invasive gas disease was defined as the isolation of streptcoccus pyogenes from a normally sterile site ( e.g. , blood , cerebrospinal fluid , pleural fluid , peritoneal fluid , pericardial fluid , joint fluid , surgical specimens , bone , and scrotal fluid ) in a noninstitutionalized resident , > 18 years of age , in a surveillance area . persons who had group a streptococcus isolated from a sterile site more than 48 hours after hospital admission were presumed to have a nosocomial infection ( 5 ) and were excluded . cases of invasive gas disease were identified through active , laboratory - based surveillance in three areas : metropolitan atlanta , georgia , from july 1 , 1997 , through june 30 , 1999 ; metropolitan baltimore , maryland , from july 1 , 1997 , through june 30 , 1999 , and the toronto - peel region , ontario , canada , from july 1 , 1997 , through december 31 , 1997 . the surveillance area population was estimated to include 9 million people ( 3,627,184 in metropolitan atlanta , 2,436,239 in the baltimore metropolitan area , and 3,008,570 in the toronto - peel region based on 1997 bureau of census estimates ) . all acute - care hospitals and laboratories serving the residents of the surveillance area were contacted biweekly and audited semiannually to identify patients with invasive gas disease . a case algorithm  was used to contact persons infected with invasive gas infection . for each case - patient identified , up to 15 separate telephone calls were made to contact the patient . to maximize the likelihood of contacting the case - patient , the telephone calls were made on 5 nonconsecutive days , including at least 1 weekend day , during each of three different time periods ( 8 a.m.noon ; noon5 p.m. ; 5 p.m.8 p.m. ) . the party was considered unavailable for that call if the telephone was allowed to ring 10 times or if an answering machine picked up the phone . persons still hospitalized when the case was identified were interviewed by phone in the hospital when feasible . case - patients were eligible if their enrollment was complete within 3-months of onset of their gas disease . non  english - speaking patients were included if the individual surveillance sites had the resources to communicate with the patients in their language . a population - based sample of matched control subjects was selected through a process of systematic , sequential - digit telephone dialing . case - patients and control subjects were matched by age group , postal or zip code , and telephone exchange . age groups were defined as follows : 1844 years of age , 4564 years of age , and > 65 years of age . matching was done on postal or zip code and telephone exchange to control for socioeconomic status . because control - subjects were identified by telephone interview , case - patients who did not have a telephone were excluded . control identification began after a case - patient had been identified , confirmed as eligible , and enrolled in the study . phone numbers for control subjects were generated by incrementally adjusting the enrolled case - patient s home phone number . for example , if an enrolled case - patient s telephone number ended in 1234 , the first phone number used to identify a control had the same area code and exchange and ended in 1235 . the numbers generated for control subjects were called a maximum of four times over several days . calling continued until 1 ) a minimum of two control subjects were enrolled per case - patient , and 2 ) all numbers that had been called at least once completed the control algorithm . as a result , more than two control subjects were enrolled for some case - patients . the purpose of completing the control algorithm was to ensure that the control group was not biased towards households that were easier to contact . when experienced surveillance personnel reached the case - patient or control subject , they explained the purpose of the study , obtained informed consent , and administered a standardized questionnaire . this study was approved by the institutional review boards at the centers for disease control and prevention and at each of the sponsoring institutions . the questionnaire included demographic information , socioeconomic status , smoking status of the interviewee , smoking status of other persons in the home , medical history , and history of alcohol and injecting drug use . within the medical history section , we differentiated between  regular  nonsteroidal antiinflammatory drug ( nsaid ) use and  new  nsaid use . new nsaid use implied that the case - patient had started using nsaids in the 2 weeks before their illness or that a control subject had started using nsaids in the 2 weeks before their interview . each case - patient and control subject were allowed to self - define  regular use  of nsaids . to screen for alcoholism , we used the cage questionnaire in which a subject is asked four questions about his or her relationship