meningitis is common and is among the most serious infections occurring in individuals with hiv infection [ 1 , 2 ] .
the etiology of meningitis in hiv - endemic areas has been significantly altered in favor of cryptococcal meningitis and tb meningitis [ 1 , 3 , 4 ] .
evidence shows that cryptococcal meningitis is the most common fungal meningitis and an important opportunistic infection in patients living with hiv [ 2 , 58 ] .
tb meningitis has also been shown to be the second most common cause of meningitis , with a case fatality rate of up to 67% among hiv - infected individuals [ 4 , 9 , 10 ] .
the symptoms of meningitis among hiv - infected individuals may vary depending on the cause . in one study done in durban , south africa , among hiv patients coinfected with tuberculosis ( tb ) ,
the most common combination of presenting clinical features for patients suspected to have meningitis was headache and neck stiffness , seen in 78.6% of patients .
the triad of headache , vomiting , and neck stiffness was observed in 35.7% whereas only 1% of patients presented with fever . in another study done in zimbabwe ,
patients with pyogenic meningitis presented with fever and marked alteration in mental status , while the main presenting feature of cryptococcal meningitis was headache .
patients with tb tended to be admitted with marked mental impairment , compared with that seen with other forms of meningitis .
the diagnosis of certain types of meningitis , particularly tb meningitis , is often difficult in resource - limited settings due to the low sensitivity of standard smear for acid - fast bacilli ( afb ) , which is often the only diagnostic assay available .
currently , the true prevalence of specific microbiological etiologies , clinical characteristics , and outcomes of meningitis in our setting are not well defined . in order to optimize patient care , the epidemiologic trends of meningitis among hiv - infected patients
should be examined frequently because any change may influence the choice of initial empiric antibiotics .
therefore , it was the aim of this study to determine the laboratory - confirmed etiological agents , clinical characteristics , and outcomes of meningitis among hiv - infected adults admitted to the medical wards of bugando medical centre with symptoms and signs of meningitis .
this was a cross - sectional study with prospective follow - up to determine in - hospital mortality / outcomes involving all hiv - infected adult patients 18 years old admitted to the medical wards of bmc for symptoms and signs of meningitis .
it is located on the shore of lake victoria where the prevalence of hiv is over 6% .
we serially enrolled all hiv - infected patients aged 18 years who were admitted to bmc medical wards with clinical suspicion of meningitis over a six - month period .
critically ill patients , patients with focal neurological signs or papilloedema , and those who had been treated for meningitis in the past one month were excluded .
all hiv - infected adults 18 years old admitted to the medical wards of bmc during the study period were screened for symptoms and signs of meningitis .
patients ( or their caretakers ) were interviewed using a standardized data collection tool / structured questionnaire to collect demographic information , clinical symptoms , and other information .
then , patients were examined within 24 hours of admission to determine the presence or absence of physical signs of meningitis .
patients with lateralizing signs and/or papilloedema on fundoscopy were excluded from the study because lumbar punctures would be contraindicated given our inability to rule out a space - occupying lesion with a computed tomography scan . for all enrolled patients , laboratory investigations including
csf analysis included biochemistry , cytology , gram stain , afb smear using ziehl - neelsen stain , tb culture , and india ink stain .
cryptococcal antigen test ( crag ) was performed using latest agglutination test kit ( calas , meridian bioscience europe , nice , france ) according to the manufacturer 's instructions .
other laboratory investigations included full blood picture , erythrocyte sedimentation rate ( esr ) , and cd4 t - cell ( cd4 ) count .
the cd4 counts were performed using automated facs calibur flow cytometry machine ( bd , san jose , usa ) .
all results were provided to clinicians who made all decisions about treatment for meningitis and other conditions .
all patients with clinical meningitis were followed up for at least 2 weeks or until the time of discharge .
patients discharged prior to 2 weeks from study enrollment were contacted at 2 weeks to determine outcomes . to test for cryptococcal meningitis , all hiv - infected patients had an additional 5 milliliters of blood collected for serum cryptococcal antigen assay .
after lumbar puncture , about 4 milliliters of csf was sent for both cryptococcal antigen and india ink staining .
testing of both serum and csf for crag relied on the cryptococcal antigen assay ( immuno - mycologics inc .
this assay is a world health organization ( who ) approved test that is used routinely for diagnosis of cryptococcal meningitis at bmc .
other bacteria were identified by gram staining of centrifuged sediment from csf and were isolated using bacterial culture on blood and chocolate agars for 72 hours .
data were double entered into microsoft excel and analyzed using stata version 11 ( college station , texas ) .
continuous variables were presented as means ( standard deviation ( sd ) ) or medians ( interquartile range ( iqr ) ) , and binary variables were presented as proportions ( % ) .
