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Jornal de Pediatria

Print version ISSN 0021-7557

J. Pediatr. (Rio J.) vol.88 no.2 Porto Alegre Mar./Apr. 2012

http://dx.doi.org/10.2223/JPED.2131 

ORIGINAL ARTICLE

 

Diarrhea associated with Shigella in children and susceptibility to antimicrobials

 

 

Maria do Rosário C. M. NunesI; Paula P. MagalhãesII; Francisco J. PennaIII; João Maurício. M. NunesIV; Edilberto N. MendesV

IDoutora, Microbiologia. Departamento de Parasitologia e Microbiologia, Centro de Ciências da Saúde, Universidade Federal do Piauí (UFPI), Teresina, PI, Brazil. Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil. Departamento de Propedêutica Complementar, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil
IIDoutora, Microbiologia. Departamento de Microbiologia, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, MG, Brazil
IIIDoutor, Pediatria. Departamento de Pediatria, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil
IVMédico. Departamento de Parasitologia e Microbiologia, Centro de Ciências da Saúde, UFPI, Teresina, PI, Brazil
VDoutor, Microbiologia. Departamento de Propedêutica Complementar, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil

Correspondence

 

 


ABSTRACT

OBJECTIVE: To evaluate the distribution and susceptibility to antimicrobials of Shigella isolated from children with acute diarrhea and without diarrhea in Teresina, state of Piauí, Brazil.
METHODS: Four hundred children aged up to 60 months were studied. Stools were collected from all the patients between January 2004 and August 2007. Shigella was identified by conventional methods and antibiogram and extended-spectrum
β-lactamase (ESBL) were performed by agar diffusion.
RESULTS: Shigellosis was only detected in children with acute diarrhea (26/250; 10.4%), especially in those aged from 6 to 24 months and in the rainy months. Shigella was susceptible to ceftriaxone, ciprofloxacin and nalidixic acid. More than half of the strains were resistant to sulphametoxazole-trimethoprim and ampicillin. ESBL was not detected.
CONCLUSIONS: S. flexneri is common in Teresina. The resistance to ampicillin and sulphametoxazole-trimethoprim gives cause for concern, as these drugs are widely used in practice and sulphametoxazole-trimethoprim is also recommended for treating children suspected of having shigellosis.

Keywords: Infectious diarrhea, Shigella flexneri, Shigella sonnei, susceptibility to antimicrobials, treatment of acute diarrhea.


 

 

Introduction

Infectious enteritis is an important cause of morbidity and mortality, especially in the less developed regions of the planet.1-3 Among others, Shigella is one of the main agents of the disease.2 It is estimated that more than 160 million human beings are infected by the microorganism annually and that approximately 1.1 million die.2 Although shigellosis, or bacillary dysentery, attacks individuals of any age or socioeconomic class, more than 99% of the cases occur in children in developing countries aged under 5 years.2,4 Among the Shigella, S. flexneri predominates in developing countries and S. sonnei in industrialized countries.2 Although the less severe cases of the disease can be cured by oral rehydration and regular feeding, it has been proposed that patients with symptoms suggesting shigellosis are treated with antimicrobials, aiming to reduce the duration and severity of the disease and the period taken to eliminate the bacterium.4-8 However, selecting an efficient therapy is rendered more difficult due to the alarming prevalence of resistant strains. Thus, the knowledge on the distribution and susceptibility to drugs of Shigella in different geographical settings is of paramount importance for the comprehension of the biology and epidemiology of shigellosis and, ultimately, for designing efficient strategies for preventing and controlling the disease.2,4,9

This study aimed to evaluate the distribution and susceptibility to antimicrobials of Shigella isolated from children with acute diarrhea and without diarrhea in Teresina, state of Piauí, Brazil.

 

Patients and methods

This investigation is part of a prospective study on the etiology of diarrhea in children in Teresina. Clinical, demographic and epidemiological data were recorded on a separate sheet. Acute diarrhea was defined as the elimination of three or more loose or liquid stools per day, or more frequently than is normal for the individual, with an evolution of up to 7 days.5-7

Stools were obtained from 400 children aged up to 60 months from a low socioeconomic level, attended to in two public hospitals of Teresina, from January 2004 to August 2007: 250 with acute diarrhea and 150 without diarrhea in the 15 days prior to the appointment. Children with a history of hospitalization or antibiotic therapy in the 15 days preceding the diarrhea were not included.

Stools were obtained after spontaneous evacuation, transferred to sterile vials containing a glycerol and phosphate 0.033 M solution (1:1), pH 7.0, transported to the laboratory in an ice bath and processed within 1 hour. The specimens were cultivated onto MacConkey agar (Himedia, Mumbai, India) and SS agar (Becton, Dickinson and Co., Sparks, MD, USA). After incubation at 35 ºC for 24 hours, five lactose-positive colonies and five lactose-negative colonies (whenever possible) were identified by means of conventional biochemical and physiological tests. The colonies identified as Shigella were submitted to agglutination reactions with specific antisera (Probac, São Paulo, Brazil) to determine the species.

