The trajectories of CD4 T lymphocytes over time in patients who have defaulted on treatment for tuberculosis in a cohort of people living with HIV, Recife/PE.

BACKGROUND: The CD4 T lymphocyte count in people living with HIV (PLHIV) is a predictor for the progression of the disease (AIDS), survival and response to antiretroviral treatment (ART). A CD4 T lymphocyte count of less than 200 cells/mm3 is indicative of a greater risk for the onset of opportunistic diseases and death. Defaulting on treatment for tuberculosis (TB) may impact immune recovery in PLHIV who are taking ART. The aim of this study was to investigate an association of the CD4 lymphocyte with TB treatment Trajectory and with death. METHODS: A cohort of PLHIV over eighteen years of age and who were taking ART and who had defaulted on pulmonary TB treatment. Latent Class analysis was used to identify different trajectories of CD4 T lymphocyte counts over time. RESULTS: Latent class 1 (High CD4 trajectory) grouped individuals together who were characterized as maintaining a low probability (0 to 29%) of a CD4 count ≤ 200 cells/mm3over time, while latent class 2 (Low CD4 trajectory) grouped individuals together with a high probability (93% to 60%), and latent class 3 (Fluctuating CD4 trajectory), grouped individuals with a fluctuating probability (66% to 0%). The chance of defaulting on treatment earlier (≤ 90 days) was four times higher in latent class 2 (Low CD4 trajectory). Although there was no statistical significance, there was a higher frequency of deaths in this same latent class. CONCLUSION: Individuals with a high probability of a CD4 count ≤ 200 cells/ mm3 should be monitored in order to avoid treatment default and thereby prevent death. New studies should be conducted with a larger sample size and a longer follow-up time in PLHIV who initiated ART treatment early so as to support clinical decisions for a better understanding of immune behavior.

Longitudinal evolution of electroencephalogram (EEG): Findings over five years of follow-up in children with Zika-related microcephaly from the Microcephaly Epidemic Research Group Pediatric Cohort (2015-2020).

OBJECTIVE: To assess the longitudinal evolution of EEG findings in children with Zika related-microcephaly (ZRM) and to evaluate the associations of these patterns with the children's clinical and neuroimaging characteristics. METHODS: As part of the follow-up of the Microcephaly Epidemic Research Group Pediatric Cohort (MERG-PC) in Recife, Brazil, we performed serial EEG recordings in a subgroup of children with ZRM to evaluate changes in background rhythms and epileptiform activity (EA). Latent class analysis was used to identify patterns in the evolution of EA over time; clinical and neuroimaging findings were compared across the identified groups. RESULTS: Out of the 72 children with ZRM who were evaluated during 190 EEGs/videoEEGs, all participants presented with abnormal background activity, 37.5% presented with an alpha-theta rhythmic activity, and 25% presented with sleep spindles, which were less commonly observed in children with epilepsy. EA changed over time in 79.2% of children, and three distinct trajectories were identified: (i) multifocal EA over time, (ii) no discharges/focal EA evolving to focal/multifocal EA, and (iii) focal/multifocal EA evolving to epileptic encephalopathy patterns (e.g., hypsarrhythmia or continuous EA in sleep). The multifocal EA over time trajectory was associated with periventricular and thalamus/basal ganglia calcifications, brainstem and corpus callosum atrophy and had less focal epilepsy, whereas the children in the trajectory which evolved to epileptic encephalopathy patterns had more frequently focal epilepsy. SIGNIFICANCE: These findings suggest that, in most children with ZRM, trajectories of changes in EA can be identified and associated with neuroimaging and clinical features.

Endocrine Dysfunction in Children with Zika-Related Microcephaly Who Were Born during the 2015 Epidemic in the State of Pernambuco, Brazil.

