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1.  Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya 
Background. Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. Materials and Methods. We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. Results. Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (−0.8 versus −0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. Conclusion. Maternal TDF use did not adversely affect infant growth compared to other regimens.
PMCID: PMC4707364  PMID: 26823647
2.  Pregnancy Outcomes of Mothers with Detectable CMV-Specific IgM Antibodies: A Three-Year Review in a Large Irish Tertiary Referral Maternity Hospital 
A retrospective audit was performed for all obstetric patients who had positive CMV IgM results between January 2012 and December 2014 in the Rotunda Hospital, Ireland. In total, 622 CMV IgM positive tests were performed on samples from 572 patients. Thirty-seven patients had a positive CMV IgM result (5.9%) on the Architect system as part of the initial screening. Three patients were excluded as they were not obstetric patients. Of the 34 pregnant women with CMV IgM positive results on initial screening, 16 (47%) had CMV IgM positivity confirmed on the second platform (VIDAS) and 18 (53%) did not. In the 16 patients with confirmed positive CMV IgM results, four (25%) had acute infection, two (12.5%) had infection of uncertain timing, and ten (62.5%) had infection more than three months prior to sampling as determined by the CMV IgG avidity index. Two of the four neonates of women with low avidity IgG had CMV DNA detected in urine. Both these cases had severe neurological damage and the indication for testing their mothers was because the biparietal diameter (BPD) was less than the 5th centile at the routine 20-week gestation anomaly scan.
PMCID: PMC4677177  PMID: 26696757
3.  The Use of Protease Inhibitors in Pregnancy: Maternal and Fetal Considerations 
Background. Previous studies examining protease inhibitor use in pregnancy and the rate of preterm and small-for-gestational-age infants have yielded conflicting results. Methods. This was a retrospective study of HIV-infected women who delivered singleton infants at our institution between 1984 and 2014. Women with protease inhibitor use were compared to women on regimens without a protease inhibitor as well as those who received no antepartum antiretroviral therapy. Infants were considered preterm if less than 37 completed weeks of gestation and small-for-gestational-age if less than 10th percentile. Results. During the study period 1,004 pregnancies met inclusion criteria. Of those, 597 received a protease inhibitor as part of their regimen, 230 ART without a protease inhibitor, and 177 no ART. There was no difference in the rate of preterm birth between groups who received ART with or without a protease inhibitor, 14% versus 13%. There was no difference in the rate of small-for-gestational-age infants between the three groups. Use of a protease inhibitor was associated with a greater fall in viral load during pregnancy, p < 0.001. Conclusion. In this population with access to prenatal care and ART, treatment with protease inhibitors was associated with a greater fall in viral load, but not an increase in small or preterm infants.
PMCID: PMC4651704  PMID: 26617456
4.  The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States 
Background. To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss) among HIV-infected women enrolled in the Women's Interagency HIV Study between 1994 and 2013. Methods. We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART) to conception, and log10 copy-years viremia in the two years before conception. Results. The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI): 0.99, 2.56) times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs): 0.80 (95% CI: 0.69, 0.92) and 1.00 (95% CI: 0.90, 1.11), resp.). Conclusions. Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.
PMCID: PMC4637076  PMID: 26582966
5.  A Retrospective Audit of Clinically Significant Maternal Bacteraemia in a Specialist Maternity Hospital from 2001 to 2014 
Maternal sepsis is a significant problem in obstetrics, with almost one in four maternal deaths related to severe sepsis. We carried out a retrospective review of clinically significant bacteraemia in obstetric patients attending Rotunda Hospital over 14 years. From 2001 to 2014, there were 252 clinically significant positive blood culture episodes in obstetric patients. There were 112,361 live births >500 g during the study period giving an overall rate of 2.24 clinically significant positive maternal blood culture episodes per 1000 live births >500 g. The median rate over the 14 years was 2.12 episodes per 1000 live births >500 g, with an interquartile range of 1.74–2.43 per 1000 live births >500 g. There was no discernable increasing or decreasing trend over the 14 years. E. coli was the most commonly isolated organism (n = 92/252, 37%), followed by group B Streptococcus (n = 64/252, 25%), Staphylococcus aureus (n = 28/252, 11%), and anaerobes (n = 11/252, 4%). These top four organisms represented three-quarters of all positive blood culture episodes (n = 195/252, 77.3%). Of note, there were only five cases of listeriosis, representing a rate of 4.4 cases per 100,000 live births >500 g. The rate of invasive group A streptococcal infection was also very low at 5.3 cases per 100,000 live births >500 g.
