Thursday, October 25, 2007

Pediatric Flu Vaccine Works Despite Strain Mismatch

Pediatric Flu Vaccine Works Despite Strain Mismatch

NEW YORK (Reuters Health) Mar 14 - Despite not being a good match for circulating influenza strains, flu vaccination still provides a considerable degree of protection in many young children, researchers report in the March issue of Pediatrics.

"The results of our investigation," Dr. Carrie M. Shuler told Reuters Health, "support recommendations for influenza vaccination of children and strengthen the evidence of the vaccine's ability to reduce substantially the burden of disease among children."

Dr. Shuler of the Georgia Department of Public Health, Atlanta and colleagues came to this conclusion after conducting a study of 290 children attending a single pediatric practice in the 2003 to 2004 flu season.

During this season, there was a less than ideal match between the vaccine and the predominantly influenza A (H3N2) viruses. Only 25% of the circulating viruses were similar antigenically to the vaccine strain in use.

To investigate what consequences this might have had, the children, all of whom had laboratory-confirmed influenza and were between 6 and 59 months old, were matched 1:2 with controls.

Compared with unvaccinated children, the efficacy of the vaccine in fully vaccinated children was 49%. Partially vaccinated children under the age of 23 months had no significant reduction in influenza. However, older partially vaccinated children showed a 65% reduction.

Thus, concluded Dr. Shuler, "we found that influenza vaccination provided protection against medically attended children who were aged 6 to 59 months during a season with a suboptimal match between vaccine and circulating strains."

Pediatrics 2007;119:e587-e595.

HPV vaccine Protects against Cervical Cancer

ACIP Recommends Quadrivalent HPV Vaccine
News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD

March 23, 2007 — The Advisory Committee on Immunization Practices (ACIP) recommends quadrivalent human papillomavirus (HPV) vaccine for girls and women aged 9 to 26 years, according to guidelines published in the March 12 Early Release issue of the Morbidity and Mortality Weekly Report.

"Genital HPV is the most common sexually transmitted infection in the United States; an estimated 6.2 million persons are newly infected every year," write Lauri E. Markowitz, MD, from the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention (proposed), and colleagues. "Although the majority of infections cause no clinical symptoms and are self-limited, persistent infection with oncogenic types can cause cervical cancer in women.... Cervical cancer rates have decreased in the United States because of widespread use of Papanicolaou testing, which can detect precancerous lesions of the cervix before they develop into cancer; nevertheless, during 2007, an estimated 11,100 new cases will be diagnosed and approximately 3,700 women will die from cervical cancer."

The guidelines represent the first ACIP statement on the use of a quadrivalent HPV vaccine licensed by the US Food and Drug Administration on June 8, 2006. This report reviews the epidemiology of HPV and associated diseases, the licensed HPV vaccine, and recommendations for vaccination among girls and women aged 9 to 26 years in the United States.

The licensed HPV vaccine is composed of HPV L1, the major capsid protein of HPV. The quadrivalent HPV vaccine is a mixture of 4 HPV type-specific noninfectious virus-like particles prepared from the L1 proteins of HPV 6, 11, 16, and 18 combined with an aluminum adjuvant.

In clinical trials, the vaccine was highly effective in preventing persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts caused by HPV types 6, 11, 16, or 18 among girls and women who had not already been infected with the respective HPV type. Although there is no evidence of protection against disease caused by HPV types with which girls and women are infected at the time of vaccination, girls and women infected with one or more vaccine HPV types before vaccination would be protected against disease caused by the other vaccine HPV types.

In clinical trials, systemic clinical adverse events were reported by a similar proportion of HPV vaccine and placebo recipients, and the maximum intensity rating of systemic clinical adverse events was mild or moderate. Vaccine-related serious adverse events occurred in less than 0.1% of persons, and included bronchospasm, gastroenteritis, headache/hypertension, vaginal hemorrhage, and injection site pain/movement impairment.

In the overall safety evaluation, 10 persons in the group that received quadrivalent HPV vaccine and 7 persons in the placebo group died during the course of the trials, but none of the deaths were considered to be vaccine related.

Quadrivalent HPV vaccine is not recommended for use in pregnancy.

Quadrivalent HPV vaccine is available as a sterile suspension for injection in a single-dose vial or a prefilled syringe, and it is administered intramuscularly as 3 separate 0.5-mL doses. The second dose should be administered 2 months after the first dose and the third dose 6 months after the first dose.

The recommended age for vaccination of girls is 11 to 12 years during the established young adolescent healthcare visit at age 11 to 12 years as recommended by several professional organizations when other vaccines are also recommended.

