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Typhoid Fever in Malaysian Children

A S Malik, DTCH, R H Malik, MBBS, Facility of Medicine and Health Sciences, UniversitiMalaysia Sarawak (UNIMAS), No.9, Lot 2341, Bormill Commercial Estate, Jalan Tun AhmadZaidi Adruce, 93150, Kuching, Sarawak, Malaysia

Introduction

Typhoid fever is still an important. health problemin developing countries with an estimatedincidence of 540-cascs/lOO,OOO population l

, Inlllorc affluent regions of the world, propersanitation has successfully diminished infectionwith Salmonella IJphi (S. /JPhO. Neverthelessboth sporadic cases and outbreaks of typhoidfever have been encountered in the developedcountries over the yean:;2.

Although the Dumber of reported cases hasdropped over the years, typhoid is still a commonfebrile illness in Malaysia'"' (Fig I). In year 1998and 1999 the highest l1lL1nber of cases werereported from Kelantan followed by Sabab,Terengganu, Selangor and Sarawak and majorityof the patients was children".

This article was accepted: 10 October 2001

478

2000

1500-

1000 ,.it'

500

a1992 1993 1994 1995 1996 1997 1998 1999

Fig. 1: No. of typhoid cases reported inMalaysian from 1992 . 99'.

In Kelantan epidemics of typhoid are COlnmon5.

The annual incidence rates of typhoid in Kelantanshow a baseline endemicity of 20 to 30 cases per100,000 population".

Med 1 Malaysia Val 56 No 4 Dec 200 I

TYPHOID FEVER IN MALAYSIAN CHILDREN

Results

Table IEpidemiological Data of 102 children, withBacteriologically Confirmed Typhoid Fever,

Admitted to HUSM (1.10.93· 3l.ll.98)

There were a total of 9292 admissions topaediatric medical wards during the study period(this docs not include admissions to special carenurselY or neonatal intensive care); 159 of themwere treated for typhoid fever including 102 withcultures positive for S. typhi. Blood culture waspositive in 77, stool culture in 14 and both bloodand stool cultures in 11 childrcn (Table I). All theisolates of S. typbi were sensitive to commonantibiotics like ampicillin, chloramphenicol and

The emergence and spread of S. typhi resistant tomultiple antibiotics is now a subject ofinternational concern. Not only has it becomeendemic in many developing countries, causingenormous morbidity and exorbitant costs oftreatment, resistant Salmonella is also beingincreasingly reported from the developed world7,~.

This paper presents the results of a prospectivestudy, which was conducted over a period ofnearly five years in Hospital Universiti SainsMalaysia (HUSM), which is one of the two referralcentres for the state of Kelantan. The aim of thisinvestigation was to study the incidence andnature of complications of typhoid fever inchildren and also to identify the risk predictors /markers of these complications. We also reviewedthe published data about typhoid fever inMalaysian and other children.

Materials and Methods

A prospective study of childrcn withbacteriologically confirmed typhoid fever causedby S. typbi or Saimonella paratypbi (5.paratypbiJ, admitted to HUSM betwecn 1stOctober 1993 and 31st August 1998 wasconducted. Children with immune deficiency,malignancy, major congenital abnormalities orsyndromes, chronic illnesses like tuberculosis orchronic renal failure or receiving steroids wereexcluded from the study. Statistical analysis wasperfonned using Chi- squares test and statisticalsignificance was defined as P<O.05. Fishers exacttest was used where indicated. It was computedusing progt"amme "STATCALC calculator" insoftware package Epi-info 6.04b.

A diagnosis of hepatitis was made when thetransaminase levels were raised to at least twicethe normal value for that age group. Patients withpancytopenia were diagnosed to have bonemarrow suppression and a diagnosis of paralyticileus was based on clinical and radiologicalfeatures such as abdominal distension, absentbowel sounds, dilated bowel loops etc.

Med J Malaysia Vol 56 No 4 Dec 2001

Aver ageMale: femaleDuration of illness

before admissionPositive history of contactContact with siblingsContact wilh parentsContact wilh cousinsContact with othersPiped water supplyWell water supplyUsage of boiled water

for drinkingPositive blood culturePositive stool cultureBoth blood and stool

culture positiveDuration of hospitalisationFollow-upRate of complicationsNutritional status

>501h percentile10lh -50th percenlile3rd - 10lh percentile<3rd percenlile

91.3 (6 - 159 months)1.2: 111.5 11 - 35 days)

47%40%7%38%15%50%50%98%

771411

16.6 (3 -32days)50%33%

41%29%10%20%

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ORIGINAL ARTICLE

co-trimoxazole. These patients were seenthroughout the year including 3 small outbreaks:July 1997, October 1997 and March 1998.

