Decoding Infection and Transmission 1 (2023) 100003

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Decoding Infection and Transmission

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Research Paper

A new scoring system to predict tuberculosis among South-Tunisian

patients with lymphocytic meningitis
Houda Ben Ayed a, d, *, Makram Koubaa b, d, Sirine Chtourou b, d, Khaoula Rekik b, d,
Fatma Hammami b, d, Chakib Marrekchi b, d, Jamel Damak c, d, Mounir Ben Jemaa b, d
a
Preventive Medicine and Hospital Hygiene Department, Hedi Chaker University Hospital, University of Sfax, Tunisia
b
Infectious Diseases Department, Hedi Chaker University Hospital, University of Sfax, Tunisia
c
Community Health and Epidemiology Department, Hedi Chaker University Hospital, University of Sfax, Tunisia
d
Extra-pulmonary Research Unity, Hedi Chaker University Hospital, Sfax, UR17SP12, Tunisia

A R T I C L E I N F O A B S T R A C T

Keywords: Background: Death and poor outcome due to Tuberculous meningitis (TBM) is greatly influenced by the delayed
Lymphocytic treatment initiation, which often occurs in lymphocytic meningitis (LM). This study aimed to propose an easy-to-
Meningitis use clinical prediction score that can accurately diagnose TBM among LM patients.
Prediction
Methods: It was a prospective cohort study including all patients with LM hospitalized at the infectious diseases
Score
Tuberculosis
department in Southern Tunisia from 2008 to 2022 were included.
Results: Among 290 LM patients, 105 cases (36.2%) had TBM. By multivariate analysis, age ≥60 years, rural
origin, symptom duration ≥5days, thrill, deteriorated general conditions, a hospital stay ≥ 10 days, complicated
forms, blood white cells count <4000/mm3, CSF/blood glucose ratio<0.5, hydrocephalus and arachnoiditis
were independent factors of TBM. Individual diagnosis indexes from 1 to 3 points were attributed to these factors
to produce an overall score ranging from 0 to 16 points. At a cut-off of 7, the predictive score had a receiver
operating characteristic (ROC) area of 0.94, a sensitivity, a specificity and a diagnosis accuracy of respectively
81%, 91.4%, and 87.5%.
Conclusions: This original study proposed a novel scoring system that can reliably identify patients with TBM at
hospital admission and could be easily used in clinical practice.

1. Introduction this global advance in tuberculosis control, case identification is still a

Tuberculosis (TB) remains a major global health problem, with the
most lethal and disabling form being tuberculous meningitis (TBM), of
which there are more than 100 000 new cases each Year.1 Death and
poor outcome due to TBM is greatly influenced by the delayed treatment
initiation, since TBM patients usually attend with unspecific signs and
symptoms of central nervous system involvement. Moreover, cerebro­
spinal fluid (CSF) smear, M. tuberculosis culture and polymerase chain
reaction (PCR) are the “gold standard” for detecting M. tuberculosis in the
CSF. However, the laboratory diagnosis for TBM is expensive,
time-consuming for decision-making, and not very sensitive.2,3
Radiological diagnostic methods, including computer tomography
(CT) and especially magnetic resonance imaging (MRI) have greatly
enhanced the diagnostic accuracy of TBM, but they are still not patho­
gnomonic for the disease and images may not occur so early.4,5 Despite
challenge and physicians are facing diagnostic impasses, because of the
limitations of these diagnostic tests, notably in
high-tuberculosis-endemic and limited resources countries. Therefore,
TBM diagnosis is often performed with clinical, epidemiological, labo­
ratory, and cerebral imaging findings. In this perspective, many studies
have tried to establish a diagnosis score using simple clinical and CSF
findings predictive of an early diagnosis of TBM. Nevertheless, most of
these scores attempted to compare TBM with another specific type of
meningitis, such as viral,6 bacterial7 and cryptococcal meningitis8 and
did not compare TBM from various forms of non-TBM among LM
patients.
In Tunisia, an intermediate-endemicity-TB-country, TB is of a public
health concern and the burden of tuberculosis is inequitable across the
country. The notification rate of TB, all forms combined, was 28.8/100
000 population and the mortality rate was 2/100 000 population.9 A

