it affects nearly 100 million people in tropical and subtropical areas of europe , africa , latin america , and asia .
most cases are chronic and asymptomatic , but severe infections such as hyperinfection syndrome ( his ) and disseminated strongyloidiasis ( ds ) occur when cellular immunity is compromised . in his ( 1.52.5  % of cases ) , manifestations are confined to the respiratory and gastrointestinal ( gi ) systems .
ds , infection with multiple organ involvement other than the respiratory and gi systems such as the brain or the skin , may have a mortality of up to 87  % .
bacterial meningitis caused by enteric flora is a potentially fatal complication of ds / his .
localized strongyloidiasis , as well as ds / his , can predispose individuals to bacterial meningitis with enteric organisms such as klebsiella pneumoniae ( k. pneumoniae ) , escherichia coli ( e. coli ) , and enterococcus spp . in the absence of evidence for strongyloidiasis outside the gi tract [ 2 , 3 ] .
human t - lymphotropic virus-1 ( htlv-1 ) is a retrovirus that infects 1020 million people worldwide .
the virus is highly prevalent in japan , sub - saharan africa , the caribbean , and south america .
southern japan is the area with the highest htlv-1 prevalence , with over 10  % of the general population being infected .
htlv-1 can be transmitted from mother to child , through sexual contact , and through contaminated blood products .
most cases are asymptomatic , but adult t cell leukemia / lymphoma ( atll ) and htlv-1-associated myelopathy / tropical spastic paresis may occur .
co - infection with s. stercoralis and htlv-1 predisposes individuals to ds / his , possibly because htlv-1 interferes with th2 cell responses to s. stercoralis , including eosinophil activation and production of interleukins and ige .
glucocorticoids , malignancies , human immunodeficiency virus ( hiv ) , organ or marrow transplantation , hypogammaglobulinemia , leprosy , tuberculosis , and malnutrition also increase the risk .
this report delineates the clinical features of bacterial meningitis associated with strongyloidiasis seen at a single center in subtropical japan , in an area endemic for both strongyloidiasis and htlv-1 .
cases with both bacterial meningitis and strongyloidiasis were extracted from a review of the discharge diagnoses for all hospitalizations at okinawa chubu hospital between january 1990 and may 2010 .
the prevalence of strongyloidiasis and htlv-1 in this area is reportedly 6.3 and 14  % , respectively .
about 39,000 patients visit the emergency department and nearly 14,000 patients are hospitalized per year .
after review , we included cases that met the following inclusion criteria : ( 1 ) typical signs and symptoms of meningitis ( headache , temperature  > 38  c , nuchal rigidity , and/or altered consciousness ) ; ( 2 ) cerebrospinal fluid ( csf ) findings consistent with bacterial meningitis , including : neutrophil ( pmn ) predominance , low glucose , high protein , high opening pressures , organisms on gram stain , or recovery of microorganisms from csf or blood ; ( 3 ) proof of coexistent strongyloidiasis ( larvae or eggs from any specimens ) .
in addition to the inclusion criteria , we collected the following data : gender , age , outcome , symptoms , csf findings , s. stercoralis results , hiv testing results , medical / social history , glucocorticoid use , colonoscopy results , and use of antibiotics and antihelminthics .
we performed a mann  whitney u - test for csf statistical analysis and a one - sided fisher s exact test for outcome statistical analysis , using stata software ( version 12.1 ; statacorp , college station , tx , usa ) .
the median age at diagnosis was 58  years and 11/21 ( 52.4  % ) patients were male .
table  1 shows the gender , age , culture results for csf and blood , results of csf gram staining , serological results for htlv-1 , specimens from which s. stercoralis was detected , past history , initial antibiotics and antihelminthics ( antibiotics were subsequently chosen according to culture results ) , and outcome of the patients .
six episodes of acute meningitis without proven concurrent strongyloidiasis were included because each of these patients had previous or subsequent episodes of proven strongyloidiasis associated with meningitis .
five of 21 patients ( 23.8  % ) had more than one episode of meningitis .
of these five patients , four were treated with thiabendazole , and one was not treated during the first episode because he was not diagnosed with strongyloidiasis . among the eight cases treated with ivermectin , none developed recurrent episodes of either strongyloidiasis or meningitis .
table  1clinical features of all episodes 
 abpc ampicillin , atll adult t cell leukemia / lymphoma , ca carcinoma , ctrx ceftriaxone , ctx cefotaxime , dm diabetes mellitus , e. coli 
 escherichia coli , gnr gram - negative rods , gpc gram - positive cocci , k. pneumoniae 
 klebsiella pneumoniae , l. lactic 
 lactococcus lactis , pmn polymorphic nuclear neutrophils , ra rheumatoid arthritis , s. bovis 
 streptococcus bovis , s. sanguinis 
 streptococcus sanguinis , vcm vancomycin 
 indicates the year when diagnosis was made 
 oral glucocorticoid was prescribed clinical features of all episodes 
 abpc ampicillin , atll adult t cell leukemia / lymphoma , ca carcinoma , ctrx ceftriaxone , ctx cefotaxime , dm diabetes mellitus , e. coli 
 escherichia coli , gnr gram - negative rods , gpc gram - positive cocci , k. pneumoniae 
 klebsiella pneumoniae , l. lactic 
 lactococcus lactis , pmn polymorphic nuclear neutrophils , ra rheumatoid arthritis , s. bovis 
 streptococcus bovis , s. sanguinis 
 streptococcus sanguinis , vcm vancomycin 
 indicates the year when diagnosis was made 
 oral glucocorticoid was prescribed table  2 summarizes the culture results for csf and blood .