PMCID: PMC4606170  PMID: 26494975
6.  Maternal Obesity and Rectovaginal Group B Streptococcus Colonization at Term 
Objective. To test the hypothesis that maternal obesity is an independent risk factor for rectovaginal group B streptococcus (GBS) colonization at term. Study Design. Retrospective cohort study of consecutive women with singleton term pregnancies admitted in labor at Barnes-Jewish Hospital (2004–2008). Maternal BMI ≥ 30 Kg/m2 (obese) or <30 Kg/m2 (nonobese) defined the two comparison groups. The outcome of interest was GBS colonization from a positive culture. Baseline characteristics were compared using Student's t-test and Chi-squared or Fisher's exact test. The association between obesity and GBS colonization was assessed using univariable and multivariable analyses. Results. Of the 10,564 women eligible, 7,711 met inclusion criteria. The prevalence of GBS colonization in the entire cohort was relatively high (25.8%). Obese gravidas were significantly more likely to be colonized by GBS when compared with nonobese gravidas (28.4% versus 22.2%, P < 0.001). Obese gravidas were still 35% more likely than nonobese women to test positive for GBS after adjusting for race, parity, smoking, and diabetes (adjusted OR 1.35 [95% CI 1.21–1.50]). Conclusion. Maternal obesity is a significant risk factor for GBS colonization at term. Further research is needed to evaluate the impact of this finding on risk-based management strategies.
PMCID: PMC4537723  PMID: 26300620
7.  Perinatal Outcomes in HIV Positive Pregnant Women with Concomitant Sexually Transmitted Infections 
Objective. To evaluate whether HIV infected pregnant women with concomitant sexually transmitted infection (STIs) are at increased risk of adverse perinatal and neonatal outcomes. Methods. We conducted a cohort study of HIV positive women who delivered at an inner-city hospital in Atlanta, Georgia, from 2003 to 2013. Demographics, presence of concomitant STIs, prenatal care information, and maternal and neonatal outcomes were collected. The outcomes examined were the association of the presence of concomitant STIs on the risk of preterm birth (PTB), postpartum hemorrhage, chorioamnionitis, preeclampsia, intrauterine growth restriction, small for gestational age, low Apgar scores, and neonatal intensive care admission. Multiple logistic regression was performed to adjust for potential confounders. Results. HIV positive pregnant women with concomitant STIs had an increased risk of spontaneous PTB (odds ratio (OR) 2.11, 95% confidence interval [CI] 1.12–3.97). After adjusting for a history of preterm birth, maternal age, and low CD4+ count at prenatal care entry the association between concomitant STIs and spontaneous PTB persisted (adjusted OR 1.96, 95% CI 1.01–3.78). Conclusions. HIV infected pregnant women with concomitant STIs relative to HIV positive pregnant women without a concomitant STI are at increased risk of spontaneous PTB.
PMCID: PMC4396884  PMID: 25918481
8.  Preconception Counseling and Care in the Setting of HIV: Clinical Characteristics and Comorbidities 
Objective. To describe the demographic and clinical characteristics of HIV-infected individuals and HIV-affected couples who were referred for preconception counseling (PCC) at a large urban US-based HIV clinic. Methods. Electronic medical records were reviewed for HIV-infected individuals and HIV-affected couples. Medical, reproductive, surgical, psychosocial, and family history data were abstracted. Univariate analyses were done. Results. There were 8 single HIV-infected women and 100 HIV-affected couples who underwent PCC. HIV-infected women were older (mean age 35 years versus 32 years, P = 0.06), were more likely to smoke (23% versus 0%, P < 0.01), and had more medical comorbidities (57% versus 33%, P = 0.04) than HIV-uninfected women. The majority of couples were serodiscordant (77%), and of these couples, 32% had a detectable plasma viral load and 33% report inconsistent condom use. Conclusions. HIV-infected women have a number of medical and psychosocial issues, including those related to HIV that may increase the risk of adverse pregnancy outcomes and HIV perinatal and sexual transmission. PCC is an important intervention to optimize maternal management to improve perinatal outcomes and minimize transmission risks.
