Characterization of sil in invasive group A and G streptococci: antibodies against bacterial pheromone peptide SilCR result in severe infection.

Group G beta-hemolytic streptococcus (GGS) strains cause severe invasive infections, mostly in patients with comorbidities. GGS is known to possess virulence factors similar to those of its more virulent counterpart group A streptococcus (GAS). A streptococcal invasion locus, sil, was identified in GAS. sil encodes a competence-stimulating peptide named SilCR that activates bacterial quorum sensing and has the ability to attenuate virulence in GAS infections. We found that sil is present in most GGS strains (82%) but in only 25% of GAS strains, with a similar gene arrangement. GGS strains that contained sil expressed the SilCR peptide and secreted it into the growth medium. In a modified murine model of GGS soft tissue infection, GGS grown in the presence of SilCR caused a milder disease than GGS grown in the absence of SilCR. To further study the role of the peptide in bacterial virulence attenuation, we vaccinated mice with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a significantly more severe illness than nonvaccinated mice. Our results indicate that the sil locus is much more prevalent among the less virulent GGS strains than among GAS strains. GGS strains express and secrete SilCR, which has a role in attenuation of virulence in a murine model. We show that the SilCR peptide can protect mice from infection caused by GGS. Furthermore, vaccinated mice that produce specific anti-SilCR antibodies develop a significantly more severe infection. To our knowledge, this is a novel report demonstrating that specific antibodies against a bacterial component cause more severe infection by those bacteria.

Invasive Disease Due to Neisseria meningitidis: Surveillance and Trends in Israel Prior to and during the COVID-19 Pandemic.

Invasive meningococcal disease (IMD) is a devastating disease with significant mortality and long-term morbidity. The COVID-19 pandemic and containment measures have affected the epidemiology of infectious pathogens. This study's aim was to assess IMD trends in Israel prior to and during the COVID-19 pandemic. The Neisseria meningitidis invasive infection is a notifiable disease in Israel. Laboratory analysis includes serogrouping and molecular characterization. The overall national IMD incidence rate (1998-2022) was 0.8/100,000 population. The IMD incidence rates declined during the pandemic years (0.3/100,000 in 2020-2022 vs. 0.9/100,000 in 1998-2019). The number of notified IMD cases declined by 65% in 2020-2022. The case fatality rate among laboratory-confirmed IMD cases was 9% (47/521, 2007-2022). Mortality risk markers included cases' age (older) and socio-economic status (lower). Overall, most Neisseria meningitidis isolates were of serogroup B (62.6%), and the most prevalent clonal complex (CC) was CC32 (24.2%). Serogroup B prevailed in cases aged 0-9 years (74.5%) and less in cases aged 10 years and above (39%). Neisseria meningitidis serogroups and CC distribution altered recently with a decline in serogroup B fraction, an increase in serogroup Y, and a decline in CC32. Ongoing IMD surveillance is necessary to assess trends in circulating strains and support decision-making on meningococcal vaccination programs.

On the Origins of Disorganized Attachment and Internal Working Models: Paper II. An Empirical Microanalysis of 4-Month Mother-Infant Interaction.

A microanalysis of 4-month mother-infant face-to-face communication predicted 12-month infant disorganized (vs. secure) attachment outcomes in an urban community sample. We documented a dyadic systems view of the roles of both partners, the roles of both self- and interactive contingency, and the importance of attention, orientation and touch, and as well as facial and vocal affect, in the co-construction of attachment disorganization. The analysis of different communication modalities identified striking intrapersonal and interpersonal intermodal discordance or conflict, in the context of intensely distressed infants, as the central feature of future disorganized dyads at 4 months. Lowered maternal contingent coordination, and failures of maternal affective correspondence, constituted maternal emotional withdrawal from distressed infants. This maternal withdrawal compromises infant interactive agency and emotional coherence. We characterize of the nature of emerging internal working models of future disorganized infants as follows: Future disorganized infants represent states of not being sensed and known by their mothers, particularly in moments of distress; they represent confusion about both their own and their mothers' basic emotional organization, and about their mothers' response to their distress. This internal working model sets a trajectory in development which may disturb the fundamental integration of the person. The remarkable specificity of our findings has the potential to lead to more finely-focused clinical interventions.

MATERNAL ANXIETY SYMPTOMS AND MOTHER-INFANT SELF- AND INTERACTIVE CONTINGENCY.