to alcohol . the likelihood of alcoholism increases with the number of times the person answers  yes  ( 7 ) . the questionnaire also asked about contact with other persons in the home , contact with children , contact with persons exhibiting symptoms of gas disease in the home , contact with other persons at work , and contact with persons with symptoms of gas disease at work . to evaluate contact with other persons in the home , the questionnaire included questions about number of persons in the home , crowding in the home ( number of persons per room ) , type of home , age of all persons living in the home , and types of relationships with all persons living in the home . to evaluate contact with children , the questionnaire asked about the number of children in the home ( i.e. , persons < 18 years of age ) , amount of time spent with children in the home , frequency of certain types of sharing behavior with children in the home ( including eating off the same plate , sharing a beverage , sleeping in the same bed ) , amount of time spent with children who did not live in the home , and frequency of sharing behavior with children who did not live in the home . the questionnaire asked whether anyone in the home had been ill in the 2 weeks before the case - patient s illness or the control subject s interview by asking about specific types of illnesses . for example , the questionnaire asked  has anyone in your household , other than yourself , had a sore throat ?  if the interviewee said yes ,  he or she was asked how many children and how many adults had a sore throat during that period . the questions asked whether anyone in the home had a sore throat ; fever ; new cough ; new runny nose ; skin infection ; a diagnosis of strep throat , an ear infection , or a sinus infection ; or died . to measure the severity of the illness , the questionnaire asked whether the ill person(s ) had visited a doctor , missed school or work , had taken antibiotics , or had been hospitalized . to evaluate exposure to both persons at work and symptomatic persons at work , the questionnaire asked which type of environment the case - patient or control subject worked in , how many hours she or he worked , how many persons were in their work environment , and whether anyone at work had been ill in the 2 weeks before the case - patient s illness or control subject interview by asking about specific types of illnesses . the questions were asked in the same manner as those asked of persons in the home . odds ratios ( ors ) for each potential risk factor were determined by using conditional logistic regression ( proc phreg , sas version 6.12 , cary , nc ) , controlling for sex and race . these ors were determined separately for age groups 1844 years of age and > 45 years of age to identify age - dependent risk factors . those variables found to have a p value > 0.20 in individual analyses were included in multivariable analysis . computer - assisted and manual forward , backward , and stepwise conditional logistic regression was done to identify risk factors independently associated with invasive gas disease . ors with 95% confidence intervals ( cis ) that do not include 1.00 , and p values < 0.05 were considered statistically significant in multivariable analysis . the questionnaire included demographic information , socioeconomic status , smoking status of the interviewee , smoking status of other persons in the home , medical history , and history of alcohol and injecting drug use . within the medical history section , we differentiated between  regular  nonsteroidal antiinflammatory drug ( nsaid ) use and  new  nsaid use . new nsaid use implied that the case - patient had started using nsaids in the 2 weeks before their illness or that a control subject had started using nsaids in the 2 weeks before their interview . each case - patient and control subject were allowed to self - define  regular use  of nsaids . to screen for alcoholism , we used the cage questionnaire in which a subject is asked four questions about his or her relationship to alcohol . the likelihood of alcoholism increases with the number of times the person answers  yes  ( 7 ) . the questionnaire also asked about contact with other persons in the home , contact with children , contact with persons exhibiting symptoms of gas disease in the home , contact with other persons at work , and contact with persons with symptoms of gas disease at work . to evaluate contact with other persons in the home , the questionnaire included questions about number of persons in the home , crowding in the home ( number of persons per room ) , type of home , age of all persons living in the home , and types of relationships with all persons living in the home . to evaluate contact with children , the questionnaire asked about the number of children in the home ( i.e. , persons < 18 years of age ) , amount of time spent with children in the home , frequency of certain types of sharing behavior with children in the home ( including eating off the same plate , sharing a beverage , sleeping in the same bed ) , amount of time spent with children who did not live in the home , and frequency of sharing behavior with children who did not live in the home . the questionnaire asked whether anyone in the home had been ill in the 2 weeks before the case - patient s illness or the control subject s interview by asking about specific types of illnesses . for example , the questionnaire asked  has anyone in your household , other than yourself , had a sore throat ?  