The seasonality of tuberculosis, sunlight, vitamin D, and household crowding

Abstract

Background: Unlike other respiratory infections, tuberculosis diagnoses increase in summer. We performed an ecological analysis of this paradoxical seasonality in a Peruvian shantytown over 4 years.

Methods: Tuberculosis symptom-onset and diagnosis dates were recorded for 852 patients. Their tuberculosis-exposed cohabitants were tested for tuberculosis infection with the tuberculin skin test (n = 1389) and QuantiFERON assay (n = 576) and vitamin D concentrations (n = 195) quantified from randomly selected cohabitants. Crowding was calculated for all tuberculosis-affected households and daily sunlight records obtained.

Results: Fifty-seven percent of vitamin D measurements revealed deficiency (<50 nmol/L). Risk of deficiency was increased 2.0-fold by female sex (P < .001) and 1.4-fold by winter (P < .05). During the weeks following peak crowding and trough sunlight, there was a midwinter peak in vitamin D deficiency (P < .02). Peak vitamin D deficiency was followed 6 weeks later by a late-winter peak in tuberculin skin test positivity and 12 weeks after that by an early-summer peak in QuantiFERON positivity (both P < .04). Twelve weeks after peak QuantiFERON positivity, there was a midsummer peak in tuberculosis symptom onset (P < .05) followed after 3 weeks by a late-summer peak in tuberculosis diagnoses (P < .001).

Conclusions: The intervals from midwinter peak crowding and trough sunlight to sequential peaks in vitamin D deficiency, tuberculosis infection, symptom onset, and diagnosis may explain the enigmatic late-summer peak in tuberculosis.

Keywords: crowding; household; seasonality; sunlight; tuberculosis; vitamin D.

Figure 1.

Study design. Abbreviations: IGRA, interferon-γ release assay; TST, tuberculin skin test.

Figure 2.

Vitamin D status for the entire study population (n = 195) by sex and season. A, Vitamin D plasma concentration. B, Vitamin D concentration replete (ie, 25OHD concentrations ≥50 nmol/L). Bars represent 95% confidence intervals. Abbreviation: 25OHD, calcifediol.

Figure 3.

Schematic demonstrating the seasonality of tuberculosis risk factors in midwinter, infection in late winter and early summer, and disease in midsummer. Letters represent months of the year. Trend lines represent 6-month moving averages of raw data that differ slightly from the 6 monthly actual counts shown in Table 2, owing to the latter being raw data. In the “tuberculosis risk factors” section, hours without sunlight is represented by the thin continuous black trend line, vitamin D deficiency by the dashed black line, and crowding by the thick continuous black trend line. The numbers stated for the incidence of tuberculosis symptom onset and tuberculosis diagnoses are the 6-month moving average data corresponding to those in Table 2. Abbreviations: IGRA, interferon-γ release assay; TST, tuberculin skin test.