Immunomodulation of allergic response in children and adolescents: What we can learn from lymphatic filarial infection.

BACKGROUND: Although it is well known that allergic diseases involve a strong Th2 immune response, with production of high levels of specific IgE allergen, knowledge on the association between filarial infection and allergies, among paediatric patients is scarce. OBJECTIVE: To evaluate the allergic response patterns in cases of filarial infection by comparing peripheral eosinophils, total IgE levels, immediate hypersensitivity and cytokine levels in children and adolescents in Brazil. METHODS: This was an exploratory study with three groups: (I) with filarial infection and without allergic diseases; (II) without filarial infection and with allergic diseases; and (III) without filarial infection and without allergic diseases. The prick test and specific IgE tests for aeroallergens were performed using five antigens. Peripheral eosinophils and total IgE were also evaluated. IL-4 and IL-5 were determined using whole-blood culture stimulated by three antigens. RESULTS: Eosinophilia and elevated levels of total IgE (≥400IU/dl) were observed in all groups. The prick test was positive in 56.6% of the cases. Group I presented hypersensitive responses similar to the allergic disease groups. In the whole-blood culture stimulated by Dermatophagoides pteronyssinus, average IL-4 production did not differ significantly among the groups, but IL5 production resulting from stimulation was greater in the allergic disease groups (p<0.05). CONCLUSIONS: The allergic response pattern in group with filarial infection was similar to that of the groups with and without allergic diseases, but the response to IL-5 in the culture stimulated by D. pteronyssinus was an exclusive characteristic of the allergic group.

Studies on forensic nursing in Brazil: a systematic review of the literature.

AIM: To identify and synthesize the national and international literature on forensic nursing in Brazil. BACKGROUND: Forensic nursing is a new specialty to the nursing practice in Brazil, being recognized by the Federal Nursing Council of Brazil in 2011. In 2016, the first forensic nursing specialization programme was authorized in the country. INTRODUCTION: The implementation of forensic nursing specialty in Brazil marks new possibilities for the nursing practice, making it possible for nurses to develop additional skills to intervene in various situations under the Brazilian Unified Healthcare System. METHODS: A systematic search of the literature was conducted using the keyword 'Forensic nursing' in combination with 'Brazil'. LILACS, MEDLINE, EMBASE, Scopus and Web of Science databases were searched. Studies were also retrieved from the grey literature. Once literature had been identified, a thematic analysis was undertaken in order to extract themes, which were: establishment of the forensic nursing specialty and its contributions to Brazil and its practical implications. RESULTS: Eight manuscripts and 20 studies from the grey literature were included in the final review. Most studies (54%) were literature reviews that indicated forensic nursing as an emerging specialty in Brazil, addressing educational, instructional, communicative or contextual aspects of the specialty in the country. DISCUSSION: In the nursing profession in Brazil, few studies exist on forensic nursing and those are limited to short communications. Although most studies address the definition of forensic nursing, others present its implications in various situations such as intimate partner violence, domestic violence, sexual abuse and elder mistreatment. CONCLUSION AND IMPLICATIONS FOR NURSING AND HEALTH POLICY: Despite the study limitations, it provides evidence that forensic nursing has been silently implemented in the country with the need for more evidence-based studies to support its constitution as a specialty in Brazil.

A socioenvironmental composite index as a tool for identifying urban areas at risk of lymphatic filariasis.

OBJECTIVE: To describe the spatial distribution of lymphatic filariasis and its relationship with the socioenvironmental risk indicator, thus identifying priority localities for interventions in endemic urban areas. METHODS: The study area was the municipality of Jaboatão dos Guararapes, State of Pernambuco, Brazil. The data sources were a parasitological survey and the 2000 demographic census. From these data, a socioenvironmental composite risk indicator was constructed using the 484 census tracts (CT) as the analysis units, based on the score-formation technique. Census tracts with higher indicator values presented higher risk of occurrences of filariasis. RESULTS: Six thousand five hundred and seven households were surveyed and 23 673 individuals were examined, among whom 323 cases of microfilaremia were identified. The mean prevalence rate for the municipality was 1.4%. The indicator showed that 73% (237/323) of the cases of microfilaremia were in high-risk areas (third and fourth quartiles) with worse socioenvironmental conditions (RR = 4.86, CI = 3.09-7.73, P < 0.05). CONCLUSIONS: The socioenvironmental composite risk indicator demonstrated sensitivity, since it was able to identify the localities with greater occurrence of infection. Because it can stratify spaces by using official and available data, it constitutes an important tool for use in the worldwide program for eliminating lymphatic filariasis.

