Cardiomyopathy, adult valve disease and heart failure in South America

Continued assessment of temporal trends in mortality and epidemiology of specific cardiovascular diseases in South America is needed to provide a scientific basis for rational allocation of the limited healthcare resources and introduction of strategies to reduce risk and predict the future burden of cardiovascular disease. The epidemiology of cardiomyopathies, adult valve disease and heart failure (HF) in South America is reviewed here. Diseases of the circulatory system are the main cause of death based on data from about 50% of the South American population. Among the cardiovascular causes of death, cerebrovascular disease is predominant followed by ischaemic heart disease, other heart diseases and hypertensive disease. Of note, cerebrovascular disease is the main cause of death in women, and race also influenced cardiovascular mortality rates. HF is the most important cardiovascular reason for admission to hospital due to cardiovascular disease of ischaemic, idiopathic dilated cardiomyopathic, valvular, hypertensive and chagasic aetiologies. Also, mortality due to HF is high, especially owing to Chagas' disease. HF and aetiologies associated with HF are responsible for 6.3% of deaths. Rheumatic fever is the leading cause of valvular heart disease. The findings have important public health implications because the allocation of healthcare resources, and strategies to reduce the risk of HF should also consider controlling Chagas' disease and rheumatic fever in South American countries.

Vaccination in Brazilian HIV-infected adults: A cross-sectional study

HIV-infected patients are at risk for vaccine-preventable infections. The Brazilian National Immunization Program provided recommendations for this population. However, the vaccine coverage reached by this program is unknown. This study aimed at evaluating the vaccine coverage of HIV-infected adults followed at Hospital das Clinicas, University of Sao Paulo School of Medicine. Data were collected on age, gender, mode of HIV transmission, Centers for Disease Classification 1993 classification (CDC/93), antiretrovirals, CD4 count, HIV viral load, and immunization charts, from April 2003 to August 2004. We interviewed 144 randomly selected patients, 74% male; mean age, 39.95 years; CDC classification: A, 40.6%; B, 19.6%; and C, 39.9%. Most of patients were undergoing highly active antiretroviral therapy (HAART; 86.8%). Mean CD4 count 442.6 cells/mm(3). Viral load less than 400 copies per milliliter in 59.4% of patients. Only 36.1% of patients were adequately immunized for diphtheria/tetanus, 54.9% for pneumococcus, 24.3% for flu, and 76.9% for hepatitis B. In relation to live attenuated vaccines, 5 patients received measles, mumps, and rubella vaccine and 7 patients yellow fever vaccine. Two patients were vaccinated against yellow fever despite CD4 less than 200 cell/mm(3). We verified poor vaccine coverage in HIV-infected patients. Vaccination campaigns and incorporation of vaccine rooms in sexually transmitted disease (STD)/AIDS clinics could improve this situation.

Modeling the risk of malaria for travelers to areas with stable malaria transmission

Background: Malaria is an important threat to travelers visiting endemic regions. The risk of acquiring malaria is complex and a number of factors including transmission intensity, duration of exposure, season of the year and use of chemoprophylaxis have to be taken into account estimating risk. Materials and methods: A mathematical model was developed to estimate the risk of non-immune individual acquiring falciparum malaria when traveling to the Amazon region of Brazil. The risk of malaria infection to travelers was calculated as a function of duration of exposure and season of arrival. Results: The results suggest significant variation of risk for non-immune travelers depending on arrival season, duration of the visit and transmission intensity. The calculated risk for visitors staying longer than 4 months during peak transmission was 0.5% per visit. Conclusions: Risk estimates based on mathematical modeling based on accurate data can be a valuable tool in assessing risk/benefits and cost/benefits when deciding on the value of interventions for travelers to malaria endemic regions.

Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in Sao Paulo, Brazil

The dengue virus has a single-stranded positive-sense RNA genome of similar to 10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1-4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in Sao Jose do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000-2001. Sixty DENV-3 from Sao Jose do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R(0) = 1.53 and values for lineage 2 of R(0) = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area.

