Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

Factors of poor prognosis of visceral leishmaniasis among children under 12 years of age. A retrospective monocentric study in Belo Horizonte, State of Minas Gerais, Brazil, 2001-2005

INTRODUTION: A major concern with the visceral leishmaniasis (VL) is its high lethality rate, even with proper treatment. Low age, prior malnutrition, disease duration prior to diagnosis, severe anemia, fever for more than 60 days, diarrhea and jaundice are known poor prognostic factors. The goals of this study are to describe the clinical and laboratory characteristics of VL among children under 12 years of age and to identify the factors associated with VL poor outcome. METHODS: Two hundred and fifty children under 12 years of age with confirmed VL admitted to Hospital João Paulo II (FHEMIG), Belo Horizonte, Brazil, between January 2001 and December 2005 were evaluated retrospectively. The primary outcome was the poor clinical evolution: sepsis, and/or pneumonia, and/or urinary tract infection, and/or of bleeding (expect epistaxis), and/or severe neutropenia (neutrophil < 500 cells/mm3). Odds ratio (crude and adjusted) and its 95% confidence interval for each variable were calculated. Values less than 0.05 were considered significant. RESULTS: Average age was 3.3 years (3.6 months-11.6 years), 71.2% were younger than 5 years and 47.2% lived in Metropolitan Area of Belo Horizonte. The mean fatality rate was 3.6%. Sixty-six (26.4%) patients presented poor evolution. After a multivariate analysis, age <18 months, abnormal respiratory physical examination on hospital admission, and platelets <85,000/mm3 remained associated with increased chance of poor evolution. CONCLUSIONS: The results suggest that patients aged between 12 and 18 months, with platelet counts bellow 85,000/mm3, and respiratory abnormalities at admission should be considered potentially severe.

Active and latent tuberculosis in prisoners in the Central-West Region of Brazil

Introduction Jailed populations exhibit high rates of tuberculosis (TB) infection and active disease. Methods A cross-sectional study was performed to estimate the prevalence of latent and active TB and to identify factors associated with latent infection in inmates. Results The prevalence of latent TB was 49%, and the prevalence of active TB was 0.4%. The presence of a Bacille Calmette-Guérin (BCG) scar (prevalence ratio (PR)=1.65; 95% confidence interval (CI): 1.09-2.50; p=0.0162) and the World Health Organization (WHO) score for active TB in prisons (PR=1.07; 95% CI: 1.01-1.14; p=0.0181) were correlated with infection. Conclusions The identification of associated factors and the prevalence of latent and active TB allows the development of plans to control this disease in jails.

Late diagnosis and HIV infection in children attending a service of specialized care for pediatric AIDS in Brazil

Introduction: This study describes the frequency of late diagnosis and HIV among children attending a pediatric AIDS clinic. Methods: Cross-sectional study in children exposed to HIV from 2005-2008. A questionnaire was given that included questions on demographics and clinical information. Results: Two-hundred twenty-one (97.8%) children were exposed to HIV during pregnancy/childbirth. A total of 193 (87.3%) children had late enrolment in the service and late access to HIV serology. The frequency of HIV was 21.3% (95% confidence interval [CI] 15.9%-26.7%). Protective factors were earlier diagnosis [odds ratio (OR)=0.17 (0.08-0.37)] and receiving complete prophylaxis [OR=0.29 (0.09-0.97)]; being born by vaginal delivery was a risk factor [OR=4.45 (1.47-13.47)]. Conclusions: There was a high frequency of late diagnosis in this patient cohort. Earlier diagnosis is an important measure for controlling HIV among children.

In vitro antimalarial activity of tigecycline against Plasmodium falciparum culture-adapted reference strains and clinical isolates from the Brazilian Amazon

Introduction: We evaluated the in vitro antimalarial activity of tigecycline as an alternative drug for the treatment of severe malaria. Methods: A chloroquine-sensitive Plasmodium falciparum reference strain, a chloroquine-resistant reference strain, and three clinical isolates were tested for in vitro susceptibility to tigecycline. A histidine-rich protein in vitro assay was used to evaluate antimalarial activity. Results: The geometric-mean 50% effective concentration (EC50%) of tigecycline was 535.5 nM (confidence interval (CI): 344.3-726.8). No significant correlation was found between the EC50% of tigecycline and that of any other tested antimalarial drug. Conclusions: Tigecycline may represent an alternative drug for the treatment of patients with severe malaria.