Congenital viral infections and the occurrence of septo-optic dysplasia, which is a combination of optic nerve hypoplasia, abnormal formation of structures along the midline of the brain, and pituitary hypofunction, support the biological plausibility of endocrine dysfunction in Zika-related microcephaly. In this case series we ascertained the presence and describe endocrine dysfunction in 30 children with severe Zika-related microcephaly from the MERG Pediatric Cohort, referred for endocrinological evaluation between February and August 2019. Of the 30 children, 97% had severe microcephaly. The average age at the endocrinological consultation was 41 months and 53% were female. The most frequently observed endocrine dysfunctions comprised short stature, hypothyroidism, obesity and variants early puberty. These dysfunctions occurred alone 57% or in combination 43%. We found optic nerve hypoplasia (6/21) and corpus callosum hypoplasia (20/21). Seizure crises were reported in 86% of the children. The most common-and clinically important-endocrine dysfunctions were pubertal dysfunctions, thyroid disease, growth impairment, and obesity. These dysfunctions require careful monitoring and signal the need for endocrinological evaluation in children with Zika-related microcephaly, in order to make early diagnoses and implement appropriate treatment when necessary.

Surgical findings in cryptorchidism in children with Zika-related microcephaly: a case series.

BACKGROUND: Complications in the urinary tract related to congenital Zika syndrome have recently been reported. One complication, cryptorchidism, has been reported by the Microcephaly Epidemic Research Group/MERG, in Pernambuco/Brazil. The present article describes for the first time the surgical findings in a case series of boys with Zika-related microcephaly and cryptorchidism, who underwent surgical testicular exploration as a contribution to better understand the possible mechanisms involved in gonads formation and descent. METHODS: A total of 7 children (11 testicular units), aged 3 to 4 years, were submitted to inguinal or scrotal orchidopexy for the treatment of palpable cryptorchidism between August 2019 and January 2020. Characteristics of the gonads and its annexes related to appendixes, testis-epididymis dissociation, gubernacular insertion, and associated hydroceles and/or hernias were described. Measures in centimetres were taken for volume calculate. RESULTS: We found a low prevalence of testicular and epididymal appendix (66.7%), a high prevalence of testis-epididymis dissociation (55.6%), low mean testicular volume for their ages (lower for older boys) and ectopic gubernacular insertion in all cases. There was no evidence of associated hydroceles and/or hernias in any case. No surgical complication was registered or reported, and all explored gonads were properly placed in the scrotal sac. CONCLUSIONS: We herein describe the surgical findings of these children's orchidopexies and discuss the possible mechanisms of viral action in embryogenesis and postnatal growth and development of the testes and annexes. These children need to be followed over time due to the higher risk of testicular atrophy and malignancy. Surgical timing seems to be relevant to avoid loss of testicular volume.

Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study.

BACKGROUND: Since 2015, the arthropod-borne viruses (arboviruses) Zika and chikungunya have spread across the Americas causing outbreaks, accompanied by increases in immune-mediated and infectious neurological disease. The spectrum of neurological manifestations linked to these viruses, and the importance of dual infection, are not known fully. We aimed to investigate whether neurological presentations differed according to the infecting arbovirus, and whether patients with dual infection had a different disease spectrum or severity. METHODS: We report a prospective observational study done during epidemics of Zika and chikungunya viruses in Recife, Pernambuco, a dengue-endemic area of Brazil. We recruited adults aged 18 years or older referred to Hospital da Restauração, a secondary-level and tertiary-level hospital, with suspected acute neurological disease and a history of suspected arboviral infection. We looked for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. We grouped patients according to their arbovirus laboratory diagnosis and then compared demographic and clinical characteristics. FINDINGS: Between Dec 4, 2014, and Dec 4, 2016, 1410 patients were admitted to the hospital neurology service; 201 (14%) had symptoms consistent with arbovirus infection and sufficient samples for diagnostic testing and were included in the study. The median age was 48 years (IQR 34-60), and 106 (53%) were women. 148 (74%) of 201 patients had laboratory evidence of arboviral infection. 98 (49%) of them had a single viral infection (41 [20%] had Zika, 55 [27%] had chikungunya, and two [1%] had dengue infection), whereas 50 (25%) had evidence of dual infection, mostly with Zika and chikungunya viruses (46 [23%] patients). Patients positive for arbovirus infection presented with a broad range of CNS and peripheral nervous system (PNS) disease. Chikungunya infection was more often associated with CNS disease (26 [47%] of 55 patients with chikungunya infection vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients). Zika infection was more often associated with PNS disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection; p≤0·0001), particularly Guillain-Barré syndrome (25 [61%] patients). Patients with Guillain-Barré syndrome who had Zika and chikungunya dual infection had more aggressive disease, requiring intensive care support and longer hospital stays, than those with mono-infection (median 24 days [IQR 20-30] vs 17 days [10-20]; p=0·0028). Eight (17%) of 46 patients with Zika and chikungunya dual infection had a stroke or transient ischaemic attack, compared with five (6%) of 96 patients with Zika or chikungunya mono-infection (p=0·047). INTERPRETATION: There is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation. FUNDING: Fundação do Amparo a Ciência e Tecnologia de Pernambuco (FACEPE), EU's Horizon 2020 research and innovation programme, National Institute for Health Research. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Cryptorchidism in Children with Zika-Related Microcephaly.

The genitourinary tract was recently identified as a potential site of complications related to the congenital Zika syndrome (CZS). We provide the first report of a series of cryptorchidism cases in 3-year-old children with Zika-related microcephaly who underwent consultations between October 2018 and April 2019 as part of the follow-up of the children cohort of the Microcephaly Epidemic Research Group, Pernambuco, Brazil. Of the 22 males examined, eight (36.4%) presented with cryptorchidism. Among 14 undescended testis cases, 11 (78.6%) could be palpated in the inguinal region. Seven of the eight children had severe microcephaly. Conventional risk factors for cryptorchidism were relatively infrequent in these children. We hypothesize that cryptorchidism is an additional manifestation of CZS present in children with severe microcephaly. As in our cases, for most of the children, the testes were located in the inguinal region, and the possible mechanisms for cryptorchidism were gubernaculum disturbance or cremasteric abnormality.

Early epilepsy in children with Zika-related microcephaly in a cohort in Recife, Brazil: Characteristics, electroencephalographic findings, and treatment response.

OBJECTIVE: To estimate the incidence of epilepsy in children with Zika-related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. METHODS: We followed a cohort of children, born during the 2015-2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. RESULTS: We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. SIGNIFICANCE: Zika-related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.

Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil.

INTRODUCTION AND OBJECTIVE: Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphisms in NAT2 associated with the development of hepatotoxicity after initiating treatment for TB in people living with HIV/AIDS (PLWHA) in Pernambuco, Northeast Brazil. MATERIAL AND METHODS: This was a prospective cohort study that investigated seven single nucleotide polymorphisms located in the NAT2 coding region in 173 PLWHA undergoing TB treatment. Hepatotoxicity was defined as elevated aminotransferase levels and identified as being three times higher than it was before initiating TB treatment, with associated symptoms of hepatitis. A further 80 healthy subjects, without HIV infection or TB were used as a control group. All individuals were genotyped by direct sequencing. RESULTS: The NAT2*13A and NAT2*6B variant alleles were significantly associated with the development of hepatotoxicity during TB treatment in PLWHA (p<0.05). Individual comparisons between the wild type and each variant genotype revealed that PLWHA with signatures NAT2*13A/NAT2*13A (OR 4.4; CI95% 1.1-18.8; p 0.037) and NAT2*13A/NAT2*6B (OR 4.4; CI95% 1.5-12.7; p 0.005) significantly increased the risk of hepatotoxicity. CONCLUSION: This study suggests that NAT2*13A and NAT2*6B variant alleles are risk factors for developing hepatotoxicity, and PLWHA with genotypes NAT2*13A/NAT2*13A and NAT2*13A/NAT2*6B should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis.

