Biomedical subjects

G J Weil

Publications and source records attributed to G J Weil.

79 records · Page 5Linked to original sources

PubMedDate not supplied

Efficient assessment of filariasis endemicity by screening for filarial antigenaemia in a sentinel population.

We have previously reported that a monoclonal antibody-based antigen detection assay (AD12) is sensitive and specific for Bancroftian filariasis in Egypt. The purpose of the present study was to demonstrate the use of this assay in a sentinel population as a means of efficiently screening for filariasis endemicity. Antigen testing was performed with finger-prick blood collected during the day from 743 schoolchildren (ages 11-16 years). The school draws students from 5 villages in Qalubia Governorate, 35 km north-east of Cairo, Egypt. The prevalence of filarial antigenaemia in the school was 17.2%. Antigenaemia rates in children from the 5 villages were 29, 20, 18, 17, and 10% (non-uniformity significant by chi 2 analysis, P = 0.02). These data agree with Ministry of Health rankings of relative endemicity for these villages based on prior night blood surveys. The village with the highest antigen prevalence in children was surveyed one year before the present study. Prevalence rates of antigenaemia and microfilaraemia at that time for a different sample of children aged 11-16 years were 33% and 22%, respectively. We conclude that antigen detection in schoolchildren of this age group is an efficient means of assessing filariasis endemicity in Egypt.

Adolescent↗

PubMedDate not supplied

Long-term efficacy of single-dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations.

Adolescent↗

PubMedDate not supplied

Detection of Wuchereria bancrofti in mosquitoes by the polymerase chain reaction: a potentially useful tool for large-scale control programmes.

Focally endemic bancroftian filariasis is targeted for elimination in the Nile delta of Egypt. Improved methods are needed for identifying endemic villages to be included in the control programme and for monitoring its success. We have evaluated the performance of a polymerase chain reaction (PCR) assay in estimating Wuchereria bancrofti infection in pools of Culex pipiens (1-25 females) from 2 adjacent villages with high (El Qolzom, 10.8%) and low (Kafr Shorafa, 2.1%) prevalence rates of human filariasis. This assay detects a repeated sequence in W. bancrofti deoxyribonucleic acid (DNA). Mosquitoes resting within houses were captured by aspiration and pooled by house. Houses were classified as positive or negative for human filarial infection based on night blood examinations of residents. The assay detected parasite DNA in mosquitoes from 60% of 25 infected houses and 24% of 25 uninfected houses. PCR processing of mosquitoes caught within houses of unknown filariasis infection status (44 in El Qolzom, 37 in Kafr Shorafa) identified 31.8% and 8.1% of houses, respectively, as containing infected mosquitoes. These results support the validity of the PCR assay for evaluating filarial prevalence in different villages. C. pipiens collected outdoors in dry ice-baited traps and tested by PCR (266 in Qolzom, 82 in Kafr Shorafa) did not contain parasite DNA. Pools of female mosquitoes (296 in Qolzom, 240 in Kafr Shorafa) captured in oviposition traps were also negative. We concluded that the PCR based assay is a powerful epidemiological tool that can be used for evaluating W. bancrofti infection in villages in the Nile delta and for monitoring the application of control programmes in filariasis endemic areas.

Animals↗

PubMedDate not supplied

Prolonged clearance of microfilaraemia in patients with bancroftian filariasis after multiple high doses of ivermectin or diethylcarbamazine.

