since 1998 , the icddr , b centre for health and population research has operated a surveillance and intervention site in kamalapur , an urban slum in dhaka , bangladesh . we initiated fever surveillance for dengue fever and dengue hemorrhagic fever in august 2000 . to identify treatable causes of fever , we obtained blood cultures from december 6 , 2000 , to october 8 , 2001 . we selected the surveillance cohort by using stratified cluster randomization and obtained informed written consent from all households . field research assistants screened household members for fever in their homes once weekly with a standardized questionnaire . we defined fever as > 3 consecutive febrile days ( reported ) for persons > 5 years of age , or any duration of fever for preschool children ( < 5 years of age ) . field research assistants referred febrile participants to our field clinic , where study physicians confirmed fever and collected clinical data by using a standard form . patients with an axillary temperature of > 38c were designated as febrile . after collecting blood for serologic tests of dengue and dengue hemorrhagic fever , we collected an additional 1 ml of blood from preschool children and > 3 ml from older persons for culture . blood cultures were transported within 2 hours to our clinical microbiology laboratory ( 12 km from the field clinic ) . specimens were processed by using standard methods with in - tube lysis centrifugation ( wampole isolator 1.5 , carter - wallace , inc . , cranbury , nj , usa ) , plated on blood , chocolate , and macconkey agar and incubated at 37c for 16 to 18 hours . colonies were evaluated with biochemical tests and confirmed by serologic identification with commercial antisera ( denka , sieken , co. , ltd . , we confirmed typhoid fever if we isolated s. typhi from blood during a febrile episode . febrile controls were culture - negative for s. typhi , paratyphi , or salmonella group d during fever . if s. typhi was isolated , then we treated the infection with 14 days of standard therapy , adjusting for antimicrobial susceptibility . first - line drugs were amoxicillin ( 40 mg / kg up to 1,500 mg orally divided 3 times daily ) or cotrimoxazole ( 10 mg / kg trimethoprim divided into 2 daily doses ) . when patients remained febrile after 72 hours or new danger signs ( e.g. , lethargy , inability to drink , cyanosis , convulsions ) , developed , treatment was considered to have failed . we treated treatment failure in persons > 12 years of age with ciprofloxacin ( 500 mg orally twice a day ) and referred younger patients to the hospital . statistical analysis was performed by using stata / se release 8.2 ( stata statistical software : release 8.0 . incidence was determined by dividing the number of cases by person - years of observation , with calculation of exact 95% confidence intervals ( cis ) . univariate analysis was performed by using 2-by-2 tables for relative odds ( ro ) and 95% cis . multivariate modeling was conducted by stepwise forward logistic regression , using all covariates significantly associated with typhoid fever in univariate analysis . covariates that were significant when age , sex , and geographic location were controlled for , were retained in the final model . we adjusted models for clustering of repeat patient visits and tested for goodness - of - fit with either pearson or hosmer - lemeshow methods ( 12 ) . research review and ethical review committees of icddr , b approved this study . during the study period , we took blood for culture from 888 ( 99.9% ) of 889 eligible study participants ; 54 ( 6.1% ) reported prior medication exposure . no positive culture reported > 1 organism ( table 1 ) , nor did any culture - positive patient have laboratory - confirmed dengue . s. typhi was isolated from 26 preschool children ( figure 1 ) and 23 older study participants ( age range 10 months50 years , median 4.0 years [ 95% ci 3.08.0 ] ) . there were 1,393 person - years of observation for preschool children and 11,014 for others . typhoid fever incidence among preschool children was 18.7 episodes/1,000 person - years and 2.1 episodes/1,000 person - years among older participants . the incidence rate difference between the 2 age groups was 16.6 cases/1,000 person - years ( 95% ci 9.423.8 ; p < 0.001 ) . preschool children 's relative risk for typhoid fever was thus 8.9 ( 95% ci 4.916.4 ) . typhoid fever among preschool