The HPV vaccine can be given as young as age 9 years, and catch-up vaccination is recommended for teens and women aged 13 to 26 years who were not previously vaccinated. It is not possible for a clinician to assess the extent to which sexually active persons would benefit from vaccination, and the risk for HPV infection might continue as long as persons are sexually active. At any age, Papanicolaou testing and screening for HPV DNA or HPV antibody are not recommended before vaccination.

The guidelines caution that vaccination is not a substitute for routine cervical cancer screening and girls and women who have received vaccination should have cervical cancer screening according to the recommended protocol.

After reviewing available data on the epidemiology and natural history of HPV, vaccine acceptability, and sexual behavior in the United States, the ACIP also considered economic and cost-effectiveness analyses presented during meetings in June 2005, October 2005, and February 2006. The ACIP HPV vaccine workgroup developed recommendation options based on the above, as well as on expert opinion of the workgroup members.

The final recommendations were presented to ACIP at the June 2006 ACIP meeting and approved at the June 2006 meeting. The guidelines also recommend long-term follow-up studies to determine duration of protection. Additional data available in the near future from clinical trials and any new information on epidemiology of HPV will be reviewed by ACIP as they become available, and recommendations will be updated as needed.

"The recommendation for routine vaccination of females aged 11 to 12 years is based on several considerations, including studies suggesting that quadrivalent HPV vaccine among adolescents will be safe and effective; high antibody titers achieved after vaccination at age 11 - 12 years; data on HPV epidemiology and age of sexual debut in the United States; and the high probability of HPV acquisition within several years of sexual debut," the authors write. "Ideally, HPV vaccine should be administered before sexual debut, and duration of protection should extend for many years, providing protection when exposure through sexual activity might occur. The vaccine has been demonstrated to provide protection for at least 5 years without evidence of waning protection."

Morbid Mortal Wkly Rep Early Release. 2007;56:1-24.
Clinical Context

The most common sexually transmitted infection in the United States is genital HPV. In the January-February 2004 issue of the Perspectives on Sexual and Reproductive Health, Weinstock and colleagues noted that the US annual HPV incidence is about 6.2 million for persons aged 14 to 44 years, with 74% occurring in ages 15 to 24 years. According to the US Cancer Statistics Working Group, in 2003, the incidence of cervical cancer in the United States was 8.1 per 100,000 or about 11,820 cases. In the February 6, 2003, issue of The New England Journal of Medicine, Munoz and colleagues reported that persistent infection with high-risk HPV types was associated with cervical cancer, low- and high-grade cervical cancer precursors, and anogenital cancer. HPV types 16 and 18 cause about 70% of cervical cancers, according to Bosch and de Sanjose in the 2003 issue of the Journal of the National Cancer Institute: Monographs.

Persistent infection with low-risk HPV types 6 and 11 has been linked to benign or low-grade cervical cancer cell changes, genital warts, and respiratory papillomatosis. A quadrivalent HPV vaccine was licensed in the United States in June 2006 for girls and women aged 9 to 26 years to prevent HPV type 6-, 11-, 16-, and 18-related cervical cancer, precursors to cervical cancer and vaginal and vulvar cancer, and anogenital warts.

In 2004, the ACIP HPV vaccine workgroup started to review published and unpublished data from HPV vaccine clinical trials, HPV epidemiology, vaccine acceptability, and sexual behavior. ACIP approved the final recommendations in June 2006. Subsequent modifications were made after the Centers for Disease Control and Prevention review. This is the first ACIP statement to summarize HPV epidemiology, the HPV quadrivalent vaccine licensed for use in the United States, and HPV vaccine recommendations for use in girls and women aged 9 to 26 years.
Study Highlights

