Historia natural de enfermedades emergentes y reemergentes en la Argentina: Zika, chikungunya y dengue (2016-2017) / OVERALL REVIEW OF THREE EMERGED OR RE-EMERGED VIRAL INFECTIOUS DISEASES: ZIKA, CHICUNGUNYA FEVER AND DENGUE (2016-2017)

El objetivo de esta revisión no exhaustiva, fue brindar un panorama de tres enfermedades infecciosas virales que emergieron o reemergieron en la Argentina durante el 2016: la enfermedad por el virus Zika, la fiebre chikungunya y el dengue. Se describen las características generales de estas enfermedades, principalmente en los aspectos epidemiológicos y las estrategias de control hasta abril de 2017. Se señala la inespecificidad de la sintomatología clínica en el período febril agudo y la necesidad de detectar en el laboratorio, anticuerpos específicos en el suero del paciente o la presencia de virus en sangre para confirmar específicamente la infección por virus dengue, Zika o chikungunya Se reseña la naturaleza dinámica y la complejidad de los factores ambientales, entre otros el calentamiento global y el cambio climático, que favorecen la emergencia y reemergencia de estas infecciones virales trasmitida por mosquitos vectores y modelada principalmente por la interacción entre el agente etiológico, el vector, el huésped y el ambiente

The aim of this non-exhaustive review is to offer an overall picture of three viral infectious diseases which emerged or reemerged in Argentina during 2016: Zika virus disease, chikungunya fever and dengue. General characteristics of these viral diseases, mainly their epidemiological aspects until April 2017 and control strategies, have been described. Non-specificity of clinical signs and symptoms during the acute febrile phase and the need of detecting specific antibodies in the patient's sera or the presence of virus in blood to confirm specifically the infection with dengue, Zika or chikungunya viruses have been pointed out. It also provides an overview of the dynamics and complexity of environmental factors, such as global warming and climatic change, that favor the emergence and reemergence of these viral infections transmitted by a mosquito vector, shaped mainly by the interaction among the etiological agent, the host, the vector, and the environment.

Cholesterol Levels in HIV- and/or HCV-Infected Drug Users Living in Argentina.

Improved understanding of cholesterol levels in HIV- and hepatitis C virus (HCV)-infected persons in Argentina will guide optimal antiretroviral therapy. The authors conducted a cross-sectional study in Argentina to describe associations between HIV, HCV, and cholesterol. Of the 202 participants, 21 were HIV infected, 15 were HCV infected, 46 were HIV/HCV coinfected, and 120 were HIV/HCV uninfected. HIV/HCV-uninfected participants had the highest total cholesterol (TC) and low-density lipoprotein (LDL) levels. Multivariate modeling revealed that HIV/HCV-coinfected patients had the lowest TC levels (-28.7 mg/dL, P < .001) compared to the HIV/HCV-uninfected reference group. Hepatitis C virus and HIV/HCV coinfection were associated with lower LDL levels (-21.4 mg/dL, P = .001 and -20.3 mg/dL, P < .0001, respectively). HIV and HIV/HCV coinfection, but not HCV alone, were associated with lower high-density lipoprotein levels (-9.1 mg/dL, P = .0008 and -6.8 mg/dL, P = .0006, respectively). Further study is needed to examine whether the more favorable lipid profile observed in HIV/HCV-coinfected persons is associated with a reduction in cardiovascular risk.

Human pegivirus molecular epidemiology in Argentina: potential contribution of Latin American migration to genotype 3 circulation.

In order to determine the human pegivirus (HPgV) genotypic diversity in Argentina taking into account the potential contribution of human migration from neighboring countries, samples from 130 Argentine injecting drug users, 116 Argentine- and 50 immigrant-pregnant women were analyzed. HPgV RNA prevalence among human immunodeficiency virus (HIV)-positive injecting drug users was similar to HIV-positive pregnant women, as was the case when comparing HIV-negative injecting drug users and HIV-negative pregnant women (P > 0.05). HPgV genotype 2 (HPgV/2) was prevalent among both Argentine injecting drug users and pregnant women, in contrast to HPgV/3 observed among pregnant women from Latin American countries with predominant indigenous populations and who had experienced their initial sexual intercourses--and possibly their source of infection--in those countries (P < 0.01). In addition, HPgV vertical and horizontal transmission was proven by molecular analysis of E2 gene and construction of identity matrixes with epidemiologically non-related isolates. This study shows that human migration from neighboring Latin American countries with predominant indigenous populations might contribute to HPgV/3 circulation in Argentina.

