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Biomedical subjects

B Muñoz

Publications and source records attributed to B Muñoz.

At least 73 records · Page 4Linked to original sources

A comparison of 6-, 12-, and 24-monthly dosing with ivermectin for treatment of onchocerciasis.

This study was designed to examine the optimal dose and interval of administration of ivermectin, the now-accepted drug of choice for onchocerciasis. Two hundred Liberians with Onchocerca volvulus infection received 100, 150, or 200 micrograms/kg ivermectin or placebo and were followed for 36 months. The reaction after the second dose of ivermectin was significantly less than after the initial dose, although it was still significant in the 200-micrograms/kg group. The skin microfilaria counts in the group treated 6-monthly with 150 micrograms/kg was significantly less than in the group treated yearly (12 and 24 months after initial therapy). Prevalence of microfilariae in the anterior chamber and punctate corneal opacities decreased progressively in all groups over 3 years. There appears to be a slight advantage, in terms of antiparasitic effect over the first 2 years, of therapy given 6-monthly compared with yearly.

Adolescent↗

Community-based treatment of onchocerciasis with ivermectin: safety, efficacy, and acceptability of yearly treatment.

The safety, acceptability, and efficacy of ivermectin during community-based mass treatment of onchocerciasis was assessed. Ivermectin was distributed three times, 1 year apart, to the population of a rubber plantation (14,000 people) in Liberia where greater than 80% of adults have Onchocerca volvulus infection. In a sample of adults, the microfilarial density was reduced by 84% after 2 years of treatment. Acceptance was as high as 98% during the third year. Adverse reactions occurred in 6-13 in 1000 people after first treatment and in only 3-4 in 1000 receiving their second or third annual dose of ivermectin; severe adverse reactions were not seen. These data show that community-based treatment with ivermectin is safe, well accepted, and effective in reducing microfilarial loads and suggest that ivermectin is the first practical drug suitable for mass treatment campaigns to control human onchocerciasis.

Adolescent↗

Epidemiology of ocular chlamydial infection in a trachoma-hyperendemic area.

The epidemiology of ocular chlamydial infection in a trachoma-hyperendemic area of Tanzania was investigated. Specimens for chlamydial isolation cultures and direct fluorescent antibody cytology were collected from 1085 children aged 1-7 years. Other data included examinations for signs of clinical trachoma and the collection of household data on risk factors. A total of 33% of children had a positive laboratory test for Chlamydia species. The most important factors for predicting chlamydial infection were the presence of a sibling with laboratory evidence of infection, increased number of flies around the house, a household that herded cattle, and practice of a local religion. Younger children and girls were at no increased risk for a positive laboratory test, although these subgroups have more clinical disease. The data are compatible with a model of less frequent episodes of reinfection as children become older.

Age Factors↗

The incidence and progression of lens opacities.

Selected clinic patients were entered into a prospective longitudinal study to assess the incidence and rate of progression of lens opacities. Ninety-seven patients aged 15 to 88 years (median 63 years) were followed for two to 35 months (median 16 months). Lenses were photographed on a photo slit lamp and retroillumination cataract camera. Photographs were graded independently and then assessed in a side-by-side comparison. The incidence rate of cortical opacity was found to be 4% and for nuclear cataract between 11% and 20%. The rates of progression were 18% to 21% for cortical opacity, 14% to 16% for nuclear opacity, and 39% to 40% for posterior subcapsular opacities. These data suggest that these simple photographic means are sufficiently sensitive to detect changes in lens clarity.

Adolescent↗

Longitudinal study of the microbiology of endemic trachoma.

A longitudinal study of trachoma in 100 members of nine Tanzanian families was conducted to assess the sources of variation in the laboratory identification of trachoma and the changes that might occur over time. Multiple conjunctival swabs were collected every 3 months for 1 year and examined by direct fluorescent-antibody cytology (DFA), enzyme immunoassay, or microimmunofluorescence serology for tear antichlamydial antibodies. DFA specimens collected 5 min apart had a discordance rate of 10% and this is attributable to sampling variation. DFA specimens collected 2 days or more apart show a 25% discordance rate. This suggests a biologic variation in shedding in addition to sampling variation. Good correlation existed between the DFA and the enzyme immunoassay. Tear serology was quite specific in predicting the presence of clinical disease and correlated with the other two antigen detection tests, although it does not seem to offer any practical advantages. These studies indicate that there is considerable variation in the shedding of chlamydia by people living in trachoma-endemic areas.

