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Am. J. Trop. Med. Hyg., 73(4), 2005, pp. 759-765
Copyright © 2005 by The American Society of Tropical Medicine and Hygiene

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CLINICAL CORRELATES OF FILARIAL INFECTION IN HAITIAN CHILDREN: AN ASSOCIATION WITH INTERDIGITAL LESIONS

LEANNE M. FOX*, SUSAN F. WILSON, DAVID G. ADDISS, JACKY LOUIS-CHARLES, MADSEN V. BEAU DE ROCHARS, AND PATRICK J. LAMMIE
Epidemic Intelligence Service, Epidemiology Program Office, and Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; Hôpital Sainte Croix, Leogane, Haiti


ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
To assess clinical findings associated with Wuchereria bancrofti infection, 192 school children in a filariasis-endemic area of Haiti underwent physical and ultrasonographic examinations and testing for circulating filarial antigen (CFA). The CFA-positive children were more likely than CFA-negative children to have severe interdigital lesions (≥1 macerated lesion with involvement of ≥4 toe web spaces) (P < 0.0001) and inguinal (P = 0.003) or crural (P = 0.004) lymph node pathology. In multivariate analysis, CFA positivity remained a significant predictor for severe interdigital lesions (P = 0.006) and inguinal lymph node pathology (P = 0.05). Ultrasound detected adult worms and lymphangectasia (diameter = 2.0–4.0 mm) in 11 (10.8%) CFA-positive children. Among CFA-positive children, ultrasonographic detection of adult worms was associated with inguinal (P = 0.01) and crural (P = 0.004) lymph node pathology and advanced pubertal stage (sexual maturity rating = 3–5) (P = 0.02). This is the first study to associate interdigital lesions with filarial infection in children.


INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Wuchereria bancrofti, the major parasite causing lymphatic filariasis (LF), is targeted for global elimination. This global program has two integral components: interrupting parasite transmission through mass treatment with antifilarial drugs and controlling filarial morbidity through clinical care for those with lymphedema or hydrocele.1 Lymphatic filariasis is considered the second leading cause of permanent disability worldwide.2,3 An estimated 44 million individuals have one or more of the clinical manifestations of filarial disease, including lymphedema and elephantiasis of the limbs, hydrocele, chyluria, pneumonitis, and recurrent bacterial infections associated with damaged lymphatics. Another 76 million persons have laboratory evidence of filarial infection, but no overt signs or symptoms of disease.4

Recurrent episodes of acute dermatolymphangioadenitis (ADLA) are considered a major risk factor for the development of chronic lymphedema and elephantiasis in LF.5–8 Acute dermatolymphangioadenitis is characterized by diffuse inflammation and swelling occasionally associated with an ascending lymphangitis and adenitis. A distal skin lesion, often an interdigital infection, frequently serves as the point of entry for bacteria precipitating ADLA.9 Frequent ADLA episodes contribute to the progression of lymphedema by repeated damage to superficial lymphatic vessels. Several studies have demonstrated that treatment and prevention of interdigital infections with basic foot and leg hygiene and topical antibiotics and antifungals can decrease the frequency of ADLA episodes.7,8,10,11 These foot care programs have proven sustainable and effective and are integral to controlling filarial morbidity, but have, thus far, been implemented primarily in adult populations in persons with demonstrable filarial disease.12

Despite estimates that greater than one-third of LF-infected persons are children, pediatric filarial disease is rarely recognized and often misdiagnosed.13 It has only recently been appreciated that filarial infection and disease are more common in children than previously thought. For example, filarial antigen prevalence among four-year-old children in Leogane, Haiti has been demonstrated to be greater than 30%.14 In addition, the finding of unexplained chronic adenopathy has been shown, both histopathologically and clinically, to be an important presentation of LF in children15 and lymphadenopathy has been associated with the detection of living adult worms on ultrasound in young children.16,17 Additionally, ultrasonography has been successfully used to better understand filarial disease in both symptomatic and asymptomatic adults18,19 and has proven helpful in assessing the subclinical manifestations of LF in children.16,17,20

The objectives of this study were to assess the clinical and subclinical manifestations associated with W. bancrofti infection in a cohort of Haitian children living in a filariasis-endemic area in an effort to improve our understanding of filarial morbidity in children.


METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study design. The protocol for this study was reviewed and approved by the Institutional Review Board of the Centers for Disease Control and Prevention and the Ethics Committee of Hôpital Sainte Croix. Written informed consent was obtained from the child’s parent or guardian and written assent was obtained from children (≥7 years of age) for participation in the study. Study participants were a subgroup (n = 192) of a cohort of children from the Leogane Commune who have participated in longitudinal filariasis studies for more than 10 years.14 This pediatric cohort was originally established to longitudinally analyze risk factors for filarial infection in children and more specifically, to test the hypothesis that in utero exposure to filarial infection constituted a risk factor for acquisition of infection.14,21 A cross-sectional clinical, ultrasonographic and laboratory evaluation was performed in November 2002. A questionnaire, physical examination and ultrasound examination were administered, an immunochromographic test (ICT) that detects filarial antigen was performed and blood was collected for later quantification of circulating filarial antigen (CFA).22 Children who had evidence of living adult worms on ultrasound were treated with diethylcarbamazine (6 mg/kg) and albendazole (400 mg) after completing the ultrasound examination. All children in this cohort study had access to antifilarial treatment through the mass drug administration (MDA) campaign that has occurred yearly in Haiti since 2000.

Laboratory evaluation. The Binax (Portland, ME) NOW® filariasis ICT, a qualitative test for CFA, was conducted for all children and was used as an initial screen to determine which children would have an ultrasound examination.23 One hundred microliters of blood were collected in capillary tubes and serum samples were separated and frozen for later testing. The Og4C3 assay (James Cook University Tropical Biotechnology Pty., Ltd., Townsville, Queensland, Australia) for CFA was conducted to quantify antigen levels.22 Antigen levels were quantified against a standard curve and were highly reproducible between assays. Quantitative antigen assay results ≥250 units were considered positive and specimens with a response ≥32,000 antigen units were assigned a fixed value of 32,000. Laboratory personnel were blinded to the infection status of the children.

Clinical evaluation. Medical history was collected in a single interview with children and their parents. Questions were asked regarding pain, redness, swelling, and warmth of the lower extremities and lymph nodes (axillary, crural, epitrochlear, inguinal, and popliteal) and a history of skin problems, such as rashes or infections on the legs, feet, or toes. Crural lymph nodes are located in the medial thigh below the superficial inguinal lymph nodes.24,25

Physical examinations were also performed on each of the children concentrating on sexual maturity, lymphadenopathy of the axillary, crural, epitrochlear, inguinal, and popliteal lymph nodes, lower extremity skin findings as well as assessment of the interdigital toe web spaces. The sexual maturity ratings (SMRs) of Marshall and Tanner26 were used to assess the secondary sexual characteristics of pubertal maturation. These SMRs comprise five stages for each sex and are based upon breast and pubic hair development in girls and genital and pubic hair development in boys.26 The presence of hydrocele or spermatic cord thickening, both of which can be indicators of filarial disease in men, was also documented for boys. Lymph node pathology was defined as the presence of tenderness, induration, or palpable irregularity of the lymph node on physical examination. Interdigital toe web space lesions were defined as scaling, fissuring, peeling, erosion, erythema, or maceration of the intertriginous area between the toe web spaces.24 Severe interdigital toe web space lesions were defined as the presence of at least one macerated lesion with involvement of four or more interdigital toe web spaces. A single examiner (LMF) performed the physical examinations in 2002 and was blinded to the infection status of the children; questionnaire administration, laboratory testing, and physical examinations were performed by separate individuals in different physical locations of the hospital.

