|ORIGINAL RESEARCH REPORT
|Year : 2020 | Volume
| Issue : 3 | Page : 74-79
Clinical and microbiological profile of enteric fever among pediatric patients in a tertiary care center in South India: A cross-sectional study
A Malini1, C Barathy2, NS Madhusudan1, C Johnson3
1 Department of Microbiology, Indira Gandhi Medical College and Research Institute, Puducherry, India
2 Department of Paediatrics, Indira Gandhi Medical College and Research Institute, Puducherry, India
3 Department of Community Medicine, Indira Gandhi Medical College and Research Institute, Puducherry, India
|Date of Submission||06-Mar-2020|
|Date of Acceptance||05-Jun-2020|
|Date of Web Publication||04-Jul-2020|
Dr. C Barathy
Department of Paediatrics, Indira Gandhi Medical College, and Research Institute (Government of Puducherry Institution), Kadirkammam, Puducherry - 605 009
Source of Support: None, Conflict of Interest: None
Introduction: Enteric fever, which is endemic in India, is a significant cause for morbidity, particularly among young children. Enteric fever is associated with high fever, abdominal pain, diarrhea, and splenomegaly. Recently, there have been increasing reports of enteric fever due to Salmonella enterica serovar Paratyphi A and multidrug resistance among Salmonella species. Objectives: The objective of this study was to know the relative occurrence of Salmonella Typhi and Salmonella Paratyphi A from blood cultures of enteric fever cases, to study the sensitivity pattern of Salmonella species isolated, to compare the clinical profiles in typhoid and paratyphoid fever, and to know their treatment outcome. Materials and Methods: It was a prospective hospital-based cross-sectional study. The demographic, clinical, and laboratory data were recorded for all cases included in the study. All clinically suspected cases of enteric fever were confirmed by blood culture and/or the Widal test. Antibiotic sensitivity was tested by the Kirby–Bauer disc diffusion method. Results were analyzed using SPSS version 21. Results: One hundred and nineteen cases were confirmed enteric fever. Their clinical profile is discussed. Out of 119 cases, 24 showed blood culture positivity. Salmonella Paratyphi A and Salmonella Typhi were isolated in the ratio of 3:1. The isolates were sensitive to ampicillin, co-trimoxazole, ceftriaxone, and azithromycin. Ceftriaxone was the most commonly used antibiotic for treatment. All patients recovered, and no mortality was encountered. Complications were seen in 33 children (27.7%), which included subclinical hepatitis, bronchitis, and pneumonia. Conclusion: Considering the blood culture results, enteric fever due to S. Paratyphi A was more common in our study. Multidrug resistance was not seen among Salmonella species. The duration of illness and complications were more with typhoid than paratyphoid cases.
Keywords: Clinical profile, cross-sectional study, multidrug resistance, paratyphoid fever, pediatrics
|How to cite this article:|
Malini A, Barathy C, Madhusudan N S, Johnson C. Clinical and microbiological profile of enteric fever among pediatric patients in a tertiary care center in South India: A cross-sectional study. J Clin Sci 2020;17:74-9
|How to cite this URL:|
Malini A, Barathy C, Madhusudan N S, Johnson C. Clinical and microbiological profile of enteric fever among pediatric patients in a tertiary care center in South India: A cross-sectional study. J Clin Sci [serial online] 2020 [cited 2021 May 16];17:74-9. Available from: https://www.jcsjournal.org/text.asp?2020/17/3/74/288903
| Introduction|| |
Enteric fever includes typhoid and paratyphoid fever caused by Salmonella enterica serovar Typhi (Salmonella Typhi) and S. enterica serovar Paratyphi (Salmonella Paratyphi) A, B, and C. Enteric fever is endemic in India and under regular surveillance by the Integrated Disease Surveillance Project. It is a significant cause of morbidity and mortality in developing nations. The incidence is estimated to be about 377 (178–801) and 105 (74–148) per 100,000 person-years for typhoid and paratyphoid, respectively, in India. The highest incidence is seen among children between 2 and 4 years. Data on mortality due to enteric fever in India are scarce. Overall case fatality rate estimated due to enteric fever is about 1%. Blood culture is the gold standard for the diagnosis of enteric fever, but the isolation rate is only about 40%–60%. In day-to-day practice, most cases are diagnosed clinically without sufficient laboratory evidence., Despite limitations like cross-reactivity, the Widal test is still widely used for the diagnosis of enteric fever.