Adolescent↗

The embryogenesis of Onchocerca volvulus over the first year after a single dose of ivermectin.

Adult Onchocerca volvulus, extracted from nodules before, and at intervals of two weeks to 12 months after, a single 150 micrograms/kg dose of ivermectin, were examined longitudinally and by sequential transverse sections. The mean number of male worms per nodule fell, and the proportion of nodules with no male worm rose, within two weeks of ivermectin and remained so for 12 months. In female worms, at intervals after ivermectin, the percentages of the length of the lower genital tracts occupied by embryos at each stage of development, or by degenerating ova, embryos and microfilariae (mfs), were recorded: (a) in un(re-)inseminated worms whose original embryogenesis was continuing and in those in which it was completed; and (b) in worms, reinseminated post-ivermectin, in which a new embryogenesis had begun. The results indicated that: (a) the time needed for the zygotes of O. volvulus to develop to mfs is 8-12 weeks; (b) nearly 40 percent of females had not resumed mf production by 12 months after treatment; (c) many intrauterine mfs had not degenerated within the first two weeks of ivermectin; (d) some of the last embryos to mature to mfs did not degenerate but accumulated temporarily in the anterior uteri 8-16 weeks after ivermectin.

Animals↗

[Intravascular coagulation in acute promyelocytic leukemia: analysis of coagulation and fibrinolysis parameters].

Eight pts with acute myeloid leukemia were studied to assess coagulation and fibrinolysis disturbances as a cause of hemorrhages associated to thrombopenia. Fibrinogen, products of fibrinogen to fibrin degradation, D-dimer, antithrombin III, protein C, plasminogen and alpha-2 antiplasmin determinations were performed at admission, during and after chemotherapy. All pts were on heparin during induction chemotherapy. Coagulation activation, which increased with the onset of chemotherapy (increases in D-dimer) and a decreasing trend at the end of the antileukemic therapy (normalization of fibrinogen levels) was observed. During the whole observation period alpha-2 antiplasmin levels remained very low. No significant changes were observed in antithrombin III or protein C levels. In conclusion, disseminated intravascular coagulation with associated thrombopenia is an important event in acute leukemia and an increased fibrinolytic activity due to low alpha-2 antiplasmin levels may take part in the genesis of hemorrhage. These data suggest that both heparin administration and the use of antifibrinolytic drugs may have a therapeutic effect.

Adolescent↗

Viability of adult Onchocerca volvulus after six 2-weekly doses of ivermectin.

Ivermectin is a safe, effective microfilaricide and microfilarial suppressant for Onchocerca volvulus; but in single doses of 100-200 micrograms/kg body weight it has no macrofilaricidal action. The present trial aimed to determine whether 6 doses of 100 micrograms/kg ivermectin, given at 2-week intervals, would kill the adult worms. Eighty-two nodules from 28 otherwise healthy adult male Liberian patients treated with this ivermectin schedule, and 102 nodules from a similar group of 25 control patients, were removed four months after the last dose of ivermectin. They were coded and assessed in a masked fashion either by routine histology or by examination of whole worms extracted from the nodules after collagenase digestion. The drug had no visible effect on adult male worms. More adult female worms were assessed as moribund or dead in the ivermectin-treated group than in the control group (for the collagenase digests P = 0.09; for the histological assessment P = 0.47). The data suggest that repeated dosage with ivermectin may lead to a slow attrition of some female worms and this possibility should be investigated in patients receiving regular doses every 3, 6 or 12 months as part of onchocerciasis control programmes.

Adult↗

Increase in mortality associated with blindness in rural Africa.

