Identification of serologic markers for school-aged children with congenital rubella syndrone

BACKGROUND: Congenital rubella syndrome (CRS) case identification is challenging in older children since laboratory markers of congenital rubella virus (RUBV) infection do not persist beyond age 12 months. METHODS: We enrolled children with CRS born between 1998 and 2003 and compared their immune responses to RUBV with those of their mothers and a group of similarly aged children without CRS. Demographic data and sera were collected. Sera were tested for anti-RUBV immunoglobulin G (IgG), IgG avidity, and IgG response to the 3 viral structural proteins (E1, E2, and C), reflected by immunoblot fluorescent signals. RESULTS: We enrolled 32 children with CRS, 31 mothers, and 62 children without CRS. The immunoblot signal strength to C and the ratio of the C signal to the RUBV-specific IgG concentration were higher (P < .029 for both) and the ratio of the E1 signal to the RUBV-specific IgG concentration lower (P = .001) in children with CRS, compared with their mothers. Compared with children without CRS, children with CRS had more RUBV-specific IgG (P < .001), a stronger C signal (P < .001), and a stronger E2 signal (P ≤ .001). Two classification rules for children with versus children without CRS gave 100% specificity with >65% sensitivity. CONCLUSIONS: This study was the first to establish classification rules for identifying CRS in school-aged children, using laboratory biomarkers. These biomarkers should allow improved burden of disease estimates and monitoring of CRS control programs. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Progress toward control of rubella and prevention of congenital rubella syndrome--worldwide, 2009.

Rubella, usually a mild rash illness in children and adults, can cause serious consequences when a pregnant woman is infected, particularly in early pregnancy. These serious consequences include miscarriage, fetal death or an infant born with birth defects (i.e., congenital rubella syndrome (CRS)). The primary purpose for rubella vaccination is the prevention of congenital rubella infection including CRS. Since 1969, several rubella virus vaccines have been licensed for use; however, until the 1990s, use of rubella-containing vaccine (RCV) was limited primarily to developed countries. In 1996, it was estimated that 110,000 infants with CRS were born annually in developing countries. In 2000, the first World Health Organization rubella vaccine position paper was published to guide introduction of RCV in national childhood immunization schedules. From 1996 to 2009, the number of countries that introduced RCV into their national routine childhood immunization programs increased by 57% from 83 countries in 1996 to 130 countries in 2009. In addition, three of the six WHO regions established rubella control and CRS prevention goals: Region of the Americas and Europe rubella elimination by 2010 and 2015, respectively, and Western Pacific Region-accelerated rubella control and CRS prevention by 2015. Also, during this time period, the number of rubella cases reported decreased from 670,894 in 2000 to 121,344 in 2009. Rubella control and prevention of CRS can be accelerated by integrating with current global measles mortality reduction and regional elimination activities.

Progress toward measles and rubella elimination in Egypt.

Measles and rubella were common infectious diseases in Egypt during the prevaccine era. Monovalent measles vaccine was introduced in 1977, and measles vaccination coverage increased from <50% to >90% from 1980 to 1999; however, measles outbreaks continued to occur at 2- to 4-year intervals during this period. After the introduction of a second routine dose of measles vaccine as a combined measles-mumps-rubella (MMR) vaccine in 1999 and the implementation of measles immunization campaigns targeting 6- to 16-year-old children during 2000-2003, reported measles cases dramatically decreased by 2003. In 2002, Egypt established a goal to eliminate measles and rubella and to prevent congenital rubella syndrome (CRS) by 2010. Large-scale rubella and measles outbreaks in 2005-2007, however, led to a revision of the plan of action to achieve the 2010 goals. A nation-wide measles-rubella immunization campaign, targeting children, adolescents, and young adults 2-20 years old, was conducted in 2 phases during 2008-2009 and achieved coverage >95%. With the decrease to record low levels of cases of measles and rubella in 2009 and 2010, Egypt should achieve measles and rubella elimination in the near future, but high coverage(>95%) with 2 doses of measles-rubella vaccine needs to be maintained, measles-rubella surveillance strengthened, and CRS surveillance developed.

Incidence of congenital rubella syndrome at a hospital serving a predominantly Hispanic population, El Paso, Texas.

