Trends and factors associated with dengue mortality and fatality in Brazil

AbstractINTRODUCTION:Studies that generate information that may reduce the dengue death risk are essential. This study analyzed time trends and risk factors for dengue mortality and fatality in Brazil from 2001 to 2011.METHODS:Time trends for dengue mortality and fatality rates were analyzed using simple linear regression. Associations between the dengue mortality and the case fatality rates and socioeconomic, demographic, and health care indicators at the municipality level were analyzed using negative binomial regression.RESULTS:The dengue hemorrhagic fever case fatality rate increased in Brazil from 2001 to 2011 (β=0.67; p=0.036), in patients aged 0-14 years (β=0.48; p=0.030) and in those aged ≥15 years (β=1.1; p<0.01). Factors associated with the dengue case fatality rate were the average income per capita (MRR=0.99; p=0.038) and the number of basic health units per population (MRR=0.89; p<0.001). Mortality rates increased from 2001 to 2011 (β=0.350; p=0.002).Factors associated with mortality were inequality (RR=1.02; p=0.001) high income per capita (MRR=0.99; p=0.005), and higher proportions of populations living in urban areas (MRR=1.01; p<0.001).CONCLUSIONS:The increases in the dengue mortality and case fatality rates and the associated socioeconomic and health care factors, suggest the need for structural and intersectoral investments to improve living conditions and to sustainably reduce these outcomes.

Spatial and spatiotemporal occurrence of human visceral leishmaniasis in Adamantina, State of São Paulo, Brazil

Abstract: INTRODUCTION : Several municipalities of the Western region of the State of São Paulo have been affected by human visceral leishmaniasis (HVL), including the City of Adamantina, where the first autochthonous cases occurred in 2004. Therefore, this study aimed to describe the spatial and spatiotemporal occurrence of HVL in Adamantina. METHODS : Secondary data regarding the occurrence of HVL in Adamantina between 2004 and 2011 were used. Incidence, mortality, and case fatality rates were calculated. We used local empirical Bayesian incidence rates to represent the occurrence of the disease in the census sector of the city. The existence of spatial and spatiotemporal clusters of cases was evaluated using scan statistics. In situ observation was performed to assess the socioeconomic and environmental characteristics of the areas with medium and high incidences. RESULTS : Adamantina reported cases in 70% of its census sectors. No differences were observed between sexes. The group aged 0-4 years presented the highest incidence and mortality rates, and the group aged 40-59 years presented the highest fatality rate. We detected a spatiotemporal cluster, which coincided with the commencement of the endemic in the city. CONCLUSIONS : The individuals most affected by the disease were children. The disease was present in areas with better and worse socioeconomic conditions. The use of spatial analysis techniques was important to achieve the study objectives.

HIV/AIDS epidemic in the State of Amazonas: characteristics and trends from 2001 to 2012

A scoping review was conducted to describe the epidemiological characteristics of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in the State of Amazonas, Brazil, from 2001 to 2012, and temporary patterns were estimated from surveillance data. The results suggest that in its third decade, the Amazon HIV/AIDS epidemic is far from being stabilized and displays rising AIDS incidence and mortality rates and late diagnoses. The data suggest that AIDS cases are hitting mostly young adults and have recently shifted toward men, both homosexual and heterosexual. AIDS cases among the indigenous people have remained stable and low. However, the epidemic has disseminated to the interior of the state, which adds difficulties to its control, given the geographical isolation, logistical barriers, and culturally and ethnically diverse population. Antiretroviral (ARV) therapy has been decentralized, but peripheral ARV services are still insufficient and too distant from people who need them. Recently, the expansion of point-of-care (POC) rapid HIV testing has been contributing to overcoming logistical barriers. Other new POC devices, such as the PIMA CD4 analyzer, will bring the laboratory to the patient. AIDS uniquely coexists with other tropical infections, sharing their epidemiological profiles. The increased demand for HIV/AIDS care services can only be satisfied through increased decentralization to peripheral health units, which can also naturally integrate care with other tropical infections and can promote a shift from vertical to integrated programming. Future challenges involve building surveillance data on HIV case notification and covering the spectrum of engagement in care, including adherence to treatment and follow-up loss.

