Sex ratio of Wuchereria bancrofti in surgical specimens from an endemic area of Brazil.

The sex ratio of adult Wuchereria bancrofti from 172 histologically diagnosed cases of lymphatic filariasis, all from an endemic area of Recife, in north-eastern Brazil, was investigated. Of 172 tissue specimens examined, 74 (43%) were lymph nodes and 98 (57%) lymphatic-vessel segments. The morphology of the worms was generally disrupted, in some cases to the point where the worms were almost completely absorbed by the granulomatous inflammatory response. Parasite gender was clearly determined in only 110 (64%) specimens, 61 (55.5 %) of which were lymph nodes and 49 (44.5%) lymphatic vessels. Eighty-seven (79.1%) of these tissue specimens contained only female worms, 17 (14.5%) both males and females, and six only males, giving an overall female:male 'specimen' ratio of 4.5:1. Of the 63 tissue specimens in which dead or degenerating worms were noted, 60 (92.2%) contained only females. All the female worms detected were gravid, regardless of whether male worms were present in the specimen. The implications of these findings for parasite dynamics, the pathogenesis of bancroftian filariasis and the interpretation of ultrasound images of living adult worms are discussed.

Interdigital lesions and frequency of acute dermatolymphangioadenitis in lymphoedema in a filariasis-endemic area.

BACKGROUND: Lymphatic filariasis (LF) is a mosquito-borne nematode infection that causes permanent lymphatic dysfunction in virtually all infected individuals and clinical disease in a subset of these. One major sequel of infection is lymphoedema of the limbs. Lymphoedema of the leg affects an estimated 15 million persons in LF-endemic areas worldwide. Acute dermatolymphangioadenitis (ADLA) in people with filarial lymphoedema causes acute morbidity and increasingly severe lymphoedema. Episodes of ADLA are believed to be caused by bacteria, and it has been shown that entry lesions in the skin play a causative role. Clinical observations suggest that interdigital skin lesions of the feet, often assumed to be fungal, may be of particular importance. OBJECTIVES: To investigate the epidemiology and aetiology of interdigital lesions (IDL) of the feet in filarial lymphoedema. METHODS: The frequency and mycological aetiology of IDL in 73 patients with filarial lymphoedema were compared with 74 individuals without lymphoedema in a region of Guyana highly endemic for Wuchereria bancrofti. RESULTS: More than 50% of patients with lymphoedema had one or more IDL (odds ratio 2.69; 95% confidence interval 1.31-5.66; P<0.005 compared with controls). The number of lesions was the strongest predictor of frequency of ADLA. Only 18% of the lesions had positive microscopy or culture for fungi (dermatophytes and Scytalidium). CONCLUSIONS: These findings highlight the importance of interdigital entry lesions as risk factors for episodes of ADLA and have implications for the control of morbidity from filarial lymphoedema.

Albendazole for lymphatic filariasis.

BACKGROUND: Mass treatment with albendazole co-administered with another antifilarial drug is part of a global programme to eliminate lymphatic filariasis. We sought reliable evidence of the effects of albendazole on the disease and the parasite. OBJECTIVES: To summarize the effects of albendazole alone or in combination with antifilarial drugs for clinical treatment and community control of lymphatic filariasis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (August 2005), CENTRAL (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to August 2005), EMBASE (1974 to August 2005), LILACS (1982 to August 2005), and reference lists. We also contacted researchers, the World Health Organization, and GlaxoSmithKline. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of albendazole alone or combined with another antifilarial drug for treating individuals with lymphatic filariasis, or for reducing transmission in endemic communities. DATA COLLECTION AND ANALYSIS: Two authors independently assessed eligibility and trial quality, and extracted data. Authors contacted investigators for missing information or clarification. MAIN RESULTS: Seven trials including 6997 participants (995 with detectable microfilariae) met the criteria. A comparison of albendazole and placebo detected no effect on microfilariae prevalence (920 participants; 3 trials); one trial (499 participants) reported significantly lower microfilariae density at six months. Albendazole performed slightly worse than ivermectin in two trials (436 participants). Compared with diethylcarbamazine (DEC), two small trials (56 participants) found little difference in microfilariae prevalence over an extended follow up. One larger trial (502 participants) found a statistically significant effect for DEC at six months, but none at three months. Microfilariae prevalence and density were statistically significantly lower with the combination of albendazole and ivermectin compared with ivermectin alone in two of three trials (649 participants). Two trials compared albendazole plus DEC with DEC alone and found no statistically significant difference in microfilariae prevalence, though one trial favoured the combination at six months (relative risk 0.62, 95% confidence interval 0.32 to 1.21; 491 participants). This trial also found a statistically significant reduction in microfilariae density. AUTHORS' CONCLUSIONS: There is insufficient evidence to confirm or refute that albendazole co-administered with DEC or ivermectin is more effective than DEC or ivermectin alone in clearing microfilariae or killing adult worms. Albendazole combined with ivermectin appears to have a small effect on microfilaraemia, but this was not consistently demonstrated. The effect of albendazole against adult and larval filarial parasites, alone and in combination with other antifilarial drugs, deserves further rigorous research.

