The California Pertussis Epidemic 2010: A Review of 986 Pediatric Case Reports From San Diego County.

BACKGROUND: The California Department of Public Health (CDPH) declared a pertussis epidemic on 23 June 2010. More cases were reported in 2010 (9146) than in any year since 1947. We describe the characteristics of pertussis epidemiology and disease from 986 reported cases in children in San Diego County (population 3.2 million). METHODS: Descriptive statistics were abstracted from CDPH pertussis case report forms that were completed by public health nurses investigating reports of positive laboratory results for pertussis and reports of illnesses compatible with pertussis. RESULTS: Of 1144 reported adult and pediatric cases, 753 (66%) were confirmed and 391 were probable/suspect. Children aged <19 years comprised 86% of all reported cases in San Diego County; of these, 22% were aged 11-18 years, 29% were aged 6-10 years, 27% were aged 1-5 years, and 22% were aged <1 year (with 70% aged <6 months). Case rates were highest in infants aged <6 months (651 per 100 000 population). Of those aged >1 year, the highest attack rates were in preschool children aged 1-5 years (114 per 100 000) and elementary school children aged 6-10 years (141 per 100 000). Of 51 children hospitalized, 82% were aged <6 months; 2 deaths occurred in these young infants. Paroxysmal cough was noted in over 70% of children in all age groups; post-tussive vomiting occurred in 36% (aged 11-18 years) to 57% (aged <6 months) of children. CONCLUSIONS: Pertussis vaccine efficacy may decrease more rapidly than previously believed, facilitating spread of pertussis in elementary school-aged children. The highest case rates and the only mortality occurred in infants aged <6 months.

Enterovirus infections: diagnosis and treatment.

Enterovirus infections are common in both children and adults and range from benign short-lived febrile illnesses to life-threatening infections. Recent developments in nucleic acid amplification techniques now allow the rapid and sensitive diagnosis of enterovirus infections, which in turn can lead to improvements in patient management that shorten hospitalizations and reduce costs. New antiviral drugs have been developed that inhibit enterovirus replication, and early clinical trials of these compounds suggest that effective therapy for enterovirus infections is now possible.

The cost to immunize during well-child visits.

The objective of this study was to determine the incremental labor costs or opportunity costs associated with the provision of immunizations in ambulatory care settings. A time and motion analysis of primary care health visits by pediatric patients was performed in 10 community clinics and 5 private primary care practices. These clinics and practices were located in areas designated as Health Professional Shortage Areas, with traditionally low immunization coverage rates and other unmet primary care needs. The outcome measure for this study was the comparative duration of the visit, contrasting well-child visits during which immunization was given with well-child visits during which no immunization was given. The results suggested that immunizations present an opportunity cost during well-child visits. The average time of patient-provider contact found in this study supports other findings showing that this time is now significantly longer than that reported in the past. In order for providers to comply with increased recommendations and requirements for preventive health care services, the allotted visit time, capitation rates, and overall clinic system effectiveness need to be reexamined.

Impact of a diagnostic cerebrospinal fluid enterovirus polymerase chain reaction test on patient management.

CONTEXT: Enterovirus (EV) infection, the most common cause of aseptic meningitis, can be rapidly diagnosed with an EV-specific reverse transcriptase polymerase chain reaction (EV-PCR) test. However, no studies have examined EV-PCR in a clinical context in which it is routinely used. OBJECTIVE: To determine the impact of EV-PCR testing on diagnosis and clinical management of suspected aseptic meningitis cases. DESIGN AND SETTING: Retrospective review of electronic medical records from a 220-bed tertiary care pediatric medical center in San Diego, Calif. PATIENTS: A total of 276 pediatric patients for whom a diagnostic EV-PCR test was performed during the calendar year 1998. MAIN OUTCOME MEASURES: Clinical parameters such as length of stay, medication use, and ancillary test use. RESULTS: One hundred thirty-seven patients (49.6%) had a positive cerebrospinal fluid EV-PCR result. Enterovirus-positive patients with results available before hospital discharge (n=95) had significantly fewer ancillary tests performed (26% vs 72% with at least 1 test performed; P<.001), received intravenous antibiotics for less time (median, 2.0 vs 3.5 days; P<.001), and had shorter hospital stays (median, 42 vs 71.5 hours; P<.001) than EV-negative patients (n=92). A positive EV-PCR result was associated with more rapid hospital discharge (median EV-PCR-to-discharge time, 5.2 hours) compared with a negative result (median EV-PCR-to-discharge time, 27.4 hours; P<.001). CONCLUSIONS: Our results suggest that a positive EV-PCR result may affect clinical decision making and can promote rapid discharge of patients, and that unnecessary diagnostic and therapeutic interventions can be reduced by use of EV-PCR testing. JAMA. 2000;283:2680-2685.