Associations of maternal self-report anxiety-related symptoms with mother-infant 4-month face-to-face play were investigated in 119 pairs. Attention, affect, spatial orientation, and touch were coded from split-screen videotape on a 1-s time base. Self- and interactive contingency were assessed by time-series methods. Because anxiety symptoms signal emotional dysregulation, we expected to find atypical patterns of mother-infant interactive contingencies, and of degree of stability/lability within an individual's own rhythms of behavior (self-contingencies). Consistent with our optimum midrange model, maternal anxiety-related symptoms biased the interaction toward interactive contingencies that were both heightened (vigilant) in some modalities and lowered (withdrawn) in others; both may be efforts to adapt to stress. Infant self-contingency was lowered ("destabilized") with maternal anxiety symptoms; however, maternal self-contingency was both lowered in some modalities and heightened (overly stable) in others. Interactive contingency patterns were characterized by intermodal discrepancies, confusing forms of communication. For example, mothers vigilantly monitored infants visually, but withdrew from contingently coordinating with infants emotionally, as if mothers were "looking through" them. This picture fits descriptions of mothers with anxiety symptoms as overaroused/fearful, leading to vigilance, but dealing with their fear through emotional distancing. Infants heightened facial affect coordination (vigilance), but dampened vocal affect coordination (withdrawal), with mother's face-a pattern of conflict. The maternal and infant patterns together generated a mutual ambivalence.

Multidrug-resistant Salmonella enterica serovar Infantis, Israel.

To determine whether rapid emergence of Salmonella enterica serovar Infantis in Israel resulted from an increase in different biotypes or spread of 1 clone, we characterized 87 serovar Infantis isolates on the genotypic and phenotypic levels. The emerging strain comprised 1 genetic clone with a distinct pulsed-field gel electrophoresis profile and a common antimicrobial drug resistance pattern.

The origins of 12-month attachment: a microanalysis of 4-month mother-infant interaction.

A microanalysis of 4-month mother-infant face-to-face communication revealed a fine-grained specification of communication processes that predicted 12-month insecure attachment outcomes, particularly resistant and disorganized classifications. An urban community sample of 84 dyads were videotaped at 4 months during a face-to-face interaction, and at 12 months during the Ainsworth Strange Situation. Four-month mother and infant communication modalities of attention, affect, touch, and spatial orientation were coded from split-screen videotape on a 1 s time base; mother and infant facial-visual "engagement" variables were constructed. We used contingency measures (multi-level time-series modeling) to examine the dyadic temporal process over time, and specific rates of qualitative features of behavior to examine the content of behavior. Self-contingency (auto-correlation) measured the degree of stability/lability within an individual's own rhythms of behavior; interactive contingency (lagged cross-correlation) measured adjustments of the individual's behavior that were correlated with the partner's previous behavior. We documented that both self- and interactive contingency, as well as specific qualitative features, of mother and infant behavior were mechanisms of attachment formation by 4 months, distinguishing 12-month insecure, resistant, and disorganized attachment classifications from secure; avoidant were too few to test. All communication modalities made unique contributions. The separate analysis of different communication modalities identified intermodal discrepancies or conflict, both intrapersonal and interpersonal, that characterized insecure dyads. Contrary to dominant theories in the literature on face-to-face interaction, measures of maternal contingent coordination with infant yielded the fewest associations with 12-month attachment, whereas mother and infant self-contingency, and infant contingent coordination with mother, yielded comparable numbers of findings. Rather than the more usual hypothesis that more contingency is "better," we partially supported our hypothesis that 12-month insecurity is associated with both higher and lower 4-month self- and interactive contingency values than secure, as a function of mother vs. infant and communication modality. Thus, in the origins of attachment security, more contingency is not necessarily better. A remarkable degree of differentiation was identified in the 4-month patterns of "future" C and D infants, classified as resistant and disorganized, respectively, at 12 months. The central feature of future C dyads was dysregulated tactile and spatial exchanges, generating approach-withdrawal patterns. The intact maternal contingent coordination overall safeguards the future C infant's interactive agency. However, future C infants likely come to expect maternal spatial/tactile impingement, and to expect to "dodge" as mothers "chase." They managed maternal touch by tuning it out, sacrificing their ability to communicate about maternal touch. They "approached" by vigilantly coordinating their facial-visual engagement with maternal facial-visual engagement, but they "withdrew" by inhibiting their facial-visual engagement coordination with maternal touch. We proposed that future C infants will have difficulty feeling sensed and known during maternal spatial/tactile impingements. The central feature of future D dyads is intrapersonal and interpersonal discordance or conflict in the context of intensely distressed infants. Lowered maternal contingent coordination, and failures of maternal affective correspondence, constituted maternal emotional withdrawal from distressed infants, compromising infant interactive agency and emotional coherence. The level of dysregulation in future D dyads was thus of an entirely different order than that of future C dyads. We proposed that the future D infant represents not being sensed and known by the mother, particularly in states of distress. We proposed that the emerging internal working model of future D infants includes confusion about their own basic emotional organization, about their mothers' emotional organization, and about their mothers' response to their distress, setting a trajectory in development which may disturb the fundamental integration of the person. The findings have rich implications for clinical intervention, with remarkable specificity for different kinds of mother and infant distress. Heightened and lowered self- and interactive contingency, in different modalities, as well as the specific behavioral qualities identified, provide a more differentiated set of concepts to guide clinical intervention.