PMCID: PMC4369898  PMID: 25838753
9.  Estimating the Attack Rate of Pregnancy-Associated Listeriosis during a Large Outbreak 
Background. In 2011, a multistate outbreak of listeriosis linked to contaminated cantaloupes raised concerns that many pregnant women might have been exposed to Listeria monocytogenes. Listeriosis during pregnancy can cause fetal death, premature delivery, and neonatal sepsis and meningitis. Little information is available to guide healthcare providers who care for asymptomatic pregnant women with suspected L. monocytogenes exposure. Methods. We tracked pregnancy-associated listeriosis cases using reportable diseases surveillance and enhanced surveillance for fetal death using vital records and inpatient fetal deaths data in Colorado. We surveyed 1,060 pregnant women about symptoms and exposures. We developed three methods to estimate how many pregnant women in Colorado ate the implicated cantaloupes, and we calculated attack rates. Results. One laboratory-confirmed case of listeriosis was associated with pregnancy. The fetal death rate did not increase significantly compared to preoutbreak periods. Approximately 6,500–12,000 pregnant women in Colorado might have eaten the contaminated cantaloupes, an attack rate of ~1 per 10,000 exposed pregnant women. Conclusions. Despite many exposures, the risk of pregnancy-associated listeriosis was low. Our methods for estimating attack rates may help during future outbreaks and product recalls. Our findings offer relevant considerations for management of asymptomatic pregnant women with possible L. monocytogenes exposure.
PMCID: PMC4345047  PMID: 25784782
10.  Acute Infectious Morbidity in Multiple Gestation 
Objectives. Physiologic and immunologic changes in pregnancy result in increased susceptibility to infection. These shifts are more pronounced in pregnancies complicated by multiple gestation. The objective of this study was to determine the association between multiple gestation and risk of infectious morbidity. Study Design. The Nationwide Inpatient Sample for the years 2008–2010 was used to identify pregnant women during admission for delivery with International Classification of Diseases codes. Logistic regression was used to compute odds ratios and 95% confidence intervals for demographic data, preexisting medical conditions, and acute medical and infectious complications for women with multiple versus singleton gestations. Results. Among women with multiple gestation, 38.4 per 1,000 women had an infectious complication compared to 12.8 per 1,000 women with singletons. The most significant infectious morbidity associated with multiple gestation was intestinal infections, pyelonephritis, influenza, and pneumonia. After controlling for confounding variables, infectious complications at delivery persisted for women with multiples, though the association was dependent on mode of delivery. Conclusions. Women with multiple gestations are at increased risk for infectious morbidity identified at the time of delivery. This association was diminished among women who had a cesarean suggesting that operative delivery is not responsible for this association.
PMCID: PMC4313678  PMID: 25684973
11.  Antiviral Treatment among Pregnant Women with Chronic Hepatitis B 
Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.
PMCID: PMC4274824  PMID: 25548510
12.  Safer Conception Needs for HIV Prevention among Female Sex Workers in Burkina Faso and Togo 
Background. Reproductive health programming for female sex workers (FSW) may include contraceptive services but rarely addresses safer pregnancy planning. Methods. Adult FSW were enrolled into a cross-sectional study across four sites in Burkina Faso and Togo using respondent-driven sampling. Sociobehavioral questionnaires and HIV counseling and testing were administered. Sample statistics and engagement in HIV treatment were described and compared using Chi-squared statistics. Results. 1,349 reproductive-aged FSW were enrolled from January to July 2013. Overall, 267 FSW (19.8%) were currently trying to conceive. FSW trying to conceive were more likely to test positive for HIV at enrollment as compared to women not trying to become pregnant (24.5% versus 17.7%, P < 0.01); however awareness of HIV status was similar across groups. Among FSW trying to conceive, 79.0% (211/267) had previously received HIV testing, yet only 33.8% (23/68) of HIV-infected FSW reported a previous HIV diagnosis. Overall 25.0% (17/68) of HIV-infected FSW trying to conceive were on antiretroviral therapy. Conclusion. FSW frequently desire children. However engagement in the HIV prevention and treatment cascade among FSW trying to conceive is poor potentiating periconception transmission risks to partners and infants. Programs to facilitate earlier HIV diagnosis for FSW and safer conception counseling are needed as components of effective combination HIV prevention services.
