Terri B. Hyde

Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infections are a leading cause of sensorineural hearing loss (SNHL) and neurological impairment. Congenital transmission of CMV can occur with maternal primary infection, reactivation, or reinfection during pregnancy. We reviewed studies of CMV shedding in bodily fluids (defined as CMV detected by culture or CMV DNA detected by polymerase chain reaction). Following diagnosis at birth, children with congenital CMV infection exhibited the highest prevalences of CMV shedding (median = 80%, number of sample population prevalences [N] = 6) and duration of shedding, with a steep decline by age five. Healthy children attending day care shed more frequently (median = 23%, N = 24) than healthy children not attending day care (median = 12%, N = 11). Peak shedding prevalences in children occurred at 1–2 years of age, confirming that young children are the key transmission risk for pregnant women. CMV shedding among children was more prevalent in urine specimens than in oral secretions (median prevalence difference = 11.5%, N = 12). Adults with risk factors such as STD clinic attendance had higher shedding prevalences (median = 22%, N = 20) than adults without risk factors (median = 7%, N = 44). In adults with risk factors, CMV was shed more frequently in urine; in adults without risk factors genital shedding was most common. The prevalence of CMV shedding in nine sample populations of pregnant women increased with advancing gestation. In seven sample populations of children with congenital CMV infection, higher viral load at birth was consistently associated with an elevated risk of SNHL. Higher CMV viral load at birth also consistently correlated with the presence of symptoms of congenital CMV at birth. Published 2011. This article is a US Government work and is in the public domain in the USA.

Impact of a Conjugate Vaccine on Community-Wide Carriage of Nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.

Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV

Congenital CMV infection is caused by in utero mother‐to‐fetus transmission and is a leading cause of birth defects and developmental disabilities. The highest risk of disability is to children born to women who have a primary infection during pregnancy, which can be detected by measuring seroconversion. We reviewed studies that reported rates of CMV seroconversion in different populations. Among pregnant women, annual seroconversion rates typically ranged from 1 to 7% (summary annual rate = 2.3%, 95% CI = 2.1–2.4%). Healthcare workers, including those caring for infants and children, had seroconversion rates similar to pregnant women (summary annual rate = 2.3%, 95% CI = 1.9–2.9%). Among day‐care providers, seroconversion rates ranged from 0 to 12.5% (summary annual rate = 8.5%, 95% CI = 6.1–11.6%). Parents whose child was not shedding CMV were much less likely to seroconvert (summary annual rate = 2.1%, 95% CI = 0.3–6.8%) than were parents who had a child shedding CMV (summary annual rate = 24%, 95% CI = 18–30%). Nevertheless, over the course of a year, most parents exposed to a CMV‐shedding child do not become infected. Other groups with elevated risk included families with a CMV‐shedding member, female minority adolescents and women attending sexually transmitted disease clinics. The relatively low rate of CMV seroconversion in most populations is encouraging for behavioural interventions and for vaccine strategies attempting to prevent infection during pregnancy. Published in 2010 by John Wiley & Sons, Ltd.

Impact of conjugate vaccine on transmission of antimicrobial-resistant Streptococcus pneumoniae among Alaskan children.