Effect of inhibitors in clinical specimens on Taq and Tth DNA polymerase-based PCR amplification of influenza A virus.

Fifteen randomly selected nasopharyngeal (NP) swab specimens (culture-negative for influenza A virus) were spiked with influenza A virus and the nucleic acids were extracted and subjected to PCR amplification with Thermus aquaticus (Taq) and T. thermophilus (Tth) DNA polymerases. Products of the expected size, and giving equivalent band intensities, were obtained from four specimens with both polymerases. Fox six specimens, less products were obtained with Taq DNA polymerase than with Tth DNA polymerase. Products were detected from five NPs only by PCR with Tth DNA polymerase. The transport medium and the calcium alginate swab fibre of the specimens were shown not to be the source of the inhibitors. The incorporation of 32P-dCTP into cDNA, and the yield of PCR products of cDNA made from control RNA template (purified from H2O spiked virus suspension) were decreased in the presence of inhibitory extracts, showing that both the reverse transcription (RT) and PCR steps in amplification with Taq DNA polymerase were sensitive to the inhibitors. In contrast, Tth DNA polymerase was more resistant to the inhibitors and viral nucleic acid from all the specimens examined could be amplified and detected in a single step by RT-PCR with Tth DNA polymerase.

Evaluation of PCR assays in presence of antibody to thermostable DNA polymerases for detection of microbial agents: avoiding false negative results for specimen containing low-titer agent.

The serial low-titer specimens of Influenza A virus and Adeno virus type 7 were tested for the presence of virus specific genes by PCR based on Tth DNA polymerase and by that based on Taq DNA polymerase, in the absence and presence of antibody to the respective DNA polymerases. Increased product DNA synthesis and higher sensitivity of detection were observed in the presence of antibody compared to those in the absence of antibody. 10- to 100- fold lower titer specimen of Influenza A virus and 10-fold lower titer specimen of Adeno virus could be detected in the presence of antibody than those detected in the absence of antibody to the appropriate DNA polymerase, in a PCR.

Weekly oral azithromycin as prophylaxis for agents causing acute respiratory disease.

Since the 1950s the U.S. military has used intramuscular injections of benzathine penicillin G (BPG) to control outbreaks of respiratory disease. In an effort to find an alternative prophylaxis, a randomized field trial was conducted among 1,016 male U.S. Marine trainee volunteers at high risk for respiratory disease. Participants were evaluated for evidence of acute respiratory infection by serological tests on pretraining and posttraining sera (63 days apart). Oral azithromycin prophylaxis (500 mg/w) outperformed BPG, preventing infection from Streptococcus pyogenes (Efficacy [E] = 84%; 95% confidence interval [CI], 63%-93%), Streptococcus pneumoniae (E = 80%; 95% CI, 50%-92%), Mycoplasma pneumoniae (E = 64%; 95% CI, 25%-83%), and Chlamydia pneumoniae (E = 58%; 95% CI, 15%-79%) in comparison with results in a no-treatment group. Azithromycin group subjects reported few side effects and less respiratory symptoms than the BPG and no-treatment groups. According to serological tests, oral azithromycin is an effective alternative prophylaxis to BPG for military populations.

Detection of Bordetella pertussis and respiratory synctial virus in air samples from hospital rooms.

OBJECTIVE: To evaluate the distribution of Bordetella pertussis and respiratory syncytial virus (RSV) in the hospital setting. DESIGN: Air samples were collected using filters in the hospital rooms of 12 children with pertussis and 27 children with RSV infection. Material eluted from these filters was subjected to RSV- and B pertussis-specific polymerase chain reaction (PCR) amplification. SETTING: Patients were hospitalized in private rooms in one of two referral centers, a university teaching hospital and a university-affiliated private children's hospital. PATIENTS: 12 children (16 days-3 years of age) with documented pertussis infection and 27 patients (10 days-7 years of age) with documented RSV infection. RESULTS: B pertussis DNA was detected in 7 (58%) of 12 rooms housing pertussis patients and in 16 (25%) of 63 total samples. B pertussis DNA was detected as far as 4 m away from the patient's bedside. The detection of B pertussis DNA in air samples did not change over the short duration of hospitalization. RSV RNA was detected in 17 (63%) of 27 rooms housing RSV-infected patients and in 32 (22%) of 143 total samples. RSV RNA was detected at distances as far as 7 m from the patient's bedside and for up to 7 days of hospitalization. CONCLUSIONS: Using PCR-based detection methods, B pertussis DNA and RSV RNA both can be detected in air samples from the hospital rooms of infected patients. Both can be detected at large distances from a patient's bedside in a minority of cases. These detection methods are suitable for further studies of control measures used to contain nosocomial infections caused by both B pertussis and RSV.

Reliability of a history of previous varicella infection in adults.

