Abstract
To examine the type distribution of pathogenic group A streptococcal (GAS) strains in Mexico, we determined the emm types of 423 GAS isolates collected from ill patients residing in Mexico (Durango or Mexico City). These included 282 throat isolates and 107 isolates from normally sterile sites. Of the other isolates, 38 were recovered from other miscellaneous infections. A total of 31 different emm types were found, revealing a broad overlap between commonly occurring emm types in Mexico and the United States. The information obtained in this study is consistent with the possibility that multivalent, M type-specific vaccines prepared for GAS strain distribution within the United States could theoretically protect against the majority of GAS strains causing disease in the two cities surveyed in Mexico.
It is possible that effective vaccines against group A streptococci (GAS) would be based upon complex combinations of antigens, including combinations of type-specific M protein components. The formulations for these vaccines would require knowledge of the types of GAS causing disease in the community. A total of 117 M protein gene (emm) types of GAS have been documented to date (6). A vaccine presently under investigation and undergoing clinical trials contains 26 different type-specific M protein fragments (8). The formulation of this vaccine was determined by the emm types historically associated with rheumatic fever and those associated with invasive disease in the United States. A similar approach is being used to formulate a vaccine based upon prevalent GAS M protein types observed in the Australian aboriginal population (3). It has been estimated that the aforementioned 26-valent vaccine (26VV) represents 78 to 80% of the type distribution seen in pharyngitis and invasive-infection GAS isolates in the United States (8). The potential coverage of this 26VV for strains causing infections in other parts of the world is unknown. Ideally, a vaccine formulated against common strains causing the majority of pharyngitis cases would also prevent the majority of rheumatic fever occurrences (a sequela of pharyngitis).
The best information presently available concerning GAS M type distribution in Mexico is based upon a recent study of 54 isolates which comprised 12 emm types (13). Of those isolates, 45 (83%) corresponded to 8 M protein types included in the 26VV that is presently being studied (8, 13). The goal of this study was to further examine GAS M type distribution in Mexico through emm typing of a diverse set of 423 GAS isolates recovered from patients in two outpatient clinics over the 10-year period from 1991 to 2000.
MATERIALS AND METHODS
Isolates.
A total of 423 GAS isolates were typed, including 211 pharyngeal isolates from children who presented symptoms of pharyngitis at the outpatient clinic in Mexico City from 1991 to 2000. An additional 71 isolates from pharyngitis patients were collected from an outpatient clinic in Durango in 1998 and 1999. Throat isolates were collected by screening blood agar plates for beta-hemolytic colonies. A total of 107 isolates were collected from normally sterile body sites, including 68 isolates recovered by needle aspiration from abscesses and subcutaneous infections. Sterile site isolates were recovered from blood culture bottles or blood agar plates directly inoculated with aseptically collected fluid from abscesses and cerebrospinal, brain, vesicle, and subcutaneous tissue sites and with aseptically collected synovial, peritoneal, and pleural fluids. An additional 35 isolates were recovered from hospitalized patients in Hospital Infantil de Mexico “Federico Gomez” in Mexico City. These latter isolates were from miscellaneous sites, including vaginal, bronchial, ear, catheter, eye, nasal, and urine sites. Cases of streptococcal toxic shock syndrome (STSS) were identified by the criteria outlined in the guidelines published by the Working Group on Severe Streptococcal Infections (18).
Serologic tests.
Strains were identified as group A by slide agglutination testing (Phadebact streptococcus tests; Boule Diagnostics AB, Huddinge, Sweden). T typing and opacity factor determination were performed as previously described (10).
Strain typing.
