consecutive patients > 2 years of age with fever ( > 38c tympanic ) who came to teaching hospital karapitiya were enrolled ( 8) .
standardized epidemiologic and clinical data and blood were obtained during acute illness and 24 weeks later . during the study ( march  october 2007 ) , the atmospheric temperature ranged from 27.5c32c ( high ) to 24c26c ( low ) , and rainfall was variable ( mean 301 mm / mo , range 36657 mm / mo ) . because rickettsial species broadly cross - react within groups ( 9,10 ) , paired serum samples were tested by using an igg indirect immunofluorescence assay ( ifa ) and rickettsia rickettsii and r. typhi antigens ( focus diagnostics , cypress , ca , usa ) to identify infections with spotted fever group ( sfgr ) and typhus group ( tgr ) rickettsial infections .
serum samples reactive at a titer of 80 were considered potentially positive and were titered . to identify scrub typhus ( st ) infections , we tested paired serum samples using igg elisa as described ( 11 ) , except for use of recombinant antigens ( 0.2 g each of r56 chimeric1 , gilliam , and kato strains ) to detect antibodies to orientia tsutsugamushi .
comparative blind testing of 200 serum samples with an established ( pooled - antigen ) quantitative assay enabled validation ( 12 ) .
acute rickettsioses ( sfgr , tgr , and st ) required a > 4-fold rise in specific igg titer or its equivalent ; patients with equal sfgr and tgr convalescent - phase titers were sfgr / tgr group - indeterminate .
igg ( titer > 160 ) in acute - phase serum defined rickettsial exposure ( seroprevalence ) .
stata ic version 11.0 ( statacorp lp , college station , tx , usa ) was used for analyses .
we analyzed paired serum samples for rickettsioses for 883 ( 81.9% ) of 1,079 patients .
median acute  convalescent phase follow - up was 21 days ( intraquartile range 1533 days ) .
acute rickettsioses were documented in 156 ( 17.7% ) patients ( table 1 ) . the increase in convalescent - phase geometric mean titer was 14-fold ( 845 ) for sfgr , 17-fold ( 920 ) for tgr , and 11-fold ( 951 ) for sfgr / tgr rickettsiae .
sfgr , spotted fever group rickettsiae ; tgr , typhus group rickettsiae ; iqr , intraquartile range ; anc , absolute neutrophil count ; alc , absolute lymphocyte count . 
n = 309 ; 6/6 with rickettsioses and rash had eschars , compared with 11/22 of those without rickettsioses ( p<0.001 ) .
acute rickettsioses were found in 19.7% of patients > 18 years of age and 10.5% of patients < 18 years of age ( p = 0.003 ) ; patients with rickettisoses were older than those without rickettsioses ( median age 34.5 vs. 28.0 years ; p = 0.005 ) ( figure 1 ) .
among patients < 18 years of age , acute rickettsioses were more common in male than in female patients ( 14.6% vs. 5.8% ; p<0.05 ) .
patients with acute st alone were older than those with other rickettsioses and those without rickettsioses ( median 36.5 vs. 34.4 vs. 28.0 years ; p = 0.02 ) and more likely to report rice paddy exposure ( 44.4% vs. 15.1% vs. 9.3% ; p = 0.001 ) .
more acute rickettsioses occurred during the july  october rains ( 70.6% of st infections and 59.7% of other rickettsioses ) , whereas more nonrickettsial infections ( 67.0% ) occurred during the drier period of march  june ( p<0.0001 ) ( figure 2 ) .
proportion of febrile patients with acute rickettsial infections by age group , southern sri lanka , 2007 .
proportion of febrile patients with acute rickettsial infections by month , southern sri lanka , march 
acute rickettsioses were clinically similar to each other and to nonrickettsial febrile illnesses , except for frequency of cough , oliguria , and conjunctival suffusion ( table 1 ) . except for a higher temperature with sfgr than with tgr infection ( mean 38.6 vs. 38.2c ; p = 0.006 ) ,
conjunctival suffusion was more common ( p = 0.004 ) with st ( 35.3% ) than with sfgr / tgr ( 12.8% ) or no rickettsiosis ( 12.8% ) .
antecedent antimicrobial drug use was commonly reported in patients with ( 45/115 [ 39.1% ] ) and without ( 195/536 [ 36.4% ] ; p = 0.58 ) rickettsioses .