In recent years, it has been reported that the incidence of enteric fever caused by Salmonella Paratyphi A has been increasing in India.,, A multicentric study conducted in Asian countries has also revealed that Salmonella Paratyphi A might be contributing to as much as 50% of all the enteric fever cases. Hence, Salmonella Paratyphi A has recently been described as an emerging pathogen. With this changing scenario of increasing incidence of Salmonella Paratyphi A, it is proposed that enteric fever prevention strategies in Asia must also focus on Salmonella Paratyphi A using bivalent vaccines.,,
Hence, this study was done to determine the relative occurrence of Salmonella Typhi and Salmonella Paratyphi A, their clinical profile, and outcome of treatment, to correlate the laboratory findings in cases of enteric fever, and to know the incidence of multidrug resistance among Salmonella species isolated from blood culture.
| Materials and Methods|| |
Study design and setting
This was a hospital-based prospective cross-sectional study done in the Departments of Microbiology and Pediatrics from August 2015 to December 2016 after Institute Ethical Clearance (IEC/PP/2015/52). It is a 750-bedded tertiary care government hospital with 90 beds in the pediatric unit.
Clinically suspected/probable enteric fever: patients with fever of ≥5 days, if associated with toxic look, coated tongue, relative bradycardia, splenomegaly, gastrointestinal complications such as hemorrhage/perforation (any two).
A confirmed case is a probable case that is laboratory confirmed by isolation of Salmonella Typhi/Salmonella Paratyphi and/or demonstration of a fourfold rise in antibody titer/specific IgM antibodies against Salmonella spp. or Widal titers of more than 1:160. Co-resistance to ampicillin, chloramphenicol, and co-trimoxazole was considered as multidrug resistance.
All the clinically suspected inpatients were enrolled in the study. The confirmed cases were taken up for data analysis. Data were collected as per the pro forma designed for the study which included the demographic profile, presenting complaints, detailed clinical history, examination findings, laboratory reports, treatment details, complications, and outcome. The data were entered into an Excel sheet. Patients with underlying respiratory infections, malaria, hepatitis, hematological, or other systemic disorders were excluded. The confirmed cases were followed up for 1 month. The other suspected cases of enteric fever diagnosed with other systemic infections or co-infections were excluded to avoid confounding clinical features.
Blood cultures were carried out by conventional method using brain–heart infusion broth, and subcultures were done at 24 h, 48 h, and on the 7th day (in case of negative culture). Subcultures were done onto MacConkey agar and blood agar and incubated aerobically at 37°C. Nonlactose fermenting isolates were identified as Salmonella Typhi and Paratyphi A by standard biochemical tests. Serotyping of the isolates was done with specific antisera (Denka Seiken, Japan). Antimicrobial sensitivity was tested using the Kirby–Bauer disc diffusion method as per the Clinical and Laboratory Standards Institute guidelines. The antibiotic discs used were ampicillin (10 μg), ciprofloxacin (5 μg), co-trimoxazole (25 μg), ceftriaxone (30 μg), chloramphenicol (30 μg), and azithromycin (15 μg) (HiMedia Laboratories Ltd., Mumbai, India). Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 29213) were used for quality control. Widal testing was done by tube method (Beacon Diagnostics Pvt. Ltd., Navsari, Gujarat, India) and was recommended after the 7th day of illness. The Widal tests with “O” and “H” titer of 1:160 or more were considered as positive. Hematology parameters and liver function tests were analyzed using Nihon Kohden Celltac 1142 and Beckman Coulter AU480, respectively.
Data were analyzed using SPSS version 21 (Statistical Product and Service Solutions, Copyright IBM Corporation 1989, 2012. USA). Descriptive statistics were used. Multivariate logistic regression was used for finding variables significantly associated with enteric fever. A comparison was done using Fisher's exact and Chi-square test, and P < 0.05 was considered significant.
| Results|| |
Out of 226 clinically suspected cases of enteric fever, 119 children had laboratory-confirmed enteric fever. Blood culture was positive in 24 children (20.2%) and Widal positive in 95 children (79.8%). There were 79 children (66.4%) with typhoid fever and 40 children (33.6%) with paratyphoid fever, considering both blood culture and the Widal test. The age-wise distribution of typhoid and paratyphoid fever is shown in [Figure 1].
|Figure 1: Age-wise distribution of typhoid and paratyphoid fever in children|
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The mean age of children with typhoid fever was 6.7 ± 3.3 years and those with paratyphoid fever was 8.3 ± 2.8 years There were 62 male children (52.1%) and 57 female children (47.9%).
Fever was high grade in 98 children (82.4%), of intermittent type in 115 children (96.6%), continuous in 3 children (2.5%), and remittent in one (0.8%). It was associated with chills and rigors in 105 (88.2%). The mean duration of fever at hospitalization was 8.4 ± 4.4 days and ranged from 5 to 30 days. The most common associated symptom was cough (n = 76, 63.9%) and vomiting (n = 59, 49.6%). The other symptoms are shown in [Table 1].
|Table 1: Distribution of clinical features between typhoid and paratyphoid fever|
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History regarding prior antibiotic therapy received could not be elicited. A similar history in other family members was present in 2 children (1.7%), and the history of travel was recorded in 3 children (2.5%). None of the children had received typhoid vaccination.
