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Compliance with the mass chemotherapy program for lymphatic filariasis.

OBJECTIVE: To evaluate compliance with the single dose mass chemotherapy program for control of filariasis, and to determine factors influencing compliance in the Gampaha district. DESIGN: A prospective study employing a pre-tested self-administered questionnaire. METHODS: Four groups comprising individuals over one year old with residence in the Gampaha district for over one year were surveyed. Data collection was started two weeks after the mass chemotherapy program. RESULTS: 2300 questionnaires were distributed, 1983 (86.2%) were returned, and 1935 (84.1%) were sufficiently complete for analysis (857 males; mean age 39 years, SD = 19.5). Over 96% had heard of filariasis and the mass chemotherapy program, but only 60.3% of those over 11 years of age were aware of asymptomatic carriage of the parasite. 1289 (66.6%) out of the total sample surveyed (1935 individuals) had obtained the diethylcarbamazine tablets, and 1221 (63.1%) had taken the drug. Of the possible demographic factors that could have influenced compliance only educational level seemed to play an independent significant role, compliance being lowest at both extremes of educational level. The main problem with compliance was obtaining the drug from distribution centres. CONCLUSIONS: Compliance with the mass chemotherapy program to control filariasis needs improvement. Strategies should include a better system for distributing the drug, and altering the content of the publicity material used by the program to target less compliant groups, and improve aspects of knowledge regarding filariasis that seem inadequate at present.

Adult↗

A geostatistical analysis of the geographic distribution of lymphatic filariasis prevalence in southern India.

Gaining a better understanding of the spatial population structure of infectious agents is increasingly recognized as being key to their more effective mapping and to improving knowledge of their overall population dynamics and control. Here, we investigate the spatial structure of bancroftian filariasis distribution using geostatistical methods in an endemic region in Southern India. Analysis of a parasite antigenemia prevalence dataset assembled by sampling 79 villages selected using a World Health Organization (WHO) proposed 25 x 25 km grid sampling procedure in a 225 x 225 km area within this region was compared with that of a corresponding microfilaraemia prevalence dataset assembled by sampling 119 randomly selected villages from a smaller subregion located within the main study area. A major finding from the analysis was that once large-scale spatial trends were removed, the antigenemia data did not show evidence for the existence of any small-scale dependency at the study sampling interval of 25 km. By contrast, analysis of the randomly sampled microfilaraemia data indicated strong spatial contagion in prevalence up to a distance of approximately 6.6 kms, suggesting the likely existence of small spatial patches or foci of transmission in the study area occurring below the sampling scale used for sampling the antigenemia data. While this could indicate differences in parasite spatial population dynamics based on antigenemia versus microfilaraemia data, the result may also suggest that the WHO recommended 25 x 25 km sampling grid for rapid filariasis mapping could have been too coarse a scale to capture and describe the likely local variation in filariasis infection in this endemic location and highlights the need for caution when applying uniform sampling schemes in diverse endemic regions for investigating the spatial pattern of this parasitic infection. The present results, on the other hand, imply that both small-scale spatial processes and large-scale factors may characterize the observed distribution of filariasis in the study region. Our preliminary analysis of a mountain range associated large-scale trend in the antigenemia data suggested that a nonlinear relationship of infection prevalence with elevation might be a factor behind such observed global spatial patterns. We conclude that geostatistic methods can provide a powerful framework for carrying out the empirical investigation and analysis of parasite spatial population structure. This study shows that their successful application, however, will crucially depend on our gaining a more thorough understanding of the appropriate geographic scales at which spatial studies should be carried out.

Adult↗

Frequency, severity, and costs of adverse reactions following mass treatment for lymphatic filariasis using diethylcarbamazine and albendazole in Leogane, Haiti, 2000.

In October 2000, 71,187 persons were treated for lymphatic filariasis using albendazole and diethylcarbamazine (DEC) or DEC alone in Leogane, Haiti. We documented the frequency of adverse reactions, severity and cost of treatment. Adverse reactions were classified as minor, moderate, or severe. Overall, 24% (17,421) of the treated persons reported one or more adverse reactions. There were 15,916 (91%) minor and 1502 (9%) moderate adverse reaction reports. Men outnumbered women 2:1 in reporting moderate problems. Three patients, representing roughly one in 25,000 persons treated, were hospitalized with severe adverse reactions judged to be treatment-associated by physician review. The cost per person treated for adverse reactions was more than twice the cost per person treated for lymphatic filariasis (dollar 1.60 versus dollar 0.71). Severe adverse reactions to lymphatic filariasis treatment using DEC with or without albendazole are uncommon. Minor and moderate reactions are more commonly reported and their management represents a challenge to lymphatic filariasis elimination programs.

