• 1.

    Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE, 2015. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 385: 430440.

    • Search Google Scholar
    • Export Citation
  • 2.

    Kotloff KL 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209222.

    • Search Google Scholar
    • Export Citation
  • 3.

    Breurec S 2016. Etiology and epidemiology of diarrhea in hospitalized children from low income country: a matched case-control study in Central African Republic. PLoS Negl Trop Dis 10: e0004283.

    • Search Google Scholar
    • Export Citation
  • 4.

    Anderson M, Sansonetti PJ, Marteyn BS, 2016. Shigella diversity and changing landscape: insights for the twenty-first century. Front Cell Infect Microbiol 6: 45.

    • Search Google Scholar
    • Export Citation
  • 5.

    Livio S 2014. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis 59: 933941.

  • 6.

    Bercion R, Njuimo SP, Boudjeka PM, Manirakiza A, 2008. Distribution and antibiotic susceptibility of Shigella isolates in Bangui, Central African Republic. Trop Med Int Health 13: 468471.

    • Search Google Scholar
    • Export Citation
  • 7.

    Qiu S 2015. Shift in serotype distribution of Shigella species in China, 2003–2013. Clin Microbiol Infect 21: 252 e5-8.

  • 8.

    Bangtrakulnonth A, Vieira AR, Lo Fo Wong DM, Pornreongwong S, Pulsrikarn C, Sawanpanyalert P, Hendriksen RS, Aarestrup FM, 2008. Shigella from humans in Thailand during 1993 to 2006: spatial-time trends in species and serotype distribution. Foodborne Pathog Dis 5: 773784.

    • Search Google Scholar
    • Export Citation
  • 9.

    Langendorf C, Le Hello S, Moumouni A, Gouali M, Mamaty AA, Grais RF, Weill FX, Page AL, 2015. Enteric bacterial pathogens in children with diarrhea in Niger: diversity and antimicrobial resistance. PLoS One 10: e0120275.

    • Search Google Scholar
    • Export Citation
  • 10.

    Rafai C, Frank T, Manirakiza A, Gaudeuille A, Mbecko JR, Nghario L, Serdouma E, Tekpa B, Garin B, Breurec S, 2015. Dissemination of IncF-type plasmids in multiresistant CTX-M-15-producing Enterobacteriaceae isolates from surgical-site infections in Bangui, Central African Republic. BMC Microbiol 15: 15.

    • Search Google Scholar
    • Export Citation
  • 11.

    Mao Y 2013. Changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010. Gut Pathog 5: 21.

  • 12.

    Shakya G, Acharya J, Adhikari S, Rijal N, 2016. Shigellosis in Nepal: 13 years review of nationwide surveillance. J Health Popul Nutr 35: 36.

  • 13.

    Kahsay AG, Muthupandian S, 2016. A review on serodiversity and antimicrobial resistance patterns of Shigella species in Africa, Asia and South America, 2001–2014. BMC Res Notes 9: 422.

    • Search Google Scholar
    • Export Citation
  • 14.

    Thompson CN, Duy PT, Baker S, 2015. The rising dominance of Shigella sonnei: an intercontinental shift in the etiology of bacillary dysentery. PLoS Negl Trop Dis 9: e0003708.

    • Search Google Scholar
    • Export Citation
  • 15.

    Bercion R, Demartin M, Recio C, Massamba PM, Frank T, Escriba JM, Grimont F, Grimont PA, Weill FX, 2006. Molecular epidemiology of multidrug-resistant Shigella dysenteriae type 1 causing dysentery outbreaks in Central African Republic, 2003–2004. Trans R Soc Trop Med Hyg 100: 11511158.

    • Search Google Scholar
    • Export Citation
  • 16.

    Levine MM, 2006. Enteric infections and the vaccines to counter them: future directions. Vaccine 24: 38653873.

  • 17.

    Levine MM, Kotloff KL, Barry EM, Pasetti MF, Sztein MB, 2007. Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road. Nat Rev Microbiol 5: 540553.

    • Search Google Scholar
    • Export Citation
  • 18.

    Noriega FR, Liao FM, Maneval DR, Ren S, Formal SB, Levine MM, 1999. Strategy for cross-protection among Shigella flexneri serotypes. Infect Immun 67: 782788.