A Shigella strain from each patient, randomly selected, was employed for testing the susceptibility of the bacterium to nalidixic acid, ampicillin, ceftriaxone, ciprofloxacin and sulphametoxazole-trimethoprim and the production of extended-spectrum β-lactamase (ESBL) by agar diffusion.10

The Yates' chi-square or Fisher's exact tests were used and the differences were taken as significant when p < 0.05.

This project was approved by the Research Ethics Committees of the Universidade Federal de Minas Gerais and Universidade Federal do Piauí. The parents and/or those in charge agreed to the child taking part by signing the free informed term of consent.

 

Results

Shigella was isolated from 26 children, all with acute diarrhea (10.4%): S. flexneri from 21 (80.8%) and S. sonnei from 5 (19.2%).

Shigellosis was most common (19/73.1%) in children up to 24 months of age, not having been detected in those under 6 months or over 48 months of age. Approximately 70% of S. flexneri was isolated from children under 2 years old and S. sonnei only from those over 2 years old.

An association between shigellosis and the patient's sex was not detected.

Shigellosis was more common in 2004 (5/22, 22.7%) than in the remainder of the study period (6/96, 6.3% for 2005; 10/195, 5.1% for 2006; 5/87, 5.7% for 2007; p = 0.012; chi-square test). Concerning the two bacterium species, only S. sonnei was associated with the year of the investigation, being more common in 2004 (for S. sonnei: 3/5, 60.0% in 2004; 0/5, 0% in 2005; 1/5, 20.0% in 2006 and 1/5, 20.0% in 2007; for S. flexneri: 2/21, 9.5% in 2004; 6/21, 2.9% in 2005; 9/21, 42.9% in 2006; 4/21, 19.0% in 2007; p < 0.001; chi-square test).

Seasonality was observed for shigellosis and for infection by S. flexneri (p = 0.007 and p = 0.022), being more frequent in the rainy months (n = 20; 76.9% and n = 16; 76.2%, respectively).

An association was observed between shigellosis and bloody stools (16/26 - 61.5%; p < 10-3; Fisher's exact test) and fever (23/26, 88.5%; p = 0.023; Fisher's exact test). There was no association between the disease and consistency of the stools and number of evacuations per day. Blood and mucous in the stools were more common in the infection by S. flexneri (14/21, 66.7% and 18/21, 85.7%, respectively) than in diarrhea by S. sonnei (4/5, 40.0% and 2/5, 40.0%, respectively) (p = 0.008 and p = 0,005, respectively; Fisher's exact test).

The results of the antibiograms of Shigella are shown in Table 1. ESBL was negative for all the samples.

 

 

Discussion

Shigellosis is an important cause of acute diarrhea all over the world, not only due to its high prevalence, but also because of the severity of the disease.1,2,4,8,10-12 As in other parts of the world, Shigella was responsible for more than 10% of the cases of acute diarrhea in Teresina. A similar frequency was observed in Trinidad11 and Israel.12 On the other hand, our findings show a higher frequency of shigellosis than that observed in the states of Paraíba (approximately 3%)13 and Rondônia (2.9%),14 Brazil. Among other reasons, these differences may result from diversity in the geographical distribution of the bacterium, characteristics of the population studied and the methodology of the investigations.

The temporal dominance of different Shigella species is still unclear. In recent decades, a drop in the global prevalence of S. dysenteriae and an increase in S. flexneri have been noted. Currently, especially in the industrialized regions, there is a greater prevalence of S. sonnei, a fact that has not yet been explained in a convincing way.2 In agreement with data reported for other less developed regions,2,14,15 we observed that more than 80% of the cases of shigellosis are associated with S. flexneri.

In areas where shigellosis is endemic, the highest rates of the infection occur in the second year of life.2 We noted similar data: most of the cases of shigellosis were identified in children aged from 6 to 24 months. The existence of several serotypes of the microorganism allows one to assume that, in the endemic regions, several episodes of the disease occur in childhood. In the first 6 months of life, children usually live in a more protected environment and receive protective factors conferred by breastfeeding. After this age, although still immunologically naïve, they come into contact with the microorganism more frequently. Consequently, they are more susceptible to the infection and develop the disease and progressive protection against the types of the microorganism circulating in that region. Thus, it is possible to explain the low frequency of shigellosis up to 6 months of age, its increase between 6 months and 2 years old and the drop after this age.

According to Naumova et al.,15 shigellosis is more common in the summer, owing to the greater recreational use of water and the precarious hygiene habits which facilitate the transmission of diarrheagenic bacteria. The predominance of shigellosis in the rainy months, the hottest months in Brazil, can also be explained by the transmission of the microorganism by the rainwater.