* Corresponding author. Hospital Hygiene Department, Hedi Chaker University Hospital, University of Sfax, Sfax, 3029, Tunisia.
E-mail address: houda.benayed@medecinesfax.org (H. Ben Ayed).

https://doi.org/10.1016/j.dcit.2023.100003
Received 24 August 2023; Received in revised form 8 September 2023; Accepted 9 September 2023
Available online 15 September 2023
2949-9240/© 2023 The Authors. Published by Elsevier B.V. on behalf of Jiangsu Institute of Parasitic Diseases. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
H. Ben Ayed et al.
recent analysis of TB disease burden in Southern Tunisia revealed a
sharp increase in incidence in this region, mainly for extrapulmonary
and neuro-meningeal forms.10
In this perspective, this study aimed to propose a reliable and an
easy-to-use clinical prediction score that can accurately diagnose TBM at
an early stage of hospital admission among patients with LM.
2. Methods
2.1. Study design and settings
We conducted a prospective cohort study including all patients with
LM hospitalized at the infectious diseases department in Hedi Chaker
University Hospital (HCUH), Southern Sfax, Tunisia, during a 16-year-
period, from 2008 to 2022. This department is a regional referral cen­
ter for the treatment of acute and chronic meningitis for adult patients.
HCUH is a 1000-bed teaching hospital that provides tertiary care for the
local community as well as for most of South Tunisian governorates,
with a wide range of medical and surgical issues.
2.2. Inclusion criteria and case definition
All patient with LM aged 15 years and older who were hospitalized
during the study period were enrolled. Each patient underwent standard
history-taking, examination, and baseline investigations including
lumbar puncture, blood samples and cerebral imaging when indicated.
The diagnosis of LM was made for all patients with clinical symptoms
suggestive of neuro-meningeal involvement (functional or physical
meningeal syndrome, cranial nerve involvement, etc.) with, on lumbar
puncture, a pathological CSF with pleocytosis: Level of white Blood Cells
≥5/mm3, with a predominance of lymphocytes (>70%), associated or
not with neutrophils. Patients were diagnosed as having TBM if they had
a positive microbiological examination, either a positive culture for a
Mycobacterium Tuberculosis and/or a positive PCR on the CSF or another
positive sample (ganglionic, pulmonary, osteoarticular, etc.). In case of
clinical meningitis symptoms with gram-negative strain or a sterile CSF
culture, TBM was retained if the patient had at least one of the following
criteria: cerebral radiological images on CT and/or MRI strongly sug­
gestive of neuro-meningeal involvement (Hydrocephalus, cerebral
edema, or basal meningeal enhancement), or a good response to anti-
tuberculosis chemotherapy. Complicated forms of LM were defined by
the occurrence of a profonde altered consciousness (Glasgow scale ≤8),
needing the patient’s transfer to an intensive care unit. Control partic­
ipants were patients diagnosed with LM, with etiology other than
tuberculosis, that were hospitalized in the same department and during
the study period to avoid selection. bias. Patients who had missing data
in the medical records and those with laboratory results evidencing
concomitant etiologies (coinfection) for the meningitis were excluded
from the analysis.
2.3. Data collection
We retrieved data that are easy to collect and promptly available
from laboratory and medical records, as well as radiological reports
using a standard case record form. We obtained information on potential
anamnestic data including demographic data, underlying diseases, and
clinical manifestations through physical examination. Laboratory find­
ings including blood routine, biochemical parameters, and CSF results of
the first lumbar puncture as well as imaging features were also collected.
2.4. Statistical analysis
Statistical analysis was performed using SPSS.20. The results of
quantitative variables were presented as mean ± Standard deviation
(SD) if they were normally distributed according to Komogrof-Smirnov
or and Shapiro-wilk tests or median and interquartile range (IQR) in
2
Decoding Infection and Transmission 1 (2023) 100003
the remaining cases, those of qualitative variables as number and per­
centage. For categorical variables, the chi-square test and Fisher exact
test were used in independent samples. Crude Odds ratios (CORs) and
95% confidence intervals (CIs) were calculated to evaluate the strength
of any association that emerged. Variables statistically associated with
TBM in the univariate analysis were included in a multivariate logistic
regression model, and a backward stepwise approach was used to
identify independent predictors of TBM (adjusted odds ratio [AOR],
95% CI, p). Any variable with a p value of <0.05 was retained in the final
model. Then, the final regression model was converted into a point-
based rule, with weighted scores assigned to each variable to generate
a clinically applicable and decision-making rule for the prediction of
TBM. To derive a simple-to-compute risk score, a diagnostic index (DI)
was attributed to of clinical variable in the final model and was calcu­
lated by relying on rounded β-coefficients of the model. For each patient,
the individual DIs that corresponded to the predictors were summed
together to produce an overall score ranging from 0 to 20 points. Model
calibration was assessed using the Hosmer–Lemeshow test for goodness
of fit. We used a bootstrapping method for internal validation and to
estimate the test characteristics of the model. The discriminatory power
of the prediction rule was expressed as the area under the receiver
operating characteristic curve (AUROC), on the joint probability of
valuable variables to determine the best cutoff point. The sensitivity,
specificity, positive and negative predictive values (PPVs, NPVs) as well
as the diagnostic accuracy of the final score were calculated at different
cutoff values.
3. Results
3.1. Description of the study population
Overall, 290 patients with LM were enrolled in this study. There were
162 males (55.8%), giving a male/female ratio of 1.2. The median age of
the study population was 30 years (IQR = [20–43]). Underlying diseases
were diabetes and hypertension in respectively 35 (12%) and 15 cases
(5.2%). A rural origin of enrolled patients was noted in 133 cases
(45.9%) (Table 1). The median duration of symptoms was 7 days (IQR =
[3-15jours]). With respect to laboratory findings, the median values of
blood white cells and platelets count were 8200/mm3 (IQR = [5920–10
970]) and 201000/mm3 (IQR = [153 250–263 000]), respectively. For
serum sodium and potassium levels in mmol/L, median values were
respectively 136 (IQR = [133.75–139] and 4 (IQR = [3.5-4-1]). As for
CSF findings, 250 patients (86.2%) had macroscopically a clear
appearance, 282 patients (97.2%) had a pleocytosis, with a median
value of 93 cells/mm3 (IQR = [50–217]) and 142 patients (48.9%) had a
CSF blood glucose ratio <0.5. The median value of CSF protein con­
centration was 0.8 g/L (IQR de [0.33–1.11]), and 233 patients (80.3%)
had a high protein level (>1 g/l). The main retained etiologies of LM
were TBM in 105 cases (36.2%), acute-benign LM in 31 cases (10.7%),
rickettsiosis in 11 cases (3.8%), West Nile, in 4 cases (1.4%), Varicella-
zoster Virus in 3 cases (1%), brucellosis in 2 cases (0.3%), Herpes Simplex
Virus, Cryptococcosis, pneumococcus, and Meningococcus and Legionellosis
in one case (0.3%), for each one. In 129 cases (44.5%), LM was non-
microbiologically documented. As for cerebral imaging, CT and MRI
were respectively conducted among 143 (49.3%) and 91 (31.4%) pa­
tients. The main radiological predictive features were arachnoiditis and
hydrocephalus in respectively 34 (11.3%) and 11 (3.8%) cases. The
median value of the total hospital stay was 10 days (IQR = [4–20]).
Tuberculous meningitis was diagnosed based on positive PCR on the CSF
in 23 cases (22%) and on other samples in 8 cases (7.6%), acid-alcohol-
resistant bacilli detected on sputum microbiological examination in 7
cases (6.7%), and on clinical, epidemiological, or imaging criteria sug­
gestive of TBM in 67 cases (63.8%). The CSF M. Tuberculosis culture was
negative in all TBM cases.
H. Ben Ayed et al. Decoding Infection and Transmission 1 (2023) 100003

