Evaluation of the genetic polymorphism of Plasmodium falciparum P126 protein (SERA or SERP) and its influence on naturally acquired specific antibody responses in malaria-infected individuals living in the Brazilian Amazon

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>P126 protein is an asexual blood-stage malaria vaccine candidate antigen. Antibodies against P126 are able to inhibit parasite growth <it>in vitro</it>, and a major parasite-inhibitory epitope has been recently mapped to its 47 kDa N-terminal extremity (octamer repeat domain – OR domain). The OR domain basically consists of six octamer units, but variation in the sequence and number of repeat units may appear in different alleles. The aim of the present study was to investigate the polymorphism of P126 N-terminal region OR domain in <it>P. falciparum </it>isolates from two Brazilian malaria endemic areas and its impact on anti-OR naturally acquired antibodies.</p> <p>Methods</p> <p>The study was carried out in two villages, Candeias do Jamari (Rondonia state) and Peixoto de Azevedo (Mato Grosso state), both located in the south-western part of the Amazon region. The repetitive region of the gene encoding the P126 antigen was PCR amplified and sequenced with the di-deoxy chain termination procedure. The antibody response was evaluated by ELISA with the Nt47 synthetic peptide corresponding to the P126 OR-II domain.</p> <p>Results</p> <p>Only two types of OR fragments were identified in the studied areas, one of 175 bp (OR-I) and other of 199 bp (OR-II). A predominance of the OR-II fragment was observed in Candeias do Jamari whereas in Peixoto de Azevedo both fragments OR-I and OR-II were frequent as well as mixed infection (both fragments simultaneously) reported here for the first time. Comparing the DNA sequencing of OR-I and OR-II fragments, there was a high conservation among predicted amino acid sequences of the P126 N-terminal extremity. Data of immune response demonstrated that the OR domain is highly immunogenic in natural conditions of exposure and that the polymorphism of the OR domain does not apparently influence the specific immune response.</p> <p>Conclusion</p> <p>These findings confirm a limited genetic polymorphism of the P126 OR domain in <it>P. falciparum </it>isolates and that this limited genetic polymorphism does not seem to influence the development of a specific humoral immune response to P126 and its immunogenicity in the studied population.</p

Homozygous Inactivating Mutation In Nanos3 In Two Sisters With Primary Ovarian Insufficiency.

Despite the increasing understanding of female reproduction, the molecular diagnosis of primary ovarian insufficiency (POI) is seldom obtained. The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. We performed mutational analysis of NANOS3 in a cohort of 85 Brazilian women with familial or isolated POI, presenting with primary or secondary amenorrhea, and in ethnically-matched control women. A homozygous p.Glu120Lys mutation in NANOS3 was identified in two sisters with primary amenorrhea. The substituted amino acid is located within the second C2HC motif in the conserved zinc finger domain of NANOS3 and in silico molecular modelling suggests destabilization of protein-RNA interaction. In vitro analyses of apoptosis through flow cytometry and confocal microscopy show that NANOS3 capacity to prevent apoptosis was impaired by this mutation. The identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology.201478746

Teste rápido para o HIV como estratégia de prevenção da transmissão vertical no Brasil

