Friday, October 30, 2009

Do Yearly Influenza Vaccinations for Children Affect Immunity Against Pandemic Strains?

From Medscape Medical News
Laurie Barclay, MD

October 29, 2009 — Whether yearly vaccinations for children against seasonal influenza might stop immunity developing against pandemic strains is debated in a personal view and reflection and reaction published online October 30 and will appear in the December print edition of The Lancet Infectious Diseases.

"Yearly vaccination is necessary because of the substantial antigenic drift of influenza viruses that necessitates the update of vaccines every year...driven by selective pressure mediated by antibodies induced by natural infection or vaccination," write Rogier Bodewes, DVM; Joost H.C.M. Kreijtz, PhD; and Guus F. Rimmelzwaan, PhD, from Erasmus Medical Center in Rotterdam, The Netherlands.

"The vaccination of healthy children aged 6–59 months against seasonal influenza has been recommended in several countries, including the USA and some European countries," the authors continue, "because the disease is an important cause of illness and admission to hospital in this age group. Although annual vaccination against seasonal influenza is beneficial for all patients at high risk, including children, vaccination of the 6–59 month age group every year against seasonal influenza might have a downside that has not been given much thought."

Previous studies, mostly in mice and other animals, have shown that infection with influenza A viruses can induce heterosubtypic immunity, which is protective immunity to influenza A viruses of other unrelated subtypes. Although heterosubtypic immunity does not offer full protection, it can limit virus replication and reduce influenza symptoms and mortality in the host.

The authors note that the ramifications of heterosubtypic immunity should be considered in humans when a new subtype of influenza A virus is introduced into the population. Pertinent examples include the novel influenza A H1N1 virus causing the present influenza pandemic and the highly pathogenic avian influenza H5N1 viruses responsible for increasing numbers of human infections, which are often fatal.

The authors suggest that an untoward effect of preventing infection with seasonal influenza viruses by vaccination might be to prevent the induction of heterosubtypic immunity to pandemic strains. Infants and other immunologically naive individuals would be at greatest risk were this to occur.

To test their theory, the authors suggest that hospitalizations and mortality rates among infants who have received yearly influenza vaccination since birth should be closely monitored and compared with those in age-matched children who were not vaccinated. The present H1N1 pandemic offers a unique opportunity to investigate heterosubtypic immunity and to determine potential harms of annual influenza vaccination.

In the meantime, the authors support the current vaccination program against H1N1 influenza and acknowledge that it will decrease morbidity and deaths in all age groups.

"Use of these pandemic influenza vaccines will override the theoretical issues associated with yearly vaccination against seasonal influenza," the study authors conclude. "The development and use of vaccines that can induce broad protective immunity might be a solution for these potential problems and we think this is a priority."

In an accompanying reflection and reaction, Terho Heikkinen, MD, and Ville Peltola, MD, from Turku University Hospital in Finland, argue that prevention of seasonal influenza in children by vaccination far outweighs the theoretical risk of preventing the induction of heterosubtypic immunity to pandemic strains. However, they agree with Dr. Bodewes and colleagues that more effective influenza vaccines that could induce broader immune responses are needed.

"The results of experimental animal studies can never be extrapolated directly to human beings, let alone form the basis of any vaccination policy," Dr. Heikkinen and Dr. Peltola write. "There is ample evidence for the great burden of influenza in young children, and this burden appears during every influenza season. By contrast, there is no clinical evidence that vaccinating children against influenza would prevent the induction of heterosubtypic immunity and thereby be disadvantageous to children in the long run."

Dr. Heikkinen and Dr. Peltola therefore advocate continuing the ongoing influenza vaccination program.

"While waiting for improved influenza vaccines, the simple question is should we let young children suffer from a severe and potentially lethal but easily preventable illness, just because there is a theoretical possibility that withholding vaccination might result in a slightly less severe illness sometime in the future?" they conclude. "We believe that the answer to this question is a simple one."

Dr. Rimmelzwaan is a consultant to Viroclinics BV. The other 2 personal view authors have disclosed no relevant financial relationships. Dr. Heikkinen has provided consultancy services to Novartis, Medimmune, GlaxoSmithKline, and Solvay. Dr. Peltola has received grants from GlaxoSmithKline and provided consultancy services to Novartis.

Lancet Infect Dis. Published online October 30, 2009.

Melamine contamination of formula milk and urinary tract stones

Melamine increases the apparent protein content of foods because of its high nitrogen content. This was probably the reason behind the recent con­tamination of infant formula milks with melamine in China. Researchers in Beijing have reported their findings in 589 children screened for urinary tract stones after possible exposure to melamine-contaminated formula milk.

Of 589 children aged up to 36 months exam­ined, 421 had received contaminated formula. On ultrasonography, 50 children had definite urinary tract stones. Eight of these had not been given the melamine-containing formula. One hundred and twelve had suspected stones and 427 no stones. Children with stones, suspected stones and no stones were equally likely to have haematuria (6%) or pyuria (3%). Glomerular function was abnormal in 10% of children with stones. Children given a high-melamine formula had a sevenfold increase in risk of stones. Prematurity was also associated with increased risk of stones. Further data are provided from Hong Kong and Taiwan in letters to the editor.

Melamine-contaminated formula increased the risk of renal tract stones.

Guan N, et al. Melamine-contaminated powdered formula and urolithiasis in young children. NEJM 2009;360:1067–1074; Langman CB. Melamine, powdered milk, and nephrolithiasis in Chinese infants. Ibid: 1139–1141 (editorial); Ho SSY, et al. Ultrasonographic evaluation of melamine-exposed children in Hong Kong. Ibid: 1156–1157 (letter); Wang I-J, et al. Melamine and nephrolithiasis in children in Taiwan. Ibid: 1157–1158 (letter).

Epinephrine and dexamethasone for viral wheeze in infants

There is uncertainty about the value of inhaled bron­chodilators and steroids for infants who wheeze. Now a multicentre trial in Canada has shown that treatment with oral dexamethasone and inhaled epinephrine (adrenaline) in the emergency depart­ment reduced rates of hospital admission.

The trial was carried out at eight centres during December to April in 2004–2007. A total of 800 infants aged 6 weeks–12 months (median age, 5 months) with a diagnosis of acute bronchiolitis (defined as a first episode of wheezing associated with signs of an upper respiratory tract infection during the peak respiratory syncytial virus season) were randomized to four treatment groups in the emergency department: epinephrine plus dexam­ethasone (ED), epinephrine plus placebo (EP), dex­amethasone plus placebo (DP), and double placebo (PP). Epinephrine was given as two doses each of 3 mL of 1:1,000 solution via a nebulizer. Dexam­ethasone was given orally in an initial dose of 1 mg/kg followed by five doses of 0.6 mg/kg at 24­hour intervals. Rates of hospital admission by day 7 were 17% (ED), 24% (EP), 26% (DP) and 26% (PP). There was a significant 35% risk reduction in the ED group, but this result became insignificant after statistical adjustment.

Giving oral dexamethasone and inhaled epine­phrine to infants with viral wheeze (paediatricians in Britain might give a diagnosis of wheezy bronchitis) may reduce the need for hospital admission.

Plint AC, et al. Epinephrine and dexamethasone in children with bronchiolitis. NEJM 2009;360:2079–2089; Frey U, von Mutius E. The challenge of managing wheezing in infants. Ibid: 2130–2133 (editorial).

