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Sensitivity of the Immunochromatographic Card Test Relative to Detection of Adult Wuchereria bancrofti Worms by Ultrasound

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  • 1 Núcleo de Ensino Pesquisa e Assistência em Filariose, Hospital das Clínicas, Departamento de Cirurgia, Centro de Ciências da Saúde, Centro de Pesquisas em Alergia e Imunologia Clínica, Faculdade de Medicina,Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil; Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil; Organização Não Governamental Amaury Coutinho para Doenças Endêmicas e Tropicais, Recife, Pernambuco, Brazil; Núcleo de Ensino e Pesquisa em Patologia, Faculdade de Ciências Médicas, Universidade Estadual do Piauí, Teresina, Piauí, Brazil

The diagnosis of active infection in bancroftian filariasis continues to pose an important and continuously evolving challenge to filariasis-endemic countries and to health personnel. Sensitivity of the immunochromatographic card test (ICT) relative to detection of adult Wuchereria bancrofti worms by ultrasound was evaluated in a retrospective study conducted in the Center for Teaching, Research and Tertiary Referral Hospital for bancroftian filariasis (Federal University of Pernambuco) in Recife, Brazil. The results showed that among 408 persons tested, the overall sensitivity of the ICT was 84.5% and varied from 52% to 100% when patients were grouped by different criteria (age, sex, presence or absence of living adult worms by ultrasound, microfilaremia status/density). The present study provides evidence that a negative antigen result should be interpreted cautiously and may help to explain the different sensitivities of the antigen test found by different investigators in settings with different transmission intensities.

INTRODUCTION

Bancroftian filariasis is a good example of successful detection of circulating antigen as an efficient tool in diagnosing active infection. Commercially available antigens tests for diagnosis of active infection in patients recognize antigen(s) of adult worms.13 Weil and others4 showed that amicrofilaremic and asymptomatic adult worm carriers of W. bancrofti are relatively common in filariasis-endemic areas and could be identified by an antigen test.

The only non-invasive tools widely available for diagnosis of active infection with W. bancrofti in amicrofilaremic persons are circulating filarial antigen (CFA) tests (immunochromatographic card test [ICT] and the Og4C3 enzyme-linked immunosorbent assay [ELISA]) and the filaria dance sign [FDS]). The FDS represents living adult worms in their natural habitat (lymphatic vessels and lymph nodes) visualized by ultrasonography.57 The ICT for filariasis (AMRAD, French’s Forest, New South Wales, Australia) was evaluated independently in three laboratories using well-characterized serum samples from patients with filariasis from Egypt and India from the World Health Organization (WHO) serum bank and from Haiti.2 The sensitivity of the ICT was comparable with that of the Og4C3 ELISA, which was considered the gold standard for the ICT.8 Many studies have evaluated the sensitivity of the ICT, including a newer version of this test (Binax, Portland, ME). Most of these studies compared the presence of circulating microfilaria (mf) measured by different methods.3,912 The CFA tests are used to monitor the efficacy of antifilarial treatment after different drug regimens1319 and to obtain evidence for interruption of transmission after mass treatment.20

As part of the monitoring process proposed by WHO21 for an area to be certified free of filariasis (i.e., having successfully eliminated lymphatic filariasis), antigen prevalence (assessed by the ICT) should be < 0.1% after completion of five years of mass drug administration in a sentinel population of 3,000 children.22 The ICT has been used to determine the actual prevalence of bancroftian filariasis in southern India,3 including the prevalence of infection after six rounds of mass treatment.23 The sensitivity of the ICT was 100%, e.g., detecting all infected persons, irrespective of adult worm burdens with or without circulating mf or unisexual infection. Although ultrasound has limitations in detecting adult worms, it can be used to identify patients with proven adult worm infection in assessing sensitivity of laboratory methods. We studied the performance of the ICT in patients infected with living adult worms detected by ultrasound as previously described for the Og4C3 ELISA.24

