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Vol 34 (3) 2010.pmd

BANGLADESH J CHILD HEALTH 2010; VOL 34 (3): 80-85 Original Articles
A Reappraisal of Clinical Characteristics of Typhoid Fever
Background: Recent reports from developing countries show that the clinical
presentation, diagnosis and treatment of typhoid have significantly altered often leading
to missed diagnosis. The incidence of complications is also reported to be variable.
The consequence of missed diagnosis is immense in terms of burden on limited
health resources and patients’ suffering. Therefore, its clinical spectrum requires
constant reappraisal to update our physicians with current knowledge. This study was
carried out to determine the changes in clinical pattern of typhoid fever.

Patients & Methods: A total of 106 children, aged up to 14 years, diagnosed primarilyas typhoid fever, were included as study population. The diagnostic criteria wereeither positive blood culture for Salmonella typhi or Salmonella paratyphi or at least afour-fold rise in antibody titre on Widal test. The study included mode of clinicalpresentations, treatment received before admission, Widal test findings and cultureand sensitivity to antibiotics. Results: The mean age of the patients was 5.2 years and males were a little than thefemales. The mean duration of illness was 11.2±3.3 days. Majority of the patientspresented with classical signs and symptoms like step ladder pattern of fever (nearly70%) coated tongue (69.8%), diarrhoea (49.1%), toxemia (68.9%), relative leucopenia(71.7%), hepatomegaly (55.7%), pain in the right hypochondrium (41.5%) andsplennomegaly (18.9%). Very few cases had a typical manifestations. Over 85% ofthe patients had raised SGPT (>40 IU/L) and 13.8% had detectable jaundice (serumbillirubin >3 mg/dl). Widal test demonstrated that about 45% of the patients’ ‘O’antibody titer increased to 4-fold, 27.4% to 8-fold or more. In case of antibody ‘H’,35.8% exhibited 4-fold and 39.7% 8-fold or more increase. Of the 103 cases, 68(66%)were positive for Salmonella typhi. Majority of the isolated organisms was sensitive tocefixime, ceftriaxone and gentamycin (83%, 84% and 82% respectively). The secondline of sensitivity was obtained to amikacin (64.2%), meropenem (50%), ciprofloxacin(46.2%), imepenem (46.2%) and azithromycin (43.4%). The least sensitive drugswere amoxicillin (28.3%), cotrimoxazole (27.4%) and chloramphenicol (22.6%). One-third (33.8%) of the patients had multidrug resistant (MDR) strains. However, Nosignificant association was found between multi-drug resistant (MDR) strains andatypical clinical manifestations. Conclusion: Clinical presentation of most typhoid fever still conforms with the classic
pattern. High fever, anorexia, coated tongue, diarrhoea, relative leucopenia and
hepatosplenomegaly are still common manifestations of typhoid fever. So, majority
of the patients could be treated blindly based on clinical diagnosis. However, treatment
should be given with first line of drugs like cefexime or ceftriaxone.

Key words: Typhoid fever, classic presentation, atypical presentation.
1. Chief Consultant, Department of Paediatrics, Central Police Typhoid fever is a systemic infectious disease caused 2. Senior Medical Officer, Central Hospital, Green Road, Dhaka by Salmonella enterica, including S enterica serotype 3. Internee Doctor, BIRDEM Hospital, Dhaka Typhi (S typhi) and serotype Paratyphi (S paratyphi).