Report of Motor Neuron Disease After HPV Vaccine

Medscape Conference Coverage, based on selected sessions at the:
American Neurological Association (ANA) 134th Annual Meeting

From Medscape Medical News

Allison Gandey

October 28, 2009 (Baltimore, Maryland) — Investigators are reporting a case of motor neuron disease after immunization with the quadrivalent vaccine Gardasil. The Merck product is designed to prevent infection with several types of human papillomavirus.

Presenting here at the 134th annual meeting of the American Neurological Association, researchers describe a case of rapidly progressive disease leading to the death of a 14-year-old girl.

Symptoms began 2 months after the last dose of Gardasil.
"Pathological features support the temporal association of the clinical presentation and vaccination and provides supporting evidence that immune-mediated reactions to the nervous system are potential risks after Gardasil vaccination," Catherine Lomen-Hoerth, MD, director of the Amyotrophic Lateral Sclerosis Center at the University of California–San Francisco, told the meeting.

"Our patient received 3 doses of Gardasil with symptom onset 2 months after her last dose," the poster presenters wrote. "Despite treatment with aggressive immunosuppression, her weakness relentlessly progressed and she died of respiratory failure 21 months after the onset of her weakness."

Postmortem evaluations revealed widespread infiltrates of T lymphocytes and macrophages in the grey and white matter at all levels of the spinal cord. Researchers also report extensive demyelination and severe loss of motor neurons.

In September, investigators presenting at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting reported cases of autoimmune disorders after immunization with Gardasil.

Two groups presented at the meeting — one identified a case of multiple sclerosis after vaccination and the second a case of neuromyelitis optica.

Other Reports of Autoimmune Disorders

Presenter Maria Bouktsi from the Interbalkan European Medical Center in Thessaloniki, Greece, told Medscape Neurology that her team is questioning whether the immuno-stimulatory properties of the human papillomavirus–like particles of the vaccine are triggering adverse effects in vulnerable patients.

It is the same question that researchers asked in a recent issue of Multiple Sclerosis (2009;15:116–119). Ian Sutton, MD, from St. Vincent's Hospital in New South Wales, Australia, and his team reported 5 cases of multiple sclerosis after vaccination with the drug. The group reported in January that patients presented with multifocal or atypical demyelinating syndromes within 21 days of immunization.

No definitive conclusions can be made based on this report, Dr. Sutton and his team noted. "It should not be overlooked that several epidemiological studies indicate that viral infection is associated with a threefold increase in the risk of a multiple sclerosis relapse," write the researchers.

7 More Cases

Lead investigator of the second group presenting on this topic said that he agrees that postmarketing pharmacosurveillance is necessary to improve safety. "[Human papillomavirus] vaccines elicit a strong inflammatory systemic immune response," said Til Menge, MD, from Heinrich-Heine University in Düsseldorf, Germany.

His group suggests that it was this inflammatory response that may have triggered a case of fulminant neuromyelitis optica in a previously healthy 17-year-old girl.

Investigators have not established a causal relationship, but they are asking clinicians to closely monitor patients for any emerging side effects.

The researchers have disclosed no relevant financial relationships.

American Neurological Association 134th Annual Meeting: Poster WIP-19. Presented October 13, 2009.

Thursday, October 29, 2009

Tanning Increases Moles in Light-Skinned Children

From Medscape Dermatology > Viewpoints
Graeme M. Lipper, MD

Arch Dermatol. 2009;145:989-996

Study Summary

The association among light-skin phototypes, heavy sun exposure, and cutaneous malignant melanoma (MM) is well established.
Excessive childhood ultraviolet B exposure leads to increased MM incidence later in life.[1-3]
Known risk factors for the development of MM include: a family history of MM, the presence of dysplastic nevi (or family history of dysplastic nevus syndrome), presence of numerous melanocytic nevi, and a history of heavy sun exposure.[2-4] Because individuals with numerous melanocytic nevi are at increased risk of developing MM,[4] Aalborg and colleagues sought to determine if children with light-skin phototypes who tan are at greater risk than their nontanning peers of developing multiple nevi, and by proxy, MM later in life.

This prospective study began with a cohort of 1145 children (ages 5-6 years) recruited from the Denver metropolitan area during 2003 and 2004. Of this initial group, 696 children completed 3 consecutive annual skin examinations. Investigators further reduced this cohort by excluding patients with red hair (considered to be a genetically distinctive group with a low baseline incidence of nevi), incomplete data, or darker skin phototypes. The remaining study population was composed of 131 very light-skinned white children without red hair and 444 darker-skinned white children without red hair. Investigators followed this cohort for the development of melanocytic nevi for 3 years. Of note, skin pigmentation was objectively determined with colorimetry analysis (Chroma Meter CR-400, Konica Minolta Sensing Americas, Inc, Ramsey, New Jersey). By comparing the skin pigmentation in photoprotected (axillary) vs photoexposed (forearm) areas of skin, investigators further stratified very light-skinned children into 2 subgroups: low tanners (n = 20) and high tanners (n = 111).

During the 3-year follow-up period, Aalborg and colleagues noted the following:

Very light-skinned children who tanned had significantly more nevi develop compared with their nontanned peers.
Minimally tanned light-skinned children had mean nevus counts of 14.8 at 6 years, 18.8 at 7 years, and 22.3 at 8 years. In contrast, light-skinned children who tanned had mean nevus counts of 21.2 at 6 years, 27.9 at 7 years, and 31.9 at 8 years.

The aforementioned association was independent of variables such as the child's base skin color, hair color, eye color, parent-reported sun exposure, hours per week in the sun, sun protection behavior, past sunburns, and vacation sun exposure.

Darker-skinned white children showed no relationship between tanning and number of nevi.


Are children with light-skin phototypes who tan at greater risk of developing melanoma later in life than their nontanned peers?
Previous studies have already shown that among white children, those with lighter-skin phototypes are 2-3 times more likely to have MM develop than those with darker-skin types.[3]
In addition, studies of light-skinned white children in Europe and Canada have demonstrated a clear association between a history of multiple or severe (blistering) sunburns and high nevi counts.[5,6]

Aalborg and colleagues now add to this important body of knowledge by showing that light-skinned white children who tan clearly develop a greater number of melanocytic nevi than their nontanned peers, even at an early age.
Because many MMs do not occur within existing nevi, the presence of multiple nevi in these young children likely serves as a marker for ultraviolet-induced skin damage and/or a genetic susceptibility to MM.
In this context, it seems clear that parents of light-skinned children should be educated about the benefits of photoprotecting their children to avoid tanning, starting at an early age.

Most Patients With Vaccine Allergy May Be Safely Vaccinated

From Medscape Medical News
Laurie Barclay, MD

October 20, 2009 — Most patients with vaccine allergy may be safely vaccinated, according to a practice parameter published in the October issue of the Annals of Allergy, Asthma & Immunology. However, the new guidelines also recommend that patients with suspected allergy to vaccines or vaccine components be evaluated by an allergist or immunologist vs simply avoiding future immunizations, which could leave patients at higher risk for infectious disease.

