1. Determinants of Penicilliosis Seasonality in Ho Chi Minh City, Vietnam Philip L. Bulterys, 1 Thuy Le, 2,3 Vo Minh Quang, 4 Kenrad E. Nelson, 5 James O. Lloyd-Smith 6,7 1 UCLA-Caltech Medical Scientist Training Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; 2 Wellcome Trust Major Overseas Program, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; 3 Hawaii Center for AIDS, University of Hawaii at Manoa, Honolulu, HI; 4 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; 5 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; 6 Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, CA; 7 Fogarty International Center, National Institutes of Health, Bethesda, MD

2. Organism: Penicillium marneffei HIV-associated opportunistic dimorphic fungus (mold at room temp, yeast at 37 o C). Endemic in South East Asia (third most common OI in the region). Usually seen in patients with CD4 < 100. Suspected mode of transmission: inhalation from environmental reservoir. Suspected reservoir: soil (not confirmed). Hosts

3. Incidence follows the season...... and HIV prevalence. (Chariyalertsak et al. JID 1996) (Vanittanakom et al. CMR 2006) Seasonality

4. Objectives All P. marneffei, Cryptococcus neoformans, and HIV-related hospital admissions to the Hospital for Tropical Disease (HTD) in Ho Chi Minh City, Vietnam from 2004-2010. High resolution temperature, humidity, wind, and precipitation data for the corresponding period. Multivariate linear regression modeling to identify factors significantly associated with P. marneffei and C. neoformans admissions. Estimate the P. marneffei incubation period by incorporating different exposure-to-admission delays in models. Methods To identify environmental factors associated with seasonal admissions of P. marneffei. To estimate the P. marneffei incubation period.

5. Results 719 HIV-infected patients admitted with P. marneffei 1,598 HIV-infected patients admitted with C. neoformans. Clinical features of P. marneffei admissions (Le et al. CID 2011): Fever (82%) Skin lesions (71%) Anorexia (62%) Hepatosplenomegaly (56%) Reticulonodular (50%) and interstitial (39%) findings on chest radiograph P. marneffei admissions were most strongly associated with humidity C. neoformans admissions were not seasonal, but associated with low wind velocity.

7. Distribution of total P. marneffei and C. neoformans admissions and mean humidity by month (2004-2009)

8. Number of Patients (2004-2009) Monthly Humidity (%) P. marneffeiC. neoformansOdds Ratio (95% Confidence Interval) <70115330 Reference 1.0 70-844361025 1.22 (0.96-1.55) ≥85126243 1.49 (1.10-2.01) Categories of Humidity and P. marneffei Admissions

9. Incubation Period Estimation P < 0.001 P < 0.005 Interpretation: Humidity predicts P. marneffei admissions, with an estimated incubation period of 1-3 weeks.

10. Summary Key Findings Humidity, not rainfall, is the most important predictor of P. marneffei admissions in Ho Chi Minh City, Vietnam. P. marneffei likely has an incubation period of 1-3 weeks. Discussion Humidity may drive infection by facilitating fungal growth in the environment, or expansion of the environmental reservoir. Fungal growth may take place on air-exposed plant and soil surfaces (rainfall  fungal growth in deeper soil and animal burrows). Earlier HIV diagnosis and seasonal antifungal drug prophylaxis (for patients in the early stages of HAART) may be helpful in preventing penicilliosis.

11. Acknowledgements Microbiology Department and Scientific and Planning Office, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam Lloyd-Smith Lab (UCLA Department of Ecology and Evolutionary Biology): Ruian Ke, Claude Loverdo, and others Funding UCLA-Caltech Medical Scientist Training Program (MSTP) and the Paul and Daisy Soros Fellowships for New Americans (PLB) Fogarty International Clinical Research Fellowship, Hawaii Center for AIDS, and Wellcome Trust Major Overseas Program (TL) De Logi Chair in Biological Sciences, and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health (JLS)