Adolescent↗

[Studies on the recurrent attacks of acute adenolymphangitis due to Malayan filariasis].

OBJECTIVE: To explore the role of filarial and bacterial infections in the recurrent attacks of acute adenolymphangitis due to malayan fialriasis. METHODS: 1. To observe the seasonal fluctuation of acute attacks by performing monthly follow-up on patients with history of acute attacks in recent years. 2. To study the relationship between bacterial infection and filarial adenolymphangitis by performing bacteria culture and anti-streptolysin O test. 3. To investigate the variation of acute attacks by controlling filariasis transmission or by treating patients with a history of recurrent acute attacks. RESULTS: 1. The peak of acute attacks in patients coincided with the peak of vector transmission season. 2. Of the 97 cases examined by bacteria culture, 90 cases were negative; of the 255 cases examined by anti-streptolysin O test, the titres in 94.1% (143/152) of the cases with first attack and simple adenolymphangitis were within normal limits, however, the titres in 27.2% (28/103) of the cases complicated with elephantiasis were increased. 3. The acute attack rate of adenolymphangitis per year reduced significantly in cases with first attack and simple adenolymphangitis after effective control of filariasis transmission. 4. There was no evidence of the reduction of acute attacks by treating patients with DEC alone. CONCLUSION: In malayan filariasis endemic areas, the main causes of recurrent attacks of acute adenolymphangitis might be the repeated filarial infections due to the persistence of filariasis transmission.

Acute Disease↗

A polymerase chain reaction assay for the survey of bancroftian filariasis.

A polymerase chain reaction (PCR) assay based on a highly repeated DNA sequence found in Wuchereria bancrofti (SspI repeat) has been modified for the survey of bancroftian filariasis in expatriate workers (Myamese, Karen and Mon) from Myanmar where human filariasis is endemic. The PCR was very sensitive with the ability to detect the presence of as little as 10 pg of parasite DNA. The primers used in this PCR also showed highly specific amplification of parasite DNA without the presence of non-specific and non-target PCR products such as Brugia malayi, Plasmodium falciparum and human DNA. The primers were used to investigate filariasis in four provinces in the central and western Thailand, Samut Songkram, Ratchaburi, Nakhon Pathom and Tak during 1997-2001. Among them, Tak and Ratchaburi are the only endemic areas of bancroftian filariasis. In this field study, 1,299 human blood samples (501 from Samut Songkram, 510 from Ratchaburi, 109 from Nakhon Pathom, and 179 from Tak) were collected and screened by PCR. The result showed that 1, 2, 3, and 33 patients from Samut Songkram, Ratchaburi, Nakhon Pathom, and Tak respectively were infected with W. bancrofti. These numbers were corresponded to the prevalence rate of infection of 0.2, 0.4, 2.8, and 18.5%, respectively. The PCR was able to detect the third-stage infectious larvae (L3) from Culex quinquefasciatus, mosquito vector of the W. bancrofti, that was experimentally fed to infected patient. The PCR screening of each of field mosquito pools from two endemic areas, Ratchaburi and Tak, showed that no L3 of W. bancrofti was detected.

Adolescent↗

Prevalence of bancroftian filariasis on the Thai-Myanmar border.

To achieve the goal of eliminating lymphatic filariasis by the year 2020, close monitoring systems and effective control strategies need to be implemented and the real disease burden needs to be assessed. Bancroftian filariasis is endemic at the Thai-Myanmar border. However, there are only limited data on the prevalence of this disease in Thailand available. We employed microscopic examination, together with ELISA kits to detect W. bancrofti-specific Og4C3 circulating antigen and specific anti-filarial IgG4 antibodies to determine the burden of bancroftian filariasis in an endemic area at the Thai-Myanmar border in Umphang District, Tak province, Thailand. A total of 433 Thai-Karen blood samples were analyzed. The microfilarial rate determined by microscope was 6% and the W. bancrofti-specific Og4C3 antigenemia rate was 22%, while the specific anti-filarial IgG4 antibody rate was 54%. There were statistically significant higher levels of W. bancrofti-specific Og4C3 antigen in the microfilaremic-antigenemic group than in the amicrofilaremic-antigenemic group (unpaired Student's t-test; p < 0.001), similar to the specific anti-filarial IgG4 antibody results (unpaired Student's t-test; p < 0.001). A statistically significant correlation of moderate degree between the presence of W. bancrofti-specific Og4C3 antigen and of specific anti-filarial IgG4 antibody was found in the amicrofilaremic group (r = 0.474, p < 0.001), but not in the microfilaremic group (r = 0.291, p > 0.05). Our study revealed a very high prevalence of bancroftian filariasis in this endemic area and thus emphasized the importance of using highly sensitive and specific diagnostic tools to evaluate the true prevalence of the disease.