Isolates were subjected to emm typing exactly as described at the following website: http://www.cdc.gov/ncidod/biotech/strep/protocols.html. Briefly, crude lysate supernatants were used as templates, amplified using a previously described primer set (17) and conventional PCR conditions, and subjected to restriction analysis as described at the above website. Representative amplicons with identical DdeI profiles as well as identical HincII and HaeIII double-digest profiles, from isolates with identical T agglutination patterns and opacity factor reactions, were sequenced to determine the predominant alleles within emm types. Sequence types and subtypes were assigned through direct matches to entries in the Centers for Disease Control and Prevention GAS emm sequence database (http://www.cdc.gov/ncidod/biotech/strep/emmtypes.html). Sequences with ≥95% identity (within bases 1 to 160), obtained with primer emmseq2 and containing no more than one alteration of the reading frame within this sequence affecting seven or fewer codons, were assigned the same emm type. Subtypes were assigned on the basis of any amino acid sequence alterations within the predicted 50 N terminal residues of the M protein. New sequence types and subtypes were screened against the GenBank database to determine whether these had been previously detected by other investigators.
RESULTS
emm-type distribution in children with pharyngitis.
The emm types of 282 GAS isolated from Mexican children presenting with pharyngitis to outpatient clinics over a 10-year period (1991 to 2000) are shown in Table 1. These include 211 isolates from an outpatient clinic in Mexico City collected over the years 1991 to 1996 and 1998 to 2000. An additional 71 isolates recovered from an outpatient clinic in Durango during years 1998 to 1999 are also included.
TABLE 1.
Pharyngeal, sterile site, and miscellaneous group A streptococcal isolates recovered in Mexico City (1991 to 2000) and Durango
| emm type | No. of pharyngeal isolates recovered from pediatric pharyngitis patients in:
|
Total no. (%) of pharyngeal isolates | No. (%) of sterile-site isolatesb | No. (%) of other isolatesc | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mexico City in the indicated year
|
Durango in 1998-1999 | ||||||||||||
| 1991 | 1992 | 1993 | 1994 | 1995 | 1996 | 1998 | 1999 | 2000 | |||||
| 1-Va | 6 | 0 | 0 | 9 | 3 | 4 | 1 | 3 | 3 | 20 | 49 (17.4) | 24 (22.9) | 9 (24) |
| 12-V | 2 | 8 | 2 | 9 | 5 | 9 | 7 | 1 | 0 | 6 | 49 (17.4) | 14 (13.3) | 4 (10.5) |
| 3-V | 2 | 4 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 13 | 22 (7.8) | 5 (4.8) | 2 (5.3) |
| 75-V | 2 | 3 | 1 | 7 | 1 | 2 | 4 | 1 | 0 | 1 | 22 (7.8) | 8 (6.7) | 2 (5.3) |
| 4 | 0 | 1 | 0 | 2 | 2 | 5 | 1 | 0 | 1 | 6 | 18 (6.4) | 4 (3.8) | 3 (7.9) |
| 2-V | 0 | 3 | 2 | 4 | 1 | 0 | 3 | 1 | 3 | 0 | 17 (6.0) | 10 (9.5) | 2 (5.3) |
| 77-V | 2 | 1 | 2 | 3 | 2 | 2 | 2 | 0 | 1 | 1 | 16 (6.0) | 3 (0.3) | 3 (15.8) |
| 22-V | 2 | 2 | 0 | 1 | 0 | 5 | 0 | 0 | 1 | 5 | 16 (5.7) | 5 (4.8) | 3 (7.9) |
| 6-V | 0 | 1 | 2 | 1 | 0 | 6 | 2 | 0 | 1 | 6 | 19 (6.2) | 8 (8.6) | 1 (2.6) |
| 9 | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 1 | 0 | 4 | 10 (3.2) | 1 (1.0) | 0 |
| 5-V | 2 | 1 | 2 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 8 (2.8) | 1 (0) | 0 |
| 18-V | 0 | 1 | 1 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 6 (3.3) | 4 (3.8) | 0 |
| 28-V | 0 | 2 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 5 (1.8) | 0 (0) | 1 (2.6) |
| 66 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 (1.4) | 1 (1.0) | 0 |
| 89-V | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 4 | 6 (2.1) | 2 (1.0) | 2 (2.6) |
| 41 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 (0.7) | 0 (0) | 0 |
| 92-V | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 4 (1.4) | 4 (3.8) | 0 |
| 78 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 (0.4) | 2 (1.9) | 1 (2.6) |