Specific summary statements in the parameter include the following:

Mild local reactions, fever, and other constitutional symptoms after vaccinations occur often and are not a contraindication to subsequent doses.
Anaphylactic reactions after vaccination are rare, with incidence of approximately 1 per million doses.
Even if the vaccine is not clearly the cause, all serious events occurring after vaccine administration should be reported to the Vaccine Adverse Event Reporting System.
Measurement of IgG antibody levels to the immunizing antigen in a vaccine suspected of causing a serious adverse reaction can determine if levels are protective and whether subsequent doses are needed.
Ideally, all suspected anaphylactic reactions to vaccines should be evaluated so that the responsible allergen may be identified.
Gelatin, egg protein, or other vaccine components are more likely than the immunizing agent itself to cause IgE-mediated reactions to vaccines.
Immediate-type allergy skin testing should be performed in patients who appear to have had an anaphylactic reaction after vaccination. This testing should help confirm that the reaction was IgE mediated and identify the responsible vaccine component.
If the intradermal skin test result is negative, it is extremely unlikely that the patient has IgE antibody to any vaccine component, and the patient can be vaccinated in the usual manner.
In a patient with a history suggesting anaphylactic reaction, however, it is prudent to vaccinate with the patient under observation and to have epinephrine and other emergency treatment available.
In patients with history and skin tests results suggesting an IgE-mediated reaction to a vaccine but who need additional doses of the suspected vaccine or other vaccines with shared ingredients, the clinician can consider administering the vaccine in graded doses while observing the patient.
There are other less common but more serious reactions to vaccines, but only a few represent absolute contraindications to future doses.
Pregnant women should not be given live vaccines.
Live vaccines should generally not be given to immunocompromised persons.
Epidemiologic studies have not supported associations between specific vaccines or vaccination in general with long-term sequelae such as atopy, autism, and multiple sclerosis.
"The 2 key points of the practice parameter are that (1) patients with suspected allergy to vaccines or vaccine components should be evaluated by an allergist/immunologist and (2) most patients with suspected allergy to vaccines can receive vaccination safely," the guidelines authors conclude.

Ann Allergy Asthma Immunol. 2009;103:S1-14.

Tuesday, October 27, 2009

Strategies for Diagnosing and Treating Dehydration in Children

From Medscape Medical News CME
Laurie Barclay , Désirée Lie,


Clinical Context

Fluid and electrolyte disturbances form diarrhea and vomiting result in 1.5 million patient visits yearly in the US and 300 deaths. Several methods are available to assess hydration and the need for rehydration and hospital admission in children.

This is a review of the clinical assessment of dehydration in children with diarrhea and vomiting and recommended strategies for rehydration at home, in the office, and in the hospital.

Study Highlights

Parental report of vomiting, diarrhea, and reduced oral intake is sensitive but not specific for identifying dehydration in children.
If tear production is normal, then the chance of dehydration is low.
The most useful individual physical signs are prolonged capillary filing time, abnormal skin turgor, and abnormal respiratory pattern.
The use of scales based on combinations of physical examination findings is better than individual clinical signs.
4 factors predict dehydration: capillary refill time of more than 2 seconds, absence of tears, dry mucous membranes, and ill appearance.
The presence of 2 or more of these suggests dehydration of at least 5%.
General appearance, degree of sunken eyes, dry mucous membranes, and reduced tear production are associated with length of hospital stay and the need for intravenous fluids in children.

Capillary refill time is performed at ambient room temperature on the sternum of infants and a finger or arm at the level of the heart in older children.
Skin turgor is performed by pinching the skin on the lateral abdominal wall at the umbilical level.
The ratio of serum urea nitrogen to creatinine, serum urea nitrogen alone, and urine specific gravity have poor sensitivity and specificity in children.
Serum bicarbonate levels less than 17 mEq/L may improve sensitivity of identifying hypovolemia, but levels less than 13 mEq/L are associated with poorer hydration and recovery with rehydration.

The American Academy of Pediatrics recommends ORT as the preferred treatment of fluid and electrolyte losses in children with mild to moderate dehydration with similar success as intravenous fluid replacement.
The same ORT can be used for replacement, maintenance, and rehydration.
ORT is contraindicated in abdominal ileus, altered mental status, or intestinal malabsorption.

Nasogastric rehydration with ORT is an alternative to intravenous rehydration.
As soon as rehydration is completed, children can return to an age-appropriate diet.
World Health Organization ORT contains 90 mEq/L of sodium vs 50 mEq for commercial ORT preparations, which also contain 25 g/L of dextrose and 30 mEq/L of bicarbonate, and they are recommended vs homemade solutions to reduce preparation errors.
For mild dehydration, 50 mL/kg of ORT solution should be administered with a spoon, syringe, or medicine cup by giving 1 mL/kg to the child every 5 minutes.
The Holliday-Segar method involves a rule of 1 oz per hour for infants, 2 oz per hour for toddlers, and 3 oz per hour for older children.
To replace ongoing losses, 10 mL/kg for every loose stool and 2 mL/kg for every emetic episode should be given.

For moderate dehydration, 100 mL/kg of ORT should be given for 4 hours in the office or emergency department; if treatment is successful, the child can be sent home for maintenance therapy by caregivers.
Severe dehydration should be managed with intravenous fluids until stabilization.
Treatment includes 20 mL/kg of lactated Ringer's solution for 10 to 15 minutes (repeated as needed), and up to 60 mL/kg may be needed within 1 hour.
Electrolyte measurements are important in severe and moderate dehydration.
Children with fever may require extra 1 mL/kg per degree centigrade every hour in addition to maintenance therapy.
Postoperatively and in those with infection or injury, 20% to 50% less fluid and fluid with higher sodium content may be needed.
Pharmacologic treatment is not indicated in diarrhea because of concerns of toxicity, and Lactobacillus has not been demonstrated to be useful.
A single dose of ondansetron can facilitate ORT by reducing vomiting and the need for intravenous treatment.

Clinical Implications

Physical signs predictive of dehydration include capillary refill time of more than 2 seconds, absence of tears, dry mucous membranes, and ill appearance.
ORT or nasogastric rehydration with ORT fluid is recommended for mild to moderate dehydration and intravenous rehydration for severe dehydration.

Monday, October 26, 2009

Ibuprofen Bests Acetaminophen/Codeine for Pediatric Arm Fracture Pain

Anthony J. Brown, MD
Désirée Lie, MD, MSEd

Ann Emerg Med. 2009;54:553-560. Abstract
Reuters Health Information 2009. © 2009 Reuters Ltd.

Clinical Context

Children with simple fractures require adequate pain relief after discharge from the emergency department (ED). Although ibuprofen potentially provides similar pain relief as opioids, ED practices vary widely, and limited data are available comparing the 2 analgesics.

This is a randomized, double-blind controlled trial of children presenting with simple arm fracture to ED during 4 years to compare the efficacy of ibuprofen vs acetaminophen with codeine on outpatient pain relief, function, and satisfaction.