* Genital HPV infection is usually transmitted by sexual intercourse with greater risk linked to increased number of sex partners.
* In the United States, 3.7% of girls reported sexual activity by age 13 years and 24% by age 15 years.
* Most significant risk factor for cervical cancer precursors and cervical cancer is persistent infection with high-risk HPV types, especially type 16.
* HPV is also associated with most vaginal intraepithelial neoplasias III (VaIN III) and vaginal cancers (especially type 16), 76% vulvar intraepithelial neoplasia (VIN) and 42% vulvar carcinoma (types 16 or 18), 90% anal squamous cell cancer, all anogenital warts (90% from types 6 and 11), and juvenile onset recurrent respiratory papillomatosis.
* HPV-related lesion treatments do not appear to affect infectiousness.
* HPV prevention methods include abstinence, monogamy with uninfected partner, and possibly condom use, but not routine HPV infection surveillance or partner treatment.
* Each 0.5-mL dose contains 20 µg of HPV 6 L1 protein, 40 µg of HPV 11 L1 protein, 40 µg of HPV 16 L1 protein, 20 µg of HPV 18 L1 protein, and 225 µg of amorphous aluminum hydroxyphosphate sulfate and also includes sodium chloride, L-histidine, polysorbate 80, sodium borate, and water.
* Vaccine efficacy is 89.5% for persistent HPV 6, 11, 16, or 18 infection; 100% for HPV 16- or 18-related cervical intraepithelial neoplasia (CIN) 2/3; 95.2% to 100% for any grade CIN; 98.9% for HPV-6, 11-, 16-, or 18-related external genital warts; and 100% for HPV 16- or 18-related VIN 2/3 or VaIN 2/3.
* If HPV vaccine-type is seropositive or HPV DNA is positive, efficacy for CIN 2/3 prevention was unclear.
* Women who received at least 1 vaccine dose and any follow-up showed efficacy of 39% for type 16- or 18-related CIN 2/3 or adenocarcinoma in situ; 46.4% for any vaccine type-related CIN; 69.1% for vaccine type-related VIN 2/3 and VaIN 2/3; and 68.5% for vaccine type-related genital warts.
* Seropositivity for all ages was 99% for HPV types 6, 11, 16, and 18.
* Serious adverse events were similar for vaccine and placebo groups (< 0.1%); 10 deaths in vaccine group were not vaccine related.
* Most common local adverse event in vaccinated subjects was pain (84%).
* The second most common adverse event from the vaccine was syncope according to the Vaccine Adverse Event Reporting System; observation for 15 minutes postvaccination should be considered.
* Special situations:
o Vaccine is not effective for existing HPV infection, cervical lesions, or genital warts.
o Breast-fed infants of 500 women who received vaccine during lactation had no events.
o Immunosuppressed girls and women can receive vaccine but might have decreased immune response and efficacy.
o Vaccine is not recommended during pregnancy, but no intervention is necessary if received (Category B classification); 1244 vaccinated women who became pregnant had no increase in spontaneous loss or congenital anomalies.
* Contraindications include moderate or severe illnesses and history of immediate hypersensitivity to yeast or any vaccine component.
* Second and third doses should be given 2 months (minimum 4 weeks) and 6 months (minimum 12 weeks) after first dose; interrupted vaccine series does not need to be restarted.
* Papanicolaou test and HPV DNA or HPV antibody testing are not needed prior to vaccination.
* Vaccine can be administered with other age-appropriate vaccines, but only data for hepatitis B vaccine exist.
* Cervical cancer screening should continue in vaccinated patients.
* HPV vaccine is not licensed for girls younger than 9 years or women older than 26 years or for boys and men.

Pearls for Practice

* Quadrivalent HPV vaccine is highly efficacious in the prevention of persistent HPV infection, cervical cancer precursor lesions, vaginal and vulvar cancer precursor lesions, and genital warts due to HPV types 6, 11, 16, or 18 in girls and women who are not infected. The most common local adverse event is pain.
* Three-dose series of the quadrivalent HPV vaccine is recommended routinely for girls and women aged 11 to 12 years, but can be given to those aged 9 to 26 years; girls and women who have received vaccination should continue to undergo recommended cervical cancer screening.

1. Which of the following statements about quadrivalent HPV vaccine is most accurate? (Required for credit)
The most common local adverse event is erythema
It is effective in prevention of cervical cancer precursor lesions
It is effective in prevention of cervical cancer precursor lesions but not genital warts
It is effective in prevention of vaginal and vulvar cancer precursor lesions but not cervical cancer precursor lesions
It is effective in prevention of genital warts but not vaginal and vulvar cancer precursor lesions

2. An 11-year-old girl receives her first quadrivalent HPV vaccine today. Which of the following statements is most accurate? (Required for credit)
The second dose of HPV vaccine is due in 6 months
If she misses the next scheduled dose, she will need to restart the vaccine series
After she receives all 3 doses, she will not need cervical cancer screening in the future
Her 9-year-old sister could receive the vaccine today

Medscape Medical News 2007. ©2007 Medscape

Influenza Vaccination Recommendations for Children

The American Academy of Pediatrics recommends annual influenza immunization (April 2007)for

(1) children with high-risk conditions who are 6 months and older;
(2) healthy children 6 through 59 months of age;
(3) household contacts and out-of-home caregivers of children with high-risk conditions and all healthy children younger than 5 years; and
(4) health care professionals,

Other children, adolescents, and adults can be immunized to decrease the impact of influenza as indicated in the Red Book: 2006 Report of the Committee on Infectious Diseases.