In vitro replication competence of a hepatitis B genotype D/A recombinant virus: dissimilar biological behaviour regarding its parental genotypes.

Hepatitis B virus (HBV) DNA recombinants contribute to ~30% of the overall full-length sequences already deposited in GenBank. However, their biological behaviour has not been analysed so far. In this study, the in vitro replication kinetics of the first D/A recombinant from the American continent differed from its parental genotypes, exhibiting higher extracellular levels of HBV DNA and hepatitis B e antigen. Southern blots of intracellular core-associated HBV DNA were in agreement with such results. Because this recombinant was obtained from an Argentinian injecting drug user belonging to a vulnerable community, these results are of singular relevance for regional public health. Further in vivo studies are urgently needed to determine the pathogenicity of these replicative competent clones.

Predominance of human lymphotropic T cell virus type 2 subtype B in urban populations of Argentina.

Human T-lymphotropic virus subtype b (HTLV-2b) infection has been described among aborigines from Northern Argentina, while HTLV-2a has been described in an injecting drug user (IDU) from a Central region, similar to the situation in Spain, the United States, and Brazil. In this study, 22 of the 26 strains analyzed from blood donors and HIV-1(+) individuals were HTLV-2b (84.6%) clustering with Amerindian references, while 4 HIV-1(+) (15.4%) were HTLV-2a. HTLV-2a sequences were closely related to Brazilian references in contrast to the previous Argentinean IDU strain that clustered with Africans and Amerindians from North America. In summary, these findings show that HTLV-2b is the major strain circulating in an urban population of Argentina. HTLV-2a/b could have been introduced from endemic South American countries such as Brazil and because of contact with other populations such as IDUs from Europe despite its introduction due to the increasing internal migration of aborigines to large urban centers. Considering this results and recent data about the dissemination of HTLV-1 in residents of Buenos Aires city, new studies among non-at-risk groups for HTLV-1/2 infection should be performed.

High rates of serum selenium deficiency among HIV- and HCV-infected and uninfected drug users in Buenos Aires, Argentina.

OBJECTIVE: To describe the prevalence of low serum Se and determine whether HIV, hepatitis C virus (HCV) and/or the types of drugs used are associated with serum Se in a cohort of infected and uninfected drug users. DESIGN: Independent correlates of low serum Se levels based on data collected from food recalls, physical examinations and clinical questionnaires were identified using multivariate regression analysis. SETTING: Buenos Aires, Argentina SUBJECTS: A total of 205 (twenty-five female and 180 male) former and current drug users. RESULTS: Drug users had an average serum Se level of 69·8 (sd 32·8) µg/d, [corrected] and 82 % were considered deficient (<85 µg/l). [corrected] Multivariate analyses found that HIV- and/or HCV-infected individuals had lower mean Se compared with healthy, uninfected drug users (HIV/HCV co-infection: -25·3 µg/l (se 7·6), P = 0·001; HIV alone: -28·9 µg/l (se 6·9), P < 0·001; HCV alone: -19·4 µg/l (se 7·1), P = 0·006). Current and previous drug use was associated with higher serum Se. Cigarette smoking and heavy alcohol consumption were not found to be associated with Se status. CONCLUSIONS: Low serum Se levels are highly prevalent among drug users in Buenos Aires, Argentina. Se supplementation and/or dietary interventions may be warranted in drug users who are at high risk for HIV and/or HCV infection.

Detection of HIV-1 dual infections in highly exposed treated patients.

BACKGROUND: Genetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B. OBJECTIVES: The aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfection STUDY DESIGN: Blood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene pol was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed. RESULTS: Five dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains. CONCLUSIONS: Our results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.

Hepatitis C virus among non-injecting cocaine users (NICUs) in South America: can injectors be a bridge?

