Invasive Infections In Children Research Articles

The many faces of Group A Streptococcal infections, case-series of invasive infections in children in Iceland

In recent months the incedence of invasive group A streptococcal infections (Streptococcus pyogenes) has increased worldwide. In the Children's Hospital Iceland 20 such cases were admitted during a four month period, until which time the avarage was one or two children admitted with an invasive GAS infection per year. To demonstrate the variability in the presentation of these invasive infections four cases were chosen for discussion in this case-series. Empyema with toxic shock syndrome, meningitis, orbital abscess and fascitis of the leg are reviewed.

Molecular Epidemiology of Haemophilus influenzae Strains with Reduced Susceptibility and Genetic Profiles of Resistance in the Postvaccination Period.

Haemophilus influenzae serotype b has been the main cause of invasive infections in children, during the prevaccination period. More than 20 years after the introduction of the conjugate vaccine against Hib, HiNT has emerged as the cause of localized infections in children and adults. The main objective of this work is to evaluate the susceptibility and resistance mechanisms of H. influenzae strains from carriers and describe the molecular epidemiology and their clonal relationships by multilocus sequence typing (MLST). Sixty-nine strains from clinical cases and asymptomatic carriers from 2009 to 2019 were analyzed, confirmed as H. influenzae, and serotyped by polymerase chain reaction. The susceptibility to antibiotics was evaluated by E-test strips. Genotyping was performed by MLST. HiNT was the most frequent in all age groups. Resistance to ampicillin, sulfamethoxazole+trimethoprim, and amoxicillin+clavulanic acid was detected, with the production of β-lactamase being the main resistance mechanism. Among 21 HiNT strains with complete allelic MLST profiles, 19 new sequence types were described, reinforcing the already reported heterogeneity of nontypeable strains, and only one clonal complex (cc-1355) was observed. Our results show a high percentage of colonization regardless of age, increased antimicrobial resistance, and high genetic diversity, along with an increased number of cases caused by HiNT strains. These findings reinforce the need for continuous surveillance for HiNT strains as it has been reported worldwide after the introduction of the Hib conjugate vaccine.

Immunoinformatics design of multi-epitope vaccine using OmpA, OmpD and enterotoxin against non-typhoidal salmonellosis

BackgroundNon-typhoidal Salmonella (NTS) is one of the important bacteria that cause foodborne diseases and invasive infections in children and elderly people. Since NTS infection is difficult to control due to the emergence of antibiotic-resistant species and its adverse effect on immune response, the development of a vaccine against NTS would be necessary. This study aimed to develop a multi-epitope vaccine against the most prevalent serovars of NTS (Salmonella Typhimurium, Salmonella Enteritidis) using an immunoinformatics approach and targeting OmpA, OmpD, and enterotoxin (Stn).ResultsInitially, the B cell and T cell epitopes were predicted. Then, epitopes and suitable adjuvant were assembled by molecular linkers to construct a multi-epitope vaccine. The computational tools predicted the tertiary structure, refined the tertiary structure and validated the final vaccine construct. The effectiveness of the vaccine was evaluated via molecular docking, molecular dynamics simulation, and in silico immune simulation. The vaccine model had good binding affinity and stability with MHC-I, MHC-II, and toll-like receptors (TLR-1, 2, 4) as well as activation of T cells, IgM, IgG, IFN-gamma and IL-2 responses. Furthermore, after codon optimization of the vaccine sequence, this sequence was cloned in E. coli plasmid vector pET-30a (+) within restriction sites of HindIII and BamHI.ConclusionsThis study, for the first time, introduced a multi-epitope vaccine based on OmpA, OmpD and enterotoxin (Stn) of NTS that could stimulate T and B cell immune responses and produced in the prokaryotic system. This vaccine was validated in-silico phase which is an essential study to reduce challenges before in vitro and in vivo studies.Graphical abstract

Identifying Patient-Centered Outcomes for Caregivers and Children With Musculoskeletal Infections.