    • Search Google Scholar
    • Export Citation
  • 19.

    von Seidlein L 2006. A multicentre study of Shigella diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology. PLoS Med 3: e353.

    • Search Google Scholar
    • Export Citation
  • 20.

    Farzam N, Ramon-Saraf R, Banet-Levi Y, Lerner-Geva L, Ashkenazi S, KublnKielb J, Vinogradov E, Robbins JB, Schneerson R, 2017. Vaccination with Shigella flexneri 2a conjugate induces type 2a and cross-reactive type 6 antibodies in humans but not in mice. Vaccine 35: 49904996.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

Serotype Distribution and Antimicrobial Resistance of Shigella Species in Bangui, Central African Republic, from 2002 to 2013

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  • 1 Laboratoire de Bactériologie, Institut Pasteur de Bangui, Bangui, Central African Republic;
  • 2 Faculté de Médecine Hyacinthe Bastaraud, Université des Antilles, Pointe-à-Pitre, France;
  • 3 Laboratoire de Microbiologie Clinique et Environnementale, Centre Hospitalier Universitaire de Pointe-à-Pitre/les Abymes, Pointe-à-Pitre, France;
  • 4 Délégation à la Recherche Clinique et à l’Innovation, Centre Hospitalier Universitaire de Nantes, Nantes, France;
  • 5 Unité des Bactéries Pathogènes Entériques, Centre National de Référence des Escherichia coli, Shigella et Salmonella, Institut Pasteur, Paris, France

Shigella is a major cause of severe diarrhea in children less than the age of 5 years in sub-Saharan Africa. The aim of this study was to describe the (sub-)serotype distribution and antimicrobial susceptibility of Shigella serogroups from Centrafrican patients with diarrhea between 2002 and 2013. We collected 443 Shigella isolates in total. The most common serogroups were Shigella flexneri (N = 243, 54.9%), followed by Shigella sonnei (N = 90, 20.3%) and Shigella dysenteriae (N = 72, 16.3%). The high diversity of (sub-)serotypes of S. flexneri and S. dysenteriae may impede the development of an efficient vaccine. Rates of resistance were high for ampicillin, chloramphenicol, tetracycline, and cotrimoxazole but low for many other antimicrobials, confirming recommendations for the use of third-generation cephalosporins (only one organism resistant) and fluoroquinolones (no resistance). However, the detection of one extended-spectrum beta-lactamase–producing Shigella organism highlights the need for continued monitoring of antimicrobial drug susceptibility.

INTRODUCTION

In 2013, 6.3 million deaths were recorded in children less than the age of 5 years, 578,000 of which were because of diarrheal disease, the second leading cause of death in this age group. Almost half of these diarrhea-related deaths occurred in sub-Saharan Africa.1 Recent studies (Torcadia for Central African Republic [CAR] and the Global Enteric Multicenter Study for other sites) in The Gambia and Mali (West Africa), Mozambique and Kenya (East Africa), and CAR (Central Africa) have confirmed the continuing importance of Shigella as a major cause of severe diarrhea in children less than the age of 5 years. Shigella spp. are the third most important pathogen in these regions.2,3

High rates of resistance to conventional antimicrobials, such as ampicillin, chloramphenicol, tetracycline, and cotrimoxazole, have been reported for Shigella spp. in many studies.4 This resistance has led to third-generation cephalosporins (C3G), fluoroquinolones, and azithromycin becoming the first-line antimicrobials for treating these infections. However, the clinical severity of shigellosis and the emergence of resistance to first-line treatments highlight the growing need to develop alternative prophylactic and therapeutic strategies. The development of a safe and effective anti-Shigella vaccine for controlling shigellosis is enshrined in WHO public health policy. However, the presence of four different serogroups (formerly known as species), Shigella flexneri, Shigella dysenteriae, Shigella boydii, and Shigella sonnei, made up of at least 50 antigenically different (sub-)serotypes may impede vaccine development.5 Indeed, the larger the number of serotypes to be included, the more complex and expensive the vaccine becomes. The lack of data from Central Africa and from very low-income countries, such as CAR,6 which suffers from long-term instability, highlights the need to improve our understanding of the spatial and temporal distribution of (sub-)serotypes in sub-Saharan Africa.7,8 Central African Republic is a resource-limited country in equatorial Africa (ranked 180/187 according to the Human Development Index in 2013). Here, we describe the (sub-)serotype distribution and antimicrobial susceptibility of Shigella species isolated from patients in CAR during the 2002–2013 period.

