21-Hydroxylase gene mutant allele CYP21A2*15 strongly linked to the resistant HLA haplotype B*14:02-DRB1*01:02 in chronic Chagas disease.

We previously reported protective haplotype HLA-B*14:02-DRB1*01:02 against chronic Chagas disease in Bolivia. The V281L mutant allele of the 21-Hydroxylase gene, CYP21A2*15, is reported to be located in the Class III region of the Human leukocyte antigen region and linked to the haplotype HLA-B*14:02-DRB1*01:02. The mutant allele might play a primary role in the pathogenesis of chronic Chagas disease in the associated HLA region. We analyzed the frequency of this allele in the same subjects for the previous one. The statistical analysis showed a significant association of the CYP21A2*15 with resistance to severe chronic Chagas disease (OR=0.207273; Pv=0.0041). However, there is no significant tendency of the mutant gene contribution to the resistance after the elimination of the HLA-B*14:02-DRB1*01:02 linked mutants (OR=0.38; Pv=0.1533). Although the frequency of the CYP21A2*15 was small, we found no primary contribution of this mutation to the protection against chronic Chagas disease.

Hantavirus pulmonary syndrome in Santa Cruz, Bolivia: outbreak investigation and antibody prevalence study.

We report the results of an investigation of a small outbreak of hantavirus pulmonary syndrome in 2002 in the Department of Santa Cruz, Bolivia, where the disease had not previously been reported. Two cases were initially reported. The first case was a physician infected with Laguna Negra virus during a weekend visit to his ranch. Four other persons living on the ranch were IgM antibody-positive, two of whom were symptomatic for mild hantavirus pulmonary syndrome. The second case was a migrant sugarcane worker. Although no sample remained to determine the specific infecting hantavirus, a virus 90% homologous with Río Mamoré virus was previously found in small-eared pygmy rice rats (Oligoryzomys microtis) trapped in the area. An antibody prevalence study conducted in the region as part of the outbreak investigation showed 45 (9.1%) of 494 persons to be IgG positive, illustrating that hantavirus infection is common in Santa Cruz Department. Precipitation in the months preceding the outbreak was particularly heavy in comparison to other years, suggesting a possible climatic or ecological influence on rodent populations and risk of hantavirus transmission to humans. Hantavirus infection appears to be common in the Santa Cruz Department, but more comprehensive surveillance and field studies are needed to fully understand the epidemiology and risk to humans.

Protective human leucocyte antigen haplotype, HLA-DRB1*01-B*14, against chronic Chagas disease in Bolivia.

BACKGROUND: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8-10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. METHODOLOGY: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% megacolon and 58.1% showed neither of them. A further 62 seropositive megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. PRINCIPAL FINDINGS: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from megacolon as well as in those with ECG alteration and/or megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011 haplotype was associated with resistance against chronic Chagas disease. CONCLUSIONS: This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

Arboviral etiologies of acute febrile illnesses in Western South America, 2000-2007.

BACKGROUND: Arthropod-borne viruses (arboviruses) are among the most common agents of human febrile illness worldwide and the most important emerging pathogens, causing multiple notable epidemics of human disease over recent decades. Despite the public health relevance, little is know about the geographic distribution, relative impact, and risk factors for arbovirus infection in many regions of the world. Our objectives were to describe the arboviruses associated with acute undifferentiated febrile illness in participating clinics in four countries in South America and to provide detailed epidemiological analysis of arbovirus infection in Iquitos, Peru, where more extensive monitoring was conducted. METHODOLOGY/FINDINGS: A clinic-based syndromic surveillance system was implemented in 13 locations in Ecuador, Peru, Bolivia, and Paraguay. Serum samples and demographic information were collected from febrile participants reporting to local health clinics or hospitals. Acute-phase sera were tested for viral infection by immunofluorescence assay or RT-PCR, while acute- and convalescent-phase sera were tested for pathogen-specific IgM by ELISA. Between May 2000 and December 2007, 20,880 participants were included in the study, with evidence for recent arbovirus infection detected for 6,793 (32.5%). Dengue viruses (Flavivirus) were the most common arbovirus infections, totaling 26.0% of febrile episodes, with DENV-3 as the most common serotype. Alphavirus (Venezuelan equine encephalitis virus [VEEV] and Mayaro virus [MAYV]) and Orthobunyavirus (Oropouche virus [OROV], Group C viruses, and Guaroa virus) infections were both observed in approximately 3% of febrile episodes. In Iquitos, risk factors for VEEV and MAYV infection included being male and reporting to a rural (vs urban) clinic. In contrast, OROV infection was similar between sexes and type of clinic. CONCLUSIONS/SIGNIFICANCE: Our data provide a better understanding of the geographic range of arboviruses in South America and highlight the diversity of pathogens in circulation. These arboviruses are currently significant causes of human illness in endemic regions but also have potential for further expansion. Our data provide a basis for analyzing changes in their ecology and epidemiology.