PMCID: PMC4227409  PMID: 25404849
13.  Cervical Dysplasia and High-Risk Human Papillomavirus Infections among HIV-Infected and HIV-Uninfected Adolescent Females in South Africa 
Background. HIV-infected adolescents may be at higher risk for high-grade cervical lesions than HIV-uninfected adolescents. The purpose of this study was to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear abnormalities between these two groups. Methods. In this cross-sectional study, we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV-uninfected adolescents in order to determine the prevalence of HR-HPV genotypes and cervical cytological abnormalities. Comparisons were made using Pearson χ2 and independent-samples t-tests analyses, and associations between demographic and behavioral characteristics and HPV infections were examined. Results. HIV-infected participants were more likely to be infected with any HPV (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%; P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections. Abnormal Pap test results were more common among HIV-infected participants (28.8% versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV infection. Conclusions. HIV-infected adolescents have an increased risk of infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV infections among our participants would not be prevented by the currently available vaccinations against HPV.
PMCID: PMC4217359  PMID: 25389377
14.  Antenatal Atazanavir: A Retrospective Analysis of Pregnancies Exposed to Atazanavir 
Introduction. There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. Methods. A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. Results. There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), “preconception” atazanavir exposure; 27 started atazanavir-based cART as “first-line” during the pregnancy; and 29 “switched” to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. Conclusions. These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy.
PMCID: PMC4190692  PMID: 25328370
15.  Maternal β-Hemolytic Streptococcal Pharyngeal Exposure and Colonization in Pregnancy 
Objectives. To report the pharyngeal colonization rate of β-hemolytic streptococci and changes in the value of antistreptolysin O (ASO) and anti-DNase B serology titers during pregnancy. Methods. Healthy pregnant women were recruited and blood was drawn in each trimester. The upper limit of normal (ULN) values for ASO and anti-DNase B was calculated for each trimester. Throat swabs were collected for culture and positive cultures were further assessed for the identification of serogroup of the isolated β-hemolytic streptococcus. Results. Out of a total of 126 pregnant women, 34.1% had positive throat cultures. Group C and group G strains were isolated in 18.2% of throat cultures while group F was detected in 13.5% of cases. The rate of colonization with GAS was 1.6%. There was an overall drop in ASO titer during pregnancy while anti-DNase B titers remained relatively unchanged. ULN values of 164IU, 157IU, and 156IU were calculated for ASO at the first, second, and third trimesters, respectively. Based on the ULN values, 28.6% of patients had recent streptococcal exposure. Conclusions. These results show that pregnant women act as a reservoir for spreading potentially immunogenic (groups C and G) and disease producing (group F) virulent strains of streptococci.
PMCID: PMC4158157  PMID: 25210420
16.  Frequent Genital HSV-2 Shedding among Women during Labor in Soweto, South Africa 
Background. Despite high herpes simplex virus type 2 (HSV-2) incidence and prevalence among women in Africa, we are unaware of published neonatal herpes reports. To assess neonatal HSV transmission potential in South Africa, we investigated the frequency of the strongest risk factors: HSV acquisition in late pregnancy and HSV shedding during labor. Methods. Women admitted in early labor to a hospital in Soweto underwent HSV serologic testing and genital swab collection for HSV PCR. HSV-2 seronegative women were assessed for seroconversion 4–6 weeks after delivery. Results. Of 390 women enrolled, 229 (58.7%) were HSV-2 seropositive. Genital HSV-2 was detected in 17.2% of HSV-2 seropositive women, including 26 of 115 HIV-positive and 13 of 110 HIV-negative women (22.6% versus 11.8%; RR, 1.91; 95% CI, 1.04–3.53; P = 0.038), but in none of 161 HSV-2 seronegative women. Among the 91 HSV-2 seronegative women followed after delivery, none seroconverted. Conclusions. HSV-2 reactivation is common among South African women during labor, especially those with HIV coinfection. To determine the epidemiology of neonatal herpes in South Africa and to investigate whether the lack of reported cases is due to alterations in immune control or HSV-2 virulence, studies evaluating acutely ill neonates for HSV and studies of maternal HSV-2 shedding patterns are needed.