if the interviewee said yes ,  he or she was asked how many children and how many adults had a sore throat during that period . the questions asked whether anyone in the home had a sore throat ; fever ; new cough ; new runny nose ; skin infection ; a diagnosis of strep throat , an ear infection , or a sinus infection ; or died . to measure the severity of the illness , the questionnaire asked whether the ill person(s ) had visited a doctor , missed school or work , had taken antibiotics , or had been hospitalized . to evaluate exposure to both persons at work and symptomatic persons at work , the questionnaire asked which type of environment the case - patient or control subject worked in , how many hours she or he worked , how many persons were in their work environment , and whether anyone at work had been ill in the 2 weeks before the case - patient s illness or control subject interview by asking about specific types of illnesses . the questions were asked in the same manner as those asked of persons in the home . odds ratios ( ors ) for each potential risk factor were determined by using conditional logistic regression ( proc phreg , sas version 6.12 , cary , nc ) , controlling for sex and race . these ors were determined separately for age groups 1844 years of age and > 45 years of age to identify age - dependent risk factors . those variables found to have a p value > 0.20 in individual analyses were included in multivariable analysis . computer - assisted and manual forward , backward , and stepwise conditional logistic regression was done to identify risk factors independently associated with invasive gas disease . ors with 95% confidence intervals ( cis ) that do not include 1.00 , and p values < 0.05 were considered statistically significant in multivariable analysis . surveillance identified 401 episodes of invasive gas disease among adults > 18 years of age ; 390 persons were traceable and were screened by surveillance personnel for possible participation . of the 390 persons with invasive gas disease , 49 were ineligible ( 36 due to nosocomial infection and 13 due to institutionalization ) . of the remaining 341 case - patients , 139 were enrolled , 24 refused to participate , 27 were not reached after exhausting the telephone case algorithm , and the rest were nonparticipants . reasons for nonparticipation included the following : refusal to allow participation by spouse or surrogate , > 3 months had elapsed since the illness , incomplete or incorrect contact information ( i.e. , wrong phone number , disconnected phone , no phone , homelessness ) , and difficulty with communication over the phone ( i.e. , poor communication skills , non  english - speaking patient ) . the number of case - patients and control subjects enrolled varied by area : 58 case - patients were from atlanta , 49 case - patients were from baltimore , and 32 case - patients were from toronto . of the 139 case - patients enrolled , 48 ( 34% ) were 1844 years of age , 54 ( 39% ) were 4564 years of age , and 37 ( 27% ) were > 65 years of age . of the 139 case - patients , 70 ( 50% ) were men , 75 ( 54% ) were white , and 60 ( 43% ) were african - american ( table 1 ) . several factors were associated with invasive gas disease among those 1844 years of age ( table 3 ) . when sex and race were controlled for , hiv seropositivity and history of injecting drug use were significantly associated with invasive gas disease ( p<0.05 ) when each variable was analyzed individually . smoking , presence of children in the home , diabetes , cancer , regular use of nsaids , corticosteroid use , and alcohol abuse were not associated with invasive gas disease . using multivariable conditional logistic regression and controlling for sex and race , we found that three risk factors were independently associated with invasive gas disease : having one or more children with a sore throat in the home in the past 2 weeks ( rr=4.93 , p=0.02 ) , hiv seropositivity ( rr=15.01 , p=0.04 ) , and history of injecting drug use ( rr=14.71 , p=0.003 ) . among those 1844 years of age , one case - patient had a history of paralysis , and no one had recent varicella infection . or , odds ratio ; ci , confidence interval ; nsaid , nonsteroidal antiinflammatory drug .  