Ivermectin treatment of bancroftian filariasis in Recife, Brazil.

To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment, the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife, Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-, and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly fever, headache, weakness, and myalgia) occurred to some degree in almost all patients but generally lasted only 24-48 hr and were easily managed symptomatically. Adverse reactions were significantly milder in those receiving the lowest (20 micrograms/kg) ivermectin dose, and they were significantly correlated with individuals' pretreatment microfilaremia levels in all groups. Posttreatment eosinophilia was a regular feature of the response to treatment, with the magnitude and kinetics also proportional to pretreatment microfilarial levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment, but all cleared without significant complications. The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin, that the drug's systemic adverse reactions are essentially those resulting from parasite clearance, and that the intensity of these reactions can be significantly reduced by using the low (20 micrograms/kg) dose of ivermectin. This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications.

Renal abnormalities in microfilaremic patients with Bancroftian filariasis.

To determine the frequency of renal abnormalities occurring with Bancroftian filarial infections and to assess the effects of treatment on such abnormalities, we initiated a prospective, hospital-based study of 20 microfilaremic and five amicrofilaremic patients with Wuchereria bancrofti infections. Thorough clinical evaluations and detailed renal assessments were made prior to treatment and at multiple time points for 60 days following a standard twelve-day course of treatment with diethylcarbamazine (DEC). There were two important findings. First, even prior to DEC treatment, almost half of the microfilaremic patients had hematuria and/or proteinuria. Second, treatment with DEC induced these same abnormalities in almost all of the remaining microfilaremic patients. However, this DEC-induced hematuria and/or proteinuria was transient, and the long-term response to DEC in all of the microfilaremic patients was resolution of the abnormal renal findings during the two-month followup period. In the amicrofilaremic study patients, no hematuria or proteinuria was detected before, during, or after treatment with DEC.

Abnormalities of the leg lymphatics are not specific for bancroftian filariasis.

Studies using conventional angiography or non-invasive scintigraphy have revealed widespread abnormalities in the lymphatics of the legs of patients with bancroftian filariasis, regardless of whether clinical lymphoedema is present. To determine if the observed changes were specific for filarial infections, we imaged the lymphatics of both legs in native residents of an area in Brazil where filariasis is not endemic. Study participants were matched by age, socioeconomic status and physical activities to patients with filariasis in Recife, evaluated in parallel. Based on textbook criteria, only one of 15 study participants had a completely normal lymphoscintigram. Modest to severe pathology of the leg lymphatics was observed in the remaining 14 residents of the non-endemic area and in 49 of 50 patients with bancroftian filariasis. These results indicated that factors other than filarial worms are a common cause of subclinical pathology of the leg lymphatics in north-eastern Brazil, and that the latter is not specific for bancroftian filariasis.

Direct assessment of the adulticidal efficacy of a single dose of ivermectin in bancroftian filariasis.

Although the potent microfilaricidal activity of ivermectin is well established, its efficacy against adult Wuchereria bancrofti is unknown. We used longitudinal ultrasound examinations for periods of 3-9 months to assess directly the macrofilaricidal effect of a single 400 micrograms/kg dose of ivermectin in 15 men from Recife, Brazil who were infected with W. bancrofti. Before treatment, microfilarial densities ranged from 3 to 3098 microfilariae per mL of blood, and movements characteristic of the living adult worm (the 'filaria dance sign') were observed by ultrasound examination of the scrotal lymphatic vessels in all 15 men. Following treatment, microfilarial density was markedly reduced in all men, but the filaria dance sign remained unchanged in both location and pattern. Eight months after treatment, a dilated lymphatic vessel was surgically removed from one patient at the site of the filaria dance sign, and 3 intact adult worms were released. When given as a single 400 micrograms/kg dose, ivermectin had no observable effect on adult W. bancrofti. Therefore, prolonged suppression of microfilaraemia following treatment with ivermectin cannot be explained by a macrofilaricidal effect of the drug. Ultrasound is a valuable new tool for directly and rapidly assessing the macrofilaricidal efficacy of antifilarial drugs in lymphatic filariasis.