Background: The impact of heptavalent pneumococcal conjugate vaccine (PCV7) on transmission of antimicrobial-resistant Streptococcus pneumoniae is an important concern for countries considering PCV7 introduction. Methods: Every winter from 2000 to 2004, as PCV7 was routinely introduced, we obtained nasopharyngeal swabs for pneumococcal culture, serotyping, and susceptibility testing from 150 children aged 3–59 months at each of 3 Anchorage, Alaska clinics. We assessed risk factors for pneumococcal carriage, including vaccination status and antimicrobial use. Results: Between 2000 and 2004, 2250 nasopharyngeal swabs from 2061 infants and children were collected. The proportion of children receiving ≥1 PCV7 vaccination increased from 0 to 89%, whereas overall pneumococcal carriage remained stable (38% versus 41%, respectively). Among S. pneumoniae carriers, we observed declines in carriage of PCV7 serotypes (from 54% to 10%, P < 0.01) and trimethoprim-sulfamethoxazole nonsusceptible strains (44% to 16%, P < 0.01), but not in PCN-nonsusceptible strains (36% versus 37%). Among PCN-nonsusceptible types, the proportion of serotype 19A strains increased from 10% to 32% (P = 0.0002). Recent β-lactam use was stable throughout the period (29% overall), whereas trimethoprim-sulfamethoxazole use declined from 6% to 2% (P = 0.02). Conclusions: PCV7 vaccination in the first 5 years did not affect overall pneumococcal carriage, but was associated with a shift in serotype distribution from PCV7 types to non-PCV7 types. With persistent pressure of some antimicrobials, reductions in carriage of antimicrobial nonsusceptible PCV7 types may be offset by increases in carriage of nonsusceptible non-PCV7 types.

Laboratory characterization of measles virus infection in previously vaccinated and unvaccinated individuals.

Waning immunity or secondary vaccine failure (SVF) has been anticipated by some as a challenge to global measles elimination efforts. Although such cases are infrequent, measles virus (MeV) infection can occur in vaccinated individuals following intense and/or prolonged exposure to an infected individual and may present as a modified illness that is unrecognizable as measles outside of the context of a measles outbreak. The immunoglobulin M response in previously vaccinated individuals may be nominal or fleeting, and viral replication may be limited. As global elimination proceeds, additional methods for confirming modified measles cases may be needed to understand whether SVF cases contribute to continued measles virus (MeV) transmission. In this report, we describe clinical symptoms and laboratory results for unvaccinated individuals with acute measles and individuals with SVF identified during MeV outbreaks. SVF cases were characterized by the serological parameters of high-avidity antibodies and distinctively high levels of neutralizing antibody. These parameters may represent useful biomarkers for classification of SVF cases that previously could not be confirmed as such using routine laboratory diagnostic techniques.

Rotavirus vaccines: current status and future considerations.

Rotavirus is the leading cause of severe diarrhea among children <5 years worldwide. Currently licensed rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction.

Seroprevalence of Measles Antibody in the US Population, 1999–2004

BACKGROUND Endemic measles transmission was declared eliminated in the United States in 2000. To ensure that elimination can be maintained, high population immunity must be sustained and monitored. Testing for measles antibody was included in the National Health and Nutrition Examination Survey (NHANES), a nationally representative survey, conducted during 1999-2004. METHODS A measles-specific immunoassay was used to measure the seroprevalence of measles antibody in NHANES participants 6-49 years of age. For analysis, participants were grouped by birth cohort. RESULTS During 1999-2004, the rate of measles seropositivity in the population overall was 95.9% (95% confidence interval [CI], 95.1%-96.5%). The highest seroprevalence of measles antibody was in non-Hispanic blacks (98.6% [95% CI, 98.0%-99.1%]). Those born during 1967-1976 had significantly lower levels of measles antibody (92.4% [95% CI, 90.8%-93.9%]) than did the other birth cohorts. Independent predictors of measles seropositivity in the 1967-1976 birth cohort were non-Hispanic/black race/ethnicity, more than a high school education, having health insurance, and birth outside the United States. CONCLUSIONS Measles seropositivity was uniformly high in the US population during 1999-2004. Nearly all population subgroups had evidence of measles seropositivity levels greater than the estimated threshold necessary to sustain measles elimination. Non-Hispanic whites and Mexican Americans born during 1967-1976 had the lowest measles seropositivity levels and represent populations that might be at increased risk for measles disease if the virus were reintroduced into the United States.

Experiences with provider and parental attitudes and practices regarding the administration of multiple injections during infant vaccination visits: lessons for vaccine introduction.

