Two simultaneous hepatitis B virus epidemics among injecting drug users and men who have sex with men in Buenos Aires, Argentina: characterization of the first D/A recombinant from the American continent.

Previous studies have revealed that hepatitis B virus (HBV)/D and HBV/F predominate among blood donors from Buenos Aires, Argentina. In the present study, blood samples from two high-risk groups were analysed: 160 corresponding to street- and hospital-recruited injecting drug users [81.2% showing the 'anti-hepatitis B core antigen (anti-HBc) only' serological pattern] and 20 to hepatitis B surface antigen (HBsAg)(+)/anti-HBc(+) men who have sex with men. HBV genotypes were assigned by polymerase chain reaction amplification followed by restriction fragment length polymorphism and confirmed by nucleotide sequencing of two different coding regions. HBV DNA was detected in 27 injecting drug users (16.9%, occult infection prevalence: 7.7%), and 14 men who have sex with men (70%). HBV/A prevailed among injecting drug users (81.8%) while HBV/F was predominant among men who have sex with men (57.1%). The high predominance of HBV/A among injecting drug users is in sharp contrast to its low prevalence among blood donors (P = 0.0006) and men who have sex with men (P = 0.0137). Interestingly, all HBV/A S gene sequences obtained from street-recruited injecting drug users encoded the rare serotype ayw1 and failed to cluster within any of the known A subgenotypes. Moreover, one of the HBV strains from a hospital-recruited injecting drug user was fully sequenced and found to be the first completely characterized D/A recombinant genome from the American continent. Data suggest that two simultaneous and independent HBV epidemics took place in Buenos Aires: one spreading among injecting drug users and another one sexually transmitted among the homosexual and heterosexual population.

AIDS heterosexual predominance in the Dominican Republic.

AIDS surveillance data from the Dominican Republic are described for 1983-89. A positive serologic test for HIV was required, and standard clinical criteria were used for defining AIDS. There were 1,202 AIDS cases (820 men, 372 women, 10 of unknown gender) reported to the Ministry of Health, for a cumulative case rate of 17 per 100,000 persons. Rapid growth of the epidemic is noted, with 43% of the total cases reported in 1989. Heterosexual exposure accounts for 53% (593) of all cases, with a male-to-female ratio of 2.2:1, resembling a World Health Organization Pattern I/II country. Prevalence is highest in and surrounding the urbanized tourist areas of Santo Domingo and Puerto Plata and in districts with a high concentration of sugar plantation barracks, where laborers from Haiti and the Dominican Republic work and live. The distribution of AIDS cases is described by transmission exposure category, age, sex, year of diagnosis, and district. The National AIDS Surveillance Program can be improved by validation of exposure transmission categories through selected case investigation and by better reporting through training of health care providers. Surveillance data will assist in targeting future public health efforts to regions and persons at highest risk.

Documentation of subtype C HIV Type 1 strains in Argentina, Paraguay, and Uruguay.

HIV subtypes B, F, and BF recombinants have been previously reported in South America. This report describes the presence of HIV-1 subtype C infection in the countries of Argentina, Uruguay, and Paraguay dating back to at least 1999. Surveillance for uncommon non-B/non-F subtype viruses circulating in South America has been conducted in samples obtained from nine countries. Peripheral blood mononuclear cells (PBMC), dried filter paper (FP), and fresh blood (FB) samples were collected from HIV-positive patients from Ecuador, Colombia, Venezuela, Peru, Chile, Bolivia, Argentina, Uruguay, and Paraguay. From a total of 2962 HIV seropositive samples examined during a 9-year period (1995-2003), only 11 (0.4%) were found to be infected with non-B/non-F HIV variants. Eight of these 11 strains were determined to be subtype C by heteroduplex mobility assay (HMA). Five of these 8 strains were further characterized by sequencing and phylogenetic analysis of the protease (Pro) and reverse transcriptase (RT) region of the genome and two were sequenced full length. One of the strains was found to be a unique BC recombinant. The spread of a third subtype of HIV, subtype C, should raise the question of its potential future role in the HIV epidemic in this region.

Underestimation of Mycobacterium tuberculosis infection in HIV-infected subjects using reactivity to tuberculin and anergy panel.

