Christian Wejse

Wejse 2007 Wejse, Christian. 2007. The role of vitamin D in the pathogenesis and treatment of tuberculosis. Bandim Health Project, Statens Serum Institut. Department of Infectious Diseases, Aarhus University Hospital, Skejby. Faculty of Health Sciences, Aarhus University. 95 p.
  Vitamin D was in the pre-antibiotic era used for treatment of tuberculosis (TB). In recent years evidence on the important role of vitamin D in the immune response towards TB, and increased risk of TB in individuals with vitamin D deficiency has been described.

The aim of this investigation was to develop a tool to describe clinical outcome of TB, to determine the relation between vitamin D and TB in a high-burden country and test vitamin D as a possible supplementary treatment in this setting. Through two years of field studies at the Bandim Health Project (BHP), a Demographic Surveillance Site in Guinea Bissau, we conducted the following studies:

Study I
We developed a clinical severity score for TB based on the WHO manual for TB and HIV and applied the score to an existing dataset of TB-patients in the study area. We assessed the score for sensitivity to change during treatment, predictive capacity for later mortality and ability to describe improvement. The TB-score showed a high degree of sensitivity to change and classified 93% of the patients had high scores at treatment start and 79% had a low score at end of treatment. Being in the highest severity class predicted subsequent mortality with high accuracy.

Study II
Vitamin D status in 362 TB-patients and 494 healthy adults was determined. We found female sex, old age, certain ethnic groups and Moslem faith to be risk factors for low vitamin D status, whereas having no formal schooling was protective. Controls with vitamin D deficiency were also at higher risk of having Latent TB infection determined as a positive Mantoux test > 10mm. We found overall lower 25 hydroxy-vitamin D (25(OH)D3)concentrations among TB patients but severe vitamin D deficiency
(25(OH)D3 < 25nmol/I) was surprisingly rare among TB patients, although this was seen in 5% (24/494) of healthy controls. These differences remained when controlling for background factors. The data suggest a role of vitamin D in TB but it may just be a symptom.

Study III
We included 365 TB-patients in a randomised double-blind placebo-controlled trial and allocated 187 patients to 100,000 IU cholecalciferol and 178 to placebo. Patients were given cholecalciferol/placebo together with directly-observed antituberculous treatment. Cholecalciferol/placebo was repeated at 5 and 8 months of treatment. The primary outcome was clinical improvement assessed by the TB-score, the secondary outcome was mortality at 12 month follow-up. The clinical score outcome showed a similar decrease in severity score among vitamin D and placebo treated. No difference in weight gain or time to sputum conversion was found in the two arms. Overall mortality was 54/365 (15%) at one year follow up and did not differ significantly among the two groups. No serious adverse effects were reported, mild hypercalcemia was a rare event and present in both treatment arms, but analysis stratified for HIV-infected raised the question of vitamin D treated HIV-1 infected TB patients had higher mortality.

In conclusion a new tool for assessment of clinical severity and prediction of outcome in tuberculosis patients in low—resource settings has been developed; hypovitaminosis D was found more prevalent among TB patients than healthy controls in a West African population but severe deficiency was rare among patients with active TB; and supplementary treatment with high dosages of vitamin D had no general beneficial effect for patients with active TB.