Predictors of immunodeficiency-related death in a cohort of low-income people living with HIV: a competing risks survival analysis.

We conducted a survival analysis with competing risks to estimate the mortality rate and predictive factors for immunodeficiency-related death in people living with HIV/AIDS (PLWH) in northeast Brazil. A cohort with 2372 PLWH was enrolled between July 2007 and June 2010 and monitored until 31 December 2012 at two healthcare centres. The event of interest was immunodeficiency-related death, which was defined based on the Coding Causes of Death in HIV Protocol (CoDe). The predictor variables were: sociodemographic characteristics, illicit drugs, tobacco, alcohol, nutritional status, antiretroviral therapy, anaemia and CD4 cell count at baseline; and treatment or chemoprophylaxis for tuberculosis (TB) during follow-up. We used Fine & Gray's model for the survival analyses with competing risks, since we had regarded immunodeficiency-unrelated deaths as a competing event, and we estimated the adjusted sub-distribution hazard ratios (SHRs). In 10 012·6 person-years of observation there were 3·1 deaths/100 person-years (2·3 immunodeficiency-related and 0·8 immunodeficiency-unrelated). TB (SHR 4·01), anaemia (SHR 3·58), CD4 <200 cells/mm3 (SHR 3·33) and being unemployed (SHR 1·56) were risk factors for immunodeficiency-related death. This study discloses a 13% coverage by highly active antiretroviral therapy (HAART) in our state and adds that anaemia at baseline or the incidence of TB may increase the specific risk of dying from HIV-immunodeficiency, regardless of HAART and CD4.

Unawareness of HIV status in pregnancy, delay in testing and conflict between information on antenatal card and interview in Recife, Brazil.

Overall HIV test coverage among pregnant women in Brazil is 62%, but only 41% in northeastern Brazil. We aimed to identify risk factors for unawareness of HIV status among pregnant women and determine test coverage up to 14th week of pregnancy. We conducted a case-control study in a reference maternity hospital for high-risk pregnancy in Recife, where 485 puerperae were interviewed about their knowledge of results of HIV testing, biological, sociodemographic and health-care data. Cases were those who were not aware of their HIV status and controls were those who were. Only 21.65% stated that they were unaware of their HIV status during pregnancy (78.35% coverage); however, test results were recorded on an antenatal card in only 48.35%. Only 22% received the result by the 14th week of pregnancy. Unawareness was associated with low schooling (odds ratio [OR] = 2.92; P = 0.006); living outside the state capital's metropolitan region (OR = 4.11; P = 0.001); test performed in the third trimester (OR = 11.6; P = 0.000); and lack of counselling (OR = 2.31; P = 0.022) in multivariate analysis. In conclusion, there has been a considerable delay in having an HIV test. Conflict of Information obtained by interview and that on the antenatal card raises questions about deficiencies in antenatal care or lack of comprehension about the HIV test.

ZikaPLAN: Zika Preparedness Latin American Network.

The ongoing Zika virus (ZIKV) outbreak in Latin America, the Caribbean, and the Pacific Islands has underlined the need for a coordinated research network across the whole region that can respond rapidly to address the current knowledge gaps in Zika and enhance research preparedness beyond Zika. The European Union under its Horizon 2020 Research and Innovation Programme awarded three research consortia to respond to this need. Here we present the ZikaPLAN (Zika Preparedness Latin American Network) consortium. ZikaPLAN combines the strengths of 25 partners in Latin America, North America, Africa, Asia, and various centers in Europe. We will conduct clinical studies to estimate the risk and further define the full spectrum and risk factors of congenital Zika virus syndrome (including neurodevelopmental milestones in the first 3 years of life), delineate neurological complications associated with ZIKV due to direct neuroinvasion and immune-mediated responses in older children and adults, and strengthen surveillance for birth defects and Guillain-Barré Syndrome. Laboratory-based research to unravel neurotropism and investigate the role of sexual transmission, determinants of severe disease, and viral fitness will underpin the clinical studies. Social messaging and engagement with affected communities, as well as development of wearable repellent technologies against Aedes mosquitoes will enhance the impact. Burden of disease studies, data-driven vector control, and vaccine modeling as well as risk assessments on geographic spread of ZIKV will form the foundation for evidence-informed policies. While addressing the research gaps around ZIKV, we will engage in capacity building in laboratory and clinical research, collaborate with existing and new networks to share knowledge, and work with international organizations to tackle regulatory and other bottlenecks and refine research priorities. In this way, we can leverage the ZIKV response toward building a long-term emerging infectious diseases response capacity in the region to address future challenges.

