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F Zicker

Publications and source records attributed to F Zicker.

At least 19 recordsLinked to original sources
PubMed2005

Dichotomy of protective cellular immune responses to human visceral leishmaniasis.

Healing/protective responses in human visceral leishmaniasis (VL) are associated with stimulation/production of Th1 cytokines, such as interferon IFN-gamma, and conversion in the leishmanin skin test (LST). Such responses were studied for 90 days in 44 adult healthy volunteers from VL non-endemic areas, with no past history of VL/cutaneous leishmaniasis (CL) and LST non-reactivity following injection with one of four doses of Alum-precipitated autoclaved Leishmania major (Alum/ALM) +/- bacille Calmette-Guerin (BCG), a VL candidate vaccine. The vaccine was well tolerated with minimal localized side-effects and without an increase in antileishmanial antibodies or interleukin (IL)-5. Five volunteers (5/44; 11.4%) had significant IFN-gamma production by peripheral blood mononuclear cells (PBMCs) in response to Leishmania antigens in their prevaccination samples (P = 0.001) but were LST non-reactive. On day 45, more than half the volunteers (26/44; 59.0%) had significantly high LST indurations (mean 9.2 +/- 2.7 mm) and high IFN-gamma levels (mean 1008 +/- 395; median 1247 pg/ml). Five volunteers had significant L. donovani antigen-induced IFN-gamma production (mean 873 +/- 290; median 902; P = 0.001), but were non-reactive in LST. An additional five volunteers (5/44; 11.4%) had low IFN-gamma levels (mean 110 +/- 124 pg/ml; median 80) and were non-reactive in LST (induration = 00 mm). The remaining eight volunteers had low IFN-gamma levels, but significant LST induration (mean 10 +/- 2.9 mm; median 11). By day 90 the majority of volunteers (27/44; 61.4%) had significant LST induration (mean 10.8 +/- 9.9 mm; P < 0.001), but low levels of L. donovani antigen-induced IFN-gamma (mean 66.0 +/- 62 pg/ml; P > 0.05). Eleven volunteers (11/44; 25%) had significantly high levels of IFN-gamma and LST induration, while five volunteers had low levels of IFN-gamma (<100 pg/ml) and no LST reactivity (00 mm). One volunteer was lost to follow-up. In conclusion, it is hypothesized that cellular immune responses to human VL are dichotomatous, and that IFN-gamma production and the LST response are not in a causal relationship. Following vaccination and probably cure of VL infection, the IFN-gamma response declines with time while the LST response persists. LST is a simple test that can be used to assess candidate vaccine efficacy.

Adult↗
PubMed2004

An epidemiological approach to study congenital Chagas' disease.

Transplacental transmission of Trypanosoma cruzi has been the focus of much attention in highly endemic areas in South America. Frequency of congenital transmission and factors associated with risk of it are still not well understood. Parasite strains may account for part of the geographical variation observed. Methodological differences between the studies do not permit a combined interpretation of results. This paper examines the epidemiological data available from Brazil, Bolivia, and Argentina and discusses possible epidemiological study design to investigate risk factors for transmission.

Journal Article↗
PubMed2001

Safety of blood supply for infectious diseases in Latin American countries, 1994-1997.

The potential risk of acquiring a transfusion-transmitted infection by the human immunodeficiency virus (HIV), hepatitis B (HBV) virus, hepatitis C (HCV) virus, or Trypanosoma cruzi was estimated for seven South American and five Central American countries during the period 1994-1997. The estimates were based on official national reports of the number of donors, blood screening coverage, and prevalence of serologic markers for infectious diseases. Coverage of screening in 1997 was 100% in 12 and 11 countries for HIV and HBV respectively. Complete screening for HCV was reported by only one country in 1994 and by six in 1997. For T. cruzi, the number of countries with 100% screening coverage increased from two in 1994 to four in 1997. In 1994, three countries showed risk of transfusion-transmitted infections for HIV, seven for HBV, eight for HCV, and seven for T. cruzi. The risk of receiving an infected blood unit and acquiring a transfusion-transmitted infection has been reduced with time in 10 of the 12 countries due to improvements in screening coverage. In Uruguay, the risk was theoretically nil from 1994-1997 because at the beginning of the study period they already had 100% blood donor screening for all infectious diseases transmitted by blood. In 1994, Colombia and Venezuela had the highest health risk associated with blood transfusion (spreading index of 101 and 62, respectively); during the period 1996-1997, Costa Rica presented the highest figures (spreading index of 53 and 83, respectively). The analysis of the potential risk associated with transfusion of tainted blood highlights the need for continuous monitoring of the safety of blood supply.

