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 (AU)

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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.

The socio-demographic, environmental and reservoir factors associated with leptospirosis in an urban area of north-eastern Brazil.

In an ecological study based on the 18 microregions that form the city of Recife, the capital of the Brazilian state of Pernambuco, associations between socio-demographic, environmental and reservoir factors and the incidence of leptospirosis in the city were investigated. Incidence over a 5-year period (2001-2005) and 14 variables were analysed, using central trend and dispersion measurements, Pearson's correlation and multiple linear regression. Variables relating to education, income, housing type, sewage system, rubbish collection and hydrographic factors were found to be significantly correlated with leptospirosis incidence (P<0.05 for each). Just two variables - the proportion of heads of households with incomes less than or equal to the legal minimum (U.S.$83.55/month), and the proportion of households from which rubbish was dumped in skips, lakes, rivers or the sea or on vacant land - explained 60% (P=0.017) of the differences in disease risk observed between the various areas of the city.

The epidemiological delimitation of lymphatic filariasis in an endemic area of Brazil, 41 years after the first recorded case.

In 2002, the status of lymphatic filariasis (LF) in the district of Jaboatão, in north-eastern Brazil, was reviewed, 41 years after the first case of the disease was recorded in the area. Current data from Jaboatão were compared with older information from the district that had been published, as official reports on filariasis cases and mosquitoes and as the result of population surveys, between 1948 and 1997. Although the first microfilaria-positive cases were detected in the district in 1959, it was not until 1993 that the national Ministry of Health categorized Jaboatão as an endemic area. In 2002, fingerprick samples of blood, each of about 50 microl, were collected at night (23.00-01.00 hours) from 4365 individuals in the district and used to make thick smears. Microfilariae were detected in the smears of blood from 33 (0.8%) of the subjects, 12 of whom were considered autochthonous cases of LF. The male subjects were significantly more likely to be microfilaraemic than the female (1.1% v. 0.4%; P<0.05) but there was no direct relationship between prevalence and age, the microfilaraemics varying in age from 6-64 years. The Socorro sub-district had the highest prevalence, of 2.9%. It is recommended that the National Programme to Eliminate Filariasis uses mass drug administrations and vector control throughout the district, regardless of the prevalences recorded in the latest survey.

[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.

Elimination of bancroftian filariasis (Wuchereria bancrofti) in Santa Catarina state, Brazil.

During the 1950s, three foci of Wuchereria bancrofti transmission were identified in the State of Santa Catarina, Brazil. In Florianópolis, São José da Ponta Grossa and Barra da Laguna community treatment of bancroftian filariasis with diethylcarbamazine (DEC) was performed using two distinct approaches, without vector control or improvements in sanitation. In two of the three communities only microfilaraemic individuals were treated, while in Barra da Laguna the entire population received DEC treatment regardless of their infection status. In both cases, transmission of the parasite was blocked and no new cases were detected in all localities for up to 10 years. Recently, a new survey in São José da Ponta Grossa and Barra communities revealed no microfilaria-positive individuals, including residents that were positive in the 1950s. These data confirm that transmission of W. bancrofti was interrupted in Santa Catarina, and mass treatment appears to be more effective than treatment of microfilaraemic individuals only.

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.

Screening of army soldiers for Wuchereria bancrofti infection in the metropolitan Recife region, Brazil: implications for epidemiological surveillance.

Between 1989 and 1995, blood surveys were performed for Wuchereria bancrofti infection in several barracks of the Brazilian army in the metropolitan Recife region. For initial screening, 60 microliters of capillary blood were examined for microfilaria. All men who tested positive had microfilaria quantified by filtration of venous blood through a polycarbonate membrane. Of 23,773 men screened, 585 (2.5%) had microfilaria (mf). Microfilarial density ranged from < 1-8706 mf/ml of blood. Thirteen individuals had ultra-low microfilarial densities (1 mf/11 ml of blood). Characterization of 174 autochthonous cases made it possible to map 8 new districts in 4 cities within metropolitan Recife region where transmission of W. bancrofti was previously unknown. Routine screening of soldiers in the military may provide important surveillance data for national programmes to eliminate transmission of W. bancrofti.

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.

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.

[Tropical filarial pulmonary eosinophilia and its differential diagnosis]. / Eosinofilia pulmonar tropical filariótica e o seu diagnóstico diferencial.

The authors present a comprehensive review of Tropical Pulmonary Eosinophilia (TPE) of filarial etiology and describe its differential diagnosis with similar syndromes. Epidemiological, clinical, diagnostic, therapeutic and phisiopathological aspects are considered, with an emphasis on new advances in our knowledge of lymphatic filariasis and their implication for improved understanding of TPE and similar syndromes. A TPE-like syndrome, which is caused by intestinal helminth infections, occurs in filariasis-endemic and non-endemic areas alike. The authors suggest guidelines for interpreting epidemiological, clinical, laboratory, radiologic (including ultrasonographic) and therapeutical data and properly diagnosing TPE syndromes. This guidelines also should be useful for physicians in areas where filariasis is not endemic but to which patients from endemic area (e.g., Greater Recife-PE, Maceió-AL and Belém-PA) frequent migrate.