Ultrasound examinations (computer sonogram 128XP/10C, 5.0-MHz transducer; Acuson, Mountain View, CA) were performed to detect evidence of adult worm infections including adult worm nests and lymphangiectasia (lymphatic dilatation) in the lymph node areas (axillary, crural, and inguinal), the breast in post-pubescent females and the scrotum for boys. Examinations were conducted for 20–30 minutes with children resting in the supine position. Ultrasonographic examinations were performed only on those children who were ICT positive, given previous data demonstrating a lower yield of adult worm detection in filarial antigen–negative individuals.17 Adult worm nests were identified based on the characteristic motility of the adult worm (filaria dance sign [FDS]). Every worm nest was confirmed in B mode, M mode, and Pulse wave Doppler mode.

Statistical methods. For the purposes of data analysis, participants were allocated to one of two groups based on detection of filarial antigenemia by enzyme-linked immunosorbent assay (ELISA); those children who had evidence of infection with W. bancrofti (CFA positive), by a quantitative CFA level > 250 antigen units, and those children who had no evidence of infection with W. bancrofti (CFA negative). Data were analyzed using Epi-Info version 6.04 (Centers for Disease Control and Prevention, Stone Mountain, GA) and SAS version 8 (SAS Institute, Cary, NC). In bivariate analyses, chi-square and two-sided Fisher’s exact tests were used to compare categorical variables; continuous variables were compared using the nonparametric Wilcoxon rank sum tests. Multivariate logistic regression with backwards elimination was used to analyze associations between clinical examination findings and circulating filarial antigen status.


RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Descriptive epidemiology. Of the 192 children examined, 97 (50.5%) were male; the mean age was 10.7 years (range = 4–19 years) and 134 (69.8%) children had an SMR stage of 1 or 2 indicating early sexual development. There was no difference in mean age or pubertal stage between the sexes. All children had ICT tests and quantitative filarial antigen testing performed. There were 102 (53.1%) children who were ICT positive. One hundred ICT-positive children and 10 ICT-negative children, a total of 110 (57.3%) children, were antigen positive by the Og4C3 ELISA, with a geometric mean filarial antigen level of 3,295.2 antigen units (range = 253.5–32,000 units, positive ≥250 units). Antigen prevalence was 58% in the 5–9-year-old age group, 56% in the 10–14-year-old age group, and 61% in the 15–19-year-old age group.

One hundred ninety-one children had data collected on medical history. Forty (20.9%) children reported a history of lower extremity problems, as defined by pain, redness, swelling, or warmth of the lower extremity and 111 (58.1%) reported a history of skin problems, such as rashes or infections on the legs, feet, or toes. In addition, 142 (74.4%) children reported a history of lymph node pain, redness, swelling, or warmth; 128 (90.1%) of these children reported the lymph node symptoms in the inguinal area and 40 (28.2%) reported the lymph node symptoms in the crural area. Although 6 (4.2%) children reported popliteal lymph node problems, this history was always shown in association with either a history of inguinal or crural lymph node involvement. Seventeen (17.5%) boys reported a history of hernia or hydrocele and 11 (11.6%) girls reported a history of lumps, pain, or swelling in the breasts. One hundred seventy-six (92.1%) children reported having taken antifilarial medications in the past. Medical history of lymph node or lower extremity problems did not differ based on sex in univariate analysis.

Clinical assessment. All 192 children had physical examinations performed. On physical examination, 52 (27.1%) children had inguinal lymph node pathology, defined as the presence of tenderness, induration, or palpable irregularity of the lymph node, 14 (7.3%) had crural lymph node pathology, 11 (5.7%) had axillary lymph node pathology, and 4 (2.1%) had epitrochlear lymph node pathology. No popliteal lymph node pathology was detected. Spermatic cord thickening was noted in six (6.2%) males. No males had hydrocele on physical examination and no children had an acute episode of bacterial ADLA at the time of the physical examination. On examination of the interdigital toe web space, 128 (66.7%) children had interdigital lesions, 22 (11.5%) of which were considered severe as defined by the presence of at least one macerated lesion with involvement of four or more interdigital toe web spaces. Of children with inguinal or crural lymph node pathology on physical examination, 31 (59.6%) and 11 (78.6%), respectively, were boys. Physical findings did not differ significantly among SMR stages, with the exception of spermatic cord thickening, which was present exclusively among post-pubescent males (P < 0.0001). Boys were more likely than girls to have crural lymph node pathology (relative risk [RR] = 3.6, 95% confidence interval [CI] = 1.0–12.5) and interdigital lesions (RR = 1.3, 95% CI = 1.1–1.7) on physical examination.

In bivariate analysis, CFA-positive children were more likely to report a history of lymph node problems in general (RR = 1.3, 95% CI = 1.1–1.5) or inguinal lymph node problems specifically (RR = 1.5, 95% CI = 1.2–1.9), or had inguinal or crural lymph node pathology on physical examination (RR = 2.2, 95% CI = 1.3–3.9 and RR = 9.7, 95% CI = 1.3–72.6, respectively) (Table 1Go). Additionally, CFA-positive children were more likely to have interdigital lesions within the toe web space (RR = 1.3, 95% CI = 1.1–1.7), as well as severe interdigital lesions (RR = 15.7, 95% CI = 2.1–114.0) on physical examination. There was a significant difference in geometric mean filarial antigen levels between children who had no interdigital lesions, 1,064.9 antigen units (range = 0–32,000) and children who had severe interdigital lesions, 4,189.1 antigen units (range = 0–32,000) (P = 0.03). Although higher geometric mean filarial antigen levels were seen as interdigital lesion severity increased from mild to severe, this was not statistically significant.


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TABLE 1
Clinical and ultrasonographic examination findings associated with circulating filarial antigen (CFA) status: bivariate analysis of 192 children, Leogane, Haiti, 2002*
 
In multivariate analysis, inguinal lymph node pathology and severe interdigital lesions on physical examination continued to be significantly associated with CFA positivity in this cohort (adjusted odds ratio [AOR] = 2.2, 95% CI = 1–4.7 and AOR = 17.7, 95% CI = 2.3–137, respectively) (Table 2Go). Advanced pubertal stage (SMR = 3–5) was also associated with CFA positivity (AOR = 2.3, 95% CI = 1.1–4.6). The presence of crural lymph node pathology was of borderline significance in this model (AOR = 7.6, 95% CI = 0.9–64.1). When multivariate analysis was used to assess the predictors of severe interdigital lesions, CFA positivity alone was strongly associated with severe interdigital lesions (AOR = 19.1, 95% CI = 2.5–145.3). Factors not associated with CFA positivity included a history of lower extremity problems or skin problems and upper extremity lymphadenopathy on physical examination.


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TABLE 2
Clinical examination findings associated with circulating filarial antigen status: multivariate analysis of 192 children, Leogane, Haiti, 2002*
 
Ultrasonographic assessment. All 102 ICT-positive children had an ultrasound examination, of whom 100 (98%) were CFA positive; there were two false-positive readings using the Binax NOW® filarial ICT. One false-positive reading was associated with a CFA level of 212.5 antigen units and one with a CFA level of 0 antigen units. Of these 102 children, 11 (10.8%) had ultrasonographic evidence of adult W. bancrofti nests, i.e., the FDS was detected (Table 3Go). The mean age of the FDS-positive children was 11.5 years (range = 7–16 years), and 10 (90.9%) were boys. The filarial dance sign was detected by ultrasound examination in the inguinal (n = 2) and crural (n = 2) lymphatics of four (3.9%) prepubescent children (SMR = 1–2), all of whom had inguinal or crural lymph node pathology and interdigital lesions on physical examination. The filarial dance sign was also detected in the intrascrotal lymphatic vessels of seven (6.9%) post-pubescent (SMR = 3–5) males. In the FDS-positive children, 11 living adult worm nests were detected, one per child, and all 11 children demonstrated lymphangiectasia (range = 2–4 mm).


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TABLE 3
Ultrasonographic examination findings on assessment of 102 Binax NOW® filarial ICT-positive children, Leogane, Haiti, 2002*
 
Detection of adult W. bancrofti nests was associated with male sex (P = 0.01) and a more advanced pubertal stage (SMR = 3–5) (P = 0.02) (Table 4Go). Additionally, children were more likely to have a positive ultrasound examination result if they had inguinal or crural lymph node pathology on physical examination (RR = 2.6, 95% CI = 1.5–4.3 and RR = 6.6, 95% CI = 2.5–17.7, respectively). The presence of interdigital lesions or severe interdigital lesions on physical examination was not significantly associated with FDS positivity. These relationships were not significantly different among SMR stages.


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TABLE 4
Clinical examination findings associated with filarial dance sign (FDS) positivity: bivariate analysis of 102 children, Leogane, Haiti, 2002*
 

DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Little is known about the natural history of LF in the pediatric population. In this study, we found an association between physical examination findings and CFA positivity in a cohort of Haitian children residing in a LF endemic area. Additionally the presence of interdigital toe web space lesions as well as inguinal and crural lymph node pathology to be associated with filarial infection in these children. We also evaluated the prevalence and location of adult worms by ultrasound in a cohort of ICT-positive children. These data highlight the importance of physical examination findings, demonstrate subclinical filarial disease, and suggest a role for the treatment and prevention of interdigital lesions in filarial-infected children.

In this pediatric cohort, the presence of interdigital toe web space lesions, particularly severe interdigital lesions, was associated with laboratory evidence of filarial infection. Interdigital lesions, or breaks in the epidermis that provide an entry point for bacteria, are central to the pathogenesis of ADLA and several studies in LF-uninfected populations have demonstrated that cellulitis occurs commonly in the presence of interdigital dermatophytosis.27,28 In adults with unilateral, lower limb lymphedema living in filariasis-endemic areas, the prevalence of interdigital lesions has been found to be higher in individuals with more advanced lymphedema when compared with their nonlymphedematous limb.29 Although the exact mechanism associating interdigital lesions and filarial infection is unknown, it has been postulated that the lymphatic dysfunction caused by LF leads to poor clearance and elimination of pathogens thereby favoring secondary fungal and bacterial infections.29 Although none of the infected children in this cohort had clinically evident lymphedema, we postulate that the subclinical lymphatic dysfunction associated with filarial infection may predispose these children to increased severity of interdigital lesions and subsequently to filarial disease progression. Alternatively, given the immunologic differences between filarial-infected and -uninfected individuals, it is possible that filarial-infected children respond differently to interdigital fungal or bacterial antigens, leading to either decreased fungal or bacterial antigen clearance or an enhanced inflammatory response.30

There are limited studies that have evaluated the microbiology of the interdigital toe web space in LF-endemic populations, although both bacteria and fungi are postulated to play a role. Olszewski and others cultured the toe web spaces of lymphedema patients and found primarily gram-positive bacterial organisms that were identical to the strains found in blood and lymph cultures from the same patients.31 Baird and others have shown that lymphedema patients with recurrent ADLA had an increased delayed-type hypersensitivity reactivity to Trichophyton, and other investigators have cultured fungi, yeast, and dermatophytes from the interdigital toe web spaces of lymphedema patients.32,33 In addition, gram-negative organisms have been cultured from interdigital toe web spaces particularly those with hyperkeratotic, macerated and erosive lesions.34,35 Our study clinically assessed interdigital lesions and bacterial and fungal cultures were not performed. Given the wide variety of both bacterial and fungal organisms in interdigital pathology, microbiologic studies are needed to further understand the ecology of the interdigital toe web space in filarial-infected individuals to better direct treatment regimens.36–38