Vaccination also recommended for older child or adolescents with underlying medical conditions eg:-
asthma or other chronic pulmonary diseases;
hemodynamically significant cardiac disease;
immunosuppressive disorders or therapy;
HIV infection;
sickle cell anemia and other hemoglobinopathies;
diseases requiring long-term salicylate therapy;
chronic renal dysfunction;
chronic metabolic disease, such as diabetes mellitus;
and any condition that can compromise respiratory function or handling of secretions or can increase the risk for aspiration.

Joseph A. Bocchini, Jr., MD,
Chairperson of the 2006-2007 Committee on Infectious Diseases

Wednesday, October 24, 2007

1/3 Atopic eczema child develop asthma

Minority of Children With Atopic Eczema Develop Asthma

NEW YORK (Reuters Health) Oct 12 - Contrary to common belief, only a minority of infants and young children with atopic eczema go on to develop asthma, according to a report in the September Journal of Allergy and Clinical Immunology.

Eczema and asthma are complex disorders brought about by an interaction of numerous genetic and environmental factors, only few of which are known, Dr. Paul L. P. Brand from Princess Amalia Children's Clinic, Zwolle in the Netherlands told Reuters Health. A simple linear progression from eczema to asthma is "an oversimplification," he added.

Dr. Brand and colleagues conducted a systematic review to assess the risk of developing asthma in children with atopic eczema during the first 4 years of life. They examined 13 prospective cohort studies.

In four birth cohort studies, atopic eczema was associated with a statistically insignificant 2.14-fold increase in the risk of developing asthma, the authors report.

In nine eczema cohort studies, the weighted prevalence of asthma at follow-up was 29.5% for the mixed group of inpatients and outpatients.

These estimates "are considerably lower than the risk estimates provided in many review articles and medical textbooks," the investigators say. "Our systematic review shows that on average, only 1 in 3 young children with atopic eczema develops asthma at the age of 6 years or older."

"The relationship between asthma and atopic eczema seems complex, and both genetic and clinical findings suggest that it is not one of simple progression of atopic eczema into asthma as popularly described in the atopic march concept," the researchers conclude.

Dr. Brand added that his group is "discussing the possibilities of conducting a large cohort study following up children with eczema until adult age."

J Allergy Clin Immunol 2007;120:565-569.

Avoid Self prescription of Cough Medicines to Infants

Infant Cough, Cold Drugs Withdrawn

Miranda Hitti

October 12, 2007 — The makers of all over-the-counter oral cough and cold medicines for infants announced that they are taking those products off the market.

"Potential misuse of these infant medicines, not product safety, is driving the voluntary withdrawal," the Consumer Healthcare Products Association (CHPA), a trade group representing the makers and distributors of over-the-counter medicines, states in a news release.

The withdrawal only applies to cough and cold medicines that refer to "infants," not to children who are at least 2 years old.

The CHPA today issued this list of branded cough and cold medicines that are being voluntarily withdrawn:

* Dimetapp Decongestant Plus Cough Infant Drops
* Dimetapp Decongestant Infant Drops
* Little Colds Decongestant Plus Cough
* Little Colds Multi-Symptom Cold Formula
* PEDIACARE Infant Drops Decongestant (containing pseudoephedrine)
* PEDIACARE Infant Drops Decongestant & Cough (containing pseudoephedrine)
* PEDIACARE Infant Dropper Decongestant (containing phenylephrine)
* PEDIACARE Infant Dropper Long-Acting Cough
* PEDIACARE Infant Dropper Decongestant & Cough (containing phenylephrine)
* Robitussin Infant Cough DM Drops
* Triaminic Infant & Toddler Thin Strips Decongestant
* Triaminic Infant & Toddler Thin Strips Decongestant Plus Cough
* TYLENOL Concentrated Infants ' Drops Plus Cold
* TYLENOL Concentrated Infants ' Drops Plus Cold & Cough

FDA Reviewing Products

In August, the FDA warned parents not to give children younger than 2 over-the-counter cough or cold medicines unless given specific directions to do so by a health care provider.

The FDA is reviewing the safety and effectiveness of nonprescription cough and cold drug use in children. An FDA panel will discuss the topic next week.

