Estimating the burden of rubella virus infection and congenital rubella syndrome through a rubella immunity assessment among pregnant women in the Democratic Republic of the Congo: Potential impact on vaccination policy.

BACKGROUND: Rubella-containing vaccines (RCV) are not yet part of the Democratic Republic of the Congo's (DRC) vaccination program; however RCV introduction is planned before 2020. Because documentation of DRC's historical burden of rubella virus infection and congenital rubella syndrome (CRS) has been minimal, estimates of the burden of rubella virus infection and of CRS would help inform the country's strategy for RCV introduction. METHODS: A rubella antibody seroprevalence assessment was conducted using serum collected during 2008-2009 from 1605 pregnant women aged 15-46years attending 7 antenatal care sites in 3 of DRC's provinces. Estimates of age- and site-specific rubella antibody seroprevalence, population, and fertility rates were used in catalytic models to estimate the incidence of CRS per 100,000 live births and the number of CRS cases born in 2013 in DRC. RESULTS: Overall 84% (95% CI 82, 86) of the women tested were estimated to be rubella antibody seropositive. The association between age and estimated antibody seroprevalence, adjusting for study site, was not significant (p=0.10). Differences in overall estimated seroprevalence by study site were observed indicating variation by geographical area (p⩽0.03 for all). Estimated seroprevalence was similar for women declaring residence in urban (84%) versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to 2886 infants (95% CI 342, 6395) born with CRS. CONCLUSIONS: In the 3 provinces, rubella virus transmission is endemic, and most viral exposure and seroconversion occurs before age 15years. However, approximately 10-20% of the women were susceptible to rubella virus infection and thus at risk for having an infant with CRS. This analysis can guide plans for introduction of RCV in DRC. Per World Health Organization recommendations, introduction of RCV should be accompanied by a campaign targeting all children 9months to 14years of age as well as vaccination of women of child bearing age through routine services

Rubella Virus Capsid Protein Modulates Viral Genome Replication and Virus Infectivity

The structural proteins (SP) of the Togaviridae can be deleted in defective interfering RNAs. The dispensability of viral SP has allowed construction of noninfectious viral expression vectors and replicons from viruses of the Alphavirus and Rubivirus genera. Nevertheless, in this study, we found that the SP of rubella virus (RUB) could enhance expression of reporter genes from RUB replicons in trans. SP enhancement required capsid protein (CP) expression and was not due to RNA-RNA recombination. Accumulation of minus- and plus-strand RNAs from replicons was observed in the presence of SP, suggesting that SP specifically affects RNA synthesis. By using replicons containing an antibiotic resistance gene, we found 2- to 50-fold increases in the number of cells surviving selection in the presence of SP. The increases depended significantly on the amount of transfected RNA. Small amounts of RNA or templates that replicated inefficiently showed more enhancement. The infectivity of infectious RNA was increased by at least 10-fold in cells expressing CP. Moreover, virus infectivity was greatly enhanced in such cells. In other cells that expressed higher levels of CP, RNA replication of replicons was inhibited. Thus, depending on conditions, CP can markedly enhance or inhibit RUB RNA replication

Exogenous Rubella Virus Capsid Proteins Enhance Virus Genome Replication

Enhanced replication of rubella virus (RuV) and replicons by de novo synthesized viral structural proteins has been previously described. Such enhancement can occur by viral capsid proteins (CP) alone in trans. It is not clear whether the CP in the virus particles, i.e., the exogenous CP, modulate viral genome replication. In this study, we found that exogenous RuV CP also enhanced viral genome replication, either when used to package replicons or when mixed with RNA during transfection. We demonstrated that CP does not affect the translation efficiency from genomic (gRNA) or subgenomic RNA (sgRNA), the intracellular distribution of the non-structural proteins (NSP), or sgRNA synthesis. Significantly active RNA replication was observed in transfections supplemented with recombinant CP (rCP), which was supported by accumulated genomic negative-strand RNA. rCP was found to restore replication of a few mutants in NSP but failed to fully restore replicons known to have defects in the positive-strand RNA synthesis. By monitoring the amount of RuV RNA following transfection, we found that all RuV replicon RNAs were well-retained in the presence of rCP within 24 h of post-transfection, compared to non-RuV RNA. These results suggest that the exogenous RuV CP increases efficiency of early viral genome replication by modulating the stage(s) prior to and/or at the initiation of negative-strand RNA synthesis, possibly through a general mechanism such as protecting viral RNA

A case-control study of human papillomavirus and cervical squamous intraepithelial lesions (SIL) in Harris County, Texas: differences among racial/ethnic groups Um estudo de caso-controle de infecção por papillomavirus humano e câncer de colo uterino em Harrys County, Texas