BACKGROUND: This study aimed to evaluate purified protein derivative (PPD) reactivity and its interrelationship with anergy panel and CD4+ lymphocytes in HIV-infected subjects as compared to PPD reactivity in HIV-uninfected individuals in a tuberculosis endemic and high Bacillus Calmette-Guérin (BCG) coverage environment. METHODS: Clients of four Mexico City HIV detection centres were screened for HIV-1 antibodies (ELISA or haemagglutination, Western Blot); reactivity to PPD (Mantoux PPD, 5TU RT-23), Candida (1:1000, 0.1 ml), and tetanus toxoid (10Lf, 0.1 ml); and CD4+ T cells. Active tuberculosis was excluded. Informed consent was obtained. RESULTS: From 5130 clients 1168 subjects were enrolled; of these 801 (68.6%) were HIV positive. Reactivity to PPD among HIV-positive subjects was found in 174 (22%), 261 (32.6%), and 296 (37%), at PPD cutoff levels of > or =10 mm, > or =5 mm, and > or =2 mm as compared to 224 (61%) of 367 HIV-negative individuals' reactors to PPD (> or =10 mm) (P < 0.001). After exclusion of anergic individuals using two cutoff levels for cutaneous allergens (< or =2 mm and < or =5 mm), PPD reactivity between HIV-infected and uninfected individuals continued to be significantly different. Only HIV-infected individuals with CD4+ T cells > or =500 cells/mm3 had similar reactivity to PPD as HIV-uninfected individuals. Variables associated with PPD reactivity were CD4+ T cell counts, BCG scar, HIV infection and age. CONCLUSIONS: PPD reactivity was useful to diagnose tuberculosis infection only among HIV-infected individuals with CD4+ counts > or =500 cells/mm3. Among individuals with lower counts, lowering cutoff levels or using anergy panel did not permit comparable reactivity as that observed among HIV-uninfected individuals.

Protection against a pathogenic strain of Junin virus by mucosal infection with an attenuated strain.

In order to determine the degree of mucosal infectivity of the attenuated XJCl3 strain of Junin virus, guinea pigs were orally or nasally inoculated. Infectivity was 85% for the oral and 100% for the nasal route, as detected by death or serum antibody development. The presence of serum antibodies was closely associated with resistance to challenge with the XJ pathogenic strain, which killed 100% of controls when inoculated by the parenteral or nasal route. However, mortality rates after mucosal infection were low, depending on the dose. Guinea pigs which survived nasal inoculation developed serum neutralizing antibodies, and were fully resistant to challenge with the XJ pathogenic strain.

Junin virus infection of Callithrix jacchus: pathologic features.

Infection of Callithrix jacchus, a New World primate, with the prototype strain of Junin virus produced a severe disease. The animals developed multifocal hemorrhages and characteristic microscopic lesions such as meningoencephalitis, interstitial pneumonia, lymphocytic depletion of lymphatic tissue, hepatocytic necrosis, and a variable decrease in bone marrow cellularity. High virus concentrations correlated with lesions, and with the presence of viral antigenic determinants as revealed by immunofluorescent methods. With the exception of central nervous system damage, the morphological features and immunohistochemical and viral findings were similar to those recorded in human Argentine hemorrhagic fever.

Acute lower respiratory infection in Argentinian children: a 40 month clinical and epidemiological study.

In a total of 1,003 children (805 inpatients and 198 outpatients) with acute lower respiratory infections (ALRI), clinical, social, and environmental data were analyzed. The major clinical entities were bronchiolitis, pneumonia, bronchitis, and laryngitis. The first two of these predominated in inpatients; pneumonia and bronchitis were more common in older children, while bronchiolitis was observed in infants. Respiratory rates of > 50/min. were more common in younger children and in cases with bronchiolitis and bronchitis. Retractions showed markedly less age-dependent variations and were present in all severe cases with different clinical diagnoses. Retractions alone or associated with cyanosis were the best indicators for severity of ALRI. Among outpatients, fever and wheezing were more common; inpatients were younger, more frequently malnourished, and from a lower socioeconomic level; family history of chronic bronchitis, crowding, and parental smoking also prevailed in this group. Family asthma and exposure to domestic aerosols was more common among outpatients. Prematurity rate (17 and 15%) of all ALRI cases was twice that of the general pediatric population and a significant difference existed between in- and outpatients under 6 months of age when perinatal respiratory pathologies predominated among inpatients. It is suggested to consider the need for assessing personal, family, and environmental risk factors in addition to clinical signs and symptoms when severe cases of ALRI are evaluated.