Assessment of the efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo.

To assess directly the effect of various doses of diethylcarbamazine (DEC) on adult Wuchereria bancrofti, 31 infected men were randomly assigned to receive an initial single DEC dose of 1 mg/kg (n = 7), 6 mg/kg (n = 10), or 12 mg/kg (n = 14). Beginning 7 d later, the dosage of DEC and duration of treatment were progressively increased for 7-10 weeks. Physical examinations were performed to detect scrotal nodules and the scrotal area was examined by ultrasound (7.5 MHz transducer) to monitor the 'filaria dance sign' (FDS), the characteristic pattern of adult worm movement. Of 53 adult worm 'nests' that were detected by ultrasound, 22 (41.5%) were DEC-sensitive (FDS became non-detectable and a nodule became palpable at the site); 20 (37.7%) were not sensitive (FDS remained unchanged and detectable and no nodule developed), and 11 (20.8%) showed mixed responses (FDS remained detectable but a palpable nodule developed). All but one sensitive or mixed response occurred within 1 week after the initial single dose. Of 39 'nests' in men who initially received a single 6 or 12 mg/kg dose of DEC, 20 (51.3%) had sensitive responses compared to 2 (14.3%) of 14 'nests' in men who received a single 1 mg/kg dose (P = 0.04). Above 6 mg/kg, the macrofilaricidal effect of DEC did not increase with dose; a significant proportion of adult W. bancrofti were not susceptible to DEC during the study period.

Evaluation of PCR-based methods for the diagnosis of infection in bancroftian filariasis.

The value of the polymerase chain reaction (PCR) in the diagnosis of Wuchereria bancrofti infection was evaluated in comparison to microscopical examination of night blood smears, Nuclepore filtration, serology and ultrasonography. No correlation was found between PCR-based deoxyribonucleic acid (DNA) probing and serology. We did not find any evidence of free filarial DNA in either blood plasma or chylocoele fluid. We conclude that the 2 PCR-based techniques evaluated are not more sensitive than Nuclepore filtration for detection of W. bancrofti microfilaraemia, need at least 1 intact microfilaria in the volume of blood used for DNA extraction, and were much inferior to ultrasonography for detection of amicrofilaraemic adult worm carriers.

Occurrence of living adult Wuchereria bancrofti in the scrotal area of men with microfilaraemia.

To determine the frequency with which living adult Wuchereria bancrofti can be detected by ultrasound in the scrotal area of men with filarial infection, we used a 7.5 MHz transducer to perform weekly ultrasound examinations on 100 microfilaraemic men (18-34 years old) from Greater Recife, Brazil. The peculiar pattern of movement that characterizes the adult worm image on ultrasound (the filaria dance sign) was detected in the lymphatic vessels of the spermatic cord in 80 men (bilaterally in 29 men). Among 20 men with no filaria dance sign, the geometric mean microfilarial density was 68/mL, compared with 238/mL and 775/mL among those with unilateral and bilateral filaria dance signs, respectively (P = 0.0001). The lymphatic vessels of the spermatic cord appear to be a common, and perhaps the principal, site of adult W. bancrofti in men with asymptomatic microfilaraemia. Studies are needed to define the relationship between the presence of filarial worms in the scrotal area and the development of filaria-associated morbidity.

Bancroftian filariasis in a paediatric population: an ultrasonographic study.

Little is known about lymphatic filariasis or the anatomical location of adult Wuchereria bancrofti in children. Seventy-eight children from Greater Recife, 23 microfilaria-positive and 55 microfilaria-negative in approximately 60 microL blood, underwent ultrasound examinations of the major superficial lymphatic vessels of the limbs, scrotal area (boys), and breast area (girls). The characteristic movements of adult worms, known as the filaria dance sign (FDS), were detected in 11 (14.1%) children. In 9 boys, the FDS was detected in lymphatic vessels of the scrotal area (8, ages 14-16) and the inguinal cord (1, age 11). In girls, the FDS was detected in a crural lymphatic vessel and an axillary lymph node. FDS detection was more common in boys (P = 0.06), older children (P = 0.001), and children with microfilaraemia (P = 0.05). Diffuse lymphangiectasia was visualized in 4 boys (ages 14-16) and 2 children had clinical signs of filariasis. These ultrasonographic findings associate W. bancrofti with both infection and disease in children.