children varied by age , with 4% in the first year of life and 85% occurring in those 2 to 4 years of age ( figure 2 ) . we investigated surveillance bias resulting from fever definition differences between age groups ( 4 ) . preschool children 's mean fever duration ( days ) prior to visiting the clinic was 4.0 ( 95% ci 3.24.8 ) and other patients ' mean duration was 4.9 ( 95% ci 2.96.8 , p = 0.37 ) . we collected 84.6% of preschool specimens and 78.3% of others ' after 3 febrile days , and 96.2% and 86.7% , respectively , by day 7 . a multivariate model showed that typhoid fever patients were more likely than febrile controls to be preschool age ( ro 2.04 ; 95% ci 1.093.82 ; p = 0.03 ) , have > 3 days of fever ( ro 2.55 ; 95% ci 1.165.63 ; p = 0.02 ) , have temperature > 39c ( ro 1.95 ; ci 1.013.80 ; p = 0.04 ) , and have mental status changes ( ro 3.94 ; ci 1.987.81 ; p < 0.02 ) . another model indicated preschool typhoid fever patients were significantly more likely than older patients to have fever > 39c ( ro 1.62 ; ci 1.212.17 ) , mental status changes ( ro 3.54 ; ci 2.255.55 ) , and crepitations ( rales ) on auscultation ( ro 4.44 ; ci 3.116.33 ) . all patients with culture - confirmed typhoid fever recovered , except for 1 child with tuberculosis . no hospitalizations , complications , or deaths occurred among confirmed typhoid fever patients . in vitro antimicrobial susceptibility testing ( table 2 ) showed a high prevalence of ampicillin , cotrimoxazole , and chloramphenicol resistance , with 27 isolates ( 55.1% ) resistant to all 3 ; ceftriaxone resistance was found in isolates from 1 preschool child . our data indicate a high infection ratio in this urban population , which is highest among preschool children . these ratios are comparable to recent regional reports ( 4,6,13 ) and indicate that typhoid fever in preschool children may be underappreciated . that preschool children have 8.9 times the risk for s. typhi infection as older persons corroborates age - specific rates in highly disease - endemic areas ( 1 ) . the antimicrobial susceptibility data indicate high ratios of in vitro resistance to standard antimicrobial agents , with a high prevalence of multidrug resistance . the degree of illness of preschool children is controversial ; some report benign bacteremia ( 5,14 ) and others have found clinical illness ( 4,13 ) . coexisting conditions , particularly pneumonia , are not only more common in preschool typhoid fever patients but also may result in misclassification and underreporting , as well as contribute to a worsening cycle of repeated infection and deaths . substantial clinical illness among preschool children argues the need for them to be enrolled in vaccination programs . the age - specific infection rates suggest vaccination in the first year of life , integrating with existing expanded programme on immunization ( epi ) schedules . this practice would require either a polysaccharide protein - conjugate vaccine to stimulate t - cell  dependent responses ( 15 ) or a live attenuated oral vaccine , since t - cell  independent responses do not mature until the child is 1824 months of age . the limitations of this study could result in an underestimate of the incidence of typhoid fever . first , this study was not designed to measure typhoid fever incidence or disease impact . although we did not find evidence of preferential selection for young children , future studies may adopt a common fever definition . second , the blood volume examined , though not inadequate , may not have been optimal . third , blood culture sensitivity is relatively low , estimated at 25%50% ( 1 ) . fourth , the 6.1% estimate of earlier medicine exposure may be an underestimate , as we did not validate these reports . if these agents were antimicrobial , the number of serovar typhi isolates recovered from peripheral blood would be reduced . fifth , we had only 10 months of observation and therefore did not attempt an estimate of disease impact , adjustments for blood culture sensitivity , or exposure to antimicrobial agents .
we confirmed a bacteremic typhoid fever incidence of 3.9 episodes/1,000 person - years during fever surveillance in a dhaka urban slum . 
 the relative risk for preschool children compared with older persons was 8.9 . 
 our regression model showed that these children were clinically ill , which suggests a role for preschool immunization .