CONTEXT: Apparent second episodes of varicella are reported in immunocompetent hosts, but laboratory confirmation of prior immune status has rarely been possible. OBJECTIVE: To evaluate adult patients with varicella who claimed to have had previous varicella to determine whether they had true second episodes or primary cases with inaccurate clinical histories. DESIGN: Adult subjects with varicella who enrolled in an antiviral treatment trial were interviewed about a history of varicella. The clinical course of varicella was documented prospectively in all subjects. Serum samples that predated the acute illness were obtained from the US Navy's central serum storage facility for subjects who reported a previous episode of varicella. These stored samples were tested in parallel by enzyme-linked immunosorbent assay, latex agglutination, and Western blot for IgG antibodies to varicella-zoster virus (VZV). PARTICIPANTS: Twenty military personnel with varicella and a history of the disease. SETTING: A military hospital in San Diego, Calif. MAIN OUTCOME MEASURE: Presence or absence of antibodies to VZV. RESULTS: Twenty (10.8%) of 184 adults with serologically confirmed acute varicella reported a prior history of varicella. The clinical course of these 20 patients did not differ from those with no history of varicella. Serum samples that had been collected a mean of 12.4 months (median, 12 months; range, 3 days to 34 months) before the incident episode were available for 19 subjects. All 19 serum samples lacked IgG antibodies to VZV. CONCLUSION: A history of previous varicella infection in adults with varicella may not be reliable. True second episodes of varicella are probably rare in immunocompetent adults.

Safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine and PedvaxHIB vaccines in healthy children twelve to eighteen months old. The MMRV Study Group.

OBJECTIVE: To determine the safety and immunogenicity of concurrent administration of measles-mumps-rubella-varicella vaccine (MMRV) and PedvaxHIB (Haemophilus influenzae type b conjugate vaccine) vs. M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later. DESIGN: Healthy children, 12 to 18 months of age, were randomly assigned to two groups to receive (1) MMRV and PedvaxHIB given concurrently or (2) M-M-R II and PedvaxHIB followed by an optional dose of VARIVAX 6 weeks later. SUBJECTS: The study group included 294 healthy children, ages 12 to 18 months, with a negative history of measles, mumps, rubella and varicella. MAIN OUTCOME MEASURES: The seroconversion rate and magnitude of antibody responses when MMRV was given concurrently with PedvaxHIB compared with the antibody responses when VARIVAX was given 6 weeks after M-M-R II and PedvaxHIB. RESULTS: Healthy children, 12 to 18 months of age, who received MMRV and PedvaxHIB concurrently showed immune responses similar to those in the control group who received M-M-RII vaccine with PedvaxHIB followed by VARIVAX 6 weeks later. Antibody titers for varicella were significantly lower when MMRV was administered than when varicella vaccine was given separately (0.712-fold difference, P = 0.028). No vaccine-related serious adverse reactions were reported, and no clinically significant differences were seen in the safety profiles of the two treatment groups. CONCLUSIONS: There were no statistically significant differences in the seroconversion rates between the two treatment groups for any of the antigens tested at 6 weeks and 1 year. Significantly lower geometric mean titers for varicella were noted in the group who received MMRV compared to VARIVAX given alone. Six-week seroconversion rates, persistence of immune responses at 1 year and the frequency of local and systemic reactions were comparable when MMRV was administered with PedvaxHIB compared with M-M-R II and PedvaxHIB followed by VARIVAX 6 weeks later.

Optimized PCR amplification of influenza A virus RNA using Tth DNA polymerase, incorporating uracil N glycosylase (UNG) in a single tube reaction.

An optimized reaction condition for amplification of influenza A virus RNA, by thermus thermophilus (Tth) DNA polymerase-based PCR, incorporating uracil N glycosylase (UNG) and dUTP in the reaction has been determined. dUTP could not be substituted for all dTTP sites when UNG was present in the reaction. The relative concentration of dUTP and dTTP has been optimized for allowing amplification of the target RNA. It has been verified that the amplified product DNA had sufficient dUTP and was digestable by UNG. Using the optimized reaction condition, influenza A virus-specific DNA fragment could be amplified and detected in 15 of 15 culture positive (for influenza A virus) nasopharyngeal specimens.

Treatment of adult varicella with sorivudine: a randomized, placebo-controlled trial.

The antiviral and clinical efficacy of sorivudine in adults with varicella was evaluated in a double-blind, placebo-controlled randomized trial. A total of 186 patients were hospitalized for isolation and treatment within 96 h of rash onset. The diagnosis of varicella was confirmed in 184 patients with paired sera. Patients were randomly assigned to receive 10 or 40 mg of sorivudine or an identical placebo once a day for 5 days. Treatment with 40 mg of sorivudine (compared with placebo) shortened the mean time to 100% crusting from 6.6 to 5.8 days (P = .004) and reduced the mean days that new lesion formed from 3.9 to 3.1 (P = .014). Mean days of cutaneous viral shedding were reduced from 3.3 in the placebo group to 2.6 in the 40-mg sorivudine group (P = .002). The effectiveness of therapy was not affected by the duration of rash before initiation of therapy. Sorivudine is a promising new agent for the treatment of varicella-zoster virus infections.

