Meira S. Halpern

The Epidemiology of Neonatal Herpes Simplex Virus Infections in California from 1985 to 1995

Comprehensive hospital discharge data completed by the California Office of Statewide Health Planning and Development was used to determine whether the proportion of infants </=6 weeks of age who were hospitalized with a diagnosis of herpes simplex virus (HSV) infection changed between 1985 and 1995. During 1985, 1990, and 1995, respectively, 11.7, 11.3, and 11.4 infants per 100,000 live births had a diagnosis of HSV (P=.98). The proportion of infants 1-42 days of age who were discharged from the hospital with a diagnosis of HSV infection did not change over this time period despite a decrease in deliveries by cesarean section and an increase in the proportion of women with a diagnosis of genital HSV infection who gave birth to infants by vaginal delivery. From 1985 to 1995 there was no decrease in the rate of secondary diagnosis of genital HSV in delivering women.

Timing of Antiretroviral Therapy Initiation and its Impact on Disease Progression in Perinatal Human Immunodeficiency Virus-1 Infection

Objective: Treatment with highly active antiretroviral therapy (HAART) reduces overall perinatal human immunodeficiency virus (HIV) type 1–related mortality. The effect of timing of HAART initiation on reduction of morbidity is not well defined. We evaluated the association of timing of HAART initiation on progression to moderate or severe disease. Methods: Retrospective, population-based study of 196 perinatally HIV-infected children followed from birth in northern California from 1988 to 2009. Results: Of 196 children, 58% received HAART and were followed for a median of 6.2 years after HAART initiation. HAART use was associated with improved survival to the age of 5 years: no HAART, 50% versus HAART, 88%; P < 0.0001. However, the advantage of initial HAART over mono or dual therapy transitioning to HAART was small and not statistically significant (P = 0.23). Starting HAART before the development of moderate or severe disease delayed the median age of diagnosis of moderate disease from 0.4 years (interquartile range, [0.3–0.8]) without HAART to 3.0 years ([interquartile range, 1.9–5.8]; P < 0.0001) with HAART. HAART initiation after progression to moderate or severe disease was associated with decreased progression to severe disease or death, respectively (moderate to severe: 8% [3/36] with HAART vs. 84% [70/83] with no HAART, P < 0.0001; severe to death: 9% [6/68] with HAART vs. 73% [49/67] with no HAART, P < 0.0001). Conclusions: In perinatal HIV infection, HAART is associated with delayed progression and reduced mortality regardless of disease severity at HAART initiation. This finding reinforces US guidelines regarding HAART initiation at >1 year of age if children present with most clinical category B diagnoses, regardless of CD4 measurements or plasma HIV RNA level.

Immunologic response to oral polio vaccine in human immunodeficiency virus-infected and uninfected Zimbabwean children.

Background: Poliovirus eradication is dependent on maintaining adequate community-wide levels of serologic protection. Many African countries with conditions that favor continued wild poliovirus propagation also have a high prevalence of pediatric human immunodeficiency virus (HIV) infection. Data are limited regarding the degree of serologic immunity conferred on HIV-infected children after immunization with oral polio vaccine (OPV). Methods: This was a cross-sectional study correlating HIV infection and neutralizing antibodies against poliovirus serotypes 1, 2, and 3 in 95 Zimbabwean children 2 months to 2 years of age, born to HIV-infected mothers, who received OPV according to the national schedule. Results: HIV-infected children had significantly lower rates of seroconversion to all 3 poliovirus serotypes than HIV-uninfected children (60%, 67%, and 47% vs. 96%, 100%, and 82%, P = 0.001, 0.0003, and 0.015 for serotypes 1, 2, and 3 in HIV-infected and uninfected children, respectively, after ≥3 OPV doses). Among poliovirus seroconverters, HIV-infected children also had significantly lower geometric mean titers against serotypes 1 and 2 than HIV-uninfected children (geometric mean titers: 198 and 317 vs. 1193 and 1056, P = 0.032 and 0.050, for serotypes 1 and 2, respectively, after ≥3 OPV doses). In addition, HIV-infected children had significantly higher levels of total IgG and significantly lower CD4% and mean weight than HIV-uninfected children. Of note, none of the HIV-infected children were receiving antiretroviral therapy, and 71% had a CD4% indicating severe immunodeficiency. Conclusions: Pediatric HIV infection is associated with a poor serologic response to OPV, which could pose an obstacle to global polio eradication.

Staphylococcal infections in children, California, USA, 1985-2009.

Young children, Black children, and those without private insurance were at higher risk for hospitalization.

Vaccine Poliovirus Shedding and Immune Response to Oral Polio Vaccine in HIV-Infected and Uninfected Zimbabwean Infants

BACKGROUND With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV. METHODS We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes. RESULTS We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0-2 OPV doses but significantly higher in the HIV-infected versus uninfected children after ≥ 3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates. CONCLUSIONS HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV.

Epidemiologic trends in penile anomalies and hypospadias in the state of California, 1985-2006.