Musculoskeletal infections (MSKI), including osteomyelitis and septic arthritis, are among the most common invasive infections in children and have the potential to cause significant morbidity. Guidelines have been developed to optimize care based on clinician-developed endpoints. Patient-centered outcomes have not been defined for children with MSKI. This study identified outcomes most important to caregivers and patients with MSKI. This was a single-center prospective qualitative study of children 6 months to 18 years of age hospitalized with MSKI from November 2019 to September 2021. Using design-research methods, patients and caregivers participated in interviews and/or completed journals to describe their experiences during acute infection and recovery from MSKI. A total of 51 patient/caregivers were approached to participate in the study, 35 of whom declined to participate, resulting in 8 interviews conducted and 14 journals collected from 16 patient/caregivers. From these, a journey map was created highlighting points of stress during the onset of symptoms, through hospitalization, and returning home with new challenges. In addition, patient-centered outcomes were identified. For caregivers, these included managing mental health, managing responsibilities, and receiving support. Both caregivers and patients shared the importance of understanding of treatment plans and responsibilities. For patients, improving mental and physical health was important. Management of children with MSKI is complex and requires a multidisciplinary team approach. Validation of the outcomes identified and development of a measurement tool are needed. Addressing the patient-centered outcomes we identified in this study can greatly improve the holistic care of children with MSKI.

High Fecal Carriage of Multidrug Resistant Bacteria in the Community among Children in Northwestern Tanzania.

Colonization of multidrug resistant (MDR) bacteria is associated with subsequent invasive infections in children with comorbidities. This study aimed to determine the resistance profile and factors associated with MDR pathogen colonization among HIV−and HIV+ children below five years of age in Mwanza, Tanzania. A total of 399 (HIV− 255 and HIV+ 144) children were enrolled and investigated for the presence of MDR bacteria. The median [IQR] age of children was 19 (10–36) months. Out of 27 Staphylococcus aureus colonizing the nasal cavity, 16 (59.5%) were methicillin resistant while 132/278 (47.2%) of Enterobacteriaceae from rectal swabs were resistant to third generation cephalosporins, with 69.7% (92/132) exhibiting extended spectrum beta lactamase (ESBL) phenotypes. The proportion of resistance to gentamicin, amoxicillin/clavulanic acid and meropenem were significantly higher among HIV+ than HIV− children. A history of antibiotic use in the last month OR 2.62 [1.1, 6.9] (p = 0.04) and history of a relative admitted from the same household in the past three months OR 3.73 [1.1, 13.2] (p = 0.03) independently predicted ESBL rectal colonization. HIV+ children had significantly more fecal carriage of isolates resistant to uncommonly used antibiotics. There is a need to strengthen antimicrobial stewardship and Infection Prevention and Control (IPC) programs to prevent the emergence and spread of MDR pathogens in children.

Comparison of Trimethoprim-Sulfamethoxazole vs. Clindamycin for the Treatment of Children with Musculoskeletal Infections

Background: 
 Musculoskeletal infections ([MSKI]; osteomyelitis, septic arthritis, pyomyositis) are common invasive infections in children. With increasing antibiotic resistance and allergies, treatment options are limited. Trimethoprim-sulfamethoxazole (TMP-SMX) has activity against common MSKI pathogens, yet pediatric MSKI outcomes data are limited. Our aim was to evaluate outcomes of children with MSKI treated with TMP-SMX compared to clindamycin. We hypothesized that outcomes would be similar between groups.
 Methods: 
 We conducted a retrospective review of children <18 years old, admitted to Riley Hospital for Children from January 2010-June 2021 treated with TMP-SMX or clindamycin for MSKI. Patients were identified by ICD-9/10 codes. Patients were excluded if TMP-SMX or clindamycin was not the main treatment, they had symptoms >30 days, hardware associated infection, or an alternative diagnosis. Treatment success was defined as no evidence of infection at the end therapy. Treatment failure was defined as antibiotic intolerance, or development of recurrent/chronic osteomyelitis. Adverse drug reactions were recorded.
 Results:
 One-hundred-sixty-three patients (30 TMP-SMX, 133 clindamycin) met eligibility criteria. The majority were non-Hispanic white males, median age of 1.75 years (IQR, 1-3.75) for the TMP-SMX group, and 7 years (IQR 3-10) for the clindamycin group. Osteomyelitis was the most common infection type in both groups (TMP-SMX 43.3%, clindamycin 54.1%). S. aureus was the most common pathogen in both groups (TMP-SMX 36.7%, clindamycin 48.1%). Of the patients that completed follow-up, 84% successfully completed treatment with TMP-SMX, compared to 86.4% with clindamycin (odds ratio [OR] 0.82; 95% CI 0.25-2.46, p=0.75). Adverse drug reactions occurred in 6.7% of the TMP-SMX group, compared to 10.5% in the clindamycin group (OR 0.61; 95% CI 0.13-2.57, p=0.52).
 Conclusions:
 Preliminary results show that TMP-SMX is well tolerated and not associated with higher risk of treatment failure compared to clindamycin in the treatment of pediatric MSKI. Randomized controlled trials to evaluate optimal treatment are needed.