Study Highlights

Included were children aged 4 to 18 years weighing less than 60 kg presenting to a level I hospital ED within 12 hours of injury (2003-2007) with a fracture of the ulna, radius, or humerus visualized on a standard 2-view radiograph with fracture diagnosis confirmed by a pediatric radiologist.
Excluded were children with an isolated posterior fat pad of the elbow, open fractures, and those who required manipulation or reduction in the ED, with developmental delay, chronic illness, allergy to the medications, or a history of bleeding or gastrointestinal tract disorders.
All treatment decisions were made by board-certified emergency pediatricians and fellows; patients received usual care including splinting by ED personnel and analgesia in the ED.
Primary outcome was failure of pain relief, defined as use of rescue medication.
Secondary outcomes were pain relief, pain medication use, pain scores, functional outcomes, and adverse effects.
Outcomes were collected in a diary given to parents and returned in a stamped, addressed envelope with 2 telephone calls made in the first 72 hours after discharge from the ED to remind parents.
Ibuprofen suspension was dosed at 10 mg/kg (100 mg/5 mL) and acetaminophen with codeine at 1 mg/kg (120 mg/5 mg per 5 mL) of the codeine content, with a maximum of 4 permitted doses in 24 hours.
The medications were matched for color and volume but not taste.
Parents were instructed to use the rescue medication if pain was not relieved (pain score ≥ 3) 1 hour after dosing of the study medication.
The modified Bieri Faces Pain Scale was the validated pain scale used for assessment by parents; children were assessed at awakening, bedtime, and before and at 1 hour after each dose.
Daily total, median, maximal, and minimum scores were collected.
Parent satisfaction was recorded daily with a Likert scale, and the Total Quality Pain Management instrument was used for parent and child on day 3.
167 children were assigned to acetaminophen with codeine and 169 to ibuprofen, with a follow-up of 75% for acetaminophen with codeine and 78% for ibuprofen.
244 children were included in the analysis after some were ineligible or lost to follow-up (116 in the acetaminophen/codeine group and 128 in the ibuprofen group).
Mean age was 8 years, half were boys, mean weight was 28 kg, 75% were white, and 9.5% to 14.1% were black.
Half were radius-only fractures, and one fifth involved the radius and ulna.
There were no significant differences in the number of doses of medication received 3 days after ED discharge, and only 7% of children used no medication.
The difference in failure of medication was not significant between the ibuprofen group (20.3%) and the acetaminophen with codeine group (31.0%).
There were no differences in total pain scores for days 0 to 3 including scores at awakening, bedtime, and before and after medication.
For functional outcomes, ibuprofen was significantly superior in return to play and eating but not for return to school and sleep functions.
60% of children had at least 1 function affected on the day of injury and 29.4% by day 3.
The risk for an adverse effect was significantly greater in the acetaminophen with codeine group (50.9%) than the ibuprofen group (29.5%).
Nausea and vomiting were significantly more common in the acetaminophen with codeine group.
86% of parents who used ibuprofen vs 67% of those using acetaminophen with codeine were very satisfied or satisfied.
27.5% in the acetaminophen group vs 10% in the ibuprofen group said they would not use the medication again.
The authors concluded that ibuprofen was similar in efficacy for pain relief in children with simple arm fracture but superior in return to function and fewer adverse effects and that ibuprofen is preferable in the outpatient management of simple arm fracture.

Clinical Implications

Ibuprofen is similar to acetaminophen with codeine in efficacy for pain relief in children with simple arm fracture.
Ibuprofen is superior to acetaminophen with codeine for return to play and eating and fewer adverse effects in the outpatient management of simple arm fracture.

Vitamin D Supplementation 2008 Recommendation

Prevention and Management of Vitamin D Deficiency in Children: Part II. Vitamin D Supplementation: Dosing Recommendations

Medscape Pediatrics

The current recommendation from both the AAP and the Lawson Wilkins Pediatric Endocrine Society is a minimum dietary intake of 400 International Units/day (10 mcg/day) for neonates, children, and adolescents.[3,4]
If this amount cannot be achieved through their normal diet, a vitamin D supplement should be administered.
Exclusively breastfed infants and those consuming less than 1 L of infant formula/day should receive 400 International Units/day of an oral liquid vitamin D product.[3,4]
The Lawson Wilkins Pediatric Endocrine Society recommends that preterm infants should receive 400 to 800 International Units of vitamin D (10 to 20 mcg) per day to compensate for decreased placental transfer in utero and decreased gastrointestinal absorption after birth.[4]

For treatment of documented vitamin D deficiency, infants may be given 1,000 to 2,000 International Units/day (25 to 50 mcg) and older children may be given up to 5,000 International Units/day (125 mcg) for 2 to 3 months.[4,8]
A variety of alternative dosing regimens have been published over the past decade.
A high-dose short-course regimen providing a total of 100,000 to 600,000 International Units (2.5 to 15 mg) over 1 to 5 days has been suggested for patients who might not adhere to longer regimens.[4]

Vitamin D dosing in children with kidney disease or other chronic illnesses should be based on serum 25(OH)D levels. Table 1 provides general recommendations for these patients. Table 2 lists dosing recommendations for children with severe or chronic deficiency states.[3–7]

Vitamin D supplements may be taken with or without food.
Administration with food may be useful to reduce stomach upset.
Calcium supplementation (30 to 75 mg/kg/day oral elemental calcium) is often necessary to maximize response in patients with vitamin D deficiency.

Patients receiving vitamin D supplementation beyond the recommended daily dietary intake should undergo periodic monitoring of serum 25(OH)D levels, using an assay for both 25(OH)D2 and 25(OH)D3, as well as serum calcium, phosphorus, and alkaline phosphatase at one and three months or until stabilized, followed by annual reassessment. Parathyroid and bone mineralization studies should be conducted as needed.[3–7]

Quadrivalent HPV Vaccine (Gardasil) Cuts Rates of Genital Warts

From Medscape Medical News
Roxanne Nelson

October 21, 2009 — The quadrivalent human papillomavirus (HPV) vaccine (Gardasil, Merck & Co) can reduce the incidence of genital warts in women and girls, and might even benefit heterosexual men. According to Australian researchers, the proportion of young women diagnosed with genital warts declined by 25% each quarter in 2008 after the initiation of an HPV vaccine program.

This is in comparison to a 1.8% increase in new cases of genital warts per quarter from 2004 to 2007, before the beginning of the vaccination initiative. The results of this analysis were published online October 16 in Sexually Transmitted Infections.

The main aim of HPV vaccination is to reduce cervical cancer (caused by HPV types 16 and 18), but Gardasil, 1 of the 2 vaccines that is available, also offers protection against genital warts (HPV types 6 and 11); Cervarix (GlaxoSmithKline), the other one, does not.

The authors note that governments in different countries are currently trying to decide which of the 2 vaccines should be included in their immunization programs, and need robust data to determine the impact of the vaccine at a population level. Beginning in 2007, Australia became one of the first countries to offer the Gardasil vaccine free of charge to girls aged 12 to 18 years, in a school-based program, and to women younger than 27 years, through general practices. The coverage rate for women between 18 and 26 years is estimated to be 65% to 70%.

Although both vaccines are licensed in Australia, only Gardasil is being used in the program. "Gardasil is the only free one at this stage," lead author Christopher K. Fairley, MBBS, PhD, told Medscape Oncology. "But one can buy Cervarix privately."

There are also no programs targeting men at this point. "It is licensed for boys, but must be purchased privately," said Dr. Fairley, who is a professor of sexual health at the University of Melbourne and director of the Melbourne Sexual Health Centre (MSHC) in Australia.

Reduced Incidence of Warts in Targeted Population

The goals of the study were to evaluate the national HPV vaccination program and to determine if it had a measurable impact on the clinical presentation of genital warts in the year after its implementation.

In this retrospective study, Dr. Fairley and colleagues compared the proportion of new patients who were diagnosed with genital warts at the MSHC from January 2004 to December 2008. During that time, 36,055 patients were seen at MSHC for the first time, and genital warts were diagnosed in 3826 (10.6%).