Comparative efficacy of three different diethylcarbamazine regimens in lymphatic filariasis.

To assess the efficacy of diethylcarbamazine (DEC) in clearing Wuchereria bancrofti microfilariae (mf) from the circulation, we conducted a single blind hospital-based therapeutic trial of 3 DEC regimens. All patients were assessed by filtration of 1 mL of venous blood taken before and 1, 3, 6 and 12 months after DEC administration. The efficacy of a 12 d course of 6 mg/kg DEC once daily was identical to that of a similar course with 2 mg/kg given 3 times daily, indicating that split-dose treatment does not improve mf clearance over single daily drug administration. Microfilarial densities in patients treated only once with 6 mg/kg DEC remained significantly higher at 1, 3, and 6 months after treatment. However, all 3 treatment regimens proved equally effective in controlling microfilaraemia after 12 months, when 41, 42 and 40% of patients in the 3 treatment groups were amicrofilaraemic. These results suggest that a single DEC dose of 6 mg/kg administered annually or biannually may be a suitable regimen to control bancroftian filariasis in Recife, Brazil.

Tolerance of diethylcarbamazine by microfilaraemic and amicrofilaraemic individuals in an endemic area of Bancroftian filariasis, Recife, Brazil.

To determine the tolerance to diethylcarbamazine (DEC) treatment of patients with Bancroftian filariasis, 193 individuals (138 asymptomatic microfilaraemic, 30 amicrofilaraemic diseased patients and 25 asymptomatic amicrofilaraemic endemic residents) were enrolled in a prospective trial with different dose schedules, in a hospital and outpatient clinic setting in Brazil. Systemic adverse reactions, localized adverse reactions, and side effects, related to microfilariae, adult worms and the drug itself, were evaluated. Systemic reactions occurred irrespective of the DEC dose and schedule in about 40% of the microfilariae carriers, but not in amicrofilaraemic diseased patients or residents; they usually consisted of microscopic haematuria, followed by fever and malaise. Localized reactions were manifested by the appearance of inflammatory reactions, mainly in the scrotal area. Nodules containing degenerating adult worms developed mainly in the scrotal lymphatics of microfilaraemic patients, diseased amicrofilaraemic patients, and residents. Drowsiness, which increased with higher doses of DEC, was the most common side effect in both microfilaraemic and amicrofilaraemic individuals, followed by nausea and gastric upset. The results indicate that the occurrence of systemic and local adverse reactions was unrelated to either the dose of DEC or the pretreatment microfilarial density. The severity of systemic reactions was proportional to the microfilarial density. Side effects were dependent on the drug dosage irrespective of infection status.

Treatment of bancroftian filariasis in Recife, Brazil: a two-year comparative study of the efficacy of single treatments with ivermectin or diethylcarbamazine.

The effectiveness of single oral doses of ivermectin (200 or 400 micrograms/kg) and diethylcarbamazine (DEC, 6 mg/kg), preceded 4 d earlier by either placebo or very small doses of these drugs, was compared, over a 2-year period, in a double-blind trial in 67 microfilaraemic Brazilian men with bancroftian filariasis. Regimens containing ivermectin alone decreased the number of microfilariae significantly faster and more effectively for the first month after treatment than regimens containing DEC alone, but the latter were significantly more effective throughout the second year after treatment (1.7-8.2% of pretreatment levels with DEC vs. 12.6-30.8% with ivermectin during that period); the higher ivermectin dose showed a tendency towards more effectiveness than the lower dose. Most effective was the combination of ivermectin (20 micrograms/kg) followed 4 d later by DEC (6 mg/kg), with reduction of microfilaraemia to 2.4% of pretreatment levels at 2 years. Adverse reactions were well tolerated with all regimens, the reactions being significantly more generalized (i.e., fever) following ivermectin and localized (i.e., scrotal inflammatory nodules around dying adult worms) following DEC. Further trials of single-dose combination therapy vs. single high doses of ivermectin or DEC should determine the ideal regimen for treatment and control of bancroftian filariasis.