Threat of Dengue to Blood Safety in Dengue-Endemic Countries

Dengue, the most common arbovirus infection globally, is transmitted by mosquito vectors. Healthcare-related transmission, including transmission by blood products, has been documented, although the frequency of these occurrences is unknown. Dengue is endemic to Singapore, a city-state in Asia. Using mathematical modeling, we estimated the risk for dengue-infected blood transfusions in Singapore in 2005 to be 1.625-6/10,000 blood transfusions, assuming a ratio of asymptomatic to symptomatic infections of 2:1 to 10:1. However, the level of viremia required to cause clinical dengue cases is person-dependent and unknown. Further studies are needed to establish the magnitude of the threat that dengue poses to blood safety in countries where it is endemic. It will then be possible to assess whether screening is feasible and to identify approaches that are most cost-effective on the basis of characteristics of local populations and seasonality of dengue.

Prognostic evaluation of early rheumatoid arthritis

The progression of rheumatoid arthritis (RA) is quite variable, ranging from very mild or subclinical forms (approx. 10%) to rapidly progressing and debilitating forms (10-15%). The majority of patients present with an intermediate stage with episodes of exacerbation separated by periods of relative inactivity, which evolves to progressive functional losses. To optimise the therapeutic management of early RA it is necessary to perform periodic evaluations of the clinical and laboratory test responses to the treatment instituted, as well as the parameters indicating disease prognosis. Composite measures are frequently used to evaluate the disease activity score (DAS), including the response criteria of the American College of Rheumatology (ACR), the response criteria and the DAS according to the European League Against Rheumatism (EULAR) and the composite indices of disease activity (CIDsA): DAS, the index of disease activity based on 28 joints (DAS 28), the simplified disease activity index (SDAI) and the clinical disease activity index (CDAI). The evaluation of prognosis includes investigation of the absence or occurrence of disease and joint damage remission. Due to the multifaceted nature of RA, no single clinical or laboratory parameter is able to describe satisfactorily the level of inflammatory activity or the disease prognosis at any given time.

First Report of the Isolation and Molecular Characterization of Rickettsia amblyommii and Rickettsia felis in Central America

During 2010, 15 adult ticks, identified as Amblyomma cajennense, were collected from horses in Cahuita and Turrialba districts, whereas 7 fleas, identified as Ctenocephalides felis, were collected from a dog in San Jose city, Costa Rica. In the laboratory, three A. cajennense specimens, two from Cahuita and one from Turrialba, were individually processed for rickettsial isolation in cell culture, as was a pool of seven fleas. Rickettsiae were successfully isolated and established in Vero cell culture from the three ticks and from a pool of seven fleas in C6/36 cell culture. The three tick isolates were genotypically identified as Rickettsia amblyommii, and the flea isolate was identified as Rickettsia felis through DNA sequencing of portions of the rickettsial genes gltA, ompA, and ompB of each isolate. In addition, other seven ticks were shown to contain rickettsial DNA. Polymerase chain reaction products of at least two of these ticks were sequenced and also showed to correspond to R. amblyommii. Overall, 66.7% (10/15) of the A. cajennense adult ticks were found to be infected with rickettsiae. This is the first report of a successful isolation in cell culture of R. amblyommii and R. felis from Central America.

Serologic Survey for Rickettsiosis in Bats from Sao Paulo City, Brazil

Blood serum samples were collected from 451 bats captured within the Sao Paulo city from April 2007 to November 2008, and individually tested by indirect immunofluorescence assay against antigens derived from five Rickettsia species reported to occur in Brazil: the spotted fever group (SFG) species R. rickettsii, R. parkeri, R. amblyommii, R. rhipicephali, and the ancestral group species R. bellii. For this purpose, an anti-bat immunoglobulin G was produced and used in the present study. Overall, 8.6% (39/451), 9.5% (34/358), 7.8% (28/358), 1.1% (4/358), and 0% (0/358) serum samples were reactive to R. rickettsii, R. parkeri, R. amblyommii, R. rhipicephali, and R. bellii, respectively. Endpoint titers of reactive sera ranged from 64 to 256. From 20 bat species of 3 different families (Molossidae, Vespertilionidae, and Phyllostomidae), 46 animals were shown to be reactive to at least one rickettsial antigen. Seropositivity per bat species ranged from 0% to 33.3%. Most of the serologically positive sera reacted with two or more rickettsial antigens. Seropositivity for SFG rickettsial antigens in the absence of reactivity against R. bellii (ancestral group species) suggests that bats from Sao Paulo city can be infected by SFG rickettsiae. The possible role of soft ticks in serving as vectors of SFG rickettsiae to bats within the Sao Paulo city, associated to its public health risks, is discussed.