Adolescent↗

Antifilarial compounds in the treatment and control of lymphatic filariasis.

Diethylcarbamazine citrate (DEC) has been used for treatment and control of lymphatic filariasis since the 1950s. Although this remarkable drug is still useful and modified strategies in its usage have been developed, a number of newer antifilarial compounds are now available. Numerous field trials evaluating their efficacy in the control of lymphatic filariasis have been conducted. In particular, ivermectin (IVM), albendazole (ALB), and DEC have been tested singly and in combinations and the results of such field studies should be evaluated. While most of the studies were based on efficacy in the clearance of microfilaraemia, a few clinical trials evaluated the adulticidal activity of these compounds. Some antibiotics are effective in killing Wolbachia bacteria symbionts of filarial worms, but their role in the chemotherapy of lymphatic filariasis is still undefined. This review of randomised controlled field studies and randomised controlled clinical trials with these compounds will summarise the findings and give recommendations on their appropriate use for the control and treatment of lymphatic filariasis.

Journal Article↗

Use of Brugia Rapid dipstick and ICT test to map distribution of lymphatic filariasis in the Democratic Republic of Timor-Leste.

The newly-introduced Brugia Rapid dipstick for filarial antibodies and ICT filarial antigen card test were used to confirm historical data on the distribution of lymphatic filariasis in the Republic of Timor-Leste. Twelve out of thirteen districts were confirmed as being endemic. Brugian filariasis predominates, with an average prevalence of 11.6%. The average prevalence of Bancroftian filariasis was 1.1%. The study demonstrated that the Brugia Rapid test can provide useful information about the distribution of Brugian filariasis in circumstances where it is difficult or impossible to obtain night blood samples for microfilariae.

Adult↗

Lack of IgG4 antibody response to carbohydrate antigens in patients with lymphatic filariasis.

It has been suggested that humans are genetically restricted from making IgG4 antibody responses to carbohydrate antigens. To test this hypothesis we examined sera from 35 patients with bancroftian filariasis (an infection known to induce very high levels of IgG4 antibodies to the parasite and known to be associated with repeated streptococcal infections) as well as from 15 normal individuals for their IgG and IgG subclass responses to streptococcal protein [streptolysin-O (SO), deoxyribonuclease B (DB)] and carbohydrate [group A carbohydrate (GAC)] antigens. Levels of IgG antibodies to all three antigens were found to be significantly higher in the filariasis patients compared to normals (P less than 0.01), and the subclass composition of these antibodies proved heterogenous. Although responses to all three antigens included IgG1, IgG2 and IgG3 antibodies and although IgG4 responses to the proteins SO and DB were significantly higher in the filariasis patients than in normals (P less than 0.001), more importantly there were no detectable anti-GAC IgG4 antibodies in either study group. These observations, coupled with our earlier finding of the absence of IgG4 responses to phosphocholine (PC) in patients with lymphatic filariasis, suggest that even the chronic antigenic stimulation of filarial helminth infection, which leads to very prominent IgG4 responses to protein antigens, cannot overcome the genetic restriction in humans for making IgG4 antibodies to carbohydrate antigens, whether of parasite or non-parasite origin.

Adolescent↗

The use of monoclonal antibodies in the detection of circulating antigens in Malayan filariasis.

Wuchereria bancrofti, Brugia malayi and Brugia timori are the causative agents of lymphatic filariasis in Indonesia but in some endemic areas, B malayi is more commonly found. Diagnosis of filariasis is normally based on clinical, parasitological and immunological examinations but those methods have limitations. The discovery of monoclonal antibodies is expected to provide a new dimension to the efforts in the development of specific and sensitive immunological tests for the various stages of filariasis infection. This preliminary report, using monoclonal antibodies and dot-blot assay in human lymphatic filariasis showed that 75% of sera from microfilaremic patients with clinical signs, 40% of sera from amicrofilaraemic patients with clinical signs, 88.8% of sera from microfilaremic patients without clinical signs and 19.6% of sera from amicrofilaremic patients without clinical signs have circulating antigens.