Table 1
Comparison of clinical, laboratory and imaging features between patients with tuberculous and non-tuberculous meningitis at initial admission.
Variables Total (n = 290) (N, %) TB meningitis (n = 105) (N, %) Non-TB meningitis (n = 185) COR [95% CI] p

History, anamnestic and clinical criteria

Age ≥60 years 52 (17.9) 29 (27.6) 23 (12.4) 2.68 [1.45–4.95] 0.0016
Female gender 128 (44.1) 55 (52.3) 73 (39.4) 1.69 [1.04–2.77] 0.034
Rural origin 133 (45.9) 61 (58.1) 72 (38.9) 2.17 [1.33–3.54] 0.002
Underlying diseases
Diabetes 35 (12) 18 (17.1) 17 (9.2) 1.25 [0.46–3.38] 0.07
Hypertension 15 (5.2) 10 (9.5) 5 (2.7) 1.8 [0.50–6.36] 0.59
Presenting symptoms
Clinical onset: symptom duration ≥5 days 164 (56.5) 92 (87.6) 72 (38.9) 11.1 [5.79–21.3] <0.001
Fever 216 (74.5) 92 (87.9) 124 (68.6) 3.48 [1.8–6.71] <0.001
Thrill 91 (31.4) 57 (54.3) 34 (18.4) 5.27 [3.09–9] <0.001
Deteriorated general conditions 108 (37.2) 75 (71.1) 33 (17.8) 11.51 [6.53–20.29] <0.001
Headache 217 (74.8) 66 (62.8) 151 (81.6) 0.38 [0.22–0.65] <0.001
Emesis 128 (44.1) 22 (20.9) 106 (57.3) 0.19 [0.11–0.34] <0.001
Photophobia 93 (32.1) 19 (18.1) 74 (40) 0.33 [0.18–0.59] <0.001
Phonophobia 77 (26.5) 16 (15.2) 61 (32.9) 0.36 [0.19–0.67] <0.001
Coughing for 2 or more weeks 23 (7.9) 4 (3.8) 19 (10.3) 0.34 [0.11–1.04] 0.05
Physical exam findings
Convulsion 23 (7.9) 4 (3.8) 19 (10.3) 0.34 [0.11–1.04] 0.05
Confusion 8 (2.7) 3 (2.9) 5 (2.7) 1.05 [0.24–4.57] 0.9
Altered consciousness 38 (13.1) 9 (8.6) 29 (15.7) 0.50 [0.22–1.11] 0.085
Neck stiffness 173 (59.6) 50 (47.6) 123 (66.4) 0.45 [0.28–0.74] 0.002
Kernig sign 83 (28.6) 33 (31.4) 50 (27.2) 1.23 [0.73–2.09] 0.42
Brudzinski sign 63 (21.7) 26 (24.7) 37 (20) 1.3 [0,74-2,33] 0.37
Cranial nerve palsy 17 (5.9) 12 (11.4) 5 (2.7) 4.64 [1.58–13.58] 0.002
Focal neurological deficit 30 (10.3) 16 (15.2) 14 (13.3) 2.19 [1.02–4.70] 0.039
Cutaneous rash 30 (10.3) 6 (5.7) 24 (12.9) 0.4 [0.16–1.02] 0.05
Disease outcome
Hospital stay ≥10 days 150 (51.7) 83 (55,3%) 67 (44,7%) 16.64 [3.8–11.6] <0.001
Complicated form 85 (29.3) 67 (63.8) 18 (9.7) 16.35 [8.72–30.66] <0.001
Sequelae 23 (7.9) 17 (16.2) 6 (3.2) 5.76 [2.19–15.12] <0.001
Relapse 6 (2.1) 4 (3.8) 2 (1.1) 3,62 [0.65–20.13] 0.19
Death 14 (4.8) 11 (10.5) 3 (1.6) 7.09 [1.93–26.06] 0.001
Laboratory data
Blood leukocyte count <4000/mm3 11 (3.8) 9 (8.6) 2 (1.1) 8.57 [1.81–40.49] 0.002
Blood platelet count <150 000/mm3 63 (29.1) 29 (27.7) 34 (18.4) 1.69 [0.96–2.98] 0.067
Hyponatremia 116 (40) 64 (60.9) 52 (28.1) 1.85 [1.13–3.02] <0.001
Hypokalemia 55 (18.9) 10 (9.5) 45 (24.3) 0.32 [0.15–0.68] 0.02
CSF white cells count/mm3 < 100 148 (51) 82 (78.1) 66 (35.7) 2.12 [1.30–3.47] <0.001
CSF protein concentration >1 g/l 233 (80.3) 96 (91.4) 137 (74) 3.73 [1,75–7.97] <0.001
CSF/Blood glucose ratio <0.5 142 (48.9) 78 (74.2) 64 (34.6) 5.46 [3.20–9.3] <0.001
Cerebral imaging findings
Hydrocephalus 11 (3.8) 10 (9.5) 1 (0.5) 19.36 [2.44–153.56] <0.001
Arachnoiditis 34 (11.3) 29 (27.6) 5 (2.7) 13.73 [5.12–36.83] <0.001

N: Number, COR; Crude Odds Ratio, CI: Confidence interval, CSF: Cerebrospinal fluid.