AIM: To investigate the factors associated with hepatitis C virus (HCV) infection among non-injecting cocaine users (NICUs) and to compare practices associated with HCV and HIV infection. DESIGN: An intercountry cross-sectional study. Setting Buenos Aires and Montevideo metropolitan areas. PARTICIPANTS: A total of 871 NICUs. MEASUREMENTS: NICUs were interviewed and their blood was drawn and used for HCV, HIV, HBV surface antigen (HbsAg), HB-anticore and Venereal Disease Research Laboratory (VRDL) antibody assays. Bivariate and multivariate logistic regression analyses included comparisons of HCV and HIV mono-infected participants with HCV-HIV seronegatives. FINDINGS: Prevalence rates were 8.8 [95% confidence interval (CI): 6.9-10.8) for HCV and 7.9 (95% CI: 6.1-9.7) for HIV. HCV-infected NICUs were twice as likely as HCV-HIV seronegatives to have shared straws for cocaine snorting or sniffing, even when adjusted for other variables. HCV prevalence rates ranged from 3.6% among NICUs who denied sharing straws and having had an injection drug user (IDU) or an HIV-positive sexual partner to 12.6% among participants who reported ever having shared straws or having had either an IDU- or HIV-positive sexual partner (χ(2) (trend) = 6.56, P = 0.01). CONCLUSIONS: Non-injecting cocaine users from South America are vulnerable to multiple infections and HCV infection appears to occur through the sharing of straws. HCV infection is associated with intimate relationships with IDUs or HIV-seropositive partners, supporting the hypothesis that HCV risk may be due primarily to risk-taking behaviour associated with drugs in this population.

HIV/STI co-infections, syphilis incidence, and hepatitis B vaccination: the Buenos Aires cohort of men who have sex with men.

In a previous cohort study among 327 men who have sex with men (MSM) in Buenos Aires, an HIV incidence rate of 3.9 per 100 persons-year was reported. Using data from this study, we determined: (a) HIV/STI co-infections; (b) clinical manifestations of incident HIV infections; (c) syphilis incidence and its associated risk factors; and (d) adherence and immune response to hepatitis B virus (HBV) vaccine. During the cohort study, 12 incident HIV infections were found. Within this group, HIV infection alone was most frequent (42%), followed by co-infection of HIV/HBV (33%), and triple co-infection of HIV/HBV/syphilis (25%). The most frequent clinical manifestations among incident HIV cases were: pharyngitis, fever, lymphadenopathy, asthenia, and myalgia. Seven new syphilis infections were detected yielding an incidence rate of 2.4 (95% CI=1.07 - 4.73) per 100 persons-year. Sex work was the only significant risk factor associated with syphilis seroconversion (hazard rate=10.93, p-value=0.033). Only 7% of cohort participants reported having received HBV vaccine. Ninety-percent of the 204 cohort members who agreed to be vaccinated completed the HBV vaccination schedule with an immune response rate of 85%. Our findings suggest the need to increase the access to serologic testing for STI and HBV immunization, as well as the developing of effective HIV/STI behavioral and educational prevention programs among MSM in Buenos Aires.

Sexual behavior and HBV infection among noninjecting cocaine users (NICUs).

The aim is to estimate HBV prevalence and the associated risks among noninjecting cocaine users (NICUs). In 2002-2003, a total of 824 NICUs from Buenos Aires (Argentina) and Montevideo (Uruguay) were interviewed using a structured questionnaire. Serologic tests were carried out for Human Immunodeficiency Virus (HIV), hepatitis B (HBV), syphilis, and others. The population was divided into two serologic groups: HBV-infected and seronegative group. Univariate and binary logistic model were developed. The results seem to indicate that, among NICUs, HBV is transmitted through sexual contact. Prevention measures, including vaccine, are needed in order to control and minimize risks. The study's limitations are noted.

Multiple infections and associated risk factors among non-injecting cocaine users in Argentina.

The aim of this study was to estimate the seroprevalence rates of human immunodeficiency virus (HIV), hepatitis B virus (HBV, core antibody), hepatitis C virus (HCV), and syphilis infections and analyze associated risk factors among 504 non-injecting cocaine users (NICU) in Buenos Aires, Argentina. Participants were interviewed in face-to-face sessions through a short structured questionnaire. Using venipuncture, 10 mL of blood was collected. Seroprevalence rates were: HIV (6.3%), HBV (9%), HCV (7.5%), and VDRL (4.2%). The risk of being infected with HIV, HBV, and HCV was significantly associated with having had a sex partner who was either a drug injector or who was known to be HIV positive. HIV and HCV infections were associated with former imprisonment, and HCV was associated with having been tattooed. Because of the rising number of NICU and the multiple infections detected, it is essential to implement prevention strategies focused on this population.