Tick-Borne Bacteria in Free-Living Jaguars (Panthera onca) in Pantanal, Brazil

Tick-borne bacteria were investigated in 10 free-living jaguars and their ticks in the Pantanal biome, Brazil. Jaguar sera were tested by indirect fluorescent antibody assays using Rickettsia rickettsii, Rickettsia parkeri, Rickettsia amblyommii, Rickettsia rhipicephali, Rickettsia felis, Rickettsia bellii, Ehrlichia canis, and Coxiella burnetii as crude antigens. All 10 jaguar sera reacted (titer >= 64) to at least one Rickettsia species; 4 and 3 sera reacted with E. canis and C. burnetii, respectively. One jaguar presented antibody titer to R. parkeri at least fourfold higher than those to any of the other five Rickettsia antigens, suggesting that this animal was infected by R. parkeri. Ticks collected from jaguars included the species Amblyomma cajennense, Amblyomma triste, and Rhipicephalus (Boophilus) microplus. No Rickettsia DNA was detected in jaguar blood samples, but an A. triste specimen collected on a jaguar was shown by PCR to be infected by R. parkeri. The blood of two jaguars and samples of A. triste, A. cajennense, and Amblyomma sp. yielded Ehrlichia DNA by PCR targeting the ehrlichial genes 16S rRNA and dsb. Partial DNA sequences obtained from PCR products resulted in a new ehrlichial strain, here designated as Ehrlichia sp. strain Jaguar. A partial DNA sequence of the 16S rRNA gene of this novel strain showed to be closest (99.0%) to uncultured strains of Ehrlichia sp. from Japan and Russia and 98.7% identical to different strains of Ehrlichia ruminantium. The ehrlichial dsb partial sequence of strain jaguar showed to be at most 80.7% identical to any Ehrlichia species or genotype available in GenBank. Through phylogenetic analysis, Ehrlichia sp. strain jaguar grouped in a cluster, albeit distantly, with different genotypes of E. ruminantium. Results highlight risks for human and animal health, considering that cattle ranching and ecotourism are major economic activities in the Pantanal region of Brazil.

ISOLATION OF Rickettsia bellii FROM Amblyomma ovale AND Amblyomma incisum TICKS FROM SOUTHERN BRAZIL

Objective. To isolate and characterize rickettsiae from the ticks Amblyomma ovale and Amblyomma incisum collected in the state of Sao Paulo. Materials and methods. Adult, free-living A. ovale and A. incisum were collected in an Atlantic rainforest area in the state of Sao Paulo, Brazil. Each tick was tested using the hemolymph assay; samples from positive ticks were placed in shell vials in order to isolate rickettsiae and subsequently grown in Vero cells. Amplification of three rickettsial genes ( gltA, htrA and ompA) was attempted using polymerase chain reaction (PCR) for each isolate obtained. Amplicons were subsequently sequenced. Results. A total of 388 A. incisum and 50 A. ovale were collected. Only one A. incisum and one A. ovale were hemolymph-test positive. Rickettsiae were successfully isolated from these ticks; however establishment in Vero cell culture was successful only for the isolate from A. ovale. Bacterial contamination in the first cell passage of the A. incisum isolate precluded successful isolation of the organism. PCR products were obtained with the gltA and htrA primers for the two isolates, but no product was obtained with the ompA primers. By BLAST analysis, partial gltA and htrA sequences of isolates from A. ovale and A. incisum were similar to the corresponding sequences of R. bellii. Conclusions. This is the first report of R. bellii infecting A. incisum and the first successful isolation from A. ovale.