Lineage analysis of circulating Trypanosoma cruzi parasites and their association with clinical forms of Chagas disease in Bolivia.

BACKGROUND: The causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU): Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon) from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism. METHODS AND FINDINGS: Between 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon). DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA) was amplified from 196 out of 306 samples (64.1%), of which 104 (53.3%) were Tc IId, 4 (2.0%) Tc I, 7 (3.6%) Tc IIb, 1 (0.5%) Tc IIe, 26 (13.3%) Tc I/IId, 1 (0.5%) Tc I/IIb/IId, 2 (1.0%) Tc IIb/d and 51 (25.9%) were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%), TPK like (48.9%) and Bug-like (1.5%). There was no significant association between Tc types and clinical manifestations of disease. CONCLUSIONS: None of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia.

Prevention of blood-borne diseases in Bolivia, 1993-2002.

This report shows the outcome of a coordinated effort by locals, foreign institutions, and an international agency, from 1996-2002, aimed at preventing transmission of blood-borne diseases in Santa Cruz, Bolivia. From 2001-2002, testing the donor pool for HIV prevented transfusion of 32 infected units and 29 infections. With 100% screening coverage, 196 hepatitis B virus (HBV)-infected units were discarded, and 177 infections of HBV were prevented between 1999 and 2002. Incomplete screening for hepatitis C virus (HCV) may have tainted nine units of blood and generated eight HCV infections in 1999. On the other hand, 600 units infected with HCV were discarded, and 540 HCV infections were prevented between 1999 and 2002. Screening for Chagas disease prevented transfusion of 10,661 tainted units and 2,133 infections from 1999 to 2002. From 1996-2002, the investment was US$1,108,000.

Immigration status and HIV-risk related behaviors among female sex workers in South America.

This study compares immigrant (i.e., foreigner) with non-immigrant (i.e., local/native) HIV-related risk behaviors among female sex workers (FSW) in South America. A total of 1,845 FSW were enrolled in Argentina, Bolivia, Ecuador, and Uruguay. According to their nationality, 10.1% of participants were immigrant FSW. Immigrant FSW were more likely to be younger in Argentina; to work in a disco/bar in Bolivia; to be single and use illegal drugs in Ecuador; and to work in a brothel, consume alcohol, and have sex with foreign clients in Uruguay. HIV-related sexual and drug use behaviors were more common among immigrant FSW in Bolivia, Ecuador, and Uruguay. Country-specific HIV/STI prevention and control programs should be developed for immigrant FSW populations in South America.

Prevalences, genotypes, and risk factors for HIV transmission in South America.

HIV cross-sectional studies were conducted among high-risk populations in 9 countries of South America. Enzyme-linked immunosorbent assay screening and Western blot confirmatory testing were performed, and env heteroduplex mobility assay genotyping and DNA sequencing were performed on a subset of HIV-positive subjects. HIV prevalences were highest among men who have sex with men (MSM; 2.0%-27.8%) and were found to be associated with multiple partners, noninjection drug use (non-IDU), and sexually transmitted infections (STIs). By comparison, much lower prevalences were noted among female commercial sex workers (FCSWs; 0%-6.3%) and were associated mainly with a prior IDU and STI history. Env subtype B predominated among MSM throughout the region (more than 90% of strains), whereas env subtype F predominated among FCSWs in Argentina and male commercial sex workers in Uruguay (more than 50% of strains). A renewed effort in controlling STIs, especially among MSM groups, could significantly lessen the impact of the HIV epidemic in South America.

Hantavirus pulmonary syndrome in Central Bolivia: relationships between reservoir hosts, habitats, and viral genotypes.

In August 2002, two cases of hantavirus pulmonary syndrome (HPS) were confirmed in Mineros and Concepcion, within the Santa Cruz Department of Bolivia. Extensive alteration of the native ecosystem, from dense forest to pasture or sugarcane, had occurred in both regions. An ecologic assessment of reservoir species associated with the human disease identified a single hantavirus antibody-positive Oligoryzomys microtis from Mineros and three hantavirus antibody-positive Calomys callosus from Concepcion. In Mineros, the virus from the O. microtis was 90% similar to sequences published for Rio Mamore virus. Viral nucleotide sequences from two C. callosus were 87-88% similar to the sequence of Laguna Negra virus. The viral sequence from the C. callosus was 99% identical to viral sequences obtained from the HPS patient in this area, implicating C. callosus as the host and Laguna Negra virus as the agent responsible for the HPS case near Concepcion.