4. Consultant, Paediatric Cardiology, Ibne Sina Hospital, Dhaka5. Assistant Professor, Paediatric Neurology, BSMMU, Dhaka It is characterized by an acute illness, the first typical Correspondence: Dr. ABM Shahidul Alam
manifestations of which are step-ladder pattern of fever, BANGLADESH J CHILD HEALTH 2010; VOL 34 (3) : 81 headache, abdominal pain, relative bradycardia, Materials and Methods:
splenomegaly, and leucopenia1,2. Each year, This descriptive study of 106 cases of enteric fever worldwide there are at least 13-17 million cases of was done over a period of 14 months from September typhoid fever, resulting in 600,000 deaths3. With the 2008 to December 2010 at the Central Hospital Ltd, adoption of sanitary and hygienic measures in the Dhaka. With the permission of the hospital authority,informed consent was obtained from each of the developed countries, there has been a marked decline participating subjects. The study was carried out to in the incidence of the disease4, although the disease determine the changes in clinical pattern of enteric is still endemic in developing countries. However, its fever. Paediatric patients up to the age of 14 years, clinical presentation, pathological and biochemical diagnosed primarily as typhoid fever, were the study manifestations and antimicrobial sensitivity pattern population. The diagnostic criteria were either positive have changed significantly posing problem to diagnosis blood culture for Salmonella typhi or Salmonella and management5. Agarwal and associates6 reported paratyphi or at least a four-fold rise(1:160) in either ‘O’ clinical features of typhoid fever to be in conformity or ‘H” antibody titres on Widal test. The variables with earlier studies7,8 and noted spleenomegaly in studied were age, sex, mode of clinical presentations, only less than one third of the cases. Multidrug treatment received before admission and laboratory resistant enteric fever is associated with prolonged duration of fever, hepatomegaly, more complication Laboratory tests performed were a complete blood and higher mortality9-11. Typhoid fever below five years count and widal test. The widal test was performed of age is uncommon and these cases have more by rapid slide agglutination method using ‘O’ or ‘H’ agglutinins. Blood specimens were cultured toevaluate the yield of Salmonella typhi or paratyphi. Durani and Rab14 reported that classical pattern of Five ml of blood was collected in thioglycolate broth.
step-ladder fever associated with relative bradycardia Culture bottles were incubated at 370 C and then was not seen in most patients. Twenty-two percent bacilli were identified according to standard cases had sudden onset of high grade fever and of techniques. Sensitivity status to different antibiotics them majority were clinically diagnosed as was studied. Sensitivity of the cultured strains were septicaemia. Diarrhoea, hepatomegaly and jaundice tested against amoxicillin, cotrimoxazole, are not commonly encountered. Diagnoses of viral chloramphenicol, ciprofloxacin, amikacin, hepatitis, bronchitis, psychosis, meningitis, meropenem, imepenem, azithromycin, cefixime, myocarditis, polyneuropathy and proximal myopathy ceftriaxone and gentamycin. The test statistics used were also made based on the presenting signs and to analysis the data were descriptive statistics, Chi-square test or Fisher’s Exact Probability test.
symptoms. Neuropsychiatric manifestations were less Spearmen correlation was done to see the relationship frequent as compared to 45% cases reported from India9,12. In a study Dutta and associates15 reported that nearly half (46.9%) of the enteric fever cases Results:
present with atypical manifestations. Atypical Out of the 106 patients, 10.4% was below 2 years, manifestations observed were burning micturation with 45.3% between 2-5 years and 44.3% 5 years or above normal urine examination (15.6%), diarrhooea, isolated 5 years old. The mean age of the patients was 5.2±2.8years and the youngest and oldest patients were 7 hepatomegaly and bone-marrow depression (each months and 14 years respectively (Table-I). Over half 6.2%) in first week. Nearly one-third (31.3%) had multi- (54%) of patients was male and the rest female.
drug resistant (MDR) strains and 50% of the cases Seventeen percent of patients presented between 5-7 with MDR strains had atypical presentation16. As it days of onset of illness, 58% between 8-14 days and results in high morbidity and mortality, reappraisal of 25% after 14 days (Fig.-1). The mean duration of presentation, course, complication and treatment is illness was 11.2±3.3 days and the shortest and longest deemed necessary. So, this study was carried out to durations were 5 and 17 days respectively. Widal test determine the changes in clinical pattern of typhoid result demonstrated that 44.3% and 27.4% of the cases had 4- and 8-fold or > 8-fold rise of ‘O’ agglutinin A Reappraisal of Clinical Characteristics of Typhoid Fever BANGLADESH J CHILD HEALTH 2010; VOL 34 (3) : 82 titers respectively, while 35.8% and 39.7% of caseshad 4- and 8-fold or >8-fold rise of ‘H’ agglutinin titersrespectively (Table-II). However, ‘O’ and ‘H’ agglutininsfor S. paratyphi did not show significant increase. Ofthe 103 patients whose blood was cultured, 68(66%)were found positive for Salmonella typhi or paratyphi(Fig.-2). Of the 68 culture positive cases, 17(25%)were S. typhi and the rest were other species of Fig.-2: Distribution of patients by blood culture findings
Distribution of patients by demographic Over 70% of the patients had step-ladder pattern of fever, 25.5% intermittent and 3.8% remittent fever(Table-III). About 70% of patients had coated tongue followed by 49.1% diarrhoea, 33% nausea/vomiting, 28.3% loss of appetite, 20.8% cough, 15.1% constipation, 13.2% headache, 12.3% relative bradycardia, 11.3% abdominal discomfort, 6.6%others. Toxemia was the predominant clinical sign (68.9%) followed by hepatomegaly (55.7%), pain in the right hypochondrium (41.5%) and splennomegaly (18.9%). Burning micturation, altered consciousness and dehydration each was found in 3.8% of the cases.