A case-control study of protection against tuberculosis by BCG revaccination in Recife, Brazil.

SETTING: Metropolitan region of Recife, Brazil. OBJECTIVE: To estimate the additional protection against tuberculosis (TB) provided by a second dose of bacille Calmette-Guérin (BCG) vaccine. DESIGN: Case-control study. Cases were cases of TB newly diagnosed by the TB control programme, independent of clinical form. Three matched neighbourhood controls were selected using a systematic routine, starting from the case's address. The matching was within the age groups 7-9, 10-14 and 15-19 years. RESULTS: Analysis was conducted among 169 cases and 477 controls. For the efficacy of BCG revaccination against TB overall, matched (crude) vaccine effectiveness (VE) was -3 (95% CI -50-29) and matched (adjusted) VE was 8 (95% CI -77-52). CONCLUSIONS: This study suggests that a second dose of BCG does not offer additional protection. Revaccination should not be offered. As large numbers of subjects are already vaccinated and vaccine appears to offer some protection in older subjects, further studies with larger sample sizes could investigate the potential efficacy of revaccination with BCG in the age group > or = 15 years.

Clinical classification of tetanus patients.

The authors propose a clinical classification to monitor the evolution of tetanus patients, ranging from grade I to IV according to severity. It was applied on admission and repeated on alternate days up to the 10th day to patients aged > or = 12 years admitted to the State University Hospital, Recife, Brazil. Patients were also classified upon admission according to three prognostic indicators to determine if the proposed classification is in agreement with the traditionally used indicators. Upon admission, the distribution of the 64 patients among the different levels of the proposed classification was similar for the groups of better and worse prognosis according to the three indicators (P > 0.05), most of the patients belonging to grades I and II of the proposed classification. In the later reclassifications, severe forms of tetanus (grades III and IV) were more frequent in the categories of worse prognosis and these differences were statistically significant. There was a reduction in the proportion of mild forms (grades I and II) of tetanus with time for the categories of worse prognostic indicators (chi-square for trend: P = 0.00006, 0.03, and 0.00000) whereas no such trend was observed for the categories of better prognosis (grades I and II). This serially used classification reflected the prognosis of the traditional indicators and permitted the comparison of the dynamics of the disease in different groups. Thus, it becomes a useful tool for monitoring patients by determining clinical category changes with time, and for assessing responses to different therapeutic measures.

Hepatitis C virus infection in a Brazilian population with sickle-cell anemia.

Patients with sickle-cell anemia submitted to frequent blood transfusions are at risk of contamination with hepatitis C virus (HCV). Determination of HCV RNA and genotype characterization are parameters that are relevant for the treatment of the viral infection. The objective of the present study was to determine the frequency of HCV infection and the positivity for HCV RNA and to identify the HCV genotype in patients with sickle-cell anemia with a history of blood transfusion who had been treated at the Hospital of the HEMOPE Foundation. Sera from 291 patients were tested for anti-HCV antibodies by ELISA 3.0 and RIBA 3.0 Chiron and for the presence of HCV RNA by RT-PCR. HCV genotyping was performed in 19 serum samples. Forty-one of 291 patients (14.1%) were anti-HCV positive by ELISA and RIBA. Both univariate and multivariate analysis showed a greater risk of anti-HCV positivity in those who had started a transfusion regime before 1992 and received more than 10 units of blood. Thirty-four of the anti-HCV-positive patients (34/41, 82.9%) were also HCV RNA positive. Univariate analysis, used to compare HCV RNA-negative and -positive patients, did not indicate a higher risk of HCV RNA positivity for any of the variables evaluated. The genotypes identified were 1b (63%), 1a (21%) and 3a (16%). A high prevalence of HCV infection was observed in our patients with sickle-cell anemia (14.1%) compared to the population in general (3%). In the literature, the frequency of HCV infection in sickle-cell anemia ranges from 2 to 30%. The serological screening for anti-HCV at blood banks after 1992 has contributed to a better control of the dissemination of HCV infection. Because of the predominance of genotype 1, these patients belong to a group requiring special treatment, with a probable indication of new therapeutic options against HCV.