The examination findings are shown in [Table 1]. Toxic look which included depressed sensorium, grunting, or gray/mottled skin was seen in 53 children (44.5%) and coated tongue in 64 (53.8%). The mean peak temperature was 39.3°C ± 0.8°C. The maximum temperature recorded was 41.4°C. The mean pulse rate was 106.0 ± 18.1 beats per minute. Mean systolic and diastolic BP was 94.6 ± 10.3 and 62.9 ± 7.1 mmHg, respectively. Hepatomegaly was noted in 55 children (46.2%) and splenomegaly in 43 (36.1%). The distribution of clinical features between typhoid and paratyphoid fever is shown in [Table 1]. There was no significant difference in clinical features between typhoid and paratyphoid (P > 0.05). If only blood culture positivity was included, rigors were more common in typhoid than paratyphoid (Fisher's exact P = 0.038), mean duration of fever at admission longer in typhoid than paratyphoid (P = 0.046), and pulse rate lower in paratyphoid than typhoid (P = 0.028).
The laboratory parameters in typhoid and paratyphoid fever are depicted in [Table 2]. Mean hemoglobin was 10.8 ± 1.4 g/dl and white blood cell (WBC) count was 7.8 ± 4.2 × 103/mm3. The mean differential neutrophil count, lymphocyte count, monocyte count, and eosinophil count were 54.9 ± 14.7, 41.4 ± 14.0, 2.3 ± 1.7, and 1.3 ± 1.6, respectively. There was no difference in mean hemoglobin, total count, and differential counts of WBCs between typhoid and paratyphoid (P > 0.05).
Blood culture yielded Salmonella Paratyphi A in 18 children (15.1%) and Salmonella Typhi in 6 children (5.1%). The ratio of Salmonella Paratyphi A and Salmonella Typhi isolation was 3:1. The sensitivity pattern is shown in [Table 3]. Multidrug resistance was not encountered.
Complications were seen in 33 children (27.7%). It included subclinical hepatitis (n = 10), bronchitis (n = 9), pneumonia (n = 7), pharyngitis/tonsillitis (n = 5), mesenteric adenitis (n = 5), shock (n = 3), dehydration (n = 1), typhoid enteritis (n = 1) and intestinal perforation (n = 1), meningitis (n = 1), hematemesis (n = 1), persistent tachycardia (n = 1), and hyponatremia (n = 1), alone or in varying combinations. Complications were comparable in typhoid fever (n = 24, 30.4%) and paratyphoid fever (n = 9, 22.5%, χ2 = 0.823, P = 0.364). If only blood culture positive was included, complications were more in typhoid than paratyphoid (Fisher's exact P = 0.35).
Parenteral antibiotics were used for 99 children (83.2%), namely ceftriaxone in 76 (63.9%), cefotaxime in 21 (17.6%), and ampicillin in 2 (1.7%). If the fever was persistent even after 6 days of antibiotics, azithromycin was added as the second line in 19 children (16%). Oral antibiotics were used primarily in 20 children (16.8%), namely cefixime (n = 14, 11.8%), azithromycin (n = 3, 2.5%), cefpodoxime (n = 1, 0.8%), and amoxicillin (n = 2, 1.7%). Dexamethasone was used for the child with meningitis.
The mean defervescence time was 5.1 ± 2.7 days overall, for typhoid 6.3 ± 2.6 days, and paratyphoid 6.6 ± 3.1 days. The mean hospital stay was 8.7 ± 3.0 days. The mean total duration of illness from the start of fever to recovery was 13.5 ± 5.4 days and was significantly longer in typhoid than paratyphoid (mean 14.3 ± 5.9 vs. 12.1 ± 3.8, respectively, t = 2.121, P = 0.036). There was no significant difference between typhoid fever and paratyphoid fever in terms of mean defervescence interval and hospital stay (P > 0.05). Only one child required surgery for intestinal perforation. All the children were discharged uneventfully, and no mortality was recorded in the present study. No case of relapse was noted in this series in 1-month follow-up period.
Enteric fever in the young (1–5 years) and older children (6–12 years)
Children ≤ 5 years were 36 (30.3%) and those above 5 years were 83 (69.7%). The features of enteric fever in both age groups are shown in [Table 4].
