Post-streptococcal complications are known to be common among Ethiopian children. Little is known, however, about the epidemiology of beta-haemolytic streptococci in Ethiopia. A total of 816 children were studied during a one-year period: 24 cases of acute rheumatic fever (ARF), 44 chronic rheumatic heart disease (CRHD), 44 acute post streptococcal glomerulonephritis (APSGN), 143 tonsillitis, 55 impetigo, and 506 were apparently healthy children. Both ARF and APSGN occurred throughout the year with two peaks during the rainy and cold seasons. The female:male ratio among ARF patients was 1.4:1 and 1:1.9 among APSGN. The monthly carrier rate of beta-haemolytic streptococci group A varied from 7.5-39%, average being 17%. T type 2 was the most frequent serotype. Marked seasonal fluctuations were noted in the distribution of serogroups among apparently healthy children. Beta-haemolytic streptococci group A dominated during the hot and humid months of February-May. Strains were susceptible to commonly used antibiotics, except for tetracycline.
The genetic diversity of group A streptococcal (GAS) isolates obtained in 1990 from Ethiopian children with various streptococcal diseases was studied by using emm gene sequence analysis. A total of 217 GAS isolates were included: 155 and 62 isolates from throat and skin, respectively. A total of 78 different emm/st types were detected among the 217 isolates. Of these, 166 (76.5%) belonged to 52 validated reference emm types, 26 (11.9%) belonged to 16 already recognized sequence types (st types) and 25 (11.5%) belonged to 10 undocumented new sequence types. Resistance to tetracycline (148 of 217) was not correlated to emm type. Isolation rate of the classical rheumatogenic and nephritogenic strains was low from cases of acute rheumatic fever (ARF) and acute glomerulonephritis (AGN), respectively. Instead, the recently discovered st types were overrepresented among isolates from patients with ARF (3 of 7) and AGN (9 of 16) (P < 0.01) compared to isolates from subjects with tonsillitis and from healthy carriers (10 of 57 and 16 of 90, respectively). In contrast to rheumatogenic strains from the temperate regions, more than half of the isolates from ARF (four of seven) carried the genetic marker for skin preference, emm pattern D, although most of them (six of seven) were isolated from throat. Of 57 tonsillitis-associated isolates, 16 (28%) belonged to emm pattern D compared to <1% in temperate regions. As in other reports emm patterns A to C were strongly associated with throat, whereas emm pattern D did not correlate to skin. This first large-scale emm typing report from Africa has demonstrated a heterogeneous GAS population and contrasting nature of GAS epidemiology in the region.Accurate identification and typing of group A hemolytic streptococci (GAS) is an essential part of epidemiological and pathogenetic studies of streptococcal diseases. A serotyping system based on antigenic variation of a surface exposed M protein and developed by Rebecca Lancefield has been in use since 1928. Although additional serotyping systems, the T and OF typing, were developed as valuable and practical substitutes, the M typing system was considered the gold standard. However, a limited supply of antisera and the high nontypeability rate among isolates, in particular those from the tropics, challenged its continued usage. In recent years, several molecular typing systems have been reported as alternatives for M typing (4,19,25). Most of the knowledge that has been accumulated concerning GAS epidemiology is based on M typing system; hence, a molecular system that correlates with this system has practical significance. The emm typing system (4, 25) which is based on sequence analysis of PCR products of the N-terminal hypervariable region of the M protein gene, concurs with M serotyping almost 1:1 (17). In addition to its simplicity, this typing system has allowed the detection of several previously unknown GAS types from different geographic regions (5,24,32,36).
Macrolide-resistant group A streptococci (MRGAS) have been recovered from many countries worldwide. However, the strain typing information that is available has been insufficient for estimating the total number of macrolide-resistant clones, their geographic distributions, and their evolutionary relationships. In this study, sequence-based strain typing was used to characterize 212 MRGAS isolates from 34 countries. Evaluation of clonal complexes, emm type, and resistance gene content [erm(A), erm(B), mef(A), and undefined] indicate that macrolide resistance was acquired by GAS organisms via >49 independent genetic events. In contrast to other collections of mostly susceptible GAS, genetic diversification of MRGAS clones has occurred primarily by mutation rather than by recombination. Twenty-two MRGAS clonal complexes were recovered from more than one continent; intercontinental strains represent nearly 80% of the MRGAS isolates under study. The findings suggest that horizontal transfer of macrolide resistance genes to numerous genetic backgrounds and global dissemination of resistant clones and their descendants are both major components of the present-day macrolide resistance problem found within this species.Penicillin and related -lactams are usually the antibiotics of choice for the treatment of infections caused by Streptococcus pyogenes (group A streptococci [GAS]). GAS have remained susceptible to penicillin despite decades of exposure (22). Macrolides are preferred for treatment of GAS infections in patients with -lactam hypersensitivity or chronic, recurrent pharyngitis due to prior treatment failure (26). Clindamycin (a lincosamide) is recommended for patients with life-threatening soft-tissue infections, such as toxic shock syndrome or necrotizing fasciitis, because it halts the exotoxin production that can lead to extensive tissue necrosis, shock, and multiple-organ failure (6).Macrolide-resistant GAS (MRGAS) is an increasingly recognized problem in many parts of the world. Two mechanisms account for most macrolide resistance in GAS. Target site modification by methylases, namely, Erm(A) subclass TR and Erm(B), leads to ribosomal modification and loss of binding by macrolide, lincosamide, and streptogramin B (MLS) antibiotics (29, 51). Macrolide efflux is mediated by MefA (M phenotype), resulting in resistance to 14-and 15-membered, but not 16-membered, ring macrolides (54). The three major resistance genes (R genes) found in GAS, erm(A), erm(B), and mef(A), are associated with mobile genetic elements (3, 18). Mutations in 23S rRNA and the L4 ribosomal protein also seem to confer macrolide resistance in at least some strains (11,33,44).Studies in Japan, Finland, and elsewhere show a strong correlation between national macrolide consumption and resistance in GAS (14,15,17,35,41,50). Between 1998 and 2001, a statistically significant increase in GAS resistant to erythromycin and azithromycin was observed in Spain (2). In Toronto between 1997 and 2001, macrolide resistance in GAS recovered from throat...
SummaryThe main virulence factor of group A streptococcus (GAS), M protein, binds plasma complement regulators factor H (FH) and FH-like protein 1 (FHL-1) leading to decreased opsonization. The M protein binding site on FH is within domain 7 in which also the age-related macular degeneration (AMD)-associated polymorphism Y402H is located. We studied if FH allotypes 402H and 402Y have different binding affinities to GAS. Plasma-derived FH allotype 402H and its recombinant fragment FH5-7(402H) showed decreased binding to several GAS strains. Growth of GAS in human blood taken from FH(402H) homozygous individuals was decreased when compared with blood taken from FH(402Y) homozygous individuals. The effect of the allotype 402H can be explained by combining the previous M protein mutagenesis data and the recently published crystal structure of FH6-8. In conclusion the data indicate that the AMD-associated allotype 402H leads to diminished binding of FH to GAS and increased opsonophagocytosis of the bacteria in blood. These results suggest that the homozygous presence of the allele 402H could be associated with decreased risk for severe GAS infections offering an explanation for the high frequency of the allele despite its association with visual impairment.
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