Yellow fever virus infectivity for Bolivian Aedes aegypti mosquitoes.

The absence of urban yellow fever virus (YFV) in Bolivian cities has been attributed to the lack of competent urban mosquito vectors. Experiments with Aedes aegypti from Santa Cruz, Bolivia, demonstrated infection (100%), dissemination (20%), and transmission of a Bolivian YFV strain (CENETROP-322).

Incidence of surgical-site infections and the validity of the National Nosocomial Infections Surveillance System risk index in a general surgical ward in Santa Cruz, Bolivia.

OBJECTIVES: To estimate the frequency of and risk factors for surgical-site infections (SSIs) in Bolivia, and to study the performance of the National Nosocomial Infections Surveillance (NNIS) System risk index in a developing country. DESIGN: A prospective study with patient follow-up until the 30th postoperative day. SETTING: A general surgical ward of a public hospital in Santa Cruz, Bolivia. PATIENTS: Patients admitted to the ward between July 1998 and June 1999 on whom surgical procedures were performed. RESULTS: Follow-up was complete for 91.5% of 376 surgical procedures. The overall SSI rate was 12%. Thirty-four (75.6%) of the 45 SSIs were culture positive. A logistic regression model retained an American Society of Anesthesiologists score of more than 1 (odds ratio [OR], 1.87), a not-clean wound class (OR, 2.28), a procedure duration of more than 1 hour (OR, 1.81), and drain (OR, 1.98) as independent risk factors for SSI. There was no significant association between the NNIS System risk index and SSI rates. However, a "local" risk index constructed with the above cutoff points showed a linear trend with SSI (P < .001) and a relative risk of 3.18 for risk class 3 versus a class of less than 3. CONCLUSIONS: SSIs cause considerable morbidity in Santa Cruz. Appropriate nosocomial infection surveillance and control should be introduced. The NNIS System risk index did not discriminate between patients at low and high risk for SSI in this hospital setting, but a risk score based on local cutoff points performed substantially better.

Molecular Epidemiology of HIV Type 1 in Ecuador, Peru, Bolivia, Uruguay, and Argentina.

Surveillance for HIV infection among people at increased risk was conducted in five countries in South America. Seroprevalence studies were conducted in more than 36,000 people in Ecuador, Peru, Boliva, Uruguay, and Argentina, along with genetic analysis of the HIV-1 strains. In all countries, the prevalence of HIV-1 among men who have sex with men (MSM) was high (3-30%), whereas the prevalence among female commercial sex workers (FCSMs) was low (0.3-6%). By envelope heteroduplex mobility assay, subtype B predominated in MSM communities and in FCSWs in Ecuador, Bolivia, and Peru. A new genetic screening assay, the multiregion hybridization assay for subtypes B and F (MHA-bf), was developed to improve large-scale genetic screening in South America. MHA-bf can screen four regions of the genome for subtype B or subtype F, and thus can detect most recombinants. The sensitivity of MHA-bf when applied to a panel of pure subtypes and CRF12_BF was 100%, and 88% of unique recombinants were also detected as recombinant. Using MHA-bf, more than 80% of samples from Ecuador, Peru, and Bolivia were classified as pure subtype B, whereas in Uruguay and Argentina this proportion was only 30 to 40%. BF recombinants were the most prevalent form of HIV-1 in Uruguay and Argentina. Subtype B is the most common subtype in countries lacking injecting drug use (IDU) epidemics, whereas BF recombinants are more common in countries where extensive IDU epidemics have been documented, suggesting the ontogeny of recombinant strains in particular risk groups in South America.

Andes virus and first case report of Bermejo virus causing fatal pulmonary syndrome.

Two suspected hantavirus pulmonary syndrome (HPS) cases from Bolivia occurred in May and July 2000 and were confirmed by enzyme-linked immunosorbent assay (ELISA)-ANDES using N-Andes recombinant antigen serology. Clot RNAs from the two patients were subjected to reverse transcription-polymerase chain reaction (PCR) amplification and sequencing. We describe two characterized cases of HPS. One was caused by infection with Bermejo virus and the other with Andes Nort viral lineage, both previously obtained from Oligoryzomys species. This is the first report of molecular identification of a human hantavirus associated with Bermejo virus.