Risk factors for hepatitis C virus transmission in the municipality of Catanduva, State of São Paulo: a case-control study

Introduction Hepatitis C virus (HCV) is primarily transmitted via contact with the blood of infected patients, although the form of contact has not been identified for a significant percentage of carriers. The present study evaluated possible risk factors for HCV transmission in a medium-sized town located in the northwest region of the State of São Paulo. Methods This was a case-control study, with the case group consisting of 190 chronic HCV carriers older than 18 years residing in the municipality of Catanduva. The control group also consisted of 190 individuals with HCV-negative serology. The groups were paired (1:1) for gender, age range (± five years), and place of residence. The same structured questionnaire was applied to all subjects, who gave written informed consent to participate in the study. The data were statistically analyzed using crude and adjusted logistic regression, and the results were expressed as odds ratios with a 95% confidence interval. Results The demographic profiles of the groups indicated a predominance of males (68.9%) and mean ages of 47.1 years (case group) and 47.3 years (control group). After adjusting for conditional regression, the following factors were found to represent risks for HCV: history of sexually transmitted disease (STD) and blood transfusion; accidents with syringes and/or needles; tattoos; and the use of non-injectable drugs and injectable medications. Conclusions The transmission of HCV via the blood route has been well characterized. Other forms of contact with human blood and/or secretions are likely to transmit the virus, although with a lower frequency of occurrence.

Ecological competition and the incidence of Acinetobacter baumannii bloodstream infections in a teaching hospital in Southeastern Brazil

IntroductionRecently, pathogen ecology has been recognized as an important epidemiological determinant of healthcare-associated infections (HAIs). Acinetobacter baumannii is one of the most important agents known to cause HAIs. It is widespread in healthcare settings and exhibits seasonal variations in incidence. Little is known about the impact of competition with other hospital pathogens on the incidence of A. baumannii infection.MethodsWe conducted an ecological study, enrolling patients who presented with healthcare-associated bloodstream infections (HA-BSIs) from 2005 to 2010 at a 450-bed teaching hospital in Brazil. HA-BSIs were said to be present when bacteria or fungi were recovered from blood cultures collected at least three days after admission. Monthly incidence rates were calculated for all HA-BSIs (overall or caused by specific pathogens or groups of pathogens). Multivariate Poisson regression models were used to identify the impacts of the incidence of several pathogens on the incidence of A. baumannii.ResultsThe overall incidence rate of HA-BSI caused by A. baumannii was 2.5 per 10,000 patient-days. In the multivariate analysis, the incidence of HA-BSI caused by A. baumanniiwas negatively associated with the incidence rates of HA-BSI due to Staphylococcus aureus (rate ratio [RR]=0.88; 95% confidence interval [CI]=0.80-0.97), Enterobacter spp. (RR=0.84; 95%CI=0.74-0.94) and a pool of less common gram-negative pathogens.ConclusionsOur results suggest that competition between pathogens influences the etiology of HA-BSIs. It would be beneficial to take these findings into account in infection control policies.

Occurrence of severe dengue in Rio de Janeiro: an ecological study

Introduction This study aimed to analyze the relationship between the incidence of severe dengue during the 2008 epidemic in Rio de Janeiro, Brazil, and socioeconomic indicators, as well as indicators of health service availability and previous circulation of the dengue virus serotype-3 (DENV-3). Methods In this ecological study, the units of analysis were the districts of Rio de Janeiro. The data were incorporated into generalized linear models, and the incidence of severe dengue in each district was the outcome variable. Results The districts with more cases of dengue fever in the 2001 epidemic and a higher percentage of residents who declared their skin color or race as black had higher incidence rates of severe dengue in the 2008 epidemic [incidence rate ratio (IRR)= 1.21; 95% confidence interval (95%CI)= 1.05-1.40 and IRR= 1.34; 95%CI= 1.16-1.54, respectively]. In contrast, the districts with Family Health Strategy (FHS) clinics were more likely to have lower incidence rates of severe dengue in the 2008 epidemic (IRR= 0.81; 95%CI= 0.70-0.93). Conclusions At the ecological level, our findings suggest the persistence of health inequalities in this region of Brazil that are possibly due to greater social vulnerability among the self-declared black population. Additionally, the protective effect of FHS clinics may be due to the ease of access to other levels of care in the health system or to a reduced vulnerability to dengue transmission that is afforded by local practices to promote health.