OBJECTIVE: To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS: Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confirmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. RESULTS: HIV prevalence in women was 6.5% (N=1,439) in Porto Alegre and 1.3% (N=3.778) in Rio de Janeiro. In Porto Alegre most of women were tested during labor (88.7%), while in Rio de Janeiro most were tested in the postpartum (67.5%). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8% and 51.1% of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8% and 27.7% newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confirmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS: The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge.OBJETIVO: Analizar la viabilidad de evaluación rápida del HIV entre gestantes en la admisión en la maternidad y de intervenciones para reducir la transmisión perinatal del HIV. MÉTODOS: Muestra de conveniencia de mujeres que desconocían su situación serológica para el HIV al ser admitidas para el parto en maternidades públicas de Rio de Janeiro (Sureste) y de Porto alegre (Sur de Brasil), entre marzo de 2000 y abril de 2002. Las mujeres fueron aconsejadas y evaluadas con prueba rápida Determine HIV1/2 en la maternidad. Infección por el HIV fue confirmada por el algoritmo brasilero para el diagnóstico de la infección por el HIV. La transmisión intra- útero fue determinada por el PCR-DNA-HIV. Fueron realizados análisis descriptivos de los datos sociodemográficos, número de gestaciones y de abortos previos, número de visitas de prenatal, momento de la evaluación para el HIV, resultado de la prueba rápida para el HIV, intervenciones recibidas por los recién nacidos y de transmisión vertical del HIV, de acuerdo con cada ciudad. RESULTADOS: La prevalencia de HIV entre las mujeres fue de 6,5% (N=1.439) en Porto Alegre y 1,3% (N=3,778) en Rio de Janeiro. La mayoría fue evaluada durante el trabajo de parto en Porto Alegre y en el postparto, en Rio de Janeiro. Ciento y cuarenta y cuatro niños nacieron de 143 mujeres infectadas por el HIV. Todos los recién nacidos recibieron al menos la profilaxia con zidovudina oral, excepto uno en cada ciudad. Fue posible evitar cualquier exposición a la leche materna en 96,8% y 51,1% de los recién nacidos en Porto Alegre y en Rio de Janeiro, respectivamente. La zidovudina inyectable fue administrada durante el trabajo de parto a 68,8% de los recién nacidos en Porto Alegre y 27,7% en Rio de Janeiro. Entre aquellos con muestras de sangre colectadas hasta 48 horas de nacimiento, la transmisión intra-útero fue confirmada en cuatro casos en Rio de Janeiro (4/47) y en seis casos en Porto Alegre (6/79). CONCLUSIONES: La estrategia se mostró factible en las maternidades de Rio de Janeiro y de Porto Alegre. Esfuerzos deben ser emprendidos para maximizar la evaluación durante el trabajo de parto. Fuerte soporte social precisa ser acoplado a esa estrategia para garantizar el acceso de dicha población al sistema de salud posterior a ser dado de alta de la maternidad.OBJETIVO: Analisar a viabilidade da testagem rápida para o HIV entre gestantes na admissão à maternidade e de intervenções para reduzir a transmissão perinatal do HIV. MÉTODOS: Amostra de conveniência de mulheres que desconheciam sua situação sorológica para o HIV quando admitidas para o parto em maternidades públicas do Rio de Janeiro, RJ, e de Porto Alegre, RS, entre março de 2000 e abril de 2002. As mulheres foram aconselhadas e testadas com teste rápido Determine HIV1/2 na maternidade. Infecção pelo HIV foi confirmada pelo algoritmo brasileiro para o diagnóstico da infecção pelo HIV. A transmissão intra-útero foi determinada pelo PCR-DNA-HIV. Foram realizadas análises descritivas dos dados sociodemográficos, número de gestações e de abortos prévios, número de visitas de pré-natal, momento da testagem para o HIV, resultado do teste rápido para o HIV, intervenções recebidas pelos recém-natos e de transmissão vertical do HIV, de acordo com cada cidade. RESULTADOS: A prevalência de HIV entre as mulheres foi 6,5% (N=1.439) em Porto Alegre e 1,3% (N=3.778) no Rio de Janeiro. A maioria foi testada durante o trabalho de parto em Porto Alegre e no pós-parto, no Rio de Janeiro. Cento e quarenta e quatro crianças nasceram de 143 mulheres infectadas pelo HIV. Todos os recém-natos receberam ao menos a profilaxia com zidovudina oral, exceto um em cada cidade. Foi possível evitar qualquer exposição ao leite materno em 96,8% e 51,1% dos recém-natos em Porto Alegre e no Rio de Janeiro, respectivamente. A zidovudina injetável foi administrada durante o trabalho de parto para 68,8% dos recém-natos em Porto Alegre e 27,7% no Rio de Janeiro. Entre aqueles com amostras de sangue coletadas até 48 horas do nascimento, a transmissão intra-útero foi confirmada em quatro casos no Rio de Janeiro (4/47) e em seis casos em Porto Alegre (6/79). CONCLUSÕES: A estratégia mostrou-se factível nas maternidades do Rio de Janeiro e de Porto Alegre. Esforços devem ser empreendidos para maximizar a testagem durante o trabalho de parto. Forte suporte social precisa ser acoplado a essa estratégia para garantir o acesso dessa população ao sistema de saúde após a alta da maternidade

Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission

Background Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. Methodology Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. Results A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. Conclusion HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT.NICHD (NICHD)(Brazilian AIDS Prevention Trials International Network), NIAID/ NIHNational Institute of Allergy and Infectious Diseases (NIAID)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Institute of Mental Health (NIMH)Boehringer Ingelheim Pharmaceuticals Inc. (BIPI)GlaxoSmithKline, on behalf of ViiV HealthcareCepheid for the testing of CTNG in a prior HPTNUCLA Children's Discovery and Innovation Institute (CDI) through the Harry Winston Fellowship AwardUCLA AIDS InstituteUCLA Center for AIDS Research (CFAR) NIH/ NIAIDUCLA Pediatric AIDS Coalition, and WestatNIH/NICHDDavid Geffen UCLA Sch Med, Los Angeles, CA 90095 USAWestat Corp, Rockville, MD USAFundacao Oswaldo Cruz FIOCRUZ, Rio De Janeiro, RJ, BrazilUS Dept State, Off Global AIDS Coordinator, Washington, DC 20520 USAElizabeth Glaser Pediat AIDS Fdn, Washington, DC USAHosp Geral Nova Iguacu, Nova Iguacu, RJ, BrazilHosp Fed Servidores Estado, Rio De Janeiro, RJ, BrazilUniv Witwatersrand, SAMRC & Perinatal HIV Res Unit, Johannesburg, South AfricaStellenbosch Univ, Tygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Sao Paulo, BrazilFdn Maternal & Infant Hlth FUNDASAMIN, Buenos Aires, DF, ArgentinaUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilEunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USAUCLA, Fielding Sch Publ Hlth, Los Angeles, CA USAUCSD Sch Med, La Jolla, CA USAUC Davis Sch Med, Davis, CA USABoston Univ, Sch Med, Boston, MA 02118 USAUniv Fed Sao Paulo, Escola Paulista Med, Sao Paulo, SP, BrazilNICHD (NICHD): HHSN267200800001C, N01-HD-8-0001Brazilian AIDS Prevention Trials International Network: NIAID/ NIH [U01 AI047986National Institute of Allergy and Infectious Diseases (NIAID): U01 AI068632, UM1AI068632, UM1AI068616, UM1AI106716NIMH: AI068632NG in a prior HPTN :040UCLA Center for AIDS Research (CFAR) NIH/ NIAID: AI02869, AI28697NIH/NICHD: HHSN275201300003CWeb of Scienc

Factors associated with unintended pregnancy in Brazil: cross-sectional results from the Birth in Brazil National Survey, 2011/2012