3.2. Predictive factors of tuberculous meningitis
On univariate analysis, anamnestic and clinical factors that were sta­
tistically associated with TBM were age ≥60 years, female gender, rural
origin, symptom duration ≥5 days, fever, thrill, deteriorated general
conditions, cranial nerve palsy, and focal neurological deficit; whereas
headache, emesis, photophobia, phonophobia, and nick stiffness were
significantly associated with non-TBM. Disease outcome criteria were also
statistically associated with TBM, mainly a hospital stay ≥ 10 days, and
higher risk of complicated forms, sequelae, and death. As for laboratory
data, blood white cells count <4000/mm3, hyponatremia, CSF white cells
count/mm3 <100, CSF protein concentration >1 g/L, and CSF/blood
glucose ratio <0.5 were statistically more frequent among TBM patients.
With respect to imaging findings, hydrocephalus and arachnoiditis were
statistically predictive of TBM (Table 1).
By multivariate analysis, age ≥60 years, rural origin, symptom
duration ≥5 days, thrill, deteriorated general conditions, a hospital stay
≥ 10 days, complicated forms, blood white cells count <4000/mm3,
CSF/blood glucose ratio <0.5, hydrocephalus and arachnoiditis were
found to be independently associated with TBM (Table 2). The results of
Hosmer-Lemshow chi-square testing (χ2 = 5.66; p = 0.69) were indic­
ative of good calibration. For internal validation, the independent var­
iables of the cohort model were found to be independently associated
with TBM, after bootstrapped selection, with similar regression
coefficients.
3.3. Risk scoring system predictive of tuberculous meningitis
A weighted score was assigned to each risk factor found to be inde­
pendently associated with TBM, conferring a diagnostic index of 1 point
for age, rural origin, deteriorated general conditions, a hospital stay ≥
10 days and for complicated forms, 2 points for symptom duration ≥5
days, thrill, CSF/Blood glucose ratio <0.5, and arachnoiditis, 3 points
for blood white cells count <4000/mm3 and 4 points for hydrocephalus.
The individual DI were added together to produce an overall weighted
score ranging from 0 to 20 points. In our study, the median score value
was 5, with extremes of 0 and 16. The AUROC of this score was 0.94
(95% CI, 0.91–0.96; p < 0.001), indicating an excellent predictive
power in discriminating TBM (Fig. 1). When high risk was defined as an
overall score of ≥2, the scoring system had an excellent sensitivity and
negative predictive value (100%), but low specificity (16.8%), PPV
(40.5%) and diagnostic accuracy (46.8%). When the cutoff was raised to
6, the sensitivity slightly decreased (86.7%) and the specificity increased
appreciably (84.9%). This cut-off level was associated with an overall
accuracy of 85.5%. At an optimal cutoff point of 7, the model had the
best performance, with a sensitivity and a specificity of respectively 81%