A positive history of contact was obtained in 47(47%) cases and 20 (20%) children had theirweight less than 3rd percentile for age. Themedian age of these 102 children was 90.5months (range 6 - 159 months). The male tofemale ratio was 1.2:1 and average duration ofillness before admission was 11.5 days (range 1 35 days) (Table 1).

Apart from fever (n~90) other common symptomswere abdominal pain or discomfort (n~56),

diarrhoea (n~44) and cough (n~4l). On physical

Table IIClinical and Laboralory Findings' in 102

Children, wilh Bacteriologically ConfirmedTyphoid Fever, Admitted 10 HUSM

(1.IM3·31.8.98)Fever 90Abdominal pain or discomforl 56Diarrhoea 44Cough 41Headache 37Conslipation 24Hepalomegaly 85.3Splenomegaly 27.5Jaundice 6Anaemia (Hb <109/LI 31leukopenia Itotal white count <5x lO'/L) 15Leukocytosis Itotal white count>12x10'/LI 18Thrombocytopenia (platelet count <150xlO'/L) 26Pancytopenia 8TO >1/80 IWidal test) 62.5TH >1/80 IWidal test) 66.6IgG (typhidot test) 92.5IgM Ityphidot test) 80.0IgM Ityphidot. Mtest) 96.2, percentage

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examination 85.3% were found to havehepatomegaly, 27.5% splenomegaly and 6patients had iaundice (Table II).

Anaemia (haemoglobin <10 giL) was present in31%, leukopenia (total white count <5x1Q'/L)in 15%, leukocytosis (total white count>12x10'/L) in 18% and thrombocytopenia(platelet count <150x10'/L) in 26% of patients.Widal test was positive [T(O»1/80] in 62.5%and IgM using dot enzyme assay~ was detectedin 80% children Cfable II).

Half of the patients had received antibioticsbefore adlnission. After admission 54% weretreated with ampicillin and defervescencewas achieved after an average period of 6.2days (maximum up to 21 days) of treatment.They were hospitalised for an average of 16.6days (range 3 ~ 32 days) and half of themcame for at least one follow-up visit. Onepatient was treated surgically for bowelperforation and peritonitis and there was nomortality (Table I).

One third of patients developed complications(Table III). Anicteric hepatitis was the mostcomlllon complication followed by bone

Table IIIComplicalions' of Bacteriologically ConfirmedTyphoid Fever in 102" Children Admilled 10

HUSM (1.1M3 ·3l.8.98)Hepatitis 19Bone marrow suppression 8Paralytic Ileus 7Myocarditis 4Psychosis 4Cholecystitis 3Osteomyelitis 2Peritonitis 1Other complications 4, percentage" 12 patients developed multiple complications


Inarrow suppression, paralytic ileus,myocarditis, psychosis and osteomyelitis.Twelve patients developed multiplecomplications. These complications were notrelated to age of patient, duration of illnessbefore admission, nutritional status of patient,level of "0" or "H" titre, positivity for IgG or IgMor treatment with ampicillin or chloramphenicol.However patients with splenomegaly,thrombocytopenia or leukopenia were at higherrisk of developing these complications. Nearly54% of children with splenomegaly, 60% withthrombocytopenia, 70.6% with leukopenia,77.8% with both spleoomegaly and leukopeniaand 78.6% with splenomegaly andthrombocytopenia developed cOluplications(Table IV).


Discussion

It has been estimated that 12 - 33 million cases oftyphoid fever occur annually throughout thedeveloping world. It causes more than half amillion deaths every year, mainly in school goingchildren, and unless sanitaly and nutritionalconditions improve, it is impossible to eradicate thi<>disease1,JO. In patients whose cause of fever couldbe established/diagnosed, typhoid was reported tobe the second most common cause of fever inMalaysia". There was a range of 1715 to 2962reported cases from 1978 to 1990 with an annualincidence of 10.2 to 17.9 per 100,000 population"but the nUlnber of reported cases has graduallydropped to 818 in 1999' (Fig. I). In our study 1.7%of children admitted to paediatric medical wards ofHUSM were treated for typhoid fever.