we analyzed clinical characteristics associated with various meningitis syndromes using the wilcoxon rank - sum and chi - squared or fisher 's exact tests where appropriate .
associations between variables were considered to be significant if the p value was < 0.05 at 95% ci .
permission to conduct the study was sought from the joint research and publication committee of cuhas / bmc .
lumbar puncture was performed by the principal investigator , observing aseptic technique , ensuring minimal trauma to patients .
all csf analyses were done as per existing hospital guidelines ; all patients found to have meningitis were treated as per existing hospital guidelines .
during the six - month study period from november 2012 to may 2013 , a total of 1971 adults were admitted to bmc medical wards . out of these , 73 were hiv - infected and had features of meningitis .
four patients refused consent , five had papilloedema , and the other four had traumatic unsuccessful lumbar punctures .
the median age of the study population was 39 years ( interquartile range [ iqr 32.547 ] ( table 1 ) ) .
the median baseline cd4 count was 89 cells / ul [ iqr 31226 ] . about one - third of the study population ( 18 , 30% ) was on antiretroviral therapy ( art ) on admission and the median duration on art was 16 months [ iqr 332 ] .
of the four classic symptoms of meningitis , 45 ( 75% ) had headache and neck stiffness , 34 ( 56.7% ) had three symptoms ( headache , fever , and neck stiffness ) , and 24 ( 40% ) had all four symptoms .
the median lumbar puncture csf opening pressure was 18  cm of h2o [ iqr 1125 ] , and 26 patients ( 43.3% ) had elevated opening pressures ( above 20  cm of h2o ) ( table 2 ) .
cryptococcal antigen was positive in both serum and csf of 11 patients ( 18.3% ) and india ink showed encapsulated yeast cells in 8 of these 11 patients ( 72.7% ) .
the median csf white blood cell ( wbc ) count was 19.5 cells / mm [ iqr 653.5 ] and the majority ( 37 , 61.7% ) had a csf lymphocytic predominance with more than 50% of wbc in csf classified as lymphocytes .
only 3 ( 5% ) of all enrolled patients had combination of all abnormal signs / features on lumbar puncture ( high lumbar puncture opening pressure , elevated csf protein , elevated csf wbc , and turbid csf appearance ) . among the 11 patients with cryptococcal antigen test positive , 10 ( 90.9% ) of them
however , all 8 patients with india ink positive had combination of three of the four signs mentioned above .
the csf gram stain was positive in 5 ( 8.3% ) and csf routine culture was positive in 5 patients ( 8.3% ) .
four of five had encapsulated yeast on gram stain and culture , and the fifth had gram - positive cocci in pairs confirmed as s. pneumoniae on culture .
stain was positive in three ( 5% ) , whereas csf tb culture was positive in these three , as well as in one additional patient , for a total of 4 ( 6.7% ) .
cryptococcal meningitis was confirmed through csf crag in 11 patients ( 18.3% ) with the india ink being positive in 8 of 11 ( 13.3% of total patients or 72.7% of confirmed cryptococcal cases ) .
three of four culture - confirmed cases diagnosed in the laboratory were afb smear - positive . among patients with cryptococcal meningitis , 2 ( 18.2% ) of them
other bacterial meningitis was confirmed in only 1 patient ( 1.7% ) , who had streptococcus pneumonia .
the majority of patients had aseptic meningitis ( 41 , 68.3% ) with abnormal findings in the csf ( i.e. , they had elevated wbc > 5 cells / mm on csf but no bacteria or fungi on microscopy or culture ) .
the other 5 patients ( 8.3% ) had sterile csf with normal wbc counts and , hence , were regarded as not having meningitis .
low recent cd4 count was a significant predictor of mortality among this population , with patients who died having a median current cd4 count of 50 [ 15100 ] , compared with 98 [ 46338 ] in those who did not die ( p = 0.01 ) .
also turbid csf was found to be a significant predictor of mortality among these patients ( p value = 0.001 ) ( table 3 ) .
this was the first cross - sectional study to determine different etiologies of meningitis among adult hiv - infected patients admitted at bmc . among 60 adult hiv - infected patients enrolled in this study , 14 ( 23% ) of them
had confirmed microbiological etiologies and 41 ( 68% ) others had no defined isolates in the csf though they had laboratory findings ( elevated csf wbc ) which were suggestive of meningitis .
our study also supports findings of other studies from sub - saharan africa that have shown cryptococcus followed by tuberculosis is one of the leading causes of meningitis diagnosed in this population [ 3 , 9 ] .
low recent cd4 count and turbid csf were significantly associated with mortality from meningitis in our study population .
as described in two previous studies done at our hospital ( bmc ) , cryptococcal meningitis remains a common cause of meningitis and death , among adult hiv / aids patients in our setting [ 6 , 11 ] .
