Robert W. Frenck

Patients with Inflammatory Bowel Disease are at Risk for Vaccine-Preventable Illnesses

BACKGROUND:Patients with chronic, immune-mediated conditions such as inflammatory bowel disease (IBD) are often treated with long-term immunosuppressive therapies, potentially increasing their risk of developing an infection. Empiric data suggest that vaccines are underutilized in immunocompromised patients, despite published guidelines recommending their use. We aimed to assess exposure risk and immunization status among patients receiving care in an IBD specialty clinic.METHODS:Patients completed a self-administered, pretested, structured questionnaire during a routine visit for the management of IBD. Survey questions related to medical and immunization histories, and exposures to known risk factors for influenza, pneumococcus, viral hepatitis, and varicella. Additionally, in a subgroup of patients who agreed to donate a sample of blood, immune status to hepatitis A (HAV), hepatitis B (HBV), and varicella was determined.RESULTS:Two hundred four patients were asked to participate in the study; 169 completed surveys and comprised the study population. Mean age was 35 yr (range 13–75 yr). One hundred forty-six respondents (86%) reported current or prior use of immunosuppressive medications. Only 45% of respondents recalled tetanus immunization within the past 10 yr, 41 (28%) reported regularly receiving flu shots, and 13 (9%) reported having received pneumococcal vaccine. The most common reasons for nonimmunization with influenza included lack of awareness (49%) and concern for side effects (18%). Responses indicated that 75 (44%) patients were at risk for HBV but only 47 (28%) had been vaccinated against the infection; of patients with previous HBV vaccination, only three of nine (33%) had measurable antibodies against hepatitis B surface antigen.CONCLUSIONS:Immunization against selected vaccine-preventable illnesses was uncommon in patients with IBD, despite the presence of significant risk factors. Efforts to improve immunization status among patients with IBD and other chronic, immune-mediated conditions are needed.

Immunosuppression Impairs Response to Pneumococcal Polysaccharide Vaccination in Patients With Inflammatory Bowel Disease

OBJECTIVES:The treatment of inflammatory bowel disease (IBD) often includes immunosuppressive medications, which may increase the risk of vaccine-preventable illnesses. We aimed to assess the impact of immunosuppression on immune responses to pneumococcal vaccination in patients with IBD.METHODS:The study design consists of a prospective controlled clinical trial. This study was carried out at a tertiary-care IBD clinic. The subjects for the study belonged to one of the following three groups: adult patients with IBD on combination TNF-blockers and immunomodulators (Group A), those without immunosuppressive therapy (Group B), and age-matched healthy controls (Group C). The treatment consisted of immunization with 23-valent pneumococcal polysaccharide vaccines (PSVs). The main outcome was immune response for five serotypes defined as a twofold or greater increase from pre-vaccination titers and ⩾1 μg post-vaccination titer.RESULTS:Sixty-four subjects participated in the study: 20 in Group A, 25 in Group B, and 19 in Group C. Pre-vaccination titers were similar among the three groups. Vaccine responses were lower in Group A than in Group B (P⩽0.01 for four out of five antigens) and Group C (P<0.01 for all five antigens). Overall vaccine response was seen in 45, 80, and 85% of Groups A, B, and C (P=0.01), respectively.CONCLUSIONS:Immune response to PSV-23 is impaired in Crohns disease (CD) patients on combination immunosuppressive therapy but is normal among non-immunosuppressed patients. Given the unpredictable likelihood for immunosuppressive therapy, newly diagnosed patients with IBD should undergo vaccination before the initiation of immunosuppressive therapy.

Azithromycin versus Ceftriaxone for the Treatment of Uncomplicated Typhoid Fever in Children

A total of 108 children aged 4-17 years were randomized to receive 7 days of azithromycin (10 mg/kg/day; maximum, 500 mg/day) or ceftriaxone (75 mg/kg/day; maximum, 2.5 g/day), to assess the efficacy of the agents for the treatment of uncomplicated typhoid fever. Salmonella typhi was isolated from the initial cultures of blood samples from 64 patients. A total of 31 (91%) of the 34 patients treated with azithromycin and 29 (97%) of the 30 patients treated with ceftriaxone were cured (P>.05). All 64 isolates were susceptible to azithromycin and ceftriaxone. Of the patients treated with ceftriaxone, 4 subsequently had relapse of their infection. No serious side effects occurred in any study subject. Oral azithromycin administered once daily appears to be effective for the treatment of uncomplicated typhoid fever in children. If these results are confirmed, the agent could be a convenient alternative for the treatment of typhoid fever, especially in individuals in developing countries where medical resources are scarce.

