Aftab Jasir

Epidemiology of Severe Streptococcus pyogenes Disease in Europe

ABSTRACT The past 2 decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data were collected through a European Union FP-5-funded program (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe (Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, and the United Kingdom) using a standardized case definition. A total of 5,522 cases were identified across the 11 countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infection showed remarkable congruence between countries. The risk of infection was highest among the elderly, and rates were higher in males than in females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue were the most common foci of infection, with 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%; it was 44% among patients who developed streptococcal toxic shock syndrome. The findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe.

Clinical and Microbiological Characteristics of Severe Streptococcus pyogenes Disease in Europe

ABSTRACT In an attempt to compare the epidemiology of severe Streptococcus pyogenes infection within Europe, prospective data were collected through the Strep-EURO program. Surveillance for severe cases of S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in 11 countries across Europe by using a standardized case definition and questionnaire. Patient data as well as bacterial isolates were collected and characterized by T and M/emm typing, and selected strains were analyzed for the presence of superantigen genes. Data were analyzed to compare the clinical and microbiological patterns of the infections across the participating countries. A total of 4,353 isolates were collected from 5,521 cases with severe S. pyogenes infections who were identified. A wide diversity of M/emm types (n = 104) was found among the S. pyogenes clinical isolates, but the M/emm type distribution varied broadly between participating countries. The 10 most predominant M/emm types were M/emm type 1 (M/emm1), M/emm28, M/emm3, M/emm89, M/emm87, M/emm12, M/emm4, M/emm83, M/emm81, and M/emm5, in descending order. A correlation was found between some specific disease manifestations, the age of the patients, and the emm types. Although streptococcal toxic shock syndrome and necrotizing fasciitis were caused by a large number of types, they were particularly associated with M/emm1 and M/emm3. The emm types included in the 26-valent vaccine under development were generally well represented in the present material; 16 of the vaccine types accounted for 69% of isolates. The Strep-EURO collaborative program has contributed to enhancement of the knowledge of the spread of invasive disease caused by S. pyogenes within Europe and encourages future surveillance by the notification of cases and the characterization of strains, which are important for vaccination strategies and other health care issues.

Molecular and clinical characteristics of invasive group A streptococcal infection in Sweden

BACKGROUND The incidence and severity of invasive group A streptococcal infection demonstrate great variability over time, which at least, in part, seems to be related to group A streptococcal type distribution among the human population. METHODS An enhanced surveillance study of invasive group A streptococcal infection (746 isolates) was performed in Sweden from April 2002 through December 2004. Noninvasive isolates from either the throat or skin (773 isolates) were collected in parallel for comparison. Clinical and epidemiological data were obtained from 88% of patients with invasive disease and were related to isolate characteristics, including T type, emm sequence type, and the presence of 9 superantigen genes, as well as pulsed-field gel electrophoresis pattern comparisons of selected isolates. RESULTS The annual incidence was 3.0 cases per 100,000 population. Among the patients with invasive disease, 11% developed streptococcal toxic shock syndrome, and 9.5% developed necrotizing fasciitis. The overall case-fatality rate was 14.5%, and 39% of the patients with streptococcal toxic shock syndrome died (P<.001). The T3/13/B3264 cluster accounted for 33% of invasive and 25% of noninvasive isolates. Among this most prevalent type cluster, emm types 89 and 81 dominated. Combined results from pulsed-field gel electrophoresis, emm typing, and superantigen gene profiling identified subgroups within specific emm types that are significantly more prone to cause invasive disease than were other isolates of the same type. CONCLUSIONS This study revealed a changing epidemiology of invasive group A streptococcal infection in Sweden, with emergence of new emm types that were previously not described. The results also suggest that some clones may be particularly prone to cause invasive disease.