Role of drug injection in the spread of HIV in Argentina and Brazil.

Drug injectors' have become the second largest HIV transmission category in Argentina and Brazil, as is the case in many pattern I countries, making up more than one-quarter of all AIDS cases reported by 1991. HIV seroprevalence data suggest that the expanding proportion of AIDS cases attributable to drug injection stems from an absolute increase in the number of AIDS cases among drug injectors, and is not merely reflective of a decline in the proportion of cases reported in other transmission categories. Results of a review of studies in Argentina and Brazil indicate that HIV seroprevalence is increasing rapidly, contrary to the situation in some pattern I countries in which HIV seroprevalence among drug injectors is either stably high or increasing only slightly. Also contrary to most pattern I countries, cocaine rather than heroin is the injected drug of choice in Argentina and Brazil. Given that injectors of cocaine are more likely to be HIV infected than are heroin injectors, differences in the type of drug injected between countries may have distinct epidemiological consequences on the spread of HIV.

PIP: AIDS cases attributable to using contaminated needles in nonmedicinal drug injection have increased in Argentina from 11.3% in 1987 to 39% in 1991. A similar increase (from 1.8% in 1985 to over 30% in 1991) occurred in Brazil. To complement existing information, data searches were conducted and personal communications from current researchers were collected for a total of 24 documents from Argentina and 18 from Brazil. The median sample size was 68 in Brazil and 188 in Argentina; most studies were from outpatient facilities, males constituted more than two-thirds of the sample in half of the studies, and the median age (when reported) was between 16 and 29 years old. Analysis of data from selected studies showed that HIV seroprevalence among drug injectors in both countries has increased rapidly, with the greatest increase occurring in Brazil. This rapid increase may also be influenced by the fact that cocaine, rather than heroin, is the drug of choice. Cocaine injection involves drawing blood into the syringe before injection and also more frequent injections. The level of seroprevalence among drug injectors varies among different subpopulations. Sexually transmitted disease clinic attenders who are IV drug users show rates of 6.58% and 51.9% seropositivity. Incarcerated persons who are drug injectors were associated with seropositivity rates of 35% (adults), 60.9% (adolescents), 53.5% (adolescents in security institutes), and 18% (female inmates who volunteered for testing), with drug injection the most important risk factor in 90.4%. Among prostitute injectors, rates were reported of 20% in 1988 and 50% in 1989-90 in the same population. Street children in Rio de Janeiro who use IV drugs (68 of 3389 surveyed) had a rate of 13.2% in 1987-88. The risk factors associated with HIV infection among drug injectors are socioeconomic status and injecting and sex practices. Co-infection patterns among drug injectors have also been found, with concomitant HIV-1 and HTLV-1 reported in 20% of 85 HIV positive drug injectors. Overall, these data suggest that there is an absolute increase in the number of AIDs cases among drug injectors rather than a decline in the proportion of cases reported in other transmission categories. Drug injector transmission poses a threat to the sex partners and offspring of injectors and provides a bridge to the heterosexual infection of women. While there is no obvious quick solution to the problem of IV drug use, there are programs which can slow the spread of HIV among injectors. It is urgent to control sexual transmission and drug injection transmission of HIV in these countries.

Nasal and intrathalamic inoculations of primates with Tacaribe virus: protection against Argentine hemorrhagic fever and absence of neurovirulence.