Perinatal analyses of Zika- and dengue virus-specific neutralizing antibodies: A microcephaly case-control study in an area of high dengue endemicity in Brazil.

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas.

Serological markers of hepatitis B and C in patients with HIV/AIDS and active tuberculosis.

Infection with hepatitis B virus (HBV) and C virus (HCV) are common in patients with HIV/AIDS and tuberculosis (TB). This is a cross-sectional study with patients infected with HIV/AIDS and active TB in Recife, Brazil, aiming to verify the prevalence of markers for HBV: antibody to hepatitis B core antigen (anti-HBc); and HCV: antibody to hepatitis C virus (anti-HCV) by chemiluminescence, and to identify the frequency of associated factors. Data were collected through questionnaires, and blood was drawn from patients for analysis. We used the chi-square test and the Fisher exact test when necessary. We conducted a bivariate logistic regression analysis and the magnitude of the associations was expressed as odds ratio (OR) with a confidence interval of 95%. Among 166 patients studied with HIV/AIDS and active TB, anti-HBc was positive in 61 patients [36.7%; 95%CI (29.4-44.6%)] and anti-HCV in 11[6.6%; 95%CI (3.4-11.5%)]. In the logistic regression analysis, male sex, and age ≥40 years were independent factors associated with the occurrence of anti-HBc. In conclusion, we verified a high frequency of HBV contact marker and a low frequency of HCV markers in patients with HIV/AIDS and TB in Recife.

Population-Based Multicentric Survey of Hepatitis B Infection and Risk Factors in the North, South, and Southeast Regions of Brazil, 10-20 Years After the Beginning of Vaccination.

A population-based hepatitis survey was carried out to estimate the prevalence of hepatitis B virus (HBV) infection and its predictive factors for the state capitals from the north, south, and southeast regions of Brazil. A multistage cluster sampling was used to select, successively, census tracts, blocks, households, and residents in the age group 10-69 years in each state capital. The prevalence of hepatitis B surface antigen (HBsAg) was lower than 1% in the north, southeast, and south regions. Socioeconomic condition was associated with HBV infection in north and south regions. Variables related to the blood route transmission were associated with HBV infection only in the south whereas those related to sexual behavior were associated with HBV infection in the north and south regions. Drug use was associated in all regions, but the type of drug differed. The findings presented herein highlight the diversity of the potential transmission routes for hepatitis B transmission in Brazil. In one hand, it reinforces the importance of national control strategies of large impact already in course (immunization of infants, adolescents, and adults up to 49 years of age and blood supply screening). On the other hand, it shows that there is still room for further control measures targeted to different groups within each region.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil.

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4⁺ lymphocyte count < 200/mm³ (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Prognostic evaluation of DNA index in HIV-HPV co-infected women cervical samples attending in reference centers for HIV-AIDS in Recife.

INTRODUCTION: Persistence of cervical infection caused by human papillomavirus (HPV) types with high oncogenic risk may lead to cervical intraepithelial neoplasia (CIN). The aim of the present study was to evaluate whether, in HIV-positive women, the presence of aneuploidy in cervical cell samples is associated with presence and evolution of CIN. METHODS: The present study had two stages. In the first stage, comprising a cross-sectional study, the association between the presence of aneuploidy seen via flow cytometry and sociodemographic characteristics, habits and characteristics relating to HPV and HIV infection was analyzed. In the second stage, comprising a cohort study, it was investigated whether aneuploidy was predictive of CIN evolution. RESULTS: No association was observed between the presence of aneuploidy and HPV infection, or between its presence and alterations seen in oncotic cytological analysis. On the other hand, aneuploidy was associated with the presence of CIN (p = 0.030) in histological analysis and with nonuse of antiretroviral therapy (p = 0.001). Most of the HIV-positive women (234/272) presented normal CD4+ T lymphocyte counts (greater than 350 cells/mm3) and showed a greater aneuploidy regression rate (77.5%) than a progression rate (23.9%) over a follow-up of up to two years. CONCLUSION: Although there was an association between the presence of cervical tissue lesions and the DNA index, the latter was not predictive of progression of the cervical lesion. This suggests that progression of the cervical lesion to cancer in HIV-positive women may also be changed through improvement of the immunological state enabled by using antiretroviral therapy.