Importancia del Laboratorio en el Diagnóstico de la Fiebre Amarilla / Importance of the Laboratory in the Diagnosis of Yellow Fever

En el contexto de un sistema de vigilancia de fiebre amarilla,el laboratorio puede ser de gran ayuda para la confirmación rápida de los casos con sospecha clínica.Desde el punto de vista de la Salud Pública,la rapidez con que un laboratorio puede confirmar casos con sospecha clínica de la enfermedad,tiene gran importancia ya que de ello dependerán las medidas de control de brote.(au)

Resultados del taller realizado en CENETROP para la padronizacion de los test serologicos de descarte para infeccion chagasica en bancos de sangre / Results of the workshop help in CENETROP for the padronizacion of the test serological of ruling out for Chagas infection in blood banks

Con la finalidad de estandarizar el test serológico y el nivel de corte para descartar a los infectados por T. cruzi en donantes de sangre se realizo el presente taller. entre las conclusiones mas importantes se destacan los siguientes acuerdos: 1) Utilizar el test de HAI en una dilucion 1/8 en todos los bancos de sangre, 2) Realizacion de talleres periodicos de padronizacion serologica, 3) Recomendar a los profesionales de la salud el uso racional de la transfusion sanguinea y 4) Soliciatr al S.N.S. la actualizacion de la resolucion ministerial sobre la reglamentacion del uso del violeta de genciana para prevenir la transmision del T. cruzi por via transfusional.

Infeccion por tripanosoma cruzi en donantes de sangre en Santa Cruz Bolivia. Influencia de la migracion / Infection by trypanosoma cruzi in donors of blood in Santa Cruz Bolivia. Influence of the migration

Se realizo un estudio retrospectivo del año 1993, de los registros del banco de sangre del Hospital San Juan de Dios para conocer la prevalencia de infeccion por tripanosoma cruzi entre los donantes de sangre y su relacion con el lugar de nacimiento. Se contabilizo el volumen total de transfusiones en los bancos de sangre de cinco centros asistenciales. El total de transfusiones realizadas durante el año 1993 en lso centros estudiados fue de 7199. Se estima que en Santa Cruz se realizan por lo menos 10.000 transfusiones por año. La prevalencia de infeccion por el T. cruzi entre los donantes del banco de sangre del Hospital San Juan de Dios fue el 48.5 por ciento (1225/2540). Se observo una diferencia significativa en la prevalencia de infeccion chagasica entre los migrantes y los oriundos de la ciudad de Santa Cruz.

Enfermedad de chagas en donantes de sangre en Santa Cruz de la Sierra / Chagas disease in blood donors in Santa Cruz de la Sierra

Se realizo una encuesta entre candidatos a donantes de sangre en tres centros hospitalarios de la ciudad para conocer la prevalencia actual de infeccion por T. cruzi en donantes de sangre y la influencia que tiene la migracion rural-urbana, en esta importante patologia. Se analizaron ademas los test serologicos que usan los bancos de sangre para destacar a los sero-positivos y el nivel de corte utilizado. Se comparo el resultado del test serologico de cada centro con el resultado obtenido en CENETROP (HAI titulo 1/8). Se observo una prevalencia de infeccion chagasica del 39.6 por ciento y no se encontro diferencia significativa entre los migrantes y los oriundos de la ciudad de Santa Cruz. Los test serologicos utilizados y los titulos para descartar a los infectados por T. cruzi son diferentes en los tres centros. Se observo muy poca concordancia entre el resultado serologico realizado en los bancos de sangre y el reslizado en CENETROP (Kappa=0.08, p=0.20). Se observo tambien un uso excesivo de transfusion sanguinea por cirugias, anemias y solo un 6.3 por ciento por hemorragias agudas.

Resúmen de los datos obtenidos por CENETROP sobre la transmisión del T. Cruzi por via transfusional en Santa Cruz, Bolivia. Durante el año 1994 / Summary of the data obtained by CENETROP on the transmission of the T. Cruzi by transfusion way in Santa Cruz, Bolivia. During the year 1994

El problema de la transmision via transfucional del T. Cruzi en Santa Cruz, ha sido reiteradamente analizado por varios investigadores. En este documento se analiza los datos obtenidos por el CENETROP, durante el año 1994. Los datos se presentan en orden cronologico.

Proyecto de reactivación de las actividades científicas del Centro Nacional de Enfermedades Tropicales (CENETROP) en Santa Cruz. Anexo 1: Documento técnico / Es

El objetivo del proyecto es equilibrio entre actividades en docencia, investigación y servicios alcanzado. Investigaciones útil y válidas en las enfermedades tropicales e infecciosas realizadas.