Manish M. Patel

Real-world impact of rotavirus vaccination.

Summary of Studies in the Current Supplement That Assess Health Impact, Indirect Benefits, or StrainChanges After Rotavirus Vaccination Location (Ref) Vaccine Key Findings InterpretationHealth impactEl Salvador(15)RV1 35%–48% decline in all cause diarrhea events(outpatient and inpatient) and 69%–81%decline in rotavirus hospitalizations amongchildren 5 yearsThe consistency of the findings across regions, predominantlyduring seasons when rotavirus predominates, withincreasing effect among children in ages with the highestvaccination rates strongly supports vaccination as theMexico (17) RV1 11%–40% reduction in all cause diarrhea primary cause of the observed declines in diarrheahospitalizations among children 5Panama (18) RV1 22%–37% reduction in all cause diarrheahospitalizations among children 5The sustained declines in disease for 2–3 year aftervaccination indicates that duration of protection in thesesettings was sufficient to impact the youngest childrenwho bear the greatest burden of severe rotavirus diarrheBelgium (20) RV1 65%–83% reduction in rotavirushospitalizationsAustralia (21) RV1 & RV5 89%–94% vaccine efficacy against rotavirushospitalizations among children 5; 68%–93% reduction in under-1 rotavirus admitsLarge declines in all-cause diarrhea hospitalizations indicatethat rotavirus may be a more important cause of childhooddiarrhea than previously estimatedUnited States(19)RV5* No rotavirus epidemic occurred in January–June 2010, the first time in 19 years of USsurveillance within this systemIndirect benefitsEl Salvador(15)RV1 41%–68% decline during 2008 in childrenolder than 2 yr who were unvaccinatedIndirect benefits of vaccination in the early (1–2) years aftervaccination suggests that young infants may be theprimary drivers of epidemic spread (at least in middle andhigh income settings)United States(23)RV5* 42%–45% reduction among children tooyoung or old to be vaccinatedAustralia (21) RV1 & RV5 50% reduction in rotavirus hospitalizationsamong children older than 2 years who wereunvaccinatedIn poorer countries such as El Salvador, the total protectionat a population level as a result of indirect benefits ofvaccination has the potential to offset the lower efficacydirectly afforded to the vaccineStrain monitoringBrazil (45) RV1 Increase in G2P 4 for 2 year after vaccination Epidemiologic assessments, such as case-control vaccineeffectiveness, and robust longitudinal surveillance areneeded to best assess interaction between rotavirusvaccination and strain ecologyAustralia (47) RV1 & RV5 G1P 8 was the predominant strain nationally,however, some transient increase in G2P 4and G3P 8 prevalence occurred in Rotarixand RotaTeq states, respectivelyExisting strain surveillance data, vaccine effectivenessresults, and the dramatic declines in disease burden incountries with rotavirus vaccination support naturalvariation in strain ecology as the likely explanation for thereported observations in short-term changes in strainsafter vaccinationUnited States(46)RV5* Higher prevalence of G3P 8 in some US citiesafter rotavirus vaccinationOngoing disease and strain surveillance is needed to assesslonger term evolution in stain ecology and potential impacton disease burden

Rotavirus Vaccine and Health Care Utilization for Diarrhea in U.S. Children

BACKGROUNDnRoutine vaccination of U.S. infants with pentavalent rotavirus vaccine (RV5) began in 2006.nnnMETHODSnUsing MarketScan databases, we assessed RV5 coverage and diarrhea-associated health care use from July 2007 through June 2009 versus July 2001 through June 2006 in children under 5 years of age. We compared the rates of diarrhea-associated health care use in unvaccinated children in the period from January through June (when rotavirus is most prevalent) in 2008 and 2009 with the prevaccine rates to estimate indirect benefits. We estimated national reductions in the number of hospitalizations for diarrhea, and associated costs, by extrapolation.nnnRESULTSnBy December 31, 2008, at least one dose of RV5 had been administered in 73% of children under 1 year of age, 64% of children 1 year of age, and 8% of children 2 to 4 years of age. Among children under 5 years of age, rates of hospitalization for diarrhea in 2001-2006, 2007-2008, and 2008-2009 were 52, 35, and 39 cases per 10,000 person-years, respectively, for relative reductions from 2001-2006 by 33% (95% confidence interval [CI], 31 to 35) in 2007-2008 and by 25% (95% CI, 23 to 27) in 2008-2009; rates of hospitalization specifically coded for rotavirus infection were 14, 4, and 6 cases per 10,000 person-years, respectively, for relative reductions in the rate from 2001-2006 by 75% (95% CI, 72 to 77) in 2007-2008 and by 60% (95% CI, 58 to 63) in 2008-2009. In the January-June periods of 2008 and 2009, the respective relative rate reductions among vaccinated children as compared with unvaccinated children were as follows: hospitalization for diarrhea, 44% (95% CI, 33 to 53) and 58% (95% CI, 52 to 64); rotavirus-coded hospitalization, 89% (95% CI, 79 to 94) and 89% (95% CI, 84 to 93); emergency department visits for diarrhea, 37% (95% CI, 31 to 43) and 48% (95% CI, 44 to 51); and outpatient visits for diarrhea, 9% (95% CI, 6 to 11) and 12% (95% CI, 10 to 15). Indirect benefits (in unvaccinated children) were seen in 2007-2008 but not in 2008-2009. Nationally, for the 2007-2009 period, there was an estimated reduction of 64,855 hospitalizations, saving approximately