There are several factors not assessed in this study that may confound the association between interdigital lesions and CFA positivity, including both environmental and host factors such as socioeconomic status, climate, household exposures, footwear, previous trauma, and immunocompetence. The children in this study reside in two areas that border the town of Leogane, a socioeconomically relatively homogeneous area. The ability to assess the role of climatic factors on the presence or severity of interdigital lesions in LF-endemic areas is challenged by the fact that LF and tinea pedis are both found in humid, tropical climates.39,40 The high prevalence of interdigital lesions in this population (66.7%) is consistent with other studies showing high rates of interdigital lesions (95.5%) and recovery of fungal pathogens (78%) in tropical communities.41,42 In this study, we did not assess the presence of interdigital lesions in the subject’s household members, the extent of occlusive footwear use, the initial epidermal integrity of the interdigital toe web space, or immunocompetence.

Other studies have suggested a role for pertinent history and physical examination findings as a marker for the ultrasonographic detection of adult worms in young children.17 In this study, we have correlated both historical data, a history of lymph node and inguinal lymph node problems, and physical examination data, crural and inguinal lymph node pathology, with filarial infection in children. Lymphadenopathy and lymph node pathology have been noted in several other studies of pediatric LF, as well as in early clinical observations of filariasis in adults, and may indicate early filarial disease, particularly in prepubescent children.15–17,43,44 Although the specificity of lymphadenopathy for LF may be low, these results continue to support the consideration of filarial disease in the differential diagnosis for lymphadenopathy in children from LF-endemic countries.15

As in other published work, these ultrasonographic findings of lymphatic dilatation provide further evidence for subclinical filarial disease in infected children.17,20 In this cohort, lymphatic dilatation (lymphangiectasia) at the site of living adult worm nests ranged from 2 to 4 mm, which is consistent with values reported in other studies.17,20 Detection of living adult worms in children was associated with male sex and advanced pubertal stage, suggesting that adult worms are more easily detected in boys, particularly once they reach puberty.20 Although other investigators have localized living adult worms in post-pubescent females and adult women,20,45 no worm nests were found upon ultrasonographic examination of 33 adolescent females in this study.

Although the number of FDS-positive children in this study was small (n = 11), the ultrasonographic examination findings in this population confirm the different location of adult worms associated with puberty. All prepubescent (SMR = 1–2) FDS-positive children (n = 4) had worms localized to either the crural or inguinal areas. There were no nests located in the intrascrotal lymphatic vessels and no hydrocele on ultrasonographic examination. Similarly, hydrocele or spermatic cord thickening was not observed on physical examination in prepubescent males. In contrast, all post-pubescent (SMR = 3–5) FDS-positive children were male (n = 7) and demonstrated adult worms in the intrascrotal lymphatics, as has been reported previously for adult males and adolescent boys.19,46 In addition, five of the seven FDS-positive post-pubescent boys had spermatic cord thickening on physical examination. These results further demonstrate that worms tend to localize to different sites before and after puberty, at least in males.

In this study, FDS positivity was associated with the physical examination findings of inguinal and crural lymph node pathology, as has been previously reported.17 We found no association between the detection of living adult worms and filarial antigen levels, or a reported history of inguinal lymph node problems as has been seen in other studies.17 This is perhaps due to our small sample size or to the treatment status of these patients. Detection of the FDS was also associated with advanced pubertal stage (SMR = 3–5), which is possibly a surrogate for older age or ease of detection of adult worms in post-pubescent children.

This study has several limitations. Due to its cross-sectional nature, we were unable to assess the direction of the association between filarial infection and the presence of severe interdigital lesions; although lymphatic dysfunction or immunomodulation secondary to W. bancrofti infection predisposing children to severe interdigital lesions makes etiologic sense. Since bacterial and fungal cultures were not obtained, this study could not assess the microbiology of these interdigital lesions. In addition, this cohort of children may not be representative of filarial-infected children worldwide, since many of these children have been previously treated or have participated in MDA with antifilarial drugs. Since participation in MDAs was self reported, we are unable to assess whether any individual child actually participated in the MDAs, and therefore are unable to assess the effect of mass drug administration on physical findings, including the presence or severity of interdigital lesions.