Surveillance of invasive meningococcal disease in the Tel Aviv District, Israel, 2007-2017.

Invasive meningococcal disease (IMD) is one of the leading causes of bacterial meningitis and septicemia in Israel. The purpose of the study was to describe the IMD in the Tel Aviv District and to identify specific populations who could benefit from vaccine introduction. In the Tel Aviv District, the incidence rates ranged from 0.4 to 1.4 cases per 100,000 population per year during 2007-2017. During the study period, seventy-nine patients (65%) occurred among children younger than four years of age. Eight deaths occurred (7%), most of them among children under the age of 1 year (5 deaths; 15%). A serogroup was identified in 82 isolates. Most of the isolates (69 cases - 84%) belonged to serogroup B (NmB). IMD clustered geographically in the city of Bnei Brak, with a predominantly Ultra-Orthodox Jewish population. It is the youngest and most densely populated city in the district. The overall incidence rates of IMD among children in Bnei Brak were more than seven times higher in children up to nine years, compared to the rest of the district. Specifically for NmB, disease rates were 9.08 times higher in children up to the age of four, and 7.74 times higher in children from five to nine years old in Bnei Brak, compared to the rest of the district. Our findings describe the burden of a vaccine-preventable disease and reinforce the need for routine 4CmenB introduction, especially in groups where the disease clusters.

Invasive meningococcal disease epidemiology and characterization of Neisseria meningitidis serogroups, sequence types, and clones; implication for use of meningococcal vaccines.

BACKGROUND AND AIMS: Neisseria meningitidis (N. meningitidis) is a Gram-negative bacterium that can cause life-threatening invasive infections referred to as invasive meningococcal disease (IMD). In the last decade the incidence of IMD in Israel is about 1/100,000 population annually. We aimed to describe the epidemiology of IMD in Israel combining epidemiological data and characterization of N. meningitidis isolates. METHODS: Invasive infection caused by N. meningitidis is a notifiable disease in Israel. Data were collected by epidemiological investigations and control measures were employed. Laboratory work-up included serogrouping, N. meningitides molecular characterization and whole-genome sequencing. RESULTS: During 1998-2017, 1349 cases of IMD were notified in Israel (mean annual incidence rate 0.94/100,000). The peak incidence rates were observed in infants under 1 year of age (10.9/100,000). Case fatality rate was 9.7%. The majority of the N. meningitidis isolates were of serogroup B (67.9%). During 2007-2017, three clonal complexes (CC) 32, 41/44 and 23 (hyper-invasive clonal complexes) were the leading CC (61%). CC32 was the leading CC causing meningococcemia and mortality. In 2017, 35 isolates were tested for 4CMenB antigens variants; of the serogroup B isolates tested 46.7% showed a match to one or more antigens (fHbp or PorA:VR1), most were ST32 (CC32). CONCLUSIONS: Preliminary analysis based on limited number of samples suggests that the 4CMenB coverage would be about half the strains; further research is necessary. Integration of clinical, epidemiological and laboratory data is essential to support decision-making on the introduction of the novel MENB vaccines in Israel.

Six-week postpartum maternal depressive symptoms and 4-month mother-infant self- and interactive contingency.