Empirical treatment for TB in HIV: lessons from a cohort study of people living with HIV treated in Recife, Brazil.

BACKGROUND: Tuberculosis (TB) is the leading cause of death related to HIV worldwide. This study analyzes the survival of People Living with HIV (PLHIV) reporting cough without bacteriological confirmation of TB and identify factors associated with death. METHODS: Prospective cohort with a consecutive sample of PLHIV, aged ≥ 18 years. Patient inclusion criteria were complaint of current cough of any duration at the time of the first study interview or during their subsequent routine visits to health services and for whom AFB sputum smear was either negative or not performed during the whole follow-up period. Kaplan-Meier method was used to calculate the probability of survival. We estimated the Hazard Ratio (HR) in bivariate and multivariate Cox regression analyses. RESULTS: Mortality was 4.6 per 100 py; 73% were receiving HAART at recruitment. Average time from the first recorded date of cough until empirical treatment for tuberculosis was six months. Mortality was higher when the CD4 count was low (HR = 5.3; CI 95%: 3.2-9.0; p = 0.000), in those with anemia (HR = 3.0; CI 95%: 1.6-5.6; p = 0.001) and with abnormal chest X-rays (HR = 2.4; CI 95%: 1.4-4.0; p = 0.001). Mortality was higher in those receiving empirical TB treatment (HR = 2.4; CI 95%: 1.4-4.0; p = 0.002), but only in those with normal X-rays, no history of tuberculosis and no bacteriology requests. Empirical treatment for TB was more frequent in PLHIV with low CD4 counts, anemia, history of opportunistic infections, weight loss, previous tuberculosis, negative bacteriology test (as opposed to not having a test) and abnormal chest X-ray. CONCLUSIONS: Higher mortality in PLHIV reporting a current cough without bacteriological confirmation of tuberculosis was identified for those with a CD4 cell count <200, abnormal chest X-ray, anemia and empirical treatment for tuberculosis. Mortality was not significantly higher in those empirically treated for TB, who had three characteristics suggestive of the disease (abnormal chest X-ray, history of TB treatment, AFB sputum smear or M.tb culture testing). Routine cohorts are not an adequate setting to evaluate the impact of empirical treatment for TB on the mortality of PLHIV.

Treatment of facial lipoatrophy with polymethylmethacrylate among patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): impact on the quality of life.

BACKGROUND: The lipodystrophy syndrome is characterized by selective loss of subcutaneous fat on the face and extremities (lipoatrophy) and/or accumulation of fat around the neck, abdomen, and thorax (lipohypertrophy). The aim of this study has been to assess the impact of polymethylmethacrylate facial treatment on quality of life, self-perceived facial image, and the severity of depressive symptoms in patients living with HIV/AIDS. METHODS: A non-randomized before and after interventional study was developed. Fifty-one patients underwent facial filling. The self-perceived quality of life, facial image, and degree of depressive symptoms were measured by the Short-Form 36 and HIV/AIDS--Targeted quality of life questionnaires, by a visual analogue scale and by the Beck depression inventory, respectively, before and three months after treatment. RESULTS: Six of the eight domains of Short-Form 36 and eight of the nine dimensions of the HIV/AIDS--Targeted quality of life questionnaires, together with the visual analogue scale and by the Beck depression inventory scores, revealed a statistically significant improvement. The only adverse effects registered were edema and ecchymosis. CONCLUSION: The treatment of facial lipoatrophy improved the self-perceived quality of life and facial image as well as any depressive symptoms among patients with HIV/AIDS.

