Very low levels of 25-hydroxyvitamin D are not associated with immunologic changes or clinical outcome in South African patients with HIV-associated cryptococcal meningitis.
BACKGROUND
Vitamin D deficiency is associated with impaired immune responses and increased susceptibility to a number of intracellular pathogens in individuals infected with human immunodeficiency virus (HIV). It is not known whether such an association exists with Cryptococcus neoformans.


METHODS
Levels of 25-hydroxyvitamin D (25[OH]D) were measured in 150 patients with cryptococcal meningitis (CM) and 150 HIV-infected controls in Cape Town, South Africa, and associations between vitamin D deficiency and CM were examined. The 25-hydroxyvitamin D levels and cryptococcal notifications were analyzed for evidence of reciprocal seasonality. Associations between 25(OH)D levels and disease severity, immune responses, and microbiological clearance were investigated in the patients with CM.


RESULTS
Vitamin D deficiency (plasma 25[OH]D ≤50 nmol/L) was present in 74% of patients. Vitamin D deficiency was not associated with CM (adjusted odds ratio, 0.93 [95% confidence interval, .6-1.6]; P = .796). Levels of 25(OH)D showed marked seasonality, but no reciprocal seasonality was seen in CM notifications. No significant associations were found between 25(OH)D levels and fungal burden or levels of tumor necrosis factor α, interferon γ, interleukin 6, soluble CD14, or neopterin in cerebrospinal fluid. Rates of fungal clearance did not vary according to vitamin D status.


CONCLUSIONS
Vitamin D deficiency does not predispose to the development of CM, or lead to impaired immune responses or microbiological clearance in HIV-infected patients with CM.
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom Botswana-University of Pennsylvania Partnership, Gaborone, Botswana Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Joseph N
JN
Jarvis
Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, United Kingdom.
Tihana
T
Bicanic
Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, United Kingdom.
Angela
A
Loyse
Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, South Africa Department of Medicine, Imperial College London, United Kingdom.
Graeme
G
Meintjes
Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, United Kingdom.
Louise
L
Hogan
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom.
Chrissy H
CH
Roberts
Transplant and Oncology Infectious Diseases Program, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Shmuel
S
Shoham
Department of Medicine, Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina.
John R
JR
Perfect
National Institute for Communicable Diseases-Centre for Opportunistic, Tropical and Hospital Infections, National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Nelesh P
NP
Govender
Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, United Kingdom.
Thomas S
TS
Harrison
D000328:Adult; D015169:Colony Count, Microbial; D003455:Cryptococcus neoformans / Q000302:isolation & purification; D016207:Cytokines / Q000134:cerebrospinal fluid; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000134:cerebrospinal fluid; D008297:Male; D016919:Meningitis, Cryptococcal / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D019798:Neopterin / Q000134:cerebrospinal fluid; D012621:Seasons; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000150:complications*
D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D014807:Vitamin D; D019798:Neopterin; C104450:25-hydroxyvitamin D
HIV; South Africa; cryptococcal meningitis; tuberculosis; vitamin D