Risk factors associated with the transmissionof Brazilian spotted fever in the Piracicaba river basin, State of São Paulo, Brazil

INTRODUCTION : Brazilian spotted fever (BSF) is a disease transmitted by ticks for which the etiological agent is Rickettsia rickettsii. The present essay evaluates the risk factors associated with the transmission of cases of BSF in the time period between 2003 and 2013 in the Piracicaba river basin, state of São Paulo. METHODS : This essay presents a retrospective study to identify the factors associated with the transmission of cases of BSF among all suspected cases identified by the System for Epidemiological Surveillance of São Paulo (CVE). After the description of temporal distribution (onset of symptoms) and the environmental and demographic variations of the confirmed and discarded cases, a multiple logistic regression model was applied. RESULTS : We searched 569 probable locations of infection (PLI) with 210 (37%) confirmed cases of BSF and 359 (63%) discarded cases. The associated variables for the confirmation of BSF in the multiple logistic model using a confidence interval (CI) of 95% were age (OR = 1.025 CI: 1.015-1.035), the presence of Amblyomma sculptum in the environment (OR = 1.629 CI: 1.097-2.439), the collection of ticks from horses (OR = 1.939 CI: 0.999-3.764), the presence of capybaras (OR = 1.467 CI: 1.009-2.138), an urban environment (OR = 1.515 CI: 1.036-2.231), and the existence of a dirty pasture (OR = 1.759 CI: 1.028-3.003). CONCLUSIONS : The factors associated with the confirmation of BSF cases included an urban environment, age, presence of the A. sculptum vector, the collection of ticks from horses, the presence of a capybara population, and a dirty pasture environment.

Natural transovarial transmission of dengue virus 4 in Aedes aegypti from Cuiabá, State of Mato Grosso, Brazil

INTRODUCTION: Dengue is the most prevalent arboviral disease in tropical areas. In Mato Grosso, outbreaks are reported every year, but studies on dengue in this state are scarce. METHODS: Natural transovarial infection of Aedes aegypti by a flavivirus was investigated in the Jardim Industriário neighborhood of Cuiabá, Mato Grosso. Eggs were collected with ovitraps during the dry, intermediate, and rainy seasons of 2012. After the eggs hatched and the larvae developed to adulthood, mosquitoes (n = 758) were identified and allocated to pools of 1-10 specimens according to the collection location, sex, and climatic period. After RNA extraction, multiplex semi-nested RT-PCR was performed to detect the four dengue virus (DENV) serotypes, yellow fever virus, West Nile virus and Saint Louis encephalitis virus. RESULTS: DENV-4 was the only flavivirus detected, and it was found in 8/50 pools (16.0%). Three of the positive pools contained females, and five contained males. Their nucleotide sequences presented 96-100% similarity with DENV-4 genotype II strains from Manaus, Amazonas. The minimum infection rate was 10.5 per 1000 specimens, and the maximum likelihood estimator of the infection rate was 11.6 (95% confidence interval: 4.8; 23.3). CONCLUSIONS: This study provides the first evidence of natural transovarial infection by DENV-4 in Ae. Aegypti in Mato Grosso, suggesting that this type of infection might serve as a mechanism of virus maintenance during interepidemic periods in Cuiabá, a city where dengue epidemics are reported every year. These results emphasize the need for efficient vector population control measures to prevent arbovirus outbreaks in the state.

Evaluation of the reference value for the Montenegro skin test

Abstract:INTRODUCTION:The Montenegro skin test (MST) has good clinical applicability and low cost for the diagnosis of American tegumentary leishmaniasis (ATL). However, no studies have validated the reference value (5mm) typically used to discriminate positive and negative results. We investigated MST results and evaluated its performance using different cut-off points.METHODS:The results of laboratory tests for 4,256 patients with suspected ATL were analyzed, and 1,182 individuals were found to fulfill the established criteria. Two groups were formed. The positive cutaneous leishmaniasis (PCL) group included patients with skin lesions and positive direct search for parasites (DS) results. The negative cutaneous leishmaniasis (NCL) group included patients with skin lesions with evolution up to 2 months, negative DS results, and negative indirect immunofluorescence assay results who were residents of urban areas that were reported to be probable sites of infection at domiciles and peridomiciles.RESULTS:The PCL and NCL groups included 769 and 413 individuals, respectively. The mean ± standard deviation MST in the PCL group was 12.62 ± 5.91mm [95% confidence interval (CI): 12.20-13.04], and that in the NCL group was 1.43 ± 2.17mm (95% CI: 1.23-1.63). Receiver-operating characteristic curve analysis indicated 97.4% sensitivity and 93.9% specificity for a cut-off of 5mm and 95.8% sensitivity and 97.1% specificity for a cut-off of 6mm.CONCLUSIONS:Either 5mm or 6mm could be used as the cut-off value for diagnosing ATL, as both values had high sensitivity and specificity.

Risk-benefit assessment of Bacillus Calmette-Guérin vaccination, anti-phenolic glycolipid I serology, and Mitsuda test response: 10-year follow-up of household contacts of leprosy patients

Abstract: INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS : Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies.