Azithromycin versus Ciprofloxacin for Treatment of Uncomplicated Typhoid Fever in a Randomized Trial in Egypt That Included Patients with Multidrug Resistance

ABSTRACT To compare clinical and bacteriological efficacies of azithromycin and ciprofloxacin for typhoid fever, 123 adults with fever and signs of uncomplicated typhoid fever were entered into a randomized trial. Cultures of blood were positive for Salmonella typhi in 59 patients and for S. paratyphi A in 3 cases; stool cultures were positive for S. typhi in 11 cases and for S. paratyphi A in 1 case. Multiple-drug resistance (MDR; resistance to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole) was present in isolates of 21 of 64 patients with positive cultures. Of these 64 patients, 36 received 1 g of azithromycin orally once on the first day, followed by 500 mg given orally once daily on the next 6 days; 28 patients received 500 mg of ciprofloxacin orally twice daily for 7 days. Blood cultures were repeated on days 4 and 10 after the start of therapy, and stool cultures were done on days 4, 10, and 28 after the start of therapy. All patients in both groups improved during therapy and were cured. Defervescence (maximum daily temperatures of ≤38°C) occurred at the following times [mean ± standard deviation (range)] after the start of therapy: 3.8 ± 1.1 (2 to 7) days with azithromycin and 3.3 ± 1.0 (1 to 5) days with ciprofloxacin. No relapses were detected. Cultures of blood and stool during and after therapy were negative in all cases, except for one patient treated with azithromycin who had a positive blood culture on day 4. These results indicated that azithromycin and ciprofloxacin were similarly effective, both clinically and bacteriologically, against typhoid fever caused by both sensitive organisms and MDRS. typhi.

Prevention of rotavirus disease: Updated guidelines for use of rotavirus vaccine

This statement updates and replaces the 2007 American Academy of Pediatrics statement for prevention of rotavirus gastroenteritis. In February 2006, a live oral human-bovine reassortant rotavirus vaccine (RV5 [RotaTeq]) was licensed as a 3-dose series for use in infants in the United States. The American Academy of Pediatrics recommended routine use of RV5 in infants in the United States. In April 2008, a live, oral, human attenuated rotavirus vaccine (RV1 [Rotarix]) was licensed as a 2-dose series for use in infants in the United States. The American Academy of Pediatrics recommends routine immunization of infants in the United States with rotavirus vaccine. The American Academy of Pediatrics does not express a preference for either RV5 or RV1. RV5 is to be administered orally in a 3-dose series with doses administered at 2, 4, and 6 months of age; RV1 is to be administered orally in a 2-dose series with doses administered at 2 and 4 months of age. The first dose of rotavirus vaccine should be administered from 6 weeks through 14 weeks, 6 days of age. The minimum interval between doses of rotavirus vaccine is 4 weeks. All doses should be administered by 8 months, 0 days of age. Recommendations in this statement also address the maximum ages for doses, contraindications, precautions, and special situations for administration of rotavirus vaccine.

Prevention of varicella: Recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule

National varicella immunization coverage using the current 1-dose immunization strategy has increased among vaccine-eligible children 19 through 35 months of age from 27% in 1997 to 88% by 2005. These high immunization rates have resulted in a 71% to 84% decrease in the reported number of varicella cases, an 88% decrease in varicella-related hospitalizations, a 59% decrease in varicella-related ambulatory care visits, and a 92% decrease in varicella-related deaths in 1- to 4-year-old children when compared with data from the prevaccine era. Despite this significant decrease, the number of reported cases of varicella has remained relatively constant during the past 5 to 6 years. Since vaccine effectiveness for prevention of disease of any severity has been 80% to 85%, a large number of cases of varicella continue to occur among people who already have received the vaccine (breakthrough varicella), and outbreaks of varicella have been reported among highly immunized populations of schoolchildren. The peak age-specific incidence has shifted from 3- to 6-year-old children in the prevaccine era to 9- to 11-year-old children in the postvaccine era for cases in both immunized and unimmunized children during these outbreaks. Outbreaks of varicella are likely to continue with the current 1-dose immunization strategy. After administration of 2 doses of varicella vaccine in children, the immune response is markedly enhanced, with >99% of children achieving an antibody concentration (determined by glycoprotein enzyme-linked immunosorbent assay) of ≥5 U/mL (an approximate correlate of protection) and a marked increase in geometric mean antibody titers after the second vaccine dose. The estimated vaccine efficacy over a 10-year observation period of 2 doses for prevention of any varicella disease is 98% (compared with 94% for 1 dose), with 100% efficacy for prevention of severe disease. Recipients of 2 doses of varicella vaccine are 3.3-fold less likely to have breakthrough varicella, compared with those who are given 1 dose, during the first 10 years after immunization. To achieve greater levels of immunity with fewer serosusceptible people, greater protection against breakthrough varicella disease, and reduction in the number of outbreaks that occur nationwide among school-aged populations, a 2-dose varicella immunization strategy is now recommended for children ≥12 months of age.