Associations of 6-week maternal depressive symptoms [Center for Epidemiological Studies Depression Scale (CES-D)] with 4-month mother-infant self- and interactive contingency patterns during face-to-face play were investigated in 132 dyads. Self- and interactive contingency (auto- and lagged cross-correlation, respectively) were assessed by multilevel time-series analysis. Infant and mother gaze, facial and vocal affect, touch, and spatial orientation behaviors were coded second-by-second from split-screen videotape, and a multimodal measure of facial-visual "engagement" was constructed, generating nine modality pairings. With higher CES-D, the self-contingency of both partners was lowered in most modalities. With higher CES-D, interactive contingency values were both heightened (in some modalities) and lowered (in others), varying by partner. These results are consistent with an optimal midrange model. With higher CES-D, interactive contingency showed the following patterns: (a) Mothers and their infants had a reciprocal orientational sensitivity; (b) mothers and infants manifested a reciprocal intermodal discordance in attention versus affect coordination, lowering gaze coordination, but heightening affective coordination; (c) infants heightened, but mothers lowered, touch coordination with partner touch-an "infant approach-mother withdraw" touch pattern. Nonlinear analyses indicated that altered self- and interactive contingency were similar at both the low ("denial") as well as the high ("endorsement") poles of depressive symptoms, in half the findings. These complex, multimodal findings define different aspects of communication disturbance, with relevance for therapeutic intervention.

Six-week postpartum maternal self-criticism and dependency and 4-month mother-infant self- and interactive contingencies.

Associations of 6-week postpartum maternal self-criticism and dependency with 4-month mother-infant self- and interactive contingencies during face-to-face play were investigated in 126 dyads. Infant and mother face, gaze, touch, and vocal quality were coded second by second from split-screen videotape. Self- and interactive contingencies were defined as auto- and lagged cross-correlation, respectively, using multilevel time-series models. Statistical significance was defined as p<.05. Regarding self-contingency, (a) more self-critical mothers showed primarily lowered self-contingency, whereas their infants showed both lowered and heightened, and (b) infants of more dependent mothers showed primarily lowered self-contingency, whereas findings were absent in mothers. Regarding interactive contingency, (a) more self-critical mothers showed lowered attention and emotion contingencies but heightened contingent touch coordination with infant touch, and (b) more dependent mothers and their infants showed heightened facial/vocal interactive contingencies. Thus, maternal self-criticism and dependency have different effects on mother-infant communication.

Macrolide, lincosamide and tetracycline susceptibility and emm characterisation of invasive Streptococcus pyogenes isolates in Israel.

Group A beta-haemolytic streptococcus (GAS) causes a variety of infections, including life-threatening illnesses. Although the species is uniformly penicillin susceptible, resistance to other antibiotics is becoming more common. We studied the prevalence of resistance and associated factors in a nationwide, prospective, population-based study of invasive infections in Israel. Isolates were collected in collaboration with 24 hospitals in Israel during 1996-1999. Minimal inhibitory concentrations (MICs) of erythromycin (ERY), clindamycin (CLI) and tetracycline (TET) were determined as well as ERY and TET resistance phenotypes and genotypes. Five hundred isolates were examined: 136 (27.2%) were not susceptible to TET, 10 (2.0%) to ERY and 5 (1%) to CLI. ERY resistance was associated with emm types 12 and 83 (P<0.001 for both). MICs of TET had a bimodal distribution distinguishing sensitive and resistant populations. Non-susceptibility to TET was mainly due to the presence of tet(M) and was associated with T types 3, 3/13/B3624 and 9 and emm types 9, 33, 64, 73, 74, 76, 77 and 83. TET susceptibility was associated with T types 1, 2 and 11, emm types 1-4, 11, 12, 22, 26 and 75 and the presence of speA and speC. In Israel, resistance of invasive GAS isolates to ERY remains low and is associated with specific T and emm types, as is TET resistance. TET resistance is less frequent than previously reported in Israel and is associated with a lower prevalence of speA and speC.

Effect of a bacterial pheromone peptide on host chemokine degradation in group A streptococcal necrotising soft-tissue infections.