Clinical isolates of Shigella were obtained between January 2002 and December 2013, from Centrafrican outpatients with diarrhea attending the Institut Pasteur in Bangui. If more than one isolate of the same (sub-)serotype and serogroup and with the same antimicrobial drug resistance phenotype was recovered from a given patient, only the first isolate was included. Shigella was identified by conventional methods and (sub-)serotyping was performed by slide agglutination assays with a complete set of antisera recognizing all the described Shigella serotypes.9 Antimicrobial drug susceptibility was assessed by the disk diffusion method, and extended-spectrum beta-lactamase (ESBL) production was evaluated in the double-disc synergy test, as previously described.10

Date, site of isolation, patient age, and gender were recorded for each isolate. We used χ2 test, Student’s t-test, and ANOVA (analysis of variance—with Lilliefors’ test for normality and Levene’s test for homoscedasticity) to compare categorical and continuous variables in univariate analysis. Multivariate logistic regression was performed to explore high rates of multidrug resistance (MDR, defined by resistance to more than five of the 13 antimicrobials tested). Factors with P values < 0.2 in univariate analysis were retained for the multivariate analysis. We considered P values < 0.05 to be statistically significant.

In total, 443 clinical isolates of Shigella were collected between January 2002 and December 2013, from 443 Centrafrican outpatients with diarrhea (238 male and 205 female patients, mean age: 27.2 years, median age: 29.5 years, 25th percentile: 8 years, 75th percentile: 40 years). The small number of organisms isolated during the study period reflects the poor access to health-care services in CAR, particularly for the laboratory diagnosis of diarrhea. Significant differences in the number of isolates obtained were also observed between years because of the economic and political crisis that occurred during the study period, further restricting patient access to health-care facilities. However, the distribution of serogroups recovered in our study for 2004–2005 was consistent with that reported for the same period in a study conducted at four health-care centers in Bangui.6 The data reported here may, therefore, be considered representative of the global situation in Bangui.

The incidence of S. dysenteriae infection has been reported to be higher in men than in women in China.11 By contrast, we found a significant association between S. dysenteriae infection and being female (odds ratio = 1.86 95% confidence interval [1.11–3.12]; P = 0.018). No significant association was found between gender and the other serogroups or between Shigella serogroup and age. Contrary to several other reports,11,12 we observed no significant seasonality in the distribution of Shigella isolates or in serogroup distribution (i.e., erratic variation between months, but no difference between the wet and dry seasons).

The most common serogroup was S. flexneri (N = 243, 54.9%), consistent with several reports from developing countries in Africa and Asia,5,13 followed by S. sonnei (N = 90, 20.3%) and S. dysenteriae (N = 72, 16.3%). Shigella boydii (N = 34, 7.7%), which is generally restricted to North and East Africa (Ethiopia and Egypt) and South Asia (Bangladesh and Nepal),13 was rarely encountered in our study (Table 1). Unsurprisingly, no significant difference in the prevalence of Shigella serogroups was observed during the study period, except for S. sonnei (P < 0.001). However, the prevalence of the S. sonnei serogroup fluctuated over time, with no significant trend (Table 1). This finding is consistent with the known distribution of Shigella serogroups in countries with a low socioeconomic level,4 CAR being one of the poorest countries of sub-Saharan Africa.