Only women younger than 28 years showed strong evidence of a significant difference in the average quarterly change between time periods; there was a 1.8% increase before the end of 2007 and a 25.1% decrease after the end of 2007 (P < .001). Heterosexual men were the only other subgroup to show a decrease in presentations for genital warts in 2008, with an average quarterly decrease of 5% (P = .031).

No reduction was seen in homosexual men or women beyond the targeted age group (>28 years).

The reduction in genital warts observed in heterosexual but not homosexual men might be consistent with a reduction in heterosexual transmission of HPV as a result of the women's vaccine program, the authors write. "These data should be of value to governments making decisions about whether to implement HPV vaccination in women and may assist in informing the choice of vaccine," they conclude.

Dr. Fairley pointed out that, when determining the cost effectiveness of vaccination, the avoided costs must be taken into account as well as the actual cost of the vaccine, if the price between them differs.

"There is also the issue of the duration of the immune response, and whether other subtypes are covered," he said. "Both these issues are currently under debate by the 2 vaccine companies."

No funding was obtained to undertake this study. Dr. Fairley reports receiving honoraria and research funding from and owns shares in CSL Biotherapies, the manufacturer of Gardasil. Coauthor Jane S. Hocking, MPH, PhD, from the University of Melbourne, reports receiving honoraria from CSL Biotherapies. Coauthor Basil Donovan, MD, from the University of New South Wales in Australia, reports receiving research funding from CSL Biotherapies and honoraria from GlaxoSmithKline and CSL Biotherapies.

Sex Transm Infect. Published online October 16, 2009. Abstract

Thursday, October 22, 2009

Cell Phones & Brain Cancer - the jury still out

From Medscape Medical News
Cell Phones and Brain Cancer -- Jury Still Out
Roxanne Nelson

October 14, 2009 — Cellular telephones have become an integral part of everyday life; they are now used by an estimated 4 billion people worldwide. But this is a relatively new technology, and there are lingering concerns about health risks, in particular a risk for brain cancer.

A new report suggests that that regular use of cell phones can result in a "significant" risk for brain tumors. But previous studies have been inconsistent. Even so, some European countries have taken precautionary measures, aimed specifically at children.

Cell phones can be made safer, and the technology to do so exists right now. For example, said Mr. Morgan, "you can get a 10,000-fold reduction in exposure simply by keeping the phone 6 inches away from the head."

There are also steps that can be taken right now to make cell phones safer to use, he said. These include using a wired headset (not a wireless headset such as a Bluetooth), using speaker-phone mode, or sending text messages; keeping the phone away from the body when not in use; avoiding use in a moving car, train, or bus, or in rural areas at some distance from a cell tower, because any of these uses will increase the power of the cell phone's radiation; and keeping the cell phone turned off until you need to use it.

The authors also recommend using a corded land-line phone whenever possible, instead of a wireless phone, and to avoid cell phones when inside buildings, particularly with steel structures. Since children face a greater health risk, they should not be allowed to sleep with a cell phone under their pillows or at the bedside, said Mr. Morgan. Ideally, those younger than 18 years should not use a cell phone at all, except for emergencies.

for full article see or

High Blood Pressure in Children

From Medscape Pediatrics
New European Society of Hypertension Guidelines for Management of High Blood Pressure in Children: An Expert Interview With Empar Lurbe, MD, PhD
Pippa Wysong

Hypertension in the pediatric population is an ongoing concern; in response, the European Society of Hypertension recently released new guidelines. Lead author Empar Lurbe, MD, PhD, spoke to Medscape about the guidelines, and why hypertension needs to be addressed in this young population. Dr. Lurbe is from the Department of Pediatrics at Consorcio Hospital General, the University of Valencia, Spain. She was the lead author of the new guidelines, "Management of High Blood Pressure in Children and Adolescents: Recommendations of the European Society of Hypertension" published in the Journal of Hypertension.[1] She spoke to Medscape's Pippa Wysong.

Medscape: Guidelines addressing hypertension in children and adolescents were published in the United States in 2004. Why are new guidelines needed now?

Dr. Lurbe: The necessity for guidelines has become increasingly clear to physicians in light of growing evidence that cases of mild hypertension in children and adolescents are much more common than previously thought. In addition, progress made in pathophysiologic and clinical research has made clear links between pediatric hypertension and cardiovascular disease later in life, highlighting the need for improved cardiovascular prevention strategies for pre-adult individuals.

The Task Force set up by the European Society of Hypertension has combined considerable amounts of scientific data with clinical experience to represent a consensus among specialists involved in the detection and control of high blood pressure (BP) in children and adolescents. It is hoped that the publication of these guidelines will call attention to the huge burden of hypertension in this young population, and encourage public policymakers to develop a global effort to improve identification and treatment of high BP among young people. Primarily, however, these guidelines provide practical strategies for diagnosing and treating hypertension in children and adolescents.

Medscape: What adverse health effects are caused by uncontrolled hypertension in children? Are they different than those in adults?

Dr. Lurbe: There has been a lot of work on the pathophysiology and epidemiology of high blood pressure in children over the past couple of decades. Hypertension can cause organ damage in the heart, blood vessels, kidney, brain, and retina. Events tend to be rare, so most of the evidence we have is based on the use of the markers of organ damage -- such as left ventricular hypertrophy and increased urinary albumin excretion. Clinical experience shows that reducing high blood pressure in conditions such as acute heart failure, hypertensive encephalopathy, and malignant hypertension improves survival and reduces sequelae in children. There is no doubt that increased blood pressure in children can lead to serious problems.

Medscape: Does hypertension tend to be accompanied by elevated cholesterol and other risk factors? Should these be screened and treated too?

Dr. Lurbe: Risk factors include comorbidities such as elevated cholesterol. This is especially true in obese hypertensive children, and those who have a family history of cardiovascular disease.

Medscape: What portion of hypertensive children become hypertensive adults? How strong is the evidence for this?

Dr. Lurbe: The roots of hypertension in adulthood tend to extend back to the childhood years. Indeed, childhood blood pressure does continue on into adulthood. This underscores the importance of controlling blood pressure control in children and adolescents.

Medscape: Should all children be regularly screened?

Dr. Lurbe: Children older than 3 years of age who are seen in a medical setting should have their BP measured. In younger children, BP should be measured under special circumstances that increase the risk for hypertension, such as under neonatal conditions requiring intensive care, congenital heart disease, renal disease, treatment with drugs known to increase BP, and evidence of increased intracranial pressure.

Medscape: As children grow, their blood pressure changes, normally. Can you explain how values for different categories have been developed?

Dr. Lurbe: We use a chart to help determine what ranges are normal for specific age, gender, and height. The 95th percentile is used as a cut-off for defining hypertension in children and adolescents. There are normative data based on auscultatory measurements from large studies of children around the world. There are extensive data based on measurements from more than 70,000 children in the United States. Blood pressure percentiles were calculated for each gender, age group, and for 7 height percentile categories. Height percentiles are based on growth charts attained from the Centers for Disease Control and Prevention. In Europe, reference values were obtained in 1991 by pooling data from 28,043 children and adolescents using auscultatory blood pressure measurements. In 1999, normative values were calculated from auscultatory data in 11,519 school children aged 5 to 17 years in Italy - data in that project included age, gender, and height.

Medscape: Is height the most important factor?

Dr. Lurbe: The values are based on age, gender, and height. Values developed for the United States reflect all 3 criteria together, and these are found on Tables 2 and 3 of the new guidelines.[1] The reason why blood pressure values are referred to in age, gender, and height percentiles is to take into account children who are unusually short or tall for their age.