Multiple infections and associated risk factors among non-injecting cocaine users in Argentina

El propósito de este estudio era estimar los índices de seroprevalencia del virus de inmunodeficiencia humano (VIH), virus de la hepatitis B (VHB, anticuerpo core), virus de la hepatitis C (VHC) e infecciones de sífilis y analizar factores de riesgo asociados entre 504 usuarios de cocaína no inyectable (UCNI) en la ciudad de Buenos Aires, Argentina. Se entrevistó a los participantes en sesiones cara a cara a través de un cuestionario estructurado corto. Usando el método de la venipunción se recogieron 10mL de sangre. Las tasas de seroprevalencia fueron: VIH (6,3 por ciento), VHB (9 por ciento), VHC (7,5 por ciento), y VDRL (4,2 por ciento). El riesgo de infección por VIH, VHB, y VHC se asoció significativamente a mantener relaciones sexuales con un compañero/a que era consumidor de la droga inyectada o que era conocido por ser VIH positivo. Las infecciones de VIH y de VHC se asociaron a haber estado encarcelado anteriormente, y la de VHC se asoció también a haber sido tatuado. Debido al número creciente de UCNI y a las infecciones múltiples detectadas, es esencial implementar estrategias de prevención centradas en esta población.

The aim of this study was to estimate the seroprevalence rates of human immunodeficiency virus (HIV), hepatitis B virus (HBV, core antibody), hepatitis C virus (HCV), and syphilis infections and analyze associated risk factors among 504 non-injecting cocaine users (NICU) in Buenos Aires, Argentina. Participants were interviewed in face-to-face sessions through a short structured questionnaire. Using venipuncture, 10mL of blood was collected. Seroprevalence rates were: HIV (6.3 percent), HBV (9 percent), HCV (7.5 percent), and VDRL (4.2 percent). The risk of being infected with HIV, HBV, and HCV was significantly associated with having had a sex partner who was either a drug injector or who was known to be HIV positive. HIV and HCV infections were associated with former imprisonment, and HCV was associated with having been tattooed. Because of the rising number of NICU and the multiple infections detected, it is essential to implement prevention strategies focused on this population.

Human immunodeficiency virus and tuberculosis in Argentina: prevalence, genotypes and risk factors.

The objective of this study was to determine the prevalence and genetic variability of human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted infections (STIs) among 205 patients with clinical diagnosis of tuberculosis (TB) in Buenos Aires in 2001. Infections with hepatitis B virus (HBV), HIV-1, hepatitis C virus (HCV), Treponema pallidum and human T-cell lymphotropic virus types I/II were diagnosed in 37/187 (19.8 %), 35/205 (17.1 %), 22/187 (11.8 %), 13/187 (7.0 %) and 4/181 (2.2 %) patients, respectively. Almost one in three participants (33.1 %) presented at least one infection in addition to TB. Multiresistance to TB drugs (isoniazid plus rifampicin) was detected in the isolates recovered from three patients. Injecting drug use was detected as the main risk factor for HIV, HBV and HCV infections. Of ten patients who died, eight were infected with HIV. HIV genetic characterization showed the presence of two different subtypes. Env subtype F was found in 13/24 samples (54.2 %) and subtype B in 11/24 samples (45.8 %) by heteroduplex mobility assay. Sequencing of the protease/RT region was performed in ten samples: three were characterized as subtype B and seven as B/F recombinants by bootscanning analysis. Phylogenetic analysis of four full-length sequences showed that three were the circulating recombinant form CRF12_BF. The results of this study suggest an urgent need to detect HIV infection in high-risk groups to prevent future HIV transmission as well as morbidity and mortality associated with TB by providing highly active antiretroviral therapy (HAART) and/or TB treatment. Collaboration between TB and HIV programmes seems to be the best approach to decrease the incidence of these diseases, especially in high-prevalence HIV settings.

HTLV-1/2 among high-risk groups in Argentina: molecular diagnosis and prevalence of different sexual transmitted infections.

The objectives of this study were to estimate the prevalence and characterize the epidemiologic patterns of HTLV-1/2 infections and co-infections with HIV, HBV (hepatitis B), HCV (hepatitis C), and Treponema Pallidum in five different high-risk groups, including injecting drug users (IDUs), female sex workers (FSWs), men who have sex with men (MSM), patients with tuberculosis (TB), and patients attending clinics for sexually transmitted infections (STIs) in Buenos Aires, Argentina. The HTLV-1/2 prevalence was 19.1% (33/173) for IDUs, 2.0% (10/613) for FSWs, 2.1% (4/187) for TB, 1.0% (4/400) for STIs and 0.4% (3/282) for MSM, respectively. Among all groups, the higher percentages of co-infection were HTLV-1/HBV (63%, 17/27) and HTLV-1/HCV (52%, 14/27). Among IDUs, there was a high percentage of co-infection of HTLV-2 with HCV (96.3%, 26/27), HIV (92.6%, 25/27), and HBV (77.8%, 21/27), respectively. In summary, HTLV-1/2 infections appear to be widely distributed among high-risk groups in a nonendemic area of Argentina being the co-infection with HBV and HCV more frequent among IDUs.