Hormone replacement therapy and the risk of breast cancer: assessment of therapy acceptance in a cohort of previously treated breast cancer patients

INTRODUCTION: In the postmenopausal period, an average of 25% of women will present symptomatic ovarian failure requiring hormonal replacement therapy. Estrogen can relieve vasomotor symptoms. Hormonal replacement therapy is generally not recommended for breast cancer patients due to the potential risk of tumor recurrence. To answer the questions about the safety of hormonal replacement therapy in this subgroup of women, it is necessary to establish the acceptance of treatment. METHODS: Between September 1998 and February 2001, a cohort of 216 breast cancer patients were asked to complete a questionnaire. All patients had completed their treatment and were informed about survival rates after breast cancer and hormonal replacement therapy. RESULTS: Among the 216 patients, 134 (62%) would refuse hormonal replacement therapy. A hundred patients were afraid of relapse (74.6%). Adjuvant tamoxifen therapy was the only statistically significant variable (70.3% versus 29.7% p=0.003). Understanding clinical stage (p= 0.045) and type of medical assistance (private versus public , p=0.033) also seemed to influence the decision. Early stage disease (p= 0.22), type of surgical procedure (radical versus conservative, p=0.67), adjuvant chemotherapy (p=0.082) or marital status (p=0.98 ) were not statistically significant in decision making. Several patients submitted to adjuvant chemotherapy (41.6%) would accept hormonal replacement therapy under medical supervision, as did most of advanced clinical stage patients (58.3%; p=0.022). CONCLUSION: There is a high level of rejection for hormonal replacement therapy among breast cancer patients when current data on tumor cure rates, and potential risks of estrogen use is available. Adverse effects of tamoxifen in the adjuvant setting may be the reason for refusal of hormonal replacement therapy .

Photosynthetic parameters and growth in seedlings of Bertholletia excelsa and Carapa guianensis in response to pre-acclimation to full sunlight and mild water stress

Light and water are important factors that may limit the growth and development of higher plants. The aim of this study was to evaluate photosynthetic parameters and growth in seedlings of Bertholletia excelsa and Carapa guianensis in response to pre-acclimation to full sunlight and mild water stress. I used six independent pre-acclimation treatments (0, 90 (11h15-12h45), 180 (10h30-13h30), 360 (09h00-15h00), 540 (07h30-16h30) and 720 min (06h00-18h00)) varying the time of exposure to full sunlight (PFS) during 30 days, followed by whole-day outdoor exposure for 120 days. Before PFS, the plants were kept in a greenhouse at low light levels (0.8 mol m-2 day-1). The PFS of 0 min corresponded to plants constantly kept under greenhouse conditions. From the beginning to the end of the experiment, each PFS treatment was submitted to two water regimes: moderate water stress (MWS, pre-dawn leaf water potential (ΨL) of -500 to -700 kPa) and without water stress (WWS, ΨL of -300 kPa, soil kept at field capacity). Plants under MWS received only a fraction of the amount of water applied to the well-watered ones. At the end of the 120-day-period under outdoor conditions, I evaluated light saturated photosynthesis (Amax), stomatal conductance (g s), transpiration (E) and plant growth. Both Amax and g s were higher for all plants under the PFS treatment. Stem diameter growth rate and Amax were higher for C. guianensis subjected to MWS than in well-watered plants. The contrary was true for B. excelsa. The growth of seedlings was enhanced by exposure to full sunlight for 180 minutes in both species. However, plants of B. excelsa were sensitive to moderate water stress. The higher photosynthetic rates and faster growth of C. guianensis under full sun and moderate water stress make this species a promissory candidate to be tested in reforestation programs.