Medscape: How should blood pressure be measured in children? Do methods change with the age of the child?

Dr. Lurbe: The diagnosis of hypertension should be based on multiple office blood pressure measurements, taken on separate occasions over time.

Medscape: Which antihypertensive agents can be used in pediatrics?

Dr. Lurbe: The agents of choice are similar to those in adults: angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, calcium antagonists, beta-blockers, and diuretics and other antihypertensive agents. There have been very few trials doing head-to-head comparisons of these agents in children.

Medscape: How strong is the evidence for their effectiveness? Are they safe?

Dr. Lurbe: Evidence for effectiveness is mostly of newer drugs, because many of the older drugs are now off-patent and studies weren't performed for the pediatric population. Recommendations in the guidelines are based primarily on a few industry-sponsored studies, and mostly case series from single centers. There is also collective clinical experience, expert opinions, and extrapolation from adult studies.

Medscape: Should doctors recommend lifestyle changes before trying drug therapy? Would lifestyle changes and weight loss be enough?

Dr. Lurbe: That might help for mild cases, but there is currently a lack of hard evidence. Studies are underway looking at lifestyle changes. With medications, generally, it is recommended that children begin with a low dose of a single drug. You don't want blood pressure to drop too rapidly. If a single drug doesn't do the trick, then combinations may be needed -- especially in severe hypertension.

Medscape: What lifestyle changes should physicians discuss with patients/parents?

Dr. Lurbe: Most interventions are common sense, such as exercise, weight loss, and a healthy diet. Some evidence suggests 40 minutes of aerobic-based exercise 3-5 times weekly improves vascular function and lowers blood pressure in children. Interventions that work together to reduce energy intake and increase activity are bound to help. Dietary trials clarifying what would work best in children are underway. Making sure diets are generally balanced, and reducing junk food is common sense.

Medscape: What does the future hold in this area?

Dr. Lurbe: A lot more research is necessary, ranging from high-quality clinical trials comparing treatments, as well as trials looking at long-term outcomes such as organ damage. There is also a need for robust values for home, office, and ambulatory blood pressure.

Medscape: You've touched on a lot of areas in the guidelines. Thanks for talking to Medscape today.


Wednesday, October 21, 2009

Routine Poliovirus Vaccination

From Morbidity & Mortality Weekly Report
Updated Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Published: 10/15/2009

This report updates Advisory Committee on Immunization Practices (ACIP) recommendations for routine poliovirus vaccination.
These updates aim to 1) emphasize the importance of the booster dose at age ≥4 years, 2) extend the minimum interval from dose 3 to dose 4 from 4 weeks to 6 months, 3) add a precaution for the use of minimum intervals in the first 6 months of life, and 4) clarify the poliovirus vaccination schedule when specific combination vaccines are used.

On June 17, 1999, ACIP recommended that all poliovirus vaccine administered in the United States be an inactivated poliovirus vaccine (IPV) beginning January 1, 2000. This policy was implemented to eliminate the risk for vaccine-associated paralytic poliomyelitis, a rare condition that has been associated with use of the live oral poliovirus vaccine (OPV). Since 1999, no OPV has been distributed in the United States. Under these ACIP recommendations, the routine IPV vaccination schedule in the United States consists of 4 doses administered at ages 2 months, 4 months, 6–18 months, and 4–6 years with the minimum interval between all IPV doses as 4 weeks.[1,2]

Since the ACIP recommendation was made 10 years ago, three different combination vaccines containing IPV have been licensed for routine use in the United States (Table). Because of potential confusion in using different vaccine products for routine and catch-up immunization, ACIP recommends the following:

The 4-dose IPV series should continue to be administered at ages 2 months, 4 months, 6–18 months, and 4–6 years.
The final dose in the IPV series should be administered at age ≥4 years regardless of the number of previous doses.
The minimum interval from dose 3 to dose 4 is extended from 4 weeks to 6 months.
The minimum interval from dose 1 to dose 2, and from dose 2 to dose 3, remains 4 weeks.
The minimum age for dose 1 remains age 6 weeks.
ACIP also is making a new recommendation concerning the use of minimum age and minimum intervals for children in the first 6 months of life. Use of the minimum age and minimum intervals for vaccine administration in the first 6 months of life are recommended only if the vaccine recipient is at risk for imminent exposure to circulating poliovirus (e.g., during an outbreak or because of travel to a polio-endemic region). ACIP is making this precaution because shorter intervals and earlier start dates lead to lower seroconversion rates.[3–5]

In addition, ACIP is clarifying the poliovirus vaccination schedule to be used for specific combination vaccines. When DTaP-IPV/Hib* (Pentacel) is used to provide 4 doses at ages 2, 4, 6, and 15–18 months, an additional booster dose of age-appropriate IPV-containing vaccine (IPV [Ipol] or DTaP-IPV† [Kinrix]) should be administered at age 4–6 years. This will result in a 5-dose IPV vaccine series, which is considered acceptable by ACIP.
DTaP-IPV/Hib is not indicated for the booster dose at age 4–6 years. ACIP recommends that the minimum interval from dose 4 to dose 5 should be at least 6 months to provide an optimum booster response. In accordance with existing recommendations, if a child misses an IPV dose at age 4–6 years, the child should receive a booster dose as soon as feasible.[2]

* Diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus, and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine.
† Diphtheria and tetanus toxoids and acellular pertussis adsorbed, and inactivated poliovirus vaccine.


Wednesday, October 7, 2009

Guidelines for Vitamin D Intake

From Medscape Medical News
American Academy of Pediatrics Updates Guidelines for Vitamin D Intake CME/CE
Laurie Barclay, MD & Désirée Lie, MD, MSEd

Pediatrics. Published online October 13, 2008. 2008;122:1142-1152.

Clinical Context

Rickets and vitamin D deficiency are preventable conditions with adequate nutritional intake of vitamin D but are still prevalent in the United States and other Western countries, particularly in exclusively breast-fed infants and in those with chronic diseases. Rickets has a peak incidence of ages 3 to 18 months and may present with hypocalcemic seizures.

This is an update of the 2003 AAP guidelines for vitamin D intake in children and adolescents, which recommended a daily intake of 200 IU of vitamin D daily beginning at 2 months of life, to account for evidence showing that a higher intake is necessary to avoid vitamin D deficiency and insufficiency.

Study Highlights

There is evidence that 400 IU of vitamin D daily not only prevents rickets but also treats the condition.
In adults, vitamin D deficiency is defined as a level of 25-hydroxyvitamin D less than 50 nmol/L and vitamin D insufficiency as a level of 50 to 80 nmol/L.
The main source of vitamin D is via skin synthesis from cholesterol after exposure to UVB light.

Those most susceptible to vitamin D insufficiency include breast-fed infants, those with low sunlight exposure, those with dark skin pigmentation that takes 5 to 10 times longer to generate vitamin D3, and those with chronic diseases such as cystic fibrosis and fat malabsorption.
Mothers who are vitamin D deficient may expose their fetuses and infants to higher risk for vitamin D deficiency after birth and during lactation, and their vitamin D status should be monitored.
Inadequate vitamin D status in pregnant women has an effect on fetal skeletal development, tooth enamel formation, and general fetal growth.
However, universal recommendations for high-dose vitamin D supplementation during pregnancy are not available at present, and recommendations for supplementation in children are thus necessary.