OBJECTIVE: The current epidemiology of rubella reveals an increase in the number of cases among adult Hispanics and an increase in the number of congenital rubella syndrome (CRS) cases among infants of Hispanic mothers. Recent rubella outbreaks have occurred primarily among adult Hispanics, many of whom are foreign-born natives of countries where rubella vaccination is not routine or has only recently been implemented. The objective of this study was to estimate the incidence of CRS in a hospital serving a predominantly Hispanic population. METHODS: Hospital charts of infants <1 year old discharged between January 1, 1994 and December 31, 1996 with International Classification of Diseases, Ninth Revision (ICD-9) discharge codes consistent with CRS were reviewed; we looked for cataracts, deafness, congenital heart defects, dermal erythropoiesis, microcephaly, meningoencephalitis, and other defects associated with CRS. We abstracted data on maternal and infant ethnicity, maternal age, gestational age, infants' birth weight, infants' clinical characteristics, and laboratory evaluation. Cases were categorized according to the Council of State and Territorial Epidemiologists' case classification for CRS. RESULTS: Of the 182 infants with 1 or more ICD-9 codes consistent with CRS, 6 (3.3%) met either the confirmed or probable case definition for CRS. Two infants met the definition for confirmed CRS. Although laboratory tests for rubella immunoglobulin M antibodies were positive for both of these infants, only 1 of the cases had been reported to the state health department. Four other infants had clinical presentations that met the definition for a probable case. One of these had been tested for rubella immunoglobulin M antibodies, and the test was negative. The other 3 had not been tested. The rate of infants meeting the definition of confirmed and probable CRS was 3.1 per 10 000 hospital births. All confirmed and probable cases were among infants born to Hispanic mothers. Maternal country of origin was Mexico for the 2 confirmed cases and 1 of the probable cases, and unknown for the remaining 3 probable cases. CONCLUSION: The rate of confirmed and probable CRS among infants in this predominantly Hispanic population is higher than the reported rate in the United States in the vaccine era, which has been reported to range from approximately 0.01-0.08 per 10 000 live births. These findings indicate a need for heightened awareness of CRS among physicians who serve populations at risk for rubella. Physicians should report all confirmed and probable CRS cases to the state health department. The lack of appropriate laboratory testing in 3 infants with probable CRS indicates that physicians should consider a diagnosis of CRS in infants with some signs consistent with CRS, particularly in areas serving high numbers of individuals at risk for rubella.

A large rubella outbreak with spread from the workplace to the community.

CONTEXT: Childhood vaccination has reduced rubella disease to low levels in the United States, but outbreaks continue to occur. The largest outbreak in the past 5 years occurred in Nebraska in 1999. OBJECTIVES: To examine risk factors for disease, susceptibility of the risk population, role of vaccine failure, and the need for new vaccination strategies in response to the Nebraska rubella outbreak. DESIGN, SETTING, AND PATIENTS: Investigation of 83 confirmed rubella cases occurring in Douglas County, Nebraska, between March 23 and August 24, 1999; serosurvey of 413 pregnant women in the outbreak locale between October 1998 and March 1999 (prior to outbreak) and April and November 1999 (during and after outbreak). MAIN OUTCOME MEASURES: Case characteristics, compared with that of the general county population; area childhood rubella vaccination rates; and susceptibility among pregnant women before vs during and after the outbreak. RESULTS: All 83 rubella cases were unvaccinated or had unknown vaccination status and fell into 3 groups: (1) 52 (63%) were young adults (median age, 26 years), 83% of whom were born in Latin American countries where rubella vaccination was not routine. They were either employed in meatpacking plants or were their household contacts. Attack rates in the plants were high (14.4 per 1000 vs 0. 19 per 1000 for general county population); (2) 16 (19%), including 14 children (9 of whom were aged <12 months) and 2 parents, were US-born and non-Hispanic, who acquired the disease through contacts at 2 day care facilities (attack rate, 88.1 per 1000); and (3) 15 (18%) were young adults (median age, 22 years) whose major disease risk was residence in population-dense census tracts where meatpacking-related cases resided (R(2) = 0.343; P<.001); 87% of these persons were born in Latin America. Among pregnant women, susceptibility rates were 13% before the outbreak and 11% during and after the outbreak. Six (25%) of 24 susceptible women tested were seropositive for rubella IgM. Rubella vaccination rates were 90.2% for preschool children and 99.8% for school-aged children. CONCLUSIONS: A large rubella outbreak occurred among unvaccinated persons in a community with high immunity levels. Crowded working and living conditions facilitated transmission, but vaccine failure did not. Workplace vaccination could be considered to prevent similar outbreaks. JAMA. 2000;284:2733-2739.

Preparing for elimination of congenital Rubella syndrome (CRS): summary of a workshop on CRS elimination in the United States.