In a double-blind trial on 37 asymptomatic microfilaraemic subjects (minimum 400 microfilariae [mf] per mL) with Wuchereria bancrofti infection, the safety, tolerability and macrofilaricidal efficacy of 12 fortnightly doses of ivermectin, 400 micrograms/kg (ivermectin group), was compared with 12 fortnightly doses of diethylcarbamazine (DEC), 10 mg/kg (DEC group), over a period of 129 weeks after treatment. A control group (LDIC group) was treated with low dose ivermectin to clear microfilaraemia, for ethical reasons. Both ivermectin and DEC in high multiple doses were well tolerated and clinically safe. Macrofilaricidal efficacy was assessed by prolonged clearance of microfilaraemia, appearance of local lesions, and reduction of circulating W. bancrofti adult antigen detected by an antigen capture enzyme-linked immunoassay based on the monoclonal antibody AD12. Mf counts fell more rapidly after ivermectin than after DEC, but low residual mf levels were equivalent in these groups after week 4. Conversely, filarial antigen levels fell more rapidly after DEC than after ivermectin, but low residual antigen levels in these groups were statistically equivalent at all times beyond 12 weeks. Mild, self-limited systemic reactions to therapy were observed in all 3 treatment groups. Local reactions, such as development of scrotal nodules, were observed in several subjects in the DEC and ivermectin groups. These results suggested that high dose ivermectin and DEC both had significant macrofilaricidal activity against W. bancrofti, but neither of these intensive therapeutic regimens consistently produced complete cures. Thus, new drugs or dosing schedules are needed to achieve the goal of killing all filarial parasites in the majority of patients.

Animals↗

PubMedDate not supplied

A polymerase chain reaction-based assay for detection of Wuchereria bancrofti in human blood and Culex pipiens.

Human blood samples and indoor-resting Culex pipiens were collected in 33 randomly selected houses from different sectors of a village in the Nile Delta of Egypt which was endemic for Wuchereria bancrofti. Blood was also collected from subjects with no history of living in filarial endemic areas. Human blood samples were divided and assessed by both membrane filtration and polymerase chain reaction (PCR). Similarly, mosquito samples were assessed by both dissection and PCR. Blood pools representing each household were tested by PCR. If a pool gave a positive result, then individual blood specimens were also tested by PCR. Of the 33 houses tested, both membrane filtration and blood pools assayed by PCR identified 14 (42.4%) 'infected houses'. PCR detected parasite deoxyribonucleic acid (DNA) in blood pools from an additional 3 households that gave negative results by membrane filtration. Of 178 endemic blood samples tested by membrane filtration, 22 (12.3%) had microfilariae and all were individually positive by PCR. Although microfilaria counts were lower in blood collected during the day than in night-collected blood, the PCR results were consistent, regardless of time of collection. All non-endemic blood samples were negative by PCR. Among the 33 houses rested, mosquito pools assayed by PCR identified 17 (51.5%) as 'infected households'. Of these, 8 houses (47%) contained at least one microfilaraemic resident. One 'infected household' was identified by mosquito dissection. We concluded that PCR is a powerful epidemiological tool for screening villages for the prevalence of W. bancrofti. PCR detection of W. bancrofti DNA in blood-fed mosquitoes could be used initially to locate endemic areas with transmission of bancroftian filariasis. PCR detection of W. bancrofti DNA in blood collected during the day could then be used to assess W. bancrofti infection rates.

Animals↗

PubMedDate not supplied

Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.

Adolescent↗

PubMedDate not supplied

Paper chromatography hybridization: a rapid method for detection of Onchocerca volvulus DNA amplified by PCR.

Prior studies have shown that Onchocerca volvulus DNA can be detected in skin snips and in black flies after polymerase chain reaction (PCR) with primers specific for repeated "O-150" DNA sequences. We have adapted a paper chromatography hybridization assay (PCHA) to detect amplified O-150 DNA and compared this method to two established methods, namely agarose gel electrophoresis (AGE) and hybridization enzyme-linked immunosorbent assay (ELISA). The minimum amounts of purified O-150 DNA detected by PCHA, AGE, and ELISA were 5, 10, and 2 ng, respectively. The three methods had similar estimated sensitivities for detecting O. volvulus DNA amplified from skin snips from African subjects with onchocerciasis (88%, 84%, and 91%, respectively). No false positive results were observed with skin snips from uninfected control subjects. The paper chromatography hybridization assay detects PCR products in 30 minutes without electricity or special equipment. This technology brings DNA detection a step closer to widespread use in field settings.

Animals↗