this finding is also in keeping with studies from muhimbili national hospital and another study done in durban , south africa [ 2 , 3 ] . in our study , the sensitivity of india ink in the diagnosing cm was high ( 72.7% ) compared to previous studies .
this could be explained by the fact that our patients were art - nave , and hence they may have had high fungal burdens and therefore a high positivity india ink csf stains , consistent with other studies [ 6 , 9 , 12 , 13 ] . among patients with culture - proven tb meningitis ,
75% had positive afb smear ; this is high sensitivity of smear microscopy compared to a study in cape town , south africa , where a very low level of 1.3% was observed .
the high sensitivity of the afb smear of 75% observed in our study could be due to the use of large volume of csf ( 10  mls ) ; this confirmed what was described previously in vietnam whereby the use of large volume csf increased the diagnostic yield for tbm from < 50% to 69% .
our study finding concurs with another study done in the philippines whereby only 4/91 ( 4.4% ) patients with chronic meningitis had confirmed tbm by culture or afb smear .
however , in that study , the additional use of another test ( like basal meningeal enhancement on contrast ct scan of the head ) demonstrated that 44 patients fulfilled the criteria of definite tbm .
the use of this test in our setting is not cost - effective . taken together , this study and ours highlight the continued challenges of diagnosing tuberculous meningitis and the urgent need for improved diagnostic resources .
diagnosis of other types of bacterial meningitis in our study may also have been complicated by the sterilizing effect of antibiotics in the csf . because antibiotics are readily available at any local pharmacy in our setting
, clinical experience suggests that most patients presenting to the hospital with fever have already tried several courses of antibiotics at home .
this is evidenced by several recent studies that documented that most patients report the use of either prescribed or self - prescribed antibiotics prior to their admission to our hospital [ 16 , 17 ] .
we suspect that some of the cases classified as aseptic meningitis may have been partially treated bacterial meningitis whose csf no longer had viable bacteria .
it was observed that , among hiv - infected patients with meningitis in this study , 36.7% died within the first 2 weeks of hospital admission .
this finding is slightly lower compared with one study done in south africa in which meningitis was associated with poor outcomes including high mortality in about 40% of diagnosed patients .
importantly , among our study patients with cryptococcal meningitis alone , the mortality rate is relatively lower at 36.4% .
though these numbers are small , our work suggests some improvement compared to previous studies done in our hospital setting which found mortality rates of 66% , which decreased to 43% after implementation of routine serial lumbar punctures for patients with cryptococcal meningitis [ 6 , 11 ] .
we have continued to use serial lumbar punctures , together with high - dose intravenous fluconazole , to manage patients admitted with cryptococcal meningitis to our hospital .
the very high 75% mortality rate for patients with tbm draws attention to the continued need for better diagnosis and treatment .
of 3 deaths , 2 had afb smear - positive , suggesting a high burden of mycobacteria .
this high mortality rate among patients with tbm is supported by another larger study done in south africa where the mortality rate was about 66.7% .
cryptococcal meningitis is the most prevalent laboratory - confirmed isolate among adult hiv - infected patients admitted with features suggestive of meningitis to the bmc medical wards .
tuberculous meningitis is the second most common cause of confirmed meningitis ; however , it remains difficult to diagnose due to challenges with diagnostic tools and likely has a higher prevalence in reality .
our work calls attention to the ongoing need for improved diagnosis and management for patients presenting with meningitis in resource - limited settings .
 
 background . 
 limited information exists on the etiologies , clinical characteristics , and outcomes of meningitis among hiv - infected patients in africa . 
 we conducted a study to determine the etiology , clinical characteristics , and outcomes of meningitis among hiv - infected adults . 
 methods . 
 a prospective cross - sectional hospital based study was conducted among hiv - infected patients aged 18 years admitted to the medical wards with symptoms and signs of meningitis . 
 sociodemographic and clinical information were collected using a standardized data collection tool . 
 lumbar puncture was performed to all patients ; cerebrospinal fluid samples were sent for analysis . results . among 
 60 hiv - infected adults clinically diagnosed to have meningitis , 55 had csf profiles consistent with meningitis . 
 of these , 14 ( 25.5% ) had a laboratory - confirmed etiology while 41 ( 74.5% ) had no isolate identified . 
 cryptococcus neoformans was the commonest cause of meningitis occurring in 11 ( 18.3% ) of patients followed by mycobacterium tuberculosis ( 6.7% ) . 
 the in - hospital mortality was 20/55 ( 36.4% ) . 
 independent predictors of mortality were low baseline cd4 count and turbid csf appearance . conclusion . 
 cryptococcal meningitis is the most prevalent laboratory - confirmed etiological agent among adult hiv - infected patients with suspected meningitis admitted to medical wards in western tanzania . 
 mortality rate in this population remains unacceptably high . 
 improving diagnostic capacity and early treatment may help to decrease the mortality rate . 
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusion