7-8-09 receive injection - next day began developing local reaction - red, hot, painful R deltoid. That night developed flu - like Sx - exhausted, body ache's headache dizzy - today, 7-10 systemic Sx improved, but present. Arm still red, painful hot but no itch.

7/15/09 3yrs old

1 -1/2 hrs after receiving vaccine patient developed swelling at site, diffuse urticaria, and noisy breathing. He was given ATARAX then EPI PEN which helped. He was taken to the E.D. The impression at the E.D. was that the allergic reaction had resolved at the time of discharge, patient to use BENADRYL and ATARAX over next 24 hrs.

1/6/09

This is a previously health 8-month-old boy with a 2-week history of runny nose and cough without fever. Three days prior to admission he developed a fever which has been a T-max of 103. He was seen in the emergency department at his referring hospital two days prior to this admission at which point he was diagnosed with bilateral otitis media. Labs were not drawn at that time. He was started on azithromycin orally for which he had received two doses when he returned to the emergency department last night due to persistent fever and irritability. At that point his bulging fontanelle was noticed and he was empirically given a dose of IM ceftriaxone 100 mg hg. Note that a lumbar puncture was attempted and yielded only a few drops of apparently bloody CSF. It is unclear to me in talking with the lab whether this was actually received by the lab. A blood culture was obtained and that is pending. Finally a urine culture was obtained, but the lab also does not have this specimen. The patient was then transported by a team originating from that hospital. He had an 10 in place as both peripheral and central access were unsuccessful. 1/6/09-records received for DOS 11/22/08-12/29/08-DC DX: Streptococcus meningitis. Streptococcus Bacteremia.admitted with C/O two week history of rhinorrhea and cough and 3 day histoy of fever to 103. Bilateral otitis media 2 days prior to admission. Irritability. Bulging fontanelles.

http://www.ajc.com/health/content/shared-auto/healthnews/flu-/631714.html

Frieden's remarks coincided closely with statements earlier Tuesday by Gregory Hartl, a spokesman for the World Health Organization in Geneva, Switzerland. He told the Associated Press that only four of 39,000 Chinese who have received the H1N1 vaccine experienced minor side effects such as headache or muscle cramps, and these effects are to be expected.

Hartl said the current H1N1 vaccine formulation ranks among the safest the WHO has seen.

Pediatr Infect Dis J. 2006 Oct;25(10):860-9. Links

Comparison of the efficacy and safety of live attenuated cold-adapted influenza vaccine, trivalent, with trivalent inactivated influenza virus vaccine in children and adolescents with asthma.Fleming DM, Crovari P, Wahn U, Klemola T, Schlesinger Y, Langussis A, Øymar K, Garcia ML, Krygier A, Costa H, Heininger U, Pregaldien JL, Cheng SM, Skinner J, Razmpour A, Saville M, Gruber WC, Forrest B; CAIV-T Asthma Study Group.

Northfield Health Centre, Birmingham, United Kingdom.

BACKGROUND: Despite their potential for increased morbidity, 75% to 90% of asthmatic children do not receive influenza vaccination. Live attenuated influenza vaccine (LAIV), a cold-adapted, temperature-sensitive, trivalent influenza vaccine, is approved for prevention of influenza in healthy children 5 to 19 years of age. LAIV has been studied in only a small number of children with asthma. METHODS: Children 6 to 17 years of age, with a clinical diagnosis of asthma, received a single dose of either intranasal CAIV-T (an investigational refrigerator-stable formulation of LAIV; n = 1114) or injectable trivalent inactivated influenza vaccine (TIV; n = 1115) in this randomized, open-label study during the 2002-2003 influenza season. Participants were followed up for culture-confirmed influenza illness, respiratory outcome, and safety. RESULTS: The incidence of community-acquired culture-confirmed influenza illness was 4.1% (CAIV-T) versus 6.2% (TIV), demonstrating a significantly greater relative efficacy of CAIV-T versus TIV of 34.7% (90% confidence interval [CI] 9.4%-53.2%; 95% CI = 3.9%-56.0%). There were no significant differences between treatment groups in the incidence of asthma exacerbations, mean peak expiratory flow rate findings, asthma symptom scores, or nighttime awakening scores. The incidence of runny nose/nasal congestion was higher for CAIV-T (66.2%) than TIV (52.5%) recipients. Approximately 70% of TIV recipients reported injection site reactions. CONCLUSIONS: CAIV-T was well tolerated in children and adolescents with asthma. There was no evidence of a significant increase in adverse pulmonary outcomes for CAIV-T compared with TIV. CAIV-T had a significantly greater relative efficacy of 35% compared with TIV in this high-risk population.

PMID: 17006278

Euro Surveill. 2009 Aug 6;14(31). pii: 19288. Links

Interim analysis of pandemic influenza (H1N1) 2009 in Australia: surveillance trends, age of infection and effectiveness of seasonal vaccination.Kelly H, Grant K.

Epidemiology Unit, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia. heath.kelly@mh.org.au

Between May and September each year, influenza sentinel surveillance is conducted in general practices in Melbourne and the state of Victoria in southern Australia. We describe the first 11 weeks of sentinel surveillance in 2009 (weeks 18-28), during which time pandemic influenza (H1N1) 2009 virus became established, and investigate the protective effect of seasonal influenza vaccine against laboratory-confirmed infection caused by the pandemic virus. At the time of reporting, the peak ILI activity in 2009 had been reached and was similar to the peak recorded in 2007 but below the peak of 2003. The proportion of cases positive for any influenza virus increased from 6% in the first week of surveillance (week 18) to 59% by week 28, during which time the proportion of influenza viruses detected as pandemic influenza increased from zero to 95%, with at least 91% of all influenza viruses confirmed as pandemic influenza by the eighth week of surveillance (week 25). The median age of all 223 patients with pandemic influenza for whom age was known was 21 years (range 2-63 years) compared with the median age of 53 patients with seasonal H1N1 influenza in 2007 or 2008 of 23 years (range 1-75 years). There was no evidence of significant protection from seasonal vaccine against pandemic influenza virus infection in any age group.

PMID: 19660248

Lancet Infect Dis. 2009 Aug;9(8):493-504. Links

Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses.Kunisaki KM, Janoff EN.

Pulmonary Section, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN 55417, USA. kunis001@umn.edu

Patients that are immunosuppressed might be at risk of serious influenza-associated complications. As a result, multiple guidelines recommend influenza vaccination for patients infected with HIV, who have received solid-organ transplants, who have received haemopoietic stem-cell transplants, and patients on haemodialysis. However, immunosuppression might also limit vaccine responses. To better inform policy, we reviewed the published work relevant to incidence, outcomes, and prevention of influenza infection in these patients, and in patients being treated chemotherapy and with systemic corticosteroids. Available data suggest that most immunosuppressed populations are indeed at higher risk of influenza-associated complications, have a general trend toward impaired humoral vaccine responses (although these data are mixed), and can be safely vaccinated--although longitudinal data are largely lacking. Randomised clinical trial data were limited to one study of HIV-infected patients with high vaccine efficacy. Better trial data would inform vaccination recommendations on the basis of efficacy and cost in these at-risk populations.

PMID: 19628174

Am J Epidemiol. 2009 Sep 1;170(5):650-6. Epub 2009 Jul 22.  Links

Influenza vaccination and mortality: differentiating vaccine effects from bias.Fireman B, Lee J, Lewis N, Bembom O, van der Laan M, Baxter R.

Kaiser Permanente, 2000 Broadway, Oakland, CA 94612, USA. bruce.fireman@kp.org

It is widely believed that influenza (flu) vaccination of the elderly reduces all-cause mortality, yet randomized trials for assessing vaccine effectiveness are not feasible and the observational research has been controversial. Efforts to differentiate vaccine effectiveness from selection bias have been problematic. The authors examined mortality before, during, and after 9 flu seasons in relation to time-varying vaccination status in an elderly California population in which 115,823 deaths occurred from 1996 to 2005, including 20,484 deaths during laboratory-defined flu seasons. Vaccine coverage averaged 63%; excess mortality when the flu virus was circulating averaged 7.8%. In analyses that omitted weeks when flu circulated, the odds ratio measuring the vaccination-mortality association increased monotonically from 0.34 early in November to 0.56 in January, 0.67 in April, and 0.76 in August. This reflects the trajectory of selection effects in the absence of flu. In analyses that included weeks with flu and adjustment for selection effects, flu season multiplied the odds ratio by 0.954. The corresponding vaccine effectiveness estimate was 4.6% (95% confidence interval: 0.7, 8.3). To differentiate vaccine effects from selection bias, the authors used logistic regression with a novel case-centered specification that may be useful in other population-based studies when the exposure-outcome association varies markedly over time.