due to missing data , for some variables , data for fewer than 48 case - patients and 115 control subjects were available . many factors were associated with invasive gas disease in adults > 45 years of age ( table 4 ) . when the results were controlled for sex and race , we found that the following factors were significantly associated with invasive gas disease ( p0.05 ) : three or more persons living in the home , any child living in the home , other smokers living in the home , diabetes mellitus , cardiac disease , chronic obstructive pulmonary disease ( copd ) , cancer , paralysis , regular use of nsaids , use of corticosteroids , and history of injecting drug use . when multivariable conditional logistic regression analysis , controlling for sex and race , was used , the following factors were independently associated with gas disease : three or more persons living in the home ( rr=2.68 , p=0.004 ) , diabetes mellitus ( rr=2.27 , p=0.03 ) , cardiac disease ( rr=3.24 , p=0.006 ) , cancer ( rr=3.54 , p=0.006 ) , and use of corticosteroids ( rr=5.18 , p=0.03 ) . or , odds ratio ; ci , confidence interval ; nsaid , nonsteroidal anti - inflammatory drug ;  due to missing data , for some variables , data for fewer than 91 case - patients and 196 control subjects were available . > 45 years of age , the only cases of cirrhosis and recent varicella infection occurred in case - patients ; five case - patients reported a history of cirrhosis , and one case - patients reported a recent varicella infection . five ( 83% ) of six persons with paralysis were in the case - patient group . this difference was significant when this variable was evaluated alone but did not reach statistical significance in multivariable analysis . none of the six patients with paralysis in this age group reported the presence of a decubitus ulcer ; two of the persons with paralysis indicated that they had open sores in other places . of the 47 patients who had a cutaneous focus of invasive gas infection ( 36 with cellulitis , 9 with necrotizing fasciitis , and 2 with an abscess ) , 39 ( 83% ) reported an open sore , bruise , or burn before the onset of invasive gas symptoms , and 5 ( 11% ) reported having been diagnosed with a skin condition in the past ( eczema , psoriasis , or seborrheic dermatitis ) . type of work environment , number of persons at work , number of hours at work , and presence of an ill person at work were not associated with invasive gas infection in either age group . this study suggests that both host and environmental factors are associated with the risk of community - acquired invasive gas disease in adults . we found that the host factors of hiv infection , diabetes , malignancy , injecting drug use , and cardiac disease were associated with an increased risk of invasive gas disease . the environmental factors associated with an increased risk were household size and the presence of a child with a sore throat . these environmental factors highlight the importance of person - to - person transmission of group a streptococcus . although previous studies have found host risk factors to be associated with invasive gas infection , this study found that the importance of host factors varied significantly by patient s age . in adults 1844 years of age , hiv infection and history of injecting drug use were associated with invasive gas disease . the association with hiv has been previously identified ( 1 ) and suggests that immune suppression increases the risk for invasive gas disease . the association with injecting drug use has been previously identified also ( 8) and may be because of the direct injection of group a streptococci from the skin into the blood . the increased risk associated with injecting drug use was independent of that related to hiv infection . because control subjects identified by random digit dialing may be reluctant to admit certain illicit behaviors and hiv infection , our ascertainment of injecting drug use and hiv infection among controls may be an underestimate ; the strong association between these two factors and invasive gas infection found in our study may be an overestimate of the true value of this association . in older adults , diabetes mellitus , cardiac disease , cancer , and corticosteroid use are associated with invasive gas infection . the association with diabetes , cancer , and corticosteroids again suggests that immune dysfunction is important in the development of this disease . an association between cardiac disease and invasive gas infection was also suggested in a recent 10-year population - based surveillance study done in the san francisco bay area ( 8) . the mechanism by which cardiac disease increases the risk of invasive gas disease is not known but warrants further study . our data also suggest that paralysis , cirrhosis , and varicella infections may be risk factors for invasive gas disease . these conditions were not common among our study participants ; thus , the power of this investigation to identify them as significant risk factors was limited . future