermediate host. The most common manifestation of the disease is hydrocele followed by lower limb lymphoedema and elephantiasis. Although filariasis is much more common entity in north India, its presentation as retroperitoneal cyst is very rare with reported incidence rate of 1/105 000. We present a case of primary retroperitoneal filariasis in a 52-year-old man, without any classic signsandsymptoms, diagnosed postoperatively after surgical resection following diagnostic uncertaintyandfailure of other medical therapies.

How elimination of lymphatic filariasis as a public health problem in the Kingdom of Cambodia was achieved.

BACKGROUND: Endemicity of lymphatic filariasis (LF) in Cambodia was proven in 1956 when microfilariae were detected in mosquitos in the Kratié province. In 2001, an extensive study confirmed the presence of both Brugia malayi and Wuchereria bancrofti microfilariae. In 2003, the Ministry of Health established a national task force to develop policies and strategies for controlling and eliminating neglected tropical diseases (NTDs), with the goal of eliminating LF by 2015. This article summarizes the work accomplished to eliminate LF as a public health problem in Cambodia. METHODS: The National Program to Eliminate Lymphatic Filariasis made excellent progress in the goal towards elimination due to strong collaboration between ministries, intensive supervision by national staff, and advocacy for mobilization of internal and external resources. Mass drug administration (MDA) with diethylcarbamazine citrate and albendazole was conducted in six implementation units, achieving > 70% epidemiological coverage for five consecutive rounds, from 2005 to 2009. In 2006, in 14 provinces, healthcare workers developed a line list of lymphedema and hydrocele patients, many of whom were > 40 years old and had been affected by LF for many years. The national program also trained healthcare workers and provincial and district staff in morbidity management and disability prevention, and designated health centers to provide care for lymphedema and acute attack. Two reference hospitals were designated to administer hydrocele surgery. RESULTS: Effectiveness of MDA was proven with transmission assessment surveys. These found that less than 1% of school children had antigenemia in 2010, which fell to 0% in both 2013 and 2015. A separate survey in one province in 2015 using Brugia Rapid tests to test for LF antibody found one child positive among 1677 children. The list of chronic LF patients was most recently updated and confirmed in 2011-2012, with 32 lymphoedema patients and 17 hydrocele patients listed. All lymphedema patients had been trained on self-management and all hydrocele patients had been offered free surgery. CONCLUSIONS: Due to the success of the MDA and the development of health center capacity for patient care, along with benefits gained from socioeconomic improvements and other interventions against vector-borne diseases and NTDs, Cambodia was validated by the World Health Organization as achieving LF elimination as a public health problem in 2016.

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.

Protective effect of diethylcarbamazine inhibits NF-κB activation in isoproterenol-induced acute myocardial infarction rat model through the PARP pathway.

The present study investigated the protective effect of diethylcarbamazine in inhibiting nuclear factor (NF)-κB activation in isoproterenol­induced acute myocardial infarction (AMI) rats through the poly ADP ribose polymerase (PARP) pathway. Male albino Wistar rats were injected subcutaneously with isoproterenol (100 mg/kg/day) for 2 days to induce an AMI model. Diethylcarbamazine (50 mg/kg) was administered by gavage for 12 days prior to the isoproterenol-induced AMI. It was noted that diethylcarbamazine significantly inhibited AMI­induced casein kinase and lactate dehydrogenase levels, and reduced the AMI­induced wet heart weight to body weight ratio in AMI rats. Diethylcarbamazine treatment significantly weakened reactive oxygen species production and reduced the levels of tumor necrosis factor (TNF)­α, interleukin­6 and NF­κB/p65 in AMI rats. Western blotting demonstrated that diethylcarbamazine significantly suppressed the AMI­induced inducible nitric oxide synthase (iNOS), transforming growth factor (TGF)­ß1, cyclooxygenase­2 (COX­2) and PARP protein expression in AMI rats. The results demonstrated that the protective effect of diethylcarbamazine inhibited isoproterenol­induced AMI through the suppression of inflammation, iNOS, TGF­ß1, COX­2 and the PARP pathway, and revealed the clinical potential of diethylcarbamazine for therapeutic and clinical applications.

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.

Multiple frailty model for clustered interval-censored data with frailty selection.

Interval-censored time-to-event data often occur in studies of diseases where the symptoms of interest are not directly observable but require lab examinations for detection. Furthermore, the independence assumption among observations may not be valid if they are from clusters. Some methods have been developed for analysing clustered interval-censored data with a shared frailty to account for overall heterogeneity. In this paper, we propose a multiple frailty proportional hazards model, where we not only account for the baseline heterogeneity and effect variation across clusters for predictors, but also quantify the probabilities of the existence of such frailties. This proposed model will be especially useful for analysing multi-center randomised clinical trials for HIV, infections or progression-free survival in oncology studies.

The Impact of Lymphatic Filariasis Mass Drug Administration Scaling Down on Soil-Transmitted Helminth Control in School-Age Children. Present Situation and Expected Impact from 2016 to 2020.

Lymphatic filariasis (LF) and soil-transmitted-helminths (STH) are co-endemic in 58 countries which are mostly in Africa and Asia. Worldwide, 486 million school-age children are considered at risk of both diseases. In 2000, the World Health Organization (WHO) established the global programme to eliminate LF by 2020. Since then, the LF elimination programme has distributed ivermectin or diethylcarbamazine citrate (DEC) in combination with albendazole, thereby also treating STH. Consequently, many school-age children have been treated for STH through the LF programme. As treatment targets towards the 2020 LF elimination goal are achieved, many countries are implementing the transmission assessment survey (TAS) and, if the LF prevalence is estimated to be less than 1%, scaling down mass drug administration (MDA). We analysed the 2014 data on preventive chemotherapy (PC) reported from LF STH co-endemic countries and projected the year and location of TAS expected to be conducted between 2016 and 2020 to assess the impact of this scaling down on STH PC. Eighty percent of all co-endemic countries that have already stopped LF MDA nationally were able to establish STH PC through schools. It is estimated that 14% of the total number of children presently covered by the LF programme is at risk of not continuing to receive PC for STH. In order to achieve and maintain the WHO 2020 goal for STH control, there is an urgent need to establish and reinforce school-based deworming programmes in countries scaling-down national LF elimination programmes.

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.

Circulating filarial antigen detection in brugian filariasis.

Human lymphatic filariasis (LF) is a major cause of disability globally. The success of global elimination programmes for LF depends upon effectiveness of tools for diagnosis and treatment. In this study on stage-specific antigen detection in brugian filariasis, L3, adult worm (AW) and microfilarial antigenaemia were detected in around 90-95% of microfilariae carriers (MF group), 50-70% of adenolymphangitis (ADL) patients, 10-25% of chronic pathology (CP) patients and 10-15% of endemic normal (EN) controls. The sensitivity of the circulating filarial antigen (CFA) detection in serum samples from MF group was up to 95%. In sera from ADL patients, unexpectedly, less antigen reactivity was observed. In CP group all the CFA positive individuals were from CP grade I and II only and none from grade III or IV, suggesting that with chronicity the AWs lose fecundity and start to disintegrate and die. Amongst EN subject, 10-15% had CFA indicating that few of them harbour filarial AWs, thus they might not be truly immune as has been conventionally believed. The specificity for antigen detection was 100% when tested with sera from various other protozoan and non-filarial helminthic infections.

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.