Table IVFeatures Related to Rate of Complications' in 102 Children with Bacteriologically Confirmed

Typhoid Fever Admilled to HUSM (1.10.93 ·3l.8.98)Clinical and Laboratory Features Developed Complications No ComplicationsSplenomegalyYes 15 13No 17 52TrombocytopeniaYes 18 12No 15 53LeukopeniaYes 12 5No (normal WBC) 17 45Splenomegaly and thrombocytopeniaYes 11 3No 11 43Splenomegaly and leukopenia~s 7 2No 9 3653.6% of children with splenomegaly developed complications.60% of children with thrombocytopenia developed complications.70.6% of children with leukopenia developed complications.78.6% of children with splenomegaly and thrombocytopenia developed complication.77.8% of children with splenomegaly and thrombocytopenia developed complications.

Med J Malaysia Vol 56 No 4 Dec 200 I

p value

0.012

0.000

0.002

0.041

0.002

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ORIGINAL ARTICLE

Typhoid is mainly a disease of children. Thereported age incidence shows considerablevariation but most reports indicate a peak in thefirst two decades of life with clnphasis on the 5 15 year age range. In our study the average agewas 7.5 years (Table I). Chao et at in theirretrospective study of paediatric patients from thesame centre reported a mean age of 7.3 years3

,

Many reports stress the occurrence of typhoidfever in the under 5-year oids with up to 50% ofcases occurring in the first 2 years of life13 , Only 3of our patients were less than 2 years old. In astudy from India the incidence rate of typhoidfever per 1000 person-years was 27.3 at age under5 years, 11.7 at 5 - 19 years, and 1.1 between 19and 40 years14 , In a report form United States, 35%of patients suffering from typhoid were less than5-years old1s . Many investigators have reportedtyphoid in neonates16

,17. The youngest patientreported by Choo et at in their study fromKelantan was 48 days old5• In anotherretrospective study of Malaysian children,youngest patient reported was 2-month-olcPll. Aswe did not include neonates in our study, ouryoungest patient was 6-month old.

Humans are the only natural reservoirs of S. typhi.To get typhoid fever implicates a direct or indirectcontact with a patient or carrier of S. typhi. Nearlyhalf of our patients had positive histoly of contact(Table I). Majority of the contacts was withsiblings and cousins, not only showing higherincidence of disease in children but also relativelypoor hygienic habits in this age group. Choo et atreported a positive history of contact in 22.6% oftheir patients, a quarter of them had their firstdegree relatives suffering from typhoid fever3•

Male to female ratio in our patients was 1.2:1,which was similar to previous reports fr01llMalaysia3•

Hl•

All our patients were Malays (representative ofKelantan population) and half of them usedwell water at home. However 98% of them,when at honle, used boiled water for drinking.Eating out is quite COlllmon in Kelantan andthere is no strict control over "sporadic" food

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stalls. S. typhi not only spreads through waterbut also can be transillitted through raw or halfcooked food19

. During our study period therewere three small outbreaks and all of themwere related to "Kencluri" - the feast followingmarriage ceremony.

Of the 102 children, 41% had a body weight morethan 50th percentile for age and 20% had lessthan 3rd percentile. Similar findings werereported earlier from our centre3• It seelllS thatpoor nutritional status does not particularlypredispose children to this infection.

Nearly half of our patients came from families oflow socia-economic status (monthly income<RM500/month) and 1/3rd from families withhigh income (monthly income >RMI000/month).We also analysed data based on income perperson per month for these families (total incomeof the family - house rent / no. of family membersdependent on total inc01lle) and found similarresults. Nearly 18% of patients came from familieswith income >RM200/person/month, showingthat in Malaysia typhoid fever affects all classes ofsociety and apart from poor sodo-econ01llicstatus, also relates to life style and eating habits ofthe family.

Average duration of illness before admission tohospital was 11.5 days; some patients reportedafter up to 35 days of illness. Similar findings arereported in previous investigations related toMalaysian patients18

. Majority of population inKelantan lives in rural areas and prefers to receivetreatment from "Bomoh", the traditional healer,before seeking help froill general pwctitioners orhospitals20

. The average duration ofhospitalisation was 16.6 days. It was the hospitalpolicy to complete the antibiotic treatment(usually for two weeks) and get "stool clearance"(three stool specimens to be collected forSalmonella culture, first specimen 24 hours aftercompletion of antibiotic treatment) before patientis discharged from the hospital. For the samereason Choo et al 3 reported the mean duration ofhospitalisation of 17.2 days.