Haemophilus influenzae type b invasive infections in children hospitalized between 2000 and 2017 in a Pediatric Reference Hospital (PRH)

BackgroundUruguay incorporated the conjugate vaccine against Haemophilus influenzae b (Hib) in 1994. In 2008, the vaccine was changed from one with natural conjugated capsular polysaccharide to one with a synthetic polysaccharide component. We describe the frequency and characteristics of invasive Hib infections in children hospitalized in a Pediatric Reference Hospital (PRH) between January 1st, 2000 and December 31st, 2017. MethodsSterile site Hib isolations from hospitalized children were included. Clinical and microbiological characteristics were analyzed. Favorable conditions for the infection were considered: incomplete immunization, immunodeficiencies and associated pathologies. Two periods are described: 1, prior to vaccine change (1/1 st/2000- 12/31/08) and 2, post-change (1/1 st/09- 12/31st/17). Results45 children were hospitalized: 5 in the first period and 40 in the second. The hospitalization rate per 10,000 discharges was 0.41 (95% CI 0.05–0.77) and 4.2/10,000 (95% CI 2.89–5.48), respectively (p < 0.01). The diagnoses at discharge were: meningitis/ventriculitis (20), pneumonia (16), bacteremia (3), epiglottitis (1), arthritis (1), cellulitis (3) and obstruction of the upper airway (1). Four children presented comorbidities. Twenty seven received less than 3 doses of anti-Hib vaccination and 18 were properly vaccinated (2 were immunodeficient). The median hospitalization was 14 days, 18 children required intensive therapy. ConclusionsObserved change may be due to: incomplete primary series, inhomogeneous vaccine coverage and immunogenicity of the synthetic polysaccharide. To reduce this public health problem, epidemiological surveillance.

Draft Genome Sequences of Two Streptococcus pneumoniae Strains Causing Invasive Infections in Children in Qatar.

Invasive pneumococcal infections are a major cause of morbidity and mortality in the pediatric population. We report the draft genomes of two clinical Streptococcus pneumoniae isolates associated with severe infections in children in Qatar. The genome statistics are described, along with the strain types and serotypes predicted from the assembled genomes.

2009. Misidentification Rate of Acinetobacter baumannii Isolated From Invasive Infections in Children

Background Acinetobacter baumannii (AB) invasive infections are known to have a worse clinical outcome than non-baumannii Acinetobacter infections. However, currently, phenotypic identification by semi-automated commercial identification systems struggle to distinguish Acinetobacter subspecies; especially the four closely related subspecies of the Acinetobacter calcoaceticus–Acinetobacter baumannii (ACB) complex. The purpose of this study was to examine the rate of misidentification of AB isolated from invasive infections in children.MethodsFrom January 2001 to December 2017, patients 18 years old and below who were treated for invasive AB infections at Seoul National University Hospital and Chungnam National University Hospital were included. Acinetobacter baumannii, identified by commercial identification systems, cultured from sterile body fluids of the study participants were prospectively collected. The DNA from the stored bacteria were isolated, and subspecies identification was carried out by PCR and sequencing of the partial gyrB gene. Clinical data were retrospectively reviewed.ResultsDuring the 17-year study period, 113 AB isolates were obtained from patients treated for invasive infections. The median age of the patients was 2 (IQR 0–7) years old and 47 (49.5%) were male. Duplicate isolates were eliminated, and a total 95 isolates underwent further investigation. The isolates were retrieved from the blood (n = 82), peritoneal fluid (n = 8), pleural fluid (n = 2), cerebrospinal fluid (n = 2), and bronchoalveolar fluid (n = 1). Of the AB isolates identified by the commercial identification systems, 55 (57.9%) were AB. Of the non-AB isolates identified by partial gyrB sequencing, 22 (23.2%) were identified as A. nosocomialis, 8 (8.4%) as A. pittii, and 1 (1.1%) as A. calcoaceticus. Non-ACB complex subspecies included A. soli (n = 3), A. seifertii (n = 3), A. iwoffii (n = 1), A. bereziniae (n = 1), and A. junnii (n = 1).ConclusionThere was a high rate of misidentification of the Acinetobacter subspecies causing invasive infections in children. Further studies are needed to analyze the burden that misidentification has on the treatment and outcome of patients with invasive infections.Disclosures H. Lee, Korean Society of Pediatric Infectious Diseases: Member, Research grant.