| 48 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.4) | 1 (1.0) | 0 |
| 49 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.4) | 1 (1.0) | 1 (2.6) |
| 76-V | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.4) | 1 (1.0) | 0 |
| 82 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 (0.4) | 1 (1.0) | 0 |
| 33-V | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 (0.4) | 1 (1.0) | 0 |
| 58 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 (0.4) | 0 (0) | 0 |
| 87 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 (0.4) | 0 (0) | 0 |
| 102 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (0.4) | 0 (0) | 0 |
| St369 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 (0.4) | 0 (0) | 0 |
| 11-V | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (2.9) | 0 |
| 59-V | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (1.9) | 0 |
| 103 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) | 1 (2.6) |
| 95 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (1.0) | 0 |
| Total | 23 | 31 | 15 | 37 | 23 | 40 | 25 | 7 | 10 | 71 | 282 | 107 | 35 |
A “V” indicates inclusion of an M type-specific component in experimental 26VV (2).
A total of 41 abscess, 27 subcutaneous tissue, 18 blood, 8 synovial fluid, 6 pleural fluid, 2 peritoneal, 2 cerebrospinal fluid, 2 ganglio, and 1 vesicle isolates were recovered.
A total of 7 bronchial, 3 catheter, 2 eye, 7 ear, 1 nasal, 6 urine, 8 vaginal, and 1 urethral isolates were recovered.
A total of 27 emm types were found among the pharyngitis isolates, all but 5 of which were also found among sterile-site isolates. The most abundant types, emm1 and emm12, were each found in 49 of the 282 total pediatric isolates recovered. The eight most common types associated with pharyngitis were each found in the majority of the surveillance years listed for Table 1. A total of 244 (87%) of the 282 pharyngitis isolates were of 15 deduced M types included within the 26VV (8). Predicted 26VV coverage of the Mexico City pharyngitis isolate set was 88%, while for the Durango pharyngitis isolate set it was 83%.
Sterile-site isolates recovered from patients living in Mexico City.
A total of 25 distinct emm types were identified among the 107 sterile-site isolates examined (Table 1), with all but 4 of these types also found among pharyngitis isolates. Types emm1 and emm12 were the most frequently recovered types among sterile sites, which is consistent with their frequency of isolation from the nasopharyngeal reservoir. Tissue and abscess cultures are listed here as normally sterile sites, because these isolates were collected aseptically with needle aspiration. Of the 107 isolates, 92 (86%), representing 16 emm types, were of deduced M types included in the 26VV.
emm types associated with streptococcal toxic shock.
A total of 31 sterile-site isolates, representing 14 emm types, were associated with independent cases of STSS. Types emm1, emm6, and emm75 were most frequently identified (four to five patients each). Types emm18 and emm22 were each recovered from three patients with STSS. Other types found associated with STSS in one to two cases included emm3, emm5, emm28, emm49, emm103, emm2, emm11, emm76, and emm89. Of these 14 emm types, 12 (comprising 29 [93.5%] of the 31 isolates associated with STSS) were among the types included in the 26VV (8).
Allelic variation within emm types.
Table 2 depicts the number of isolates subjected to emm sequence analysis. As described in Materials and Methods, we reliably deduced the emm types of large sets through emm sequence analysis of representatives of each cluster of isolates that shared identical T agglutination profiles, opacity factor reactions, emm amplicon DdeI restriction profiles, and emm amplicon HincII and HaeIII restriction profiles. The allelic types or subtypes of the selected amplicons that were sequenced are indicated.
TABLE 2.