Blood Donors↗
PubMed2000

Transfusion-transmitted infectious diseases in Argentina, 1995 through 1997.

BACKGROUND: Assessment of the safety of the blood supply, the quality of screening procedures, and the risk of transfusion transmission of infectious diseases in any country can be estimated by reviewing the records of blood donations and screening procedures and the prevalence of serologic markers of infectious diseases. STUDY DESIGN AND METHODS: Information on blood donors, particularly the number of screened donors, and on the prevalence of serologic markers of infectious diseases was available from Argentina for 1995 through 1997. This information permitted the estimation of the risks and costs of preventing transfusion transmission of infectious diseases within the country during this period. RESULTS: Screening coverage was higher in the private sector. The proportion of donors screened for HIV increased from 84.52 percent in 1995 to 97.97 percent in 1997; in the same period, serologic screening for HbsAg increased from 83.71 percent to 98.48 percent; that for HCV from 69. 92 percent to 97.83 percent; and that for syphilis from 87.94 percent to 98.71 percent. One hundred percent of donors were screened for Trypanosoma cruzi throughout the period. The overall prevalence of HIV per year varied from 2.42 to 3.36 per 1,000 donors; that of HBV, from 5.80 to 9.76 per 1,000; of HCV, from 7.39 to 16.61 per 1,000; and of syphilis, from 5.25 to 7.65 per 1,000. The overall prevalence of antibodies to T. cruzi ranged from 36.53 to 49.20 per 1,000 donors. The overall index of the spread of infectious viral disease through blood transfusion decreased from 47. 74 per 10,000 donations in 1995 to 4.75 per 10,000 in 1997. The ratio of acquired infections to donations improved from 1:209 to 1:2, 102 during the same period. The risk of T. cruzi infection from 1995 through 1997 was, in theory, nil, given the 100-percent screening. The greatest threat to the quality of the blood supply throughout the period studied was HCV. CONCLUSION: The status of the blood supply in Argentina improved steadily from 1995 to 1997, as shown by the increase in screening coverage.

Animals↗
PubMed1999

A randomised, double-blind, controlled trial of a killed L. major vaccine plus BCG against zoonotic cutaneous leishmaniasis in Iran.

Safety and efficacy of killed (autoclaved) L. major promastigotes, ALM, mixed with BCG against zoonotic cutaneous leishmaniasis was tested in healthy volunteers (n = 2453) in a randomized double blind trial vs. BCG as control. Side-effects were similar in both groups but tended to be slightly more frequent and prolonged in the ALM + BCG group. Leishmanin skin test conversion (induration > or =5 mm) was significantly greater in the ALM + BCG than in the BCG group (36.2% vs. 7.9% on day-80 and 33% vs. 19%, after 1 year, respectively). Cumulative incidence rates for 2 years, were similar in both groups (18.0% vs. 18.5%). However, LST responders on day 80 (> or =5 mm) had a significantly lower incidence (35%) of CL during the first year than non-responders. A single dose of ALM + BCG is not sufficiently immunogenic to provide a measurable response when compared to BCG alone. A single dose of this vaccine has been shown to be safe with no evidence of an exacerbating response following natural infection; hence, multiple doses or other adjuvants should be considered to increase its immunogenicity.

Adolescent↗
PubMed1998

Randomised vaccine trial of single dose of killed Leishmania major plus BCG against anthroponotic cutaneous leishmaniasis in Bam, Iran.