Protection Against Invasive Infections in Children Caused by Encapsulated Bacteria.

The encapsulated bacteria Streptococcus pneumoniae, Neisseria meningitis, Haemophilus influenzae, and Streptococcus agalactiae (Group B Streptococcus) have been responsible for the majority of severe infections in children for decades, specifically bacteremia and meningitis. Isolates which cause invasive disease are usually surrounded by a polysaccharide capsule, which is a major virulence factor and the key antigen in protective protein-polysaccharide conjugate vaccines. Protection against these bacteria is largely mediated via polysaccharide-specific antibody and complement, although the contribution of these and other components, and the precise mechanisms, vary between species and include opsonophagocytosis and complement-dependent bacteriolysis. Further studies are required to more precisely elucidate mechanisms of protection against non-type b H. influenzae and Group B Streptococcus.

Catheter-related Saccharomyces cerevisiae Fungemia Following Saccharomyces boulardii Probiotic Treatment: In a child in intensive care unit and review of the literature

Although Saccharomyces boulardii is usually a non-pathogenic fungus, in rare occasions it can cause invasive infection in children. We present the case of an 8-year-old patient in pediatric surgical intensive care unit who developed S. cerevisiae fungemia following probiotic treatment containing S. boulardii. Caspofungin was not effective in this case and he was treated with amphotericin B. We want to emphasize that physicians should be careful about probiotic usage in critically ill patients.

Molecular characteristics of penicillin-binding protein 2b, 2x and 1a sequences in Streptococcus pneumoniae isolates causing invasive diseases among children in Northeast China.

Streptococcus pneumoniae is one of the common pathogens causing severe invasive infections in children. This study aimed to investigate the serotype distribution and variations of penicillin-binding proteins (PBPs) 2b, 2x and 1a in S. pneumoniae isolates causing invasive diseases in Northeast China. A total of 256 strains were isolated from children with invasive pneumococcal disease (IPD) from January 2000 to October 2014. All strains were serotyped and determined for antibiotic resistance. The amplicons of penicillin-binding domains in pbp1a, pbp2b and pbp2x genes were sequenced for variation identification. The most prevalent serotypes of isolates in IPD children were 19A, 14, 19F, 23F and 6B. 19A and 19F were the most frequent serotypes of penicillin-resistant S. pneumoniae (PRSP), which present with high resistance to amoxicillin, cefotaxime, ceftriaxone and meropenem. The numbers of amino acid substitutions of penicillin-non-susceptible S. pneumoniae (PNSP) isolates were higher than those of penicillin-sensitive S. pneumoniae isolates in all the PBP genes (p < 0.01). The patterns of amino acid mutation in PBP2b, PBP2x and PBP1a were unique and different from those of other countries. All of the serotype 19A and 19F PRSP isolates carried 25 amino acid mutations, including Ala618 → Gly between positions 560 and 675 in PBP2b and Thr338 → Ala substitutions in PBP2x. The amino acid alterations in PBP2b, PBP2x and PBP1a from S. pneumoniae were closely associated with resistance to β-lactam antibiotics. This study provides new data for further monitoring of genetic changes related to the emergence and spread of resistance to β-lactam antibiotics in China.

Investigation on the Factors Affecting Cronobacter sakazakii Contamination Levels in Reconstituted Powdered Infant Formula.