MATERIALS AND METHODS

This retrospective study was conducted in the Center for Teaching, Research and Tertiary Referral Hospital for Bancroftian Filariasis (NEPAF, Federal University of Pernambuco) in Recife, Brazil and was reviewed and approved by the Ethical Committee of Hospital das Clinicas, University Federal of Pernambuco in Recife, Brazil. Information was obtained from patients’ charts and included age, sex, the presence or absence of FDS as detected by ultrasonography, previous antifilarial treatment, mf density obtained by the polycarbonate membrane technique in ≥ 1 mL of venous nocturnal blood, ICT result, and nodule biopsy, if performed. All patients provided written informed consent. Patients seen at NEPAF (if they lived in areas where transmission is known to take place) were routinely tested for active filarial infection by a membrane filtration technique (except for patients with limb lymphedema for whom the antigen test is preferentially conducted initially); tested by the ICT (when available) and by ultrasonography using a 7.5-MHz transducer targeting the peripheral lymph nodes and lymphatic vessels, irrespective of the patient’s clinical presentation; and examined for the presence of lymphangiectasia with or without FDS. The patients were divided in two groups: 1) those with FDS irrespective of mf status and 2) those without FDS and with circulating mf (control group).

Inclusion criteria.

Group 1.

Patients were included in this group regardless of age or sex if they 1) were positive for FDS in at least three ultrasound examinations conducted by two different persons within a two-week period, 2) had been tested at least once with the ICT, 3) had never been treated with diethylcarbamazine (DEC) or ivermectin before their first consultation at NEPAF, and 4) had information on mf density for at least 1 mL of blood. This group was divided into three subgroups: 1A, those ≤ 17 years of age with ultra-low mf density (< 1 mf/mL of blood) or no circulating mf; 1B, those ≥ 18 years of age with ultra-low mf density or no circulating mf; and 1C, those with ≥ 1 mf/mL of blood.

Group 2.

Patients were included in this group if they 1) were negative for FDS in at least three ultrasound examinations conducted by two different persons within a two-week period; 2) had ≥ 1 mf/mL of blood; 3) had been tested at least once with the ICT, 4) had never been treated with DEC or ivermectin before the first consultation at NEPAF, 5) had at least one physical examination for nodules and ultrasonography of peripheral lymph nodes and lymphatic vessels (including those in the intrascrotal contents) at pretreatment and 7 and 30 days after DEC treatment with a single dose of 6 mg/kg, and 6) did not have any condition, such as lymphedema of scrotal wall, previous hernia repair, previous intrascrotal surgery, or tense hydrocele, that could interfere with physical examination of scrotal contents. These patients were divided in 2 subgroups: 2A, children 5–17 years of age, and 2B, persons ≥ 18 years of age.

Definitions and tests.

Amicrofilaremia in children and adolescents was defined as a negative result with 6 mL of blood (if no mf were detected in 1 mL, an additional 5 mL was obtained and examined within 7–15 days). Amicrofilaremia in adults was defined as a negative result with 11 mL of venous blood (if no mf were detected in 1 mL, an additional 10 mL was obtained and examined within 7–15 days). Ultra-low mf density was defined as that < 1 mf/mL of blood. A filtration technique was conducted with venous blood collected between 11:00 pm and 1:00 am. Blood was filtered through a 3-μm polycarbonate membrane, stained, and examined by microscopy.

The ICT was conducted with nocturnal blood sample obtained for membrane filtration; 100 μL of blood (measured with calibrated pipette) was tested. Blood was stored overnight at 8–10°C before use the next day. All patients with negative ICT results for the nocturnal blood sample were re-tested with 100 μL of capillary blood obtained during the day and collected into calibrated tubes containing heparin. As per procedures for ICT quality control used at NEPAF, before the ICT, two cards from each box were tested randomly with known antigen-positive and antigen-negative serum samples from the NEPAF serum bank by the Og4C3 ELISA. All cards were read at the same time by two examiners (maximum variation was 30 seconds between examiners) within the time prescribed by the manufacturer (Binax) (each observer had his/her sheet completed independently). A positive result was a test band recognized by the two examiners. A negative result was no test band recognized by the two examiners. A borderline result was disagreement between the two observers regarding the presence or absence of a band.

Ultrasound examinations were performed using a portable machine (SSD-500; Aloka, Tokyo, Japan) equipped with 7.5-MHz transducer. Lymphatic vessels of the arms and limbs, intrascrotal and inguinal areas, and peripheral lymph nodes were examined in adult males. Peripheral lymphatic vessels (including breasts) and lymph nodes were examined in females and children. The scrotal sac and inguinal cord was examined in boys. The first ultrasound examination was conducted the day after the ICT by persons who were unaware of the ICT results of the patients who were being examined. Filaria dance sign, which is the peculiar, active, random movement of echogenic structures seen by ultrasound in the B or M mode, indicates living W. bancrofti adult worms.5 Lymphangiectasia was defined as tubular anechoic structures in intrascrotal contents seen by ultrasound with no flow as checked by color Doppler ultrasound. Normal intrascrotal contents were defined as the absence of hydrocele, nodules, or lymphangiectasia detected by ultrasound and/or physical examination. Abnormal intrascrotal contents was defined as lymphangiectasia, nodules, or hydrocele alone or in combination detected by ultrasound and/or physical examination.

The DEC provocative test (PT) was used to detect living W. bancrofti adult worms by the incidence of lymphatic vessel nodules25 or adenitis6 after antifilarial therapy with DEC (a single dose of 6 mg/kg).26,27 The test result was considered positive if a nodule or adenitis were detected within seven days after drug intake.26,28 Patients in group 2 received treatment with DEC and were followed up to 12 months after the PT with physical and ultrasound examinations as described above, with at least four examinations within the follow-up period. Patients in group 1 received antifilarial treatment (DEC, a single dose or 6 mg/kg/day for 12 days).

Statistical analysis.

A two-tailed binomial test was used to compare proportions with hypothesized values. Difference in proportions was tested using Fisher’s exact test or Pearson’s chi-square test. Comparison of two geometric means was done using a two-tailed Student’s t-test on log-transformed data. Statistical analysis was performed with Stata version 9.2 (Stata Corporation, College Station, TX).

RESULTS

Patients selected for this study were seen between the second half of 1999 and the end of 2004. Overall, 408 (373 males and 35 females) patients with proven filarial infection (adult worms carriers and or circulating mf) were selected for the study. The mean age of the participants was 25.5 years (SD = 11.7 years), with ages ranging from 6 to 72 years. The sensitivity of the ICT was 82.1% (335 of 408). The ICT with capillary blood collected during the day was conducted for all persons with negative results for nocturnal venous blood samples (73 patients). All results showed 100% agreement.

Characteristics of patients in group 1 are shown in Table 1. The FDS in group 1A was found in the lymph nodes in all cases, except for for two boys (11 and 14 years of age) in which adult worms were found in the inguinal cord. Among 25 patients in group 1A, all were mf negative in 1 mL of blood and 7 (28%) (3 females and 4 males) were mf positive in 6 mL of blood. The mf density varied from 2 to 5 in 6 mL of blood (geometric mean = 0.43/mL). In Group 1B, FDS was found in intrascrotal lymphatic vessels in all males and in the breasts of three females (a 26-year-old woman with a positive ICT result and 34-year-old woman and a 37-year old woman with negative ICT results). Among 84 patients in group 1B, all were mf negative in 1 mL of blood and only 8 (9.5%) were mf positive in 11 mL of blood. The geometric mean mf density of positive persons was 0.25/mL (range = 1–8/11 mL of blood ); among them, the ICT result was positive in 5 (62.5%). Only 15 patients had ICT results that disagreed among the two examiners (borderline bands). These results were excluded from the study. All of these results were in men; all men had a nest of living adult worms detected by ultrasound (FDS) in intrascrotal lymphatic vessels.

Results for group 2 are shown in Table 2. In Group 2A, no abnormalities were detected in the physical examination or by ultrasound in any patient pre-DEC PT. Likewise, no nodules, acute hydroceles, or signs or symptoms of adenitis were observed in any patients after antifilarial treatment (up to 30 days) and in longer follow-up periods (one year). This group was screened by thick blood smears in the field and patients were referred to NEPAF for antifilarial treatment. Many were part of a larger study on mf clearance after antifilarial treatment.29 In group 2B, physical examination of scrotal contents in males before the DEC PT showed nodules in 12 patients with evidence of previous living worms in intrascrotal lymphatic vessels.26 Among them, six had negative ICT results. Among the six persons with negative CFA results, a nodule biopsy specimen was obtained from three persons; all had calcified filarial granulomas from which it was not possible to determine the sex of the parasite. Chronic, small, flaccid hydroceles were found in six patients (including one with an ipsi-lateral nodule). However, these hydroceles did not interfere with the physical examination. One patient had a bilateral hydrocele (with an ipsi-lateral nodule on the left side).

Tubular anechoic structures compatible with lymphangiectasia (alone or in combination with other signs) were seen in 41 persons. These structures could be an indication of current or past infection by living adult worms in intrascrotal lymphatic vessels.27 After the DEC PT, none of the patients in group 2B had nodule formation in any area of peripheral lymphatic vessels or lymph node accessible by physical examination, except for intrascrotal vessels. Twenty-four patients (38%) developed nodules within seven days after drug intake, which indicated that living adult worms that were not previously visualized by ultrasound. Among these patients, nine (37.5%) had negative ICT results and four developed small, flaccid, acute, ipsi-lateral hydroceles. Nine (14.3%) of 63 patients had a false-negative ICT result when active infection was shown by the DEC PT.

Performance of the DEC PT and ICT in patients in group 2B are shown in Table 3 relative to results of physical and ultrasound examination of intrascrotal contents (normal and abnormal). In the follow-up period longer than seven days, new nodules appeared in four patients and FDS was detected for the first time in six patients. One patient had a new nodule four months after treatment with DEC and also had FDS in the same nest classified as a mixed reaction (dead and alive adult worms in the same location of the lymphatic vessel segment).28 Details of these 10 patients with the new abnormalities detected within 12-month follow-up are shown in Table 4. Seventeen patients who were mf positive and negative by ultrasound had negative ICT and DEC PT results. Among them, 12 did not have any additional evidence of infection in the longer follow-up period. Their mean age was 40.5 years (SD = 12.1 years) and the mean geometric mf density was 12 mf/mL (Table 5).

DISCUSSION

To our knowledge, this study is the first to evaluate the performance of the ICT using blood from patients with living adult worms detected by ultrasonography in peripheral lymph nodes and lymph vessels. The results showed that the sensitivity of the ICT was 84.5% and varied from 52% to 100% when patients were grouped by different criteria (age, sex, mf status/density). Only one study made the same comparison in studying the sensitivity of the Og4C3 ELISA,24 and it demonstrated the low sensitivity (67%) of this test in infected amicrofilaremic men. A positive result in an antigen test for bancroftian filariasis before antifilarial treatment is not a false-positive test result with respect to filarial infection when compared with different methods available (i.e., Knott test, counting chamber,30 and thick smear31). The ICT was able to detect an important fraction of the population who had negative results in other tests. Analysis of mf frequency distribution among persons in Pondicherry, India showed that approximately 5% of mf-negative persons had false-negative results, and the proportion of false-negative persons varied between 5% and 20% for different age classes.32 These findings could partly explain the superiority of ICT compared with the thick smear. Because of its high sensitivity, convenience, and commercial availability, the ICT was considered a gold standard compared with other older parasitologic techniques.

In the absence of other evidence of infection, a negative antigen test result was accepted by most researchers as indicative of the absence of infection. A study by Weil and others4 using monoclonal antibody AD12.1 clearly demonstrated that none of the antigen detected by immunoblot was present in antigen-negative persons living in a filariasis-endemic area. Conversely, all antigen-positive serum samples contained the 200-kD antigen previously identified by this antibody. A study by Pani and others12 reported a low sensitivity (71.9%) for the ICT among 89 Indians positive by filtration analysis of 1 mL of blood. Our study provides evidence that an antigen-negative result should be interpreted cautiously and may help to explain the different sensitivities of the antigen test found by different investigators in settings with different transmission intensities.

A survey using CFA tests (Og4C3 ELISA and ICT) conducted by Omar and others33 of Indian expatriate workers in Saudi Arabia among 302 persons (210 men and 92 women) found 32 antigen-positive persons. Using a 60-μL thick smear, the investigators found only 10 men (31.3%) who were mf carriers. On the basis of the lower sensitivity found in persons with ultra-low mf densities or amicrofilaremic persons in the present study and the study by Rocha and others,24 we speculate that some of the persons negative by the ICT/Og4C3, especially males, could be infected. In such situations, treatment with a single dose of DEC for risk populations should be considered. The ICT may be useful in monitoring the potential risk of introducing bancroftian filariasis into a country. However, because the sensitivity of antigen tests is less than 100%, caution should apply when the ICT is used for individual diagnosis. The cautious interpretation of a negative ICT result should also be taken into consideration when the decision to use individual antifilarial treatment is based primarily on the testing of persons from areas not endemic for filariasis who have spent some time in filariasis-endemic areas.

Data for group 2 (in which W. bancrofti infection was inferred by circulating mf) gave us additional important information. Group 2A, which was screened by thick blood smear in the field, showed the highest sensitivity of the ICT (100%). Conversely, this group also provided an important reminder of how difficult it is to evaluate the macrofilaricidal efficacy of DEC by physical examination (presence of nodules in lymph vessels and/or adenitis as an indicator of adult worm death) because all persons in this group were negative by the DEC PT. One explanation would be that the macrofilaricidal effect of DEC was less effective than in the adult population,28 or that granuloma formation (expected to cause adenitis or lymphangitis) is often a silent clinical event. Conversely, group 2B, which was composed of microfilaremic men who had no living adult worms detected by ultrasound and who were further characterized by the DEC PT and followed-up for 12 months, supported the occurrence of false-negative ICT results (14.3% were ICT negative and DEC PT positive), and also raised the possibility of residual mf carriers (e.g., without the female adult worm).

There is evidence that residual circulating mf without active infection might occur in filariasis-endemic populations. McCarthy and others34 in a study in Mauke (Cook Island where mass DEC treatment had been undertaken five years earlier) that used the Og4C3 ELISA (Steel C, unpublished data) showed that of 27 persons mf positive by a filtration technique with 1 mL of blood, 6 (22%) were CFA negative before individual antifilarial treatment, which reduced the sensitivity of the CFA assay to 78%. According to the investigators, except for one person with 80 mf/mL, the number of mf was low (1–3 mf/mL). They considered the result as a false-negative result and the most likely explanation given for the discrepancy was the much lower intensity of infection in this population (defined according to the presence of at least one pair of adult worms) compared with other areas where CFA assays have been evaluated.13,3537 Chanteau and others38 also found, using the Og4C3 ELISA, a sensitivity ranging from 75% for mf densities ≤ 50/mL to a 100% for mf densities > 50/mL. We detected 13 (20.6%) of 63 mf-positive persons negative for adult worms by 1) the absence of FDS (both before and during the follow-up period), 2) negative DEC PT results and no new nodules or FDS in follow-up period, and 3) no circulating antigen detected by the ICT. Some of these 13 patients may have been non-active infected persons (i.e., persons with no living adult worms) in spite of circulating mf (geometric mean = 11 mf/mL).

Because the lifespan of W. bancrofti mf has been determined indirectly by modeling39 to be 6–24 months, it is reasonable that circulating mf could survive after the death of the adult female worm, especially if parasite death is not drug induced, or in persons in whom not all mf were killed by anti-filarial treatment. Nodules found pre-treatment were seen in five patients with negative ICT results (Table 5) and biopsy specimens from three of them contained calcified (dead) worms. Conversely, it is not known what a negative ICT result in a low-density mf carrier means in terms of transmission interruption in different periods during and after five years of mass treatment.

It not possible with the methods currently available to establish the minimal parasitologic criteria for determining when a given patient will have a positive CFA test result. As shown in other studies24,34,38,40 and our study, the presence of circulating mf (irrespective of the volume of blood examined) is not always sufficient to give a positive CFA test result. Conversely, the absence of circulating mf (unisexual infection or both sexes located in different lymphatic vessels), even when a sufficient amount of blood is filtered, does not prevent positive CFA results in patients with infection proven by ultrasonography, as shown in the present study and by others.6,24

In bancroftian filariasis, the period in which the adult worm, once dead, continues to release substances detected by current CFA tests is still not clear. In human tissues, the time course of complete absorption of the dead worm is unknown, but it seems reasonable to assume that antigen(s) released by dead worms will disappear more rapidly from circulation in patients whose worms are calcified.4143 Calcification of a dead parasite constitutes an important factor in terminating the tissue inflammatory response, reducing or even abolishing the source of parasite material.44

Although many studies have focused on different populations with different gold standard tests, variables will interfere with the sensitivity of antigen tests. One variable is the age of the population, where it is expected that younger age groups will have a lower adult worm load,45 as well sex differences in the intensity of infection. The relationship of ICT sensitivity changes with endemicity also has been demonstrated,8 which make this factor an important one, particularly where negative predictive values would help in interpretation of test results. Unfortunately, prevalence of infection in a given area is usually not known within a filariasis-endemic village, city, or country, which makes the accuracy of prevalence not always reliable. It is not known whether different strains also play a role in the sensitivity of the test (e.g., nocturnally periodic strains compared with sub-periodic strains found in Papua New Guinea). Overall, it is important to highlight what target population (or person, together with all clinical information possible) the antigen sensitivity is linked with to better interpret the results.

Interpretation of ICT results in different settings post-control measures is also an important issue. In addition to the lack of knowledge about antigen decay after successful antifilarial treatment in areas of different endemicity, amicrofilaremic adult worm carriers or persons with ultra-low mf density (e.g., in areas using ivermectin and albendazole for mass treatment) could be at increased risk for false-negative test results. This study also raises questions about the suitability of using children as sentinel populations for control programs because reduced transmission may result in a much longer period before a child acquires her or his first worm, which results in a shift of the age-specific distribution of infection, and lower sensitivity of the ICT in amicrofilaremic adult worm carriers in younger persons. Thus, the current WHO recommendations for testing 3,000 children may need to be revisited. The sensitivity of the ICT was assumed to be 100% when these criteria were proposed.22 The ICT has revolutionized diagnosis of active infection of W. bancrofti and seems to be well suited for field application. However, it is important to take into consideration different sensitivities in different groups of persons in interpreting results of individual diagnosis and those of sentinel populations after control interventions to interrupt transmission. Thus, diagnosis of active infection in bancroftian filariasis continues to pose an important and continuously evolving challenge to filariasis-endemic countries and health personnel.

The results of our study are limited by certain factors. All patients came from the same filariasis-endemic area (greater Recife), which had different levels of prevalence and exposure to infective larvae. It was not possible to determine by ultrasound the numbers of adult worms or their sexes, which could provide more information on the parasitologic status of persons with negative results in the ICT. A parallel comparison with the Og4C3 ELISA was not part of our study, although it is accepted that the performance of the ICT is comparable with that of the Og4C3 ELISA.2 Conversely, the Og4C3 ELISA could provide useful information on FDS-positive patients who have borderline ICT results. Finally, our study was a retrospective study and it was not possible to obtain a completely representative sample.