Animals↗

Detection of circulating antigens and parasite specific antibodies in filariasis.

In Peninsular Malaysia, only Wuchereria bancrofti and Brugia malayi are reported to cause human filariasis. Brugia pahangi infects many of the same animal hosts as the zoonotically transmitted subperiodic B. malayi. There is a well-recognized need for improved diagnostic techniques for lymphatic filariasis. Parasite antigen detection is a promising new approach, and it will probably prove to be more sensitive and specific than clinical, microscopic and antibody-based serological methods. We recently generated monoclonal antibodies (MAb XC3) from in vitro culture products of adult B. pahangi (B.p. IVP). Filarial antigenemia was quantitated in various hosts including the sera from 6 Malaysian Aborigines with acute lymphatic filariasis. In hosts infected with brugian filariasis and dirofilariasis, antigenemia was scored ranging from 90 ng/ml to 960 ng/ml. None of the control animal and human sera had antigenemia above 90 ng/ml. In addition, MAb XC3 and B.p. IVP were applied in several seroepidemiological surveys among household cats in Kuala Selangor in order to correlate information gathered for future studies of possible cases of human infection. Out of the 81 cats surveyed, 10 (12.35%) and 5 (6.17%) were parasitologically positive for B. pahangi and B. malayi, respectively. However, 21 (25.92%) were antigenemia positive when serologically investigated with MAb XC3. Antifilarial antibodies to B.p. IVP by direct ELISA showed very high cross-reactivity with non-filarial gut worm infections. 16 (19.75%) cats had reciprocal titers ranging from 320 to 2,560. Only 1 (1.23%) cat from this group was antigenemic.

Animals↗

Lymphatic filariasis in immigrants from developing countries.

Lymphatic filariasis is caused by a nematodal infection with Wuchereria or Brugia species. It occurs in endemic areas throughout the tropical parts of the world, with a predilection for developing countries where poor socioeconomic conditions are favorable for mosquito vector breeding. Between 1983 and 1993, more than 3 million immigrants to the United States reported their native residence to be a country with areas of endemic filariasis. These immigrants comprise approximately 1 percent of the U.S. population. Thus, it is likely that patients with lymphatic filariasis present within the American health care system and may be overlooked. The primary care physician should be familiar with the clinical presentation, diagnostic procedures and treatment of lymphatic filariasis.

Developing Countries↗

Pilot experiments in the control of bancroftian filariasis in Japan and Ryukyu.

In this paper the author reviews the literature on the distribution and epidemiology of filariasis in Japan and discusses the extensive programme of research on the disease that is at present being carried out there. As part of this programme, comparative pilot experiments were started in 1958, in several areas of differing filariasis endemicity, with the object of determining the most effective and economical methods for preventing and treating the disease. The results so far obtained from these pilot experiments, which are still in progress, suggest that a close approach to the eradication of filariasis from the endemic areas could be reached through the administration of diethylcarbamazine at a suitable dosage to microfilaria carriers and the simultaneous application of control measures against the vector mosquitos.

Animals↗

Albendazole for lymphatic filariasis.

