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Andrew T Pavia

Publications and source records attributed to Andrew T Pavia.

16 recordsLinked to original sources

Hidden Burden of a Measles Outbreak Revealed by Genomic and Transmission Models.

Declining childhood vaccination rates have fueled a resurgence of measles in the United States. Surveillance systems may not accurately measure the true extent of outbreaks. As of May 2026, the largest ongoing measles outbreak in the United States originated along the Utah-Arizona border in a community with high vaccine exemption rates and limited engagement with healthcare systems, leading to incomplete testing and reporting. To quantify the true outbreak size, we used two independent approaches with complementary data sources: a phylodynamic analysis and an agent-based model. Both methods found significant underreporting, estimating the true outbreak size to be 3.1- to 4.8-fold larger than reported, with confirmed cases representing only 20.96%-32.5% total infections. These findings suggest that substantial underreporting of measles occurs, especially in tight knit communities. The use of complementary analytical approaches to evaluate completeness of reporting can reveal the extent of measles transmission and aid control efforts.

Journal Article↗

Antiviral management of seasonal and pandemic influenza.

The goals of antiviral treatment for influenza are to decrease symptoms and functional disability and, more important, to decrease associated complications, hospitalizations, and mortality. Four drugs have been approved for treatment of and prophylaxis against influenza in the United States, but they are underutilized. The M2 ion channel inhibitors amantadine and rimantadine are effective for prophylaxis, and they decrease the duration of symptoms if they are used for early treatment of influenza A. The rapid emergence of resistance during therapy and, recently, the circulation of resistant H3N2 viruses in the community have decreased the usefulness of these M2 ion channel inhibitors. Early therapy with neuraminidase (NA) inhibitors, either oseltamivir or zanamivir, reduces the duration of symptoms, the duration of disability, and the risk of lower respiratory tract complications. Oseltamivir has been shown to decrease antibiotic use, the number of hospitalizations, and, probably, the risk of death after influenza. NA inhibitors might provide substantial benefits in the treatment of pandemic influenza, with reductions in the numbers of hospitalizations and deaths occurring if such treatment (1) is made available in sufficient time, through rapid distribution, and (2) is available in sufficient quantities as a result of stockpiling. Both of the aforementioned NA inhibitors are highly effective for prophylaxis. Geographically targeted mass chemoprophylaxis might contain the spread of a pandemic virus, but multiple hurdles to successful implementation exist. Resistance to oseltamivir occurs with the H274Y variant in viruses that contain N1; however, to date, such variants have been less fit, have not been transmitted from person to person, and have retained susceptibility to zanamivir. Alternative agents and approaches, including parenteral and combination therapy, for the treatment of influenza are needed in the near and long term.

Amantadine↗

Seasonal and pandemic influenza: recommendations for preparedness in the United States.

There is a continued need to improve the state of preparedness for a potential influenza pandemic in the United States despite the publication of a pandemic influenza plan by the Department of Health and Human Services. Of particular importance are the sense of urgency for a coordinated response plan, an allocation of adequate funds to deal with this issue, and the need for a national leader to coordinate the development and execution of a national plan, including its relationship to the control of seasonal influenza. In addition, an infrastructure needs to be established in the United States to enable the rapid development and large-scale production of a safe and effective vaccine for new influenza strains; methods to treat influenza pneumonia need to be evaluated; a coordinated public health response needs to be defined; a nationally developed blueprint to deal with logistics of pandemic prevention is required; and there is a need to establish reliable communication systems on a national and local basis, to provide accurate information to the lay public, health care workers, and the agricultural sector.

Antiviral Agents↗

Predictors of fatality in postdiarrheal hemolytic uremic syndrome.

OBJECTIVES: Describe the cause of deaths among patients with postdiarrheal hemolytic uremic syndrome (HUS) and identify predictors of death at the time of hospital admission. METHODS: Case-control study of 17 deaths among patients with HUS identified from the Intermountain HUS Patient Registry (1970-2003) compared against all nonfatal cases. RESULTS: Of the 17 total deaths, 15 died during the acute phase of disease. Two died because treatment was withdrawn based on their preexisting conditions, and 1 died because of iatrogenic cardiac tamponade; they were excluded from analysis. Brain involvement was the most common cause of death (8 of 12); congestive heart failure, pulmonary hemorrhage, and hyperkalemia were infrequent causes. Presence of prodromal lethargy, oligoanuria, or seizures and white blood cell count (WBC) >20 x 10(9)/L or hematocrit >23% on admission were predictive of death. In multivariate analysis, elevated WBC and elevated hematocrit were independent predictors. The combination of prodromal dehydration, oliguria, and lethargy and admission WBC values >20 x 10(9)/L and hematocrit >23% appeared in 7 of the 12 acute-phase deaths. CONCLUSIONS: Diarrheal HUS patients presenting with oligoanuria, dehydration, WBC >20 x 10(9)/L, and hematocrit >23% are at substantial risk for fatal hemolytic uremic syndrome. Such individuals should be referred to pediatric tertiary care centers.

