Pregnancy outcomes in the medical management of glaucoma: An international multicenter descriptive survey.

PURPOSE: To determine if glaucoma medications are associated with pregnancy and/or postnatal complications. METHODS: Multicenter descriptive survey. Subjects were female patients 18-45 years who were previously pregnant with a diagnosis of glaucoma or ocular hypertension prior to pregnancy. Chart review queried diagnosis, glaucoma severity, and race. Survey questions were asked for each pregnancy and queried pregnancy age, medications used, and pregnancy outcomes/complications. RESULTS: 114 pregnancies of 56 patients (mean 2.0 pregnancies per patient) were included. Three pregnancies with therapeutic abortion were excluded from further analysis. Mean age during pregnancy was 29.1 ± 5.7 years. Of the 111 pregnancies, 20 (18.0%) used no medications and 91 (82.0%) used at least one medication. Medications were topical carbonic anhydrase inhibitors (n = 45), beta-blockers (n = 55), alpha-agonists (n = 56), and prostaglandin analogues (n = 28). Outcomes were: preterm contractions/labour (6.3%), miscarriage (4.5%), stillbirth (4.5%), induction of labour (11.9%), emergency/unplanned caesarean delivery (13.9%), neonatal intensive care unit (NICU) stay (15.8%), congenital anomalies (8.1%), and low birth weight (10.9%). Fisher exact test assessed outcome associations with individual agents, use of any agent, and different number of agents. Alpha-agonist use was associated with NICU stay: 25.5% rate (p = 0.012) in alpha-agonist use. Most of the alpha-agonist use NICU stays occurred in pregnancies with third trimester use. All other associations were not statistically significant. CONCLUSIONS: The data from this survey suggest an overall favourable safety profile for topical glaucoma medications in pregnancy, but further investigation is needed. Caution should be employed regarding third trimester alpha-agonist use owing to association with NICU stay.

Genetic characterization of E2 region of Chikungunya virus circulating in Odisha, Eastern India from 2010 to 2011.

Chikungunya virus (CHIKV) infection has caught attention yet again as it rages around the globe affecting millions of people. The virus caused epidemic outbreaks affecting more than 15,000 people in Odisha, Eastern India since 2010. In this study, complete genetic characterization of E2 gene of CHIKV circulating in Odisha from 2010 to 2011 was performed by virus isolation, RT-PCR, molecular phylogenetics and bioinformatics methods. Phylogenetic analyses revealed the circulation of Indian Ocean Lineage (IOL) strains of ECSA genotype of CHIKV in Odisha. Several mutations were detected in the E2 gene, viz. E2-R82G, E2-L210Q, E2-I211T, E2-V229I and E2-S375T which had various adaptive roles during the evolution of CHIKV. The CHIKV E2 peptide 57KTDDSHD6³ was predicted to be the most probable T-cell epitope and peptide 84FVRTSAPCT9² predicted to be the common T and B cell epitope having high antigenicity. The amino acid positions 356-379 and 365-385 were predicted to be transmembrane helical domains and indicated E2 protein anchorage in intracellular membranes for effective interaction with the host receptors. Positive selection pressure was observed in five specific sites, 210, 211, 318, 375, and 377 which were observed to be fixed advantageously in most viral isolates. Structural modeling revealed that E2 gene of CHIKV was composed of 3 domains and the major adaptive mutations were detected in domain B, which can modulate binding of CHIKV to host cells, while the transmembrane domain in domain C and the epitopes were located in domain A, which was found to be most conserved. This is the first report from Eastern India demonstrating a predictive approach to the genetic variations, epitopic regions and the transmembrane helices of the E2 region. The results of this study, combined with other published observations, will expand our knowledge about the E2 region of CHIKV which can be exploited to develop control measures against CHIKV.

Molecular investigations of chikungunya virus during outbreaks in Orissa, Eastern India in 2010.