Table 1

Distribution of the most frequent Shigella serogroups and (sub-)serotypes in Bangui, Central African Republic, 2002–2013

Shigella200220032004200520062007200820092010201120122013TotalP
Serogroups/serotypesN = 14N = 22N = 59N = 60N = 82N = 51N = 26N = 11N = 8N = 39N = 44N = 27N = 443
n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)
flexneri*8 (57.1)14 (63.6)34 (57.6)34 (56.7)49 (59.8)32 (62.7)9 (34.6)5 (45.4)5 (62.5)18 (46.2)22 (50.0)13 (48.1)243 (54,9)NS
  100001 (1.2)00000001 (0.2)NS
  1a00001 (1.2)0001 (12.5)01 (2.3)03 (0.7)0.03
  1b05 (22.7)11 (18.7)13 (21.7)15 (18.3)5 (9.8)3 (11.5)02 (25.0)2 (5.1)2 (4.5)1 (3.7)59 (13.3)0.03
  1c1 (7.1)06 (10.2)002 (3.9)0000009 (2.0)0.002
  2a7 (50.0)5 (22.7)3 (5.1)8 (13.3)3 (3.7)6 (11.8)01 (9.1)01 (2.6)6 (13.6)040 (9.0)< 0.001
  3a007 (11.9)2 (3.3)7 (8.5)8 (15.7)3 (11.5)1 (9.1)1 (12.5)2 (5.1)3 (6.8)4 (14.8)38 (8.6)NS
  3b00001 (1.2)000001 (2.3)02 (0.5)NS
  4a01 (4.5)003 (3.7)7 (13.7)2 (7.7)1 (9.1)02 (5.1)5 (11.4)4 (14.8)25 (5.6)0.02
  4c002 (3.4)4 (6.7)2 (2.4)1 (2.0)0001 (2.6)0010 (2.3)NS
  6a03 (13.6)5 (8.5)7 (11.7)15 (18.3)3 (5.9)1 (3.8)2 (18.2)1 (12.5)10 (25.6)4 (9.1)3 (11.1)64 (14.4)NS
  7000000000001 (3.7)1 (0.2)NS
  8000000001 (12.5)0001 (0.2)NS
  90000001 (3.8)000001 (0.2)NS
  y00001 (1.2)00000001 (0.2)NS
  Prov93-119000000000001 (3.7)1 (0.2)NS
  Prov96-204000000000001 (3.7)1 (0.2)NS
sonnei4 (28.6)1 (4.5)7 (11.9)9 (15.0)9 (11.0)8 (15.7)9 (34.6)4 (36.4)1 (12.5)18 (46.2)13 (29.5)7 (25.9)90 (20.3)< 0.001
dysenteriae05 (22.7)11 (18.6)12 (20)15 (18.3)6 (11.8)6 (23.1)01 (12.5)3 (7.7)6 (13.6)7 (25.9)72 (16.3)NS
  203 (13.6)8 (13.6)7 (11.7)9 (11.0)3 (5.9)1 (3.8)0002 (4.5)033 (7.4)NS
  302 (9.1)05 (8.3)5 (6.1)1 (2.0)1 (3.8)002 (5.1)3 (6.8)019 (4.3)NS
  400001 (1.2)2 (3.9)1 (3.8)00002 (7.4)6 (1.3)NS
  120000002 (7.7)001 (2.6)03 (11.1)6 (1.3)0.03
boydii2 (14.3)2 (9.1)7 (11.9)4 (6.7)9 (11.0)4 (7.8)2 (7.7)2 (18.2)002 (4.5)034 (7.7)NS
  11 (7.1)1 (4.5)2 (3.4)1 (1.7)2 (2.4)000001 (2.3)08 (1.8)NS
  20002 (3.3)4 (4.9)01 (3.8)1 (9.1)00008 (1.8)NS
  4003 (5.1)1 (1.7)01 (2.0)01 (9.1)00006 (1.3)NS
  181 (7.1)01 (1.7)01 (1.2)01 (3.8)000004 (0.9)NS
Undetermined0 (0)0 (0)0 (0)1 (1.7)0 (0)1 (2.0)0 (0)0 (0)1 (12.5)0 (0)1 (2.3)0 (0)4 (0.9)NS

Shigella flexneri serotypes proposed for inclusion, along with S. sonnei, in a quadrivalent broad-spectrum Shigella vaccine are shown in bold.

Only the four most frequent serotypes are shown.