Forty-seven persons were identified with visual impairment (visual acuity of 6/60 or less in their better eye) during a population-based survey in 1986 of eye disease in three villages in central Tanzania. Four years later, 41 (87%) of them and 70 (82%) of 84 age-, sex-, and village-matched controls with normal functional vision (visual acuity 6/18 or better in the better eye) were traced, and those who were still alive were re-examined. The remainder were reported to be alive but had moved to other villages. Deaths among those aged 40-79 years amounted to 10 among the 37 visually impaired and 7 among the 70 sighted controls. This gave an excess mortality rate (odds ratio) of 3.33 times (1.03-11.04, 95% Cl) among the visually impaired compared to their age-matched controls. The excess mortality rate for visually impaired women was 4.11 (0.72-25.5) and 2.71 (0.50-15.2) for visually impaired men. Nine out of 25 with vision of less than 3/60 in their better eye had died. The higher mortality rate among the visually impaired suggests that, in this environment, blindness is not only associated with considerable disability but is also associated with a shortened life expectancy, especially for women.

Adolescent↗

A comparison of two photographic systems for grading cataract.

Two different systems for classifying lens opacities were compared: the Lens Opacity Classification System version II (LOCS II) and the system developed at Johns Hopkins University. Using the two systems, slit-lamp photographs of the nucleus and retroillumination lens photographs of 100 eyes were graded. Each photograph was graded independently by three trained observers, and the time taken to grade the photographs was similar. Each system uses photographs to define the severity of nuclear opacity and nuclear color, and each showed good interobserver agreement (kappa statistic, greater than 0.6). The method of classifying cortical and posterior subcapsular opacity varied, and although interobserver agreement was acceptable in each system, it was somewhat higher with the Hopkins system. Because different standards and definitions are used to define severity with each system, there was some variation in the classification of individual photographs and corresponding differences in the proportion of photographs in each grade of severity. These data provide a useful cross reference for future comparison of studies using these systems.

Aged↗

Improvement in severe onchocercal skin disease after a single dose of ivermectin.

PURPOSE: Skin disease is the most common clinically important manifestation of onchocerciasis. Ivermectin, a newly available drug, is well tolerated and effective in Onchocerca volvulus infection. However, little information is available regarding its effect on onchocercal skin disease. The purpose of this study was to examine, in patients with well-characterized onchodermatitis, the effect of a single dose of ivermectin. SUBJECTS AND METHODS: Twenty-one persons with severe onchodermatitis were followed over a 6-month period. In order to evaluate the effect of ivermectin on their skin lesions, photographic transparencies were made before treatment and at 3 and 6 months after treatment. These were then evaluated in a blinded fashion. RESULTS: Following a single dose of 150 micrograms/kg, there was a significant improvement in dermatitis in the first 3 months after treatment. All 14 persons with the worst skin disease showed improvement. The drug had no demonstrable effect on depigmented lesions over the period of observation. Treatment was well tolerated. CONCLUSION: Single-dose ivermectin shows promise as the first acceptable treatment for severe onchocercal dermatitis.

Adolescent↗

Pregnancy outcome after inadvertent ivermectin treatment during community-based distribution.

Ivermectin is the drug of choice for community-based treatment of onchocerciasis. Since pregnancy testing during mass distribution campaigns is not feasible, the safety of ivermectin in pregnancy must be established. During a 3-year study, ivermectin was distributed to the population of a rubber plantation (14,000 people) in Liberia. Only 31% of women were aware of their pregnancy status during the first month; it was calculated that about half of women in the first trimester of pregnancy are likely to be treated inadvertently. 203 children born to women inadvertently treated during pregnancy were identified. In this limited sample, there was no significant difference in birth defects between treated and untreated mothers in the same population or compared with a reference population. Children of treated and untreated mothers showed no difference in developmental status or disease patterns. Further surveillance is necessary; however, since no major effects of ivermectin on pregnancy outcome were detected, there seems no need to change existing strategies of ivermectin distribution.

Abnormalities, Drug-Induced↗

Impact of mass treatment of onchocerciasis with ivermectin on the transmission of infection.

Onchocerciasis is a major blinding disease that, until recently, has been essentially untreatable. Ivermectin is a safe and effective drug for the mass treatment of onchocerciasis and when used on an individual basis, it reduces the ability of the treated person to transmit Onchocerca volvulus infection. In the present study, the effect of community-based ivermectin treatment on the degree of transmission within the community was assessed by determining the incidence of new infection in children. Ivermectin was distributed annually on three occasions to the eligible members of a population of approximately 14,000 people living on a rubber plantation in a forest area endemic for onchocerciasis. After 2 years, the prevalence of infection in 5-year-old children decreased by 21%. The annual incidence in an uninfected cohort of children decreased by 35% and, after age-specific adjustment, the reduction in incidence in 7- to 12-year-old children was 45%. Thus, community-based distribution of ivermectin led to a significant reduction in incidence of new infection. These findings suggest that ivermectin can be important in reducing the transmission of onchocerciasis.