High Disease Burden of Diarrhea Due to Enterotoxigenic Escherichia coli among Rural Egyptian Infants and Young Children

ABSTRACT The incidence of enterotoxigenic Escherichia coli diarrhea among Egyptian children was 1.5 episodes per child per year and accounted for 66% of all first episodes of diarrhea after birth. The incidence increased from 1.7 episodes per child per year in the first 6 months of life to 2.3 in the second 6 months and declined thereafter.

Universal High-Level Primary Metronidazole Resistance in Helicobacter pylori Isolated from Children in Egypt

ABSTRACT Antimicrobial susceptibility testing was performed on 48 isolates of Helicobacter pylori recovered from Egyptian children undergoing routine endoscopies. The isolates were universally highly resistant to metronidazole, but resistance to other tested antimicrobial agents was rare (4% for clarithromycin, erythromycin, and azithromycin resistance versus 2% for ciprofloxacin and ampicillin resistance). Use of metronidazole for the treatment of H. pylori in Egypt should be avoided.

Astrovirus Diarrhea in Egyptian Children

This study describes the epidemiology of astrovirus diarrhea among a population-based cohort of 397 children aged <3 years residing in rural Egypt from 1995 to 1998. The age-specific incidence rates of astrovirus diarrheal episodes per person-year were 0.38 for infants aged <6 months, 0.40 for those aged 6-11 months, 0.16 for those aged 12-23 months, and 0.05 for those aged 24-35 months. The overall incidence rate of astrovirus diarrhea was the same as that of rotavirus diarrhea, 0.19 episodes per person-year. Astrovirus infection was pathogenic and associated with severe dehydration in 17% of the cases. The most frequent serotype was HAstV-1, and, in order of decreasing frequency, HAstV-5, HAstV-8 and HAstV-3, HAstV-6, HAstV-4, and HAstV-2. In determining whether astrovirus diarrhea was associated with a reduced incidence of subsequent disease, there was evidence to suggest HAstV-1 homotypic immunity but not heterotypic immunity. Because we observed 38% of the incidence of astrovirus diarrhea to occur in infants aged <6 months, a candidate astrovirus vaccine would have to confer immunity very early in life.

Sensitivity and Specificity of Various Tests for the Diagnosis of Helicobacter pylori in Egyptian Children

OBJECTIVES. Many noninvasive methods (using breath, blood, and stool samples) are available to diagnose Helicobacter pylori. However, because the noninvasive tests are proxy measures of the infection, they need validation before use. Factors that may affect test validity include patient age, gender, and geographic location. Because no data were available on the validation of noninvasive tests for the diagnosis of H pylori among children in the Middle East, this study was performed. METHODS. Children between 2 and 17 years of age evaluated at the Cairo University School of Medicine pediatric gastroenterology clinic who were already scheduled for upper endoscopy were eligible for enrollment in the study. At the time of endoscopy, 3 biopsies were collected and used for rapid urease, histology, and culture, respectively. All children also donated a sample of stool and blood and had a urea breath test performed. Stool and serum samples were tested for the presence of H pylori by using commercially available enzyme-linked immunosorbent assay–based technology. The sensitivity, specificity, and positive and negative predictive values were calculated for each noninvasive test used in the study. Receiver operating curves also were charted to determine optimal cut points for the various tests when used in the current study cohort. RESULTS. One hundred eight children were enrolled in the study, with 52 children being under 6 years of age. The urea breath test and HpStar (DakoCytomation, Norden, Denmark) stool enzyme-linked immunosorbent assay kit had the highest sensitivity and specificity (sensitivity and specificity: 98 and 89 [urea breath test] and 94 and 81 [HpStar], respectively), whereas the serologic kit had an unacceptably low sensitivity (50%). The sensitivity of neither the urea breath test nor the HpStar tests was affected by subject age, but specificity of the HpStar test, although still high, was significantly lower among children under 6 years. Receiver operating curves found optimal cut points of the urea breath test at 6.2 δ over baseline and of the HpStar at 0.25 enzyme-linked immunosorbent assay units. CONCLUSION. The urea breath test and HpSTAR stool antigen kit are reliable tests for the noninvasive diagnosis of H pylori among children living in the Middle East.