Med J Malay,;a Vol 56 No 4 Dec 200]

Seasonal Variations

It is believed that typhoid fever shows a seasonalpattern usually with greater prevalence in therainy season21

,21. In contrast Cboo et at in an earlierstudy from Kelantan reported a high incidenceduring the hot dry season''I. Yap el at did not findany seasonal variation but about half of theircases were admitted during dry months of May,June and Julyls. In our study patients were seenthroughout the year and there was no significantseasonal variations.

Symptoms and Signs

The concept of a 'typical' clinical picture inchildhood typhoid is inappropriate andmisleading. The severity and duration of illnessvaries greatly from child-to-child. As typhoid isboth a septicaemia and toxaemia, any tissue ororgan system can be involved in a variety of ways.At presentation, patient may be a sick lookingchild with 'toxic' appearance or a comfortablehealthy looking child who does not have anysymptom except fever.

Fever is the most constant presenting sYlnptom;90% of our patients presented with this complaint.Choo et al; reported fever in 100% and Yap et al18 in 98% of their patients. Fever is usually high(39 - 40°C) and may be intermittent or remittent.Rigors or chills may occur with high fever and itis safe to use acetalllinophen or ibuprofen tocontrol fever2.~, however generally it does notrespond to acetaminophen or there is only apartial response. As noted in previous reportsJ·13

we also did not find any evidence of relativebradycardia and none of our patients was foundto have rose spots,

Apart fr01ll fever the other common symptoms inour patients were abdominal pain or discomfortfollowed by diarrhoea, cough, vomiting,headache and constipation (Table II). In an earlierreport from our centreJ the five most commonsymptoms (apart from fever) included; diarrhoea,vomiting, cough abdominal pain and headache.

Med J Malaysia Val 56 No 4 Dec 200 I


Yap et at also reported similar frequency of theseclinical features l8

• Contrary to common belief,diarrhoea is a relatively common presentationthan constipation; 44% of our patients haddiarrhoea and only 24% presented withconstipation. Other authors3,l5,18 have reportedsimilar findings. However Sinha et al in theirprospective study in Delhi, did not reportdiarrhoea in their 5-year-old and above patientsand only in 14% of their younger patients14

.

Reported frequency of diarrhoea in typhoid feverreveals geographic variations of between 30% and50%21,22.24. Cough has been reported as a commonsymptom of typhoid fever in children3•

18 and ourinvestigation provided similar results (Table II).

Hepatomegaly (85.3% of patients) followed bysplenomegaly (27.5%) was the most commonclinical findings in our investigation. All thepatients who had splenomegaly also hadhepatomegaly. Two other investigations ofMalaysian children reported similar Hndings·\18.Sinha et al ,., reported splenomegaly in 26% oftheit 5-years-old and above patients and in 14% oftheir younger patients.

Diagnosis

To make a diagnosis of typhoid fever, blood andstool specimens of all 159 children, suspected tohave this illness, were cultured and only 102(64%) had positive results. Blood culture waspositive in 77, stool culture in 14 and both bloodand stool cultures were positive in 11 children(Table I). Since blood and stool cultures werepositive in the 1st, 2nd and 3rd week of illness,as also shown previouslyl.14, it is important toculture blood and stool regardless of the stage ofillness. All urine cultures were negative for S.typhi and similar results have been reportedpreviollsly as well". S. paratyphi A was isolatedform one patient.

As 54% of 159 children had received antibioticsbefore admission, our culture positivity rate waslow (64%). However it is interesting to note that50% of the children who were treated with

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ORIGINAL ARTICLE

antibiotics before admission had positive blood orstool culture. Many reasons including suboptimum doses taken by these patients canexplain this inconsistency. This findingunderscores the importance of cultures of S. typhieven in patients who had received antibioticsbefore admission.