Rapidly recurrent enteroviral meningitis in non-immunocompromised infants caused by different viral strains.

Repeated episodes of enteroviral meningitis occurring within a 1-month period in two non-immunocompromised infants were investigated using molecular techniques to distinguish persistent or recrudescent infection from new infection. Viral RNA from cerebrospinal fluid was amplified by polymerase chain reaction, cloned, and the nucleic acid sequences determined. This analysis demonstrated that both infants had recurrent episodes of meningitis caused by new infection with a distinct enterovirus strain. The molecular methods that were employed should prove useful in similar clinical settings as well as for the study of enteroviral outbreaks. These cases also illustrate the potential for rapid reinfection of infants with different viruses of the same genus.

Rhabdomyolysis associated with acute varicella infection.

We report two cases of intense, generalized rhabdomyolysis complicating varicella-zoster virus (VZV) infections, one in an adolescent and one in a young adult male. In both cases, myoglobinuria and weakness of large muscle groups developed within 5 days of the onset of vesicular lesions. A muscle biopsy from one of the individuals showed muscle fiber necrosis in the absence of acute inflammatory infiltrates or vasculitis. Culture of the muscle biopsy specimen for VZV was negative; however, the VZV genome was detected by the polymerase chain reaction. Both patients recovered fully after treatment with hydration therapy alone.

Diagnosis of enteroviral meningitis by using PCR with a colorimetric microwell detection assay.

A 5-h, user-friendly PCR assay for the diagnosis of enteroviral meningitis was developed. Reverse transcription and amplification were performed in a one-step reaction using rTth polymerase. Carryover contamination was prevented with dUTP and uracil N-glycosylate. Detection was performed colorimetrically on a microwell titer plate. Sensitivity, specificity, positive predictive value, and negative predictive value were 94.7, 97.4, 94.7, and 97.4%, respectively.

Enteroviral meningitis in infancy: potential role for polymerase chain reaction in patient management.

STUDY OBJECTIVE: To evaluate the performance characteristics and potential clinical utility of a polymerase chain reaction (PCR) assay for enteroviral RNA in comparison to viral culture in infants under 3 months of age with meningitis. SPECIMENS AND TESTING: Specimens were obtained from a collection of cerebrospinal fluid specimens from infants under 3 months of age (excluding those in the neonatal intensive care unit) undergoing lumbar puncture at St. Louis Children's Hospital during a 12-month period. Those tested by PCR included all 27 with pleocytosis, 8 others from infants without pleocytosis but from whom an enterovirus was cultured, and 10 from infants who did not have pleocytosis and had a negative viral culture of cerebrospinal fluid. Viral cultures were performed at the discretion of physicians caring for individual patients. RESULTS: PCR was positive for enteroviral RNA on cerebrospinal fluid (CSF) specimens from 11 of 12 patients with definite or probable enteroviral meningitis, as well as on 6 of 13 with possible enteroviral meningitis, and was negative on all 10 with absence of pleocytosis and negative enteroviral cultures. CSF viral cultures were negative in 6 of the patients in whom PCR was positive. Viral cultures had minimal impact on patient management. In contrast, under study assumptions, PCR could have saved an average of 1.2 days of hospitalization per patient in the 27 patients with CSF pleocytosis. CONCLUSIONS: Enterovirus PCR performed on CSF is a sensitive and specific method for the diagnosis of enteroviral meningitis. This method has the potential for improving the accuracy of diagnosis in young infants and for saving costs by allowing earlier diagnosis and discharge from the hospital when clinically appropriate.

Diagnosis of enteroviral central nervous system infection by polymerase chain reaction during a large community outbreak.

Enteroviruses are common causes of localized and systemic infection in patients of all ages and are the most frequent cause of epidemic aseptic meningitis in the United States. We have developed a polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) for rapid diagnosis of enteroviral meningitis. This assay was applied to 257 CSF specimens during a large community outbreak of enterovirus disease; 109 (97%) of 112 enterovirus culture-positive CSF samples contained enterovirus RNA. In addition 35 (66%) of 53 samples from patients with suspected central nervous system disease with negative or no CSF viral cultures were positive by enterovirus PCR. The enterovirus PCR detected 13 different enterovirus serotypes. PCR results are available within 24 hours compared with a mean of 6.8 days for enterovirus culture. The clinical characteristics of 141 patients with enterovirus central nervous system disease are presented. This study demonstrates the usefulness of enterovirus PCR for the rapid diagnosis of enterovirus central nervous system disease and the potential for PCR tests to shorten hospitalization.