Buenos Aires cohort of men who have sex with men: prevalence, incidence, risk factors, and molecular genotyping of HIV type 1.

The prevalence, incidence, risk factors, and molecular genotyping of HIV-1 infection among men who have sex with men (MSM) were assessed through a prospective cohort study. The study was conducted in Buenos Aires from February 2003 to December 2004. Sociodemographic, sexual risk behavior data, and blood samples for HIV testing were collected at baseline and at 6 and 12 months. Cox regression analysis was applied to determine risk factors associated with HIV seroconversion. HIV-positive samples were analyzed by partial (pro/RT) and full-length genome sequencing. Of 811 HIV-negative participants evaluated at baseline, 327 volunteers that fulfilled the inclusion criteria were enrolled. Retention rates at 6 and 12 months were 97.2% and 91.5%, respectively. Twelve MSM seroconverted for HIV infection [incidence rate = 3.9 (95% CI = 2.0-6.7) per 100 person-years]. HIV seroconversion was associated with a greater number of different sexual contacts in the preceding 6 months (> or =10, hazard ratio = 3.3, 95% CI: 1.1-10.4). By partial pro/RT genotyping analysis, 83% HIV-positive samples were subtype B and 17% samples were BF recombinants, most of these being unique recombinant forms. This study describes for the first time the recruitment and follow-up of a cohort of MSM in Argentina. Retention rates and HIV incidence rate were high. These data should be considered as a promising potential population for HIV vaccine trials.

First report of an HIV-1 triple recombinant of subtypes B, C and F in Buenos Aires, Argentina.

We describe the genetic diversity of currently transmitted strains of HIV-1 in men who have sex with men (MSM) in Buenos Aires, Argentina between 2000 and 2004. Nearly full-length sequence analysis of 10 samples showed that 6 were subtype B, 3 were BF recombinant and 1 was a triple recombinant of subtypes B, C and F. The 3 BF recombinants were 3 different unique recombinant forms. Full genome analysis of one strain that was subtype F when sequenced in pol was found to be a triple recombinant. Gag and pol were predominantly subtype F, while gp120 was subtype B; there were regions of subtype C interspersed throughout. The young man infected with this strain reported multiple sexual partners and sero-converted between May and November of 2004. This study reported for the first time the full genome analysis of a triple recombinant between subtypes B, C and F, that combines in one virus the three most common subtypes in South America.

HIV seroincidence estimates among at-risk populations in Buenos Aires and Montevideo: use of the serologic testing algorithm for recent HIV seroconversion.

Using the serological testing algorithm for recent HIV seroconversion, we estimated annualized incidences (per 100 person-years) of HIV-1 infection in different at-risk groups in Buenos Aires and Montevideo, during a 5-year period between 1998 and 2003. HIV-positive serum samples from 9 serosurveys conducted among men who have sex with men, patients attending clinics for a sexually transmitted infections consult (STIs), female commercial sex workers, injecting drug users (IDUs), noninjecting cocaine users (NICUs), asymptomatic women screened for HIV infection, and patients with tuberculosis were used. HIV incidences were as follows: 6.7 for men who have sex with men, 2.0 for STIs, 1.3 for female commercial sex workers, 0.0 for Argentinean IDUs, 10.3 for Uruguayan IDUs, 3.1 for Argentinean NICUs, 4.4 for Uruguayan NICUs, and 2.4 for patients with tuberculosis. Among asymptomatic women screened for HIV infection, incidence rose from 0.4 in 1998 to 4.6 in 1999 and to a high of 10.2 in the year 2000. Unexpectedly, high HIV incidences were detected among at-risk groups in Buenos Aires and Montevideo. This pattern shows an emerging HIV epidemic among heterosexuals stemming from core HIV-infected at-risk groups. There is an urgent need for development and implementation of specific prevention strategies to address this burgeoning epidemic.