PMCID: PMC4054931  PMID: 24963269
17.  Predischarge Postpartum Methicillin Resistant Staphylococcus aureus Infection and Group B Streptococcus Carriage at the Individual and Hospital Levels 
Background. We sought to characterize the relationship between individual group B streptococcus (GBS) colonization and pre-discharge postpartum methicillin resistant Staphylococcus aureus (MRSA) infection in United States women delivering at term. We also sought to examine the association between hospital GBS colonization prevalence and MRSA infection. Materials and Methods. Data was from the Nationwide Inpatient Sample, a representative sample of United States community hospitals. Hierarchical regression models were used to estimate odds ratios adjusted for patient age, race, expected payer, and prepregnancy diabetes and hospital teaching status, urbanicity, ownership, size, and geographic region. We used multiple imputation for missing covariate data. Results. There were 3,136,595 deliveries and 462 cases of MRSA infection included in this study. The odds ratio for individual GBS colonization was 1.2 (95% confidence interval: 0.9 to 1.5). For a five-percent increase in the hospital prevalence of GBS colonization, the odds ratio was 0.9 (95% CI: 0.1 to 5.6). Conclusions. The odds ratio estimate for the association of hospital GBS prevalence with MRSA infection is too imprecise to make conclusions about its magnitude and direction. Barring major bias in our estimates, individual GBS carriage does not appear to be strongly associated with predischarge postpartum MRSA infection.
PMCID: PMC3963373  PMID: 24729672
18.  Postnatal Cytomegalovirus Exposure in Infants of Antiretroviral-Treated and Untreated HIV-Infected Mothers 
HIV-1 and CMV are important pathogens transmitted via breastfeeding. Furthermore, perinatal CMV transmission may impact growth and disease progression in HIV-exposed infants. Although maternal antiretroviral therapy reduces milk HIV-1 RNA load and postnatal transmission, its impact on milk CMV load is unclear. We examined the relationship between milk CMV and HIV-1 load (4–6 weeks postpartum) and the impact of antiretroviral treatment in 69 HIV-infected, lactating Malawian women and assessed the relationship between milk CMV load and postnatal growth in HIV-exposed, breastfed infants through six months of age. Despite an association between milk HIV-1 RNA and CMV DNA load (0.39 log10 rise CMV load per log10 rise HIV-1 RNA load, 95% CI 0.13–0.66), milk CMV load was similar in antiretroviral-treated and untreated women. Higher milk CMV load was associated with lower length-for-age (−0.53, 95% CI: −0.96, −0.10) and weight-for-age (−0.40, 95% CI: −0.67, −0.13) Z-score at six months in exposed, uninfected infants. As the impact of maternal antiretroviral therapy on the magnitude of postnatal CMV exposure may be limited, our findings of an inverse relationship between infant growth and milk CMV load highlight the importance of defining the role of perinatal CMV exposure on growth faltering of HIV-exposed infants.
PMCID: PMC3958696  PMID: 24723745
19.  High Rate of Chronic Villitis in Placentas of Pregnancies Complicated by Influenza A/H1N1 Infection 
Introduction. Pandemic influenza A/H1N1 infection during pregnancy has a negative impact on several aspects of pregnancy outcome. As yet, no elucidating mechanism has been revealed for these effects. We investigated whether placentas of pregnancies complicated by 2009 influenza A/H1N1 infection demonstrated an increased rate of chronic villitis and whether this villitis was caused by influenza virus. Methods. We performed a cohort study on 145 pregnant outpatients during the 2009-2010 influenza A H1N1 pandemic. The placentas of patients with influenza infection were examined for histologic signs of chronic villitis. In case of villitis, polymerase chain reaction (PCR) on influenza virus was performed on placental tissue. Results. 29 patients had influenza infection. Placentas of 15 of these patients were collected and examined. In 7 cases (47%) chronic villitis was detected. Placental weight and birth weight of the neonates did not differ between cases with and without chronic villitis. In all cases PCR was negative for influenza. Conclusion. In our series, chronic villitis was present in a high proportion of placentas of pregnancies complicated by 2009 influenza A/H1N1 infection. We could not demonstrate the presence of influenza virus in placental tissue.