Callithrix jacchus marmosets were inoculated by different routes with two stocks of Tacaribe virus, one from suckling mouse brain and another from human diploid MRC5 cells. All 12 primates inoculated by nasal route developed neutralizing serum antibodies without any clinical signs. All 6 primates receiving the mouse brain-Tacaribe virus were protected against lethal challenge with pathogenic XJ strain of Junin virus, while protection was also conferred in 4 out of 6 primates receiving the diploid cell-Tacaribe virus stock. Intramuscular (i.m.) inoculation also elicited antibodies and conferred protection to 4 primates receiving the diploid cell-virus stock. Intrathalamic (i.t.) inoculation of mouse brain-virus stock caused no clinical signs or histopathologic changes in groups of 3 primates each examined on days 33 and 90 post-infection (p.i.). All primates developed antibody response, but no virus could be detected in their brain. Thus, Tacaribe virus proved harmless and immunogenic in Callithrix jacchus and protected most marmosets against challenge with the lethal XJ strain of Junin virus.

Passive immunity against Junín virus in mice.

Passive immunity, naturally acquired from immune mothers or artificially induced by the administration of homologous hyperimmune serum, conferred on suckling mice a high degree of resistance against infection with Junín virus. Maternal antibodies in the circulating blood of the young were not detectable in the first days after birth, but rised rapidly from the 8th to the 20th day of lactation. By cross-foster nursing experiments it was shown that the greater part of the transmission of passive immunity occurred after birth, although there was transmission of a significant, though small part, before birth. The virus passage from mothers to offspring was excluded, since Junín virus was not recovered from brains, livers, spleens and kidneys of uninfected young, born from infected mothers.

Junin virus infection of Calithrix jacchus: haematological findings.

Haematological changes produced by experimental Junin virus infection of a platyrrhine monkey, Callithrix jacchus were studied. Normocytic and normochromic anaemia appeared after 7 days post infection (p. i.), and increased steadily until day 21 p. i. Reticulocytes and circulating erythroblasts were elevated during the anaemia, reached a peak on day 7 p. i., and disappeared later. Platelets and leukocytes showed a significant decrease from days 14 and 18 p. i., respectively. These alterations could be attributed to the damage of bone marrow and lymphatic tissue.

Hantavirus infection in laboratory and wild rodents in Argentina.

Serum samples from urban and laboratory rats, laboratory mice and wild and laboratory cricetids in Argentina were tested by immunofluorescence and plaque reduction neutralization tests to investigate prevalence of anti-Hantavirus antibodies. A total of 102 sera were obtained from laboratory rodents in 4 different animal-rooms, 31 from harbor rats and 30 from wild cricetids in 1985-1987. Anti-Hantavirus antibodies were detected in 22.5% of Rattus norvegicus in 3 of the animal-rooms but harbor rats were found to be free of Hantavirus infection. Previously, the presence of anti-Hantavirus antibodies had been demonstrated in the sera obtained from laboratory workers in these same 3 animal-rooms; it can be concluded that the laboratory rats were the source of this human infection. On the contrary, laboratory mice and cricetids failed to show Hantavirus infection while the wild vesper mouse Calomys musculinus (the main Junin virus reservoir) showed a prevalence of 23.5%. The presence of Hantavirus infection is hereby reported for the first time in wild C. musculinus and in laboratory R. norvegicus in Argentina.

Hantavirus pulmonary syndrome in Argentina. Possibility of person to person transmission.

In March 1995 the first case of a familiar outbreak of Hantavirus pulmonary syndrome (HPS) was notified in El Bolson, in the South of Argentina. Until December 15, 1996, a total of 77 cases of HPS had been notified with 48% mortality, distributed in three geographical areas of the country, South, North and Center. During 1996, of the 19 cases from El Bolsón, three were local physicians, one of whom -during the prodrome of her illness- travelled to Buenos Aires to be attended. In the hospital, two of the physicians who assisted her, developed HPS 27 and 28 days after the first contact. These data suggest for the first time the possibility of interhuman transmission of the Hantavirus responsible for the pulmonary syndrome.

[Human immunodeficiency virus infection associated with tuberculosis]. / Asociación de la infección por el virus de la inmunodeficiencia humana (HIV) y tuberculosis.