Pulmonary Embolism Mortality in Brazil from 1989 to 2010: Gender and Regional Disparities

Abstract Background: A significant variation in pulmonary embolism (PE) mortality trends have been documented around the world. We investigated the trends in mortality rate from PE in Brazil over a period of 21 years and its regional and gender differences. Methods: Using a nationwide database of death certificate information we searched for all cases with PE as the underlying cause of death between 1989 and 2010. Population data were obtained from the Brazilian Institute of Geography and Statistics (IBGE). We calculated age-, gender- and region-specific mortality rates for each year, using the 2000 Brazilian population for direct standardization. Results: Over 21 years the age-standardized mortality rate (ASMR) fell 31% from 3.04/100,000 to 2.09/100,000. In every year between 1989 and 2010, the ASMR was higher in women than in men, but both showed a significant declining trend, from 3.10/100,000 to 2.36/100,000 and from 2.94/100,000 to 1.80/100,000, respectively. Although all country regions showed a decline in their ASMR, the largest fall in death rates was concentrated in the highest income regions of the South and Southeast Brazil. The North and Northeast regions, the lowest income areas, showed a less marked fall in death rates and no distinct change in the PE mortality rate in women. Conclusions: Our study showed a reduction in the PE mortality rate over two decades in Brazil. However, significant variation in this trend was observed amongst the five country regions and between genders, pointing to possible disparities in health care access and quality in these groups.

Mortality from Circulatory System Diseases and Malformations in Children in the State of Rio de Janeiro

Abstract Background: The epidemiological profile of mortality in a population is important for the institution of measures to improve health care and reduce mortality Objective: To estimate mortality rates and the proportional mortality from cardiovascular diseases and malformations of the circulatory system in children and adolescents. Methods: This is a descriptive study of mortality from cardiovascular diseases, malformations of the circulatory system, from all causes, ill-defined causes and external causes in children and adolescents in the state of Rio de Janeiro from 1996 to 2012. Populations were obtained from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística - IBGE) and deaths obtained from the Department of Informatics of the Unified Health System (DATASUS)/Ministry of Health. Results: There were 115,728 deaths from all causes, 69,757 in males. The annual mortality from cardiovascular diseases was 2.7/100,000 in men and 2.6/100,000 in women. The annual mortality from malformations of the circulatory system was 7.5/100,000 in men and 6.6/100,000 in women. Among the specific causes of circulatory diseases, cardiomyopathies had the highest rates of annual proportional mortality, and from malformations of the circulatory system, it occurred due to unspecified malformations of the circulatory system, at all ages and in both genders. Conclusion: Mortality from malformations of the circulatory system was most striking in the first years of life, while cardiovascular diseases were more relevant in adolescents. Low access to prenatal diagnosis or at birth probably prevented the proper treatment of malformations of the circulatory system.

A simple method to purify biologically and antigenically preserved bloodstream trypomastigotes of Trypanosoma cruzi using Deae-cellulose columns

A method to purify trypanosomastigotes of some strains of Trypanosoma cruzi (Y, CL, FL, F, "Berenice", "Colombiana" and "São Felipe") from mouse blood by using DEAE-cellulose columns was standardized. This procedure is a modification of the Lanham & Godfrey methods and differs in some aspects from others described to purify T. cruzi bloodstream trypomastigotes, mainly by avoidance of prior purifications of parasites. By this method, the broad trypomastigotes were mainly isolated, accounting for higher recoveries obtained with strains having higher percentages of these forms: processing of infected blood from irradiated mice could be advantageous by increasing the recovery of parasites (percentage and/or total number) and elution of more slender trypomastigotes. Trypomastigotes purified by this method presented normal morphology and motility, remained infective to triatomine bugs and mice, showing in the latter prepatent periods and courses parasitemia similar to those of control parasites, and also reproducing the polymorphism pattern of each strain. Their virulence and pathogenicity also remained considerably preserved, the latter property being evaluated by LD 50 tests, mortality rates and mean survival time of inoculated mice. Moreover, these parasites presented positive, clear and peripheral immunofluorescence reaction at titres similar to those of control organisms, thus suggesting important preservation of their surface antigens.