Cough, diarrhea, and respiratory complications were significantly higher in the 1–5-year age group compared to the 6–12-year age group. Chills, headache, and arthralgia were significantly higher in the 6–12-year age group. Anemia was significantly higher in 1–5 years, whereas neutrophilia was higher in the 6–12-year age group. There were no significant differences in other symptoms, examination findings, laboratory work-up, and treatment outcome (P > 0.05).
Gender differences in typhoid and paratyphoid fever in children
Arthralgia was significantly more common in male children than female children (Fisher's exact P = 0.034). A significantly higher proportion of male children had complications compared to female children (Chi = 5.665, P = 0.017). There was no significant gender difference in the other clinical features and laboratory profiles of children with enteric fever (P > 0.05).
| Discussion|| |
This study describes the clinical and microbiological features of enteric fever which continues to be a public health problem. The most common age group susceptible to typhoid is 5–19 years. The youngest child in this study was 11 months of age, and the majority of the cases (69.6%) were above 5 years of age. One-third of the cases were <5 years of age.
The predominant symptoms were cough, chills, vomiting, headache, abdominal pain, diarrhea, and myalgia, consistent with that reported in the literature., Cough was higher in our study than that reported by Singh et al. (39%). Anorexia, constipation, and abdominal distension were low in our study, in contrast to that reported by Laishram and Singh.
In our study, younger children had more diarrhea and respiratory complications. Headache, chills, and myalgia were more common among older children which could be due to their ability to express the symptoms.
The common physical findings were coated tongue (53.8%), hepatomegaly (46.2%), toxic look (44.5%), and splenomegaly (36.1%), similar to that reported by Laishram. The coated tongue was reported as only 11% in one study. Hepatomegaly was more common than splenomegaly. Similarly, diarrhea was more common than constipation in children in the present study similar to that reported by Laishram and Singh.
The predominant laboratory finding was normal leukocyte count (63.8%), followed by eosinopenia (50.6%) in the present study. Normal leukocyte has been reported in other studies as well., Eosinopenia is known to occur in 70% of children with enteric fever and was low in our study probably because of the reliance on the Widal test. Thrombocytopenia reported in a few studies (14%–26%) was lower compared to the present study (32.8%)., It is a marker for severity and complications in typhoid fever. In our study, there was no statistical significance between thrombocytopenia and the occurrence of complications.
The blood culture yield in our study was about 20.2%. A study in Nepal had a blood culture yield of 38.6%. Some studies have reported an even lower yield of 5%–28%., The low yield in our study may be related to prior antibiotic use before hospitalization and the time of presentation to health facility. The mean duration of fever at the presentation in our study was 8.6 ± 4.8 days reducing the yield. It may also be related to a low volume of blood sample collected. Salmonella Paratyphi A was more commonly isolated than Salmonella Typhi (3:1).
Blood culture is the gold standard test. Widal test, despite its drawbacks, is still a commonly used test for diagnosis as no other serodiagnostic test is as sensitive, specific, and cost-effective enough. In actual practice, most of the cases of enteric fever are diagnosed clinically without proper laboratory evidence and consequently treated presumptively with antibiotics.
Complications were seen in 27.7% in the present study, lower than that reported by Comeau. The most common was a respiratory complication.
One-third of all the enteric cases were paratyphoid fever. Some studies have shown no clinical difference between typhoid and paratyphoid. Although the clinical features are comparable with typhoid, in our study, we have observed that paratyphoid was more common in older children and had a shorter course of illness when compared with typhoid. There was no gender difference in our study regarding the proportion of enteric fever, similar to the observation made by Khan, but a male preponderance was noted by Fazil et al.,
Salmonella Paratyphi A and Salmonella Typhi in the study showed ≥90% sensitivity to the antibiotics tested except for ciprofloxacin where almost all the isolates were resistant. Fortunately, no multidrug resistance was encountered in the present study. However, there are few reports of multidrug resistance and beta-lactamase production among Salmonellae from India.,, Timely data are essential not only to introduce vaccination programs for typhoid but also to identify populations at risk so that public health interventions can be carried out effectively. Infant immunization with conjugate vaccines could help address the problem of enteric fever among children.
| Conclusion|| |
Enteric fever continues to be a public health problem. Enteric fever due to S. Paratyphi A was more common in our study than S. Typhi, based on blood culture isolation. Younger children had more diarrhea and respiratory complications. Although there were no significant differences in clinical features, the total duration of illness and complications were more with typhoid than paratyphoid cases. Salmonella isolated from blood culture was mostly sensitive to ampicillin, co-trimoxazole, ceftriaxone, and azithromycin.
Limitations of our study
It is a hospital-based study where only indoor patients were included, less number of blood culture-positive cases, and a majority of them were diagnosed based on clinical features and the Widal test.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]