research into the association between invasive gas disease and paralysis should include evaluation of the possible contribution of skin disruption . varicella infection is a well - documented risk factor in the development of invasive gas disease among children ( 1,914 ) . the hypothesis that nsaid use might increase the risk of necrotizing fasciitis in children with varicella was first suggested by brogan et al . ( 11 ) , and later observations by peterson et al . supported it ( 12 ) . several mechanisms by which nsaid use might influence the incidence or severity of gas infections have been proposed ( 15 ) . a recent prospective , multicenter case - control study did not find that nsaid use increases the risk of necrotizing gas infections ( 16 ) . instead , their data suggested that children with varicella were apt to take nsaids because they were ill from varicella as opposed to nsaids being a risk factor for later acquisition of invasive gas disease . a large proportion of the patients with invasive gas disease had a cutaneous form of the disease , and a large portion of those with cutaneous disease reported an open sore , bruise , or burn before the onset of invasive gas symptoms . other studies have found an association between invasive bacterial diseases and cigarette smoking ( 17,18 ) . a true association may have been undetectable because of the difficulty in ascertaining smoking status over the telephone . other studies have found an association between invasive gas disease and alcoholism ( 1 ) . the sensitivity of the cage questions ( 7 ) may be lower in phone interviews than in face - to - face interviews . our study found that environmental exposures were important in the development of invasive gas infection . specifically , we found that environmental exposures are related to age . in younger adults , exposure to school - aged children with a sore throat increased the risk of invasive gas disease . household studies in the 1950s showed that school - aged children are most likely to introduce group a streptococcus into a household and that symptomatic children are more efficient transmitters of infection than are asymptomatic children ( 4 ) . surveillance in toronto demonstrated that the risk of colonization in the household is associated with younger age and 4 or more hours of contact with the infected person per day ( 1 ) . more recently , the role of transmission among household contacts has been demonstrated in studies of community gas outbreaks and household contacts of patients with invasive gas ( 19,20 ) . these studies suggest that infections among children may represent an important reservoir for infections in adults . the statistical power of this study to detect the association between gas infection and certain known risk factors , such as concomitant varicella infection , was limited . because we matched subjects in terms of socioeconomic status , we were unable to examine socioeconomic variables in our analysis . this study included only people who have phones , and risk factors for invasive gas disease may differ between people who do not have phones and those who do . the results from this risk factor study can shape current and future strategies to prevent invasive gas disease . currently , these findings may help refine recommendations for prophylaxis of close contacts of persons with invasive gas disease . vaccines for gas disease are being developed . identifying those at greatest risk of invasive gas disease is important in developing vaccination recommendations . our data suggest that vaccination should be considered for those with history of injecting drug use , hiv infection , diabetes mellitus , cardiac disease , cancer , and use of corticosteroids . our data also suggest that vaccination will provide benefits to those who receive the vaccine and to those with whom they live .
we conducted a case - control study to identify risk factors for invasive group a streptococcal ( gas ) infections , which can be fatal . 
 case - patients were identified when streptoccus pyogenes was isolated from a normally sterile site and control subjects ( two or more ) were identified and matched to case - patients by using sequential - digit telephone dialing . 
 all participants were noninstitutionalized surveillance area residents , > 18 years of age . 
 conditional logistic regression identified the risk factors for invasive gas infection : in adults 18 to 44 years of age , exposure to one or more children with sore throats ( relative risk [ rr]=4.93 , p=0.02 ) , hiv infection ( rr = 15.01 , p=0.04 ) , and history of injecting drug use ( rr=14.71 , p=0.003 ) ; in adults > 45 years of age , number of persons in the home ( rr=2.68 , p=0.004 ) , diabetes ( rr= 2.27 , p=0.03 ) , cardiac disease ( rr=3.24 , p=0.006 ) , cancer ( rr= 3.54 , p=0.006 ) , and corticosteroid use ( rr=5.18 , p=0.03 ) . 
 thus , host and environmental factors increased the risk for invasive gas disease .