PMCID: PMC3947755  PMID: 24693211
20.  Performance of BVBlue Rapid Test in Detecting Bacterial Vaginosis among Women in Mysore, India 
Bacterial vaginosis (BV) is the most common cause of abnormal vaginal discharge in reproductive age women. It is associated with increased susceptibility to HIV/STI and adverse birth outcomes. Diagnosis of BV in resource-poor settings like India is challenging. With little laboratory infrastructure there is a need for objective point-of-care diagnostic tests. Vaginal swabs were collected from women 18 years and older, with a vaginal pH > 4.5 attending a reproductive health clinic. BV was diagnosed with Amsel's criteria, Nugent scores, and the OSOM BVBlue test. Study personnel were blinded to test results. There were 347 participants enrolled between August 2009 and January 2010. BV prevalence was 45.1% (95% confidence interval (CI): 41.5%–52.8%) according to Nugent score. When compared with Nugent score, the sensitivity, specificity, positive predictive value, negative predictive value for Amsel's criteria and BVBlue were 61.9%, 88.3%, 81.5%, 73.7% and 38.1%, 92.7%, 82.1%, 63.9%, respectively. Combined with a “whiff” test, the performance of BVBlue increased sensitivity to 64.4% and negative predictive value to 73.8%. Despite the good specificity, poor sensitivity limits the usefulness of the BVBlue as a screening test in this population. There is a need to examine the usefulness of this test in other Indian populations.
PMCID: PMC3913452  PMID: 24526829
21.  Effect of Highly Active Antiretroviral Therapy (HAART) and Menopause on Risk of Progression of Cervical Dysplasia in Human Immune-Deficiency Virus- (HIV-) Infected Women 
Background. More HIV-infected women are reaching older age and menopause, but there is limited information on cervical squamous intraepithelial lesions (SILs) on these women. Methods. To assess the effect of HAART and menopause on SILs in HIV-infected women, we reviewed the results of Papanicolaou (Pap) tests obtained between 1991 and 2011 on 245 women. Progression to SILs was determined by comparing Pap test results. The association of HAART and transition to menopause on SILs was assessed using survival analysis. Results. Women receiving HAART had a 52% reduced risk in the progression to SILs compared to women receiving any other antiretroviral regimen or no regimen (CI: 0.33–0.70, P = 0.0001). A greater increase of CD4+ cell counts was associated with a greater reduction on the risk of progression to SILs. Menopausal women had a 70% higher risk of progression to SILs than premenopausal women (CI: 1.11–2.62, P < 0.0001), adjusting for HIV medications, CD4+ count, duration of HIV infection, moderation effect of menopause by age, prior IV drug use, and smoking. Conclusion. HAART had a positive long-term effect on the progression to SILs. However, being younger and menopausal increases the risk of progression.
PMCID: PMC3878554  PMID: 24453469
22.  Clinical Characteristics of Turkish Women with Candida krusei Vaginitis and Antifungal Susceptibility of the C. krusei Isolates  
Objective. Candida krusei causes approximately 1% of vulvovaginal candidiasis (VVC) cases and is naturally resistant to fluconazole. Antifungal testing may be required if C. krusei vaginitis fails to respond to non-fluconazole therapy, particularly in patients with recurrent infections. Design. We investigated the clinical characteristics and antifungal susceptibility profile of vaginal C. krusei isolates. Between 2009 and 2012, we identified 560 unrelated Candida spp.-positive vaginal cultures, of which 28 (5.0%) were C. krusei. These isolates were analyzed according to host factors and the clinical forms of VVC, and their in vitro susceptibility to 10 antifungal agents was tested using a reference microdilution method. Results. We observed that perineal laceration and increased age (>50 years) were significant predictors of C. krusei in vaginal samples (P < 0.05). All isolates were susceptible to amphotericin B, caspofungin, ketoconazole, and miconazole. Additionally, susceptible dose-dependent and resistant rates were found for fluconazole as 42.9% and 57.1%, respectively. Remarkably, only 42.9% and 67.9% of the isolates were susceptible to itraconazole and voriconazole, respectively. Conclusions. Understanding local susceptibility patterns, especially those of non-C. albicans Candida species, can significantly aid in the selection of an effective antifungal agent. The in vivo response of C. krusei vaginitis to various antifungal therapeutics remains unknown and requires further research.