BACKGROUND: A vaccine consisting of a single dose of whole-cell autoclave-killed Leishmania major (ALM) mixed with BCG was assessed in comparison with BCG alone against anthroponotic (human to human transmission) cutaneous leishmaniasis in a randomised double-blind trial in Bam, Iran. METHODS: 3637 schoolchildren, aged 6-15 years, with no history of cutaneous leishmaniasis and no response to a leishmanin skin test, were randomly assigned to receive 1 mg ALM mixed with BCG (n = 1839), or BCG alone (n = 1798). Safety of the vaccine and the incidence of confirmed cases of cutaneous leishmaniasis were followed up for 2 years. FINDINGS: Side-effects were those usually associated with BCG vaccination, but tended to persist longer in the ALM + BCG group. After exclusion of four cases occurring within 80 days of vaccination (one in the ALM + BCG group and three in the BCG group), the 2-year incidence of cutaneous leishmaniasis did not differ significantly between vaccine and BCG groups: 2.8% vs 3.3%, respectively (total cases 112). A sex-stratified analysis showed that in boys the vaccine conferred a protective efficacy of 18% and 78% for the first and second years, respectively--a crude 2-year overall protection of 55% (95% CI 19-75%, p < 0.01). In the first 9 months after vaccination, there was a non-significant excess of cases in the ALM + BCG group (25 vs 16), whereas the incidence of cutaneous leishmaniasis thereafter was significantly reduced in the ALM + BCG group (27 vs 44, p < 0.05). INTERPRETATION: A single dose of ALM + BCG was safe and more immunogenic than BCG alone, as measured by leishmanin skin test. The exact reason for the apparent protective effect of the vaccine in boys is unknown, and may be a chance finding. However, since boys are more exposed to the infection, which is indicated by higher disease prevalence in boys in this study population, the preferential protective effect in boys may have resulted from a greater booster effect produced by repeated exposure to infected sandflies. Booster injections or alternative adjuvants should be tried to improve the potential efficacy of this vaccine.

Adjuvants, Immunologic↗
PubMed1998

Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children.

As part of a major epidemiologic study on Chagas' disease, we compared the prevalence of electrocardiographic (ECG) abnormalities among 141 school children 7-12 years of age and seropositive for Trypanosoma cruzi, and 282 age-, sex-, and school-matched seronegative children in an endemic area in Brazil. The prevalence of ECG abnormalities was 11.3% among seropositive children and 3.5% among seronegative children (odds ratio = 3.5, 95% confidence interval [CI] = 1.5-8.4). The prevalence rate of ECG alterations was 10.7% for seropositive males versus 8.9% for seropositive females. Complete right bundle branch block (CRBBB), which is highly suggestive of Chagas' disease cardiopathy, was diagnosed in nine (6.4%) seropositive children and in only one (0.3%) seronegative child (odds ratio = 18.5, 95% CI = 2.3-146.5, attributable fraction = 58.3%). Five incident new cases of CRBBB were diagnosed after a 36-month follow-up of seropositive children who were enrolled in an independent clinical field trial. No case of frequent and/or multifocal ventricular premature beats was found in the cohort of children. The surprisingly high frequency of early ECG abnormalities, which indicates a rapid evolution from infection to disease, suggests the existence of endemic areas with a particular accelerated disease progression that was not described before. Under such conditions, a public health chemotherapy program focusing on the treatment of young seropositive children would be recommended.

Chagas Disease↗
PubMed1996

Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection.

BACKGROUND: Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection. METHODS: Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection. FINDINGS: Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001). INTERPRETATION: The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy.

Animals↗
PubMed1996

Protective efficacy of BCG against leprosy in São Paulo.

The case-control study reported here evaluated the protective effect of BCG vaccine against leprosy in São Paulo, Brazil. Seventy-eight patients under age 16 who had been diagnosed as having leprosy (cases) and 385 healthy individuals (controls) were selected and matched by sex, age, place of residence, and type of exposure to leprosy (intradomiciliary or extradomiciliary). The cases were drawn from an active patient registry and from a group of new leprosy cases treated at 50 health centers in the cities of Bauru and Ribeirão Preto in the state of São Paulo. In order to estimate the protective effect of BCG, the prevalences of BCG scars in cases and controls were compared. The presence of one or more scars was associated with an estimated protective efficacy of 90% (95% confidence interval: 78% to 96%). Stratified analysis by age group, sex, socioeconomic level, and clinical form of the disease revealed no significant differences in the protection provided by the vaccine. However, it seems clear that more data will be needed in order to accurately assess the true relevance of BCG for leprosy control programs.

Adolescent↗
PubMed1995

Chronic malnutrition and Trypanosoma cruzi infection in children.

