Pediatric Infectious Disease Newsletter
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May 2009  

Do febrile infants with bronchiolitis get severe bacterial infections? 
A study from the AAP's Pediatric Research in Office Settings (PROS) network addresses this question. Bronchiolitis was diagnosed in 218 (7%) of 3066 enrolled infants under 3 months of age. None with bronchiolitis had a serious bacterial illness. Among the remaining patients without bronchiolitis, serious bacterial illness included 14 with bacterial meningitis (0.5%), 49 with bacteremia (1.7%), and 167 with UTI (5.9%). Predictors of IV antibiotic use in children with bronchiolitis included initial ill appearance, age <30 days, and fever >38.5. (Luginbuhl LM, et al. Pediatrics 2008;122:947-54.)
Maternal Flu Immunization
We know that higher cord blood levels of influenza antibodies correlate with delayed onset and decreased severity of influenza infection in young infants. Administration of influenza vaccine to pregnant women may offer protection for their young infants, especially since influenza vaccination is not offered to infants until 6 months of age. Maternal immunization resulted in a 63% reduction in lab-confirmed cases of influenza illness in infants under 6 months old. Reductions of any respiratory illness with fever were seen in 29% of the infants and in 36% of the mothers. Infant antibody levels are higher if the mother was immunized <6 months before delivery. (Zaman K, et al. New Engl J Med 2008;359:1555-64.)
Vaccines Do Not Cause Autism
There have been proposed hypotheses that vaccines are the cause of autism. These hypotheses include multiple vaccines "overwhelming" the immune system, combination vaccines such as MMR (measles-mumps-rubella) injuring the intestinal mucosa  and allowing brain-damaging proteins to enter, and thimerosol (preservative containing ethyl mercury) as a toxin damaging the brain.  There have been 13 studies since 1998 that have failed to support a link between MMR and autism, as well as 7 studies that have failed to support an association between thimerosol and autism.

Another proposed theory is that immunizing an infant with multiple vaccines causes autism by weakening the immune system. This theory has multiple flaws. First, with current advances in vaccine development, the total immunologic load has decreased despite the increased number of childhood vaccinations.  Of the 14 vaccines, there are <200 proteins or polysaccharides as compared to >3000 in 7 vaccines given 29 years ago. Secondly, vaccines only represent a small fraction of what a child's immune system is exposed to on a regular basis through food and the environment.  A virus will trigger a greater immune response that exceeds even that of multiple immunizations.  Thirdly, vaccines do not weaken the immune response. On the contrary, they provide a strong immune response to viruses that otherwise can actually predispose an unimmunized child to develop secondary bacterial infections (examples: varicella/S. pyogenes infection and influenza/secondary bacterial pneumonia with S. aureus or S. pneumoniae). Lastly, autism is not an immune-mediated disease like multiple sclerosis. There is no evidence of immune activation or inflammatory lesions like autoimmune CNS diseases. Recently, scientific data published in Science (2008) suggests autism is caused by genetic variation in neuronal circuitry that affects synaptic development.

Overall, There have been twenty epidemiologic studies showing no link between MMR or thimerosol as a cause of autism.  These studies have been done around the world with large diverse populations.

Gerber JS and Offit PA. Clinical Infectious Disease 2009;48 (4): 456-461
Suggestions for Addressing Vaccine Refusals
Parents often express reasonable concern about immunization safety after encountering the wide variety of misleading internet and television information on purported vaccine adverse effects. During a recent symposium at a major infectious diseases conference, several physicians and journalists on the panel discussed the best ways to talk to parents and the media about this hot issue. Although they recognized some benefit of educating parents on how the scientific method applies to vaccine safety research, most agreed that the most effective messages that one can convey are 1) that multiple studies fail to demonstrate an association between autism and MMR, and 2) that most of the vaccine-preventable diseases still exist endemically in this country. Giving case examples of patients you have seen with such diseases can have a significant impact on convincing families of the importance of immunizations. They also agreed that many parents cannot process or understand excessive scientific information, so be brief with the science. (2008 ICAA/IDSA, Washington, DC, October 25-28.)
 
What do we know about the effectiveness of various regimens for decolonization of MRSA in adults and children?
Seven controlled randomized trials for MRSA decolonization are shown in the table below.   All populations studied are adult and almost all were either hospitalized or in another type of healthcare facility.  The results of the studies cannot be compared because of the following:  1) the populations studied were diverse; 2) some studies only determined nasal colonization/decolonization; 3) lengths of treatment were variable; and 4) duration of follow-up. In addition, earlier studies involved hospital-associated MRSA (HA-MRSA) rather than community-acquired MRSA (CA-MRSA) and the two most recent studies do not distinguish between HA- or CA-MRSA strains.   This is important since HA-MRSA and CA-MRSA have different biological characteristics that affect antibiotic susceptibility and that may influence the sites of colonization. 
All except the most recent study showed no statistical significance between the arms.  Of note is that the most recent study by Simor, et al., used a combination of 2 topical agents and 2 systemic agents to achieve decolonization in 74% of patients for 3 months.
 