Migration and urban schistosomiasis. The case of São Lourenço da Mata, northeast of Brazil.

A population-based case-control design was used to investigate the association between migration, urbanisation and schistosomiasis in the Metropolitan Region of Recife, Northeast of Brazil. 1022 cases and 994 controls, aged 10 to 25, were selected. The natives and the migrants who come from endemic areas have a similar risk of infection. On the other hand, the risk of infection of migrants from nonendemic areas seems to be related with the time elapsed since their arrival in São Lourenço da Mata; those who have been living in that urban area for 5 or more years have a risk of infection similar to that of the natives. Those arriving in the metropolitan region of Recife mostly emigrate from "zona da mata" and "zona do agreste" in the state of Pernambuco. Due to the changes in the sugar agroindustry and to the increase in the area used for cattle grazing these workers were driven to villages and cities. The pattern of urbanisation created the conditions for the establishment of foci of transmission in São Lourenço da Mata.

Identification of risk factors for death from tetanus in Pernambuco, Brazil: a case-control study.

A case-control study was conducted to identify risk factors for death from tetanus in the State of Pernambuco, Brazil. Information was obtained from medical records of 152 cases and 152 controls, admitted to the tetanus unit in the State University Hospital, in Recife, from 1990 to 1995. Variables were grouped in three different sets. Crude and adjusted odds ratios, p-values and 95% confidence intervals were estimated. Variables selected in the multivariate analysis in each set were controlled for the effect of those selected in the others. All factors related to the disease progression - incubation period, time elapsed between the occurrence of the first tetanus symptom and admission, and period of onset - showed a statistically significant association with death from tetanus. Similarly, signs and/or symptoms occurring on admission or in the following 24 hours (second set): reflex spasms, neck stiffness, respiratory signs/symptoms and respiratory failure requiring artificial ventilation (third set) were associated with death from tetanus even when adjusted for the effect of the others.

Bancroftian filariasis in two urban areas of Recife, Brasil: the role of individual risk factors.

Bancroftian filariasis is spreading in towns of endemic areas in Recife, northeastern Brazil, where it is a major public health problem. This paper deals with the prevalence of microfilaraemia and filarial disease in two urban areas of Recife, studying their association with individual characteristics and variables related to the exposure to the vectors. The parasitologic survey was performed through a "door-to-door" census and microfilaraemia was examined by the thick-drop technique using 45 microliters of peripheral blood collected between 20:00 and 24:00 o'clock. 2,863 individuals aged between 5 and 65 years were interviewed and submitted to clinical examination. Males aged between 15 and 44 years old presented the greatest risk of being microfilaraemic. Microfilaraemia was also significantly associated with no use of bednet to sleep. The risk of being microfilaraemic was greater among those who had lived in the studied areas for more than 5 years. The overall disease prevalence was 6.3%. Males presented the greatest risk of developing acute disease. The risk of developing chronic manifestations was also greater among males and increased with age. We found no association between time of residence, bednet use, microfilaraemia and acute and chronic disease. We may conclude that in endemic areas there are subgroups of individuals who has a higher risk of being microfilariae carriers due to different behaviours in relation to vector contact.

Radiographic features of pulmonary tuberculosis in patients infected by HIV: is there an objective indicator of co-infection?

This study aimed to compare the radiographic characteristics of patients with pulmonary tuberculosis (TB) and human immunodeficiency virus (HIV) infection with those of HIV-negative patients. In all, 275 TB patients attending the outpatients clinics at the University Hospital/UFPE, were studied from January 1997 to March 1999. Thirty nine (14.2%) of them were HIV(+), with a higher frequency of males in this group (p=0.044). Seventy-five percent of the HIV(+) patients and 19% of the HIV(-) had a negative tuberculin test (PPD) (p < 0.001). The proportion of positive sputum smears in the two groups was similar. The radiological finding most strongly associated with co-infection was absence of cavitation (p < 0.001). It may therefore be concluded that the lack of cavitation in patients with pulmonary TB may be considered a useful indicator of the need to investigate HIV infection. This approach could contribute to increasing the effectiveness of local health services, by offering appropriate treatment to co-infected patients.