Symptoms of shigellosis include acute abdominal pain, fever and bloody stools. Diarrhea may be initially watery and large in volume evolving into frequent small volume bloody mucoid stools.2 In this study, fever and bloody stools were associated with the disease. Due to the more aggressive nature of the process, stools containing blood and mucous were more common in children infected by S. flexneri.

Less than 20% of the Shigella was susceptible to all the antimicrobial drugs tested. As with other bacteria, the sensitivity of Shigella to antibiotics has been changing and is affected by the habits of each population, explaining geographical differences,4,9,11 making the development of regional studies needed. Besides rehydration and regular feeding, treatment with antibiotics is advisable if shigellosis is suspected.4-6 In this study, all the samples of Shigella were susceptible to  ceftriaxone, ciprofloxacin and nalidixic acid and more than 50% resistant to ampicillin and sulphametoxazole-trimethoprim, similarly to data reported for other regions.4,9,14 Thus, sulphametoxazole-trimethoprim and ampicillin are not recommended for treating diarrhea, aiming at eliminating Shigella in the region studied. Ceftriaxone is an expensive option and ciprofloxacin is to be used with caution in children2. Nalidixic acid is efficacious in vitro and would be an accessible choice. However, although it was the drug of choice for treating shigellosis between 1995 and 2005, its practical efficacy is considered to be low, even for samples of the bacterium considered to be sensitive in vitro.4

So, our data contribute to increasing knowledge about the distribution and the susceptibility profile of Shigella and, consequently, for designing strategies for preventing and controlling shigellosis.

 

References

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3. Melli LC, Waldman EA. Temporal trends and inequality in under-5 mortality from diarrhea. J Pediatr (Rio J). 2009;85:21-7.         [ Links ]

4. World Health Organization. Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteriae 1. Geneva: World Health Organization; 2005. 64 p.         [ Links ]

5. Brasil. Ministério da Saúde. Assistência e controle das doenças diarréicas. Brasília: Ministério da Saúde; 1993.         [ Links ]

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7. Guarino A, Albano F, Ashkenazi S, Gendrel D, Hoekstra JH, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe. J Pediatr Gastroenterol Nutr. 2008;46:S81-122.         [ Links ]

8. Tauxe RV, Puhr ND, Wells JG, Hargrett-Bean N, Blake PA. Antimicrobial resistance of Shigella isolates in the USA: the importance of international travelers. J Infect Dis. 1990;162:1107-11.         [ Links ]

9. Peirano G, Souza FS, Rodrigues DP; Shigella Study Group. Frequency of serovars and antimicrobial resistance in Shigella spp. from Brazil. Mem Inst Oswaldo Cruz 2006;101:245-50.         [ Links ]

10. National Committee for Clinical Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. 15th informational supplement M100-S15. Wayne, PA: National Committee for Clinical Laboratory Standards; 2005.         [ Links ]

11. Orrett FA. Prevalence of Shigella serogroups and their antimicrobial resistance patterns in southern Trinidad. J Health Popul Nutr. 2008;26:456-62.         [ Links ]

12. Ziv T, Heimann AD, Azuri J, Leshno M, Cohen D. Assessment of the underestimation of childhood diarrhoeal disease burden in Israel. Epidemiol Infect. 2011;139:1379-87.         [ Links ]

13. Moreno AC, Filho AF, Gomes Tdo A, Ramos ST, Montemor LP, Tavares VC, et al. Etiology of childhood diarrhea in the northeast of Brazil: significant emergent diarrheal pathogens. Diagn Microbiol Infect Dis. 2010;66:50-7.         [ Links ]

14. Silva T, Nogueira PA, Magalhães GF, Grava AF, Silva LH, Orlandi PP. Characterization of Shigella spp. by antimicrobial resistance and PCR detection of ipa genes in an infantile population from Porto Velho (Western Amazon region), Brazil. Mem Inst Oswaldo Cruz 2008;103:731-3.         [ Links ]

15. Naumova EN, Jagai JS, Matyas B, De Maria A Jr, MacNeill IB, Grifiths JK. Seasonality in six enterically transmitted diseases and ambient temperature. Epidemiol Infect. 2007;135:281-92.         [ Links ]

 

 

Correspondence:
Edilberto Nogueira Mendes
Avenida Professor Alfredo Balena, 190, sala 423
CEP 30130-100 – Belo Horizonte, MG - Brazil
E-mail: enmendes@medicina.ufmg.br

Manuscript submitted Apr 21 2011,
accepted for publication Jul 27 2011.

 

 

Financial support: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) and Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais (PRPq/UFMG).
No conflicts of interest declared concerning the publication of this article.
Suggested citation: Nunes MR, Magalhães PP, Penna FJ, Nunes JM, Mendes EN. Diarrhea associated with Shigella in children and susceptibility to antimicrobials. J Pediatr (Rio J). 2011;88(2):125-8.