Vitamin D levels in breast milk vary from less than 25 IU/L to 78 IU/L, and infants who are exclusively breast-fed are at increased risk for deficiency.

Vitamin D supplementation should begin at birth or in the first few days of life with 400 IU per day for breast-fed and partially breast-fed infants.
Supplementation should be continued unless the infant is weaned to 1 L per day or 1 quart per day of vitamin D–fortified formula or whole milk.

Whole milk should not be used until after age 12 months, and reduced-fat milk is recommended for those with obesity.
All non–breast-fed infants and older children ingesting less than 1 L per day of vitamin D–fortified milk or formula should receive 400 IU of vitamin D daily.
Adolescents are at increased risk for vitamin D deficiency because the intake of milk was reduced by 36% between the 1970s and the 1990s.
Adolescents should be encouraged to drink milk daily (100 IU per 8-oz serving) and to consume vitamin D–fortified foods (cereals and eggs).
1 L of vitamin D–fortified milk daily is required to meet the daily vitamin D recommendations for adolescents.
Without adequate dietary intake, adolescents should be supplemented with 400 IU of vitamin D daily.
According to available evidence, serum levels of 25-hydroxyvitamin D in infants and adolescents should be 50 nmol/L or higher.
In children with additional risk factors for vitamin D deficiency, such as those with chronic diseases, those receiving seizure medications, or those with fat malabsorption, higher doses of vitamin D may be needed daily.
In these children, levels of 25-hydroxyvitamin D should be monitored every 3 months until normal levels have been achieved with vitamin D supplementation.
Pediatricians and other healthcare professionals should make vitamin D supplements readily available to children in their community, especially those at risk for deficiency or insufficiency.

Pearls for Practice

Vitamin D supplementation at 400 IU per day should begin within the first few days of life and is especially recommended in breast-fed children, and supplementation may be higher for children with additional risk factors.
Adolescents who do not consume adequate vitamin D in their diet should have an intake of 400 IU of vitamin D supplements daily.

Reports of Autoimmune Disorders After HPV Vaccine Raise Questions

From Medscape Medical News

Allison Gandey

September 23, 2009 (Düsseldorf, Germany) — Investigators have identified cases of autoimmune disorders after immunization with the quadrivalent vaccine Gardasil. The Merck product is designed to prevent infection with several types of human papillomavirus.

Presenting here at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, researchers emphasized that they have not established a causal relationship between the vaccine and autoimmune problems but would like clinicians to monitor patients for any emerging adverse effects.

Two groups presented on this subject at the meeting: one identified a case of multiple sclerosis after vaccination, and the second a case of neuromyelitis optica. The studies reportedly received no outside funding.

"We will need to determine whether the incidence of autoimmune disorders is the same in the general population as in those who are vaccinated," lead investigator Maria Bouktsi from the Interbalkan European Medical Center in Thessaloniki, Greece, said in an interview.

Dr. Bouktsi pointed out this is especially important considering that the primary population for vaccination is young females and that many are already at increased risk for multiple sclerosis.

Dr. Bouktsi and her team are questioning whether the immuno-stimulatory properties of the human papillomavirus–like particles of the vaccine are triggering adverse effects in vulnerable patients.

It is the same question that researchers asked in a recent issue of Multiple Sclerosis (2009;15:116–119). Ian Sutton, MD, from St. Vincent's Hospital in New South Wales, Australia, and his team reported 5 patients who developed multiple sclerosis after vaccination with Gardasil. The group reported in January that patients presented with multifocal or atypical demyelinating syndromes within 21 days of immunization.

Causal Relationship Not Established, but Link Worth Investigating

No definitive conclusions can be made based on this report, Dr. Sutton and his team noted. "It should not be overlooked that several epidemiological studies indicate that viral infection is associated with a threefold increase in the risk of a multiple sclerosis relapse," write the researchers.

Lead investigator of the second group presenting on this topic at the meeting told Medscape Neurology he agrees that postmarketing pharmacosurveillance is necessary to improve safety. "Human papillomavirus vaccines elicit a strong inflammatory systemic immune response," said Til Menge, MD, from Heinrich-Heine University in Düsseldorf, Germany.

His group suggests that it was this inflammatory response that may have triggered a case of fulminant neuromyelitis optica in a previously healthy 17-year-old girl.

Researchers suggest data are insufficient to justify making firm recommendations regarding treatment of patients with multiple sclerosis.

Dr. Bouktsi added, "A prospective case-control study of patients with multiple sclerosis or clinically isolated demyelinating syndromes receiving the Gardasil vaccine may provide relevant safety data in this population."

The researchers have disclosed no relevant financial relationships.

European Committee for Treatment and Research in Multiple Sclerosis: Poster 308 and 514. Presented September 10 and 11, 2009.

Friday, October 2, 2009

Death After Cervarix Propels HPV Vaccination Into Headlines Again

From Medscape Medical News

September 30, 2009 (updated October 1, 2009) — The sudden death of a 14-year-old British girl shortly after she received Cervarix, a vaccine against human papillomavirus (HPV) to prevent cervical cancer, hit headlines worldwide yesterday. Today, however, the death is being reported as unlikely to have been related to the vaccine. The next day, a postmortem revealed that the girl had a large tumor in her chest cavity.

This is not the first time that a death has been reported after HPV vaccination; many of the other cases have been reported after inoculation with Gardasil in the United States, although there has been no proof of causality. Some of these deaths have also received wide media attention, and last month a mother who lost her daughter after HPV vaccination testified before a US Food and Drug Administration (FDA) advisory committee meeting.

In the latest incident, Natalie Morton, of Coventry in the United Kingdom, died on the same day that she received the vaccine at school as part of a national HPV vaccination program. She collapsed less than 2 hours after the injection, which was the first dose of a planned 3-dose course.

A preliminary postmortem revealed that she had "a serious underlying medical condition which was likely to have caused death," according to Caron Grainger, MD, joint director of public health in Coventry.

"We are awaiting further test results. However, indications are that it is most unlikely that the vaccination was the cause of death," Dr. Grainger said in a statement.

In response to the news of the death, several health authorities in the United Kingdom announced that they were temporarily suspending their HPV vaccination programs.

The Department of Health said all vaccines from the same batch (HPV1 Cervarix AHP VA04 3BB) would be quarantined as a precaution.

"No link can be made between the death and the vaccine until all the facts are known and a postmortem takes place," the Department wrote in a letter to health professionals. "As a purely precautionary measure, it is important that all stocks of Cervarix vaccine from the above batch are quarantined until the above incident has been fully investigated."

Further details were revealed the following day at a hearing at Coventry Magistrates' Court. Deputy coroner Louise Hunt said the postmortem revealed a large tumor that had "heavily infiltrated" the heart and had extended into the left lung. A pathologist told the inquest that the condition was "so severe that death could have arisen at any point," according to a report on BBC News.

Cervarix in UK, But Gardasil Elsewhere

The UK national program of HPV vaccination began last year, offering the vaccine through schools to all girls in the 12- to 13-year-old age range. A catch-up program for older girls, up to 18 years, was launched just recently, with the aim of covering all girls under 18 years by 2011. An estimated 1.4 million girls in the United Kingdom have already received the vaccine.

The United Kingdom chose to use Cervarix, manufactured by GlaxoSmithKline, for its national program, whereas many other countries — including the United States and Australia — chose to use Gardasil from Merck & Co. In fact, Cervarix is not available in the United States, and may not be for some time yet, it now appears.