In order to detect an association between HIV infection and tuberculosis (TB), 130 TB inpatients were studied one of whom presented a pulmonary disease due to Mycobacterium avium intracellulare. All had advanced TB, 95.4%, with pulmonary localization. Serum anti-HIV antibodies were detected by ELISA and their presence confirmed by immunoblotting in 4 (3.1%) individuals, three males and one female, with different degrees of pulmonary TB. Of the males, 1 was bisexual, 2 were promiscuous, and the female was the sexual partner of a non symptomatic HIV-infected man. No immunological disturbances or other AIDS related alterations were observed. There was one case of miliary TB, but neither atypical X-ray abnormalities nor extrapulmonary involvement were found. Tuberculin reaction was positive in three of the four HIV infected patients. Clinical, radiological and bacteriological evolution were favorable. Adverse drug reaction occurred in two cases, one of them presenting serious toxidermia caused by isoniazid. Of the 130 individuals, 12 presented risk factors for HIV infection so that the prevalence of anti-HIV antibodies presented here, 4 cases out of 12, is consistent with data from previous reports for high risk populations.

Serological evidence of human Hantavirus infection in Argentina, Bolivia and Uruguay.

A serological survey was conducted in 1985-1987 to determine the presence of infection for Hantavirus in the general population in Argentina, Uruguay, Paraguay and Bolivia, as well as among rodent-exposed laboratory workers in Argentina. Out of 748 individuals tested by immunofluorescence 20 proved positive for Hantaan virus 76/118 strain of whom 16 also reacted against Seoul virus 80/39 strain and 2 against Puumala virus Sotkamo strain. Ten out of 72 Argentine laboratory workers were positive for the first 2 viruses by ELISA, immunofluorescence and/or plaque reduction neutralization test, in 4 of whom recent infection was demonstrated by IgM antibody presence. Inapparent Hantavirus infection was thus demonstrated for the first time in 2.7% of regional inhabitants, together with 13.9% among rodent-exposed laboratory workers. Our data established the existence of human Hantavirus infection nearly 10 years before the recognition of clinical cases of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome in Argentina.

Antiviral effect of ribavirin on Junin virus replication in vitro.

The effect of Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) on the replication in vitro of Junin virus, the causative agent of Argentine Hemorrhagic Fever (AHF), was examined. A concentration as low as 3.12 micrograms/ml of the drug inhibited the cytopathic effect observed five days post-infection (pi) on Vero cells. On the other hand, a concentration of 25 micrograms/ml reduced the virus yield and specific antigen formation to undetectable levels. This same concentration of Ribavirin prevented plaque formation under methylcellulose. The high sensitivity of Junin virus to Ribavirin in vitro, the low toxicity of the drug for mammals and the therapeutic effect observed on in vivo infections with other arenaviruses, makes Ribavirin a promising antiviral agent that deserves testing on AHF primate models before clinical trials are undertaken.

[Detection of laboratory infections caused by Junín virus using the neutralization and immunofluorescence technics comparatively]. / Detección de infecciones de laboratorio por virus Junín utilizando comparativamente las técnicas de neutralización e inmunofluorescencia.

To study Junin virus infection among laboratory workers and to compare immunofluorescence and neutralization tests, blood samples were taken from 48 individuals, of which 42 were considered high risk personnel. None of the 16 low risk workers exhibited antibodies. Neutralizing antibodies were detected in 15 high risk laboratory workers. Nine of the latter were already known to carry antibodies from a previous survey in 1978. Titers detected were either at previous levels or slightly higher. Of the remaining 6 out of the 15 positive cases, 3 showed mild clinical and subclinical infection, equivalent to a 12% incidence rate over the 1978-1980 period. An adequate correlation was observed between neutralization and immunofluorescence test: 66.6% for both positive tests and 97.1% for both negative tests. Although the immunofluorescence test ies easier to perform the neutralization test appears to be more reliable clinically. The overall prevalence rate of neutralizing antibodies among non-vaccinated personnel was almost 19%, which warns against the health hazard involved in Junin virus handling.

[Association of the infection of the thymus and bone marrow with the establishment of persistent infection with Junin virus in 2 genera of rodents]. / Asociación de la infección del timo y médula ósea con el establecimiento de la infección persistente con virus Junín en dos géneros de roedores.