The distribution of T. cruzi infection overlaps regions with high prevalence of child malnutrition. We examined the possible association between T. cruzi infection and chronic malnutrition. In a cross-sectional survey conducted among 1900 7-12 year-old schoolchildren in 60 village schools in central Brazil, anthropometric measurements (NCHS) taken from 153 children with at least two positive serological tests for antibodies against T. cruzi (IIF, ELISA, IHA) were compared to two age and sex seronegative matched classmates. Information on children's medical history and socio-economic status (SES) were collected from parents of the participants. Seropositive children had a 2.4-fold risk (95% CI 1.4-4.0) of being stunted (z-score < 2.0 of height-for-age) when compared to uninfected children even after adjusting for confounding variables. Being underweight (z-score < -2.0 of weight-for-age) was also statistically associated with seropositivity to T. cruzi (OR = 2.8, 95% CI 1.4-5.6). No statistical evidence of multiplicative interaction between nutritional status and SES was detected. Further studies on nutrition and metabolism are required to look into a possible physiopathological mechanism for this association.

Animals↗
PubMed1995

Risk factors for Trypanosoma cruzi infection among children in central Brazil: a case-control study in vector control settings.

This population-based case-control study was conducted in northern Goias State, central Brazil, in rural settings under vector control surveillance. One hundred forty-nine children seropositive for Trypanosoma cruzi antibodies, selected in a cross-sectional survey carried out in village schools, were compared with 298 seronegative classmate controls matched for age, sex, and place of residence. Information on potential environmental, familiar, and social economic risk factors for T. cruzi infection was collected during household visits, and interviews with parents and entomologic inspections of domestic and peridomestic environments were conducted. The presence of triatomines in dwellings or evidence of triatomine colonization was found to be statistically associated with seropositivity in children. The presence of exuviae and a report of triatomines indoors or outdoors by householders in the past were strong predictors of an infected child. Children from seropositive mothers had a 3.9-fold increase in the risk of having anti-T. cruzi antibodies after adjusting for the confounding variables, including triatomine capture, mother's age, and family size in multivariate analysis. Parent's report of vector presence showed a 97.7% sensitivity in identifying a dwelling with at least one seropositive child. The possibility of transplacental T. cruzi transmission and its implication for Chagas' disease control were considered.

Adult↗
PubMed1995

Evaluation of risk factors for house infestation by Triatoma infestans in Brazil.

An active entomologic survey was conducted by a team of trained health workers in a rural area endemic for Chagas' disease in central Brazil. They used pyrethrum as a flushing agent and 4,232 houses were inspected for triatomine bugs both inside and in the immediate environs. Houses with Triatoma infestans or evidence of an established colony were identified and defined as infested houses (cases). The building and environmental characteristics of 161 randomly selected infested houses were compared with 161 matched, noninfested houses (controls) that were the shortest distance from the infested house. Domestic and peridomestic potential risk factors associated with house infestation by Triatoma infestans were assessed by logistic regression analysis. Incomplete house construction (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.5-4.1) was confirmed as a risk factor related to the presence or evidence of Triatoma infestans in the dwellings. The study also disclosed a statistically significant association between the presence of rats (OR = 1.6, 95% CI = 1.1-2.6) and indoor crop storage (OR = 2.3, 95% CI = 1.1-5.2) and house infestation. Further experimental field studies using tagged rodents should be conducted to assess their epidemiologic role in the domestic chain of Trypanosoma cruzi transmission.

Analysis of Variance↗
PubMed1995

Spatial patterns of leprosy in an urban area of central Brazil.

Reported is the spatial variation of leprosy in an urban area of Brazil and its correlation with socioeconomic indicators. From November 1991 to October 1992 a total of 752 newly diagnosed leprosy patients who were attending all outpatient clinics in Goiânia city, central Brazil, were identified. A database o leprosy cases was set up linking patients' addresses to 64 urban districts. Leprosy cases were detected in 86% of the districts and three risk strata were identified. The highest-risk area for leprosy was in the outskirts of the city and detection rates increased on moving from more developed to poorer areas. The risk of detecting leprosy cases was 5.3-fold greater (95% CI: 3.8-7.4) in the outskirts of the town than in the central zone. Discussed are the methodological issues related to leprosy case ascertainment, completeness and reliability of information, and the interpretation of the spatial distribution of leprosy per unit area. Highlighted also are the lack of leprosy control activities in primary health care units and the usefulness of geographical analysis in planning health services.

Adolescent↗