Children Born to Mothers with Rash During Zika Virus Epidemic in Brazil: First 18 Months of Life.

OBJECTIVE: To better understand the clinical spectrum and course of congenital Zika syndrome (CZS) during the first 18 months of life of children whose mothers had rash during pregnancy. METHODS: This longitudinal observational study evaluated the clinical progress from birth until 18 months of life of children of mothers who developed rash during or up to 3 months before gestation. Maternal rash occurred from November 2015 to May 2017. The study subjects were divided into three groups: children whose mothers tested positive by RT-qPCR for Zika virus (ZIKV) (Group 1), children whose mothers tested negative by RT-qPCR for ZIKV (Group 2), and children whose mothers did not undergo any testing for ZIKV (Group 3) but tested negative for other congenital infections. RESULTS: Between April 2016 and July 2018, we studied 108 children: 43 in Group 1, 26 in Group 2 and 39 in Group 3. The majority of children were admitted into the study within 6 months of life. CZS was diagnosed in 26 children, equally distributed in Groups 1 and 3. Of 18 children with microcephaly, 6 were in Group 1 (1 postnatal) and 12 were in Group 3 (5 postnatal). Maternal rash frequency was 10 times higher during the first trimester than in the other trimesters (OR: 10.35; CI 95%: 3.52-30.41). CZS was diagnosed during the follow-up period in 14 (54%) cases. Developmental delays and motor abnormalities occurred in all children and persisted up to 18 months. Epilepsy occurred in 18 (69%) of the cases. CONCLUSIONS: Infants born of mothers exposed to ZIKV during pregnancy showed progression of developmental, motor and neurologic abnormalities even if they were born asymptomatic. Continued postnatal monitoring of such newborns is necessary to preclude disability-associated complications.

Clinical features and laboratory findings of human parvovirus B19 in human immunodeficiency virus-infected patients.

Immunocompromised patients may develop severe chronic anaemia when infected by human parvovirus B19 (B19V). However, this is not the case in human immunodeficiency virus (HIV)-infected patients with good adherence to highly active antiretroviral treatment (HAART). In this study, we investigated the clinical evolution of five HIV-infected patients receiving HAART who had B19V infections confirmed by serum polymerase chain reaction. Four of the patients were infected with genotype 1a strains and the remaining patient was infected with a genotype 3b strain. Anaemia was detected in three of the patients, but all patients recovered without requiring immunoglobulin and/or blood transfusions. In all cases, the attending physicians did not suspect the B19V infections. There was no apparent relationship between the infecting genotype and the clinical course. In the HAART era, B19V infections in HIV-positive patients may be limited, subtle or unapparent.

Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1ß and CCL2/MCP-1 in dengue fever and parvovirosis.

Dengue virus (DENV) and parvovirus B19 (B19V) infections are acute exanthematic febrile illnesses that are not easily differentiated on clinical grounds and affect the paediatric population. Patients with these acute exanthematic diseases were studied. Fever was more frequent in DENV than in B19V-infected patients. Arthritis/arthralgias with DENV infection were shown to be significantly more frequent in adults than in children. The circulating levels of interleukin (IL)-1 receptor antagonist (Ra), CXCL10/inducible protein-10 (IP-10), CCL4/macrophage inflammatory protein-1 beta and CCL2/monocyte chemotactic protein-1 (MCP-1) were determined by multiplex immunoassay in serum samples obtained from B19V (37) and DENV-infected (36) patients and from healthy individuals (7). Forward stepwise logistic regression analysis revealed that circulating CXCL10/IP-10 tends to be associated with DENV infection and that IL-1Ra was significantly associated with DENV infection. Similar analysis showed that circulating CCL2/MCP-1 tends to be associated with B19V infection. In dengue fever, increased circulating IL-1Ra may exert antipyretic actions in an effort to counteract the already increased concentrations of IL-1ß, while CXCL10/IP-10 was confirmed as a strong pro-inflammatory marker. Recruitment of monocytes/macrophages and upregulation of the humoral immune response by CCL2/MCP-1 by B19V may be involved in the persistence of the infection. Children with B19V or DENV infections had levels of these cytokines similar to those of adult patients.