BACKGROUND: Mass treatment with albendazole, co-administered with another antifilarial drug, is being promoted as part of a global programme to eliminate lymphatic filariasis. OBJECTIVES: To assess the effects of albendazole on patients or populations with filarial infection, and on morbidity in patients with filarial infection; and to assess the frequency of adverse events for albendazole both given singly or in combination with another antifilarial drug (diethylcarbamazine or ivermectin). SEARCH STRATEGY: We searched the Cochrane Infectious Disease Group's trial register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2003), MEDLINE (September 2003), EMBASE (September 2003), LILACS (September 2003); and checked the reference lists and contacted experts, international organizations, and a pharmaceutical company. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials of albendazole singly or in combination with anti-filarial drugs in people or populations with lymphatic filariasis. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility and trial methodological quality. We calculated relative risks (RR) with 95% confidence intervals (CI) for binary outcomes, and where appropriate, combined them in a meta-analysis using the fixed effect model or random effects model. MAIN RESULTS: Four small studies met the inclusion criteria (a total of 2473 children and adults, of whom 536 had detectable microfilariae). No effect of albendazole on microfilaraemia was demonstrated in two studies (placebo controlled, RR 0.97, 95%CI 0.87 to 1.09, n = 195). When compared to ivermectin, albendazole performed worse (RR 0.84, 95% CI 0.72 to 0.98, 2 studies of patients initially microfilariae positive, n = 198). When compared to diethylcarbamazine, no statistically significant difference was detected, but numbers were small (n = 56). Two studies compared albendazole plus ivermectin to ivermectin alone on the presence of microfilaraemia. Results were mixed: one study showed the combination to be more effective (RR 0.27, 95% CI 0.11 to 0.70, n = 52), but the other did not demonstrate a statistically significant difference (RR 1.04, 95% CI 0.87 to 1.25, n = 145). A further study compared albendazole plus diethylcarbamazine to diethylcarbamazine alone and did not demonstrate a difference on microfilaraemia prevalence (RR 1.57, 95% CI 0.44 to 5.60, n=35). No study examined the effects of the drugs on adult worms. REVIEWER'S CONCLUSIONS: There is insufficient reliable research to confirm or refute whether albendazole alone, or co-administered with diethylcarbamazine or ivermectin, has an effect on lymphatic filariasis.

Albendazole↗

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.

Albendazole↗

Urine lipids in patients with a history of filariasis.

The presence of lipids in postprandial urine was assessed in 116 patients with a history of filariasis and 70 normal individuals using a biochemical autoanalyzer. Urinary triglycerides (TGs) ranging from 10 to 1955 mg/dl were detected in 13 individuals with a history of chyluria, including 3 with TG levels ranging from 233 to 1955 mg/dl and cholesterol levels of 6-35 mg/dl. Three patients who had a filarial history but without chyluria were also found to have urinary TGs (13-15 mg/dl) without detectable cholesterol. Neither TGs nor cholesterol were detected in the urine of normal individuals. Fluctuations in postprandial urine lipid contents were measured by time course determinations of urinary TG and cholesterol in 17 patients with filariasis and a history of chyluria, 16 patients with filariasis and hydrocele and 16 normal individuals. The level of urine lipid excretion was found to increase within 1-4 h postprandially, with urinary TG levels ranging between 7.8 and 1284 mg/h in eight patients and urinary cholesterol levels between 1.2 and 138 mg/h in seven patients with a history of chyluria. To evaluate the origin of the urine lipids in hematochyluria, fish oil containing 360 mg eicosapentaenoic acid (EPA) and 240 mg docosahexaenoic acid (DHA) was prescribed to a patient with hematochyluria. The excretion of EPA and DHA in urine was increased postprandially in the patient, similar to the elevation of urinary TG and cholesterol. The profile of fatty acids from urine samples showed it was of dietary origin. Our results suggest that postprandial urine lipids, especially TG, might be used as markers for the clinical evaluation of chyluria.

Adult↗

Application of a biochemical key to study transmission of malaria and Bancroftian filariasis in sibling species of the Anopheles gambiae complex in north-eastern Tanzania.

A biochemical key was applied in order to study transmission of malaria and Bancroftian filariasis in Anopheles gambiae sensu stricto, An. arabiensis and An. merus in different localities in north-eastern Tanzania. The technique was found to be a useful additional taxonomic tool for field entomologists. Significant differences between species in the rate of infection with Bancroftian filariasis were obtained between An. gambiae s.s. and An. funestus (P less than 0.005) and between An. funestus and An. arabiensis (P less than 0.0001). There were also significant differences between most of the investigated localities in the rate of filarial infection. However, there were no significant differences between the three species or between localities with respect to malaria sporozoite rates. Possible reasons for the observed variation between species and localities with respect to vectorial activity for Bancroftian filariasis are discussed.

Alcohol Oxidoreductases↗

Immunosuppression in bancroftian filariasis.

Immunological function in Filipino patients with bancroftian filariasis, manifested as either asymptomatic microfilaraemia or chronic obstructive disease, was compared with that found in healthy control subjects living in the same area. As a group, patients with filariasis had raised serum IgG levels, impairment of antibody responses to tetanus and typhoid vaccines, and suppression of delayed hypersensitivity skin reactions to heterologous antigens. This immunosuppression in filariasis may result from antigenic competition and may contribute to the development of secondary infections.

Antibody Formation↗