Studies in search of a suitable experimental insect model for xenodiagnosis of hosts with Chagas' disease: 2 - Attempts to upgrade the reliability and the efficacy of xenodiagnosis in chronic Chagas' disease

In order to upgrade the reliability of xenodiagnosis, attention has been directed towards population dynamics of the parasite, with particular interest for the following factors: 1. Parasite density which by itself is not a research objective, but by giving an accurate portrayal of parasite development and multiplication, has been incorporated in screening of bugs for xenodiagnosis. 2. On the assumption that food availability might increase parasite density, bugs from xenodiagnosis have been refed at biweekly intervals on chicken blood. 3. Infectivity rates and positives harbouring large parasite yields were based on gut infections, in which the parasite population comprised of all developmental forms was more abundant and easier to detect than in fecal infections, thus minimizing the probability of recording false negatives. 4. Since parasite density, low in the first 15 days of infection, increases rapidly in the following 30 days, the interval of 45 days has been adopted for routine examination of bugs from xenodiagnosis. By following the enumerated measures, all aiming to reduce false negative cases, we are getting closer to a reliable xenodiagnostic procedure. Upgrading the efficacy of xenodiagnosis is also dependent on the xenodiagnostic agent. Of 9 investigated vector species, Panstrongylus megistus deserves top priority as a xenodiagnostic agent. Its extraordinary capability to support fast development and vigorous multiplication of the few parasites, ingested from the host with chronic Chagas' disease, has been revealed by the strikingly close infectivity rates of 91.2% vs. 96.4% among bugs engorged from the same host in the chronic and acute phase of the disease respectively (Table V), the latter comporting an estimated number of 12.3 x 10[raised to the power of 3] parasites in the circulation at the time of xenodiagnosis, as reported previously by the authors (1982).

A Comparison of Two Brazilian Populations of Culex quinquefasciatus (Say, 1823) from Endemic and Non-endemic Areas to Infection with Wuchereria bancrofti (Cobbold, 1877)

Culex quinquefasciatus is known to be an efficient insect host of Wuchereria bancrofti. In Brazil Cx. quinquefasciatus is widely distributed throughout the country and is often abundant in and around human habitations. In contrast, Bancroftian filariasis is limited to three foci in Brazil. Experiments were undertaken to compare the vector capacities of Cx. quinquefasciatus originating from Maceió (Alagoas), one of the endemic areas of W. bancrofti infection in Brazil, and Belo Horizonte (Minas Gerais), a non endemic area. Laboratory-reared Cx. quinquefasciatus were dissected 20 days after blood feeding on microfilaraemic patients. Survival rates and the number of infective larvae that developed did not differ in female mosquitoes of different origins. Thus both populations of Culex were susceptible to infection with W. bancrofti

Simuliid blackflies (Diptera: Simuliidae) and ceratopogonid midges (Diptera: Ceratopogonidae) as vectors of Mansonella ozzardi (Nematoda: Onchocercidae) in northern Argentina

Mansonella ozzardi, a relatively non pathogenic filarial parasite of man in Latin America, is transmitted by either ceratopogonid midges or simuliid blackflies. In the only known focus of the disease in north-western Argentina the vectors have never been incriminated. This study investigated the potential vectors of M. ozzardi in this area. The only anthropophilic species of these Diptera families biting man at the time of the investigation were Simulium exiguum, S. dinellii, Culicoides lahillei and C. paraensis. Using experimentally infected flies S. exiguum and both species of Culicoides allowed full development of microfilariae to the infective stage, with C. lahillei being a more competent host than S. exiguum. Based on these data, biting rates and natural infectivity rates it is probable that at the begininning of the wet season C. lahillei is the main vector of M. ozzardi and both C. paraensis and S. exiguum secondary vectors. Additionally, it was found that a single dose of ivermectin was ineffectual in eradicating M. ozzardi from infected individuals in this area.

Eye colour as a genetic marker for fertility and fecundity of Triatoma infestans (Klug, 1834) Hemiptera, Reduviidae, Triatominae

Eye colour of Triatoma infestans is controlled at a single autosomal locus, with black-eye as the dominant gene and red-eye as the recessive. Inheritance of these characters follows a classical Mendelian system, enabling eye colour to be used as a marker for studies of mating frequency. We found no significant differences in oviposition rates and egg hatching rates irrespective of parental phenotypes. Different mating schedules between red-eye and black-eye parents showed that eye colour did not affect mating competence. Females mated with a single male or with different males together or in succession produced similar numbers of fertile eggs, with the eye colour of the offspring reflecting exposure to the different males. We conclude that although a single mating can provide sufficient sperm for the whole reproductive life of the female, multiple matings can result in balanced assortative sperm usage from the spermatheca.