Observed variation within type-specific regions of emm genes in Mexico and the United States
| emm type | Total no. of isolates | No. of emm-sequenced isolates | Type and/or subtype(s) detected by direct sequencing (no. of isolates) | Differences compared to reference type | Corresponding type(s) or subtype(s) found in 1,066 consecutive U.S. invasive isolates emm typed by direct sequencing during 2000-2001a (no. of isolates) |
|---|---|---|---|---|---|
| emm1 | 82 | 4 | emm1 (4) | None | emm1 (188) |
| emm1.8 (1) | |||||
| emm1.9 (1) | |||||
| emm1.11 (1) | |||||
| emm1.13 (1) | |||||
| emm1.14 (1) | |||||
| emm12 | 67 | 8 | emm12 (8) | None | emm12 (89) |
| emm12.8 (1) | |||||
| emm22 | 24 | 9 | emm22 (9) | None | emm22 (25) |
| emm75 | 32 | 11 | emm75 (11) | None | emm75 (30) |
| emm75.1 (1) | |||||
| emm3 | 29 | 11 | emm3.1 (10) | N31 to T31 | emm3.1 (82) |
| S41 to N41 | emm3.4 (21) | ||||
| emm3.5 (1) | N31 to T31 | emm3.2 (1) | |||
| emm3.7 (1) | |||||
| emm3.8 (1) | |||||
| emm3.9 (1) | |||||
| emm3.11 (1) | |||||
| emm6 | 28 | 8 | emm6 (7) | None | emm6.1 (6) |
| emm6.3 (1) | K34 to N34 | emm6 (5) | |||
| T37 to D37 | emm6.4 (2) | ||||
| E38 to Q38 | emm6.5 (2) | ||||
| emm6.2 (1) | |||||
| emm2 | 29 | 8 | emm2 (8) | None | emm2 (25) |
| emm77 | 22 | 13 | emm77 (13) | None | emm77 (38) |
| emm4 | 25 | 8 | emm4 (8) | None | emm4 (16) |
| emm4.1 (1) | |||||
| emm89 | 10 | 5 | emm89 (5) | None | emm89 (54) |
| emm89.1 (4) | |||||
| emm89.5 (1) | |||||
| emm9 | 11 | 7 | emm9.2 (7) | E7 to G7 | emm9.2 (3) |
| emm9 (1) | None | ||||
| emm18 | 10 | 5 | emm18.3 (5) | D20 to G20 | emm18 (11) |
| emm18.4 (2) | |||||
| emm18.6 (1) | |||||
| emm5 | 9 | 5 | emm5.8193b (2) | A1 to T1 | emm5.8193b (5) |
| emm5.4 (1) | A1 to T1 | emm5.6 (4) | |||
| 15E to 15A | emm5.14 (4) | ||||
| Insertion KSNLERK at 44 | emm5 (1) | ||||
| A1 to T1 | emm5.7 (1) | ||||
| emm5.9 (1) | A16 to V16 | emm5.8 (1) | |||
| L17 to I17 | emm5.10 (1) | ||||
| A1 to T1 | |||||
| emm5.10 (1) | G5 to S5 | ||||
| emm92 | 8 | 5 | emm92 (4) | None | emm92 (6) |
| emm28 | 6 | 3 | emm28 (3) | None | emm28 (80) |
| emm78 | 4 | 3 | emm78 (3) | None | emm78 (2) |
| emm49 | 3 | 3 | emm49.1 (3) | A1 to V1 | emm49 (14) |
| V11 to A11 | emm49.1 (2) | ||||
| emm66 | 3 | 3 | emm66 (3) | None | emm66 (1) |
| emm33 | 2 | 2 | emm33 (2) | None | emm33 (6) |
| emm41 | 2 | 2 | emm41.2 (2) | 29P to 29A | emm41.2 (13) |
| emm48 | 2 | 2 | emm48 (2) | None | emm48.1 (2) |
| emm11 | 2 | 2 | emm11 (2) | None | emm11 (28) |
| emm11.1 (4) | |||||
| emm76 | 2 | 2 | emm76 (2) | None | emm76 (7) |
| emm76.1 (1) | |||||
| emm59 | 2 | 2 | emm59 (2) | None | emm59 (6) |
| emm82 | 2 | 2 | emm82 (2) | None | emm82 (63) |
| emm103 | 2 | 2 | emm103 (2) | None | Not present |
| emm58 | 1 | 1 | emm58 (1) | None | emm58 (7) |
| emm58.1 (1) | |||||
| emm87 | 1 | 1 | emm87 (1) | None | emm87 (3) |
| emm87.3 (2) | |||||
| emm87.1 (1) | |||||
| st369 | 1 | 1 | st369 (1) | None | st369 (1) |
| emm95 | 1 | 1 | emm95 | None | Not present |
| emm102 | 1 | 1 | emm102.2 | Deletion of codons 41-51 | emm102.2 (12) |
Designations in bold represent types also found in sample set from Mexico (column 4). All sequences are available at the website http://www.cdc.gov/ncidod/biotech/strep/emmtypes.htm and can be downloaded from the websites ftp://ftp.cdc.gov/pub/infectious_diseases/biotech/emmsequ/ and ftp://ftp.cdc.gov/pub/infectious_diseases/biotech/emmtransl/.
