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↗

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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.

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Second case of ocular parastrongyliasis from Sri Lanka.

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Adult↗

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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↗

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Accuracy of the potential acuity meter in predicting the visual outcome in cases of cataract associated with macular degeneration.

In order to ascertain the accuracy and specificity of the Potential Acuity Meter (PAM) in the preoperative evaluation of likely postoperative visual acuity in cases of cataract associated with age-related macular degeneration (ARMD), we studied the results in 130 cases, 54 of whom had preoperatively proved or suspected ARMD associated with a cataract. All of them were operated with extracapsular extraction and implantation of an intraocular lens (IOL), and final visual acuity was established when all the patients were visited three months postoperatively. A positive linear correlation was found between normal ocular fundus and PAM prediction (r = 0.77), and in the group of patients with preoperatively confirmed ARMD (r = 0.77). No difference was found between the preoperative PAM estimation and the final visual acuity in both groups. The PAM prediction was less accurate in cases with doubtful preoperative ARMD (r = 0.58) for whom showed PAM the highest score of false negatives in favor of the final visual acuity. Our results show that PAM is a reliable clinical technique for the prediction of visual results after cataract surgery in cases with preoperatively proved or doubtful macular pathology. To the best of our knowledge, this is the first report regarding the sensitivity and specificity of the PAM in diseased or suspicious maculas associated with cataract.

Aged↗

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Pathogenicity of turkey coronavirus in turkeys and chickens.

We designed this study to compare the replication potential of turkey coronavirus (TCV) and its effect in chickens and turkeys and to study the effect of singleand combined infection of turkey poults with TCV and astrovirus. We studied the pathogenicity of TCV in experimentally inoculated turkey poults and chickens by observing the dinical signs and gross lesions. Two trials were conducted with 1-day-old and 4-wk-old specific-pathogen-free turkey poults and chickens. One-day-old turkey poults developed diarrhea at 48 hr postinoculation. Poults euthanatized at 3, 5, and 7 days postinoculation had flaccid, pale, and thin-walled intestines with watery contents. The 4-wk-old turkeys had no clinical signs or gross lesions. One-day-old and 4-wk-old chicks developed no clinical signs or gross lesions although the TCV was detected in gut contents of the birds throughout the experimental period (14 days). In another experiment, mean plasma D-xylose concentrations in 3-day-old turkey poults inoculated with TCV, turkey astrovirus, or a combination of both viruses were significantly lower than in the uninoculated controls.

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Correction of hyperopia induced by photorefractive keratectomy using non-contact Ho:YAG laser thermal keratoplasty.

PURPOSE: To evaluate the safety and effectiveness of non-contact holmium:YAG laser thermal keratoplasty in correcting hyperopia induced by photorefractive keratectomy (PRK). METHODS: Non-contact holmium:YAG laser thermal keratoplasty was applied to 14 eyes with significant hyperopia induced by PRK. The mean spherical equivalent refraction before holmium:YAG laser thermal keratoplasty was +4.20 +/- 1.80 diopters (D) (range, +1.75 to +6.25 D). The results were evaluated 12 months after holmium:YAG laser thermal keratoplasty. RESULTS: No sight-threatening complications occurred. Recovery of spectacle-corrected visual acuity took from 2 to 6 weeks. The immediate significant myopic shift that developed in all eyes gradually receded over 6 to 8 weeks. All eyes were relatively stable after 9 months. At 12 months, there was no statistically significant difference (p < .005) between the mean preoperative spectacle-corrected visual acuity (0.71 +/- 0.12) and the mean postoperative uncorrected visual acuity (0.65 +/- 0.28). At 12 months there was a mean increase of 4.60 +/- 1.20 D in central keratometric power. Total regression did not occur in any eye. CONCLUSIONS: Non-contact holmium:YAG laser thermal keratoplasty offers a safe and effective alternative to correct PRK-induced hyperopia.

Adult↗

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Correction of hyperopia with non-contact Ho:YAG laser thermal keratoplasty.

