Table 2.
Univariate and multivariate analysis of factors associated with clinical severity of 99 non-HIV CM patients.
| Variable | Univariate analysisa |
Multivariate analysis |
|||
|---|---|---|---|---|---|
| Mild group |
Severe group |
p value | OR (95% CI) | p value | |
| (n = 68) | (n = 31) | ||||
| Symptoms at presentation | |||||
| Vomiting | 28/68 (41·2) | 21/31 (67·7) | 0·014 | ||
| Epilepsy | 10/68 (14·7) | 11/31 (35·5) | 0·019 | ||
| CSF | |||||
| Cryptococcal antigen (≥1:1280) | 32/68 (47·1) | 22/31 (71·0) | 0·027 | ||
| Cytokine (pg/mL) | |||||
| IL-1β | 2·06 (1·26, 4·06) | 3·22 (2·33, 6·23) | 0·008 | ||
| IL-1ra | 395·04 (188·90, 1236·57) | 931·71 (449·10, 3008·76) | 0·003 | ||
| IL-2 | 4·32 (2·10, 6·48) | 7·33 (3·79, 12·38) | 0·003 | ||
| IL-4 | 1·28 (0·84, 1·93) | 1·76 (1·33, 2·48) | 0·017 | ||
| IL-6 | 837·81 (168·22, 2796·41) | 2673·00 (1233·49, 9831·26) | 0·003 | ||
| IL-8 | 708·11 (429·33, 1500·46) | 1905·49 (988·96, 3079·69) | 0·000 | ||
| IL-10 | 38·84 (25·12, 66·00) | 81·16 (43·91, 128·84) | 0·000 | 2·97 (1·49–5·90) | 0·002 |
| IL-12 | 3·95 (1·58, 6·69) | 5·72 (3·26, 9·11) | 0·010 | ||
| IL-13 | 4·31 (2·35, 12·25) | 9·11 (3·56, 21·69) | 0·029 | ||
| IL-15 | 22·18 (16·24, 32·23) | 31·16 (23·03, 41·14) | 0·001 | ||
| Eotaxin | 11·62 (7·97, 16·54) | 14·68 (11·04, 22·60) | 0·020 | ||
| IFN | 40·89 (22·34, 64·92) | 65·48 (43·80, 95·57) | 0·002 | ||
| MCP-1 | 205·16 (121·07, 431·35) | 367·25 (234·56, 726·76) | 0·003 | ||
| MIP-1α | 9·41 (4·68, 16·28) | 19·25 (8·97, 28·97) | 0·000 | ||
| PDGF-bb | 6·09 (3·71, 10·29) | 7·38 (5·68, 12·29) | 0·049 | ||
| MIP-1β | 83·51 (55·30, 119·20) | 151·82 (105·73, 227·85) | 0·000 | ||
| TNF-α | 31·68 (19·11, 65·08) | 52·34 (37·42, 79·49) | 0·005 | ||
| VEGF | 16·75 (13·68, 25·09) | 22·15 (19·51, 34·45) | 0·008 | ||
| Blood | |||||
| Positive culture of Cryptococcus | 11/67 (16·4) | 12/29 (41·4) | 0·009 | ||
| CRP (>8·20 mg/L) | 26/65 (40·0) | 19/28 (67·9) | 0·014 | 6·24 (1·61–24·18) | 0·008 |
| Pretreatment cranial MRI | |||||
| Ventriculomegaly | 5/60 (8·3) | 13/30 (43·3) | 0·000 | 11·23 (2·58–48·96) | 0·001 |
| TLR SNP | |||||
| rs5743604 C/C | 22/68 (32·4) | 17/31 (54·8) | 0·034 | ||
| rs3804099 C/T | 32/68 (47·1) | 8/31 (25·8) | 0·046 | ||
Data are n (%) or median (IQR). Missing data not provided by the sites are indicated by the denominators in each variable. HIV = human immunodeficiency virus. CM = cryptococcal meningitis. CSF = cerebrospinal fluid. MRI = magnetic resonance imaging. CRP=C-reactive protein. IL = interleukin. IFN = interferon. MCP = monocyte chemo attractant protein. MIP = macrophage inflammatory protein. PDGF = platelet-derived growth factor. TNF = tumor necrosis factor. VEGF = vascular endothelial growth factor. TLR = Toll-like receptor. SNP = single nucleotide polymorphism. Odds ratio for all numerical variables are per quartile increase, and for binary variables represent presence versus absence.
Factors included in the initial univariate analysis not shown in the table: [1] clinical factors: age, sex, predisposing factors, vital signs at presentation (fever, headache, and cranial nerve palsy), CSF examinations (CSF pressure, white blood cell count, lymphocyte count, glucose level, protein level, positive Indian ink smear, and positive culture for Cryptococcus), blood tests (cryptococcal antigen ≥1:1280, erythrocyte sedimentation rate, procalcitonin, D-dimmer, and serum calcium), Cryptococcus strain (Cryptococcus gatti), pretreatment cranial MRI (meningeal enhancement and single/multiple parenchymal lesions) and treatment (time to diagnosis >90 days, Amphotericin B-based treatment, and surgical intervention); [2] CSF cytokines: IL-5, IL-7, IL-9, IL-17, fibroblast growth factor-basic, granulocyte-colony stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-induced protein-10, and RANTES; [3] TLR SNPs: rs5743563, rs1927907, rs3796508, rs5743794, rs164637, and rs352140.