Factors associated with participation in a campaign of mass treatment against lymphatic filariasis, in Leogane, Haiti.

In October 2000, to interrupt transmission of Wuchereria bancrofti, an intense health-education campaign followed by a mass drug administration (MDA) with diethylcarbamazine and albendazole was undertaken in Leogane, Haiti. Three months after the MDA, which was the first in the study area, a knowledge-attitude-practice (KAP) survey, with a cluster-sample design and probability sampling, was undertaken, to determine the existing knowledge of the local residents, their attitudes toward the MDA, and the possible reasons for non-compliance. Questionnaire-based interviews were used to explore the KAP of 304 subjects (one randomly chosen resident aged > 14 years from each selected household) in 33 communities. Most (93%) of the interviewees were aware of filariasis and 72% knew at least one clinical sign of the disease. Awareness of the MDA was high (91%). The most frequently mentioned sources of information were other people (56%) and radio announcements (33%). More than 80% of the respondents encouraged other people to take the drugs distributed in the MDA and 63% had been treated. The primary reasons given for failing to take the drugs were absenteeism during the distribution (17%), use of contraceptive drugs (12%) and pregnancy (11%). In a multivariate analysis, being male [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.5-7.4], knowing that a mosquito transmits the disease (OR = 2.6; CI = 1.2-5.4), and having learned about the MDA through posters and banners (OR = 2.9; CI = 1.2-7.5) were found to be positively associated with taking the drugs. Information from such post-treatment surveys should be useful in developing better health communication for subsequent MDA.

Short report: documentation of iodine deficiency in Haitian schoolchildren: implication for lymphatic filariasis elimination in Haiti.

In this study we documented unexpected moderate-to-severe iodine deficiency in Haitian schoolchildren although they live in a coastal community where presumably they have access to iodine-containing seafood. This fact combined with the lack of an iodized salt supply and endemic lymphatic filariasis makes community distribution of diethylcarbamazine-fortified, iodized salt an attractive strategy for elimination of lymphatic filariasis and iodine deficiency disorders in this area of Haiti. Combining lymphatic filariasis elimination with other public health interventions is one strategy to increase its public health benefit and maximize the impact of limited public health resources.

Cryptosporidium parvum-specific antibody responses among children residing in Milwaukee during the 1993 waterborne outbreak.

A major gastroenteritis outbreak among >400,000 residents of Milwaukee, Wisconsin, in April 1993 was attributed to Cryptosporidium parvum oocysts in drinking water. Plasma specimens obtained from children (6 months to 12 years old) for routine blood lead level surveillance March-May 1993 were assayed by ELISA for levels of IgG antibody against the immunodominant Triton-17 and 27-kDa C. parvum antigens. Over a 5-week period, the seroprevalence for antibodies to the 2 antigens increased from 15% to 82% and from 17% to 87%, respectively, in samples from children living in southern ZIP code areas (n=218), whereas smaller increases (20% to 43% and 22% to 46%, respectively) were noted among samples from children living in northern ZIP code areas (n=335; P<.0001). The results demonstrate that C. parvum infection was much more widespread than previously appreciated and confirm that infection was associated with residence in the area served by the southern water treatment plant.

A community-based trial for the control of lymphatic filariasis and iodine deficiency using salt fortified with diethylcarbamazine and iodine.

