The classic symptoms: inspiratory whoop, post-tussive emesis and paroxysmal cough may be absent in adults and adolescents with pertussis. A recent study published in JAMA reviewed the diagnostic value of using these classically described symptoms to determine if a patient had pertussis.

Retrospective data was collected (January 1966- April 2010) and studies were included if they met the following criteria: subjects >5 years of age and with cough-illness confirmed as pertussis. Three studies met inclusion criteria.

There were a total of 484 patients ranging in age from 5-83 years. The sensitivity of paroxysmal cough was high at 86-100% but the specificity for pertussis was low, ranging from 12-35%. Post-tussive emesis had sensitivity of 33-70% and specificity of 61-83%. Lastly, inspiratory whoop had a sensitivity of 26-67% and specificity of 72-85%. The investigators were unable to find any studies which contained data that assessed for prolonged cough (also a characteristic of pertussis).

These three studies assessed were during non-outbreak periods of pertussis in the post-vaccination era. Therefore, this data cannot be applied to the outbreak setting. The bottom line: when evaluating a patient with cough, take into account all factors, including duration of cough, pertussis immunization history and potential exposures.

JAMA 2010; 304(8):890-896.

Most people know that T. whipplei has been long associated with Whipple disease described in the adult literature.  The literature suggests that transmission occurs by oral-oral or fecal-oral routes. It has been isolated in the saliva (PCR) and stool (PCR) of asymptomatic subjects and may be found in the environment.  In one study published in Clin Gastroenterology (2009), T. whipplei DNA was isolated from 44% of fecal samples in 150 Senegalese children. These were all healthy children.

In a recent study published in Emerging Infectious Disease, investigators described children with acute gastroenteritis caused by T. whipplei. The organism was detected by PCR in 15% of symptomatic children (341 stool samples) with diarrhea. Forty-seven specimens were also tested from asymptomatic children 2-4 years of age and the organism was not found. Thirty-six percent of the children with diarrhea were co-infected with other pathogens.  However, co-infection was significantly less frequent in children with higher concentrations of T. whipplei DNA in their stool. Of interest, those children with positive test were more likely to have had "exposure to sand boxes." It is possible that T. whipplei may be causing more episodes of gastroenteritis than previously thought. It should be remembered that this organism might be found in association with other GI pathogens.

Clin Infect Dis 2010;51 (October 15)
Emerg Infect Dis 2010; 16:776-782

We evaluate many children in our outpatient infectious disease clinic with recurrent and prolonged upper respiratory infections. Many of these children are in daycare. You can expect up to 8 upper respiratory infections (each year) in children 1-6 years of age. This is considered normal. When you factor in daycare, this number might be higher. 

Asymptomatic children in daycare may also shed their germs (both viruses and bacteria) and other children may acquire these microorganisms and become symptomatic. Most of these symptomatic children do not have an underlying immunodeficiency. Many of these children are treated with unnecessary courses of antibiotics because of their prolonged viral illness.

Pappas et. al assessed the duration of the common cold in school-aged children. A similar study was done in the 1960's in adults.

Pappas found of the 81 colds studied, the common symptoms were cough, sneeze, nasal congestion and rhinnorrhea (last two symptoms occurring the most often). 73% of these children had symptoms beyond 10 days after onset. Rhinovirus was detected in 46% and bacteria were isolated in 29% from NP aspirate culture including:  S. pneunoniae, H. influenzae, and M. catarrhalis. This study has some very informative take home messages:

1. Colds last more than one week.
2. We should not immediately place children on antibiotics after 7-10 days of symptoms.
3. Do not culture "boogers."  Bacteria will grow!

It is important to educate the families in your practice.

Pediatr Infect Dis J 2008;27:8-11
Adamkeiwicz and Quie, Report on Ped ID, 1992 1992

In June of 2010, an outbreak of Vibrio mimicus associated with crayfish was reported in Washington State. Four people who had eaten crayfish left over from a party the night prior were sickened. Two required hospitalization in the ICU for severe dehydration and acute renal failure. CDC investigators learned that the sickened people ate left over (cooked) crayfish which had been placed in a cooler that previously contained raw crayfish. The cooler had not been cleaned before the cooked crayfish were placed inside of it.

