Airborne dust and high temperatures are risk factors for invasive bacterial disease

Abstract

Background: The Sahel region of West Africa has the highest bacterial meningitis attack and case fatality rate in the world. The effect of climatic factors on patterns of invasive respiratory bacterial disease is not well documented.

Objective: We aimed to assess the link between climatic factors and occurrence of invasive respiratory bacterial disease in a Sahel region of Niger.

Methods: We conducted daily disease surveillance and climatic monitoring over an 8-year period between January 1, 2003, and December 31, 2010, in Niamey, Niger, to determine risk factors for bacterial meningitis and invasive bacterial disease. We investigated the mechanistic effects of these factors on Streptococcus pneumoniae infection in mice.

Results: High temperatures and low visibility (resulting from high concentrations of airborne dust) were identified as significant risk factors for bacterial meningitis. Dust inhalation or exposure to high temperatures promoted progression of stable asymptomatic pneumococcal nasopharyngeal carriage to pneumonia and invasive disease. Dust exposure significantly reduced phagocyte-mediated bacterial killing, and exposure to high temperatures increased release of the key pneumococcal toxin pneumolysin through increased bacterial autolysis.

Conclusion: Our findings show that climatic factors can have a substantial influence on infectious disease patterns, altering density of pneumococcal nasopharyngeal carriage, reducing phagocytic killing, and resulting in increased inflammation and tissue damage and consequent invasiveness. Climatic surveillance should be used to forecast invasive bacterial disease epidemics, and simple control measures to reduce particulate inhalation might reduce the incidence of invasive bacterial disease in regions of the world exposed to high temperatures and increased airborne dust.

Keywords: Meningitis; Neisseria meningitidis; Streptococcus pneumoniae; climate; dust; pollution.

Fig 1

Temporal changes in the causative agent and number of cases of bacterial meningitis in Niamey, Niger. Nm, Neisseria meningitidis.

Fig 2

Temporal changes in the number of meningitis cases with climatic factors in Niamey. Visibility is defined as the maximal distance from which an observer can distinctly see an object on a horizontal plane. RH, Relative humidity; T, temperature.

Fig 3

Relative risks for meningitis by maximal temperature from a threshold of 39.5°C. The gray zone corresponds to the 95% CI of the risks at greater than a maximal ambient temperature of 39.5°C. A significant effect was observed from a maximal ambient temperature of 39.5°C, and no significant effect was found at less than this value.

Fig 4

Inhaled dust and exposure to high temperatures increase invasiveness of S pneumoniae in mice. Mice were colonized with S pneumoniae serotype 2 strain D39 or a Niger serotype 1 meningitis isolate (ST303) and challenged intranasally with dust at 2 and 4 days after colonization. Mice were kept at room temperature (21°C) or 40°C, as indicated for 10 minutes before and 20 minutes after infection and dust/PBS exposure. A-C, CFU per milligram of tissue in the nasopharynx (Fig 4, A), lungs (Fig 4, B), and brain (Fig 4, C) at 7 days after infection. D, Kaplan-Meier survival curve. Asterisks represent significance in 1-way ANOVA with the Dunn posttest (Fig 4, A-C) or log-rank analysis (Fig 4, D). *P < .05, **P < .01, and ***P < .001.

Fig 5

Dust exposure inhibits phagocytosis, and high temperatures induce pneumococcal autolysis and PLY release. A and B, ELISA quantification of macrophage inflammatory protein 2 (MIP-2; Fig 5, A) and flow cytometric determination of neutrophil (Gr-1^high; Fig 5, B) numbers in lungs at day 5 after infection. C, Killing (as a percentage of total bacteria added) of D39 by J774 macrophages and HL-60 neutrophils with or without preincubation of phagocytes with dust. D, Triton X-100–induced autolysis of serotype 2 (D39) and its autolysin-deficient ΔlytA strain grown at either 37°C or 40°C. E, Hemolytic activity measured as increased OD after lysis of sheep erythrocytes. F, ELISA-calculated PLY concentration in filtered supernatant of D39 and ΔlytA grown at either 37°C or 40°C until A600 reached 1.0. Results are representative of 3 independent experiments and are shown as means ± SEMs. Asterisks represent significance in 1-way ANOVA with the Dunn posttest. *P < .05, **P < .01, and ***P < .001.