Uptake, impact, and effectiveness of rotavirus vaccination in the United States: review of the first 3 years of postlicensure data.

278 million in treatment costs.nnnCONCLUSIONSnSince the introduction of rotavirus vaccine, diarrhea-associated health care utilization and medical expenditures for U.S. children have decreased substantially.

Trends in national rotavirus activity before and after introduction of rotavirus vaccine into the national immunization program in the United States, 2000 to 2012.

Background: Rotavirus vaccine was recommended for routine use in US infants in 2006. Before the introduction of vaccine, rotavirus was the most common cause of severe gastroenteritis in children <5 years of age in the United States. Methods: We reviewed published data to summarize the US experience during the first 3 years of its rotavirus vaccination program. Results: Rotavirus seasons have been delayed and diminished in magnitude during the postvaccine era compared with the prevaccine era. Hospitalizations, emergency department visits, and outpatient visits due to gastroenteritis have declined dramatically in children <5 years of age including in children age-ineligible to have received vaccine, suggesting indirect benefits of vaccination. Rotavirus vaccine has been widely accepted by pediatricians. Vaccine coverage is steadily increasing but remains lower than coverage levels of other routine infant immunizations. Conclusions: The implementation of routine childhood immunization against rotavirus has rapidly and dramatically reduced the large health burden of rotavirus gastroenteritis in US children. Continued monitoring of rotavirus diarrhea is needed to determine if immunity wanes as vaccinated children get older and to better quantify the indirect benefits of vaccination. Ongoing surveillance will also enable monitoring of the long-term impact of vaccination on rotavirus epidemiology.

Fentanyl-associated Fatalities Among Illicit Drug Users in Wayne County, Michigan (July 2005–May 2006)

Background: Rotavirus vaccine introduction in the United States in 2006 led to substantial declines in rotavirus detections during 2007 to 2010. To further evaluate the long-term impact of the vaccine program, we assessed trends in rotavirus testing and detection in the 2010 to 2011 and 2011 to 2012 seasons compared with prevaccine seasons from 2000 to 2006. Methods: We examined data from July 2000 to June 2012 from 50 to 70 laboratories reporting to the National Respiratory and Enteric Viruses Surveillance System to compare rotavirus season timing and peak activity in the pre- and postvaccine introduction eras. To assess trends in rotavirus testing and detection, we restricted the analyses to 25 laboratories that consistently reported for ≥26 weeks for each season from 2000 to 2012. Results: The threshold for the start of the rotavirus season was never achieved nationally during the 2011 to 2012 season, and the 2010 to 2011 season was 8 weeks shorter in duration than the prevaccine baseline. During these seasons, nationally, the number of positive rotavirus tests declined 74%–90% compared with the prevaccine baseline and the total number of tests performed annually declined 28%–36%. The annual proportion positive at the 25 consistently reporting laboratories remained below 10% in both seasons compared with a prevaccine baseline median of 26%. A pattern of biennial increases in rotavirus activity emerged during the 5 postvaccine seasons from 2007 to 2012, but activity remained substantially below prevaccine levels. Conclusions: A substantial and sustained decline in rotavirus activity below the prevaccine baseline was observed in all 5 postvaccine introduction years, affirming the long-term health benefits of the US rotavirus vaccination program.

Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State, Brazil

BackgroundDuring the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users. The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users.MethodsBaseline prevalence of fentanyl- and heroin-associated deaths was estimated from January to May 2005 based on recorded cause of death (determined by the medical examiner (ME)) using the Wayne County, MI, USA toxicology database. The database was then queried for both FHFs and NFHFs between July 1, 2005 and May 12, 2006. A FHF was defined as having fentanyl or norfentanyl (metabolite) detected in any postmortem biological sample and either (1) detection of heroin or its metabolite (6-acetylmorphine) and/or cocaine or its metabolite (benzoylecgonine) in a postmortem biological specimen or (2) confirmation of fentanyl abuse as the cause of death by the ME or a medical history available sufficient enough to exclude prescription fentanyl or other therapeutic opioid use. A NFHF was defined as detection of heroin, 6-acetylmorphine (heroin metabolite) or morphine in any postmortem biological specimen, heroin overdose listed as the cause of death by the ME, and absence of fentanyl detection on postmortem laboratory testing. Information was systematically collected, trended for each group and then compared between the two groups with regard to demographic, exposure, autopsy, and toxicology data. Logistic regression was performed using SAS v 9.1 examining the effects of age, gender, and marital status with fentanyl group status.ResultsMonthly prevalence of fentanyl-associated fatalities among illicit drug users increased from an average of two in early 2005 to a peak of 24 in May, 2006. In total, 101 FHFs and 90 NFHFs were analyzed. The median age of decedents was 46 and 45xa0years for the fentanyl and non-fentanyl groups, respectively. Fentanyl-contaminated heroin-associated fatalities (FHFs) were more likely to be female (pu2009=u20090.003). Women aged over 44xa0years (ORu2009=u20094.67;95xa0% CIu2009=u20091.29–16.96) and divorced/widowed women (ORu2009=u200914.18;95 % CIu2009=u20091.59–127.01) were more likely to be FHFs when compared to women aged less than 44xa0years and single, respectively. A significant interaction occurred between gender and age, and gender and marital status. Most FHFs had central (heart) blood samples available for fentanyl testing (nu2009=u200996; 95xa0%): fentanyl was detected in most (nu2009=u200991; 95xa0%). Of these, close to half had no detectable heroin (or 6-acetylmorphine) concentrations (nu2009=u200937; 40.7xa0%). About half of these samples had detectable cocaine concentrations (nu2009=u200920; 54xa0%). Median fentanyl concentration in central blood samples was 0.02xa0μg/ml (nu2009=u200991, range <0.002–0.051xa0μg/ml) and 0.02xa0μg/ml (nu2009=u200932, range <0.004–0.069xa0μg/ml) in peripheral blood samples. The geometric mean of the ratio of central to peripheral values was 2.10 (median C/Pu2009=u20091.75). At autopsy, pulmonary edema was the most frequently encountered finding for both groups (77xa0%).ConclusionIllicit drugs may contain undeclared ingredients that may increase the likelihood of fatality in users. Gender differences in fentanyl-related mortality may be modified by age and/or marital status. These findings may help inform public health and prevention activities if fatalities associated with fentanyl-contaminated illicit drugs reoccur.

Superwarfarin and Glass Ingestion with Prolonged Coagulopathy Requiring High‐Dose Vitamin K1 Therapy

INTRODUCTIONnFollowing introduction of routine infant rotavirus vaccination, severe diarrhea hospitalization rates declined among children aged <5 years throughout Brazil. Ensuring equity of rotavirus vaccine impact is important in countries that self-finance immunization programs. The objective of this study was to examine rotavirus vaccine impact on diarrhea admission rates among children aged <5 years in Brazils public health system, according to area-based measures of human development in the state of São Paulo, Brazil.nnnMETHODSnEcological analysis of public health system hospitalization rates for acute gastroenteritis among children aged <5 years in the state of São Paulo, Brazil, according to five categories of municipal development based on a modified Human Development Index for municipalities. Acute gastroenteritis hospitalization rates among children aged <5 years after national rotavirus vaccine introduction (2008-2011) were compared to rates in pre-vaccine years (2000-2005) to calculate percent decline in rates (1-rate ratio) and 95% confidence intervals (CI) for each municipal development category. Direct hospitalization costs during the two periods were compared.nnnRESULTSnAnnual rates declined by 40% (95% CI, 39-42%) from 631 diarrhea hospitalizations per 100,000 person years pre-rotavirus vaccination to 377 per 100,000 post-vaccination among children aged <5 years and 50% (95% CI, 48-52%) from 1009 to 505 per 100,000 among infants. Highest rates were observed in least developed municipalities. Significant declines of 26-52% among children <5 years and 41-63% among infants were observed in all categories of municipal development. Lower diarrhea hospitalization rates resulted in annual savings of approximately 2 million USD for the state of São Paulo. Savings in direct hospitalization costs benefitted municipalities in all five categories.nnnCONCLUSIONnThe introduction of rotavirus vaccination was associated with substantial reductions of diarrhea-related admissions at all levels of municipal development in São Paulo State, Brazil.