Child↗

Safety of and compliance with community-based ivermectin therapy.

In a study of the safety, acceptability, and efficacy of ivermectin for community-based mass treatment of onchocerciasis, the drug was issued twice, one year apart, to the population of a rubber plantation (14,000 people) in Liberia, where over 80% of the adults have Onchocerca volvulus infection. The plantation microfilarial load in a sample of adults was reduced by 86% 6 months after initial treatment and by 78% after 1 year. Compliance was 97% with each round of treatment. After the initial treatment of 7699 people, 101 (1.3%) had moderate adverse reactions. After re-treatment only 37 (0.5%) people had moderate adverse reactions. No ivermectin-related death or severe adverse reactions occurred. The data show that community-based treatment with ivermectin is well accepted and effective in reducing microfilarial loads. Ivermectin is likely to provide the first realistic means of chemotherapy-based control of onchocerciasis on a mass scale.

Adolescent↗

Effects of multiple monthly doses of ivermectin on adult Onchocerca volvulus.

This paper assesses the effects on adult Onchocerca volvulus of monthly doses of ivermectin (150 micrograms/kg) given over 4, 8, and 12 months to patients in Guatemala. Nodules were removed 4 months after the last dose; the adult O. volvulus were extracted by collagenase digestion, studied by histological techniques, and compared with worms from untreated patients. Twelve monthly doses killed a proportion of the adult worms (12% of males and 22% of females), leaving the remainder relatively unaffected and the females slowly resuming embryogenesis. After 8 and 12 doses, a number of female worms had resumed embryogenesis in 1 genital tract only, and in 1 female a total degeneration of 1 ovary was seen. Ivermectin also led to a marked drop in the number of male worms in nodules. No serious adverse reactions occurred and the treatment was well accepted.

Animals↗

Visible light and risk of age-related macular degeneration.

Sunlight exposure has been suggested as a cause of AMD. To examine this, we collected detailed histories of ocular sun exposure in 838 watermen who work on the Chesapeake Bay. The presence and severity of AMD was assessed in stereo macular photographs. Macular changes were classified into four grades of increasing severity ranging from the presence of 5 or more drusen (AMD-1) to extensive geographic atrophy or disciform scars (AMD-4). Previously, we found no association between AMD and ocular exposure to either UV-B (290 to 320 nm) or two bands of UV-A (320 to 340 nm and 340 to 400 nm). We have undertaken further analysis to determine whether ocular exposure to violet light (400 to 450 nm), blue light (400 to 500 nm), or all visible light (400 to 700 nm) was associated with AMD. Ocular exposure was estimated using model computations of ambient irradiance and estimates of the ratio of ocular to ambient exposure. Compared to age-matched controls, established cases (AMD-4), but not milder cases, had significantly higher exposure to both blue and visible light over the preceding 20 years (Wilcoxon sign rank test, P = 0.027). There was no difference in exposure at younger ages. These data suggest that high levels of exposure to blue and visible light late in life may be important in causing AMD.

Adult↗

Hygiene factors and increased risk of trachoma in central Tanzania.

Trachoma remains the major infectious cause of blindness in many developing areas, especially where hygiene is poor. The practices and behaviors associated with an increased risk of trachoma were studied in central Tanzania, where a stratified random cluster sample of 8409 people was examined. Data were collected on family and individual characteristics and behaviors and on trachoma status. Overall, 60% of the children aged 1 to 7 years had active inflammatory trachoma, and 10% of those aged 60 years or older had trichiasis. Regression analysis showed that active inflammatory trachoma in children was associated with the characteristics of the more traditional families and several measures of poor personal hygiene. Two important risk factors for severe inflammatory trachoma were poor facial cleanliness in children (odds ratio of 1.7 [1.17, 2.50]) and household fly density (odds ratio of 1.63 [1.17, 2.29]). Both factors are potentially amenable to intervention. These data suggest that an intervention strategy aimed at these hygiene measures would provide an effective method of controlling trachoma in this region, and a similar approach may be useful in other areas.

Adult↗