Trade Group's Comments

"It 's important to point out that these medicines are safe and effective when used as directed, and most parents are using them appropriately," CHPA President Linda Suydam, DPA, says in a news release.

"The reason the makers of over-the-counter, oral cough and cold medicines for infants are voluntarily withdrawing these medicines is that there have been rare patterns of misuse leading to overdose recently identified, particularly in infants, and safety is our top priority," says Suydam.

The CHPA and its member companies have recommended to the FDA that the labels on all over-the-counter cough and cold medicines for children 2 and older be strengthened from "ask a doctor" before using to "do not use" in children under age 2. That way, parents will be aware that these products are not recommended for infants.

The CHPA states it made those recommendations in preparation for next week's FDA panel meeting.

"These medicines are — and always have been — safe at recommended doses," says Suydam.

She adds that "these voluntary actions are being taken out of an abundance of caution. The vast majority of parents and caregivers safely use these medicines to help relieve their children's symptoms."

"But as with all medicines, it's important that parents read over-the-counter medicine labels carefully, use these medicines only as directed, and store them safely out of the reach of children," says Suydam.

WebMD Health News 2007

Monday, October 15, 2007

Thermerosal Preservative in Vaccines

"Weight of Evidence" Against Thimerosal Causing Neuropsychological Deficits

Susan Jeffrey

September 26, 2007 — A new study from the Centers for Disease Control and Prevention (CDC) does not appear to support a causal association between early exposure to mercury from thimerosal-containing vaccines or immune globulins and deficits in neuropsychological functioning among children now aged 7 to 10 years.

Out of 328 tests assessing these outcomes, the number of significant associations was about 5%, as would be expected for a chance finding, lead author William W. Thompson, PhD, from the CDC's Vaccine Safety Datalink Team, told Medscape Neurology & Neurosurgery.

"So at the end of the day, we think the weight of the evidence does not support a causal association between thimerosal exposure and 42 neuropsychological outcomes that we tested," Dr. Thompson said.

Their report is published in the September 27 issue of the New England Journal of Medicine.

However, the authors point out that their study did not look at autism spectrum disorders and so cannot answer the thorny question of a causal link there that has been the focus of litigation. This question is also the subject of 2 Perspective articles in the same issue of the Journal.

"We have a separate autism case-control study that we're doing that's assessing whether thimerosal from vaccines is associated with the risk for autism," Dr. Thompson noted. "That study is ongoing, and we hope to have a manuscript submitted for publication in the next year."

Thimerosal Removed From Vaccines

Thimerosal has been used as a preservative in vaccines since the 1930s, the researchers write. It is 49.6% mercury by weight and is metabolized into ethyl mercury and thiosalicylate.

In 1999, the Food and Drug Administration (FDA) estimated that infants immunized according to the recommended schedule could receive amounts of mercury in excess of limits set by the Environmental Protection Agency for exposure to methyl mercury, they note. "As a precautionary measure, the Public Health Service and the American Academy of Pediatrics [AAP] urged vaccine manufacturers to remove thimerosal from all infant vaccines as soon as was practical and recommended that studies be carried out to understand better the risks associated with mercury exposure from thimerosal-containing vaccines," the authors write.

This study is a follow-up to a previous analysis by the CDC published in 2003, Dr. Thompson said. Using computerized databases from 3 large health maintenance organizations (HMOs), the previous researchers found increasing exposure to thimerosal was associated with a greater likelihood of tics in 1 population and of language delay in another, but no significant associations were found in the third population (Verstraeten T. et al. Pediatrics. 2003;112:1039-1048).

In the current study, the authors aimed to have a more rigorous and comprehensive approach using a similar design to previous studies of prenatal exposure to methyl mercury from fish consumption, Dr. Thompson said.

"Our study improved on previous thimerosal studies by enrolling children on the basis of thimerosal exposure, independent of health status; prospectively assessing neuropsychological functioning independently of exposure and healthcare-seeking behavior; and collecting extensive information on potential confounders, including medical history and socioeconomic and educational factors that could influence a child's health and development," the authors write.

They also sought the advice of a panel of external experts, including vaccine advocacy groups, to compile the outcomes of interest. "In the end, we had 42 neuropsychological outcomes that we looked at and had extensive information on vaccine histories," Dr. Thompson said. The panel also had significant input on review of the results and draft of the final manuscript, he noted.

In all, 1047 children between the ages of 7 and 10 years were enrolled from 4 HMOs that participate in the CDC's Vaccine Safety Datalink. Exposure to thimerosal was determined using computerized health records, medical records, personal immunization records, and maternal interviews. They assessed the association between current neuropsychological performance and exposure to mercury in the prenatal period, birth to 28 days, and the first 7 months of life.

"Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal," the authors write.

"We present 378 tests in the manuscript, and when you run that many statistical tests, you're likely to get some chance findings," Dr. Thompson noted. Of the 378 tests, there were 19 statistically significant associations; 12 of these showed better outcomes with increasing thimerosal exposure, and 7 associated poorer outcomes with increasing exposure. The differences were small and mostly sex-specific.

Statistical significance on 19 tests, about 5% of the total, "is exactly what you would expect by chance," he said.

However, some of these associations may require further investigation, he added. One of these was an association of thimerosal exposure and tics among boys, important because a similar relationship was also seen in 2 previous studies, including the one by Verstraeten et al.

"We're in ongoing discussions within the CDC and with the National Center for Birth Defects and Developmental Disabilities regarding whether we should follow up on that or not," he said. Results from another ongoing study, called the Thimerosal Italy Study, which is also assessing tics as an outcome, will give more information on how to proceed on that finding, he noted.

Thimerosal has been removed from all vaccines with the exception of some influenza vaccines, Dr. Thompson said. However, parents can request thimerosal-free vaccines for their children.

Perspectives: Thimerosal and Autism

Researchers in the current study emphasize that their study did not assess autism spectrum disorders in relation to thimerosal exposure. In the 2 Perspective articles, a lawyer and a physician look at the impact that the fear of a potential link with autism has had on the use of vaccines and on litigation related to this question of causation.

In one of these, Paul A. Offitt, MD, chief of the division of infectious diseases at the Children's Hospital of Philadelphia, in Pennsylvania, calls the fallout from the decision to withdraw thimerosal from vaccines a "cautionary tale."

"Although the precautionary principle assumes that there is no harm in exercising caution, the alarm caused by the removal of thimerosal from vaccines has been quite harmful," he writes. "For instance, after the July 1999 announcement by the CDC and AAP, about 10% of hospitals suspended use of the hepatitis-B vaccine for all newborns, regardless of their level of risk. One 3-month-old child born to a Michigan mother infected with hepatitis-B virus died of overwhelming infection."

And there has been other fallout, he writes. The idea that thimerosal causes autism has given rise to a "cottage industry of charlatans offering false hope, partly in the form of mercury-chelating agents."

Many parents choose not to have their children immunized for influenza because some preparations of vaccine still contain thimerosal. "By choosing not to vaccinate their children, these parents have elevated a theoretical (and now disproved) risk above the real risk of being hospitalized or killed by influenza.

"During the next few years, thimerosal will probably be removed from influenza vaccines and the court cases will probably settle down," Dr. Offitt concludes. "But the thimerosal controversy should stand as a cautionary tale of how not to communicate theoretical risks to the public; otherwise, the lesson inherent in the collateral damage caused by its precipitous removal will remain unlearned."

In a second Perspective, Stephen D. Sugarman, JD, professor at the University of California, Berkley School of Law, outlines some of the process and current state of suits related to the causation question between childhood vaccines and autism.

Thousands of autism claims are pending, he writes. "In 2002, to resolve such claims more expeditiously, the VICP [Vaccine Injury Compensation Program] announced that some test cases would examine the general causation question, putting aside the question of harm to any particular child. Although this process was supposed to take only 2 years, the first of 9 test cases was heard just this past summer, with many witnesses testifying on each side. A special section of the US Court of Federal Claims administers the VICP, and judges running this so-called vaccine court are not expected to begin to decide these cases until 2008. Department of Justice lawyers appear in opposition to the claimants."

The study was supported by the Centers for Disease Control and Prevention, in Atlanta, Georgia. Dr. Thompson reports being a former employee of Merck; disclosures for other coauthors appear in the paper. Dr. Offit reports serving on the scientific advisory board of Merck and being the coinventor of the bovine-human reassortant rotavirus vaccine, RotaTeq, on which he holds a patent.

N Engl J Med. 2007;357:1281-1292, 1275-1277, 1278-1279.

New Dosing Schedule for Combined Hepatitis Vaccine

New Dosing Schedule for Combined Hepatitis Vaccine

The FDA has approved an alternate accelerated dosing schedule for Twinrix, the combined hepatitis A and B vaccine, according to an MMWR article.

The original schedule consists of doses at 0, 1, and 6 months for people aged 18 and over. The new schedule is 0, 7, and 21-30 days, and a fourth dose at 1 year.