Joint pain and muscle pain was negligible. Jaundiceand epistaxis were rare (0.9%) (Table-IV). About 72%of the cases exhibited relative leucopenia (6000–11000/mm3 of blood) and 15.1% absolute leucopenia(<6000/mm3 of blood). One-third (33%) of the caseswas found anaemic (haemoglobin <10gm/dl) andnearly 20% had raised ESR (>50 mm in 1st hour). Outof 29 cases, raised SGPT (>40 IU/L) and raised serumbillirubin were found in 25 (86.2%) and 4 (13.8%) casesrespectively (Table-V).
Fig.-1: Distribution of patients by duration of illness (days)
Distribution of the patients by Widal test findings BANGLADESH J CHILD HEALTH 2010; VOL 34 (3) : 83 Table-IV
commonly available antibiotics like amoxicillin, cotrimoxazole and chloramphenicol16).
Sensitivity of salmonellae typhoid or paratyphoid to Hematological and biochemical findings Discussion
The clinical profiles of typhoid fever are diverse and atypical manifestation often makes a serious diagnostic problem, especially in childhood. Thepresent study intended to assess the changing pattern of typhoid fever found mean age of the patients to be 5.2 years and the lowest and highest ages were 7 months and 14 years respectively. Males and females had almost equal representation in the population.
The mean duration of illness at presentation was 11.2±3.3 days and the shortest and longest durations Majority of the patients in our study presented with step-ladder pattern of fever, coated tongue, toxemia, relative lecopenia and hepatomegaly, which conformswith classical presentation described by Dutta15. He As shown in table VI, the majority of the isolated studied clinical presentation of 32 bone marrow culture organisms was sensitive to cefixime, ceftriaxone and positive patients and described classical typhoid fever gentamycin (83%, 84% and 82% respectively). Thesecond line of sensitivity was obtained to amikacin to be characterized by insidious onset of sustained (64.2%), meropenem (50%), ciprofloxacin (46.2%), fever, severe headaches, malaise, anorexia, a non imepenem (46.2%) and azithromycin (43.4%). The productive cough (in the early stage of the illness), a least sensitive drugs were amoxicillin (28.3%), cotrimoxazole (27.4%) and chloramphenicol (22.6%).
hepatosplenomegaly. Diarrhoea and abdominal pain One-third (33.8%) of the culture positive cases had are also common manifestations15. Very few cases multidrug resistant (MDR) strains (resistant to three were presented with atypical manifestation. Atypical A Reappraisal of Clinical Characteristics of Typhoid Fever BANGLADESH J CHILD HEALTH 2010; VOL 34 (3) : 84 manifestations observed were burning micturation with MDR strains and atypical manifestations. Nevertheless normal urine examination (15.6%), diarrhoea (6.2%) resistance to commonly available antibiotics has and encephalopathy (3.1%) in the first week, isolated emerged as a significant problem resulting in hepatomegaly (6.2%), pneumonitis (3.1%) and bone protracted illness and increased treatment cost.
marrow depression (6.2%). The present study revealed Conclusion
relative leucopenia as the common feature of typhoidfever as more than 70% of the patients had WBC The study concluded that the clinical pattern of typhoid count in the range of 6000-11000/mm3 and 15% below fever did not change much from the classic pattern of 6000/mm3 though majority of them had been suffering typhoid fever. Anorexia, coated tongue, diarrhoea,relative bradycardia, relative neucopenia, from the disease for more than 7 days.
hepatosplenomegaly are still common manifestations Our study showed that majority (86.2%) of the patients of typhoid fever. Very few cases had atypical had raised SGPT (>40 IU/L) and 13.8% had detectable manifestation. Atypical manifestations are usually jaundice (serum billirubin >3 mg/dl). Morgenstern and seen in cases of infection acquired by resistant Hayes16 studied the course of liver involvement during microorganisms. So majority of the patients could be the first three weeks of typhoid fever in 20 patients treated blindly based on clinical diagnosis. However, and found almost consistent result with present study.
treatment should be given with first line of drugs like In their study, hepatomegaly was found during the cefexime or ceftriaxone. Second and third line of 2nd or 3rd week more often than in the 1st week (36% antibiotics can be used only if the isolated organisms vs. 11%), whereas jaundice was detectable in 9% of are found sensitive to a particular antibiotic.