PMID: 19625341

AIDS. 2000 Dec 1;14(17):2781-5. Links

Effect of influenza vaccination on disease progression among HIV-infected persons.Sullivan PS, Hanson DL, Dworkin MS, Jones JL, Ward JW; Adult and Adolescent Spectrum of HIV Disease Investigators.

Division of HIV/AIDS Prevention-Surveillance and Epidemiology, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. pss0@cdc.gov

OBJECTIVE: To describe the effect of influenza vaccination on long-term change in CD4 count and HIV RNA level, and on progression to AIDS or death. DESIGN AND SETTING: A longitudinal medical record review set in 113 medical clinics in 10 United States cities. PATIENTS: A total of 36,050 HIV-infected persons aged > or = 13 years in care for HIV infection. MAIN OUTCOME MEASURES: Change in CD4 count and HIV RNA level at follow-up (3-12 months after vaccination); hazard ratios (HR) for association of influenza vaccine with progression from baseline CD4 or HIV RNA level to AIDS and to death. RESULTS: The median CD4 count among all persons decreased 28 cells/year during follow-up, with no difference in change in CD4 count between the 8007 (40%) vaccinated (median = 6 months, vaccine to follow-up CD4 count) and the 11,794 unvaccinated persons. In a viral load subanalysis, median HIV RNA level decreased 90 copies/ml per year among all persons during follow-up; decreases were not different between vaccinated and unvaccinated persons (median = 7 months, vaccine to follow-up HIV RNA level determination). Influenza vaccination was weakly associated with decreased risk of progression to clinical AIDS [HR 0.93; 95% confidence interval (CI), 0.87-0.99], but not associated with time to death (HR, 0.97; CI, 0.93-1.01). CONCLUSIONS: No negative long-term effect of influenza vaccination on CD4 counts, HIV RNA levels, or progression to AIDS or death was found in this HIV-infected population. These data suggest that physicians should not withhold influenza vaccine because of concerns about long-term detrimental effects of increased viral replication.

PMID: 11125897

J Infect Dis. 2008 Feb 15;197(4):490-502. Links

Rapid decline of influenza vaccine-induced antibody in the elderly: is it real, or is it relevant?Skowronski DM, Tweed SA, De Serres G.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada. danuta.skowrinski@bccdc.ca

Advisory committees have cautioned that influenza vaccine-induced antibody declines more rapidly in the elderly, falling below seroprotective levels within 4 months. We conducted a literature review to assess this assertion. The articles that were included in this review reported antibody levels > or =4 months after influenza immunization in persons > or =60 years old, interpretable in the context of annual influenza vaccine-approval criteria (seroprotection/seroconversion) specified by the Committee for Proprietary Medicinal Products (CPMP) for the elderly. The final review included 14 studies; 8 of which reported seroprotection rates. Seroprotection exceeding CPMP criteria was maintained > or =4 months after influenza immunization in all 8 of the studies reporting this for the H3N2 component and in 5 of the 7 studies reporting this for the H1N1 and B components. In determining whether CPMP criteria were met at season's end, primary antibody response appeared to be more relevant than secondary antibody decline. Both studies reporting seroprotection rates that failed CPMP criteria > or =4 months after influenza immunization for each of the H1N1 and B components had also reported failed seroprotection at 1 month after immunization. If initially achieved after immunization, seroprotection rates of 70%-100% were maintained not just at 4 months (2 studies) but also at 5 months (2 studies) and even at >6 months (4 studies), for the H3N2 and H1N1 vaccine components. Seroprotection rates appeared less consistent for the B vaccine component, throughout the postimmunization period. Seroconversion appears to vary substantially and inversely with preimmunization titers but not with age. In 2 of 6 studies reporting seroconversion alone, CPMP criteria were still met at 4 months. In the other 4 studies, the main reason for failure at 4 months was primary failure at 1 month. A total of 6 studies compared antibody persistence by age, and no consistent differences were found on that basis. The historic concern that the influenza vaccine-induced antibody response in the elderly declines more rapidly and below seroprotective levels within 4 months of immunization should be reconsidered.