Junin virus infection of immune system organs was correlated with persistence establishment in the mouse and rat. Rockland mice under 24 or at 72 and 120 h of age received 10(4) pfu of Junin virus XJ strain by ic route. Separately, two groups of mice under 24 h old were infected with the same dose of XJ or XJCl3 strain by the same route respectively. Results showed that higher thymus virus titer correlated with greater survival. In turn, the former also seemed to correlate with decreasing age at inoculation time, although there was considerable strain dependence. In order to correlate replication levels in thymus with clinical progress in mice, animals under 24 h of age were inoculated with XJ. At 14 days pi apparently healthy mice from this batch were separated from those presenting severe neurologic sings. In the asymptomatic mice, thymus titers ranged from 1.7 to 3.2 log, while no virus was found in thymus harvested from obviously ill animals. However brain virus titers in the two groups proved similar. To confirm these findings, 72 h old Wistar rats were inoculated in with 10(4) pfu of either Junin virus strain: with XJ strain (90% survival) virus could be readily isolated from thymus and bone marrow at day 7 pi, whereas with XJCl3 (5% survival) no virus could be rescued from any organ tested. Therefore, our results strongly suggest a close correlation between productive thymic infection and Junin virus persistence establishment in these rodents, depending on immune response regulation rather than on viral variation.

[Preliminary study on the presence of arbovirus in the populations of Corrientes and Misiones]. / Estudio preliminar sobre la presencia de arbovirus en poblaciones de Corrientes y Misiones.

Human seroprevalence of Flavivirus was determined by hemagglutination inhibition tests on 479 sera from Misiones and 49 from Corrientes provinces. Paraná and Uruguay river bank communities from Argentina and neighbouring countries carry out frequent traffic across the rivers. With the aim of searching for a possible introduction of Dengue virus from Brasil or/and Paraguay, reactivity among people from Paraná and Uruguay river communities was compared with those from mountain communities. Two sera from Ituzaingó (Corrientes Province) were positive for Dengue 2. In Misiones, 3 sera from Oberá and 2 from Montecarlo were reactive for Dengue 2 and 1 serum from Puerto Iguazú was reactive for Dengue 1. Seroprevalence among the river population was significatively higher than among the mountain population. Likewise, populations on Paraná river showed more positive sera than those on Uruguay river; 54% of the samples possessed titers for SLE virus higher than for Dengue or Yellow fever. Anti-alphavirus (EEE and WEE) antibodies tested in sera from Misiones people showed a complementary distribution pattern to flavivirus. Seroprevalence of anti-alphavirus antibodies was higher in the mountain than in the river populations.

[Serologic response measured by complement fixation in children with acute respiratory infection]. / Respuesta serológica medida por fijación de complemento en niños con infección respiratoria aguda.

The aim of this work was to evaluate the sensitivity of complement fixation for serological diagnosis of lower acute respiratory infections (ARI) in small children in comparison with direct methods such as indirect immunofluorescence (IIF) on nasopharyngeal aspirate and tissue culture isolation. Sera from children under 5 year of age with ARI were studied by complement fixation for 6 respiratory viruses (respiratory syncytial virus (RSV), adenovirus, influenza A and B and parainfluenza 1 and 3). In all, 264 pairs of serum samples from children with viral ARI diagnosis (n:135) or from doubtful cases (n:90) were studied. Thirty nine sera were anticomplementary. In samples from confirmed viral ARI patients, seroconversion was detected in 38%, whereas from those with a doubtful diagnosis it was only 14%. Seroconversion for RSV and adenovirus was 39% and 50%, respectively. On correlating seroconversion for the 6 viruses according to age group, 20% positivity was found in the 0-5 month-old group, 35% in the 6-10 month-old and 30% in those over 11 months of age. For RSV alone, 0-5 month-old patients presented 25% seroconversion, and in those over 6 months of age the percentage exceeded 60% (p less than 0.001). Complement fixation test sensitivity vs direct methods (IIF and/or culture) was 38.5%). Our findings confirm the low sensitivity of complement fixation to detect antibodies in ARI, particularly in children under 6 months of age and support the higher efficacy of direct diagnostic methods. However, complement fixation serology is useful for epidemiological studies in children over 6 months of age, since over 60% of RSV were readily detected.