Table 1

Characteristics of patients in group 1 and ICT sensitivity*

Mf negative or ultra-lowMf positive
CharacteristicTotalGroup 1A (≤ 17 years old)Group 1B (≥ 18 years old)Group 1C (≥ 18 years old)
* ICT, immunochromatographic card test; Mf = microfilaria; NA: not applicable; Group 1A = children and adolescents with ultra-low mf density or no mf in 6 mL of blood; Group 1B = adults with ultra-low mf density or no mf in 11 mL of blood; Group 1C = mf positive in 1 mL of blood; NA = not applicable.
Number (%) of patients307 (100)25 (8.1)84 (26.4)198 (64.5)
Males/females291/1618/781/3192/6
Mean (range) age, years (SD)25.9 (6–72) (11.4)8.8 (6–14) (1.9)33.0 (18–72) (11.7)25.1 (13–64) (9.2.)
Geometric mean mf density (range)/mL of blood
    1 mL (range)00127.6 (2–16,010)
    6 mL (range)1.3 (0–5)NANA
    11 mL (range)NA1.1 (0–6)NA
ICT sensitivity, %84.5 (260/307)52 (13/25)60.7 (51/84)98.9 (196/198)
Table 2

Characteristics of patients in group 2 (microfilaria positive in 1 mL of blood and FDS negative) and ICT sensitivity*

CharacteristicTotalGroup 2A (≤ 17 years old)Group 2B (≥ 18 years old)P
* FDS = filarial dance sign; ICT = immunochromatographic card test; mf = microfilaria; PT = provocative test.
† By Student’s t-test for log-transformed data.
‡ By Fisher’s exact test.
No. of patients1013863
Males/females82/1919/1963/0
Mean age (range), years24.3 (8–57)13.4 (8–17)30.9 (18–57)
Geometric mean mf density (range)/mL of blood53.7 (5–3,772)214.05 (5–3,772)23.3 (1–2,886)0.001†
ICT sensitivity, %74.2 (75/101)100 (38/38)58.7 (37/63)< 0.001‡
PT sensitivity, %23.8 (24/101)0 (0/38)38.1 (24/63)< 0.001‡
Table 3

Performance of the PT for DEC and ICT in patients in group 2B according to physical and ultrasound examination of intrascrotal contents*

CharacteristicTotalNormal resultsAbnormal resultsP
* PT = provocative test; DEC = diethycarbamazine; ICT = immunochromatographic card test; Mf = microfilaria.
† By binomial test.
‡ By Student’s t-test for log-transformed data.
§ By Fisher’s exact test.
¶ By chi-square test.
No. of patients (%)63 (100)15 (23.8)48 (76.2)0.001†
Mean age, years (range), SD30.9 (18–57) 11.333.9 (18–55) 13.130 (18–57) 10.6
Geometric mean Mf density (range)/mL of blood23.3 (1–2,886)9.12 (1–83)31.32 (1–2,886)0.014‡
Positive PT and ICT results (%)15 (23.8)2/1513/480.49§
Negative PT and ICT results (%)17 (27)7/1510/480.09§
Positive ICT result (%)22 (34.9)5/1517/480.87¶
Positive PT result (%)9 (14.3)1/1508/480.67§
ICT sensitivity, %58.7 (37/63)46.6 (7/15)62.5 (30/48)0.28¶
PT sensitivity, %38.1 (24/63)20.3 (3/15)43.7 (21/48)0.13§
Table 4

Details of patients in group 2B with a new nodule or new nest of worms in the longer follow-up period*

PatientAge, yearsMf/mLTime, monthsICTPTIntrascrotal contents pre-PT
* Mf = microfilaria; ICT = immunochromatographic card test; PT = provocative test; − = negative; + = positive.
† Time of nodule detection after diethylcarbamazine PT.
‡ Small and flaccid.
Nodules by physical examination
7451545Ipsi-lateral hydrocele‡
1627563+Ipsi-lymphangiectasia
454949Normal
6418164+Ipsi-lateral lymphangiectasia
New nests by ultrasonography
2318724++Normal
372524Normal
4549412Normal
553573Contra-lateral nodule pre-PT
571815+Normal
6418164+Ipsi-lateral lymphangiectasia
Table 5

Details of patients in group 2B with negative ICT and PT results and no evidence of infection in the follow-up period up to 12 months after DEC PT (e.g., new nodule or new FDS)*