The first three doses of the new schedule provide protection equivalent to the first two doses of the original schedule. The new schedule is useful if travel or potential exposure is expected before the second dose (at 1 month) on the original schedule.

MMWR article (Free)

GlaxoSmithKline revised package insert (Free PDF)

Sunday, October 7, 2007

Flu Vaccination Helps the Elderly Avoid Hospitalization, Death

Physician's First Watch for October 4, 2007
David G. Fairchild, MD, MPH, Editor-in-Chief

Flu Vaccination Helps the Elderly Avoid Hospitalization, Death

A long-term study in New England Journal of Medicine adds to previous short-term evidence indicating that influenza vaccination reduces the risk of hospitalization for pneumonia or influenza, as well as all-cause mortality, among community-dwelling elderly adults.
Researchers evaluated data, covering 10 flu seasons, from HMOs across the U.S. After multivariate adjustment, vaccinated adults ages 65 and older were 27% less likely to be hospitalized for pneumonia or influenza during the flu season — and 48% less likely to die from any cause — compared with unvaccinated adults. The risk reductions remained significant in a sensitivity analysis designed to control for residual confounding.
The authors call for strategies to improve the "stagnant" vaccination rates in this population. In addition, an editorialist stresses the importance of immunizing those in frequent contact with the elderly, noting the "appalling" vaccination rates among healthcare workers, who "can easily serve as vehicles of doom for their unsuspecting patients."
NEJM article (Free)
NEJM editorial (Subscription required) -->


Saturday, October 6, 2007

Antibiotics: To take or not to take?


I wrote this article in a local newspaper fortnightly column in Oct 2001 - the information is just as relevant today.


dr tan


911 and the ongoing anthrax scare has converted the chronic kia-su among us into terminal kia-si cases. Should we stock up antibiotics or be secretly popping them in the (now-not-so-unlikely) event some white powder lands on our desk?

Antibiotics can stop some infections and save lives, but when inappropriately used can cause more harm than good. They do not work against viruses or fungal infections. For these, you need anti-virals and anti-fungals respectively.

Before doctors prescribe antibiotics, there are some questions they must ask. Does the patient have an infection? What pathogens are likely? Are there epidemiological clues as to whether the cause is bacterial, viral or non infectious? Will it benefit from antibiotic therapy? Which antibiotic (group), what route, dose, and dosing frequency? How urgent is treatment? Will the site of infection be reached? Does anything about the patient (child, pregnant or lactating woman, elderly) limit the choice of agent? Do the benefits of treatment outweigh the potential adverse effects of the antibiotics? Does treatment need review or monitoring? What duration of treatment is needed?

Antibiotics are ‘smart bombs” that specifically target bacterial cells or parts thereof.
(Users must be smart too!)

The basis of anti-microbial treatment is to arrest the growth of the causal pathogen while the body’s immune defense system kills it. In order to avoid unwanted toxic effects, most antibiotics are chosen because they damage certain critical components of the bacterial cell, but not the host or human cell.

Each antibiotic group works in different ways. Penicillins interfere with the cell wall synthesis of new cells or damage the proteins in the existing cell wall making the bacteria susceptible to being “blown up”. Others act like detergents on the cell membrane, causing them to leak or break up. Tetracyclines (eg. doxycycline – the drug currently used in the treatment of those who have potentially been exposed to Anthrax spores) stops the bacteria from producing proteins for its new cell. Quinolones (ciprofloxacillin is in this category) act on the bacterial genes by disrupting the DNA replication, hence disrupting cell multiplication. Because they act at the genetic level, its use is not recommended in children below 18years.

Antibiotics do not work against all infections

Antibiotics only work against bacteria. They do not work at all against infections caused by viruses, fungus or parasites. Each antibiotic group is effective against a range of bacteria – this is called its spectrum of activity. The spectrum may be extended by adding another agent with a different spectrum.

Penicillins as a group are good for many of the bacteria causing skin, throat or chest infections, (and venereal disease like gonorrhoea or syphilis) but are not effective at all against those that cause gut or urine infections. For example, when newborn babies are admitted for suspected infection , they are usually put on a cocktail of a penicillin and an aminoglycoside, the later to cover the gut or urine bacteria that the neonate may have picked up from passing through the mother’s birth canal.

Before starting antibiotics, skin swabs , blood, urine or cerebrospinal fluid have to be sent for cultures to try to identify the responsible organisms. These are inoculated onto specific media plates or broth to incubate. If nothing grows within 24 hours, the laboratory will usually report “no growth”. This helps the doctors to review the need for discontinuation or change of antibiotics which had been empirically started.

