Laboratory-confirmed invasive meningococcal disease: effect of the Hajj vaccination policy, Saudi Arabia, 1995 to 2011.

Saudi Arabia (SA) experienced two large invasive meningococcal disease (IMD) outbreaks during the 2000 and 2001 Hajj pilgrimages. In 2002, polysaccharide quadrivalent ACWY vaccines became mandatory for Mecca and Medina pilgrims/residents older than two years. This study aimed to analyse IMD surveillance data among citizens, residents and pilgrims in SA from 1995 to 2011, focusing on changes before and after the new vaccination policy. For all laboratory-confirmed IMD cases in the national surveillance database from 1995 to 2011, serogroup and age were retrieved. The cases' seasonal distribution as well as the case fatality ratios (CFR) were obtained. For Saudi citizens/residents and Hajj pilgrims, annual rates were calculated using mid-year population estimates. The Student's t-test was used to compare means between the pre-epidemic (1995-1999) and post-epidemic (2002-2011) periods, excluding outbreak years. From 1995 to 2011, laboratories notified 1,103 cases. Between the pre- and post-epidemic periods, mean annual IMD rates decreased from 0.20 (standard deviation (SD): 0.1) to 0.06 cases/100,000 (SD: 0.06; p=0.02), mean numbers of Hajj-related cases from 13 (SD: 9.3) to 2 cases/year (SD: 2.3; p=0.02) and the mean age from 31 (SD: 1.3) to 18 years (SD: 1.4; p<0.01). The CFR in Saudi citizens (10.4) was lower than among foreign pilgrims (28.9) and decreased from 19.3% (SD: 1.8) in the pre-epidemic to 11.4% (SD: 7.0; p=0.04) in the post-epidemic phase. The decrease of annual IMD rates, CFR and Hajj-related cases between the pre- and post- vaccine era suggests a possible positive effect of the mandatory ACWY vaccination for pilgrims/residents in Mecca and Medina. Regular surveillance with an annual data analysis is necessary to monitor trends and circulating serotypes and to implement appropriate public health measures to avoid new IMD epidemics during upcoming Hajj seasons.

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.

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.

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.

New antimicrobial peptide active against Gram-positive pathogens.

BACKGROUND & OBJECTIVES: Human and animal cystatins have been shown to inhibit the replication of certain viruses and bacteria, though it is not directly demonstrated that the effects are due to protease inhibitory capacity of the cystatins. We report antibacterial properties of a novel antimicrobial peptidyl derivative, (2S)-2-(N(alpha)-benzyloxycarbonyl-arginyl-leucylamido)-1-[(E)-cinnamoylamido]-3- methylbutane, structurally based upon the aminoterminal segment of the inhibitory centre of the human cysteine protease inhibitor, cystatin C. METHODS: Clinical isolates of group A, B, C and G streptococci were collected. The antibacterial activity of Cystapep 1 derivative was tested by agar well diffusion method. RESULTS: Cystapep 1, displayed antibacterial activity against several clinically important Gram-positive bacteria. It displayed minimal inhibitory and bactericidal concentrations of about 16 microg/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. INTERPRETATION & CONCLUSION: Cystapep 1 also showed high activity against methicillin-resistant Staph. aureus (MRSA) and multi-antibiotic resistant coagulase negative staphylococci (CNS), suggesting its mechanism of action to be different from most currently used antibiotics.

Unusual occurrence of M type 77, antibiotic-resistant group A streptococci in southern Sweden.

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 emm sequence 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. ermB was 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.

High rate of tetracycline resistance in Streptococcus pyogenes in Iran: an epidemiological study.

Streptococcus pyogenes, a major human pathogen, is still considered susceptible to beta-lactams, but for other relevant antibiotics, highly variable resistance rates have been reported. Since no data were available from Iran, we tested 1,335 throat isolates from two different regions of the country for their antibiotic susceptibilities and, for comparison, a collection of 80 strains isolated from 1989 to 1991. Erythromycin resistance was uncommon (0.6%), whereas an overall high rate of tetracycline resistance was found, increasing between 1989-1991 and 1995-1997 from 23 to 42%. The tetracycline-resistant strains belonged to more than 10 different T types, the majority being types 4, 11, and B3264. By conventional M typing of 406 tetracycline-resistant isolates, more than 20 different M types were found. Approximately 50% of the strains were nontypeable by T agglutination as well as serological M typing; however, by genotyping by a combined PCR-capture-enzyme-linked immunosorbent assay, many of these strains were successfully emm typed. We conclude that the high rate of tetracycline resistance among Iranian S. pyogenes isolates is due to multiclonal dissemination of resistance within the streptococcal population rather than epidemic spread of single clones.

Isolation rates of Streptococcus pyogenes in patients with acute pharyngotonsillitis and among healthy school children in Iran.

We examined three populations from the Tehran region and the North part of Iran (Gilan), in all more than 5000 individuals, for carriage of Streptococcus pyogenes (group A streptococci; GAS). Children or adults with acute pharyngotonsillitis and healthy school children harboured GAS in 34-1, 20.0 and 21.0%, respectively. Typing of 421 randomly selected isolates showed a predominance of M-types M4, M5, M11, M12, as well as the provisional type 4245; however, many of the isolates were T and M non-typable. Forty-three percent of all strains were opacity factor (OF) negative. The type distribution differed markedly from that reported in 1973-4, when M types 1 and 12 were predominant.

Survey of macrolide resistance phenotypes in Swedish clinical isolates of Streptococcus pyogenes.

Two hundred selected Swedish clinical strains of Streptococcus pyogenes, identified as erythromycin-resistant and isolated between 1980 and 1988, and 37 consecutive, resistant strains from 1989-90 were examined for resistance phenotype by disc diffusion. Strains constitutively resistant to macrolides, lincosamides and streptogramin B were absent in 1980-85 but accounted for 10% in 1986-88. The majority of the isolates belonged to a recently reported, non-inducible phenotype, described as having low-level resistance to erythromycin and sensitivity to clindamycin (82% in 1980-85, 50% in 1986-88). A significant proportion of the isolates did not agree with any known phenotype and therefore were considered as having one of three novel resistance subphenotypes. Most of the 37 strains from 1989-90 belonged to a novel subphenotype.