Widal agglutination test was done in 96, typhidotin 80 and typhidot-M' in 26 of these 102 culturepositive patients. In Widal test "0" or "H" titre of2~1/80 was interpreted as positive (Tahle II). Ascontroversy surrounds the "significant levels" of"0" or "H" titre3,2~ it is not possible to compare theresults of different investigations. Chao et at 25

found that an "0" and lor "H" titre of 21/40carries a sensitivity and specificity of 89%. Yap etat chose higher titres of "0", yet 99% of theirpatients had positive Widal test18

•

The rise in "H" titres often higher than that of "0"titres, as seen in our children (Table II), was alsoreported previously3. Contrary to common beliefthat raised "0" titres are of higher diagnostic valuethan "H" titre6, Chao et at 27 found that a raised"H" titre is more sensitive than a raised "0" titreyet with a similar high specificity. Rise in hoth "0"and "H" titre was found to he of equalsignificance by other investigators lil

•

Typically Widal titres are believed to rise todiagnostic values in the second week of illness.Our investigations showed that significantnumber of patients achieved that titre within firstweek of illness. Other investigators have reportedsimilar findings 3,25,l6.

From the above discussion it is reasonable toconclude that: (1) Widal agglutination test is auseful diagnostic tool, (2) the length of history offever does not affect the initial Widal titre inculture positive cases and (3) rise in both "0" and"H" should be given equal significance.

Typhidot and Typhidot-M tests detect antibodiesto a 50-kD outer membrane protein of S. typhi 29•.'l0.These IgM and IgG antihodies persist in

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circulation for 2.6 and 5.4 months respectively'll.These tests were developed in School of MedicalSciences of Universiti Sains Malaysia32 and havebeen evaluated by many investigators9•.'1.'I. Resultsof these tests in our patients are summarised inTable II. Our findings of usefulness of these testsand their superiority to Widal test both in earlyand later part of illness confirm the results ofearlier reports.

Haematological Abnormalities

Haematological derangements are common intyphoid fever. Significant changes includeanaemia, leukopenia, eosinophilia, thrombocytopeniaand sub-clinical disseminated intravascularcoagulation3

,j. Anaemia and thrombocytopeniawere the most common abnormalities in ourpatients (Table II). Majority had normal leukocytecount. Yap et al reported similar results in theirpaediatric patients'". Slightly higher figures werereported from our centre previously'l. None of ourpatients developed clinical manifestations ofdisseminated intravascular coagulation.

Children with typhoid, initially not anaemic, mayrapidly develop severe anaemia because ofcombination of haemolysis, toxic marrowdepression and occult blood 10ss13. Anaemia inour patients may not be entirely due to typhoidfever, as we did not investigate these patients forother causes but none of them had frank rectalbleeding or had occult blood positive in theirstools. Khosla et al 34 reported similar results intheir adult patients except leukopenia, which wasmore common in their series.

Treatment and Outcome

Although resistance to common antibiotics hasbeen reported'l5..'16

, it is not a major problem inMalaysia like other countries14,15,37,38. All theisolates in our investigation were sensitive tocommonly used antibiotics (ampicillin,chloramphenicol, co-trimoxazole). During ourstudy period it was the hospital policy not to use


the cephalosporin group of antibiotics fortreatment of typhoid fever. Chloramphenicol andampicillin were used without any specific criteriafor their selection. Fifty four percent of ourpatients were treated with ampicillin and restwith chloramphenicol. Both these antibioticswere tolerated well by children without anysignificant side effects. In only one patient, whodeveloped pancytopenia after hospitalisation,treatment was changed from chloramphenicol toampicillin. There was no mortality or permanentdisability. Clinical and bacteriological relapseoccurred in 4 (4%) patients. All of them wereinitially treated with ampicillin and weresuccessfully retreated with the same antibiotic.Other investigators l8 have reported similarincidence of relapse. Two patients becamecarriers and were being followed up closely. Dueto intermittent excretion of s. ~yphi in stool ofcarriers and with poor follow-up rate (50% in thisstudy), the carrier rate in our study is likely to bean underestlinate.

Complications

Reports based on retrospective data have shownthat complications of typhoid fever are C01nmonboth in children3 and adults39• However somecomplications are more common in children thanin adults13 .

The incidence of c01nplications of typhoid fever(both in adults & children) is reported from 13%to 38%·w. In our investigation, 1/3 of culturepositive children developed complications(Table 1II). Anicteric hepatitis was the mostcommon complication followed by bonemarrow suppression, paralytic ileus,myocarditis, psychosis and cholecystitis. Chao etal 3 in their retrospective data fro1n the samearea in 1988 reported gastritis, bronchitis, ileus,psychosis, encephalopathy, gastrointestinalbleeding and myocarditis as complications oftyphoid fever in children.