No randomized controlled trials for decolonization of MRSA in children have been conducted. 
 
Randomized controlled trials evaluating decolonization regimens for MRSA on various adult pt populations
 
 
Author/
Year Published
# pts Treatment Regimens Days Rx Wks F/U Eradication Rate Statistical significance
Peterson (1990) 21 Rifampin + ciprofloxacin 14 24 27 NS
Rifampin + TMP/SMX 40
Walsh (1993) 94 Rifampin + novobiocin 7 2 67 NS
Rifampin + TMP/SMX 53
Muder (1994) 35 Rifampin 5 2 70 NS (all combinations due to low power, very wide CI's)
Minocycline 38
Rifampin + minocycline 50
No treatment 14
Parras (1995) 84 Mupirocin 5 4 45 NS
Fusidic acid + TMP/SMX (q day dosing) 69
Harthbarth (1999) 102 Clorhexidine + mupirocin 5 4 25 NS
Clorhexidine + placebo 18
Dryden (2004) 224 Mupirocin 2% nasal ointment, chlorhexidine 4% soap, silver sulfadiazine 1% cream 5 2 49 NS
Tea tree 10% cream, tea tree 5% body wash 41
*Simor (2007) 146 Clorhexidine + mupirocin + rifampin + doxycycline 7 days 7 12 74 Sig
 
*Simor AE, Phillips E, McGeer A, Konvalinka A, Loeb M, Devlin HR, Kiss A.  Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization. Clin Infect Dis. 2007 Jan 15;44(2):178-85. Epub 2006 Dec 14. 
 
Discordance Between Staphylococcus aureus Nasal Colonization and Skin Infections in Children
A brief report by Chen, et al, showed that there was discordance between MRSA and MSSA nasal colonization and MRSA and MSSA wound infections in children. 

As part of a prospective, randomized study examining outpatient treatment for skin and soft tissue infections (SSTI), 95 children with infection had cultures of their wound and anterior nares.  For the 64 children with MRSA cultured from wound, 31% had MRSA isolated from anterior nares, 12% had MSSA isolated form anterior nares and 50% had neither MRSA or MSSA isolated.  Almost all isolates where shown to be PFGE type USA300, the predominant circulating CA-MRSA strain.  This report suggests that MRSA nasal colonization in children may not be as strongly related to MRSA SSTIs if the etiologic agent is CA-MRSA. 

In many adult studies on colonization with MRSA, the nares is not the predominant site that is colonized. Instead, the throat and rectum may be colonized.  Studies in children also suggest that the throat may be the most common site for isolation of MRSA in carriers.

The implications of these findings are that 1) only examining the nares for MRSA colonization may result in significant under-detection of MRSA colonization in children and adults, and 2) MRSA colonization of the throat and rectum may prevent most MRSA decolonization regimens from being successful.

Chen AE, Cantey JB, Carroll KC, Ross T, Speser S, Siberry GK
Discordance Between Staphylococcus aureus Nasal Colonization and Skin Infections in Children.  Pediatr Infect Dis J. 2009 Jan 21. 
Another large multistate Salmonella outbreak
As of January 12, 2009, 410 persons infected with the outbreak strains of Salmonella typhimurium have been reported from 43 states.  To date, Florida is one of 7 states with no reported cases related to this outbreak.  Among the 388 persons with dates available, illnesses began between September 3 and December 31, 2008, with most illnesses beginning after October 1, 2008. Patients range in age from <1 to 98 years; 48% are female. Among persons with available information, 18% were hospitalized and the infection may have contributed to three deaths.  Preliminary data indicates that the outbreak may be associated with peanut butter produced by a specific manufacturer that is distributed by King Nut Companies.  On January 10, 2009, King Nut Companies, a distributor of peanut butter manufactured by Peanut Corporation of America, issued a voluntary recall of peanut butter distributed under the King Nut label. In addition, King Nut Companies also issued a voluntary recall of Parnell's Pride peanut butter distributed by King Nut, which is produced by the same manufacturer. The recalled products have lot codes beginning with "8". No other King Nut products are included in this voluntary recall.