Acute attacks in the extremities of persons living in an area endemic for bancroftian filariasis: differentiation of two syndromes.

The natural history of lymphatic disease in human filariasis remains unclear, but recurrent episodes of acute lymphangitis are believed to constitute a major risk factor for the development of chronic lymphoedema and elephantiasis. Prospective analysis of 600 patients referred to the filariasis clinic of the Centro de Pesquisas Aggeu Magalhães/FIOCRUZ in Recife, Brazil, indicated that 2 distinct acute syndromes accompanied by lymphangitis occur in residents of this filariasis-endemic area. One syndrome, which we call acute filarial lymphangitis (AFL), is caused by the death of adult worms. It is relatively uncommon in untreated persons, usually is asymptomatic or has a mild clinical course, and rarely causes residual lymphoedema. The second syndrome, of acute dermatolymphangioadenitis (ADLA), is not caused by filarial worms per se, but probably results from secondary bacterial infections. ADLA is a common cause of chronic lymphoedema and elephantiasis in Recife as well as in other areas of Brazil where lymphatic filariasis is not present. The syndromes of AFL and ADLA can be readily distinguished from each other by simple clinical criteria.

[Evaluation of the indirect immunofluorescence test for the diagnosis of bancroftian filariasis using microfilariae W. bancrofti as the antigen, in Recife-PE, Brazil]. / Avaliação do teste de imunofluorescência indireta para diagnóstico da filariose bancroftiana usando a microfilária de W. bancrofti como antígeno, em Recife-PE, Brasil.

The authors analysed the indirect immunofluorescence assay, for the diagnosis of bancroftian filariasis using papain treated W. bancrofti microfilariae as antigen, widely used in Recife-Brazil. Sera from 50 patients with several clinical forms of the disease including asymptomatic carriers, tropical pulmonary eosinophilia, elephantiasis, filarial fever and chyluria were analysed. For the control group, 50 individuals were selected, living at least 5 years in endemic area, with neither previous DEC treatment nor clinical-laboratory evidences of the disease, called normals endemic. The sensitivity and specificity were analysed taking into account different cut off values. It was not possible to differentiate infected individuals from the control group. It was not even possible to establish any correlation with IMF titers among different clinical presentation of the disease. Crossed reactions with various intestinal helminths were considered, but no relationship was found.

[History of lymphatic filariasis in Pernambuco. I. Epidemiologic and control aspects]. / História da filariose linfática em Pernambuco. I. Aspectos epidemiológicos e de controle.

This paper is a review of lymphatic bancroftian filariasis in the State of Pernambuco. Brazil. It shows that reports have existed since the 1st decade of the century. Knowledge of the disease in several areas during different periods makes a retrospective analyses very interesting, particularly in Great Recife. It is in the city that the epidemiological and control aspects of the diseases are examinations in details.

[Bancroftian filariasis in urban areas of Alagoas State, Northeast Brazil: study in the general population]. / Filariose bancroftiana em áreas urbanas do Estado de Alagoas, nordeste do Brasil: estudo em populaçao geral.

In order to assess the present status of lymphatic filariasis in Alagoas State, Brazil, hemoscopic surveys were carried out in the human population of the three different physiographic regions of the State. Blood samples were collected by thick smear technique taken after 10:00 p.m. From a total of 101 cities of the State, 10 were randomly selected, Bancroftian filariasis was only found in Maceió, the capital of Alagoas State. In a cross-sectional survey conducted among the general population of 4 neighborhoods in the city, 10,973 individuals were examined, 226 were microfilaraemic with prevalence in the city neighborhoods ranging from 0 to 5.4%. Prevalence rates and microfilariae density were significantly higher in males. Among the examined inhabitants born out of Maceió, microfilariae carriers had lived a significantly longer time in endemic areas than the amicrofilaraemic subjects. Based on the data obtained in the present study, measures to avoid expansion of bancroftian filariasis in the region were established.