BACKGROUND: Necrotising soft-tissue infections due to group A streptococcus (GAS) are rare (about 0.2 cases per 100000 people). The disease progresses rapidly, causing severe necrosis and hydrolysis of soft tissues. Histopathological analysis of necrotic tissue debrided from two patients (one with necrotising fasciitis and one with myonecrosis) showed large quantities of bacteria but no infiltrating neutrophils. We aimed to investigate whether the poor neutrophil chemotaxis was linked with the ability of group A streptococcus (GAS) to degrade host chemokines. METHODS: We did RT-PCR, ELISA, and dot-blot assays to establish whether GAS induces synthesis of interleukin 8 mRNA, but subsequently degrades the released chemokine protein. Class-specific protease inhibitors were used to characterise the protease that degraded the chemokine. We used a mouse model of human soft-tissue infections to investigate the pathogenic relevance of GAS chemokine degradation, and to test the therapeutic effect of a GAS pheromone peptide (SilCR) that downregulates activity of chemokine protease. FINDINGS: The only isolates from the necrotic tissue were two beta-haemolytic GAS strains of an M14 serotype. A trypsin-like protease released by these strains degraded human interleukin 8 and its mouse homologue MIP2. When innoculated subcutaneously in mice, these strains produced a fatal necrotic soft-tissue infection that had reduced neutrophil recruitment to the site of injection. The M14 GAS strains have a missense mutation in the start codon of silCR, which encodes a predicted 17 aminoacid pheromone peptide, SilCR. Growth of the M14 strain in the presence of SilCR abrogated chemokine proteolysis. When SilCR was injected together with the bacteria, abundant neutrophils were recruited to the site of infection, bacteria were cleared without systemic spread, and the mice survived. The therapeutic effect of SilCR was also obtained in mice challenged with M1 and M3 GAS strains, a leading cause of invasive infections. INTERPRETATION: The unusual reduction in neutrophils in necrotic tissue of people with GAS soft-tissue infections is partly caused by a GAS protease that degrades interleukin 8. In mice, degradation can be controlled by administration of SilCR, which downregulates GAS chemokine protease activity. This downregulation increases neutrophil migration to the site of infection, preventing bacterial spread and development of a fulminant lethal systemic infection.

Distressed mothers and their infants use a less efficient timing mechanism in creating expectancies of each other's looking patterns.

The prediction of events and the creation of expectancies about their time course is a crucial aspect of an infant's mental life, but temporal mechanisms underlying these predictions are obscure. Scalar timing, in which the ratio of mean durations to their standard deviations is held constant, enables a person to use an estimate of the mean for its standard deviation. It is one efficient mechanism that may facilitate predictability and the creation of expectancies in mother-infant interaction. We illustrate this mechanism with the dyadic gaze rhythm of mother and infant looking at and looking away from each other's faces. Two groups of Hi- and Lo-Distress mothers were created using self-reported depression, anxiety, self-criticism and childhood experiences. Lo-Distress infants (controls) used scalar timing 100% of the time, about double that of Hi-Distress infants. Lo-Distress mothers used scalar timing about nine times as much as Hi-Distress mothers. The diminished use of scalar timing patterns in Hi-Distress mothers and infants may make the anticipation of each other's gaze patterns more difficult for both partners.

Infant gaze, head, face and self-touch at 4 months differentiate secure vs. avoidant attachment at 1 year: a microanalytic approach.

The study attempted to distinguish avoidant vs. secure infants at 1 year from 4-month infant behavior only, during a face-to-face play interaction with the mother. Thirty-five 4-month-old infants were coded second by second for infant gaze, head orientation, facial expression and self-touch/mouthing behavior. Mother behavior was not coded. At 1 year, 27 of these infants were classified as secure (B), and 8 as avoidant (A) attachment in the Ainsworth Strange Situation. Compared with the B infant, the future A infant spent less time paying 'focused' visual attention (a look of a minimum 2 seconds duration) to the mother's face. Only if the A infant engaged in self-touch/mouthing behavior did its focused visual attention match that of the B. Markovian t to t+1 transition matrices then showed that both for future A and for future B infants, focused visual attention on the mother constrained the movements of the head to within 60 degrees from center vis-à-vis, defining head/gaze co-ordination within an attentional-interpersonal space. However, infant maintenance of head/gaze co-ordination was associated with self-touch/mouthing behavior for the A infant but not the B. Positive affect was associated with a disruption of head/gaze co-ordination for the A but not the B. Whereas the B had more variable facial behavior, potentially providing more facial signaling for the mother, the A had more variable tactile/mouthing behavior, changing patterns of self-soothing more often. Thus, infants classified as A vs. B at 12 months showed different behavioral patterns in face-to-face play with their mothers as early as 4 months.

The cross-modal coordination of interpersonal timing: six-week-olds infants' gaze with adults' vocal behavior.