INTRODUCTION An increasing proportion of childhood immunization visits include administration of multiple injections. Future introduction of vaccines to protect against multiple diseases will further increase the number of injections at routine immunization childhood visits, particularly in developing countries that are still scaling up introductions. Parental and healthcare provider attitudes toward multiple injections may affect acceptance of recommended vaccines, and understanding these attitudes may help to inform critical decisions about vaccine introduction. METHODS We conducted a systematic review of the literature to examine factors underlying reported parental and healthcare provider concerns and practices related to administration of multiple injections during childhood vaccination visits. RESULTS Forty-four articles were identified; 42 (95%) were from high income countries, including 27 (61%) from the USA. Providers and parents report concerns about multiple injections, which tend to increase with increasing numbers of injections. Common parental and provider concerns included apprehension about the pain experienced by the child, worry about potential side effects, and uncertainty about vaccine effectiveness. Multiple studies reported that a positive provider recommendation to the parent and a high level of concern about the severity of the target disease were significantly associated with parental acceptance of all injections. Providers often significantly overestimated parental concerns about multiple injections. DISCUSSION Providers may play a critical role in the decision for a child to receive all recommended injections. Their overestimation of parental concerns may lead them to postpone recommended vaccinations, which may result in extra visits and delayed vaccination. More research is needed on interventions to overcome provider and parental concern about multiple injections, particularly in developing countries.

Azithromycin Prophylaxis during a Hospital Outbreak of Mycoplasma pneumoniae Pneumonia

Outbreaks of Mycoplasma pneumoniae (MP) in closed communities can have a high attack rate and can last several months. Azithromycin chemoprophylaxis has not been evaluated as a means of limiting transmission. This randomized, double-blinded placebo-controlled trial of azithromycin was conducted among asymptomatic hospital employees during an MP outbreak. Oropharyngeal swabs were obtained for detection of MP by polymerase chain reaction, and questionnaires were administered to assess clinical illness. Of the 147 employees who were enrolled, 73 received azithromycin and 74 received placebo. Carriage was similar within and between groups at weeks 1 and 6 (9.6% vs. 6.7% and 10.3% vs. 13.2%, respectively). Four episodes of clinically significant respiratory illness occurred in the azithromycin group versus 16 episodes in the placebo group (protective efficacy, 75%; 95% confidence interval, 28%-91%). Use of azithromycin prophylaxis in asymptomatic persons during an MP outbreak in a closed setting may be of value in reducing clinical illness.

Laboratory confirmation of measles in elimination settings: experience from the Republic of the Marshall Islands, 2003

OBJECTIVE To highlight the complications involved in interpreting laboratory tests of measles immunoglobulin M (IgM) for confirmation of infection during a measles outbreak in a highly vaccinated population after conducting a mass immunization campaign as a control measure. METHODS This case study was undertaken in the Republic of the Marshall Islands during a measles outbreak in 2003, when response immunization was conducted. A measles case was defined as fever and rash and one or more of cough, coryza or conjunctivitis. Between 13 July and 7 November 2003, serum samples were obtained from suspected measles cases for serologic testing and nasopharyngeal swabs were taken for viral isolation by reverse transcriptase polymerase chain reaction (RT-PCR). FINDINGS Specimens were collected from 201 suspected measles cases (19% of total): of the ones that satisfied the clinical case definition, 45% were IgM positive (IgM+) and, of these, 24% had received measles vaccination within the previous 45 days (up to 45 days after vaccination an IgM+ result could be due to either vaccination or wild-type measles infection). The proportion of IgM+ results varied with clinical presentation, the timing of specimen collection and vaccination status. Positive results on RT-PCR occurred in specimens from eight IgM-negative and four IgM+ individuals who had recently been vaccinated. CONCLUSION During measles outbreaks, limiting IgM testing to individuals who meet the clinical case definition and have not been recently vaccinated allows for measles to be confirmed while conserving resources.