The goal of eliminating indigenous rubella and congenital rubella syndrome (CRS) in the United States in the near future is now within reach, because rubella incidence has been sustained at record-low levels since the mid-1990s. Effective prevention strategies to eliminate CRS and rubella require improvement in the surveillance of CRS and congenital rubella infection (CRI). The purpose of the workshop was to review rubella and CRS epidemiology, as well as current clinical, diagnostic, and laboratory practices, to determine whether new strategies are needed to achieve and document CRS elimination. Workshop participants agreed that surveillance for CRS must be strengthened, particularly through augmented laboratory capabilities, and the case definition for CRS must be revised to reflect the current scientific information available. Further studies of methods are needed to identify high-risk populations and geographic areas for rubella and CRS and to enhance identification of infants with CRS.

Changing epidemiology of congenital rubella syndrome in the United States.

To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome (CRS) and to identify missed opportunities for maternal vaccination, data from CRS cases reported to the National Congenital Rubella Syndrome Registry (NCRSR) from 1985 through 1996 were analyzed. Missed opportunities for maternal vaccination were defined as missed postpartum, premarital, and occupational opportunities, that is, times when rubella vaccination is recommended but was not given. From 1985 through 1996, 122 CRS cases were reported to the NCRSR. The most frequent CRS-related defect was congenital heart disease. Of the reported infants with CRS, 44% were Hispanic. Of 121 known missed opportunities for rubella vaccination among 94 mothers of infants with indigenous CRS, 98 (81%) were missed postpartum opportunities. CRS continues to occur in the United States. Hispanic infants have an increased risk of CRS. Missed opportunities for postpartum rubella vaccination were identified for 52% of indigenous CRS cases.

Nonperinatal nosocomial transmission of Candida albicans in a neonatal intensive care unit: prospective study.

Nosocomial Candida albicans infections have become a major cause of morbidity and mortality in neonates in neonatal intensive care units (NICUs). To determine the possible modes of acquisition of C. albicans in hospitalized neonates, we conducted a prospective study at Grady Memorial Hospital, Atlanta, Ga. Clinical samples for fungal surveillance cultures were obtained at birth from infants (mouth, umbilicus, and groin) and their mothers (mouth and vagina) and were obtained from infants weekly until they were discharged. All infants were culture negative for C. albicans at birth. Six infants acquired C. albicans during their NICU stay. Thirty-four (53%) of 64 mothers were C. albicans positive (positive at the mouth, n = 26; positive at the vagina, n = 18; positive at both sites, n = 10) at the time of the infant's delivery. A total of 49 C. albicans isolates were analyzed by restriction endonuclease analysis and restriction fragment length polymorphism analysis by using genomic blots hybridized with the CARE-2 probe. Of the mothers positive for C. albicans, 3 of 10 were colonized with identical strains at two different body sites, whereas 7 of 10 harbored nonidentical strains at the two different body sites. Four of six infants who acquired C. albicans colonization in the NICU had C. albicans-positive mothers; specimens from all mother-infant pairs had different restriction endonuclease and CARE-2 hybridization profiles. One C. albicans-colonized infant developed candidemia; the colonizing and infecting strains had identical banding patterns. Our study indicates that nonperinatal nosocomial transmission of C. albicans is the predominant mode of acquisition by neonates in NICUs at this hospital; mothers may be colonized with multiple strains of C. albicans simultaneously; colonizing C. albicans strains can cause invasive disease in neonates; and molecular biology-based techniques are necessary to determine the epidemiologic relatedness of maternal and infant C. albicans isolates and to facilitate determination of the mode of transmission.

A coccidioidomycosis outbreak following the Northridge, Calif, earthquake.

OBJECTIVE: To describe a coccidioidomycosis outbreak in Ventura County following the January 1994 earthquake, centered in Northridge, Calif, and to identify factors that increased the risk for acquiring acute coccidioidomycosis infection. DESIGN: Epidemic investigation, population-based skin test survey, and case-control study. SETTING: Ventura County, California. RESULTS: In Ventura County, between January 24 and March 15, 1994, 203 outbreak-associated coccidioidomycosis cases, including 3 fatalities, were identified (attack rate [AR], 30 cases per 100,000 population). The majority of cases (56%) and the highest AR (114 per 100,000 population) occurred in the town of Simi Valley, a community located at the base of a mountain range that experienced numerous landslides associated with the earthquake. Disease onset for cases peaked 2 weeks after the earthquake. The AR was 2.8 times greater for persons 40 years of age and older than for younger persons (relative risk, 2.8; 95% confidence interval [CI], 2.1-3.7; P<.001). Environmental data indicated that large dust clouds, generated by landslides following the earthquake and strong aftershocks in the Santa Susana Mountains north of Simi Valley, were dispersed into nearby valleys by northeast winds. Simi Valley case-control study data indicated that physically being in a dust cloud (odds ratio, 3.0; 95% CI, 1.6-5.4; P<.001) and time spent in a dust cloud (P<.001) significantly increased the risk for being diagnosed with acute coccidioidomycosis. CONCLUSIONS: Both the location and timing of cases strongly suggest that the coccidioidomycosis outbreak in Ventura County was caused when arthrospores were spread in dust clouds generated by the earthquake. This is the first report of a coccidioidomycosis outbreak following an earthquake. Public and physician awareness, especially in endemic areas following similar dust cloud-generating events, may result in prevention and early recognition of acute coccidioidomycosis.

