Zulma Medeiros

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.

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.

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 (χ2‐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.

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.

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.

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.

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 ˜ 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 μl 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 > I mf/20 or 60 μl blood smear at night could be identified during daytime hours by filtration of I ml venous blood

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

SummaryBetween 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 μl 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 23773 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.

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 SUCAMs 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.

Human toxocariasis: frequency of anti-Toxocara antibodies in children and adolescents from an outpatient clinic for lymphatic filariasis in Recife, Northeast Brazil

In a transversal study on a sample of 386 children and adolescents from an outpatient clinic for filariasis in Recife, Northeast Brazil, the frequency of anti-Toxocara antibodies and its relation to age, gender, number of peripheral eosinophils, Wuchereria bancrofti microfilariae and intestinal helminths was determined. The total anti-Toxocara IgG antibody frequency was 39.4%, by ELISA technique. The difference in frequency between males (40.1%) and females (37.6%) was not statistically significant. The 6 to 10-year-old subset presented the highest frequency of anti-Toxocara antibodies (60%), and within this age group there was a statistically significant male bias. There was also a significant association between the number of eosinophils and the presence of anti-Toxocara antibodies. Intestinal parasite frequency was 52.1%, but no association was found between this data and the presence of anti-Toxocara antibodies. In the present sample, 42.2% of the patients were Wuchereria bancrofti carriers, however, again this was not associated with the presence of anti-Toxocara antibodies. In conclusion, anti-Toxocara antibodies were highly prevalent in this sample. The present data show that there is no cross correlation between anti-Toxocara IgG antibody and the presence of intestinal helminths and filariasis.