PMID: 18275271

Neurotoxicology. 2009 Oct 1. [Epub ahead of print]

Delayed Acquisition of Neonatal Reflexes in newborn Primates receiving A Thimerosal-containing HepatitiS B Vaccine: influence of gestational age and Birth weight.Hewitson L, Houser LA, Stott C, Sackett G, Tomko JL, Atwood D, Blue L, White ER, Wakefield AJ.

Department of Obstetrics and Gynecology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; Thoughtful House Center for Children, Austin, TX, 78746.

This study examined whether acquisition of neonatal reflexes and sensorimotor skills in newborn rhesus macaques (Macaca mulatta) is influenced by receipt of the single neonatal dose of Hepatitis B (HB) vaccine containing the preservative thimerosal (Th). HB vaccine containing a standardized weight-adjusted Th dose was administered to male macaques within 24 hours of birth (n=13). Unexposed animals received saline placebo (n=4) or no injection (n=3). Infants were raised identically and tested daily for acquisition of 9 survival, motor, and sensorimotor reflexes by a blinded observer. In exposed animals there was a significant delay in the acquisition of three survival reflexes: root, snout and suck, compared with unexposed animals. No neonatal responses were significantly delayed in unexposed animals compared with exposed. Gestational age (GA) and birth weight were not significantly correlated. Cox regression models were used to evaluate the main effects and interactions of exposure with birth weight and GA as independent predictors and time-invariant covariates. Significant main effects remained for exposure on root and suck when controlling for GA and birth weight such that exposed animals were relatively delayed in time-to-criterion. There was a significant effect of GA on visual follow far when controlling for exposure such that increasing GA was associated with shorter time-to-criterion. Interaction models indicated that while there were no main effects of GA or birth weight on root, suck or snout reflexes there were various interactions between exposure, GA, and birth weight such that inclusion of the relevant interaction terms significantly improved model fit. This, in turn, indicated important influences of birth weight and/or GA on the effect of exposure which, in general, operated in a way that lower birth weight and/or lower GA exacerbated the detrimental effect of vaccine exposure. This primate model provides a possible means of assessing adverse neurodevelopmental outcomes from neonatal Th-containing HB vaccine exposure, particularly in infants of lower GA or low birth weight. The mechanism of these effects and the requirements for Th is not known and requires further study.

PMID: 19800915

Toxicol Appl Pharmacol. 2009 Sep 2. [Epub ahead of print] Links

Mercury toxicokinetics-dependency on strain and gender.Ekstrand J, Nielsen JB, Havarinasab S, Zalups RK, Söderkvist P, Hultman P.

Molecular and Immunological Pathology, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.

Mercury (Hg) exposure from dental amalgam fillings and thimerosal in vaccines is not a major health hazard, but adverse health effects cannot be ruled out in a small and more susceptible part of the exposed population. Individual differences in toxicokinetics may explain susceptibility to mercury. Inbred, H-2-congenic A.SW and B10.S mice and their F1- and F2-hybrids were given HgCl(2) with 2.0 mg Hg/L drinking water and traces of (203)Hg. Whole-body retention (WBR) was monitored until steady state after 5 weeks, when the organ Hg content was assessed. Despite similar Hg intake, A.SW males attained a 20-30% significantly higher WBR and 2- to 5-fold higher total renal Hg retention/concentration than A.SW females and B10.S mice. A selective renal Hg accumulation but of lower magnitude was seen also in B10.S males compared with females. Differences in WBR and organ Hg accumulation are therefore regulated by non-H-2 genes and gender. Lymph nodes lacked the strain- and gender-dependent Hg accumulation profile of kidney, liver and spleen. After 15 days without Hg A.SW mice showed a 4-fold higher WBR and liver Hg concentration, but 11-fold higher renal Hg concentration, showing the key role for the kidneys in explaining the slower Hg elimination in A.SW mice. The trait causing higher mercury accumulation was not dominantly inherited in the F1 hybrids. F2 mice showed a large inter-individual variation in Hg accumulation, showing that multiple genetic factors influence the Hg toxicokinetics in the mouse. The genetically heterogeneous human population may therefore show a large variation in mercury toxicokinetics.