Chikungunya virus (CHIKV), an arthritogenic alphavirus, is transmitted to humans by mosquitoes of genus Aedes, mainly Aedes aegypti and Aedes albopictus. The resurgence of CHIKV in different parts of India is a point of major public health concern. In 2010, chikungunya outbreaks with high epidemic magnitude were recorded in coastal areas of Orissa, Eastern India, affecting more than 15,000 people coupled with severe arthralgia and prolonged morbidites. Detailed entomological, serological and molecular investigation of this unprecendented outbreak was carried out by collecting and studying 1359 mosquito samples belonging to A. albopictus, A. aegypti, A. vittatus, A. edwardsii and Culex species and 220 patients serum from the affected areas. In this study, CHIKV specific IgM capture-ELISA and reverse-transcription PCR (RT-PCR) were done to detect recent infection of CHIKV in serum samples and adult mosquitoes collected from the affected areas. The high maximum likelihood estimate (MLE) (15.2) in A. albopictus mosquitoes indicated that it was the principal vector involved in transmission of CHIKV in Orissa. Phylogenetic analysis revealed that the CHIKV strains involved in the outbreak belonged to the Indian Ocean Lineage (IOL) group within the East, Central and South African (ECSA) genotype. Genetic characterization of envelope glycoprotein (E1 and E2) genes revealed that all the CHIKV isolates from Orissa had the E1-A226V mutation that enhances viral dissemination and transmissibility by A. albopictus mosquitoes along with E2-L210Q and E2-I211T mutations, which play an epistatic role with E1-A226V mutation in adaptation of CHIKV to A. albopictus by increasing its midgut infectivity, thereby favoring its vectorial capacity. Our results showed the involvement of A. albopictus vector in the recent outbreaks in Orissa and circulation of IOL strains of ECSA genotype of CHIKV with E1-A226V, E2-L210Q and E2-I211T mutations in vectors and patients serum.

Genetic characterization of type A foot-and-mouth disease virus 3A region in context of the reemergence of VP359-deletion lineage in India.

The 3A region of foot-and-mouth disease virus has been implicated in host range and virulence. Here we analyzed the 3A region of serotype A virus in view of the emergence of a variant group in India with an amino acid deletion at an antigenically critical position of capsid protein, VP3. The 3A region exhibited extreme variability with 38% of the amino acid positions showing substitutions and the C-terminal third (127-151) region was most flexible. Genotype inclusive grouping of type A foot-and-mouth disease virus as observed in 1D region based phylogeny was much less apparent at 3A region possibly due to independent evolution of nonstructural and structural protein coding regions. Akin to the 1D region, the VP3(59)-deletion group maintained its phylogenetic distinctness even at the 3A region and was found to be diverging with time. Twelve lineage specific signature amino acid residues, of which four were identified to be experiencing positive selection, indicates fixation of advantageous mutations in a lineage specific manner. Six positions, all located in the hypervariable C-terminal third, were identified to be under positive selection and were presumed to be imparting the virus certain advantage accounting for its adaptability to wide host spectrum and rapid dissemination. A significant change of Q(44)H was noted only in the older lineage (VIIb) of the deletion group at a position where Q(44)R mutation is associated with guinea pig adaptation. As this site has been detected to be under positive selection, such a lineage specific substitution is thought to have imparted certain temporary advantage to the virus during its possible adaptation in wild or some understudied domestic hosts and must not have seriously compromised fitness upon readaptation in bovines. A conserved hydrophobic transmembrane domain from position 59 to 76 could be predicted which possibly anchors 3A to intracellular membranes for successful interaction with RNA replication complex.

Comparative analysis of the large fragment of the 5' untranslated region (LF-5' UTR) of serotype A foot-and-mouth disease virus field isolates from India.

India is endemic for foot-and-mouth disease (FMD) and in recent years a unique group within serotype A, carrying a codon deletion at an antigenically critical site in capsid protein VP3 has emerged (VP3(59)-deletion group). This tempted us to analyze the noncoding region, which is an under represented area, though critically associated with virus biology and pathogenesis. Analysis of the large fragment of 5' untranslated region (LF-5' UTR) of type A FMD virus revealed discrepancy in the overall tree topology between LF-5' UTR and 1D region possibly due to independent evolution of coding and noncoding regions. The VP3(59)-deletion group maintained its phylogenetic distinctness even at the LF-5' UTR. Eighteen lineage specific signatures detected here support independent evolutionary paths for the lineages. Extensive deletions of 45 and 89 nucleotides corresponding to the pseudoknot region were noticed. Conservation pattern in the 'A(253)AACA' motif in the cre/bus stem-loop indicates the importance of first three 'A' residues in VPg uridylylation. Of the three polypyrimidine tract binding protein (PTB) binding sites mapped on the internal ribosome entry site (IRES), the pyrimidine tract (Py tract) in the loop of domain 2 was found to be maximally conserved and it might be the major PTB binding site. Strikingly, a deletion group lineage specific transversion was noticed in the Py tract at the 3' end of IRES without significantly affecting its in vitro infectious titer. Hence, we presume that for efficient cap-independent viral translation, either a minimum number of pyrimidine residues rather than a complete Py tract or a Py tract tolerating transversions only at specific locations and a core motif 'CUUU' within the Py tract is essential.