Experimental Infection of Amblyomma aureolatum Ticks with Rickettsia rickettsii

We experimentally infected Amblyomma aureolatum ticks with the bacterium Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever (RMSF). These ticks are a vector for RMSF in Brazil. R. rickettsii was efficiently conserved by both transstadial maintenance and vertical (transovarial) transmission to 100% of the ticks through 4 laboratory generations. However, lower reproductive performance and survival of infected females was attributed to R. rickettsii infection. Therefore, because of the high susceptibility of A. aureola turn ticks to R. rickettsii infection, the deleterious effect that the bacterium causes in these ticks may contribute to the low infection rates (< 1%) usually reported among field populations of A. aureolatum ticks in RMSF-endemic areas of Brazil. Because the number of infected ticks would gradually decrease after each generation, it seems unlikely that A. aureolatum ticks could sustain R. rickettsii infection over multiple successive generations solely by vertical transmission.

Experimental Infection of Rhipicephalus sanguineus Ticks with the Bacterium Rickettsia rickettsii, Using Experimentally Infected Dogs

We evaluated if Rickettsia rickettsii-experimentally infected dogs could serve as amplifier hosts for Rhipicephalus sanguineus ticks. In addition, we checked if Rh. sanguineus ticks that acquired Ri. rickettsii from dogs could transmit the bacterium to susceptible hosts (vector competence), and if these ticks could maintain the bacterium by transstadial and transovarial transmissions. Uninfected larvae, nymphs, and adults of Rh. sanguineus were allowed to feed upon three groups of dogs: groups 1 (G1) and 2 (G2) composed of Ri. rickettsii-infected dogs, infected intraperitoneally and via tick bites, respectively, and group 3 composed of uninfected dogs. After larval and nymphal feeding on rickettsemic dogs, 7.1-15.2% and 35.8-37.9% of the molted nymphs and adults, respectively, were shown by polymerase chain reaction (PCR) to be infected by Ri. rickettsii, confirming that both G1 and G2 dogs were efficient sources of rickettsial infection (amplifier host), resulting in transstadial transmission of the agent. These infected nymphs and adults successfully transmitted Ri. rickettsii to guinea pigs, confirming vector competence after acquisition of the infection from rickettsemic dogs. Transovarial transmission of Ri. rickettsii was observed in engorged females that had been infected as nymphs by feeding on both G1 and G2 dogs, but not in engorged females that acquired the infection during adult feeding on these same dogs. In the first case, filial infection rates were generally <50%. No tick exposed to G3 dogs was infected by rickettsiae in this study. No substantial mortality difference was observed between Ri. rickettsii-infected tick groups (G1 and G2) and uninfected tick group (G3). Our results indicate that dogs can be amplifier hosts of Ri. rickettsii for Rh. sanguineus, although only a minority of immature ticks (<45%) should become infected. It appears that Rh. sanguineus, in the absence of horizontal transmission, would not maintain Ri. rickettsii through successive generations, possibly because of low filial infection rates.

Experimental Infection of the Opossum Didelphis aurita by Rickettsia felis, Rickettsia bellii, and Rickettsia parkeri and Evaluation of the Transmission of the Infection to Ticks Amblyomma cajennense and Amblyomma dubitatum