This is one of the first studies to clinically assess LF-infected and -uninfected children and to associate interdigital lesions with filarial infection in children, possibly as a cofactor in the pathogenesis of filarial disease progression. These data also continue to suggest a role for pertinent physical examination findings, specifically crural and inguinal lymph node pathology, as manifestations of filarial infection in children. They also provide evidence for subclinical disease in LF-infected children as demonstrated by ultrasound, including living adult worm nests and lymphangiectasia. Further population-based studies describing the prevalence and severity of interdigital lesions and their relationship to filarial infection are needed, as are studies to improve our understanding of the microbiology and immunology of these lesions in filariasis.

Lymphatic filariasis elimination programs currently promote lymphedema management for affected adults that focuses on skin hygiene and early treatment of bacterial ADLA episodes.1,47,48 However, they do not uniformly address the prevention of clinical disease in children, many of whom already have subclinical disease. It is therefore a research and programmatic priority to determine the degree to which bacterial ADLA and lymphedema can be prevented in children in LF-endemic areas through education programs focused on basic hygiene regimens, skin care, and recognition and treatment of interdigital lesions. This information is critical in determining the optimal approach to treatment and prevention of filarial disease in the pediatric population, a necessary focus for current filariasis elimination efforts.

Received April 12, 2005. Accepted for publication May 16, 2005.

Acknowledgments: We thank Bruce W. Furness for assistance with the ultrasonographic examinations and Jean-Marc Brissau, Marc André Ledain, Yves Gerry Clerfé, and the Hôpital Sainte Croix Filariasis Team for their assistance with the project. We are especially indebted to the children of Leogane who participated in this study.

Financial support: This project was supported by the Emerging Infections Program of the Centers for Disease Control and Prevention. A Bill & Melinda Gates Foundation grant to Notre Dame University provided salary support for Dr. Madsen V. Beau de Rochars.

* Address correspondence to LeAnne M. Fox, Center for International Health and Development, Boston University School of Public Health, 85 East Concord Street, Boston, MA 02118. E-mail: lfox{at}bu.edu or leanne.fox{at}childrens.harvard.edu Back

Authors’ addresses: LeAnne M. Fox, Center for International Health and Development, Boston University School of Public Health, 85 East Concord Street, Boston, MA 02118, Telephone: 617-414-1209, Fax: 617-414-1261, E-mail: lfox{at}bu.edu or leanne.fox{at}childrens.harvard.edu. Susan F. Wilson, New Jersey Medical School, Newark, NJ 07101, Telephone: 973-220-8547, swiss_miss31{at}yahoo.com. David G. Addiss, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341-3724, Telephone: 770-488-7760, Fax: 770-488-7761, E-mail: dga1{at}cdc.gov. Jacky Louis-Charles and Madsen V. Beau de Rochars, Filariasis Program, Hôpital Sainte Croix, Leogane, Haiti, Telephone: 509-512-1868, Fax: 509-235-1845, E-mail: jlouisch{at}yahoo.com and mbeauder{at}nd.edu. Patrick J. Lammie, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30341-3724, Telephone: 770-488-4054, Fax: 770-488-4108, E-mail: pjl1{at}cdc.gov.

Reprint requests: LeAnne M. Fox, Center for International Health and Development, Boston University School of Public Health, 85 East Concord Street, Boston, MA 02118.


REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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T. McPHERSON, M. P. FAY, S. SINGH, R. PENZER, and R. HAY
HEALTH WORKERS' AGREEMENT IN CLINICAL DESCRIPTION OF FILARIAL LYMPHEDEMA.
Am J Trop Med Hyg, March 1, 2006; 74(3): 500 - 504.
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