3
H. Ben Ayed et al. Decoding Infection and Transmission 1 (2023) 100003

Table 2 other causes of acute LM might be an important issue, since the detec­
Multivariate logistic regression results for the diagnosis of tuberculous menin­ tion of microorganisms in CSF samples by microscopy or culture tech­
gitis and the corresponding diagnostic indexes of the scoring system. niques had low positive rates, which might render early diagnosis
Predictive finding β regression AOR [95% p Diagnostic difficult. Thus, a major stumbling block in TBM research had been the
coefficient CI] index score absence of a single reference standard test or standardized diagnostic
(points) criteria. Considering this, another approach to improving rapid diag­
Age ≥ 60 years 1.2 3.5 0.045 1 nosis in TBM, particularly in resource-limited countries is to develop
[1–11.9] easy-to-use diagnostic scores. This study proposed a new predictive
Rural origin 1.4 4.2 0.002 1
model of TBM that could be a useful tool for physicians.
[1.6–10.7]
Symptom duration 1.6 5 0.003 2 Bacteriological findings were poor, accounting for only 6.7% of acid-
≥ 5 days [1.7–14.4] alcohol-resistant bacilli and 22% of positive CSF-PCR from all TBM
Thrill 1.9 6.8 0.001 2 cases. These rates were lower than those reported in previous studies
[2.5–18.1] (30.5% of positive cultures).11 Although direct microscopy of acid-fast
Deteriorated general 1.4 4.1 0.002 1
conditions [1.7–10.3]
bacilli (AFB) smears is quick and relatively inexpensive, traditional
Blood leukocyte 3 20.6 0.017 3 visualization of CSF to evaluate for AFB by microscopy has been
count < 4000/ [1.7–48.5] demonstrated to have a poor sensitivity of 10–20%.12 This limitation is
mm3 likely due to the small number of bacilli in CSF, as TBM is a pauciba­
CSF/Blood glucose 1.52 4.6 0.001 2
cillary infection.13 Large CSF volumes can increase sensitivity by up to
ratio < 0.5 [1.8–11.5]
Arachnoiditis 1.8 6.3 0.006 2 60%.14 Cultures have a higher sensitivity than microscopy (50–70%),12
[1.7–23.4] but results can take several weeks to return, which might delay the
Hydrocephalus 4 55 [4–74.6] 0.003 4 diagnosis and then increase the risk of mortality. As for PCR techniques,
Complicated form 1.45 4.3 0.002 1
[1.7–10.8]
Hospital stay ≥ 10 1.48 4.4 0.002 1
days [1.6–11.4] Table 3
AOR: Adjusted Odds Ratio, CI: Confidence interval, CSF: Cerebrospinal fluid. Diagnostic performance of the new weighted score predictive of tuberculosis
with various cutoff points in patients with lymphocytic meningitis.
Cut- Sensitivity Specificity Positive Negative Diagnostic
and 91.4%, and accurately predicted 87.5% of the total negative and off (%) (%) predictive predictive accuracy
positive cases. At higher cut-off of 10, the model achieved a 100% of point value (%) value (%) (%)
specificity and PPV (Table 3). ≥2 100 16.8 40.5 100 46.8
≥4 98.1 53.5 54.4 98 69.6
4. Discussion ≥6 86.7 84.9 76.5 91.8 85.5
≥7 81 91.4 84.2 89.4 87.5
≥8 63.8 97.8 94.4 82.6 85.5
In countries with a high prevalence of TB, discriminating TBM from ≥10 27.6 100 100 70.9 73.8

Fig. 1. Abbreviation: ROC: Receiver-operator characteristic; CI: Confidence interval, AUROC: Area Under the Receiver-operator characteristic curve.