This work evaluated the infection of opossums (Didelphis aurita) by Rickettsia felis, Rickettsia bellii, and Rickettsia parkeri and their role as amplifier hosts for horizontal transmission to Amblyomma cajennense and/or Amblyomma dubitatum ticks. Infection in D. aurita was induced by intraperitoneal inoculation with R. felis (n = 4 opossums), R. bellii (n = 4), and R. parkeri (n = 2). Another group of six opossums were inoculated intraperitoneally with Leibovitz-15 sterile culture medium, representing the uninfected groups (n = 2 opossums simultaneously to each infected group). Opossum blood samples collected during the study were used for DNA extraction, followed by real-time polymerase chain reaction targeting the rickettsial gene gltA, hematology, and detection of Rickettsia spp.-reactive antibodies by indirect immunofluorescence assay. Opossums were infested with uninfected A. cajennense and/or A. dubitatum for 30 days postinoculation (DPI). Flat ticks molted from ticks fed on opossums were allowed to feed on uninfected rabbits, which were tested for seroconversion by immunofluorescence assay. Samples of flat ticks were also tested by real-time polymerase chain reaction. Inoculated opossums showed no clinical abnormalities. Antibodies to Rickettsia spp. were first detected at the second to fourth DPI, with detectable titers until the 150th DPI. Rickettsemia was detected only in one opossum inoculated with R. parkeri, at the eighth DPI. Only one A. cajennense tick (2.0%) previously fed on a R. parkeri-inoculated opossum became infected. None of the rabbits infested with opossum-derived ticks seroconverted. The study demonstrated that R. felis, R. bellii, and R. parkeri were capable to produce antibody response in opossums, however, with undetectable rickettsemia for R. felis and R. bellii, and very low rickettsemia for R. parkeri. Further studies must be done with different strains of these rickettsiae, most importantly the strains that have never gone through in vitro passages.

Experimental Infection of Opossums Didelphis aurita by Rickettsia rickettsii and Evaluation of the Transmission of the Infection to Ticks Amblyomma cajennense

The present study evaluated the infection of opossums (Didelphis aurita) by Rickettsia rickettsii and their role as amplifier hosts for horizontal transmission of R. rickettsii to Amblyomma cajennense ticks. Three groups of opossums were evaluated: on day 0, group 1 (G1) was inoculated intraperitoneally with R. rickettsii; group 2 (G2) was infested by R. rickettsii-infected ticks; and group 3 (G3) was the uninfected control group. Opossum rectal temperature was measured daily. Blood samples were collected every 2 to 4 days during 30 days, and used to (1) inoculate guinea pigs intraperitoneally; (2) extract DNA followed by real-time polymerase chain reaction (PCR) targeting the rickettsial gene gltA; (3) study hematology; (4) detect R. rickettsii-reactive antibodies by indirect direct immunofluorescence assay (IFA). Blood was also collected every 10 days from days 30 to 180, to be tested by serology. Opossums were infested by uninfected A. cajennense larvae and nymphs from days 3 to 15. Engorged ticks were collected and allowed to molt in an incubator. Thereafter, the subsequent flat ticks were allowed to feed on uninfected rabbits, which were tested for seroconversion by IFA. Samples of flat ticks were also tested by real-time PCR. All G1 and G2 opossums became infected by R. rickettsii, as demonstrated by real-time PCR or/and guinea pig inoculation, but they showed no clinical abnormality. Rickettsemia was first detected at days 2 to 8, lasting intermittently till days 1 to 30. Approximately 18% and 5% of the flat ticks previously fed on G1 and G2 opossums, respectively, became infected by R. rickettsii, but only the rabbits infested with G1-derived ticks seroconverted. The study demonstrated that R. rickettsii was capable of infecting opossums without causing illness and developing rickettsemia capable of causing infection in guinea pigs and ticks, although the infection rate in ticks was low.

Osler-Weber-Rendu Syndrome - Dental Implications

Osler-Weber-Rendu syndrome (OWRS) is a rare hereditary, autosomal dominant disease characterized by a local angiodysplasia. Its clinical characteristics are vascular hamartomas of the skin and oral mucosa, arteriovenous malformations in the lungs, liver, kidney and brain, and episodes of epistaxis. The oral lesions, which become apparent through hemorrhagic telangiectasia, may be the first sign of the disease. This is a case report of a 74-year-old woman whose diagnosis of OWRS was established by her dentist based on the presence of telangiectasia in the skin and oral mucosa, reports of frequent nosebleeds of unknown etiology and a family history of telangiectasia. Amputation of a lower limb and comorbidities, such as cardiopathy, nephropathy and rheumatic disorders, completed the profile. OWRS causes major vascular changes that can be diagnosed initially by a dentist. In this article, we describe the skills and knowledge that dentists need to monitor patients with OWRS properly.