Healthcare for children with congenital Zika syndrome: analysis of access to social rights.

The objective of this study was to describe if the victims of the Zika have access to essential public policies to guarantee social rights. METHODS: We used a cross-sectional study of a historical cohort of children with congenital Zika syndrome (CZS) in a reference hospital. CZS diagnosis was based on the Ministry of Health protocol. The variables analyzed were sociodemographic and social rights of children. RESULTS: Of the 161 children seen from April 2016 to July 2018, 42 were diagnosed with CZS. Of these, 37 children participated in the study and 75.7% of them had severe neurological disorders. Anticonvulsants were used by 73% of the children, with 81% paid by families. The families were also responsible for purchasing nutritional formulas and diapers in, respectively, 79% and 100% of cases, and 89% of the children had access to rehabilitation therapy, although 70% of them faced several barriers to do it. Of the 24 working mothers, 83% did not return to the labor market after the birth of their children. CONCLUSIONS: The results showed that the families were at an intersection between the integral activity of caring for a child with severe disabilities and inefficient and omissive public authorities, a disincentive and discouraging context that made them give up in seeking their rights.

Audiological Findings in Children Suspected to Have Been Exposed to the Zika Virus in the Intrauterine Period.

OBJECTIVE: To evaluate auditory manifestations in children born to mothers who had exanthema during pregnancy, suspected to have been exposed to the Zika virus (ZIKV). STUDY DESIGN: Prospective observational. SETTING: Tertiary referral center. PATIENTS: Children born in Rio de Janeiro, Brazil, between April 2016 and September 2017, who were referred for newborn hearing screening (NHS). INTERVENTION: The NHS was performed by the automated brainstem auditory-evoked potential test at an intensity of 30 dBHL (decibels Hearing Level) with the result presented as "PASS/FAIL." A follow-up test was performed 6 months after the first examination. MAIN OUTCOME MEASURES: Hearing outcomes by audiological assessment. RESULTS: Ninety-eight children were recruited and 78 underwent the NHS test. In the first evaluation, the FAIL NHS result was observed in 4 of the 78 children. Three were diagnosed with sensorineural hearing loss and one had conductive loss. Including the first and second evaluation, the frequency of audiological alterations was 5.1%. Of the four children diagnosed with hearing loss, two were carriers of ZIKV, one had suspected ZIKV infection, and one was asymptomatic with confirmed exposure to the virus. There was no progression of hearing loss or other hearing abnormality in the children by the time of the second evaluation. The group of nonexposed children (negative quantitative reverse transcription polymerase chain reaction for ZIKV) showed no hearing loss. CONCLUSION: Uni or bilateral sensorineural hearing loss was diagnosed in asymptomatic children at birth. These observations highlight the importance of periodic follow-up of patients with congenital Zika syndrome to better understand their long-term auditory clinical outcome.

Seroepidemiological study of human parvovirus B19 among human immunodeficiency virus-infected patients in a medium-sized city in Rio de Janeiro, Brazil.

Parvovirus B19 (B-19) may cause chronic anaemia in immunosuppressed patients, including those infected with human immunodeficiency virus (HIV). We studied single serum samples from 261 consecutive HIV-infected patients using an enzyme immunoassay to detect IgG antibodies to B-19. The seroprevalence of B-19-IgG was 62.8%. The differences in seroprevalence across gender, age, educational categories, year of collection of the serum samples, clinical and antiretroviral therapy characteristics, CD4+ count, CD4+ and CD8+ percentage and CD4+/CD8+ ratios were neither substantial nor statistically significant. There was a non-significant, inverse association between B-19 seropositivity and plasma HIV load and haemoglobin level. Our results indicated that 37.1% of patients might be susceptible to B-19 infection and remained at risk for being infected, mainly during epidemic periods. As B-19 infection can be treated with immune globulin preparations, it may be included in the diagnostic approach toward chronic anaemia in HIV-infected patients.

Post-surgical atypical mycobacteriosis in 125 patients in Rio de Janeiro.