In order to determine if a Salmonella isolate is part of an outbreak, medical laboratories that identify Salmonella from patient samples are required by law to send all isolates of Salmonella to their State Health Department.  The State Laboratory perform a special DNA analysis test called pulsed-field gel electrophoresis (PFGE) pattern on the isolates.  PFGE is a molecular method to examine the DNA of each Salmonella isolate by producing a "genetic fingerprint" that is used to identify specific strains of the bacteria.  The genetic fingerprint of each isolate is entered in a large internet database called PulseNet that is maintained by CDC.  This database allows the CDC to do a rapid analysis of all isolates to see if any isolates have the same genetic fingerprint.  If they do, the CDC will conduct a multistate investigation in cooperation with State Health Departments to try to determine the source of the bacteria and take steps to halt the outbreak. 

There have been several other large multistate Salmonella outbreaks.

An outbreak of Salmonella Saint-Paul occurred from April through August, 2008.  At least 1442 persons infected with Salmonella saintpaul with the same genetic fingerprint were identified in 43 states, the District of Columbia, and Canada. Four cases were reported in Florida.  At least 286 persons were hospitalized, and the infection might have contributed to two deaths.  Preliminary epidemiologic and microbiologic results indicated that jalape�o peppers were a major vehicle by which the pathogen was transmitted.  Serrano peppers and possibly tomatoes were also vehicles. Contamination of produce items might have occurred on the farm or during processing or distribution; the mechanism of contamination has not been determined.

Between Jan 2006 and October 2008, the CDC determined that 79 cases salmonellosis caused by Salmonella schwarzengrund with an indistinguishable genetic fingerprint occurred in humans through the transmission of the Salmonella from contaminated dry dog food manufactured in a Mars Petcare US facility in Pennsylvania.  Many of the persons affected were children.  The plant was closed down in July 2008. No cases occurred in Florida.

Between January 1, 2007 and October 29, 2007, at least 272 cases of Salmonella caused by isolates of Salmonella I 4,[5],12:i:- with an indistinguishable genetic fingerprint were collected from ill persons in 35 states, including Florida.  The CDC investigation indicated that eating Banquet brand pot pies produced by the ConAgra Foods company was the likely source of the illness.  This finding lead to the recall of lots of suspected contaminated pot pies.  Although the pot pies were contamined with Salmonella, the bacteria would have been killed if the pot pies were heated according to package instructions.
 
Advice to your patients on preventing infection with Salmonella
Foods of animal origin may be contaminated with Salmonella; people should not eat raw or undercooked eggs, poultry, or meat. Raw eggs may be unrecognized in some foods, such as homemade Hollandaise sauce, Caesar and other homemade salad dressings, tiramisu, homemade ice cream, homemade mayonnaise, cookie dough, and frostings. Poultry and meat, including hamburgers, should be well cooked, not pink in the middle. Persons also should not consume raw or unpasteurized milk or other dairy products. Produce should be thoroughly washed.

Cross-contamination of foods should be avoided. Uncooked meats should be kept separate from produce, cooked foods, and ready-to-eat foods. Hands, cutting boards, counters, knives, and other utensils should be washed thoroughly after touching uncooked foods. Hand should be washed before handling food, and between handling different food items.

People who have salmonellosis should not prepare food or pour water for others until their diarrhea has resolved.  Many health departments require that restaurant workers with Salmonella infection have a stool test showing that they are no longer carrying the Salmonella bacterium before they return to work.

People should wash their hands after contact with animals, pet food and animal feces. Reptiles are particularly likely to have Salmonella, and it can contaminate their skin. Reptiles and amphibians (including turtles) are not appropriate for small children and should not be in the same house as an infant, immunodeficient person or person pre-disposed to infection with salmonella (i.e. sickle cell disease).  Salmonella carried in the intestines of chicks and ducklings contaminates their environment and the entire surface of the animal. Children can be exposed to the bacteria by simply holding, cuddling, or kissing the birds. Children should not handle baby chicks or other young birds.  Furthermore, a recent multistate outbreak of Salmonella was caused by contaminated pet food.

For additional information on the multistate Salmonella outbreaks that have occurred since 2006, see http://www.cdc.gov/salmonella/outbreaks.html.  For additional information on Salmonella, see http://www.cdc.gov/nczved/dfbmd/disease_listing/salmonellosis_gi.html#7.
 
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In This Issue
Do febrile infants with bronchiolitis get severe bacterial infections?
Maternal Flu Immunization
Vaccines Do Not Cause Autism
Suggestions for Addressing Vaccine Refusals
What do we know about the effectiveness of various regimens for decolonization of MRSA in adults and children
Discordance Between Staphylococcus aureus Nasal Colonization and Skin Infections in Children
Another large multistate Salmonella outbreak
Advice to your patients on preventing infection with Salmonella
H1N1 Swine Influenza
A New Virus for Italy
Accelerated Pertussis Immunization of Infants
Anti-Vaccinationists (Not a New Phenomenon)
A Demonstration Against Vaccination
New Pattern of Influenza Virus Resistance
David M. Berman, D.O.
Juan Dumois III, M.D.
Shirley Jankelevich, M.D.
Allison Messina, M.D.
Dale Bergamo, M.D.
Patricia Emmanuel, M.D.
Jorge Lujan-Zilbermann, M.D.
Carina A. Rodriguez, M.D.
Katie Namtu, Pharm.D.