[Internal validity in cross-sectional studies: comments based on an investigation on the association between socioeconomic factors and schistosomiasis]. / Validade interna em estudos de corte transversal: reflexões a partir de uma investigação sobre esquistossomose mansônica e condições socioeconômicas.

The purpose of this paper was to make some comments on validity based on an investigation developed in an urban area in the Greater Metropolitan Area of Recife, Brazil, the objective of which was to study the association between socioeconomic factors and schistosomiasis. It discusses the distortion in the odds ratio that may be introduced either by the way individuals are selected for the study or by the way the information is collected. The article describes the mechanisms used by the authors to avoid bias when planning or conducting the investigation and considerations were made on how these types of bias could have influenced the results.

[Evaluation of a social and environmental indicator used in the identification of lymphatic filariasis transmission in urban centers]. / Avaliação de indicador sócio-ambiental utilizado no rastreamento de áreas de transmissão de filariose linfática em espaços urbanos.

The concept of a "socially organized space" supported by new analytical techniques and mapping of health events has guided innovative methodological developments in public health interventions. This study aimed to evaluate a social/environmental indicator constructed with a scoring methodology to stratify areas in the city of Olinda by different levels of risk for Bancroftian filariasis transmission. The study mapped areas and the location of sample households and identified all residents ages 5 to 65 years as part of the parasitological survey. Among the 3,232 individuals who had blood samples taken, 42 were microfilaremic (1.3% prevalence). Global statistical analysis of filarial case distribution has suggested spatial clustering. Some 85.7% of positive individuals resided in the two strata with the highest transmission risk. The high sensitivity of the proposed indicator for predicting the places where the vast majority of filariasis cases occurred justifies its use in planning and implementing interventions.

[Surveillance of endemic diseases in urban areas: the interface between census tract maps and morbidity data]. / Vigilância de doenças endêmicas em áreas urbanas: a interface entre mapas de setores censitários e indicadores de morbidade.

In this article we discuss the methodological issues associated with the creation of a surveillance system for endemic diseases in urban areas based on analysis of populations at risk and on spatially referenced epidemiological indicators. We comment on the system's basic requirements, selection criteria for socioeconomic variables, and methodological steps to combine these variables so as to construct a census-based deprivation index. We also present the ways we solved some operational problems related to generation of digitized census tracts maps and linkage of morbidity data from different sources. This approach, spatial organization into account in surveillance of endemic diseases, exemplified here by tuberculosis and leprosy, allows for the interaction of several official data sets from census and health services in order to geographically discriminate inner-city risk strata. Criteria for constructing these risk strata were considered a useful tool for health planning and management activities for the control of endemic diseases in cities.

[Epidemiological pattern of lymphatic filariasis in children living in endemic areas]. / Perfil epidemiológico da filariose linfática em crianças residentes em áreas endêmicas.

OBJECTIVE: Lymphatic filariasis still represents a major public health problem in the city of Recife. In spite of the fact that previous surveys had already shown high frequency of microfilaraemia in pediatric population, the prevalence of filarial disease and the microfilaraemic pattern of this group were unknown. This paper describes the clinical-epidemiological pattern of filariasis in children and adolescents living in two highly endemic areas of Recife. METHODS: The parasitological survey was done through a census carried out between December 1990 and July 1991. Thick drop technique (45 micro l) was performed on a total of 1,464 children and adolescents between the ages of 5 and 14, of whom 967 were submitted to clinical examination. Positive cases had their blood recollected (60 micro l) to measure the microfilaraemic density. RESULTS: The microfilaraemia prevalence was 6.4 %. In the age groups of 5 to 9 and 10 to 14 a microfilaraemia prevalence of respectively 4.6% and 8.3% was observed. The microfilaraemic density varied from 3 to 864 microfilariae per 60 microl of blood, there having been no statistically significant difference between the sexes and age groups (p<0.05). 6 cases (0.6 %) of acute filarial disease and 11 of chronic filarial disease (1.1%) were identified, hydrocele being the principal manifestation found. Lymphadenopathy was found in 22% of the children, statistical association with microfilaraemia being observed (p<0.001). CONCLUSIONS: The results of the parasitological survey show the strong presence of children in the contingent of microfilaraemic individuals, indicating an early and intense exposure to filariasis in the population studied.