Background Unintended pregnancy, a pregnancy that have been either unwanted or mistimed, is a serious public health issue in Brazil. It is reported for more than half of women who gave birth in the country, but the characteristics of women who conceive unintentionally are rarely documented. The aim of this study is to analyse the prevalence and the association between unintended pregnancy and a set of sociodemographic characteristics, individual-level variables and history of obstetric outcomes. Methods Birth in Brazil is a cross-sectional study with countrywide representation that interviewed 23,894 women after birth. The information about intendedness of pregnancy was obtained after birth at the hospital and classified into three categories: intended, mistimed or unwanted. Multinomial regression analysis was used to estimate the associations between intendedness of a pregnancy, and sociodemographic and obstetric variables, calculating odds ratios and 95 % confidence intervals. All significant variables in the bivariate analysis were included in the multinomial multivariate model and the final model retaining variables that remained significant at the 5 % level. Results Unintended pregnancy was reported by 55.4 % of postpartum women. The following variables maintained positive and significant statistical associations with mistimed pregnancy: maternal age < 20 years (OR = 1.89, 95 % CI: 1.68–2.14); brown (OR = 1.15, 95 % CI: 1.04–1.27) or yellow skin color (OR = 1.56, 95 % CI: 1.05–2.32); having no partner (OR = 2.32, 95 % CI: 1.99–2.71); having no paid job (OR = 1.15, 95 % CI: 1.04–1.27); alcohol abuse with risk of alcoholism (OR = 1.25, 95 % CI: 1.04–1.50) and having had three or more births (OR = 2.01, 95 % CI: 1.63–2.47). The same factors were associated with unwanted pregnancy, though the strength of the associations was generally stronger. Women with three or more births were 14 times more likely to have an unwanted pregnancy, and complication in the previous pregnancies and preterm birth were 40 % and 19 % higher, respectively. Previous neonatal death was a protective factor for both mistimed (OR = 0.61, 95 % CI: 0.44–0.85) and unwanted pregnancy (OR = 0.44, 95 % CI: 0.34–0.57). Conclusions This study confirms findings from previous research about the influence of socioeconomic and individual risk factors on unintended pregnancy. It takes a new approach to the problem by showing the importance of previous neonatal death, preterm birth and complication during pregnancy as risk factors for unintended pregnancy

Phylogeographic Analysis of HIV-1 Subtype C Dissemination in Southern Brazil

The HIV-1 subtype C has spread efficiently in the southern states of Brazil (Rio Grande do Sul, Santa Catarina and Paraná). Phylogeographic studies indicate that the subtype C epidemic in southern Brazil was initiated by the introduction of a single founder virus population at some time point between 1960 and 1980, but little is known about the spatial dynamics of viral spread. A total of 135 Brazilian HIV-1 subtype C pol sequences collected from 1992 to 2009 at the three southern state capitals (Porto Alegre, Florianópolis and Curitiba) were analyzed. Maximum-likelihood and Bayesian methods were used to explore the degree of phylogenetic mixing of subtype C sequences from different cities and to reconstruct the geographical pattern of viral spread in this country region. Phylogeographic analyses supported the monophyletic origin of the HIV-1 subtype C clade circulating in southern Brazil and placed the root of that clade in Curitiba (Paraná state). This analysis further suggested that Florianópolis (Santa Catarina state) is an important staging post in the subtype C dissemination displaying high viral migration rates from and to the other cities, while viral flux between Curitiba and Porto Alegre (Rio Grande do Sul state) is very low. We found a positive correlation (r2 = 0.64) between routine travel and viral migration rates among localities. Despite the intense viral movement, phylogenetic intermixing of subtype C sequences from different Brazilian cities is lower than expected by chance. Notably, a high proportion (67%) of subtype C sequences from Porto Alegre branched within a single local monophyletic sub-cluster. These results suggest that the HIV-1 subtype C epidemic in southern Brazil has been shaped by both frequent viral migration among states and in situ dissemination of local clades

High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

<p>Abstract</p> <p>Background</p> <p>Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL) and tegumentary leishmaniasis (ATL) have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function.</p> <p>Methods</p> <p>To address this issue we analyzed CD4⁺T absolute counts and the proportion of CD8⁺T cells expressing CD38 in <it>Leishmania</it>/HIV co-infected patients that recovered after anti-leishmanial therapy.</p> <p>Results</p> <p>We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4⁺T cell counts under 200 cells/mm³, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm³). Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4⁺T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8⁺T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects.</p> <p>Conclusions</p> <p><it>Leishmania </it>infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4⁺T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.</p