Herpesvirus infections in persons infected with human immunodeficiency virus.

Herpesviruses are among the most common causes of infections of humans. Viruses in this family share the unique biological property of being able to establish latency and to recur. Furthermore, chronic excretion of virus is not uncommon. In the immunocompromised host, including persons with human immunodeficiency virus (HIV) infection, herpesvirus disease can be particularly severe, resulting in chronic, persistent, active infection and, in some cases, life-threatening disease. The most pathogenic of the herpesviruses in patients with AIDS include herpes simplex viruses, human cytomegalovirus, and varicella-zoster virus. Disease caused by Epstein-Barr virus, particularly opportunistic malignancies, has been recognized. A new herpesvirus that is associated with Kaposi's sarcoma was recently described. On the other hand, disease caused by human herpesviruses 6 and 7 in persons infected with HIV remains to be unequivocally recognized. Prevention of exposure to herpesviruses, disease, and recurrence requires different measures than those for some of the other opportunistic infections in HIV-infected patients; this is because herpesvirus disease develops in most of these individuals as a result of reactivation rather than primary infection. Thus, approaches to the prevention and control of herpesvirus infections must be individualized according to both the type of virus as well as the type of infection (i.e., primary or recurrent). We discuss recommended measures for the prevention and control of these infections.

Opportunistic candidal infections in patients infected with human immunodeficiency virus: prevention issues and priorities.

Mucosal candidiasis (oropharyngeal, esophageal, and vulvovaginal candidiasis) has been among the most prominent opportunistic infections in persons infected with human immunodeficiency virus (HIV). Esophageal candidiasis, an AIDS-defining illness, accounted for 15% of the AIDS-defining illnesses in adults and adolescents diagnosed in the United States through 1992. The diagnosis of oropharyngeal and vaginal candidiasis is based on clinically consistent signs and symptoms and a positive culture or a positive gram, KOH, or calcofluor stain, whereas the diagnosis of esophageal and pulmonary candidiasis is based on histopathology. Although a prospective controlled trial showed that prophylaxis with fluconazole can reduce the risk of mucosal candidiasis in patients with advanced HIV disease, routine primary prophylaxis is not recommended because of the effectiveness of therapy for acute disease, the low mortality associated with mucosal candidiasis, the potential for development of drug-resistant candidal infection, and the cost of prophylaxis. The probability of recurrences increases as CD4 counts decline. Nonetheless, many experts do not recommend chronic prophylaxis to prevent recurrent oropharyngeal and vulvovaginal candidiasis, for the same reasons that primary prophylaxis is not recommended. However, if recurrences are frequent or severe following documented esophageal candidiasis, long-term suppressive therapy with fluconazole should be considered.

Treatment options for vulvovaginal candidiasis, 1993.

Vulvovaginal candidiasis (VVC), the second most common form of vaginitis, particularly affects women of childbearing age. Since the 1970s, several new agents have become available for the treatment of VVC. This review focuses on options for the treatment of this condition, critically evaluating the relevant published studies. For the treatment of acute episodes of VVC in nonpregnant women, several topical and oral antifungal agents are clinically and mycologically effective. Topical agents should be considered the first line of therapy; however, oral agents are sometimes associated with better compliance among patients. For acute episodes in pregnant women, a topical agent is the treatment of choice. Until data become available on the treatment of VVC in women infected with human immunodeficiency virus (HIV), the same approach as that used for women without HIV infection should be considered as previously written. For recurrent VVC, the optimal maintenance therapy has not yet been established; however, administration of low-dose oral ketoconazole (100 mg/d) has proven effective. Well-designed studies of the best therapy for VVC in women with HIV infection and for recurrent VVC are urgently needed.