INTRODUCTION: The growing incidence of post-surgical atypical mycobacteriosis (PSAM) may be related to the increased use of low- and medium-complexity video-assisted surgery. METHODS: Between April 2007 and June 2009, 125 patients were referred from the State Health Department of Rio de Janeiro for the treatment of confirmed, probable, or suspected PSAM. RESULTS: Laparoscopic cholecystectomy was the most frequent surgical procedure (48.8%) among patients. Clarithromycin, ethambutol, and terizidone were used to treat 113 patients for a mean duration of 226 days. CONCLUSIONS: Despite the need for multidrug therapy and long treatment duration, most included patients adhered to treatment and experienced cure without relapse.

Influence of vaccine-preventable diseases and HIV infection on demand for an infectious diseases service in Rio de Janeiro State, Brazil, over 22 years - Part II (1995-2016).

Patients' data during daily clinical care are extremely important for improving the allocation of healthcare resources and for assessing healthcare demands. The prospective gathering of these data over decades allowed us to describe the trends of infectious diseases in a tertiary hospital. The results concerning the period between 1965 and 1994 described the exponential increase in the incidence of HIV infection and its important effects on our institutional mortality. The present study describes the demand for the same hospital between 1995 and 2016. There were 4,691 admissions and the main causes of admissions were, in descending order, HIV infection (1,312, 28.0%), noninfectious diseases (447, 9.5%), meningoencephalitis (432, 9.2%), soft tissue infections (427; 9.1%), tuberculosis (272, 5.8%), pneumonias (212, 4.5%) and leptospirosis (212, 4.5%). There were 864 readmissions; most due to HIV infections (65.2%). The institutional mortality fell from 16.9% in the first two years to 5.0% in the last two years of the study. The case-fatality rates among the HIV patients decreased from more than 40% to approximately 5% over the study period. In the last two decades, the hospital experienced a decrease in demand due to vaccine-preventable diseases. The demand for children has fallen and the demand for patients over the age of 50 has increased. These results reflect the improvement in public health standards over more than half a century and the positive effects of the National Immunization Program. They also illustrate the sharp decline in the HIV case-fatality rate after the introduction of combined antiretroviral therapy.

Simultaneous circulation of arboviruses and other congenital infections in pregnant women in Rio de Janeiro, Brazil.

BACKGROUND: Arboviruses (Zika, dengue and chikungunya) represent a major risk for pregnant women, especially because their vertical transmission can lead to neurological damage in newborns. Early diagnosis can be difficult due to similar clinical presentation with other congenital infections that are associated with congenital abnormalities. OBJECTIVES: To investigate the circulation of arboviruses and other pathogens responsible for congenital infections, reporting clinical aspects and geographic distribution of maternal rash in a metropolitan region of Rio de Janeiro (Brazil). METHODS: Cross-sectional study with pregnant women presenting rash attended at the Exanthematic Diseases Unit (Niterói, Rio de Janeiro) from 2015 to 2018. Diagnosis of arboviruses was performed by real-time PCR (RT-qPCR) and laboratorial screening for syphilis, toxoplasmosis, rubella, cytomegalovirus and HIV was assessed. Demographic data was used for georeferencing analysis. FINDINGS: We included 121 pregnant women, of whom Zika virus was detected in 45 cases (37.2%), chikungunya in 33 (27.3%) and dengue in one (0.8%). Five patients presented syphilis, and we observed one case each of listeria, cytomegalovirus, and a syphilis-toxoplasmosis case. Similarity of clinical symptoms was observed in all groups; however, 84.8% of patients with chikungunya presented arthralgia. Following the decline of Zika cases, chikungunya infection was mostly observed during 2017-2018. Considering pregnant women infected with arboviruses and other infections, 41% resided in urban slums, mostly in Niterói. MAIN CONCLUSIONS: Simultaneous circulation of arboviruses and other agents responsible for congenital infections were observed; however, we did not identify co-infections between arboviruses. In this scenario, we emphasize the importance of adequate prenatal care to provide an accurate diagnosis of maternal rash.

Predictive factors of dengue severity in hospitalized children and adolescents in Rio de Janeiro, Brazil.