Difference in the in-hospital mortality of unstable angina pectoris between men and women

PURPOSE: To assess differences in the in-hospital mortality (HM) rate between men and women with unstable angina pectoris (UA) according to age, depression of the ST segment, history of previous acute myocardial infarction (AMI), and risk factors for coronary heart disease. METHODS: From October 96 to March 98, 261 patients with UA were selected. Logistic regression models were developed to adjust the association between sex and HM for possible influence of covariables, such as hypertension, diabetes mellitus, dyslipidemia, sedentary lifestyle, smoking, and familial history of early coronary heart disease. RESULTS: HM due to UA was approximately three times higher in women (9.3%; 12/129) than in men (3.0%; 4/132) accounting for a relative risk of 3.07; 95% confidence interval (CI) =1.02-9.27. In logistic regression models, the association between sex and death was not significantly altered when the following parameters were considered: age, depression of the ST segment, history of previous AMI and risk factors for coronary heart disease. The nonadjusted and adjusted odds ratio (OR) for the distinct covariables were 3.28 (CI 95%=1.03-10.45) and 3.14 (CI = 95% = 0.88-11.20), respectively. CONCLUSION: Similarly to AMI, HM in UA is higher in women than in men. Age, risk factors for coronary heart disease, and depression of the ST segment in the electrocardiogram on patients' admission to the hospital did not significantly influence the association between sex and death.

Prognostic factors of rheumatic mitral stenosis during pregnancy and puerperium

OBJECTIVE: To identifity characteristics associated with complications during pregnancy and puerperium in patients with rheumatic mitral stenosis. METHODS: Forty-one pregnant women (forty-five pregnancies) with mitral stenosis, followed-up from 1991 to 1999 were retrospectively evaluated. Predictor variables: the mitral valve area (MVA), measured by echocardiogram, and functional class (FC) before pregnancy (NYHA criteria).Maternal events: progression of heart failure, need for cardiac surgery or balloon mitral valvulotomy, death, and thromboembolism. Fetal/neonatal events: abortion, fetal or neonatal death, prematurity or low birth weight (<2,500g), and extended stay in the nursery or hospitalization in newborn ICU. RESULTS: The mean ± SD of age of the patients was 28.8±4.6 years. The eventful and uneventful patients were similar in age and percentage of first pregnancies. As compared with the level 1 MVA, the relative risk (RR) of maternal events was 5.5 (95% confidence interval (CI) =0.8-39.7) for level 2 MVA and 11.4 (95% CI=1.7-74.5) for level 3 MVA. The prepregnancy FC (FC > or = II and III versus I) was also associated with a risk for maternal events (RR=2.7; 95% CI=1.4-5.3).MVA and FC were not importantly associated with these events, although a smaller frequency of fetal/neonatal events was observed in patients who had undergone balloon valvulotomy. CONCLUSION: In pregnant women with mitral stenosis, the MVA and the FC are strongly associated with maternal complications but are not associated with fetal/neonatal events. Balloon mitral valvulotomy could have contributed to reducing the risks of fetal/neonatal events in the more symptomatic patients who had to undergo this procedure during pregnancy.

Electrocardiographic Alterations in Patients Hospitalized with Leptospirosis in the Brazilian City of Salvador

OBJECTIVE: To report the frequency and types of electrocardiographic alterations in patients with leptospirosis in the first 24 hours of hospitalization. METHODS: We analyzed the electrocardiograms of 157 patients admitted to the Hospital Couto Maia in the city of Salvador, in the State of Bahia, Brazil, from March 1998 to June 1999. The electrocardiograms were performed in the first 24 hours after hospital admission, independent of the clinical manifestations of the patients. RESULTS: The mean ± SD for patients' age was 35.5± 13.7 (median = 32) years, and jaundice was present in 95.5% of them. Alterations in the electrocardiogram were detected in 68.2% (107/157) of the patients (95% confidence interval = 60.6% - 75.1%). Atrial fibrillation was the most frequent arrhythmia, occurring in 10.8% (17/157) of the patients. Other frequent findings were alterations in ventricular repolarization detected in 38.9% (61/157) of patients and first-degree atrioventricular block in 10.2% (16/157). The patients with atrial fibrillation were older and had higher levels of creatinine and aminotransferases. CONCLUSION: In this sample, approximately 2/3 of the patients had electrocardiographic alterations after hospital admission. Of the major arrhythmias, atrial fibrillation was the most frequent, and the patients with this arrhythmia had evidence of more severe disease. The relation between the presence and type of electrocardiographic alteration and the prognosis of leptospirosis is yet to be assessed.