PURPOSE Using statewide data, we evaluated whether the changing incidence of penile anomalies and hypospadias is reflected in the diverse California population of newborn males over the past 20 years. METHODS Discharge data from all California hospitals, prepared by the OSHPD (Sacramento, CA) was reviewed for the years 1985-2006 for male infant births with an ICD-9 code (752.6) for hypospadias, epispadias or other penile anomalies. Trends were examined by Generalized Estimation Equations for Poisson regression. RESULTS From 1985 to 2006, the birth incidence of newborn penile anomalies increased in California from 47 to 57 cases per 10,000 newborn discharges, yet the trend for hypospadias alone appears stable from 1997. The rates for penile anomalies in newborns increased 1.4% annually (p < 0.001). All racial/ethnic groups analyzed showed this increase (p < 0.001 for each). During the study period there was a 2% increase per year in plural births (p < 0.001). Interestingly, the rate of change in penile anomaly incidence was greater in males of plural births compared to their singleton cohorts (2% vs 1% annually) (p < 0.001). The birth incidence of cleft palate, another congenital anomaly known to be stable over time, remained unchanged over this period. CONCLUSIONS From 1985 to 2006 in California the incidence of penile anomalies increased in a statistically significant manner, but the incidence of hypospadias appears stable for the last decade. Our data support the notion that different racial/ethnic groups have distinct incidences of penile anomaly formation and that an association with plural births appears to be present.

Trends in Hospitalization for Pediatric Pyelonephritis: A Population Based Study of California From 1985 to 2006

PURPOSE We examined trends in pediatric hospitalization for pyelonephritis from 1985 to 2006 and identified factors associated with admission. MATERIALS AND METHODS We performed a population based analysis of hospital discharges using the Office of Statewide Health Planning and Development database to evaluate trends in California regarding pediatric hospitalizations for pyelonephritis from 1985 to 2006. Multivariable logistic regression was performed to identify factors associated with admission for pyelonephritis. RESULTS A total of 46,300 children were hospitalized for pyelonephritis in California from 1985 to 2006. The overall rate of hospitalization for pyelonephritis increased by greater than 80%, from 17 per 100,000 children in the California population in 1985 to 31 per 100,000 in 2005. This change was primarily due to the nearly ninefold increase in pyelonephritis hospitalizations observed in children younger than 1 year, from 28 per 100,000 in 1985 to 238 per 100,000 in 2005. Among children younger than 1 year males without private insurance and of nonwhite race had increased odds of hospitalization, while females with private insurance and of Asian race had increased odds of hospitalization, compared with nonprivate insurance and white race, respectively. CONCLUSIONS A significant increase in hospital admissions for pyelonephritis, primarily in children younger than 1 year, occurred in California between 1985 and 2006. Further studies are needed to establish the cause of this striking increase and to determine why certain pediatric populations are at increased risk for hospitalization.

Shedding of Oral Poliovirus Vaccine (OPV) by HIV-Infected and -Uninfected Mothers of OPV-Vaccinated Zimbabwean Infants

Community circulation of oral poliovirus vaccine (OPV) likely begins with household transmission. We analyzed stool collected from Zimbabwean mothers who were infected with human immunodeficiency virus (HIV) and those who were uninfected with HIV 1 to 24 weeks after infant oral poliovirus vaccination. Overall, only 5% of the mothers had detectable OPV (16 of 304) despite high infant shedding rates. OPV shedding was similar between HIV-infected mothers and those who were uninfected (11 [6.4%] of 171 vs 5 [3.8%] of 133, respectively) and between mothers of HIV-infected infants and those of uninfected infants (2 [3.5%] of 57 vs 9 [6.3%] of 144, respectively). Mothers of vaccinated infants are unlikely to shed OPV, even when they are infected with HIV.

Trends in Hospitalizations for Intussusception in California in Relationship to the Introduction of New Rotavirus Vaccines, 1985-2010.

Background: The new rotavirus vaccines RV5 and RV1 have been associated with small increase in intussusception risk in active vaccine surveillance studies. It is unclear what the impact might be on the overall trends of intussusception hospitalizations at a large population basis. Methods: We conducted an ecological study of hospital discharges of infants with intussusception discharge diagnosis using the California Office of Statewide Health Planning and Development database (1985–2010). We measured incidence rates (IR) of intussusception hospitalizations per 100,000 births within 3 periods (1985–1997; 2000–2005; 2006–2010) related to past, pre-introduction and post-introduction of the new rotavirus vaccines. We estimated slopes of yearly IRs within each period, changes in slopes between periods and IR ratios (IRR) of the mean IRs between periods. We did subgroup analyses for 5 age-subgroups. We also analyzed intussusception hospitalizations of infants who also had a surgical repair and/or radiologic reduction procedure code (restricted cohort). Results: We identified 6241 intussusception hospitalizations; 4696 also had pertinent procedure codes. There was an upward trend in yearly IRs during 2006–2010 (+2 excess cases per 100,000 births per year; P = 0.023); the change in slopes between 2006–2010 and 2000–2005 was +3.2 excess cases per 100,000 births per year (P = 0.052), and the IR in 2006–2010 was 10% higher than in 2000–2005 (IRR: 1.10; 95% confidence intervals: 1.01–1.19). The IRR in 2006–2010 versus 2000–2005 for the 6–14 weeks age-subgroup was 1.90 (95% confidence intervals: 1.33–2.74). In the restricted cohort, trends were similar, though not nominally significant. Conclusions: We documented at a population-level a small increased risk in intussusception hospitalizations post-introduction of the new rotavirus vaccines.