k. pneumoniae was the most frequent pathogen , followed by streptococcus bovis ( s. bovis ) and e. coli .
no organism was isolated from csf or blood cultures in 14/33 ( 42.4  % ) episodes . among culture - negative cases ,
gram - positive cocci ( gpc ) were detected in csf and/or blood cultures in 9/33 ( 27.3  % ) episodes . 

table  2summary of culture resultsorganismcsf culture ( % ) blood culture ( % ) 
 k. pneumoniae 
 5 ( 15.2)7 ( 21.2 ) 
 s. bovis 
 5 ( 15.2)5 ( 15.2 ) 
 e. coli 
 2
( 6.1)3 ( 9.1 ) 
 l. lactis 
 1 ( 3.0)1 ( 3.0 ) 
 enterococcus spp.1 ( 3.0)0 
 s. sanguinis 
 1 ( 3.0)0negative18 ( 54.5)18 ( 54.5)one case of mixed infection with k. pneumoniae and s. bovis is included in the blood culture results 
 k. pneumoniae 
 klebsiella pneumoniae , s. bovis 
 streptococcus bovis , e. coli 
 escherichia coli , l. lactis 
 lactococcus lactis , s. sanguinis 
 streptococcus sanguinis 
  summary of culture results one case of mixed infection with k. pneumoniae and s. bovis is included in the blood culture results 
 k. pneumoniae 
 klebsiella pneumoniae , s. bovis 
 streptococcus bovis , e. coli 
 escherichia coli , l. lactis 
 lactococcus lactis , s. sanguinis 
 streptococcus sanguinis 
  serology for htlv-1 was positive in 16/21 ( 76.2  % ) patients , including two cases of acute atll and four cases with smoldering atll . among five cases without htlv-1 ,
two had previous neurosurgeries , two were diagnosed with malnutrition , and one received glucocorticoid for uveitis .
three patients had negative hiv test results ( patients 6 , 13 , and 17 ) , but no other patients were examined for hiv due to the low prevalence in japan .
twenty - seven of 33 cases ( 81.8  % ) improved without neurological complications and 6/33 episodes ( 18.2  % ) ended in fatalities .
only patient 21 received three doses of dexamethasone , 0.15  mg / kg every 8  h , which was discontinued after strongyloidiasis was diagnosed . all patients with gpc meningitis recovered without neurological complications , except for patient 20 , who developed acute atll and died .
there was no significant difference in outcome between culture - positive cases and culture - negative cases .
fatal cases comprised 4/19 ( 21.0  % ) in culture - positive cases and 2/14 ( 14.2  % ) in culture - negative cases ( p - value 0.490 ) . among 33 episodes of meningitis , fever was seen in 31 ( 93.9  % ) , headache in 30 ( 90.9  % ) , nausea and vomiting in 27 ( 81.8  % ) , rigors in 17 ( 51.5  % ) , and altered mental status in 15 ( 45.5  % ) .
s. stercoralis was detected in the stool in 26/33 ( 78.8  % ) episodes , in gastric juice in 10/33 ( 30.3  % ) episodes , in sputum in 5/33 ( 12.1  % ) episodes , and in ascites in 1/33 ( 3.0  % ) episodes .
s. stercoralis was detected only in the gi tract specimens in 23/33 ( 69.7  % ) cases . only two patients underwent colonoscopy ; patient 13 had diverticulosis and patient 21 had benign adenoma , both of whom had s. bovis meningitis .
nineteen of 21 ( 90.5  % ) patients , including one patient with previously resected colon cancer , did not undergo colonoscopy .
medians and interquartile ranges of csf cell count , pmn percentage , sugar , csf / blood sugar ratio , and protein were 1,440/mm ( 5402,500 ) , 84  % ( 7196 ) , 48  mg / dl ( 2564 ) , 39  % ( 1253 ) , and 117  mg / dl ( 84237 ) , respectively . there were no significant differences between culture - positive and culture - negative cases .
we present a series of 21 patients with neutrophil - dominant meningitis associated with strongyloidiasis , including 14 cases with negative csf and blood cultures .
s. bovis was the etiology for six patients , all of whom were positive for htlv-1 .
s. bovis is a gpc in the gut flora of 1016  % of healthy individuals .
it may cause bacteremia , endocarditis , and meningitis in patients with gi lesions or colon cancer , and in neonates [ 7 , 8 ] .
s. bovis has been reported as a rare cause of bacterial meningitis associated with strongyloidiasis .
only four cases of bacterial meningitis due to s. bovis have been reported with strongyloidiasis ; three had defective cellular immunity ( two with hiv and one due to steroids ) and one was reportedly immunocompetent [ 6 , 911 ] .