amoxicillin and cephalosporins were administered most frequently in both groups ( 16.8% and 20.3% ; p = 0.40 ) , but infrequent administration of doxycycline ( 0.9% and 1.1% ; p = 0.82 ) was recorded for 813 patients with paired serum samples , including 139 with acute rickettsioses .
rickettsioses were rarely clinically identified when present ( 3/139 , sensitivity 2.2% , 95% ci 0.447% 6.2% ) .
rickettsioses were also infrequently confirmed when diagnosed clinically ( 3 sfgr rickettsioses among 9 with suspected scrub typhus ; positive predictive value 33.3% , 95% ci 7.5 70.1 ) and rarely treated appropriately ( 2/9 given doxycycline , 1 with sfgr rickettsiosis ) .
patients with rickettsioses were hospitalized longer than others ( median 5 vs. 4 days ; p = 0.01 ) , although the proportion hospitalized was similar .
no one with confirmed rickettsioses died , but 11 of 12 patients died before follow - up . at enrollment , 292 ( 33.1% )
however , only 59 ( 20.2% ) had a 4-fold increase in titer , and 97 ( 62.2% ) of 156 acute infections were identified as rickettsioses by seroconversion .
exposures to rodents and rice paddies were associated with tgr rickettsiae and o. tsutsugamushi igg ( table 2 ) .
farmers were more likely ( p = 0.01 ) to have igg against o. tsutsugamushi ( 5.7% ) than sfgr / tgr rickettsiae igg alone ( 4.3% ) or no rickettsial igg ( 1.5% ) .
if igg titer > 160 at either sampling were used to denote rickettsial exposure ( preexisting or acute ) , 342 ( 38.7% ) patients had exposure to sfgr and/or tgr rickettsiae . if a lower titer ( > 80 ) were used , 398 ( 45.1% ) had such exposure . similarly , 121 ( 13.7% ) patients had either acute- or convalescent - phase igg against o. tsutsugamushi .
sfgr , spotted fever group rickettsiae ; tgr , typhus group rickettsiae ; iqr , interquartile range . 
we documented endemic rickettsioses as a major cause of acute febrile illness in southern sri lanka .
underrecognition of rickettsioses could reflect nonspecific clinical features , limited diagnostic tools , lack of awareness that rickettsioses occur or cause severe illness , and absence of evidence - based local algorithms for acute febrile illness .
studies in neighboring regions have used flawed methods , including spectrum bias , small sample size , selective enrollment , and testing acute - phase serum only . in many instances ,
clinical features were not predictive ( 5,13 ) ; however , older age was reported with rickettsioses ( 14 ) and lymphadenopathy and rapid respiratory rate with st compared with tgr rickettsiosis ( 4 ) .
although part of the rickettsial triad , rash is often absent initially ( 10 ) and among unselected febrile patients ( 5,14 ) .
sfgr / tgr cross - reactions and apparent co - infections could also impair clinical differentiation of specific rickettsioses .
laboratory abnormalities associated with st ( 3 ) could reflect disease severity , not etiology , and such testing is often unavailable .
divergent conclusions might reflect different study populations , diagnostic criteria , reference groups , features evaluated , or real geographic differences .
confirmation required follow - up ( return or home visit ) ; the us centers for disease control and prevention no longer accepts a single high titer to confirm r. rickettsii infection ( 10 ) . we required a 4-fold rise in titer even for seroconversions because ifa results are subjective , even among experts .
we used r. rickettsii as a surrogate antigen , which could be less sensitive for detecting local sfgr .
we chose elisa for st because a commercial ifa was not available and ifa as a standard for st has been questioned ( 15 ) .
optimal clinical management of acute rickettsioses requires development of locally tested , evidence - based algorithms for acute febrile illness .
 we studied rickettsioses in southern sri lanka . 
 of 883 febrile patients with paired serum samples , 156 ( 17.7% ) had acute rickettsioses ; rickettsioses were unsuspected at presentation . 
 additionally , 342 ( 38.7% ) had exposure to spotted fever and/or typhus group rickettsioses and 121 ( 13.7% ) scrub typhus . 
 increased awareness of rickettsioses and better tests are needed . 
The Study
Conclusions