An increase in the frequency of S. sonnei isolates relative to S. flexneri has been reported worldwide, in regions in which sanitation and clean water provision have been improved.14 Such interactions between these two serogroups were detected here, by analyzing the negative correlation between proportions and incidence, which was strong year after year (r = −0.8164; P = 0.001), whereas an erratic pattern was observed between years (Table 1). Five serotypes/subserotypes of S. flexneri accounted for 50.9% of all isolates: 6 (14.4% of the total), 1b (13.3%), 2a (9.0%), 3a (8.6%), and 4a (5.6%). Only minimal changes in serotype distribution were observed from year to year, for most of the (sub-)serotypes, and any significant variation detected was inconsistent (Table 1). Shigella dysenteriae serotype 1, which is a source of great concern as it has caused devastating epidemics of shigellosis in various developing countries, including CAR,15 was recovered only rarely in our laboratory (one organism in 2006).

No significant cross-reactions are known between serotypes in S. dysenteriae (15 serotypes) and S. boydii (20 serotypes), but major cross-reactions were observed for 14 of the 19 serotypes of S. flexneri, because of a degree of antigenic relatedness attributable to a common repeating tetrasaccharide unit.16 Thus, a multivalent vaccine including O antigens from S. flexneri 2a and 3a, in addition to direct protection against S. flexneri 2b and 3b, would provide cross-protection against S. flexneri 1a, 1b, 4a, 4b, 5a, 5b, 7b, X, and Y.17,18 Extrapolating these data to humans, a multivalent vaccine including S. sonnei (only one serotype described) and S. flexneri 2a, 3a, and 6 would have provided direct protection for 52.3% and cross-protection for 72.9% of these infections. This level is lower than that estimated for two multicenter studies at four sites in Africa and nine sites at Asia,5,19 in which a quadrivalent vaccine including the serotypes listed previously would have provided protection against at least 85% of the serotyped organisms. However, these cross-reactions remain theoretical and discrepancies exist between data for humans and animals, as highlighted by the appearance of cross-reactive type six antibodies in humans, but not in mice, after vaccination with S. flexneri 2a conjugate.20 Together with the considerable diversity of (sub-)serotypes in two of the three major serogroups (S. flexneri and S. dysenteriae) recovered in our study, this constitutes a real barrier to the development of a cheap, safe vaccine providing broad coverage against Shigella.

The ability of Shigella to acquire antimicrobial drug resistance rapidly is a major challenge in the control of infections with this bacterium. Overall, resistance rates to antimicrobials were low during the study period, for all classes other than conventional antimicrobials (chloramphenicol [62%], amoxicillin [64%], cotrimoxazole [92%], and tetracycline [98%]), confirming recommendations for first-line treatment based on C3G and fluoroquinolones (Table 2). However, although no resistance to ciprofloxacin was detected, we report the first case of ESBL-producing Shigella (S. flexneri) in sub-Saharan Africa, which is of major concern. Unlike S. sonnei, the S. flexneri, S. dysenteriae, and S. boydii serotypes were all strongly associated with high rates of MDR (Table 2). After adjustment for gender and serogroup, multivariate analysis highlighted a significant contribution of the antimicrobial drug resistance pattern of S. sonnei to the rates of MDR of Shigella isolates (OR = 0.02 95% CI [0.007–0.65]; P < 0.001), despite the lower prevalence of S. sonnei than that of S. flexneri (Table 3).

Table 2

Percentage resistance to specific antibiotics in Shigella species in Bangui, Central African Republic, from 2002 to 2013

Shigella flexneri (%)Shigella sonnei (%)Shigella dysenteriae (%)Shigella boydii (%)Unknown (%)Total (%)
N = 243N = 90N = 72N = 34N = 4N = 443
Amoxicillin7219856810064
Co-amoxiclav621304
Ticarcillin7119856510061
Cefoxitin000000
Cefotaxime000000
Amikacin000000
Gentamicin000000
Nalidixic acid001000
Ciprofloxacin000000
Chloramphenicol742085327562
Sulfonamides9298969110094
Cotrimoxazole9097948810092
Tetracycline9899999710098
Table 3

Determinants of the high rates of multidrug resistance (defined by resistance to more than five of the 13 antibiotics tested) in Shigella spp. strains from Bangui, Central African Republic, 2002–2013