The purpose of this study was to examine the hypothesis that 6-week-old infants are capable of coordinated interpersonal timing within social interactions. Coordinated interpersonal timing refers to changes in the timing of one individual's behavior as a function of the timing of another individual's behavior. Each of 45, first-bom 6-week-old infants interacted with his or her mother and a stranger for a total of 14 minutes. The interactions were videotaped and coded for the gaze behavior of the infants and the vocal behavior of the mothers and strangers. Time-series regression analyses were used to assess the extent to which the timing of each of the infants' gazes was coordinated with the timing of the adults' vocal behavior. The results revealed that (a) coordinated timing occurs between infants and their mothers and between infants and strangers as early as when infants are 6 weeks old, and (b) strangers coordinated the timing of their pauses with the infants to a greater extent than did mothers. The findings are discussed in terms of the role of temporal sensitivity in social interaction.

A locus of group A Streptococcus involved in invasive disease and DNA transfer.

Group A streptococcus (GAS) causes diseases ranging from benign to severe infections such as necrotizing fasciitis (NF). The reasons for the differences in severity of streptococcal infections are unexplained. We developed the polymorphic-tag-lengths-transposon-mutagenesis (PTTM) method to identify virulence genes in vivo. We applied PTTM on an emm14 strain isolated from a patient with NF and screened for mutants of decreased virulence, using a mouse model of human soft-tissue infection. A mutant that survived in the skin but was attenuated in its ability to reach the spleen and to cause a lethal infection was identified. The transposon was inserted into a small open reading frame (ORF) in a locus termed sil, streptococcal invasion locus. sil contains at least five genes (silA-E) and is highly homologous to the quorum-sensing competence regulons of Streptococcus pneumoniae. silA and silB encode a putative two-component system whereas silD and silE encode two putative ABC transporters. silC is a small ORF of unknown function preceded by a combox promoter. Insertion and deletion mutants of sil had a diminished lethality in the animal model. Virulence of a deletion mutant of silC was restored when injected together with the avirulent emm14-deletion mutant, but not when these mutants were injected into opposite flanks of a mouse. DNA transfer between these mutants occurred in vivo but could not account for the complementation of virulence. DNA exchange between the emm14-deletion mutant and mutants of sil occurred also in vitro, at a frequency of approximately 10-8 for a single antibiotic marker. Whereas silC and silD mutants exchanged markers with the emm14 mutant, silB mutant did not. Thus, we identified a novel locus, which controls GAS spreading into deeper tissues and could be involved in DNA transfer.

Group G streptococcal bacteremia in Jerusalem.

Group G Streptococcus (GGS) can cause severe infections, including bacteremia. These organisms often express a surface protein homologous to the Streptococcus pyogenes M protein. We retrospectively studied the characteristics of patients from the Hadassah Medical Center with GGS bacteremia from 1989 to 2000. Ninety-four cases of GGS bacteremia were identified in 84 patients. The median age was 62 years, 54% were males, and 92% had underlying diseases (35% had a malignancy, and 35% had diabetes mellitus). The most frequent source for bacteremia was cellulitis (61%). emm typing of 56 available isolates disclosed 13 different types, including 2 novel types. Six patients had recurrent bacteremia with two to four bacteremic episodes, five had chronic lymphatic disorders, and two had emm type stG840.0 in every episode. Recurrent bacteremia has not been described for invasive group A Streptococcus. We describe an entity of recurrent GGS bacteremia, which is associated with lymphatic disorders and possibly with emm stG840.0.

emm typing of M nontypeable invasive group A streptococcal isolates in Israel.

We performed emm typing of M nontypeable invasive group A streptococcal (GAS) isolates collected in a prospective population-based study in Israel. One hundred twenty of 131 isolates (92%) had emm sequences compatible with GAS, consisting of 51 different emm types. Eleven isolates were found to be group G streptococcus. Of the 120 isolates, 55 (46%) belonged to 32 types for which there were no typing sera available in the Streptococcal Reference Laboratory in Israel. The other 65 (64%) isolates, consisting of 19 types, had sera available and therefore could have been serotyped. Forty-three isolates had T and emm types which were not correlated according to standard M-typing protocols and were therefore missed. The principal effect of emm typing was the addition of 32 types not previously identified in Israel and the discovery of new associations between emm and T types. emm typing did not significantly change the proportion of M types; the five most common types were 3, 28, 2, 62, and 41. Twenty different types comprised 80% of all isolates. No new emm sequences were discovered. emm typing emphasized the unusually low incidence of M1 strains causing severe disease in Israel. As serological typing of GAS becomes more problematic due to lack of sera and the appearance of new emm types, reference laboratories should replace M typing with emm sequence typing. Development of a GAS vaccine relies on the emm type distributions in different geographical locations. In our study, 7% of isolates (types 41 and 62) are not included in a 26-valent vaccine that is being studied.