Yesterday, the FDA announced that it was postponing its decision on approval of Cervarix, saying that it needed more time to consider the data, even though an FDA advisory committee meeting recently voted overwhelmingly for approval, as previously reported by Medscape Oncology.

The UK decision to choose Cervarix and not Gardasil has been questioned in the British press, with newspapers pointing out that the reasons behind the choice were never revealed, but is widely speculated to have been based on cost, with Cervarix being cheaper.

But the 2 vaccines also differ from each other in a key aspect.

Cervarix protects against 2 types of HPV virus (types 16 and 18), which together account for about 70% of all cervical cancer. Gardasil also protects against these, but in addition offers protection against HPV types 6 and 11, which cause genital warts. This extra activity means that Gardasil is also indicated for the prevention of genital warts in girls and women, and could be used for this indication in boys and men (it was recommended for approval for this use at the recent FDA advisory committee meeting).

However, the main purpose behind the development of these vaccines was to prevent cervical cancer, and for this indication, Cervarix is the better of the 2 vaccines, according to expert Diane Harper, MD, from the University of Missouri–Kansas City School of Medicine.

Dr. Harper has been involved in clinical trials with both vaccines, and was approached by Medscape Oncology for comment. As previously reported, Dr. Harper said that Cervarix was longer lasting, resulted in higher antibody titers, and offered wider cross protection against other HPV types than Gardasil.

But Dr. Harper has also been very vocal in emphasizing that these vaccines are not the only way to protect against cervical cancer, and she has repeatedly stressed that even when they are used, it remains vital to screen for cervical cancer with regular Pap tests.

She has joined in with questions over the benefit–risk analysis of HPV vaccination that have been raised, most recently in an editorial in the Journal of the American Medical Association (JAMA), as reported by Medscape Oncology.

That August 19 issue of JAMA also published details of adverse events that have been reported with Gardasil during its 2.5 years on the market (JAMA. 2009;302:750-757). These reports were made to the US Vaccine Adverse Event Reporting System, which is operated jointly by the FDA and the Centers for Disease Control and Prevention (CDC). The authors emphasized that a report of an adverse event does not necessarily mean there is a causal link. The paper noted that 12,424 reports of adverse events had been received, of which 772 (6.2%) were for serious adverse events, including 32 deaths.

This is a sobering reality.
In the United States, the death rate from cervical cancer (3 of 100,000 women, according to statistics from the CDC) is currently similar to the rate of reported serious adverse events from Gardasil (3.4 of 100,000 doses distributed), Dr. Harper pointed out. "This is a sobering reality," she said. "Would a parent accept such a rate of serious adverse events if the same cancer prevention can occur with continued Pap screening? Is there any acceptable level of risk of serious adverse events, including death, to prevent genital warts?"

A debate about the HPV vaccine is running on Medscape's Green Mountain Doc blog, written by Katharine Hikel, MD, who specializes in writing about women's health issues. Her post, entitled "'One Less Sucker' — Gardasil," criticized the marketing of this product, questioned whether it was medically necessary, and highlighted its adverse event rate.

"The rush-to-market approach for this questionable product, with billions spent on promotion, has completely [over-ridden] good judgment, critical analysis, and clear thinking on the part of providers," Dr. Hikel writes. She asserts that this has put millions of women "needlessly at risk."

In contrast, many cervical cancer specialists have spoken up in favor of HPV vaccination, as previously reported by Medscape Oncology. Maurie Markman, MD, professor of gynecologic medical oncology at the University of Texas MD Anderson Cancer Center in Houston, and an editorial advisor to Medscape Oncology, has repeatedly emphasized the benefits of the vaccine and the unique opportunity that it offers for protection from cervical cancer. He has spoken reassuringly about the safety of the vaccine, most recently in his videoblog "How Safe Is the HPV Vaccine?"

This view was echoed recently by the Society of Gynecologic Oncologists (SOG), which said that HPV vaccination represented a "paradigm-shifting prevention strategy for cervical cancer." In a statement released to the recent FDA advisory committee meeting, the SOG said: "The public-health value of the protection afforded by HPV vaccination overwhelmingly outweighs the self-limiting local side effects and even the rare but more serious effects that may or may not be vaccine-related."

Dr. Harper reports having received honoraria from Merck & Co and GlaxoSmithKline, and institutions at which she has worked have received funding from both companies to support clinical trials on HPV vaccines. Dr. Markman reports having received grants for educational activities from Eli Lilly and serving as an advisor or consultant for Genentech, Celgene Corporation, Tibotec, and Boehringer Ingelheim.

Thursday, October 1, 2009

Bacterial Coinfection May Have Contributed to H1N1 Deaths

From Medscape Medical News
Laurie Barclay, MD

September 30, 2009 — Bacterial coinfection with Streptococcus pneumoniae may have contributed to deaths in the United States from 2009 H1N1 influenza, according to the results of a study reported online first in the September 29 issue of the Morbidity and Mortality Weekly Report. The Centers for Disease Control and Prevention (CDC) are therefore urging pneumococcal vaccination when indicated.

"Our influenza season is off to a fast start and unfortunately there will be more cases of bacterial infections in people suffering from influenza," CDC Epidemiologist Matthew Moore, MD, said in a news release. "It's really important for people, especially those at high risk for the serious complications from influenza, to check with their provider when they get their influenza vaccine about being vaccinated against pneumococcus."

In an analysis of lung tissue specimens from 77 confirmed fatal US cases of 2009 H1N1, in which deaths occurred from May 1 to August 20, 2009, bacterial coinfections were present in 22 (29%) cases. These fatal cases were defined as influenza-like illness or postmortem findings suggesting viral pneumonia and laboratory-confirmed 2009 pandemic influenza A (H1N1) virus infection by real time reverse transcriptase–polymerase chain reaction.

Of the 22 cases with bacterial coinfection, 10 were caused by S pneumoniae, 7 by S aureus, 6 by S pyogenes, 2 by S mitis, and 1 by Haemophilus influenzae. In 4 cases, there were multiple pathogens. Median age was 31 years (range, 2 months – 56 years), and half were men. The cases were reported from California, Hawaii, Illinois, New Jersey, New York, Texas, Utah, and Virginia.

Of the 21 patients with known previous medical history, 16 had underlying medical conditions associated with increased risk for influenza-associated complications, and 15 had indications for vaccination with 23-valent pneumococcal polysaccharide vaccine.

The CDC is recommending that:

pneumococcal conjugate vaccine be given to all children younger than 5 years, as per current guidelines, and
all persons aged 65 years and older, as well as those aged 2 to 64 years with high-risk conditions, receive the 23-valent pneumococcal polysaccharide vaccine, as described on the CDC's Web site.

Limitations of this report are that the cases do not come from a systematic sample and might not be representative of all pandemic H1N1 deaths or all pandemic H1N1 deaths associated with bacterial pneumonia. Not all potential bacterial pathogens were evaluated, patient information was limited, and evaluation of bacterial coinfections was performed at autopsy.

"The findings in this report also underscore the importance of managing patients with influenza who also might have bacterial pneumonia with both empiric antibacterial therapy and antiviral medications," the editors conclude. "In addition, public health departments should encourage the use of pneumococcal vaccine, seasonal influenza vaccine, and, when the vaccine becomes available, pandemic influenza A (H1N1) 2009 monovalent vaccine."

Morb Mortal Wkly Rep. Published online September 29, 2009.