4
H. Ben Ayed et al.
they were not available previously in limited resources countries. A
recent metanalysis reported that MTB/RIF had a good sensitivity
(80.5%) according to a WHO review, and a specificity of 97.8%,
compared to traditional result.15 Based on these results, the WHO at that
time recommended the use of Xpert MTB/RIF as the preferred initial test
for the diagnosis of TBM.16
Because of the low sensitivity and the difficult use of these tech­
niques, the establishment of a diagnostic scoring system based on clin­
ical and routine laboratory examinations in the local context is
warranted. Some data and methods exist for comparison of TBM with
bacterial meningitis, such as Thwaites’ scoring system and the Lancet
scoring system that have been commonly used to improve diagnostic
accuracy. Clinically, most cases of TBM and bacterial can be differen­
tiated by CSF and serum laboratory findings. Nevertheless, some re­
searchers reported that Thwaites’ diagnostic scoring system was highly
effective in the differential diagnosis of TBM and initially treated BM,
but not TBM and partially treated bacterial meningitis.17 This study
suggested a simple new score for the diagnosis of TBM based on clinical,
laboratory and imaging results. High weighted diagnosis indexes were
attributed to hydrocephalus (4 points) and arachnoiditis (2 points),
which emphasized on the importance of cerebral imaging in diagnosing
TBM. Keeping in mind that it is not necessarily to have abnormal CT or
MRI findings or non-specific signs such as cerebral oedema in patients
with TBM, other imaging outcomes has been reported as independent
predictors of TBM diagnosis, such as meningeal enhancement, brain
parenchyma nodules (tuberculomas) and arachnoiditis,18–20 as opposed
to hydrocephalus. These discrepancies could be due to the stage of the
pathology process, and that not all patients included in this study
routinely undergo spinal cord MRI.
Some studies on TBM have emphasized that hyponatremia and cra­
nial nerve palsy are frequently associated with poor outcomes.21
Furthermore, TBM classically presents with an insidious onset of
symptoms that can lead to a delay in treatment initiation. This finding
could explain that worse neurological stage (complicated forms), longer
hospital stay, advanced age and systemic symptoms were also strong
predictors of TBM. In addition, CSF laboratory data are a vital part of the
diagnosis of the central nervous system infections. Similar to our result,
CSF/blood glucose ratio was widely reported in literature as a potential
predictor of TBM (6,22,23), although it best predicted bacteriologically
confirmed form.
Given that delay in initiating treatment leads to poor prognosis,
empirical anti-TB treatment is often initiated based on the non-specific
CSF parameters without evidence supporting etiology. Although it is
lifesaving for these patients, it also exposes them to several unnecessary
toxicities. Thus, establishing a diagnosis rule incorporating a maximum
of TB arguments is of an utmost need to better predict specifically TBM
patients. The present study has allowed a rapid diagnosis of TBM among
all LM using a new score, including clinical, biology, and imaging data
patients with a good performance. Some scoring systems using clinical
and laboratory characteristics have been developed and identified in
multivariate logistic regression analysis potential predictors of TB; such
as age, medical history, WBC count, CSF total WBC count, and CSF
neutrophil ratio. Sensitivities and specificities of the above scores varied
widely, ranging from 50% to 90%, suggesting that diagnostic rules
behave differently in different settings and populations.24–26 For this
reason, it is necessary to establish our own diagnostic scoring system
among Tunisian population. To facilitate its application in current
clinical practice, we propose a diagnostic score with different cut-off
values, to be applicable at different clinical circumstances. At a
threshold of 2, the score had an excellent sensitivity, but a low speci­
ficity, suggesting that TBM could be perfectly excluded for patients with
a score of <2 points at admission. If only subjects with a score of 6 or
above had been given empiric anti-TB therapy, 84.9% of patients would
have received appropriate initial therapy and only 15.1% would have
been treated too broadly. Even if the cut-off point is raised to 7, the
sensitivity remains high and the specificity increases to 91.4%,
5
Decoding Infection and Transmission 1 (2023) 100003
reflecting that only 8.6% of patients with non-TBM would receive
inappropriately an anti-TB treatment. This threshold presented the
better diagnostic accuracy (87.5%) and could be applicable in
mass-screening and in TB high-risk populations as well.
The present score accurately predicted TBM with high specificity and
sensitivity values at different cut-off points, which constitutes a strength
of our study. Moreover, the spectrum of patients in our study comprises
mainly patients with non-microbiologically confirmed meningitis, as
opposed to most of previous studies, which corresponds more closely to
routine clinical practice and its challenges. Another interesting point is
that our model was not exclusively used for subgroups, such as bacterial
or viral meningitis, but included all LM patients.
However, this study had some limitations. Firstly, this was an
observational study, which introduced the risk of incomplete informa­
tion from medical records, data for some of the variables were missing
and could not be introduced into the logistic regression analysis. Sec­
ondly, not all patients underwent cerebral imaging, which may under or
overestimate some covariates in the model. Finally, our model was only
internally validated using bootstrapping, justifying that multicenter and
nation-wide studies are warranted to externally validate the clinical
performance of this scoring system.
5. Conclusion
This original study provided an insight into the clinical, biological,
and imaging predictors of TBM among LM patients. We proposed a novel
scoring system that can reliably identify patients with TBM at hospital
admission and could be easily used in clinical practice. This cost-
effective strategy is of a great benefit in settings with limited microbi­
ological diagnostic support and could be generalized also to those with a
high TB prevalence and limited resources countries. Further validation
studies on this novel predictor should be perused to guide appropriate
anti-TB treatment and to improve the prognosis of this infection.
Ethics approval and consent to participate
Ethical considerations were conducted according to The Declaration
of Helsinki. Ethics approval was obtained from the Institutional Ethics
Review Board. Data were collected from medical records without patient
contact, and these data were collected with confidentially and ano­
nymity. All data were anonymized for use in writing and preparing this
manuscript.
Consent for publication
All data presented in this study were approved and all authors con­
sent for publication.
Fundings
None.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgment
None.
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