PMCID: PMC3874352  PMID: 24396265
23.  Benzoyl Peroxide Formulated Polycarbophil/Carbopol 934P Hydrogel with Selective Antimicrobial Activity, Potentially Beneficial for Treatment and Prevention of Bacterial Vaginosis 
The human vagina is colonized by a variety of indigenous microflora; in healthy individuals the predominant bacterial genus is Lactobacillus while those with bacterial vaginosis (BV) carry a variety of anaerobic representatives of the phylum Actinobacteria. In this study, we evaluated the antimicrobial activity of benzoyl peroxide (BPO) encapsulated in a hydrogel against Gardnerella vaginalis, one of the causative agents of BV, as well as indicating its safety for healthy human lactobacilli. Herein, it is shown that in well diffusion assays G. vaginalis is inhibited at 0.01% hydrogel-encapsulated BPO and that the tested Lactobacillus spp. can tolerate concentrations of BPO up to 2.5%. In direct contact assays (cells grown in a liquid culture containing hydrogel with 1% BPO or BPO particles), we demonstrated that hydrogels loaded with 1% BPO caused 6-log reduction of G. vaginalis. Conversely, three of the tested Lactobacillus spp. were not inhibited while L. acidophilus growth was slightly delayed. The rheological properties of the hydrogel formulation were probed using oscillation frequency sweep, oscillation shear stress sweep, and shear rate sweep. This shows the gel to be suitable for vaginal application and that the encapsulation of BPO did not alter rheological properties.
PMCID: PMC3870611  PMID: 24382940
24.  The Effect of Cotrimoxazole Prophylactic Treatment on Malaria, Birth Outcomes, and Postpartum CD4 Count in HIV-Infected Women 
Background. Limited data exist on cotrimoxazole prophylactic treatment (CPT) in pregnant women, including protection against malaria versus standard intermittent preventive therapy with sulfadoxine-pyrimethamine (IPTp). Methods. Using observational data we examined the effect of CPT in HIV-infected pregnant women on malaria during pregnancy, low birth weight and preterm birth using proportional hazards, logistic, and log binomial regression, respectively. We used linear regression to assess effect of CPT on CD4 count. Results. Data from 468 CPT-exposed and 768 CPT-unexposed women were analyzed. CPT was associated with protection against malaria versus IPTp (hazard ratio: 0.35, 95% Confidence Interval (CI): 0.20, 0.60). After adjustment for time period this effect was not statistically significant (adjusted hazard ratio: 0.66, 95% CI: 0.28, 1.52). Among women receiving and not receiving CPT, rates of low birth weight (7.1% versus 7.6%) and preterm birth (23.5% versus 23.6%) were similar. CPT was associated with lower CD4 counts 24 weeks postpartum in women receiving (−77.6 cells/μL, 95% CI: −125.2, −30.1) and not receiving antiretrovirals (−33.7 cells/μL, 95% CI: −58.6, −8.8). Conclusions. Compared to IPTp, CPT provided comparable protection against malaria in HIV-infected pregnant women and against preterm birth or low birth weight. Possible implications of CPT-associated lower CD4 postpartum warrant further examination.
PMCID: PMC3865641  PMID: 24363547
25.  Medical and Infectious Complications Associated with Pyelonephritis among Pregnant Women at Delivery 
Objective. Pyelonephritis is a common cause of antepartum admission and maternal morbidity. Medical complications associated with pyelonephritis during delivery are not well described; thus the objective of this study was to estimate medical, infectious, and obstetric complications associated with pyelonephritis during the delivery admission. Study Design. We conducted a retrospective cohort study using the Nationwide Inpatient Sample (NIS) for the years 2008–2010. The NIS was queried for all delivery-related discharges. During the delivery admission, the ICD-9-CM codes for pyelonephritis were used to identify cases and were compared to women without pyelonephritis. A multivariable logistic regression model was constructed for various medical, infectious, and obstetric complications among women with pyelonephritis compared to women without, while controlling for preexisting medical conditions and demographics. Results. During the years 2008–2010, there were 26,397 records with a diagnosis of pyelonephritis during the delivery admission, for a rate of 2.1 per 1000 deliveries. Women with pyelonephritis had increased associated risks for transfusion, need for mechanical ventilation, acute heart failure, pneumonia, pulmonary edema, acute respiratory distress syndrome, sepsis, acute renal failure, preterm labor, and chorioamnionitis, while controlling for preexisting medical conditions. Conclusions. Pyelonephritis at delivery admissions is associated with significant medical and infectious morbidity.
PMCID: PMC3804393  PMID: 24194632

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