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-Smith6,7

1UCLA-Caltech Medical Scientist Training Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA; 2Wellcome Trust Major Overseas Program, Oxford

University Clinical Research Unit, Ho Chi Minh City, Vietnam; 3Hawaii Center for AIDS, University of Hawaii at Manoa, Honolulu, HI; 4Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam;

5Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;

6Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, CA; 7Fogarty International Center, National Institutes of Health, Bethesda, MD

Organism: Penicillium marneffei• HIV-associated opportunistic dimorphic fungus (mold at room temp, yeast at 37o 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

Incidence follows the season ...

... and HIV prevalence.

(Chariyalertsak et al. JID 1996)

(Vanittanakom et al. CMR 2006)

Seasonality

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.

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.

Jan Feb March April May June July Aug Sept Oct Nov Dec0tan19a566019

0tan9a56609

0tan29a566029

0tan19a566019

0tan10a566010

0tan30a566030

0tan20a566020

0tan11a566011

0tan1a56601

0tan29a566029

0tan4a56604

0tan9a56609

0tan14a566014

0tan19a566019

0tan24a566024

0tan29a566029

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Mean Humidity (%) P. marneffei C. neoformans

Tot

al N

umbe

r of C

ases

(200

4-20

09)

Mea

n H

umid

ity (%

)

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

Number of Patients (2004-2009)

Monthly Humidity (%)

P. marneffei C. neoformans Odds Ratio (95% Confidence Interval)

<70 115 330 Reference1.0

70-84 436 1025 1.22 (0.96-1.55)

≥85 126 243 1.49 (1.10-2.01)

Categories of Humidity and P. marneffei Admissions

0tan27a566027 0tan29a566029 0tan2a56602 0tan4a5660448tan27a566027

0tan28a566028

12tan28a566028

24tan28a566028

36tan28a566028

48tan28a566028

0tan28a566028

12tan28a566028

24tan28a566028

36tan28a566028

48tan28a566028

HumidityPrecipitation

Incubation Period (weeks)

Bet

a fo

r A

ssoc

iati

on (

SE)

Incubation Period Estimation

P < 0.001

P < 0.005 P < 0.005

Interpretation: Humidity predicts P. marneffei admissions, with an estimated incubation period of 1-3 weeks.

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.

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)