We conducted a case-control study of the association between SIL and HPV among whites (W), African Americans (AA), and Hispanics (H) in Harris County, Texas. Cases were identified at M.D. Anderson Cancer Center Colposcopy Clinic. Controls were identified among women obtaining routine Pap screening at two Harris County Health Department Clinics. HPV was detected by a PCR-based fluorescent assay. Dichotomous and polytomous logistic regression models were used to estimate adjusted odd ratios (AOR) and 95% confidence intervals (CI) for SIL among racial/ethnic groups and grade of disease. Prevalence of HPV infection was 64% in low grade SIL (LSIL), 84% in high grade SIL (HSIL), and 19% in controls. Risk of SIL was higher in H than in W and AA, AOR 29.5 (12.4-70.5), 15.3 (6.0-33.8), and 5.8 (2.6-12.6), respectively. Similarly, racial/ethnic differences were observed for both LSIL (AOR = 16.6, 7.7, and 4.3, respectively) and HSIL (AOR = 78.6, 34.6, and 14.2, respectively). Findings support the association between SIL and HPV and differences in the strength of the association with LSILs and HSILs. Data also suggest a higher risk for H and a lower risk for AA.Foi realizado um estudo caso-controle para analisar a associação entre lesões intra-epiteliais escamosas do colo uterino (SIL) e HPV entre mulheres brancas, negras e latinas em Harris County, Texas. Os casos foram identificados na M. D. Anderson Cancer Center Colposcopy Clinic, e os controles foram obtidos realizando-se exame de Papanicolau em duas clínicas do Departamento de Saúde. O HPV foi detectado por meio de ensaio de PCR (primer MY09/MY11). Foram construídos modelos de regressão logística para estimar as odds ratios ajustadas (AOR), e seus intervalos de confiança de 95% (IC) de SIL entre os grupos étnicos e graus da doença. A prevalência de HPV nas SIL de baixo grau (LSIL) foi de 64%; nas de alto grau (HSIL), 84%; e 19% nos controles. O risco de SIL foi maior em mulheres latinas que em brancas e negras, sendo observadas, respectivamente, as seguintes AOR: 29,5 (12,4-70,5); 15,3 (6,0-33,8); e 5,8 (2,6-12,6). De forma similar, foram observadas diferenças para ambos LSIL (AOR, respectivamente, de 16,6; 7,7 e 4,3) e HSIL (AOR de 78,6; 34,6 e 142). Os resultados apóiam a existência de associação entre SIL e HPV, diferenças na força de associação com SILs e HSILs, e sugerem risco mais elevado para mulheres latinas e menor para mulheres negras

A case-control study of human papillomavirus and cervical squamous intraepithelial lesions (SIL) in Harris County, Texas: differences among racial/ethnic groups

We conducted a case-control study of the association between SIL and HPV among whites (W), African Americans (AA), and Hispanics (H) in Harris County, Texas. Cases were identified at M.D. Anderson Cancer Center Colposcopy Clinic. Controls were identified among women obtaining routine Pap screening at two Harris County Health Department Clinics. HPV was detected by a PCR-based fluorescent assay. Dichotomous and polytomous logistic regression models were used to estimate adjusted odd ratios (AOR) and 95% confidence intervals (CI) for SIL among racial/ethnic groups and grade of disease. Prevalence of HPV infection was 64% in low grade SIL (LSIL), 84% in high grade SIL (HSIL), and 19% in controls. Risk of SIL was higher in H than in W and AA, AOR 29.5 (12.4-70.5), 15.3 (6.0-33.8), and 5.8 (2.6-12.6), respectively. Similarly, racial/ethnic differences were observed for both LSIL (AOR = 16.6, 7.7, and 4.3, respectively) and HSIL (AOR = 78.6, 34.6, and 14.2, respectively). Findings support the association between SIL and HPV and differences in the strength of the association with LSILs and HSILs. Data also suggest a higher risk for H and a lower risk for AA

Seroprevalence of rubella virus antibodies among pregnant women in the Center and South-West regions of Cameroon.

Rubella infection in early pregnancy can lead to miscarriages, fetal death, or birth of an infant with congenital rubella syndrome (CRS). In Cameroon, like in many developing countries, rubella surveillance is not well-established. The aim of this study was to determine the prevalence of rubella virus specific antibodies among pregnant Cameroonians. We conducted a cross-sectional study for rubella infection among pregnant women attending antenatal clinics in the Center and South-West regions of Cameroon. Demographic data and blood were collected and tested for rubella specific antibodies (IgG and IgM), and for the IgM positive cases, IgG avidity and real time PCR was done. From December 2015 to July 2017, 522 serum samples were collected and tested from pregnant women. The seroprevalence of rubella specific IgG was 94.4%, presumably due to immunity induced by wild-type rubella virus. The seroprevalence of rubella specific IgM was 5.0%, possibly indicating rubella infection. However, IgG avidity testing of the IgM positive cases detected high avidity IgGs, ranging from 52.37% to 87.70%, indicating past rubella infection. 5.6% (29/522) of the participants had negative results for IgG to rubella virus, indicating susceptibility to rubella infection. None of the participants had received a rubella containing vaccine (RCV), but 51% (266/522) of the pregnant women lived in a house with a child with records of at least one dose of RCV. Rubella virus RNA was not detected in the urine of any IgM positive case. Findings from this study show that rubella infection is significant in Cameroon. Some pregnant women are still susceptible to rubella infection. For a better management of rubella infection in pregnancy in Cameroon, consideration should be taken to investigate for IgG-avidity test in cases with positive rubella IgM result to distinguish between recent from past rubella infection