we detected six cases in a single center over 20  years , which suggests that the incidence of s. bovis meningitis in patients with strongyloidiasis may be higher than previously suspected .
this interaction could impact the management of meningitis in geographic areas where htlv-1 and strongyloidiasis are endemic .
the practice guidelines for the management of bacterial meningitis published by the infectious diseases society of america ( idsa ) recommend dexamethasone for adults with suspected pneumococcal meningitis , with dosage continued if the csf gram stain shows gram - positive diplococci .
this approach risks exacerbating strongyloidiasis in cases of meningitis due to gpc associated with strongyloidiasis , which can not be reliably distinguished from pneumococci on gram stain .
glucocorticoid use is the strongest known risk factor for disseminated strongyloidiasis , due to the acquired defect in cell - mediated immunity .
glucocorticoids may act as ecdysteroids that accelerate the conversion of larvae from the rhabditiform state to the invasive filariform state [ 1 , 13 ] .
one case of ds was reported after only a single dose of dexamethasone prior to stereotactic radiosurgery .
distinguishing pneumococcal meningitis from meningitis due to other gpc on clinical grounds or gram stain alone is problematic .
a modified approach to corticosteroid use in gpc meningitis would , therefore , be advisable in areas where strongyloidiasis is endemic .
patients with non - pneumococcal meningitis do not benefit from steroids , which are given to mitigate the harmful csf inflammatory response .
patients with underlying immunologic diseases are less likely to mount self - damaging inflammatory responses .
the good clinical outcomes seen in our cases , which were managed without glucocorticoids , may be attributable to these factors .
a comprehensive microbiology approach using expanded techniques such as rapid latex agglutination testing may be helpful for the early identification of patients that can safely receive glucocorticoids , if this testing is locally available . of our cases ,
42.4  % had negative cultures of both blood and csf despite clinical meningitis and csf pleocytosis , which were clinically indistinguishable from culture - positive cases .
the postulated mechanism by which strongyloidiasis causes bacteremia and meningitis is that parasitic ulceration / perforations of the intestinal mucosa create a portal of entry for enteric bacteria to reach the bloodstream .
mantovani et al .   suggested that the bacteria are co - transported with the migrating parasites .
this hypothesis assumes that the parasite invades the meninges without any attending bacteria , and that s. stercoralis alone induces the intense inflammatory changes that mimic the csf findings of bacterial meningitis .
given that the sensitivity of csf or blood cultures in patients with bacterial meningitis is reportedly  > 70  % [ 1719 ] , our frequent observation of culture - negative suppurative meningitis lends support to this hypothesis . among 14 patients treated with thiabendazole for s. stercoralis , four ( 28.6  % ) developed recurrence after treatment ; no patient treated with ivermectin relapsed .
these facts suggest that ivermectin may eradicate s. stercoralis more effectively than thiabendazole , in which case ivermectin should be considered for patients with underlying immunodeficiency or associated meningitis .
the fact that s. stercoralis was detected only in gi tract specimens in 69.7  % of cases supports the previously suggested theory that localized strongyloidiasis can cause enteric meningitis
. limitations of this retrospective report of a single - center experience include the low percentage of cases in which colonoscopy excluded an additional portal of entry , such as structural lesions / cancers , and the infrequency of hiv testing .
however , during the long - term follow - up of our geographically restricted cases , neither colon cancer nor hiv was diagnosed in any patient .
another limitation is a lack of information regarding the s. bovis speciation ( streptococcus gallolyticus or streptococcus infantarius ) .
further observation of the association between these three infectious entities in additional institutions and other geographical areas will help establish the generalizability and importance of these observations .
in areas where strongyloidiasis and human t - lymphotropic virus-1 ( htlv-1 ) are endemic , clinical meningitis is surprisingly common and frequently recurrent .
culture - negative meningitis and streptococcus bovis meningitis may represent a larger proportion of cases than the meningitis seen in non - tropical areas .
clinicians should be aware that these cases may represent a special scenario in which the conventional use of glucocorticoids can pose a previously unrecognized hazard .
further study is needed in order to clarify the mechanisms by which these infections interact , and to define the prevalence and significance of accompanying structural colonic lesions .
 meningitis caused by enteric flora is a known complication of strongyloidiasis , and human t - lymphotropic virus-1 ( htlv-1 ) predisposes individuals to severe strongyloidiasis . 
 we reviewed the clinical features of bacterial meningitis associated with strongyloidiasis seen at a single center in subtropical japan , in an area endemic for both strongyloidiasis and htlv-1 . 
 we found 33 episodes in 21 patients between 1990 and 2010 . 
 the results were remarkable for the high incidence of meningitis due to gram - positive cocci ( 27.3  % ) , especially streptococcus bovis , and culture - negative cases ( 42.4  % ) . given the high incidence of gram - positive meningitis , a modified approach to corticosteroid use would be advisable in areas where strongyloidiasis is endemic , due to the potentially adverse consequences of glucocorticoid therapy . 
Introduction
Methods
Results
Discussion
Conclusion