PatientAge, yearsMf/mL pre-PTIntrascrotal contents pre-PT
* ICT = immunochromatographic card test; PT = provocative test; DEC = diethylcarbamazine; FDS = filarial dance sign; Mf = microfilaria.
† Calcified adult worms.
12172Nodule (biopsy)†
3223Lymphangiectasia
102735Lymphangiectasia plus nodule (biopsy)†
133862Lymphangiectasia
17452Normal
225259Nodule plus ipsi-lateral hydrocele
28441Normal
41551Normal
503869Lymphangiectasia plus nodule (biopsy)†
515727Lymphangiectasia
583910Nodule
60489Normal

*

Address correspondence to Gerusa Dreyer, Organização Não Governamental Amaury Coutinho para Doenças Endêmicas e Tropicais, Rua Conselheiro Portela, 665, Sala 120, Graças, Recife, Pernambuco, Brazil, CEP 52020-030. E-mail: dreyer-g@uol.com.br

Authors’ addresses: Gerusa Dreyer, Núcleo de Ensino Pesquisa e Assistência em Filariose, Hospital das Clínicas, Universidade Federal de Pernambuco, Avenida Prof. Moraes Rego s/n, Cidade Universitária, Recife, Pernambuco, Brazil, CEP 50670-900, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, FIOCRUZ, Avenisa Prof. Moraes Rego s/n, Cidade Universitária, Recife, Pernambuco, Brazil, CEP 50670-420, e Organização Não Governamental Amaury Coutinho para Doenças Endêmicas e Tropicais, Rua Conselheiro Portela, 665, Sala 120, Graças, Recife, Pernambuco, Brazil, CEP 52020-030, Telephone: 55-81-3426-4348, Fax: 55-81-3442-6195, E-mail: dreyer-g@uol.com.br. Renato Lins, Organização Não Governamental Amaury Coutinho para Doenças Endêmicas e Tropicais, Rua Conselheiro Portela, 665, Sala 120, Graças, Recife, Pernambuco, Brazil, CEP 52020-030, E-mail: natocl@hotmail.com. Joaquim Norões, Departamento de Cirurgia, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Avenida Prof. Moraes Rego s/n, Cidade Universitária, Recife, Pernambuco, Brazil, CEP 50670-900 e Organização Não Governamental Amaury Coutinho para Doenças Endêmicas e Tropicais, Rua Conselheiro Portela, 665, Sala 120, Graças, Recife, Pernambuco, Brazil, CEP 52020-030, E-mail: jnoroes@hotmail.com. José Ângelo Rizzo, Estrada de Apipucos 235/ 1901, CEP 52071-000, Recife, Pernambuco, Brazil e Centro de Pesquisas em Alergia e Imunologia Clínica, Faculdade de Medicina, Universidade Federal de Pernambuco, Pernambuco, Brazil CEP 52020-030, E-mail jarizzo@hotlink.com.br. José Figueredo-Silva, Núcleo de Ensino e Pesquisa em Patologia, Faculdade de Ciências Médicas, Universidade Estadual do Piauí. Rua Olavo Bilac, 2335 Centro-Sul, Teresina, Piaui, Brazil, CEP 64001-280 e Organização Não Governamental Amaury Coutinho para Doenças Endêmicas e Tropicais, Rua Conselheiro Portela, 665, Sala 120, Graças, Recife, Pernambuco, Brazil, CEP 52020-030, E-mail: figueredo_silva@hotmail.com.

Acknowledgments: We thank Izabely Costa for technical assistance with reading the ICT results and performing the ICTs with capillary blood, Patrick Lammie for critically reading and providing valuable suggestions on the original manuscript, and J. Natal Figueiroa for statistical advice.

Financial support: This study was supported by the nongovernmental organization Amaury Coutinho, Recife, Brazil. The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses.

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Author Notes

Reprint requests: Gerusa Dreyer, Organização Não Governamental Amaury Coutinho para Doenças Endêmicas e Tropicais, Rua Conselheiro Portela, 665, Sala 120, Graças, Recife, Pernambuco, Brazil, CEP 52020-030, E-mail: dreyer-g@uol.com.br.
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