Cause of Death↗

Epidemiology, complications, and cost of hospitalization in children with laboratory-confirmed influenza infection.

BACKGROUND: Influenza causes significant morbidity among children. Previous studies used indirect case ascertainment methods with little cost data. We sought to measure the burden of laboratory-confirmed influenza from hospitalized children. METHODS: We conducted a retrospective cohort study during 3 viral seasons at Primary Children's Medical Center (Salt Lake City, UT). Children < or = 18 years of age who were hospitalized with laboratory-confirmed influenza infection were included. Outcomes included hospitalization rates, complications including intensive care unit stays, mechanical ventilation, length of stay, and total hospital costs. RESULTS: A total of 325 children had hospitalizations attributable to influenza over 3 viral seasons: 28% < 6 months of age, 33% between 6 and 23 months of age; and 39% > 2 years of age; 37% had high-risk medical conditions. Population-based rates of hospitalization for Salt Lake County residents ranged from 6.3 to 252.7 per 100,000 children. The highest rates were in children younger than 6 months, and rates decreased with increasing age. Forty-nine (15%) children had an ICU stay; 27 required mechanical ventilation, and half of these patients were > 2 years of age. Total hospital cost for the cohort was 2 million dollars; 55% was accounted for by children > 2 years of age. Length of stay and total hospital costs were significantly higher in all children > 2 years of age compared with children < 6 months of age and were comparable to all children 6 to 23 months of age. CONCLUSIONS: Proven influenza infection in children results in substantial hospital resource utilization and morbidity. Nationwide, the median hospital costs may total 55 million dollars. Our data support the Advisory Committee on Immunization's recommendations to expand the use of influenza vaccine to children > 2 years of age.

Adolescent↗

Temporal trends of invasive disease due to Streptococcus pneumoniae among children in the intermountain west: emergence of nonvaccine serogroups.

BACKGROUND: Use of the heptavalent pneumococcal conjugate vaccine (PCV-7 [Prevnar]) has been associated with decreased a incidence of invasive pneumococcal disease (IPD) among children in the United States. METHODS: Cases of IPD in children < 18 years of age insured by or receiving health care from Intermountain Health Care during 1996-2003 were identified. Isolates of S. pneumoniae from children with IPD treated at Primary Children's Medical Center (PCMC; Salt Lake City, UT) during 1997-2003 were serogrouped. Temporal trends of IPD, serogroup distribution of pneumococci, and antibiotic resistance among pneumococci were analyzed. RESULTS: A total of 1535 cases of IPD were identified. The rate of IPD decreased 27% after the introduction of PCV7. Among children with IPD who were cared for at PCMC, disease in 73% was caused by PCV7 serogroups in 1997-2000, compared with 50% in 2001-2003 (P < .001), and the percentage of isolates resistant to penicillin decreased from 34% in 1997-2000 to 22% in 2001-2003 (P = .04). The percentage of IPD cases that were empyema increased from 16% to 30% (P = .015), and the percentage of severe cases of IPD increased from 57% to 71% (P = .026). Children with IPD due to non-PCV7 serogroups were older, were more likely to have parapneumonic empyema, and had longer hospital stays. CONCLUSIONS: The incidence of IPD in the IMW decreased by 27% after the introduction of the PCV7 vaccine. During the postvaccine period (2001-2003), there were significant decreases in the proportion of cases of IPD caused by PCV7 and antibiotic-resistant serogroups. These benefits were accompanied by a significant increase in the proportion of IPD cases due to non-PCV7 serogroups, with increases in the incidence of empyema and severe IPD.

Adolescent↗

Vaccine effectiveness during a varicella outbreak among schoolchildren: Utah, 2002-2003.