Cardiotoxicity after Massive Amantadine Overdose

A 23‐year‐old man was brought to the emergency department after eating four boxes of brodifacoum‐containing rodenticide over a 4‐day interval and pieces from approximately two bottles of glass over the previous 2 weeks. He was asymptomatic but his prothrombin time was markedly elevated with an international normalized ratio (INR) of 37.8. A plain abdominal film showed diffuse radiopaque foreign bodies, presumably glass, in the large and distal small intestines. Treatment for ingested glass consisted of stool softeners and bulk‐forming laxatives. The patient developed mild gingival bleeding and received fresh frozen plasma (FFP) infusions and vitamin K1 orally. At a vitamin K1 dosage of 300 mg/day, the INR corrected to less than 2.0 and the patient was discharged taking that dosage. He returned 26 days later with hematuria and flank pain, and his INR was 189. He was administered FFP and packed red blood cells, and his vitamin K1 dosage was increased to 800 mg/day; his INR returned to baseline. Compliance with taking the vitamin K1, which required ingestion of 60–160 tablets/day, was a serious problem, requiring numerous follow‐up calls and visits to the patient at home and work. At 5‐month follow he was doing well. Compliance with large daily doses of vitamin K1 for treatment of “superwarfarin” ingestion may be poor because of the duration of treatment and large number of pills required. A more concentrated formulation may be advantageous for management of patients with brodifacoum poisoning.

Public Health Investigation After the Discovery of Ricin in a South Carolina Postal Facility

IntroductionAmantadine hydrochloride is an antiviral medication used as therapy for parkinsonism and as a cognitive enhancer. We report 2 cases of massive, acute ingestion of amantadine hydrochloride confirmed with serial serum levels.Case ReportsA 47-year-old woman presented to the emergency department (ED) 30 minutes after ingesting 10 g of amantadine (150 mg/kg) by her report. Initial ECG revealed a sinus rhythm with rate of 93 bpm, and a QRS of 84 msec. While in the ED, the patient sustained a pulseless cardiac arrest and the monitor revealed ventricular tachycardia. She was successfully defibrillated. Postdefibrillation ECG showed a sinus rhythm (rate = 82 bpm), QRS of 236 msec, and QTc of 567 msec. The serum potassium was 1.0 mEq/L (1.0 mmol/L). The patient was given 300 ml (300 cc) 3% sodium chloride IV over 10 minutes. Ten minutes after completion of the hypertonic saline infusion, the patient’s ECG abnormalities resolved and the QRS was 88 msec. Her potassium was repleted over the next 11 hours postpresentation, and she also received an IV bolus of 4 g of magnesium sulfate immediately after the cardiac arrest. No further hypotension, dysrhythmia, conduction delay, or ectopy was noted during the patient’s hospital stay. The second case involved a 33-year-old female patient who presented 1 hour after ingesting 100 tablets of amantadine hydrochloride (100 mg/tab). Initial ECG revealed sinus tachycardia with a QRS of 113 msec, an R wave in lead aVR of 4–5 mm and a QTc of 526 msec. Her serum potassium was 3.0 mEq/L (3.0 mmol/L), her serum calcium was 9.4 mg/dl (2.35 mmol/L), and serum magnesium was 2.1 mg/dl (0.86 mmol/L) on labs drawn at initial presentation. The patient was intubated for airway protection, and her potassium was repleted and corrected over the next 9 hours. Her ECG abnormalities improved 8 hours after initial presentation and normalized at approximately 14 hours postingestion. The patient was discharged home 11 days after her ingestion.ConclusionAcute amantadine toxicity manifests with life-threatening cardiotoxicity. Concurrent, often profound, hypokalemia may complicate the administration of sodium bicarbonate in the management of cardiac dysrhythmias.

Monitoring of rotavirus vaccination in Morocco: establishing the baseline burden of rotavirus disease.

OBJECTIVESnIn October 2003, a package containing ricin and a note threatening to poison water supplies was discovered in a South Carolina postal facility, becoming the first potential chemical terrorism event involving ricin in the United States. We examined the comprehensive public health investigation that followed and discuss the lessons learned from it.nnnMETHODSnAn investigation consisting primarily of environmental sampling for ricin contamination, performance of health assessments on affected personnel, and local, regional, and national surveillance for ricin-associated illness.nnnRESULTSnLaboratory analysis of 75 environmental sampling specimens revealed no ricin contamination. Health assessments of 36 affected employees were completed. Local surveillance initially identified 3 suspected cases, and national surveillance identified 399 outliers during the 2-week period after the incident. No confirmed cases of ricin-associated illness were identified.nnnCONCLUSIONSnA multifaceted and multidisciplinary approach is required for an effective public health response to a chemical threat such as ricin. The results of all of the described activities were used to determine that the facility was safe to reopen and that no public health threat existed.