A four-fold rise in somatic (O) agglutination titres in Butter T. Typhoid fever. In: eds. Wyngaarden JB, paired sera during the second week supports the Smith LH, and Bennett JC. Cecil textbook of diagnosis of enteric fever, provided vaccine had not been given recently (PHAC, 2005). As more than 70% of our patients exhibited at least a four-fold increasein somatic (O) agglutination titers, they could be Pearson RD, Guerrant RL. Enteric fever and other considered diagnostic of the disease. Although two- causes of abdominal symptoms with fever. In: thirds (66%) of the blood culture gave a positive result, Mandell GL, Bennett JE, Dolin R, editors.
Principles and Practice of Infectious Diseases, they cannot be reliably considered as diagnostic, for 5th ed. Churchill Livingstone: New York; 2000.
sensitivity of blood culture alone is only 50% to 70% (PHAC, 2005). Clegg et al17. conducted a study inPapua New Guinea (PNG) in 1992 to re-evaluate the WHO. The World Health Report, Report of the Widal slide agglutination test as a rapid diagnostic test for typhoid fever. This was in response to an apparent increase in the number of false positive Widal paratyphoid fever in travellars. Lancet, 2005; 5: slide agglutinations occurring using an ‘O’ cut-off titer greater than or equal to 40 which was previously shown Gulati PD, Saexena SN, Gupta PS, Chuttani to be appropriate in 1987. The results of the re- HK. Changing pattern of typhoid fever. Am J Med evaluation indicated that the Widal test using a diagnostic cut-off titer of 40 or more lacked specificityand was no longer appropriate for this population and Agarwal KS, Singh SK, Kumar N. A study of a new ‘O’ antibody titer of 160 or greater was then current trend in enteric fever. J Common Dis 1998; recommended as a diagnostic titer for typhoid fever in Thisyakorn U, Mansuwan P, Taylor DN. Typhoid Out of 68 culture positive cases, 23(33.8%) had MDR and paratyphoid fever in 192 hospitalised childrenin Thailand. Am J Dis Child 1987;141: 862-65.
strains. In South East Asian nations, 5% or more ofthe strains of the bacteria have already been resistant Arora RK. Multidrug resistant typhoid fever: a to several antibiotics3. However, cross-tab analysis study of an outbreak in Calcutta. Indian Pediatr did not reveal any significant associations between BANGLADESH J CHILD HEALTH 2010; VOL 34 (3) : 85 Bhutta ZA. Impact of age and drug resistance 15. Dutta TK, Beeresha Ghotekar LH. Atypical on mortality in typhoid fever, Arch Dis Child 1996; manifestations of typhoid fever. J Postgrad Med 10. Kaul PB. Multidrug resistant Salmonella typhi 16. Kumar S, Rizvi M, Berry N. Rising prevalence of infection: Clinical profile and therapy. Indian epidemiological study. Med Microbiol 2008; 57: Buch NA. Enteric fever – A changing sensitivity pattern: Clinical profile and outcome. IndianPediatr 1994; 31: 981-85.
17. Morgenstern R, Hayes PC. The liver in typhoid fever: always affected, Not just a complication.
12. Sharma A, Gathwal G. Clinical profile and outcome in enteric fever. Ind J Pediatr 1993; 30: The Am J Gastroenterol 2008; 86 : 1235-39.
18. Clegg A, Passey M, Omena M, Karigifa K, Suve 13. Mishra S. Clinical profile of multi drug resistant N. Re-evaluation of the widal agglutination test typhoid fever. Indian Pediatr 1991; 28: 1171-74.
in response to the changing pattern of typhoid 14. Durrani AB, Rab SM. Changing spectrum of fever in the highlands of Papua New Guinea. Acta typhoid. J Pak Med Assoc 1996; 46: 50-52.

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