If the media plates shows bacteria growth, the bacteria can then be microscopically identified and their sensitivity to different groups of antibiotics tested. This is called “culture and sensitivity” (C&S). When the C&S report say that the bacteria isolated is resistant to the antibiotics being used, the doctors will have to consider changing the antibiotic to one to which it is sensitive.

Antibiotic abuse promotes survival of resistant bacteria strains

Usually antibiotics kill bacteria or stop them from growing. However, some bacteria have become resistant to specific antibiotics so the antibiotics no longer work against them. Resistant bacteria develop faster when antibiotics are used too often or are not used correctly. Buying antibiotics over the counter to treat yourself may be priming your body’s germs to develop resistance, and make future treatment of infections more problematic, costly and potentially life threatening.

Antibiotics whenever prescribed must be taken in the right dose, with the correct timing and for the right reasons.

Do not expect antibiotics to cure every illness. Do not take antibiotics for colds or the flu.
Sore throat, cough or bronchiolitis are usually caused by viruses. A runny nose and yellow or green mucus do not necessarily mean you need an antibiotic. However, if you have a problem with your tonsils, sinuses, lungs or an illness that lasts a long time, bacteria may actually be the cause. Your doctor may use an antibiotic.

On the other hand, there are some conditions where antibiotic use is mandatory. This must be emphasized as some parents are increasingly unhappy about putting their kids on antibiotics. A bacteria called Beta Streptococcus causing sore throats or skin infections in children must be eradicated with antibiotics. In some susceptible children, failure to kill this bacteria early may cause them to produce antibodies which unfortunately attack the heart, joints and kidneys producing rheumatic heart disease, rheumatic fever, and acute glomerulonephritis respectively. Once a child has been diagnosed to have any of these conditions, they will be required to take penicillin daily for the rest of their life to prevent further debilitating damage to their susceptible organs. In this case not taking antibiotic is not an option!

Likewise, people with holes in the heart, abnormal or artificial valves or implants will need to protect themselves by taking antibiotics prophylactically before all surgical and all dental procedures. This is because such procedures invariably seed bacteria into the blood stream. If these “opportunists” are not killed on entry, they may colonize the abnormal structures and cause a serious life threatening infection. Killing bacteria before they get a chance to settle down and multiply is called “chemo-prophylaxis”.

Smart use of Antibiotics

When a doctor tells you to take an antibiotic “three times a day” (tds) he often forgets to tell you that his day is 24 hours while yours is 12! This is a world of difference. If you took antibiotics at 7am, 12am & 7pm (your tds), your overnight antibiotic blood level will fall below the effective levels necessary to inhibit bacterial growth.

Some of the newer (more expensive) antibiotics can be taken once a day. Others need twice to four times a day dosing. Those that are rapidly cleared by the kidneys or liver will need more frequent dosing. If one dose is omitted for whatever reason, the next dose should be taken when you remember, without increasing the dose. It is quite important to take the antibiotics in the frequency as prescribed. Changing arbitrarily a tds dosing (8 hourly) to o.d (once a day) is not good, as the drug level in the blood may not reach the “killing concentration” needed.

If you or your child really hate taking medicines and find it easier to take the least possible doses, please inform your doctor. There are alternatives (unfortunately they tend to be more expensive!).

But do give drugs and antibiotics (and doctors) some time, before you decide they do not work and run to the next doctor/pharmacy/chinese sinseh. Oral antibiotics may need a good 24 hours before you feel its full effect, because the drug level in the blood takes time to build up and because the bacteria population takes time to fall. Injection antibiotics work faster , especially if given intravenous in the hospital setting, but the risks associated with the injection has to be worth the speed.

Changing doctors and medications every six to eight hours is not smart, not just for your pocket.

Tuesday, October 2, 2007

Germ Proof your house!

General Housekeeping - Daily Decontamination of Toys, Floor, Furniture, walls

Home & floors should be cleaned daily (water & detergent)
Surfaces should be cleaned with a low-level disinfectant.
Regular cleansing of toys in a dishwasher or washing machine decreases germ contamination & eliminates organic material

Wear Disposable gloves to clean up any blood or body fluid spillage to protect yourself from picking up germs and contaminating or infecting yourself.
Wash area with detergent & disinfect with a freshly prepared solution of 1:10 household bleach applied for at least 30 seconds and wiped after the minimum contact time.

how to produce a 1 in 10 dilution? -
(10 ml chlorox to 90 ml water)

Be careful with fabrics and colored stuff - sorry if the color comes off!!

dr tan poh tin