Vibrio mimicus, when it carries the gene that encodes cholera toxin, causes severe watery diarrhea. It is known to be associated with raw seafood including oysters, fish, turtle eggs, prawns, squid and crayfish. Cross contamination of cooked seafood should be avoided. Properly cooking seafood substantially decreases the risk of illness.

MMWR/October 29, 201Vol 29/N.42

With a recent publication by Kaguelidou and colleagues addressing the use of ciprofloxacin in the neonatal population and the recent influx of inquiries we have received from healthcare practitioners about the safe use of fluoroquinolones (FQ) in pediatric patients, a brief review of this topic is justified.¹

Many prescribers are hesitant to use FQ in children due to reports of cartilage toxicity of weight-bearing joints in juvenile animals. In addition, in 2008 the FDA ordered a boxed warning for increased risk of tendonitis and tendon rupture with FQ use. However, this warning did not comment about the use in children or adolescents and stated that the risks are increased specifically in people older than 60. A comprehensive review published in 1997 concluded that quinolone arthropathy described in juvenile animals does not correlate with use of FQ in children and adolescents. A small incidence of arthralgias and myalgias were documented but were transient; they disappeared when the drug was discontinued and appear to be no more prevalent than with other antibiotics.² A large multi-center, prospective, non-blinded cohort study evaluated adverse effects in children receiving FQ versus other antibiotics. All events of arthralgias and myalgias occurred within the first 2 weeks of FQ therapy and resolved within 20 days. No tendonopathies were reported.³

FQ use in the neonatal population has also been shown to be safe. A prospective study established in 2006 found no osteoarticular problems or joint deformities in pre-term neonates treated with ciprofloxacin who were followed-up for an average of 28 months.⁴ Most recently, a systematic review of ciprofloxacin use in neonates reported an absence of osteoarticular toxicity in patients receiving ciprofloxacin for any neonatal infectious condition.¹

Based on available evidence, FQ may safely be used in our pediatric and neonatal patient populations with appropriate monitoring. However, in an era of increasing antimicrobial resistance, prescribers must be judicious in their prescribing of antimicrobial agents and reserve FQ and other broad-spectrum agents for patients who truly need them. FQ may be considered for those patients with multi-drug resistant (MDR) infections (e.g. levofloxacin for resistant Streptococcus pneumoniae), pseudomonas infections in which an oral option is appropriate, empiric therapy for febrile neutropenic patients who may be candidates for oral/home therapy, and cystic fibrosis patients with MDR/pseudomonas infections.

¹ Kaguelidou F et al. Ciprofloxacin Use in Neonates. Pediatr
     Infect Dis J. 2011;30(2) [published ahead of print
     www.pidj.com]
 

² Burkhardt JE, Walterspiel JN, Schaad UB. Quinolone
     arthropathy in animals versus children. Clin Infect
     Dis.1997;25:1196-1204
 

³ Chalumeau M, Tonnelier S, D'Athis P et al. Fluroquinolone

     safety in pediatric patients; a prospective, multi-center
     comparative cohort study in France. Pediatrics. 
     2003;111(6):e714-19
 

⁴ Ahmed AS et al.Ciprofloxacin Treatment in Pre-term
     Neonates in Bangladesh. Pediatr Infect Dis J.
     2006;25:1137-41

Saccharomyces boulardii, like many probiotics, has been marketed in the US for >50 years as a dietary supplement to promote digestive health. The recent increase in the incidence and severity of C.difficile infection has lead to the increased use of S.boulardii as an adjunct therapy for this disease.  This "new" use of a probiotic as a drug rather than dietary supplement, however, poses new questions in how the safety of this product is evaluated for patients¹.

According to FDA definition, a "drug" is an article intended for the "diagnosis, cure, mitigation, treatment or prevention of a disease" and must go through a rigorous application and approval process in order to insure safety and efficacy before it can be administered to humans. Probiotics, like all other dietary supplements, however, have always fallen under the umbrella of "foods" and are regulated by the FDA's Center for Food Safety and Applied Nutrition. Unlike drugs, dietary supplements do not need FDA approval before they can be marketed for use in humans. The manufacturer needs only to notify the FDA of the product's release. Also, the manufacturer of the product need not submit any evidence to the FDA substantiating the safety or benefit of the product either before or after marketing. Only since 2006, in fact, have the manufacturers of dietary supplements been required to notify the FDA of any serious adverse events associated with their products.