OBJECTIVES: In the context of a chickenpox outbreak involving 2 Utah elementary schools, we conducted an investigation to assess vaccine effectiveness, describe illness severity, and examine risk factors for breakthrough varicella (ie, varicella in those who have been vaccinated). METHODS: All parents were asked to complete a questionnaire about their child's medical history. Parents of children with recent varicella were interviewed, and vaccination records were verified. Lesions were submitted for polymerase chain reaction testing. RESULTS: Questionnaires were returned for 558 (93%) of 597 students in school A and 924 (97%) of 952 students in school B. A total of 83 schoolchildren (57 unvaccinated and 26 vaccinated) had varicella during the October 2002 through February 2003 outbreak period. An additional 17 cases occurred among household contacts, including infants and adults. Polymerase chain reaction analysis recovered wild-type varicella. Vaccine effectiveness was 87%. With 1 notable exception, vaccinated children tended to have milder illness. Risk factors for breakthrough varicella included eczema, vaccination > or =5 years before the outbreak, and vaccination at < or =18 months of age. Restricting analysis to children vaccinated > or =5 years before the outbreak, those vaccinated at < or =18 months of age were more likely to develop breakthrough varicella (relative risk: 9.3; 95% confidence interval: 1.3-68.9). CONCLUSIONS: The vaccine, administered by >100 health care providers to 571 children during a 7-year time period, was effective. Risk factors for breakthrough varicella suggest some degree of biological interaction between age at vaccination and time since vaccination.

Adult↗

Placebo-controlled, double-blind trial of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome in North America.

UNLABELLED: BACKGROUND. Ribavirin is active in vitro against hantaviruses, but the findings of an open trial of the use of intravenous ribavirin for the treatment of hantavirus cardiopulmonary syndrome (HCPS) were inconclusive. METHODS: Subjects with suspected HCPS in the prodrome or cardiopulmonary phase but without shock were eligible for randomization to receive either intravenous ribavirin (33 mg/kg [<or=2 g], followed by 16 mg/kg [<or=1 g] given every 6 h for 4 days and by 8 mg/kg [<or=.5 g] given every 8 h for 3 days) or placebo (administered for 7 days or until the initial Sin Nombre virus antibody test result was confirmed to be negative). The primary outcome was survival at day 28 of the study without the need for extracorporeal membrane oxygenation (ECMO). RESULTS: Thirty-six subjects were enrolled in the trial from March 1996 through July 2001, at which point the study was terminated prematurely because of both the slow rate of accrual of subjects and the findings of a futility analysis. Of the 36 subjects enrolled, 23 (all of whom were enrolled during the cardiopulmonary stage of HCPS) had HCPS confirmed by serologic testing. The severity of illness at entry into the study was similar among the 10 subjects with HCPS who received ribavirin and the 13 subjects with HCPS who received placebo. The proportion of subjects who survived and who did not require ECMO was similar among ribavirin recipients and placebo recipients (70% vs. 62%, respectively); 2 ribavirin recipients and 2 placebo recipients died, including 3 of 7 subjects treated with ECMO. The frequency of adverse events, including anemia, was similar between treatment groups. CONCLUSIONS: The rate of accrual of subjects in the present study was inadequate to clearly assess the safety or efficacy of ribavirin in the treatment of HCPS. However, ribavirin was well tolerated, and the lack of trends supporting the use of intravenous ribavirin suggests that it is probably ineffective in the treatment of HCPS in the cardiopulmonary stage.

Adult↗

Adenoviral infections in children: the impact of rapid diagnosis.

BACKGROUND: Adenovirus (ADV) infections were difficult to diagnose in the past, and many infections were unrecognized. Direct fluorescent assay (DFA) for the rapid diagnosis of ADV infection, as part of a viral respiratory panel, became available at Primary Children's Medical Center (Salt Lake City, UT) in December 2000. OBJECTIVE: To describe children with ADV infection diagnosed by DFA and viral culture and document the impact of rapid ADV testing on patient care. METHODS: DFA testing for respiratory viruses including ADV was performed on nasal wash specimens with parallel viral culture. Chart review was performed for all ADV-positive patients identified from microbiology records between December 2000 and May 2002. RESULTS: Of 1901 patients positive for respiratory viruses, 143 (7.5%) were ADV-positive by DFA or culture. The mean age of ADV-positive children was 23 months; 90% were <or=60 months old. Eighty percent were previously healthy, and 56% required admission with a mean length of stay of 3.4 days. The most common diagnoses included fever (31%), bronchiolitis (24%), and pneumonia (14%). Other conditions included suspected Kawasaki disease (KD) and hepatitis. Forty-six percent of ADV-positive children were given antibiotics at presentation, but only 2 (1.4%) had documented bacterial infection (one had Escherichia coli urinary tract infection and one had Moraxella catarrhalis bacteremia). Thirty-six percent of children had a change in management based on positive ADV DFA. In children with suspected KD (n = 5), 100% had positive ADV DFA, and immune globulin was withheld in 4. One immunocompetent patient with fulminant liver failure received cidofovir treatment after a positive ADV DFA and recovered before liver transplant. CONCLUSIONS: ADV is a common infection in young children and often results in admission and unnecessary antibiotic therapy. Identifying ADV as the cause of illness can favorably impact care and in some instances may be life-saving. DFA testing for ADV should be considered for infants and children requiring admission for fever, respiratory illness, suspected KD, and hepatitis.