INTRODUCTION: Dengue is one of the most important mosquito-borne infections. Severe cases are more frequently observed in adults. However, in 2008, the State of Rio de Janeiro, Brazil, experienced a severe dengue epidemic that primarily affected children and caused many cases of dengue hemorrhagic fever (DHF) and death. METHODS: A cross-sectional analytical study was conducted to examine laboratory diagnosis and clinical epidemiologic factors for confirmed dengue cases in patients aged less than 16 years, from January to June 2008, at a municipal hospital in the City of Rio de Janeiro, Brazil. Variables associated with severe outcomes and P values less than .05 were evaluated by means of a logistic regression model. RESULTS: Of the 419 dengue cases studied, 296 were classified as DHF and 123 as classical dengue. Six patients who had DHF died. In multivariate analysis, some laboratory and clinical variables were independently associated with DHF: age 5 years or older (odds ratio [OR], 4.94; 95% confidence interval [CI], 1.30-18.71), abdominal pain (OR, 8.59; 95% CI, 3.17-23.27), hepatomegaly (OR, 15.87; 95% CI, 5.38-46.85), and positive tourniquet test (OR, 10.84; 95% CI, 3.96-29.71). Hypoalbuminemia occurred more frequently than hemoconcentration in DHF cases, and high aminotransferase levels were associated with severity. CONCLUSIONS: Age greater than 5 years, abdominal pain, painful hepatomegaly, and positive tourniquet test were predictors of DHF. The high frequency of hepatic impairment suggests that acetaminophen should be avoided in severe cases of dengue.

Healthcare for children with congenital Zika syndrome: analysis of access to social rights / Atendimento das crianças com síndrome da Zika congênita: análise do acesso aos direitos sociais

Abstract The objective of this study was to describe if the victims of the Zika have access to essential public policies to guarantee social rights. Methods: We used a cross-sectional study of a historical cohort of children with congenital Zika syndrome (CZS) in a reference hospital. CZS diagnosis was based on the Ministry of Health protocol. The variables analyzed were sociodemographic and social rights of children. Results: Of the 161 children seen from April 2016 to July 2018, 42 were diagnosed with CZS. Of these, 37 children participated in the study and 75.7% of them had severe neurological disorders. Anticonvulsants were used by 73% of the children, with 81% paid by families. The families were also responsible for purchasing nutritional formulas and diapers in, respectively, 79% and 100% of cases, and 89% of the children had access to rehabilitation therapy, although 70% of them faced several barriers to do it. Of the 24 working mothers, 83% did not return to the labor market after the birth of their children. Conclusions: The results showed that the families were at an intersection between the integral activity of caring for a child with severe disabilities and inefficient and omissive public authorities, a disincentive and discouraging context that made them give up in seeking their rights.

Resumo Este estudo teve como objetivo analisar se as vítimas da epidemia da Zika têm acesso às políticas públicas essenciais à garantia dos direitos sociais. Métodos: Estudo transversal de uma coorte histórica de crianças com síndrome da Zika congênita (SZC) em um hospital de referência. Utilizou-se o protocolo do Ministério da Saúde para o diagnóstico de SZC. As variáveis analisadas foram características sociodemográficas e direitos sociais das crianças. Resultados: Das 161 crianças avaliadas de abril/2016 a julho/2018, 42 apresentavam SZC. Destas, 37 participaram do estudo, 75,7% com grave comprometimento neurológico. Anticonvulsivantes eram utilizados em 73% dos casos, 81% custeados pelas famílias. As famílias ainda custeavam fórmulas nutricionais (79%) e fraldas (100%). A terapia de reabilitação era realizada por 89% das crianças, embora 70% enfrentassem diversas barreiras para tal. Das 24 mães que trabalhavam, 83% não retornaram ao mercado de trabalho após o nascimento dos filhos. Conclusões: As famílias estavam situadas na interseção entre a atividade integral de cuidado de um filho com deficiências graves e a ineficiência e omissão do poder público, um contexto de desincentivo e desalento que, vencendo-as pelo cansaço, fazia com que muitas acabassem desistindo de tentar buscar seus direitos.

Molecular diversity of human parvovirus B19 during two outbreaks of erythema infectiosum in Brazil.