Risk of coronary heart disease among HIV-infected patients: a multicenter study in Brazil.

Cardiovascular disease has emerged as a crescent problem among HIV-infected population. This study aimed to determine the 10-year risk of coronary heart disease using the Framingham risk score among HIV-infected patients from three regions of Brazil. This is a pooled analysis of three cohort studies, which enrolled 3,829 individuals, 59% were men, 66% had white skin color, and mean age 39.0 ± 9.9 years. Comparisons among regions showed that there were marked differences in demographic, socioeconomic, clinical, and HIV-related characteristics. Prevalence of Framingham score ≥10 was 4.5% in the Southern, 4.2% in the Midwest, and 3.9% in the Northeast of Brazil. The Framingham score ≥10 was similar between regions for males, patients aged ≥60 years, with obesity, central obesity, hypertension, and diabetes mellitus. Women were three times more likely to have coronary heart disease in 10 years than men. Hypertension and diabetes increased more than four times the risk of coronary heart disease, followed by central obesity, obesity, and prehypertension. The use of antiretroviral agents and time since HIV diagnosis were not risk factors for coronary artery disease in 10 years. In conclusion, hypertension and diabetes are the strongest independent predictors of 10-year risk of coronary heart disease among HIV-infected population.

Incremental costs of treating tetanus with intrathecal antitetanus immunoglobulin.

OBJECTIVE: To estimate the incremental cost of delivering intrathecal tetanus immunoglobulin compared to an intramuscular option. METHODS: To compare the two interventions, costs were estimated using standard cost methodology. Cost categories were personnel, overhead, consumables, antibiotics to treat infection, gases for respiratory assistance and immunoglobulin. Tetanus patients, aged 12 years or older, who were part of a randomised controlled clinical trial conducted in a referral hospital in Recife, Brazil, were allocated to two groups: a control group (58) and a study group (62). Patients allocated to the control group received 3000 international units (IU) of human immunoglobulin, with preservative, intramuscularly. The study group received the same quantity of immunoglobulin also intramuscularly plus an intrathecal dose of 1000 IU of a human immunoglobulin, free of preservatives, to prevent irritation of the meninges and avoid the need for corticosteroids. Thus, the difference between the two groups was the exclusive use of intrathecal immunoglobulin. The outcome measurements were clinical progression, hospital stay, respiratory assistance and respiratory infection. RESULTS: Delivering intrathecal immunoglobulin to patients saved a total of US$ 60 389, in a 10-day intensive care treatment, by preventing a worsening of their tetanus severity (e.g. from Grade I to Grades II, III, IV). Substantial cost saving was also observed in terms of hospital stay (US$ 173 104). CONCLUSIONS: Intrathecal treatment of tetanus is cost saving. This intervention deserves consideration by doctors and decision-makers as a mean of saving resources while maintaining high-quality health outcomes.

Prevalence and risk factors of Hepatitis C virus infection in Brazil, 2005 through 2009: a cross-sectional study.

