NIOSH Publication No. 2005-109: Histoplasmosis — Protecting Workers at Risk	December 2004

Contents Disclaimer Foreword Authors and Acknowledgments   What is Histoplasmosis?   How is Histoplasmosis Diagnosed?   Where are H. capsulatum spores found?   Who can get histoplasmosis and what jobs and activities put people at risk for exposure to H. capsulatum spores? Should workers who might be exposed to H. capsulatum have pre-exposure skin or blood tests? What can be done to reduce exposures to H. capsulatum?   What are the advantages and disadvantages of various kinds of respirators for protecting workers against exposure to H. capsulatum? What personal protective equipment other than respirators should workers wear? What other infectious agents are health risks for workers who disturb accumulations of bat droppings or bird manure? Where can I get more information about infectious diseases and answers to questions about worker health and safety? References   Appendix

This document is also available in PDF format. 2005-109.pdf (Full Document) 42 pages, 677kb 2005-109FS.pdf (Worker/Employer Recommendations) 2 pages, 125kb 2005-109FS-sp.pdf (Worker/Employer Recommendations in Spanish) 2 pages, 127kb Related Resources/Publications: New NIOSH Method Offers Faster Way To Identify Risk For Job-Related Histoplasmosis - NIOSH Update Dec 16, 2002 The Prevention and Control of Wildlife Damage Series External Link: http://www.ces.ncsu.edu/ nreos/wild/wildlife/wdc/

Histoplasmosis
Protecting Workers at Risk

Foreword

This booklet is a revised edition of the NIOSH document Histoplasmosis:Protecting Workers at Risk, which was originally published in September 1997. The updated information in this booklet will help readers understand what histoplasmosis is and recognize activities that may expose workers to the disease-causing fungus Histoplasma capsulatum. The booklet also informs readers about methods they can use to protect themselves and others from exposure.

Outbreaks of histoplasmosis have shared similar circumstances:People who did not know the health risks of breathing in the spores of H. capsulatum became ill and sometimes caused others nearby to become ill when they disturbed contaminated soil or accumulations of bird or bat manure. Because they were unaware of the hazard, they did not take protective measures that could have prevented illness.

This booklet will help prevent such exposures by serving as a guide for safety and health professionals, environmental consultants, supervisors, and others responsible for the safety and health of those working near material contaminated with H. capsulatum. Activities that pose a health risk to workers at these sites include disturbance of soil at an active or inactive bird roost or poultry house, excavation in regions where this fungus is endemic, and removal of bat or bird manure from buildings.

Local, State, and national public health professionals may also find this booklet useful for understanding the health risks of exposure to H. capsulatum so that they can provide guidance about work practices and personal protective equipment. The appendix consists of a fact sheet about histoplasmosis printed in English and Spanish. This fact sheet is intended to help educate workers and the general public about this disease. We urge employers, health agencies, unions, and cooperatives to distribute the fact sheet to all potentially exposed workers.

John Howard, M.D. Director, National Institute for Occupational Safety and Health Centers for Disease Control and Prevention

What is histoplasmosis?

Histoplasmosis is an infectious disease caused by inhaling the spores of a fungus called Histoplasma capsulatum. Histoplasmosis is not contagious; it cannot be transmitted from an infected person or animal to someone else. ⁽¹⁾

H. capsulatum is a dimorphic fungus, which means it has two forms. ^(2,3) It is a mold (mycelial phase) in soil at ambient temperatures, and after being inhaled by humans or animals, it produces a yeast phase when spores undergo genetic, biochemical, and physical alterations. ⁽³⁾ Spores of H. capsulatum are oval and have two sizes. Macroconidia (large spores) have diameters ranging from 8 to 15 micrometers (µm), and microconidia (small spores) range from 2 to 5 µm in diameter. ⁽³⁾ Yeast cells of H. capsulatum have oval to round shapes and diameters ranging from 1 to 5 µm. ^(3–5)