Practically, what this means is that there is little information regarding the safe use for S.boulardii or any other probiotic. What has been learned -- mainly from independent case reports and studies -- is that probiotics are generally safe in otherwise healthy, immunocompetent people. However, there are populations of patients for whom they are
not completely safe. Saccharomyces fungemia, for example has been reported in numerous studies particularly in patients with digestive disease, indwelling central lines, and in ICUs². Another study, which investigated the safe handling of freeze-dried S.boulardii, found that the act of opening a packet of the substance was associated with heavy air and surface contamination of the surrounding environment. Live yeast organisms from the opened packet persisted on counter tops for >2 hrs and on the hands of the personnel handling the packet even after handwashing.

Some experts suggest that healthcare providers wear gloves when handling probiotic products and that the products should not be opened near patients with central lines or near any sterile site. Careful risk assessment of the pros and cons of their use in specific patients is important, as is vigilant reporting of any adverse events associated with their use.

¹ EID Vol 16, No 11 Nov 2010
² CID Vol 40. 1625-34. 2005

One of the more common reasons people fail to get their yearly influenza vaccine is the false belief that the vaccination can actually cause "the flu."  Even reassurance that the inactivated flu "shot" does not contain ANY live virus often fails to convince those who have come down with flu like symptoms within days of getting vaccinated. Indeed, it is human nature to associate events that happen close in time as being proof of "cause and effect."

Recently one of us was posed this question by a friend: "I know this shot made me sick! I just got my flu vaccine and the next day, I got the flu! What are the odds of THAT?"

Funny you should ask! A study done in the winter of 2005 in Sweden attempted to answer that very question, namely -- what is the period prevalence of self-defined influenza-like illness during a random week in the middle of winter? How did these researchers figure this out? They called! ... about 872 Swedish people.

Investigators used random-digit dialing to call 1070 households in Sweden. A total of 872 people agreed to participate in a phone survey where they were asked, quite simply, if anyone in their household had had "the flu" within the past week. Results revealed that an across-the-board 7.7% prevalence of self-reported flu for week 7 (Feb 14-20) of 2005. Broken down by age, the prevalence was highest in the youngest age groups: 15.6% prevalence in ages 0-4 years and 13% in the 5-14 year old age group. The group with the lowest incidence of disease was those 65 years and older. Only 11% of the people called reported having had their influenza vaccination. Seventy-five percent of those who reported having been vaccinated were over 65 years of age.

Of course, this study overestimated the incidence of actual culture-proven influenza disease, since a great many cases of self-reported flu (AKA influenza-like illness) were likely to be other respiratory illnesses which manifest similar symptoms. However, considering that most people who claim to have "come down with the flu" after their vaccine do not have culture proven influenza either, we thought this phone survey provided very good insight!

So, what are the odds of getting any flu-like illness on a given week in early winter? About 1 in 13.

Eurosurveillance Vol 10 (12) Dec 1 2005.

An experimental study done in two French primary schools assessed the impact of the use of alcohol-based hand sanitizer on gastroenteritis. This simple, yet elegant study compared two similar size schools in Olivet, France during a seasonal viral gastroenteritis epidemic.

School A, the experimental group, had investigators instruct children to use hand sanitizer upon entering the classroom (twice each morning, and twice each afternoon) and after using the restroom. The classroom teacher ensured compliance. School B, the control group, was not supplied with alcohol sanitizer. The students in school B were simply given general instruction in proper hand washing technique after using the restroom.

By the end of the 4 months of observation, 155 children were reported (by parents) to have had at least one episode of gastroenteritis. These numbers included 64 children from School A (24.5%) and 91 (42%) from School B. The average number of gastroenteritis episodes per child was 0.31 in the experimental group (School A) and 0.53 in the control group (School B) (P<0.001). Average number of school days lost was also significantly less in School A than School B (0.19 days lost per student vs 0.55 days lost per student.) And, the average number of visits to the doctor was similarly less: 0.09 visits per student in School A and 0.18 in School B.