Adenoviridae↗

A randomized trial to study first-line combination therapy with or without a protease inhibitor in HIV-1-infected patients.

OBJECTIVE: To compare one protease inhibitor (PI)-based and two PI-sparing antiretroviral therapy regimens. METHODS: International, open label, randomized study of antiretroviral drug-naive patients, with CD4 lymphocyte counts >/= 200 x 106 cells/l and plasma HIV-1 RNA levels > 500 copies/ml. Treatment assignment to stavudine and didanosine plus indinavir or nevirapine or lamivudine. Primary study endpoint was the percentage of patients with plasma HIV-1 RNA levels < 500 copies/ml after 48 weeks in the intention-to-treat analysis (ITT). RESULTS: In total, 298 patients were enrolled. After 48 weeks, the percentage of patients in the indinavir, nevirapine and lamivudine arms with HIV-1 RNA < 500 copies/ml was 57.0%, 58.4% and 58.7%, respectively, in an ITT analysis. After 96 weeks of follow-up, these percentages were 50.0%, 59.6% and 45.0%, respectively. The percentage of patients with HIV-1 RNA < 50 copies/ml was significantly less for those allocated to lamivudine in an on-treatment analysis after 48 and 96 weeks of follow-up. Patients in the nevirapine arm experienced a smaller increase in the absolute number of CD4 T lymphocytes. There were no significant differences in the incidence of serious adverse events. CONCLUSIONS: A comparable virological response can be achieved with first-line PI-base and PI-sparing regimens. The triple nucleoside regimen utilized may be less likely to result in viral suppression to < 50 copies/ml, while the nevirapine-based regimen is associated with a lower increase in CD4 T lymphocytes.

Adolescent↗

Serious bacterial infections in febrile infants younger than 90 days of age: the importance of ampicillin-resistant pathogens.

BACKGROUND: Intrapartum antibiotic prophylaxis against group B Streptococcus (GBS) has reduced the occurrence of serious bacterial infections (SBI) in young infants caused by GBS. Recommendations for initial antibiotic therapy for the febrile infant 1 to 90 days old were developed when infections with GBS were common and antibiotic resistance was rare. OBJECTIVE: To document the pathogens responsible for SBI in recent years in febrile infants 1 to 90 days old and the antibiotic susceptibility of these organisms. METHODS: The results of bacterial cultures from infants 1 to 90 days old evaluated for fever at Primary Children's Medical Center in Salt Lake City, Utah, between July 1999 and April 2002 were analyzed. Antibiotic susceptibility profiles were collected and patient records were reviewed to determine if initial antibiotic therapy was changed following the identification of the organism. RESULTS: Of 1298 febrile infants enrolled from the Primary Children's Medical Center emergency department, 105 (8%) had SBI. The mean age of the infants with SBI was 39 days (range 2-82 days) and 2 (2%) were <7 days. SBI included urinary tract infection (UTI; 67%), bacteremia (16%), bacteremia and UTI (6%), bacteremia and meningitis (5%), meningitis (2%), abscess (2%), meningitis and UTI (1%), and meningitis and gastroenteritis (1%). Eighty-three (79%) of 105 episodes of SBI were caused by Gram-negative bacteria, including 92% of UTI, 54% of bacteremia, and 44% of meningitis cases. The most common pathogen was Escherichia coli (61%). Other Gram-negative pathogens were responsible for 19% of SBI. Staphylococcus aureus was the most common Gram-positive pathogen, causing 8% of SBI. GBS accounted for 6% of SBI. Of the 105 pathogens, 56 (53%) were resistant to ampicillin. Of the pathogens causing meningitis, UTI, and bacteremia, 78%, 53%, and 50%, respectively, were resistant to ampicillin. Antibiotic therapy was changed in 54% of cases of SBI following identification of the organism. CONCLUSIONS: In Utah, ampicillin-resistant Gram-negative bacteria are the most common cause of SBI in febrile infants <90 days old. This finding impacts antibiotic selection, especially in cases of meningitis. Local surveillance of pathogens and antibiotic susceptibility patterns is critical to determine appropriate antibiotic therapy.