Med J Malaysia Vol 56 No 4 Dec 2DO 1


Hepatitis

The documented incidence of hepatitis in typhoidfever (both in adults and children) varies widelyfrom less than 1% to 26% of patients39 . In ourinvestigation 19% of children developed thisc01nplication. Six of these patients wereinvestigated for other viral causes of hepatitis(hepatitis A, B, C & E virus) and were found to benegative. The liver function tests were repeated in3 of these children before being released fromhospital and were documented to be normal. Ofthese 19 children, 11 were males, blood culturewas positive in 17 and 12 of them were treatedwith ampicillin. Only 4 patients developed clinicaljaundice. The level of serum bilirubin was low ornormal in majority of patients, which may explainthe failure to identify this complication in aretrospective study conducted earlier in the samecentre-~. Seven of these patients developedmultiple complications.

In contrast to the previous vievt°, in our study,development of this complication was not relatedto delay in treatment, nutritional status or sex ofpatients and clinical jaundice was not a commonfeature however hepatomegaly was detected inall of these patients.

Bone Marrow Suppression

Eight of our patients who presented withpancytopenia were diagnosed to have bonemarrow suppression. The blood culture waspositive in 7 and stool culture in 2 of thesepatients; 5 of them were males. These childrenwere not investigated for other causes ofpancytopenia but all of them had normal bloodcounts at the end of treatment for typhoid fever.As samples for blood investigations werecollected hefore treatment with antibiotics wasstarted, pancytopenia was therefore unlikely dueto chloramphenicol therapy. Two patients withpancytopenia, who were treated withchloramphenicol under close 1nonitoring,

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ORIGINAL ARTIClE

responded well to the treatment. One patient whodeveloped pancytopenia after receivingchloramphenicol is not included in this group.

Gastrointestinal Complications

Salmonella infection in the gut involves localinflammation, lymphatic absorption of toxins anddirect pOliai spread of infection so that there isintestinal infection of variable extent. Intestinalperforation and paralytic ileus are corrunonlyreported complications. Intestinal perforation canoccur at almost any time and Inay be theprecipitative cause for admission41

, In our seriesperitonitis was diagnosed in only one patient whowas directly admitted to paediatric surgical wardand needed laparotomy. Seven other patientsdeveloped paralytic ileus (Table III) and weretreated conservatively with tluids, electrolytes andantibiotics. All our patients recovered completely.

Myocarditis

Electrocardiographic changes suggestive ofmyocarditis are rather common in typhoid feverbut the incidence of true myocarditis is low bothin adult patients'12 and children. Yap et al in theirretrospective study of 54 Malaysian children didnot report any case of Inyocarditis Jil

• We made thediagnosis of myocarditis based on clinicalfeatures, EeG changes and echocardiographyfindIngs and only 4 children fulfilled the criteria.A previous study from the saIne institutionreported only one of 137 children developing thiscomplication3•. On the other hand in anotherseries from Kelantan l Kean et al reported EeGabnormalIties In half and myocarditis in 1/3 oftheir 60 patientsH . This discrepancy could be dueto difference in definition of myocarditis as wellas in methodology of studies.

Psychosis

Four children who presented with emotionalupset and derangement of personality and loss ofcontact with reality and with delusions,

486

hallucinations or illusions were diagnosed to havepsychosis. These symptoms were not related todrug ingestion and settled within few days aftertreatment for typhoid was started. Noantipsychotic drugs were used for treatment inthese children.

Neuropsychiatric complications have beenreported in from as low as 2.3% to as high as 84%of typhoid patients, with acute psychosis in 0.6%of these patients'H. In an earliec retrospectivestudy from our centre, psychosis was reported in2.2% of paediatric patients3• None of our patientsdeveloped other reported neuropsychiatriccOlnplications such as cerebellitis, meningoencephalitis, aphasia or deafness"".Neuropsychiatric complications have beenreported more CQnlmon in patients withmultidrug-resistant S. ~yphi infection'l\ none of ourpatients had infection with resistant S. typhi.