So, what does this mean? You know that little bottle of Purell mom always carries in her purse? It might prevent you from getting diarrhea. Think about that next time you make fun of mom!

PIDJ Volume 29. Number 11. Nov 2010.

It is well known that neither the immunization against pertussis nor the disease itself confers long lasting immunity. And while routine vaccination of infants and young children is important in preventing severe illness and death from pertussis, it does not effectively reduce the spread of pertussis in the population.

In 1999 the reduced antigen content diphtheria and acellular pertussis vaccine (called Tdap in the US, and dTpa in Europe) was licensed first in Germany (Boostrix) for older individuals ages 10-64 years of age in attempt to curb disease and decrease the spread of pertussis to infants. At this time, one dose of Tdap is recommended for people ages 10-64. No recommendations for booster vaccination with Tdap have been made yet, though the issue of waning immunity in the years following Tdap vaccination has been speculated.

Mertsola, J¹  et al have conducted a study in which included 75 Finnish adolescents 10 ten years out from their first Tdap vaccine. Of these children, 64.6% maintained seroprotective antibody to pertussis (in contrast, 98.8% and 97.5% maintained their immunity to the diphtheria and tetanus components). They were all given a second dose of Tdap as a booster, and then had their sera tested again one month after the booster dose. At one month post booster, all subjects showed seroprotective levels of antibody against all three components. During the 4 day follow-up after the booster vaccine, 9.9% reported local pain severe enough to temporarily limit activity, 17.3 and 18.5% respectively reported significant redness or swelling at the injection site, and 8.6% reported temperature > 37.5C. None of the participants sought medical attention for these symptoms, all of which resolved.

Booster vaccination against pertussis throughout life may help to prevent antibody decay over time and could potentially cause substantial reduction of pertussis spread². Prevention of spread among adolescent and adult populations may be the only way to completely eliminate the threat of this disease to young infants, who are at the very highest risk of morbidity and mortality from this disease.

¹Mertsola J, Van Der Meeren O, He Q, et al. Decennial
     administration of a reduced antigen content diphtheria
     and tetanus toxoids and acellular pertussis vaccine in
     young adults. Clin Infect Dis 2010;51:656-62.

²Cherry JD. The present and future control of pertussis. Clin
     Infect Dis 2010;51:663-7.

Once thought to be a disease only of the tropical or subtropical developing world, Hepatitis E is now known to be endemic in industrialized nations.¹ HEV causes acute, usually self-limited hepatitis and is transmitted via the fecal-oral route. It has the potential to cause more severe disease in persons with underlying immunodeficiencies or chronic hepatic disease and in pregnant women, where case fatality rates are as high as 20%.

Though once suspected to be a disease spread by poor sanitation conditions, a substantial body of data now suggest that HEV is a zoonotic disease with pigs and wild boars being a common source.¹

A recent study from France² by Colson et al highlights the risks of undercooked pork in the form of a popular pig liver sausage (figatellu) as the route of infection of HEV by performing a carefully detailed case control study of 3 families in France. In their study, three patients with HEV disease plus 15 members of their three different families served as the subjects. HEV RNA was detected in serum samples from the patients and in the figatellu they injested. Acute or recent HEV infection was diagnosed (by anti HEV IgM and IgG immunoassay) in 7 of the 13 individuals who ate raw figatellu and of 0 of 5 who did not. All of the persons with symptomatic HEV disease ate raw figatellu. All of the persons who tested positive (even though they may be been asymptomatic) had eaten the raw sausage as well. The clinical attack rate was 36% and the attack rate by viral markers was 71%.

Their findings were significant enough that the French public health authorities now require the labeling of figatellu to state "Produit a cuire (cuisson a coeur)" or "Product to cook (cook thoroughly)." Cooking to an internal temperature of 71C for 5 min, or boiling for 5 min, effectively inactivates the virus.