Is arterial stiffness in HIV-infected individuals associated with HIV-related factors?

We investigated the association between pulse wave velocity (PWV) and HIV infection, antiretroviral treatment-related characteristics, viral load, immune status, and metabolic changes in a cross-sectional study nested in a cohort of HIV/AIDS patients who have been followed for metabolic and cardiovascular changes since 2007. The study included patients recruited from the cohort (N = 261) and a comparison group (N = 82) of uninfected individuals, all enrolled from April to November 2009. Aortic stiffness was estimated using the carotid-femoral PWV (Complior-Artech, Paris, France). The groups were similar with respect to age, metabolic syndrome, diabetes mellitus, Framingham score, and use of antihypertensive and hypolipidemic medications. Hypertension was more frequent among the controls. Individuals with HIV had higher triglyceride, glucose and HDL cholesterol levels. Among individuals with HIV/AIDS, those with a nadir CD4+ T-cell count <200 cells/mm³ had a higher PWV (P = 0.01). There was no statistically significant difference when subjects were stratified by gender. Heart rate, age, male gender, and blood pressure were independently correlated with PWV. Nadir CD4+ T-cell count did not remain in the final model. There was no significance difference in PWV between HIV-infected individuals and uninfected controls. PWV was correlated with age, gender, and blood pressure across the entire population and among those infected with HIV. We recommend cohort studies to further explore the association between inflammation related to HIV infection and/or immune reconstitution and antiretroviral use and PWV.

Survival of HIV-infected patients after starting tuberculosis treatment: a prospective cohort study.

OBJECTIVES: To estimate the probability of survival and to evaluate risk factors for death in a cohort of persons living with human immunodeficiency virus (PLHIV) who had started tuberculosis (TB) treatment. METHODS: A prospective cohort study was conducted between June 2007 and December 2009 with HIV-infected patients who had started anti-tuberculosis treatment in the State of Pernambuco, Brazil. Survival data were analysed using the Kaplan-Meier estimator, the log-rank test and the Cox model. Hazard ratios and their respective 95%CIs were estimated. RESULTS: Of a cohort of 2310 HIV-positive individuals, 333 patients who had commenced treatment for TB were analysed. The mortality rate was 5.25 per 10,000 person-years (95%CI 4.15-6.63). The probability of survival at 30 months was 74%. Risk factors for death in the study population were being female, age ≥30 years, having anaemia, not using highly active antiretroviral therapy (HAART) during treatment for TB and disseminated TB. Protective factors for death were a CD4 lymphocyte count >200 cells/mm(3) and treatment for TB having started in an out-patient clinic. CONCLUSIONS: The use of HAART can prevent deaths among HIV-TB patients, corroborating the efficacy of starting HAART early in individuals with TB.

Randomized clinical trial comparing the efficacy of the vaginal use of metronidazole with a Brazilian pepper tree (Schinus) extract for the treatment of bacterial vaginosis.

A 7.4% vaginal extract of the Brazilian pepper tree (Schinus terebinthifolius Raddi) was compared with 0.75% vaginal metronidazole, both manufactured by the Hebron Laboratory, for the treatment of bacterial vaginosis, used at bedtime for 7 nights. The condition was diagnosed using the combined criteria of Amsel and Nugent in two groups of 140 and 137 women, aged between 18 and 40 years. Intention-to-treat analysis was performed. Women were excluded from the study if they presented delayed menstruation, were pregnant, were using or had used any topical or systemic medication, presented any other vaginal infections, presented hymen integrity, or if they reported any history suggestive of acute pelvic inflammatory disease. According to Amsel's criteria separately, 29 patients (21.2%) treated with the extract and 87 (62.1%) treated with metronidazole were considered to be cured (P < 0.001). According to Nugent's score separately, 19 women (13.9%) treated with the extract and 79 (56.4%) treated with metronidazole were considered to be cured (P < 0.001). Using the two criteria together, the so-called total cure was observed in 17 women (12.4%) treated with the extract and in 79 women (56.4%) treated with metronidazole (P < 0.001). In conclusion, the cure rate for bacterial vaginosis using a vaginal gel from a pepper tree extract was lower than the rate obtained with metronidazole gel, while side effects were infrequent and non-severe in both groups.