Inpatient Consultation:
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Phone: 727-767-4160
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H1N1 Swine Influenza
Recommendations for the management of Swine influenza continue to change rapidly. Rather than summarize the current recommendations, the following websites provide the most up-to-date information: 
 
Centers for Disease Control and Prevention
 
A New Virus for Italy
 
The town of Ravenna in northern Italy experienced an outbreak of fever and arthralgias in 2007. Other symptoms included headache, rash, emesis and myalgias. Samples from human patients and local mosquitoes yielded Chikungunya virus, which had not been detected in Italy before. A member of the Alphavirus genus, this virus is endemic to countries around the Indian Ocean. It was introduced to Italy by a traveler to India. However, the Aedes albopictus mosquito that served as the vector was introduced into Italy in a shipment of used tires from Georgia, USA.  The disease usually lasts a few days to weeks, but some patients may develop chronic fatigue and joint pains. Serologic testing can be done by the CDC's Arbovirus Diagnostic Lab. (Eurosurveillance 2007;12[47], www.eurosurveillance.org)
Accelerated Pertussis Immunization of Infants
The incidence of pertussis disease peaks at 1 month of age and trails off in older infants. Although pertussis vaccine usually is given to infants at 2, 4 and 6 months of age, the CDC guidelines state that the first dose can be given as early as 6 weeks of age. Vaccine effectiveness in infants is 46%, 80%, and 82% after one, two, and three doses, respectively. Shinall et al,1 recently studied the potential effect of routine administration of pertussis vaccine to U.S. infants at 6 weeks of age, with the subsequent 2 doses given at 2 and 4 months of age. They estimated that such a schedule in the U.S. would prevent 1236 pertussis cases (9%), 898 hospitalizations (9%), and 7 deaths (6%). Giving the second and third doses of pertussis vaccine two weeks early might prevent an additional 923 cases, 520 hospitalizations, and 2 deaths. Infants under 6 weeks of age may benefit from additional protection if their mothers are given Tdap vaccine during the 2nd or 3rd trimester of pregnancy, as recommended by the AAP.2 (1. Shinall MC, et al. Pediatrics 2008;122:1021-6; 2. AAP. Pediatrics 2006;117:965-78.) 
Anti-Vaccinationists (Not a New Phenomenon)
Osler's Condemnation of Anti-Vaccinationists

"I would like to issue a Mount Carmel-like (mountain in Israel) challenge to any ten unvaccinated priests of Baal (a false god or idol). I will take ten selected vaccinated persons, and help in the next severe epidemic, with ten unvaccinated persons (if available!). I should choose three Members of Parliament, three anti-vaccination doctors, if they could be found, and four anti-vaccination propagandists. And I will make this promise----neither to jeer or to jibe when they catch the disease, but to look after them as brothers; and for the three or four who are certain to die I will try to arrange the funerals with all the pomp and ceremony of an anti-vaccination demonstration."
 
Man's Redemption of Man. New York: 1915:46-7 
A Demonstration Against Vaccination
"This demonstration occurred recently in the town of Leicester, England, as a result of legal proceedings against a very large number of persons who had refused to comply with the law requiring vaccination.  Twenty thousand people were in attendance, the procession being reviewed by the mayor, and the public meeting presided over by a member of the municipal council.  Jenner was hung in effigy; and public sympathy was excited by the parading of those who had suffered imprisonment or attachment for goods as the penalty of non-conformity with the law. One of the absurd features of the procession was a wagon containing children who had not been vaccinated, and labeled 'they that are whole need not a physician.'  The corporation of the city proposes, for the future, to rely upon prompt notification and isolation of each case of variola as it occurs."
 
The Archives of Pediatrics July 1885: Hygiene and Therapeutics pg 412 (editorial from an article published in April 1885 Boston Med. and Surg. Jour.)
New Pattern of Influenza Virus Resistance 
The Centers for Disease Control and Prevention reports that preliminary results of antiviral resistance tests of this season's flu virus isolates indicate that a majority of influenza A isolates (H1N1 type) are resistant to oseltamivir (Tamiflu) while remaining sensitive to the adamantane drugs, amantadine and rimantadine. None of the fewer influenza A (H3N2 type) or influenza B isolates were resistant to oseltamivir, and all viruses were sensitive to zanamivir (Relenza). The CDC recommends that empiric therapy of flu infections this season consist of zanamivir alone for any flu virus type, oseltamivir alone for type B only, or a combination of oseltamivir and rimantadine for type A or if the flu virus type is unknown. (www.cdc.gov/flu)