¹Dalton HR, Bendall R, Ijaz S, Banks M. Hepatitis E: an
     emerging infection in developed countries. Lancet Infect Dis
     2008;8:698-709.
²Colson P, Borentain P, Queyriaux B, et al. Pig liver sausage 
     as a source of hepatitis E virus transmission to humans.
     J Infect Dis 2010;202:825-34.

For several years, OB/GYN guidelines have recommended offering oral acyclovir or valacyclovir in the last 4 weeks of gestation to pregnant women with a history of recurrent genital herpes (Obstet Gynecol 2007;109(6);1489-98). Such prophylaxis reduces cervical shedding of virus at delivery and the number of caesarean sections for genital lesions. A recent report shows that such prophylaxis is not completely effective in preventing neonatal transmission. The report describes 7 infants whose mothers were on antiviral prophylaxis for 3-28 days. This report does not provide detailed data on the efficacy of antiviral prophylaxis. In summary, antiviral prophylaxis in the last 4 weeks of pregnancy may be good for women with a history of genital herpes during pregnancy, but it is not 100% effective in preventing neonatal transmission. We still have to consider neonatal herpes in sick neonates born to these women.

Pinninti S, et al. Infectious Dis Society Am 48th Annual Meeting, 10/22/2010, abstract 570

Among infants who were treated for neonatal herpes, at least half will develop recurrent disease during the first year of life. An earlier study showed that neurologic sequelae developed in 21% of infants who had 3 or more recurrences within the first 6 months of life (NEJM 1991;324:450-4). This data has led to attempts to prevent recurrences by using prophylactic oral acyclovir given to these babies from the time they complete the IV course of acyclovir through 6 months of age. The results of a new, multicenter, prospective, placebo-controlled study revealed that infants given such prophylaxis had significantly better performance on Bayley Scales of Infant Development Mental Scores at 12 months of age. The incidence of neutropenia did not differ between the two study groups.

Kimberlin D et al. Infectious Dis Society Am 48th Annual Meeting, 10/22/2010, abstract 810.

During the past decades, studies from the United States, Finland, Sweden, the Netherlands, the United Kingdom, and Scotland showed an increase in the incidence of oropharyngeal squamous cell carcinomas (OSCCs).  Furthermore, there is an increase in the proportion of OSCCs that are human papillomavirus (HPV)-positive.

Multiple studies have shown an increase in the number of head and neck cancers with detectable HPV.  While HPV has been detected in ≈25% of all head and neck squamous cell carcinomas, which includes cancers of the oral cavity, oropharynx, hypopharynx, larynx, sinonasal tract, and nasopharynx, 45%-100% of cases of OSCCs were reported to be HPV positive.

An case-control epidemiological study in 2007 led by researchers from Johns Hopkins University implicated HPV exposure and infection as strong risk factors for oropharyngeal cancer in the US, independent of tobacco and alcohol use, which are two other important risk factors for the disease.

The mortality and morbidity of oropharyngeal cancers in the US is not trivial.  The National Cancer Institute estimates that in 2010, 25,420 men and 11,120 women were diagnosed with oropharyngeal cancers and that 7,880 men and women died of these cancers.

It is significant that HPV 16 was found to be highly prevalent (45-100%) in OSCCs in numerous studies from several different countries.  It is speculated that changes in sexual practices may be a factor for the increase in incidence of OSCC. 

As we well know, the two HPV vaccines available in the US provide protection against both high-risk types of HPV, HPV-16 and HPV-18, which are responsible for cervical carcinoma.  The effects of HPV vaccination of the adolescent and young adult female population should result in a lower viral prevalence and, possibly, a reduced incidence of oropharyngeal cancers and other HPV-associated cancers.  While the vaccine has not been studied for efficacy in preventing OSCC, future studies may show that increasing use of the HPV vaccine may prevent the majority of these OSCC and other non-cervical cancers associated with HPV infection. 

Ramqvist T, Dalianis T. Oropharyngeal cancer epidemic and
     human papillomavirus. Emerg Infect Dis [serial on the
     Internet]. 2010 Nov 12. 
     http://www.cdc.gov/EID/content/16/11/1671.htm

D'Souza G et al. Case-control study of human papillomavirus
     and oropharyngeal cancer. N Engl J Med. 2007 May 10;356
     (19):1944-56.