Clinical and Epidemiological Aspects of Invasive Streptococcus pyogenes Infections in Denmark during 2003 and 2004

ABSTRACT Active surveillance of invasive group A streptococcal (GAS) infections was conducted in Denmark during 2003 and 2004 as a part of the Strep-EURO initiative. The main objective was to improve understanding of the epidemiology of invasive GAS disease in Denmark. During the 2 years, 278 cases were reported, corresponding to a mean annual incidence of 2.6 cases per 100,000 inhabitants. The vast majority of isolates, 253 (91%), were from blood, with the remaining 25 (9%) being from cerebrospinal fluid, joints, or other normally sterile sites. The mean case fatality rate (CFR) was 20%, with the rate being higher in patients more than 70 years of age (36.5%). For streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis the CFRs were 53% and 25%, respectively. Out of 16 T types recorded, three predominated: T28 (23%), T1 (22%), and the cluster T3/13/B3264 (14%). Among 29 different emm types, emm28 and emm1 accounted for 51% of strains, followed by emm3 (11%), emm89 (7%), and emm12 (5.5%). Low resistance rates were detected for macrolide-lincosamide-streptogramin B (MLSB) antibiotics (3%) and tetracycline (8%); two isolates exhibited coresistance to tetracycline and macrolides. Of nine pyrogenic exotoxin (superantigen) genes examined, speA and speC were identified in 58% and 40% of the strains, respectively; either of the genes was present in all strains causing STSS. Most strains harbored speG (99%). ssa was present in 14% of the isolates only. In Denmark, as in comparable countries, GAS invasive disease shows a sustained, high endemicity, with involvement of both established and emerging streptococcal emm and T types.

The epidemiology of severe Streptococcus pyogenes associated disease in Europe

Several European countries reported outbreaks of severe disease caused by Streptococcus pyogenes in the late 1980s. This marked a departure from the previous decades, where very few such outbreaks were noted. These changes in disease occurrence formed part of a global phenomenon, the reasons for which have yet to be explained. Results of surveillance activities for invasive S. pyogenes infection within Europe over the past fifteen years identified further increases in many countries. However, variations in surveillance methods between countries preclude robust comparisons being made, illustrating the need for a unified surveillance strategy across Europe. This was finally embodied in the Strep-EURO programme, introduced in 2002.

Invasive disease caused by Haemophilus influenzae in Sweden 1997–2009; evidence of increasing incidence and clinical burden of non‐type b strains

Introduction of a conjugated vaccine against encapsulated Haemophilus influenzae type b (Hib) has led to a dramatic reduction of invasive Hib disease. However, an increasing incidence of invasive disease by H. influenzae non-type b has recently been reported. Non-type b strains have been suggested to be opportunists in an invasive context, but information on clinical consequences and related medical conditions is scarce. In this retrospective study, all H. influenzae isolates (n = 410) from blood and cerebrospinal fluid in three metropolitan Swedish regions between 1997 and 2009 from a population of approximately 3 million individuals were identified. All available isolates were serotyped by PCR (n = 250). We observed a statistically significant increase in the incidence of invasive H. influenzae disease, ascribed to non-typeable H. influenzae (NTHi) and encapsulated strains type f (Hif) in mainly individuals >60 years of age. The medical reports from a subset of 136 cases of invasive Haemophilus disease revealed that 48% of invasive NTHi cases and 59% of invasive Hif cases, respectively, met the criteria of severe sepsis or septic shock according to the ACCP/SCCM classification of sepsis grading. One-fifth of invasive NTHi cases and more than one-third of invasive Hif cases were admitted to intensive care units. Only 37% of patients with invasive non-type b disease had evidence of immunocompromise, of which conditions related to impaired humoral immunity was the most common. The clinical burden of invasive non-type b H. influenzae disease, measured as days of hospitalization/100 000 individuals at risk and year, increased significantly throughout the study period.