With the exception of types emm3, emm6, emm9, emm18, emm5, emm49, emm41, and emm102, each of which represented a number of emm type variants (subtypes), the type-specific regions of each amplicon that encode mature M protein residues 1 to 50 shared identity to the corresponding sequences in CDC type reference strains (1) (all sequences can be found at the website http://www.cdc.gov/ncidod/biotech/strep/emmtypes.html and are downloadable at the website http://www.cdc.gov/ncidod/biotech/strep/doc.htm; type reference strain emm sequence types are indicated by the lack of a decimal point [e.g., emm1]). Except for types emm6, emm18, emm49, emm48, emm103, and emm95, the most common type or subtype sequence found among Mexico isolates was also the most common sequence found among 1,066 invasive isolates recovered in the United States from 1999 to 2001 and subjected to consecutive emm sequencing (Table 2). Types emm103 and emm95 were not seen within this set of 1,066 invasive U.S. isolates. These U.S. isolates represent population-based invasive disease surveillance from California (3-county San Francisco Bay area), Connecticut, Georgia, Maryland (6-county Baltimore area), Minnesota, New York (7-county Albany and 8-county Rochester-Albany areas), Oregon (3-county Portland area), Tennessee (11 urban counties), and Colorado (5-county Denver area; this area was added in 2001).
The degree of sequence conservation within specific emm type-defining regions was high, with the majority of allelic differences due to one or two single-base missense substitutions. Most of these subtype variants (Table 2, column 2) occurred as single isolates; however, subtypes emm3.1, emm3.4, emm9.2, emm18.3, emm5.8193b, emm49.1, emm41.2, and emm102.2 occurred in multiple isolates. With the exception of emm18.3, all of these subtypes were also recently represented within the sample set of 1,066 consecutively sequence-typed invasive isolates at the Centers for Disease Control and Prevention (Table 2, column 4). With the exception of subtypes emm3.1 and emm3.4, none of the subtypes listed in columns 2 and 4 of Table 2 are presently found in the GenBank database. All types and subtypes described in Table 2 are available for downloading and BLAST searches at the following website: http://www.cdc.gov/ncidod/biotech/strep/doc.htm.
New sequence type st369.
Remarkably, only one new sequence type was found among the 423 isolates. Type st369 (from a pediatric pharyngitis patient) shared only about 40% identity over its predicted N-terminal 50 residues with several different types. Coincidentally, a blood isolate with this same sequence from an individual residing in California had been identified during the 2001 population-based surveillance of invasive GAS in the United States (Centers for Disease Control and Prevention Active Bacterial Core surveillance; unpublished data). These two isolates are potentially representatives of the same clone, since in addition to sharing 100% identity over the entire 670 sequenced bases of emm, both were T type 3, opacity factor negative, and sof PCR negative. The deduced partial ST369 sequence (GenBank accession no. AY058214), while sharing very little similarity to other known M proteins within the type-specific region (roughly residues 23 to 72) (Fig. 1), shared strong similarity within its partial signal sequence (residues 1 to 22) and residues 73 to 240 with corresponding sequences of many other GAS emm genes (a comparison with its best overall match with the type emm69.1 deduced peptide sequence is shown in Fig. 1).