To evaluate the effectiveness of salt fortified with diethylcarbamazine (DEC) and iodine for elimination of Bancroftian filariasis and iodine deficiency, all consenting residents of Miton, Haiti (n = 1,932) were given salt fortified with 0.25% diethylcarbamazine and 25 ppm of iodine for one year. Wuchereria bancrofti microfilaria prevalence and intensity, antigenemia, and urinary iodine were measured before and one year after salt distribution began. To measure the effect of DEC-fortified salt on adult worm motility, 15 microfilaria-positive men were examined by ultrasound of the scrotal area. Entomologic surveys were conducted to determine the proportion of W. bancrofti-infected Culex quinquefasciatus. After one year of treatment, the prevalence and intensity of microfilaremia were both reduced by more than 95%, while antigenemia levels were reduced by 60%. The motility of adult worms, as detected by ultrasound, was decreased, but not significantly, by DEC-fortified salt. The proportion of vector mosquitoes carrying infective stage larvae decreased significantly from 2.3% in the nine months before the intervention to 0.2% in the last three-month follow-up period. Iodine deficiency, which had been moderate to severe, was eliminated after one year of iodized salt consumption. The DEC-fortified salt was well accepted by the community and reduced microfilaremia and transmission to low levels in the absence of reported side effects. Based on these results, salt cofortified with DEC and iodine should be considered as a concurrent intervention for lymphatic filariasis and iodine deficiency elimination programs.

Malaria, intestinal parasites, and schistosomiasis among Barawan Somali refugees resettling to the United States: a strategy to reduce morbidity and decrease the risk of imported infections.

In 1997, enhanced health assessments were performed for 390 (10%) of approximately 4,000 Barawan refugees resettling to the United States. Of the refugees who received enhanced assessments, 26 (7%) had malaria parasitemia and 128 (38%) had intestinal parasites, while only 2 (2%) had Schistosoma haematobium eggs in the urine. Mass therapy for malaria (a single oral dose of 25 mg/kg of sulfadoxine-pyrimethamine) was given to all Barawan refugees 1-2 days before resettlement. Refugees >2 years of age and nonpregnant women received a single oral dose of 600 mg albendazole for intestinal parasite therapy. If mass therapy had not been provided, upon arrival in the United States an estimated 280 (7%) refugees would have had malaria infections and 1,500 (38%) would have had intestinal parasites. We conclude that enhanced health assessments provided rapid on-site assessment of parasite prevalence and helped decrease morbidity among Barawan refugees, as well as, the risk of imported infections.

Evaluation of the whole blood filariasis ICT test for short-term monitoring after antifilarial treatment.

The immunochromatographic (ICT) filariasis test is a rapid screening tool that will be useful for defining the prevalence and distribution of Wuchereria bancrofti as part of the global program to eliminate lymphatic filariasis. To address questions about its usefulness for monitoring control programs, we used the ICT filariasis test to assess residual antigen levels following antifilarial treatment. Our results demonstrate that antigen levels persist in microfilaria-negative persons for up to three years after treatment. Different strategies for monitoring control programs may have to be considered.

An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis.

This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole + ivermectin or albendazole + diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90,635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n = 1538), ivermectin (9822), DEC (576), albendazole + ivermectin (7470), albendazole + DEC (69,020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80-90% of the 'at risk' populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin + albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.

Proposed panel of diagnostic criteria, including the use of ultrasound, to refine the concept of 'endemic normals' in lymphatic filariasis.

Although living adult Wuchereria bancrofti worms can be detected by ultrasound examination of the scrotal area in approximately 80% of men infected with this filarial parasite, the location of the adult worms in the remaining 20% remains unclear. To determine this, 32 individuals who had W. bancrofti microfilaraemia but no adult worms detectable on ultrasound were treated with diethylcarbarmazine (DEC), either with a single 6 mg/kg dose (n = 13) or with a 12-day course of 6 mg/kg per day (n = 19). They were then monitored with serial physical and ultrasound examinations. Thirteen (41%) subjects developed small, single scrotal nodules 12 h to 7 days after treatment; this rate was unaffected by the dose of DEC. No nodules were detected outside the scrotal area. All 5 men with lymphangiectasia suspected on ultrasound before treatment developed scrotal nodules, compared to 8 (29.6%) of 27 men without ultrasonographic evidence (P = 0.006). Thus, using both ultrasound and 'provocative' treatment with DEC, adult W. bancrofti can be detected in the scrotal area of an estimated 88% of infected men. Because no single diagnostic test for W. bancrofti infection is completely sensitive, a panel of tests, including ultrasound, is proposed to identify with greater accuracy 'endemic normals' for immunological and epidemiological studies.