PMID: 19732784

Eur J Pediatr. 2007 Sep;166(9):935-41. Epub 2007 Jan 20. Links

Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines.Marques RC, Dórea JG, Fonseca MF, Bastos WR, Malm O.

Fundação Universidade Federal de Rondônia, Porto Velho, RO, Brazil.

Because of uncertainties associated with a possible rise in neuro-developmental deficits among vaccinated children, thimerosal-preserved vaccines have not been used since 2004 in the USA (with the exception of thimerosal-containing influenza vaccines which are routinely recommended for administration to pregnant women and children), and the EU but are widely produced and used in other countries. We investigated the impact of thimerosal on the total Hg in hair of 82 breast-fed infants during the first 6 months of life. The infants received three doses of the hepatitis-B vaccine (at birth, 1 and 6 months) and three DTP (diphtheria, tetanus, and pertussis) doses at 2, 4 and 6 months, according to the immunization schedule recommended by the Ministry of Health of Brazil. The thimerosal in vaccines provided an ethylmercury (EtHg) exposure of 25 microgHg at birth, 30, 60 and 120 days, and 50 microgHg at 180 days. The exposure to vaccine-EtHg represents 80% of that expected from total breast milk-Hg in the first month but only 40% of the expected exposure integrated in the 6 months of breastfeeding. However, the Hg exposure corrected for body weight at the day of immunization was much higher from thimerosal- EtHg (5.7 to 11.3 microgHg/kg b.w.) than from breastfeeding (0.266 microgHg/kg b.w.). While mothers showed a relative decrease (-57%) in total hair-Hg during the 6 months lactation there was substantial increase in the infant's hair-Hg (446%). We speculate that dose and parenteral mode of thimerosal-EtHg exposure modulated the relative increase in hair-Hg of breast-fed infants at 6 months of age.

PMID: 17237965

http://www.ccohs.ca/oshanswers/chemicals/chem_profiles/mercury/health_mercury.html#_1_2

What are the long term health effects of exposure to Mercury?

The harmful effects of long-term exposure to elemental mercury are generally thought to be caused by inhalation exposure. However, mercury liquid and vapour are absorbed through the skin in small amounts and this route of exposure can contribute to the overall exposure. Effects following absorption through the skin are expected to be similar to those reported for long-term inhalation exposure.

Mercury levels in urine are often used as a general indicator of how much exposure to mercury has occurred. As a result, urine mercury levels rather than airborne levels are provided in some of the reports which compare mercury exposures to specific health effects. Urine mercury levels are reported in micrograms/gram of creatinine (a component of the urine). The relationship between airborne mercury levels and urine mercury levels is complicated and depends on many factors, including other sources of mercury exposure and between individual differences. Several studies indicate that an airborne exposure of 0.025 mg/m3 mercury compares to approximately 37 micrograms of mercury/gram of creatinine in the urine. Urine mercury levels in adults without occupational exposure are typically less than 3 micrograms/gram of creatinine. Sources of non-occupational exposure to inorganic mercury include new dental fillings.

In this review, urinary mercury levels below 35 micrograms/gram of creatinine are considered to reflect relatively low mercury exposure; 35 to 50 micrograms/gram of creatinine reflects moderate exposure; 50 to 100 micrograms/gram of creatinine reflects moderately high exposure and above 100 micrograms/gram of creatinine reflects high exposure.

EFFECTS ON THE NERVOUS SYSTEM: Effects on muscle coordination, mood, behaviour, memory, feeling and nerve conduction have been reported following long-term occupational exposure to mercury. These effects are often observed in employees with moderately high or high exposure to mercury. At lower exposures, the results are inconclusive with no effects being reported in some studies and mild effects reported in other studies. Although improvement has been observed upon removal of the person from the source of exposure, it is possible that some of the changes may be irreversible. The nervous system effects of mercury toxicity are sometimes referred to as "Mad Hatter's Disease" since mercurous nitrate was used in making felt hats.