PURPOSE: To assess the potential of non-contact holmium:YAG laser thermal keratoplasty to safely and effectively correct hyperopia up to +5.00 diopters (D). METHODS: Non-contact laser thermal keratoplasty with a holmium:YAG laser using energies ranging from 215 to 255 mJ with 6, 7, and 8-min ablation zone diameters, was applied to 57 sighted eyes of 42 hyperopic patients in a controlled study. All patients were followed for 15 months after surgery. RESULTS: Preoperative spectacle-corrected visual acuity returned to baseline levels from 2 to 6 weeks after treatment. Regression of effect was evident in all eyes, and after 15 months was total in 18 eyes (31.5%). The mean cycloplegic refraction before surgery was +3.80 +/- 0.22 D (range, +1.50 to +5.00 D); after surgery, it was +1.40 +/- 0.12 at 3 months, +1.69 +/- 0.19 D at 6 to 8 months, and +1.73 +/- 0.16 D at 15 months. At the end of the study, 41 eyes (71.9%) had an uncorrected visual acuity of 20/40 or better. Thirty-two eyes (58.8%) were within +/- 1.00 D of the intended refraction. Patient age and central pachymetric values were significantly correlated with regression (ANOVA, (p less than .005). CONCLUSIONS: Regression of initial effect can be large with non-contact holmium:YAG laser thermal keratoplasty. We think the technique works best up to +3.00 D in older individuals with central corneal thickness less than 525 microns. Algorithms to improve the final results should include an initial calculated overcorrection adjusted on variables that influence regression such as patient age and corneal thickness.

Adolescent↗

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Viral agents associated with poult enteritis and mortality syndrome: the role of a small round virus and a turkey coronavirus.

Intestinal samples from turkey poults affected with poult enteritis and mortality syndrome (PEMS) were examined for viruses by immune electron microscopy and double-stranded RNA virus genome electropherotyping. Turkey coronavirus (TCV), avian rotaviruses, reovirus, and a yet undefined small round virus (SRV) were detected. The SRV and TCV were isolated and propagated in turkey embryos. Challenge of specific-pathogen-free turkey poults with SRV, TCV, or both resulted in mortality and clinical responses similar to those of natural PEMS. Our experiments indicate that SRV and TCV are possibly important agents in the etiology of PEMS and the combination of these infections might result in outbreaks with high mortality. The severity of clinical signs and mortality of PEMS are postulated to be partly related to the virus agents involved in individual outbreaks.

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Experimental bovine coronavirus in turkey poults and young chickens.

The DB2 calf strain of bovine coronavirus (BCV) was used to inoculate 1-day-old specific-pathogen-free (SPF) turkey poults in three trials. In all trials, the birds developed clinical signs of enteritis at 48-72 hr postinoculation. Birds euthanatized at 3, 5, and 7 days postinoculation (DPI) had flaccid, pale intestines with watery contents, and the ceca were markedly enlarged with frothy contents. Coronavirus particles were detected by immune electron microscopy with BCV antibodies from the intestinal contents of birds killed at 3, 5, 7, and 12 DPI. Body weights of inoculated poults killed at 3, 5, and 7 DPI were significantly reduced as compared with controls. Hemagglutinating antibodies were detected in sera of convalescent birds at 12 DPI. However, experimental inoculation of 1-day-old SPF chicks in two trials with the same virus resulted in no clinical signs or macroscopic or microscopic lesions. No coronaviruses were detected from intestinal contents, and there were no significant differences in body weights of inoculated and noninoculated control chicks.

Animals↗

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Antigenic and genomic relatedness of turkey-origin coronaviruses, bovine coronaviruses, and infectious bronchitis virus of chickens.

In earlier studies in our laboratory, we found that bovine coronavirus (BCV) was pathogenic for 1-day-old turkey poults. This finding prompted us to study the antigenic and genomic relatedness of turkey origin coronaviruses (TOCVs) to BCV. A one-step reverse transcription (RT)-polymerase chain reaction (PCR) targeting a 730-base pair fragment of the nucleocapsid (N) gene of BCV and a nested PCR targeting a 407-base pair fragment of the N gene were used in an attempt to detect TOCV from North Carolina, Indiana, and a prototype turkey coronavirus (TCV) obtained from the American Type Culture Collection. Both the one-step RT-PCR and the nested PCR amplified cell culture-passaged isolates of calf diarrhea strains of BCV but none of the 15 tested TOCVs or transmissible gastroenteritis coronavirus of swine. TOCVs also did not cross-react in a BCV antigen-capture (AC) enzyme-linked immunosorbent assay (ELISA) system with monoclonal antibodies (MAbs) against N, spike glycoprotein, and hemagglutinin esterase glycoprotein proteins of BCV as coating antibodies. The same TOCVs could be detected with primers designed from the genome of infectious bronchitis virus (IBV) of chickens. These primers amplified a 1082-base pair region spanning portions of the membrane glycoprotein (M) and N protein genes of IBV and TCV. The TOCVs also cross-reacted in an AC-ELISA with MAbs against the M and subunit 2 of spike glycoprotein of IBV.

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