Ampicillin Resistance↗

An epidemiological investigation of a sustained high rate of pediatric parapneumonic empyema: risk factors and microbiological associations.

We investigated the increasing incidence of pediatric empyema during the 1990s at Primary Children's Medical Center in Salt Lake City. Of 540 children hospitalized with community-acquired bacterial pneumonia (CAP) who were discharged from 1 July 1993 through 1 July 1999, 153 (28.3%) had empyema. The annual population incidence of empyema increased during the study period from 1 to 5 cases per 100,000 population aged <19 years. Streptococcus pneumoniae was identified as the most common cause of CAP with or without empyema; serotype 1 accounted for 50% of the cases of pneumococcal empyema. Patients with empyema were more likely to be >3 years old, to have > or =7 days of fever, to have varicella, and to have received antibiotics and ibuprofen before admission to the hospital, compared with patients without empyema (P<.0001 for each factor). The increasing incidence of empyema was associated with infection due to S. pneumoniae serotype 1, outpatient treatment with certain antibiotics, ibuprofen use, and varicella.

Child↗

The effect of rapid respiratory viral diagnostic testing on antibiotic use in a children's hospital.

BACKGROUND: Acute viral respiratory disease is the most common reason for pediatric hospitalization in the United States. Viral illnesses may be mistaken for bacterial infection, and antibiotic therapy may be prescribed. Overprescribing of antimicrobials for viral illness is a factor contributing to increasing antimicrobial resistance among bacterial pathogens encountered in pediatrics. OBJECTIVE: To determine if the availability of a rapid diagnostic test for respiratory viruses would affect antibiotic use in a children's hospital. DESIGN: Retrospective medical record review. SETTING: A 232-bed urban children's hospital. PARTICIPANTS: All hospitalized infants and children who underwent rapid testing (SimulFluor Respiratory Screen; Chemicon International Inc, Temecula, Calif) for respiratory viruses by direct fluorescent assay (DFA) during 2 successive winter seasons. MAIN OUTCOME MEASURES: Rates of antibiotic prescribing in DFA-positive and DFA-negative patients during the 2 study periods. RESULTS: During the first winter season, DFA-positive patients had fewer days using intravenous antibiotics (2.4 vs 4, P =.04), fewer days using oral antibiotics (0.25 vs 2.5, P =.04), and fewer discharge prescriptions for oral antibiotics (37% vs 52%, P =.02) when compared with DFA-negative patients. Intravenous antibiotics were initiated less often for DFA-positive patients during the second winter season than during the first (26% vs 44%, P =.008). CONCLUSIONS: Direct fluorescent assay testing was associated with a decrease in inappropriate antibiotic use. The availability of rapid viral diagnostics is an important tool for decreasing antibiotic prescribing in pediatric patients.

Adolescent↗

Cerebral aneurysms in a child with acquired immune deficiency syndrome during rapid immune reconstitution.

A 12-year-old boy with perinatally acquired human immunodeficiency virus infection an d Centers for Disease Control and Prevention class C3 disease presented with acute onset of confusion and a right-sided movement disorder 5 months after beginning a new antiretroviral regimen. His CD4 count had been below 50 cells/microL for 4 years but had abruptly risen to more than 250 cells/microL. Computed tomographic and magnetic resonance imaging scans showed cerebral aneurysms and new cerebral lesions consistent with ischemic strokes. The presentation during immune reconstitution suggests that cerebral aneurysms in pediatric patients with acquired immune deficiency syndrome can result from an immune-mediated response to chronic vascular infection.

Acquired Immunodeficiency Syndrome↗

Recurrent hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) in children follows a diarrheal prodrome (D+) approximately 90% of the time, and recurrence due to enteric reinfection with Shiga toxin producing E. coli (e.g., O157:H7) can occur but is rare. It is not well recognized that nondiarrheal (D-) recurrences can also follow an episode of D+ HUS; we report 2 unrelated females who experienced multiple D- episodes following an initial episode of D+ HUS. We also present an HUS classification system that includes recurrence risk. It illustrates that recurrence is seen most frequently with familial HUS but can also occur in cases that are secondary to drugs, cancer, and pregnancy.

Female↗