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.

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 the Og4C3 ELISA in Wuchereria bancrofti infection: infected persons with undetectable or ultra-low microfilarial densities.

The recently developed Og4C3 ELISA, which detects circulating Wuchereria bancrofti antigen, appears promising for use in epidemiological surveys, but its sensitivity is unknown in persons with ultra-low microfilarial densities. We used the Og4C3 to test the sera of 282 persons who were microfilaria-positive in 1-16 ml of blood, 18 persons who were microfilaria-negative but who had ultrasonographic or biopsy evidence of adult W. bancrofti infection, and 63 lifelong residents of a non-endemic area of Brazil. A total of 276 (97.9%) persons with detectable microfilaraemia tested positive (optical density > 0.033). At microfilarial densities of < 1, 1-30, and > 30 microfilariae per ml of blood, the sensitivity of the Og4C3 was 72.2, 97.6 and 100%, respectively (chi 2-test for trend, P < 10(-6)). The assay was positive in 66.7% of amicrofilaraemic persons with evidence of adult worm infection and in one (1.6%) of 63 residents of the non-endemic area (specificity, 98.4%). Our findings support the increasingly widespread use of the Og4C3 for field investigations and epidemiological assessments. However, the sensitivity of the assay may be low in persons who are microfilaria-negative or with densities of < 1 microfilaria per ml.

[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.

Ultrasonographic evidence of abnormal lymphatic vessels in young men with adult Wuchereria bancrofti infection in the scrotal area.

PURPOSE: We determined the prevalence and magnitude of dilatation of the lymphatic vessels of the spermatic cord in men infected with Wuchereria bancrofti, which is known major cause of hydrocele in the tropics. MATERIALS AND METHODS: Scrotal ultrasound was performed with a 7.5 MHz, transducer in 78 men from Recife, Brazil (endemic for filariasis) and in 15 from a nonendemic area. RESULTS: Among men from Recife the lymphatic vessels were dilated (1.3 to 15.0 mm., mean 3.8) at the location of the adult worm. Vessel diameter was not associated with hydrocele. CONCLUSIONS: Lymphatic dilation was observed in all men with ultrasonographically detectable W. bancrofti infection, even those who were asymptomatic.

Epidemiological study of bancroftian filariasis in Recife, northeastern Brazil.

Wuchereria bancrofti in Pernambuco was first documented in 1952 (Azevedo & Dobbin 1952), and since then it has been reported in surveys carried out in selected areas of Recife. Several surveys were carried out from 1981 to 1991 by SUCAM. In the 1985 SUCAM's report the disease is considered under control. The CPqAM Filariasis Research Program was established in 1985 and a filarial survey was carried out in the town of Olinda, Greater Recife. In order to verify the real epidemiological situation, a study was conducted in the city of Recife. 21/36 of the Special Zones of Social Interest (ZEIS), were randomly selected for the present study. From 10,664 persons screened, 683 were positive and the prevalence rate for microfilaraemia (mf) varied from 0.6% to 14.9%. A mean mf prevalence of 6.5%, showed that the infection occurs in a wide geographic distribution in Greater Recife and that the intensity of transmission is a real and potential threat to public health in affected communities. Mf rate among males and females differed significantly. Due to the rapid increase in population, unplanned urban settlements, poor sanitary facilities and the favorable geographical conditions to the development of the vector, filariasis may actually be increasing in Recife.

Studies on the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae in paired samples of capillary and venous blood from Recife, Brazil.

We examined the periodicity and intravascular distribution of Wuchereria bancrofti microfilariae (mf) and determined the effect of these parasite properties on the accuracy of blood filming and filtration methods for diagnosis of bancroftian filariasis in the endemic area of Recife, Brazil. Microfilariae in both venous and capillary blood exhibited a nocturnal periodicity pattern with a relatively high amplitude. Overall, capillary blood contained approximately 1.25 times the number of mf present at the same time in the same volume of venous blood. However, the ratio of mf present in capillary and venous blood varied over a 24-hour period, so that the fewest mf were present in the capillary bed of the skin at the time when biting activity of the local Culex vector is the lowest. Twenty or 60 microliters blood films did not reliably detect carriers with fewer than 100 or 60 mf/ml venous blood, respectively, and were thus inadequate for the identification of low density mf carriers. In contrast, all carriers with > 1 mf/20 or 60 microliters blood smear at night could be identified during daytime hours by filtration of 1 micromilligram venous blood.