Certain strains of Cronobacter sakazakii can cause serious invasive infections in children, mainly those <2 months old and fed with powdered infant formula (PIF). The infectious dose of C. sakazakii is unknown but evidence suggests that it is approximately 1000 colony forming units (CFU). PIF is currently considered safe if its end-product C. sakazakii level is <1 CFU/g. In this study, we determined the lag time, generation time (GT), and growth rate of five pooled C. sakazakii isolates to evaluate the factors affecting contamination levels in reconstituted PIF. 1.71 log CFU/ml of C. sakazakii were inoculated into 100 and 3000 ml of reconstituted PIF and incubated at 22 and 35°C. Growth was evaluated over a 24-h period. ComBase was used for modeling. In 3000 ml, the growth rate was 0.45 ± 0.02 log CFU/h with a lag phase of 3 ± 0.05 h and GT of 0.67 h at 22°C, while the growth rate was 0.73 ± 0.01 log CFU/h with a lag phase of 0.45 ± 0.03 h and GT of 0.41 h at 35° C. Cronobacter sakazakii grows rapidly in reconstituted PIF, especially at 35° C.

Salmonella meningitis in children at Texas Children's Hospital

Salmonella spp., a common cause of gastroenteritis, can result in invasive infections in children. While reported in developing countries, Salmonella meningitis has rarely been described in the United States. To evaluate the incidence and clinical characteristics of Salmonella meningitis at Texas Children's Hospital, we conducted a retrospective chart review to identify children up to 18 years of age with positive cerebrospinal fluid cultures for Salmonella from 2000 to 2010. Salmonella meningitis occurred in 7 of 112 (6.5%) cases of invasive Salmonella infection in children at our institution. Non-typhi Salmo- nella species were isolated in all cerebrospinal fluid samples, but only one had bacteremia. Patients were otherwise healthy infants under 4 months of age with no travel history. The most frequent symptoms at presentation included irritability, fever and diarrhea. Management and treatment regimens were varied. All infants survived and recovered without sequelae. Patients who received longer duration of intravenous antibiotics had a longer hospital stay, required central venous access, and developed side effects from medications. Non-typhi Salmonella meningitis was exclusively diagnosed in healthy infants younger than 4 months of age, and was not associated with high morbidity or mortality. Evaluation for meningitis is warranted in infants with gastro- enteritis and systemic symptoms such as fever and irritability. The management of non-typhi Salmonella meningitis in children is not standardized and deserves further evaluation.

The association of serotype and pulsed-field gel electrophoresis genotype in isolates of Streptococcus pneumoniae isolated in Israel

The relationship between Streptococcus pneumoniae isolates causing invasive infections in children admitted to a single center in central Israel was examined by pulsed-field gel electrophoresis (PFGE) and serotyping. Although there was a close correlation between serotype and PFGE clone, the genetic diversity varied by serotype, with some genotypes comprising multiple serotypes. Additionally, clones C and D were associated with higher penicillin minimum inhibitory concentrations. Serotyping alone may be insufficient for epidemiological mapping of pneumococcal isolates in the era of pneumococcal conjugate polysaccharide vaccines.

1669Genetic Diversity of Pneumolysin and Pneumococcal Histidine Triad Protein D of Streptococcus pneumoniae Isolated from Invasive Infections in Children

1669Genetic Diversity of Pneumolysin and Pneumococcal Histidine Triad Protein D of Streptococcus pneumoniae Isolated from Invasive Infections in Children

Prise en charge des infections invasives et graves à streptocoque du groupe A

The group A streptococcus (GAS) is the 5(th) responsible pathogen of invasive infections in children in France. These particularly severe diseases are dominated in children by soft tissue infection, isolated bacteremia but also osteoarthritis. Other complications are rare in France such as lung infections, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). More unusual localizations such as meningitis, neonatal infections, severe ear and throat and gastrointestinal infections and vascular disorders are also described. Based on published series, mortality ranging from 0-8 % of cases, is high but still lower than that observed in adults. Probabilistic antibiotherapy includes a β-lactam with anti-SGA but also anti-staphylococcal (predominantly methi-S in France) activity such as clavulanic acid- amoxicillin followed by amoxicillin as soon as identification of SGA is performed. The addition of an anti-toxin antibiotic such as clindamycin is recommended particularly in NF or STSS or clinical signs suggestive of toxin production by the SGA (rash, gastrointestinal signs, hemodynamic disorders). The use of intravenous polyvalent immunoglobulins must also be discussed in NF and STSS. In all cases surgery should be discussed. The prognosis of these potentially very severe infections is related to their early diagnosis and treatment. A better understanding of the pathophysiology of these infections may optimize their management but also their prevention.