FIG. 1.
Comparison of the st369 and the subtype emm69.1 deduced partial amino acid sequences. Residues 1 to 23 are part of the signal sequence, and the arrowhead shows the predicted cleavage points. The region which includes residues 23 to 70 is the approximate location of the hypervariable type-specific domain typical of all M proteins.
DISCUSSION
This study indicates that the M protein type distribution within a diverse set of GAS clinical isolates recovered from Mexico City during the past 10 years and from Durango during 1998 to 1999 is similar to the type distribution found within U.S. invasive GAS isolates. In fact, a current 26VV formulated for usage within the United States (8) would theoretically be effective against 86% of the 423 GAS isolates described here, which represent 17 of the M types included in this vaccine. It must be noted here that the type emm4 isolates (which were the fifth most frequently occurring pharyngeal isolates in this study) have not been included in this calculation, since it has been determined that M4 peptides do not elicit opsonic antibodies (8). Nonetheless, component(s) within the 26VV did elicit bactericidal antibodies against five of seven type emm4 isolates tested (8).
To achieve the maximum coverage of multivalent, M type-based vaccines within individual countries or regions in the world, different formulations would be based upon specific emm sequence types predominant for these areas. Such determinations would optimally entail multiyear surveillance, since changes in serotype distributions do occur over extended time periods (16) and in local communities, very rapid shifts in M type can occur within the same pharyngitis season (October to April) (11). In addition, the data presented here were not necessarily representative of the entire country of Mexico. For these reasons, we hope that emm typing-based surveillance is continued and expanded to locations throughout Mexico. Such surveillance would be important in evaluations of the feasibility of multivalent M-based vaccines in Mexico and would also be required to monitor vaccine effects on GAS populations subsequent to vaccine introduction. With vaccines targeted toward a subset of common M types, there is the possibility that strains with rarely occurring M types could increase in number.
We and others have analyzed several isolate collections (sterile site and pharyngeal and skin isolate) in various countries during the past 7 years. Although most isolate collections have not been population based, it still appears that targeted areas within Argentina, Chile, Mexico, Western Europe, Asia, and North Africa (authors' unpublished data) (for examples, see references 2, 4, 7, 12, and 14) share extensive overlap in common emm type distribution with the United States (15), which makes the concept of multivalent M protein-based vaccines more attractive. However, predominant emm types found in clinical isolates within specific areas of New Zealand, Australia, Chile, Malaysia, India, Nepal, Egypt, and New Guinea overlap less extensively with common emm types found in the United States (authors' unpublished data) (for examples, see references 3, 5, 9, and 12).
It is well established that there is a strong immunological response to the type-specific regions of several of the different M proteins (for examples, see reference 2). In view of this fact, one might expect a continuum of sequences (correlating to this region of the M protein through the generation of immune escape variants) rather than the distinct, closely similar sequences that have been observed within each sequence type of current isolates as well as of decades-old M type reference strains. In each of the areas that we have tested, it appears that a limited number of precisely defined type-specific sequence types account for the majority of isolates. On the basis of these observations, it appears likely that these strict sequence constraints observed within each sequence type are required for M protein functions that are vital for the success of this species.
Acknowledgments
We gratefully acknowledge the Emerging Infections Program (EIP)/Active Bacterial Core surveillance (ABCs) partners at the EIP/ABCs sites and at the CDC Division of Bacterial and Mycotic Diseases. We thank Juan Carlos Tinoco, who provided the streptococcal isolates from Durango City.
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