This study was conducted to provide information on the genetic diversity of human parvovirus B19 (B19V) circulating in the municipality of Niterói, Rio de Janeiro, Southeast Brazil during 1996-2006, a period with two distinct outbreaks of B19V infection: 1999-2000 and 2004-2005. A total of 27 sera from patients with erythema infectiosum and five sera from HIV-infected patients that tested positive for B19V DNA during the study period were analyzed. To genotype B19V strains, a semi-nested PCR for partial amplification of the capsid gene was performed and sequence analysis revealed that 31 sequences belonged to subgenotype 1a (G1a) of the main genotype 1 and one sequence was characterized as subgenotype 3b (G3b). The phylogenetic tree supported the division of the G1a into two well-defined clades with 1.3% of divergence. The low diversity of the G1a strains may be explained by the fact that all patients had acute B19V infection and 30/32 sera were collected during two distinct outbreaks. The G3b strain was from an HIV-infected patient who seroconverted to anti-B19 IgG antibodies in September/2005. This is the first report of G3b in the state of Rio de Janeiro.

Post-surgical atypical mycobacteriosis in 125 patients in Rio de Janeiro

Abstract INTRODUCTION: The growing incidence of post-surgical atypical mycobacteriosis (PSAM) may be related to the increased use of low- and medium-complexity video-assisted surgery. METHODS: Between April 2007 and June 2009, 125 patients were referred from the State Health Department of Rio de Janeiro for the treatment of confirmed, probable, or suspected PSAM. RESULTS: Laparoscopic cholecystectomy was the most frequent surgical procedure (48.8%) among patients. Clarithromycin, ethambutol, and terizidone were used to treat 113 patients for a mean duration of 226 days. CONCLUSIONS: Despite the need for multidrug therapy and long treatment duration, most included patients adhered to treatment and experienced cure without relapse.

Predictive factors of dengue severity in hospitalized children and adolescents in Rio de Janeiro, Brazil

Abstract INTRODUCTION: Dengue is one of the most important mosquito-borne infections. Severe cases are more frequently observed in adults. However, in 2008, the State of Rio de Janeiro, Brazil, experienced a severe dengue epidemic that primarily affected children and caused many cases of dengue hemorrhagic fever (DHF) and death. METHODS: A cross-sectional analytical study was conducted to examine laboratory diagnosis and clinical epidemiologic factors for confirmed dengue cases in patients aged less than 16 years, from January to June 2008, at a municipal hospital in the City of Rio de Janeiro, Brazil. Variables associated with severe outcomes and P values less than .05 were evaluated by means of a logistic regression model. RESULTS: Of the 419 dengue cases studied, 296 were classified as DHF and 123 as classical dengue. Six patients who had DHF died. In multivariate analysis, some laboratory and clinical variables were independently associated with DHF: age 5 years or older (odds ratio [OR], 4.94; 95% confidence interval [CI], 1.30-18.71), abdominal pain (OR, 8.59; 95% CI, 3.17-23.27), hepatomegaly (OR, 15.87; 95% CI, 5.38-46.85), and positive tourniquet test (OR, 10.84; 95% CI, 3.96-29.71). Hypoalbuminemia occurred more frequently than hemoconcentration in DHF cases, and high aminotransferase levels were associated with severity. CONCLUSIONS: Age greater than 5 years, abdominal pain, painful hepatomegaly, and positive tourniquet test were predictors of DHF. The high frequency of hepatic impairment suggests that acetaminophen should be avoided in severe cases of dengue.

Toxoplasma gondii antibody profile in HIV-1-infected and uninfected pregnant women and the impact on congenital toxoplasmosis diagnosis in Rio de Janeiro, Brazil.