BACKGROUND: Hepatitis C chronic liver disease is a major cause of liver transplant in developed countries. This article reports the first nationwide population-based survey conducted to estimate the seroprevalence of HCV antibodies and associated risk factors in the urban population of Brazil. METHODS: The cross sectional study was conducted in all Brazilian macro-regions from 2005 to 2009, as a stratified multistage cluster sample of 19,503 inhabitants aged between 10 and 69 years, representing individuals living in all 26 State capitals and the Federal District. Hepatitis C antibodies were detected by a third-generation enzyme immunoassay. Seropositive individuals were retested by Polymerase Chain Reaction and genotyped. Adjusted prevalence was estimated by macro-regions. Potential risk factors associated with HCV infection were assessed by calculating the crude and adjusted odds ratios, 95% confidence intervals (95% CI) and p values. Population attributable risk was estimated for multiple factors using a case-control approach. RESULTS: The overall weighted prevalence of hepatitis C antibodies was 1.38% (95% CI: 1.12%-1.64%). Prevalence of infection increased in older groups but was similar for both sexes. The multivariate model showed the following to be predictors of HCV infection: age, injected drug use (OR = 6.65), sniffed drug use (OR = 2.59), hospitalization (OR = 1.90), groups socially deprived by the lack of sewage disposal (OR = 2.53), and injection with glass syringe (OR = 1.52, with a borderline p value). The genotypes 1 (subtypes 1a, 1b), 2b and 3a were identified. The estimated population attributable risk for the ensemble of risk factors was 40%. Approximately 1.3 million individuals would be expected to be anti-HCV-positive in the country. CONCLUSIONS: The large estimated absolute numbers of infected individuals reveals the burden of the disease in the near future, giving rise to costs for the health care system and society at large. The known risk factors explain less than 50% of the infected cases, limiting the prevention strategies. Our findings regarding risk behaviors associated with HCV infection showed that there is still room for improving strategies for reducing transmission among drug users and nosocomial infection, as well as a need for specific prevention and control strategies targeting individuals living in poverty.

Periodontitis as a risk factor for preeclampsia.

BACKGROUND: Periodontitis is an inflammatory process caused by a specific group of microorganisms, resulting in the destruction of the tooth-supporting tissue and the resorption of the alveolar bone. Therefore, periodontitis has been considered a risk factor for preeclampsia because infection is one of the factors involved in the etiology and pathogenesis of preeclampsia. The aim of the present study is to determine whether periodontitis is a risk factor for preeclampsia and to identify other possible risk factors. METHODS: A case-control study was performed with 574 puerperae under care at the university hospital at the Universidade Federal de Pernambuco in the city of Recife, Brazil. Data collection was preceded by a training exercise and a pilot study. Biologic and socioeconomic data were collected along with medical and dental records. A periodontal examination was performed on all dental elements to determine probing depth and gingival recession. The association between periodontitis and preeclampsia was first adjusted for the variables within each block, and adjusted for the variables of all blocks in the final multivariate model. RESULTS: The multivariate logistic regression analysis showed that, after adjustment for other risk factors, periodontitis remained an independent risk factor for preeclampsia (adjusted odds ratio [OR] = 8.60, confidence interval [CI] = 3.92 to 18.88, P < 0.001 and adjusted OR = 2.03, 95% CI = 1.43 to 2.90, P < 0.001, when using the Centers for Disease Control and Prevention/American Academy of Periodontology definition). CONCLUSION: The results suggest that within the population studied, periodontitis was a risk factor for preeclampsia.

Maternal periodontitis as a risk factor for prematurity.

BACKGROUND: The aim of this study was to investigate maternal periodontitis associated with prematurity. METHODS: We carried out a case-control study including 718 puerperae who experienced a spontaneous delivery: 360 cases (premature) and 358 controls (full-term). Sociodemographic, obstetric, prenatal, perinatal and periodontal data were obtained within 48 h after delivery. Periodontitis was defined as probing depth ≥ 4 mm and attachment loss ≥ 3 mm at same site, for ≥ 4 teeth. RESULTS: Periodontitis was associated with prematurity (odds ratio 6.95; confidence interval 3.69-13.09). Prematurity was associated with maternal age < 20 years, family income < one minimum salary, maternal schooling < 8 years, premature birth history, premature membrane rupture, ruptured membranes > 24 h, smoking, urinary tract infection, leukorrhea, pre-eclampsia, prenatal consultations < 3 and precarious housing. After multivariate confounder adjustments, periodontitis remained independently associated with prematurity (odds ratio 6.05; confidence interval 3.01-12.16). CONCLUSIONS: Periodontitis is strongly associated with prematurity, indicating necessity for regular periodontal investigation and treatment during pregnancy.