Prevalence of human Salmonellosis in Ethiopia: a systematic review and meta-analysis

BackgroundHuman Salmonellosis is one of the major diseases in Ethiopia and several factors including under and mal-nutrition and HIV-AIDS may substantially contribute to its occurrence. Despite its importance, surveillance and monitoring systems are not in place and a comprehensive picture of its epidemiology is not available. The objectives of this study were to systematically review and estimate the prevalence of the disease and identify the dominant serogroups and serotypes in Ethiopia.MethodsPublished studies on Salmonellosis in Ethiopia were electronically and manually searched. Eligible studies were selected by using inclusion and exclusion criteria. Generic, methodological and statistical information were extracted from the eligible studies. The extracted data included sample sizes, the numbers of Salmonella positive samples, serogroups and serotypes. The variations in prevalence estimates attributable to heterogeneities were assessed and pooled prevalence was estimated by the random effects model.ResultsTwenty studies carried out between 1974 and 2012 were eligible. The pooled prevalence estimates of Salmonella in stool samples of diarrheic children, diarrheic adults and carriers were 8.72%, 5.68%, and 1.08% respectively. Invasive infections in children (5.71%) and adults (0.76%) were significantly different (p < 0.001). Non-typhi isolates accounted for 57.9% of the isolates from patients. Serogroup D occurred more frequently than serogroups C and B. S. Concord, S. Typhi, S. Typhimurium and S. Paratyphi were dominant and accounted for 82.1% of the serotypes isolated from patients.ConclusionThe prevalence of Salmonellosis is considerable and most infections are due to four serotypes. The results imply the need for a policy to promote public hygiene and regularly screen individuals in contact with food items for public consumption.

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae isolated from invasive infections after optional use of the 7-valent conjugate vaccine in Korea, 2006–2010

This study examined the serotype distribution and antimicrobial resistance of pneumococcal isolates from invasive infections in children between 2006 and 2010, when the 7-valent pneumococcal conjugate vaccine (PCV7) was offered as an optional vaccine in Korea. Among 140 isolates collected from 8 centers, the common serotypes were 19A (22.9%), 19 F (12.1%), and 6B (8.6%). Between 2006 and 2010, PCV7 serotypes decreased from 62.5% to 21.4% (P = 0.002), whereas three 13-valent pneumococcal conjugate vaccine (PCV13)–specific serotypes (3, 6A, and 19A) increased from 18.8% to 42.9% (P = 0.016). Among 102 multidrug-resistant isolates, the proportion of PCV7 serotypes decreased from 65.2% to 21.7% (P = 0.001), and 3 PCV13-specific serotypes increased from 17.4% to 47.8% (P = 0.008). Optional PCV7 vaccination has influenced the proportion of PCV7 serotypes in Korea, resulting in a decrease, whereas the proportions of 3 PCV13-specific serotypes, particularly 19A, have increased.

Bacterial Respiratory Pathogens in Children With Inherited Immune and Airway Disorders

Children with primary immunodeficiencies, sickle cell disease and cystic fibrosis are at risk to develop invasive bacterial infections caused by respiratory tract pathogens, in particular Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. This review article evaluates the role of nasopharyngeal colonization by these pathogens in the high prevalence of respiratory and invasive infections in children with inherited disorders affecting the immune system or the respiratory tract. We conclude that respiratory and invasive diseases that occur in children with primary immunodeficiencies or sickle cell disease are probably a result of increased nasopharyngeal colonization rates compared with healthy children. However, when the inherited disorder is characterized by local airway abnormalities such as in cystic fibrosis, enhanced nasopharyngeal colonization does not seem to play a major role in invasive disease risk. As the evidence for the role of nasopharyngeal colonization in disease risk in these specific patient groups partly comes from experimental studies and animal models, longitudinal studies in children are needed. Detailed understanding of the effect of colonization on the development of respiratory and invasive infections in children with primary immunodeficiencies, sickle cell disease or cystic fibrosis provides a justification for the selective introduction of vaccination and prophylactic antibiotic treatment. Recommendations for the use of (preventive) therapeutic strategies in these patient groups taking into account disease-specific immunologic mechanisms underlying colonization and disease are described.