An in vitro model for dengue virus infection that exhibits human monocyte infection, multiple cytokine production and dexamethasone immunomodulation

An important cytokine role in dengue fever pathogenesis has been described. These molecules can be associated with haemorrhagic manifestations, coagulation disorders, hypotension and shock, all symptoms implicated in vascular permeability and disease worsening conditions. Several immunological diseases have been treated by cytokine modulation and dexamethasone is utilized clinically to treat pathologies with inflammatory and autoimmune ethiologies. We established an in vitro model with human monocytes infected by dengue virus-2 for evaluating immunomodulatory and antiviral activities of potential pharmaceutical products. Flow cytometry analysis demonstrated significant dengue antigen detection in target cells two days after infection. TNF-alpha, IFN-alpha, IL-6 and IL-10 are produced by in vitro infected monocytes and are significantly detected in cell culture supernatants by multiplex microbead immunoassay. Dexamethasone action was tested for the first time for its modulation in dengue infection, presenting optimistic results in both decreasing cell infection rates and inhibiting TNF-alpha, IFN-alpha and IL-10 production. This model is proposed for novel drug trials yet to be applyed for dengue fever.

Plasmodium falciparum gametocyte carriage, emergence, clearance and population sex ratios in anaemic and non-anaemic malarious children

Anaemia in falciparum malaria is associated with an increased risk of gametocyte carriage, but its effects on transmission have not been extensively evaluated in malarious children. Plasmodium falciparum gametocyte carriage, emergence, clearance, population sex ratios (SR) (defined as the proportion of gametocytes that are male), inbreeding rates and temporal changes in SR were evaluated in 840 malarious children. Gametocyte carriage pre-treatment was at a level of 8.1%. Anaemia at enrolment was an independent risk factor for gametocyte carriage post-treatment. The emergence of gametocytes seven days post-treatment was significantly more frequent in anaemic children (7/106 vs. 10/696, p = 0.002). In the initially detected gametocytes, the proportion of children with a male-biased SR (MBSR) (> 0.5) was significantly higher in anaemic children (6/7 vs. 3/10, p = 0.027). Pre-treatment SR and estimated inbreeding rates (proportion of a mother's daughters fertilised by her sons) were similar in anaemic and non-anaemic children. Pre-treatment SR became more female-biased in non-anaemic children following treatment. However, in anaemic children, SR became male-biased. Anaemia was shown to significantly increase gametocyte emergence and may significantly alter the SR of emerging gametocytes. If MBSR is more infective to mosquitoes at low gametocytaemia, then these findings may have significant implications for malaria control efforts in endemic settings where malaria-associated anaemia is common.

Reduction in morbidity and mortality from childhood diarrhoeal disease after species A rotavirus vaccine introduction in Latin America : a review

Countries in Latin America were among the first to implement routine vaccination against species A rotavirus (RVA). We evaluate data from Latin America on reductions in gastroenteritis and RVA disease burden following the introduction of RVA vaccine. Published literature was reviewed to identify case-control studies of vaccine effectiveness and population-based studies examining longitudinal trends of diarrhoeal disease reduction after RVA vaccine introduction in Latin American countries. RVA vaccine effectiveness and impact on gastroenteritis mortality and hospitalization rates and RVA hospitalization rates are described. Among middle-income Latin American countries with published data (Mexico, Brazil, El Salvador and Panama), RVA vaccine contributed to a gastroenteritis-associated mortality reduction of 22-41%, a gastroenteritis-associated hospitalization reduction of 17-51% and a RVA hospitalization reduction of 59-81% among children younger than five years of age. In Brazil and El Salvador, case-control studies demonstrated that a full RVA vaccination schedule was 76-85% effective against RVA hospitalization; a lower effectiveness of 46% was seen in Nicaragua, the only low-income country with available data. A growing body of literature offers convincing evidence of "real world" vaccine program successes in Latin American settings, which may be expanded as more countries in the region include RVA vaccine in their immunization programs.