Is arterial stiffness in HIV-infected individuals associated with HIV-related factors?

We investigated the association between pulse wave velocity (PWV) and HIV infection, antiretroviral treatment-related characteristics, viral load, immune status, and metabolic changes in a cross-sectional study nested in a cohort of HIV/AIDS patients who have been followed for metabolic and cardiovascular changes since 2007. The study included patients recruited from the cohort (N = 261) and a comparison group (N = 82) of uninfected individuals, all enrolled from April to November 2009. Aortic stiffness was estimated using the carotid-femoral PWV (Complior-Artech, Paris, France). The groups were similar with respect to age, metabolic syndrome, diabetes mellitus, Framingham score, and use of antihypertensive and hypolipidemic medications. Hypertension was more frequent among the controls. Individuals with HIV had higher triglyceride, glucose and HDL cholesterol levels. Among individuals with HIV/AIDS, those with a nadir CD4+ T-cell count <200 cells/mm³ had a higher PWV (P = 0.01). There was no statistically significant difference when subjects were stratified by gender. Heart rate, age, male gender, and blood pressure were independently correlated with PWV. Nadir CD4+ T-cell count did not remain in the final model. There was no significance difference in PWV between HIV-infected individuals and uninfected controls. PWV was correlated with age, gender, and blood pressure across the entire population and among those infected with HIV. We recommend cohort studies to further explore the association between inflammation related to HIV infection and/or immune reconstitution and antiretroviral use and PWV.

Randomized clinical trial comparing the efficacy of the vaginal use of metronidazole with a Brazilian pepper tree (Schinus) extract for the treatment of bacterial vaginosis

A 7.4 percent vaginal extract of the Brazilian pepper tree (Schinus terebinthifolius Raddi) was compared with 0.75 percent vaginal metronidazole, both manufactured by the Hebron Laboratory, for the treatment of bacterial vaginosis, used at bedtime for 7 nights. The condition was diagnosed using the combined criteria of Amsel and Nugent in two groups of 140 and 137 women, aged between 18 and 40 years. Intention-to-treat analysis was performed. Women were excluded from the study if they presented delayed menstruation, were pregnant, were using or had used any topical or systemic medication, presented any other vaginal infections, presented hymen integrity, or if they reported any history suggestive of acute pelvic inflammatory disease. According to Amsel’s criteria separately, 29 patients (21.2 percent) treated with the extract and 87 (62.1 percent) treated with metronidazole were considered to be cured (P < 0.001). According to Nugent’s score separately, 19 women (13.9 percent) treated with the extract and 79 (56.4 percent) treated with metronidazole were considered to be cured (P < 0.001). Using the two criteria together, the so-called total cure was observed in 17 women (12.4 percent) treated with the extract and in 79 women (56.4 percent) treated with metronidazole (P < 0.001). In conclusion, the cure rate for bacterial vaginosis using a vaginal gel from a pepper tree extract was lower than the rate obtained with metronidazole gel, while side effects were infrequent and non-severe in both groups.

Risk factors associated with death in children admitted to a paediatric intensive care unit.

The aim of this study was to identify fatal risk factors for children admitted to the paediatric intensive care unit of the Instituto Materno Infantil de Pernambuco, a referral hospital in Recife, a city in the north-east of Brazil. A survey was performed from June 1996 to January 1997. Risk was quantified by the crude and adjusted odds ratio. The 95 per cent confidence interval, likelihood ratio statistics, and the probability (p < 0.05) value were used to test for statistical significance. An association was established between death in children admitted to the paediatric intensive care unit and: (1) age below 2 years old; (2) use of mechanical ventilation and central venous catheter; (3) presence of hospital-acquired infection; (4) length of hospital stay of 2 days or less; and (5) Class 4 clinical severity, according to the Clinical Classification System (CCS). These results allow the identification of the children with a greater risk of death and may contribute to improvements in handling groups of patients with poor prognosis.