A classic sign of mercury toxicity is a fine tremor, usually of the fingers, hands or arms and occasionally the eyelids, lips, tongue, and whole body. Many occupational studies indicate that tremors become more pronounced with longer exposures to mercury. Tremors are thought to be a sensitive indicator for long-term low-level exposure to mercury vapour. One report described tremors in employees with average exposures as low as 0.026 mg/m3 for an average of 15 years.

Behaviour and personality changes such as irritability, excitation and shyness, psychotic reactions such as delirium and hallucinations, loss of appetite, tiredness, sleeplessness, short-term memory loss and impaired nerve conduction have also been reported following long-term exposure. In one study, subtle behaviourial effects were detected in dentists with moderate mercury exposure.

Damage to the nerves of the arms and legs (polyneuropathy) has been reported in employees with high exposures. Reduced sensation and strength in the arms and legs, muscle cramps and decreased nerve conduction have been observed. Employees with episodes of very high exposure appear to be more at risk of developing these effects. Studies of employees in a chlor-alkali plant showed mild polyneuropathy in employees exposed to high levels of mercury. Signs included abnormalities in nerve conduction tests with reduced sensation and increased tremor of the arm.

EFFECTS ON THE KIDNEY: Many occupational studies indicate that moderate to high exposure to mercury can cause harmful effects on the kidneys. When urine mercury levels are low to moderate, the results are inconclusive with no effects being reported in some studies and mild effects reported in others.

Early indicators of kidney injury include increased levels of protein in the urine (proteinuria) and increased levels of certain enzymes in the blood and urine. Proteinuria is commonly observed in studies reporting kidney effects. Less often, changes to the structure of the kidneys have been shown. An increase in deaths from kidney disease in people occupationally exposed to mercury was not observed in one study.

SKIN SENSITIZATION: Allergic skin sensitization has been reported in people with occupational exposure to mercury liquid or vapour. Once a person is sensitized to a chemical, contact with even a small amount causes outbreaks of dermatitis with symptoms such as skin redness, itching, rash and swelling. This can spread from the hands or arms to other parts of the body. Occupational skin sensitization to mercury has been observed in people exposed to mercury in dental amalgams, tattoos or breakage of medical instruments. Positive patch tests were obtained in a dentist, five doctors, a nurse's aid, a mercury recycling employee and a pipeline repairman who had developed of red, dry, itchy skin (contact dermatitis) following occupational exposure. Previous history of allergies was not discussed for any of these cases. Skin sensitization to mercury has also been reported in the general public.

EFFECTS ON THE DIGESTIVE SYSTEM: Limited information suggests that long-term exposure to mercury vapour can cause inflammation and ulceration of the inside of the mouth, sore gums, drooling, diarrhea and other effects on the digestive system. No exposure information is reported, but presumably the concentrations were high.

EFFECTS ON THE HEART: Mercury may affect the heart producing increased blood pressure and/or heart rate. Two studies of employees with long-term exposure to low levels of mercury showed no effects on blood pressure or heart rhythm, as measured by electrocardiogram (ECG). A few other studies have shown effects on the heart including increased blood pressure and heart rate and abnormal ECG results. More deaths due to cardiovascular problems were observed in employees exposed to mercury in the chlor-alkali industry. These studies are limited by factors such as exposure to other potentially harmful chemicals at the same time and weak exposure information.

EFFECTS ON THE IMMUNE AND ENDOCRINE SYSTEMS: In most studies, effects on the immune and endocrine systems were not observed in employees exposed to mercury. However, altered immune response has been suggested in a few studies.

EFFECTS ON THE RESPIRATORY SYSTEM: Very little information is available regarding effects on the respiratory system from long-term exposure. Two studies reported persistent cough in employees exposed to mercury vapour for several weeks. Another study reported no respiratory symptoms, X-ray abnormalities or impaired pulmonary function in employees exposed to mercury vapour levels up to 0.27 mg/m3 for more than 6 years.