Rate of multidrug resistance % (n)Univariate analysisMultivariate analysis
Yes (N = 216)No (N = 227)OR (95% CI)PAdjusted OR (95% CI)P
Male48.6 (105)57.7 (131)0.72 (0.49–1.05)0.0860.76 (0.50–1.14)0.189
Q4 age*21.8 (47)23.3 (53)0.91 (0.58–1.43)0.689
flexneri62.5 (135)47.6 (108)1.84 (1.26–2.69)0.0020.41 (0.04–3.85)0.436
sonnei6.9 (15)33.0 (75)0.15 (0.08–0.27)< 0.00010.07 (0.01–0.66)0.019
dysenteriae25.6 (55)7.5 (17)4.22 (2.36–7.56)< 0.00011.03 (0.10–10.05)0.978
boydii3.7 (8)11.5 (26)0.30 (0.13–0.67)0.0030.10 (0.01–1.10)0.059
Undefined1.4 (3)0.5 (1)3.18 (0.33–31.03)0.317

Q4 age-defined extreme population quartile.

Serogroup.

The data reported here are particularly important, given the difficulty of carrying out such studies in countries with inadequate health-care systems. The high diversity of S. flexneri and S. dysenteriae (sub-)serotypes observed here may act as a major obstacle to the development of a vaccine. Resistance to front-line antimicrobials is low, but it will be important to continue monitoring antimicrobial drug susceptibility in Shigella isolates.

Acknowledgments:

We thank Isabelle Carle, Monique Lejay-Collin, Malika Gouali, and Corinne Ruckly for excellent technical assistance.

REFERENCES

  • 1.

    Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE, 2015. Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 385: 430440.

    • Search Google Scholar
    • Export Citation
  • 2.

    Kotloff KL 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209222.

    • Search Google Scholar
    • Export Citation
  • 3.

    Breurec S 2016. Etiology and epidemiology of diarrhea in hospitalized children from low income country: a matched case-control study in Central African Republic. PLoS Negl Trop Dis 10: e0004283.

    • Search Google Scholar
    • Export Citation
  • 4.

    Anderson M, Sansonetti PJ, Marteyn BS, 2016. Shigella diversity and changing landscape: insights for the twenty-first century. Front Cell Infect Microbiol 6: 45.

    • Search Google Scholar
    • Export Citation
  • 5.

    Livio S 2014. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin Infect Dis 59: 933941.

  • 6.

    Bercion R, Njuimo SP, Boudjeka PM, Manirakiza A, 2008. Distribution and antibiotic susceptibility of Shigella isolates in Bangui, Central African Republic. Trop Med Int Health 13: 468471.

    • Search Google Scholar
    • Export Citation
  • 7.

    Qiu S 2015. Shift in serotype distribution of Shigella species in China, 2003–2013. Clin Microbiol Infect 21: 252 e5-8.

  • 8.

    Bangtrakulnonth A, Vieira AR, Lo Fo Wong DM, Pornreongwong S, Pulsrikarn C, Sawanpanyalert P, Hendriksen RS, Aarestrup FM, 2008. Shigella from humans in Thailand during 1993 to 2006: spatial-time trends in species and serotype distribution. Foodborne Pathog Dis 5: 773784.

    • Search Google Scholar
    • Export Citation
  • 9.

    Langendorf C, Le Hello S, Moumouni A, Gouali M, Mamaty AA, Grais RF, Weill FX, Page AL, 2015. Enteric bacterial pathogens in children with diarrhea in Niger: diversity and antimicrobial resistance. PLoS One 10: e0120275.

    • Search Google Scholar
    • Export Citation
  • 10.

    Rafai C, Frank T, Manirakiza A, Gaudeuille A, Mbecko JR, Nghario L, Serdouma E, Tekpa B, Garin B, Breurec S, 2015. Dissemination of IncF-type plasmids in multiresistant CTX-M-15-producing Enterobacteriaceae isolates from surgical-site infections in Bangui, Central African Republic. BMC Microbiol 15: 15.

    • Search Google Scholar
    • Export Citation
  • 11.

    Mao Y 2013. Changing trends and serotype distribution of Shigella species in Beijing from 1994 to 2010. Gut Pathog 5: 21.

  • 12.

    Shakya G, Acharya J, Adhikari S, Rijal N, 2016. Shigellosis in Nepal: 13 years review of nationwide surveillance. J Health Popul Nutr 35: 36.

  • 13.

    Kahsay AG, Muthupandian S, 2016. A review on serodiversity and antimicrobial resistance patterns of Shigella species in Africa, Asia and South America, 2001–2014. BMC Res Notes 9: 422.

    • Search Google Scholar
    • Export Citation
  • 14.

    Thompson CN, Duy PT, Baker S, 2015. The rising dominance of Shigella sonnei: an intercontinental shift in the etiology of bacillary dysentery. PLoS Negl Trop Dis 9: e0003708.

    • Search Google Scholar
    • Export Citation
  • 15.

    Bercion R, Demartin M, Recio C, Massamba PM, Frank T, Escriba JM, Grimont F, Grimont PA, Weill FX, 2006. Molecular epidemiology of multidrug-resistant Shigella dysenteriae type 1 causing dysentery outbreaks in Central African Republic, 2003–2004. Trans R Soc Trop Med Hyg 100: 11511158.

    • Search Google Scholar
    • Export Citation
  • 16.

    Levine MM, 2006. Enteric infections and the vaccines to counter them: future directions. Vaccine 24: 38653873.

  • 17.

    Levine MM, Kotloff KL, Barry EM, Pasetti MF, Sztein MB, 2007. Clinical trials of Shigella vaccines: two steps forward and one step back on a long, hard road. Nat Rev Microbiol 5: 540553.

    • Search Google Scholar
    • Export Citation
  • 18.

    Noriega FR, Liao FM, Maneval DR, Ren S, Formal SB, Levine MM, 1999. Strategy for cross-protection among Shigella flexneri serotypes. Infect Immun 67: 782788.

    • Search Google Scholar
    • Export Citation
  • 19.

    von Seidlein L 2006. A multicentre study of Shigella diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology. PLoS Med 3: e353.

    • Search Google Scholar
    • Export Citation
  • 20.

    Farzam N, Ramon-Saraf R, Banet-Levi Y, Lerner-Geva L, Ashkenazi S, KublnKielb J, Vinogradov E, Robbins JB, Schneerson R, 2017. Vaccination with Shigella flexneri 2a conjugate induces type 2a and cross-reactive type 6 antibodies in humans but not in mice. Vaccine 35: 49904996.

    • Search Google Scholar
    • Export Citation

Author Notes

Address correspondence to Sebastien Breurec, Centre Hospitalier Universitaire de Pointe-à-Pitre/les Abymes, Laboratoire de Microbiologie Clinique et Environnementale, Route de Chauvel, Pointe-à-Pitre, France, E-mail: sebastien.breurec@chu-guadeloupe.fr or François-Xavier Weill, Centre National de Référence des Escherichia coli, Shigella et Salmonella, Unité des Bactéries Pathogènes Entériques, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France, E-mail: francois-xavier.weill@pasteur.fr.

Financial support: The French National Reference Center for Escherichia coli, Shigella, and Salmonella is funded by the Institut Pasteur and Santé Publique France. The Unité des Bactéries Pathogènes Entériques belongs to the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence funded by the French Government as part of the Investissement d'Avenir program (grant no. ANR-10-LABX-62-IBEID).

Authors’ addresses: Sebastien Breurec, Faculté de Médecine, Universite des Antilles, Pointe-a-Pitre, France, E-mail: sbreurec@gmail.com. Clotaire Rafaï, Manuella Onambele, Thierry Frank, and Alain Farra, Laboratoire de Bactériologie, Institut Pasteur de Bangui, Bangui, République Centrafricaine, E-mails: clotairerafai@yahoo.fr, onambelemanu@yahoo.fr, thierryfrank@yahoo.fr, and farra_alain@yahoo.fr. Arnaud Legrand, DRCI, Centre Hospitalier Universitaire de Nantes, Nantes, France, E-mail: arnaud.legrand@chu-nantes.fr. François-Xavier Weill, Unité des Bactéries Pathogènes Entériques, Centre National de Référence des Escherichia coli, Shigella et Salmonella, Institut Pasteur, Paris, France, E-mail: fxweill@pasteur.fr.

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