Unusual Occurrence of M Type 77, Antibiotic-Resistant Group A Streptococci in Southern Sweden

ABSTRACT For many years group A streptococci of T type 28 (T28) have been common in southern Sweden; however, since 1995 resistance to both macrolide-lincosamide-streptogramin B (MLS) antibiotics and tetracycline was observed among T28 isolates, which prompted the present studies on clonal relatedness of antibiotic-resistant T28 strains. By extended T typing, 95 of 100 examined tetracycline-resistant strains showed the combination T9-T13-T28; of these, 94 belonged to M type 77 (M77) and one belonged to M73. Three strains were T28-M28 and two were T28-M nontypeable. The serological M77 was confirmed by PCR capture enzyme-linked immunosorbent assay,emm amplicon restriction profiling, and emmsequence typing. Fifty strains were examined for superantigen genes:speA was detected in three blood isolates only, whereas all isolates harbored speB, and only two of the strains were negative for speC. Eighty-nine of the 100 strains were also macrolide resistant, of which 59 were inducibly MLS resistant (IR) and 21 were constitutively MLS resistant (CR), 6 were noninducibly resistant (NI), and 3 had novel subphenotypes recently reported by our group. Resistance genes were determined by PCR and hybridization methods. Eighty-four of the 100 strains harbored tetM. ermBwas detected in all CR and IR strains, and mefA was found in all NI strains; both ermB and mefA were identified in two strains with novel subphenotypes. Pulsed-field gel electrophoresis showed that these antibiotic-resistant M77 strains belonged to at least five different clones.

Are current rapid detection tests for Group A Streptococci sensitive enough? Evaluation of 2 commercial kits

A new, 1-step, enzyme-linked immunoassay kit for detection of Group A Streptococci (GAS) in throat samples (QuickVue In-Line One-Step Strep A Test; Quidel Corporation, San Diego, CA) was evaluated for use in a study comprising 536 patients in 8 primary healthcare centres. Compared to conventional culture at the clinical microbiology laboratory, the sensitivity achieved was 73.9% and the specificity 86.8%; these figures were not affected to any major extent by broth enrichment of samples before culturing or following PCR testing of the cysteine proteinase gene for independent diagnosis of GAS. It was also found that most samples containing low numbers of GAS were missed by the rapid test. We therefore evaluated the kit in use in our area (TestPack Plus Strep A Test; Abbott Laboratories, Chicago, IL) in a separate study of 615 patients. Somewhat increased sensitivity (82.8%) and specificity (96.1%) were obtained. As current antigen tests depend on subjective judgement of test outcome, improvements in test design or provision of more detailed instructions may be desirable in order to achieve optimal results.

New antimicrobial cystatin C-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus and multiresistant coagulase-negative staphylococci.

We describe the synthesis and antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)‐2‐(Nα‐benzyloxycarbonyl‐arginyl‐leucylamido‐1‐[(E)‐cinnamoylamido]‐3‐methylbutane, structurally based upon the inhibitory centre of the human cysteine protease inhibitor, cystatin C. The derivative, here called Cystapep 1, displayed antibacterial activity against several clinically important gram‐positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 μg/ml for both Staphylococcus aureus and Streptococcus pyogenes. In radial agar diffusion assays, groups A, B, C and G streptococci as well as staphylococci were generally susceptible to the action of Cystapep 1, whereas pneumococci and enterococci were less susceptible. No activity against gram‐negative bacteria was observed. Cystapep 1 also showed high activity against methicillin‐resistant S. aureus (MRSA) and multiantibiotic‐resistant coagulase‐negative staphylococci (CNS), suggesting that its mechanism of action differs from those of most currently used antibiotics.

Effects of a large-scale introduction of the pneumococcal polysaccharide vaccine among elderly persons in Stockholm, Sweden

In October 1998 Stockholm County launched a 3-year vaccination campaign with the 23-valent pneumococcal polysaccharide vaccine (PPV-23) directed towards all elderly persons. We analysed the impact of this campaign on the incidence and serotype distribution of invasive pneumococcal disease (IPD) in Stockholm County, where the vaccine coverage was 36%, as compared to Skåne County, where no vaccination campaign was performed. The incidence of vaccine-type IPD in Stockholm declined significantly during the study period (1997-2001) in elderly persons, from 50 to 28.9/100,000, but not in other age groups in Stockholm, nor in any age group in Skåne.