Effects of Environmental Exposures on: Pneumocystis jirovecii Pneumonia (PcP) Hospital Admissions; and Antibody Levels to Major Surface Glycoprotein among HIV-infected Patients from San Francisco

Abstract

Pneumocystis is an opportunistic pathogen for subjects with a compromised immune system, including patients with HIV+ infection, post organ-transplant patients, malignancy cancer patients and those receiving immunosuppressive drugs. Previous studies showed that about 85% of HIV-infected patients developed PcP at some time during their illness. However, with the introduction of HAART and the use of PcP prophylaxis, the frequency of PcP has decreased over time. In spite of this reduction in incidence, PcP currently is the second leading cause of morbidity among HIV-infected patients in the U.S. Although PcP causes serious outcomes in immunocompromised patients, some epidemiologic features are still puzzling scientists. Researchers are still struggling to agree on the mode of transmission and the effects of environmental factors.

The Major Surface Glycoprotein (Msg) is a crucial protein complex in Pneumocystis pathogenicity and is involved in host-organism interaction. This protein is encoded by a multicopy gene family and is capable of antigenic variation to allow Pneumocystis to evade the host immune response. However, the immunologic study of this organism has been hindered because Pneumocystis is difficult to grow, making it difficult to obtain native Msg in a large amount for Seroepidemiology studies. Recently, studies have used Msg as the main antigen to develop different recombinant fragments. Although studies showed that there are geographic variations and seasonal variation in antibody responses to Msg, no study has analyzed the effects of environmental factors on antibody levels to Msg fragments.

In the first aim of the study, the case-crossover design was used to identify environmental factors associated with PcP hospital admissions in San Francisco General Hospital (SFGH). Environmental data were collected from the National Air Quality database. Data from 457 HIV+ patients with advanced stages of HIV+ disease were analyzed. A significant seasonal variation of PcP hospital admissions was found (p<0.05). Increased of temperature and SO₂ levels was significantly associated with PcP hospital admissions (p<0.05). However, the effects of SO2</sub> were modified by the presence of CO.</sub>

In the second aim of the study, the influence of environmental factors on antibody levels to Msg fragments was determined. One hundred and thirty nine serum specimens sampled at the time of PcP admissions were analyzed. The levels of environmental factors at admission and two weeks before admission were measured, and Tobit regression models were used to determine the association between the environmental factors and antibody levels. It was found that after controlling for other environmental parameters, temperature measured at the time of admission was significantly associated with IgG antibody responses to both MsgC and MsgA. However, temperature measured two weeks before hospital admission was only significantly associated with IgG antibody levels to MsgA. There was a significant seasonal variation in antibody levels to MsgA, but not to MsgC.

In conclusion, this study shows that among environmental factors, temperature and SO₂ are independent risk factors for hospital admissions for HIV+ patients with PcP infection in San Francisco. It also shows that temperature fluctuations have significant effects on antibody levels to Pneumocystis infection.