Cholecystitis

Enteric fever associated with cholecystitis has areported incidence of 2.8% to 12.5%; 60% of thesepatients have acalculus diseasel,5. It is usually dueto toxic dilatation of gallbladder. In our seriesultrasonography was performed on patients withone or luore of the following features: righthypochondrial or diffuse abdominal pain;abdominal distension, tender hepatomegaly;positive Murphy's sign or a palpable gallbladder.Based on the presence of increased gallbladdersize, gallbladder thickness and other findings46 adiagnosis of acalculus cholecystitis was lnade in 2patients. Both of these children were also ictericand had elevated seruin alkaline phosphataselevels and were managed conselvatively. One ofthese patients had elevated transaminase levelsbringing in the possibility of hepatitis as well.Another patient who presented with ilealperforation and peritonitis was, on laparotomy,found to have gangrenous necrosis of gallbladder.S. typbi was cultured from the gallbladder fluid inthis child. A similar case of a Malaysian patientwas reported earlierHl

• In another earlierretrospective study of 137 typhoid patients frolu


our centre cholecystitis was not reported as acomplication3 . With the widespread use ofabdominal ultrasonography, acute acalculuscholecystitis in typhoid fever is becomingincreasingly easy to recognise.

Osteomyelitis

Salmonella usually causes osteomyelitis inpatients with sickle cell disease"7, haematologicalmalignancy or with pre-existing bone pathology;sites usually affected are femur or tibia. Two ofour patients developed this complicationaffecting th~ir tibiae. One patient had congenitalaniridia and optic atrophy of the right eye. Therewas no evidence of Wilm's tumor or any othermalignancy in this patient. The other patient hadevidence of haemolytic jaundice (jaundice withhaemoglobinuria and increased reticulocytecount). His G6PD level was normal and therewas no evidence of thalassaemia, spherocytosisor sickle cell disease and actual cause ofhaemolysis could not be established. Histransaminase levels were raised but screening forhepatitis vinlses was negative. In the course oftreatment this patient developed pancytopeniaand the treatment was changed fromchloramphenicol to ampicillin. Choo et al in theirretrospective study from our centre did not reportany case with this complication3

.

Other Complications

Other complications in our patients included:pneUlllonia, haemolytic anaemia, and syndromeof inappropriate release of antidiuretic hormone(SIADH). Many pulmonary complications oftyphoid fever such as bronchitis, pneumonia, lungabscess, empyema and adult respiratory distresssyndrome (ARDS) have been reported".Pneumonia may occur very early in the diseaseand may indeed be the presenting feature or mayarise later. Radiological evidence of pneumoniaoccurs in up to 1/3 of cases and may be evidentin 50% or more of autopsies on fatal cases!!.Surprisingly very few pulmonary complications

Med J Malaysia Val 56 No 4 Dec 2001


have been reported in Malaysian patients. Choo etal reported bronchitis in 3.7% of their paediatricpatients'. Yap et al did not report any pulmonarycomplication in their series1

!!. In many patientswho have other complications of typhoid feverpneumonia may be an indirect complication or"complication of a complication". Only onepatient in our series developed pneumonia butthis patient also had paralytic ileus and mighthave developed pneumonia due to aspiration.

I-Iaemolysis is a rare reported complication oftyphoid fever4'. Probably if all cases ofanaemia due to typhoid fever are investigated,more patients may be identified to havehaemolysis as it contributes to development ofanaemia in typhoid feverB

. One of our patientsdeveloped this complication. This patient hadother complications as well but there was noobvious predisposing factor for haemolysis inthis patient.

Two of our patients developed SIADH andboth of them had other complications as well.Both these patients developed severehyponatraemia «120mmo1!L) and were foundto have low plasma osmolality. Chao et al intheir retrospective study reportedhyponatraemia «130mmo1!L) in 16.1% of theirpatients'. It was not possible to establishwhether SIADH was a direct or indirectcomplication in our patients.

Predictors of Complications

Following factors did not influence the rate ofcomplications in our patients: age at admission,duration of illness before admission, use ofantibiotics before admission, nutritional status ofpatient at the time of admission, level of "0" or"E" titre, presence or absence of IgM or IgG andtreatment with chloramphenicol or ampicillinafter admission.

However it was found that a child withsplenomegaly, leukopenia or thrombocytopeniahad higher risk of developing a complication. A

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ORIGINAL ARTICLE

child with both splenomegaly andthrombocytopenia or leukopenia had nearly 2.5times higher risk of developing a complication(Table IV).

From above discussion it is concluded that (1)

complications of childhood typhoid fever are

common, (2) anicteric hepatitis, bone marrowsuppression and paralytic ileus are three mostcommon complications and (3) a child withsplenomegaly, leukopenia or thrombocytopeniais more likely to develop complications.

10. Institute of Medicine. New vaccine development:establishing priorities. Vol II. National AcademicPress. Washington DC, 1986.

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