Assessment of combined ivermectin and albendazole for treatment of intestinal helminth and Wuchereria bancrofti infections in Haitian schoolchildren.

This randomized, placebo-controlled trial investigated the efficacy and nutritional benefit of combining chemotherapeutic treatment for intestinal helminths (albendazole) and lymphatic filariasis (ivermectin). Children were infected with Ascaris (29.2%), Trichuris (42.2%), and hookworm (6.9%), with 54.7% of children having one or more of these parasites. Wuchereria bancrofti microfilaria were found in 13.3% of the children. Children were randomly assigned to treatment with placebo, albendazole, ivermectin, or combined therapy. Combination treatment reduced the prevalence of Trichuris infections significantly more than either drug alone. Combination therapy also significantly reduced the prevalence and density of W. bancrofti microfilaremia compared with placebo or ivermectin alone. Only combination therapy resulted in significantly greater gains in height (hookworm-infected children) or weight (Trichuris-infected children) compared with the placebo group. Combined albendazole and ivermectin was a more efficacious treatment for intestinal helminth and W. bancrofti infections in children and resulted in nutritional benefits not found with either drug alone.

New cryptosporidium genotypes in HIV-infected persons.

Using DNA sequencing and phylogenetic analysis, we identified four distinct Cryptosporidium genotypes in HIV-infected patients: genotype 1 (human), genotype 2 (bovine) Cryptosporidium parvum, a genotype identical to C. felis, and one identical to a Cryptosporidium sp. isolate from a dog. This is the first identification of human infection with the latter two genotypes.

Declining CD4+ T-lymphocyte counts are associated with increased risk of enteric parasitosis and chronic diarrhea: results of a 3-year longitudinal study.

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

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.

Direct assessment in vivo of the efficacy of combined single-dose ivermectin and diethylcarbamazine against adult Wuchereria bancrofti.

When ivermectin and diethylcarbamazine (DEC) are given simultaneously in a single dose to persons with Wuchereria bancrofti infection, the resulting suppression of microfilaraemia is more profound and sustained than when either drug is given alone. To assess whether this effect is a result of enhanced macrofilaricidal efficacy, we used ultrasound to monitor the adult worms in the scrotal area of men with W. bancrofti microfilaraemia. Twenty-one men were treated simultaneously with DEC (6 mg/kg) and either 200 micrograms/kg or 400 micrograms/kg of ivermectin (11 and 10 men, respectively). Ten other men received a single 200 micrograms/kg dose of ivermectin followed 5 d later by a 6 mg/kg dose of DEC (sequential treatment). All men became amicrofilaraemic after treatment and all except one remained so for one year. Cessation of adult worm movement, indicative of death of all the adult worms in a given 'nest', was observed in none of 30 nests in men who received simultaneous treatment and in 3 of the 19 nests (16%) in the men who received sequential treatment (P = 0.05). Scrotal nodules were detected in 5 of 21 men (24%) who received simultaneous treatment and in 8 men (80%) who received sequential treatment (P < 0.01). Thus, co-administration of ivermectin with DEC seems to interfere with the macrofilaricidal action of DEC. These findings have implications both for treatment of the individual patient and for community-based drug distribution programmes designed to interrupt transmission of W. bancrofti.

Ultrasonographic detection of living adult Wuchereria bancrofti using a 3.5-MHz transducer.

Adult Wuchereria bancrofti can be readily detected by ultrasound in the lymphatic vessels of the spermatic cord with a 7.5-MHz transducer, but most ultrasound machines in developing countries are equipped with 3.5-MHz transducers. To assess the potential for ultrasound as a tool for diagnosis and epidemiologic assessment in lymphatic filariasis, we compared the performance of 3.5-MHz and 7.5-MHz transducers in 61 men in Recife, Brazil. All men had three ultrasound examinations using a 3.5 MHz transducer and an examination with a 7.5-MHz probe. Using the 7.5-MHz transducer, adult W. bancrofti were detected in 41 men; 81 adult worm nests were detected. Sixty-four (79%) nests were detected with the 3.5-MHz probe, each on all three examinations. The 3.5-MHz probe correctly identified 35 (85.4%) of 41 men as infected; sensitivity increased with lymphatic vessel diameter. Ultrasonographic examination with a 3.5-MHz transducer is a sensitive method for detection of adult W. bancrofti in men and merits consideration as a tool for rapid epidemiologic assessment.