OBJECTIVE: Compare the anti-T. gondii IgG titer between HIV-1 infected and non HIV-1 infected pregnant women and report three cases of congenital toxoplasmosis resulting from reactivation of infection during pregnancy of HIV-1 infected women. METHODS: This study was conducted among 2,270 pregnant women with chronic Toxoplasma gondii infection (absence of IgM and presence of IgG), including 82 HIV-1 infected and 2,188 non-infected women. RESULTS: The average anti-T. gondii IgG titer was 127 for the 2,188 non-HIV-1 infected women, and 227 for the 82 HIV-1-infected women (p = 0,007). These results suggested that higher anti-T. gondii IgG titers in HIV-1-infected pregnant women may not be indicative of an elevated risk for fetal infection. In this study three cases of congenital toxoplasmosis that resulted from infection reactivation during pregnancy of HIV-1-infected women were manifested by fetal death, symptomatic infection, and infant without symptoms, respectively. In two of these women, a ten-fold increase in IgG levels above used cutoff was observed (2,320 UI/mL and 3,613 UI/mL, respectively). In the third pregnant women anti-T. gondii IgG titers during pregnancy did not rise despite the occurrence of congenital toxoplasmosis (204; 198; 172 UI/mL). CONCLUSIONS: Congenital toxoplasmosis resulting reactivation of infection during pregnancy in the studied group leads us to believe that it is a public health problem, especially in our population, in which seroprevalence of T. gondii infections is high. These findings also suggest that special attention is necessary during pregnancy, because the serologic diagnosis may not be indicative of toxoplasmosis reactivation.

Molecular diversity of human parvovirus B19 during two outbreaks of erythema infectiosum in Brazil

Abstract This study was conducted to provide information on the genetic diversity of human parvovirus B19 (B19V) circulating in the municipality of Niterói, Rio de Janeiro, Southeast Brazil during 1996-2006, a period with two distinct outbreaks of B19V infection: 1999-2000 and 2004-2005. A total of 27 sera from patients with erythema infectiosum and five sera from HIV-infected patients that tested positive for B19V DNA during the study period were analyzed. To genotype B19V strains, a semi-nested PCR for partial amplification of the capsid gene was performed and sequence analysis revealed that 31 sequences belonged to subgenotype 1a (G1a) of the main genotype 1 and one sequence was characterized as subgenotype 3b (G3b). The phylogenetic tree supported the division of the G1a into two well-defined clades with 1.3% of divergence. The low diversity of the G1a strains may be explained by the fact that all patients had acute B19V infection and 30/32 sera were collected during two distinct outbreaks. The G3b strain was from an HIV-infected patient who seroconverted to anti-B19 IgG antibodies in September/2005. This is the first report of G3b in the state of Rio de Janeiro.

Congenital toxoplasmosis transmitted by human immunodeficiency-virus infected women.

We report the occurrence of congenital toxoplasmosis in three infants born to HIV infected women who had high anti-toxoplasma IgG and negative IgM during pregnancy. We briefly reviewed available literature and discussed the possible transmission mechanisms of congenital toxoplasmosis among HIV infected pregnant women. Serum samples were tested for Toxoplasma gondii IgM and IgG antibodies using commercial enzyme immunoassay and IgG-avidity tests. In the first case, fetal death occurred at 28th week of gestation. In the second case, congenital toxoplasmosis was diagnosis at 6th month of life; and in the third case, an HIV-infected newborn, congenital toxoplasmosis was asymptomatic. These cases point out to the possibility of enhanced maternal-fetal transmission of T. gondii infection by HIV-infected women chronically infected, which may have important public health consequences, considering that increasing frequency of HIV-infection has been observed among women of childbearing age around the world.

Clinical features and laboratory findings of human parvovirus B19 in human immunodeficiency virus-infected patients

Immunocompromised patients may develop severe chronic anaemia when infected by human parvovirus B19 (B19V). However, this is not the case in human immunodeficiency virus (HIV)-infected patients with good adherence to highly active antiretroviral treatment (HAART). In this study, we investigated the clinical evolution of five HIV-infected patients receiving HAART who had B19V infections confirmed by serum polymerase chain reaction. Four of the patients were infected with genotype 1a strains and the remaining patient was infected with a genotype 3b strain. Anaemia was detected in three of the patients, but all patients recovered without requiring immunoglobulin and/or blood transfusions. In all cases, the attending physicians did not suspect the B19V infections. There was no apparent relationship between the infecting genotype and the clinical course. In the HAART era, B19V infections in HIV-positive patients may be limited, subtle or unapparent.