Histoplasmosis primarily affects a person’s lungs, and its symptoms vary greatly. The vast majority of infected people are asymptomatic (have no apparent ill effects), or they experience symptoms so mild they do not seek medical attention and may not even realize that their illness was histoplasmosis. ⁽⁶⁾ If symptoms do occur, they will usually start within 3 to 17 days after exposure, with an average of 10 days. ⁽¹⁾ Histoplasmosis can appear as a mild, flu-like respiratory illness and has a combination of symptoms, including malaise (a general ill feeling), fever, chest pain, dry or nonproductive cough, headache, loss of appetite, shortness of breath, joint and muscle pains, chills, and hoarseness. ^(1,3,6–8)

A chest X-ray of a person with acute pulmonary histoplamosis will commonly show a patchy pneumonitis, which eventually calcifies. ⁽³⁾

Several years ago, pulmonary calcifications were thought to be associated with healed tuberculosis, when a person had actually had histoplasmosis instead. During the same period, individuals with histoplasmosis were admitted mistakenly to tuberculosis sanatoriums. ⁽⁹⁾ Unfortunately, some histoplasmosis patients acquired tuberculosis while residing in open wards with tuberculosis patients. ⁽³⁾

Chronic lung disease due to histoplasmosis resembles tuberculosis and can worsen over months or years. Special antifungal medications are needed to arrest the disease. ^{(1,5,6,10–12)} The most severe and rarest form of this disease is disseminated histoplasmosis, which involves spreading of the fungus to other organs outside the lungs. Disseminated histoplasmosis is fatal if untreated, ^(1,13) but death can also occur in some patients even when medical treatment is received. ⁽¹²⁾ People with weakened immune systems are at the greatest risk for developing severe and disseminated histoplasmosis. Included in this high-risk group are persons with acquired immunodeficiency syndrome (AIDS) or cancer and persons receiving cancer chemotherapy; high-dose, long-term steroid therapy; or other immuno-suppressive drugs. ^{(6,12,14–18)}

A person who has had histoplasmosis can experience reinfection after reexposure to H. capsulatum. Persons with immunity to H. capsulatum who become reinfected will usually experience a heightened inflammatory response, but they will have a less severe illness of shorter duration than what resulted from the primary infection. ^(3,5)

Not to be confused with reinfection, reactivation of latent (inactive) histoplasmosis can occur in elderly and immunocompromised individuals years after infection by H. capsulatum. ^(2,5) The metabolic activity of dormant yeasts and the methods that enable a microorganism to escape elimination by a host’s immune system are unknown. ⁽¹⁹⁾

Impaired vision can develop in some people because of a rare condition called “presumed ocular histoplasmosis syndrome.” ^{(3,5,20–22)} The factors causing this condition are poorly understood, and there is no scientific basis establishing H. capsulatum as its cause. ⁽⁵⁾ Results of laboratory tests suggest that presumed ocular histoplasmosis is associated with hypersensitivity to H. capsulatum and not from direct exposure of the eyes to the microorganism. What delayed events convert the condition from asymptomatic to symptomatic are also unknown. ⁽²³⁾ This syndrome should not be confused with the involvement of the eye associated on rare occasions with disseminated histoplasmosis. ^(3,5) Because the lesions of presumed ocular histoplasmosis syndrome do not progress, treatment is not necessary; however, treatment is essential with active cases of histoplasmosis of the eye. ⁽²⁴⁾

How is histoplasmosis diagnosed?

Histoplasmosis can be diagnosed by identifying H. capsulatum in clinical samples of a symptomatic person’s tissues or secretions, testing the patient’s blood serum for antibodies to the microorganism, and testing urine, serum, or other body fluids for H. capsulatum antigen. ⁽³⁾ On occasion, diagnosis may require a transbronchial biopsy. ⁽¹⁴⁾

Culturing of H. capsulatum

Culturing clinical specimens is a standard method of microbial identification, but the culturing process for isolating H. capsulatum is costly and time-consuming. ⁽²⁵⁾ To complicate matters, positive results are seldom obtained during the acute stage of the illness, except from clinical specimens from patients with disseminated histoplasmosis. ^{(6,12,14,25–27)} However, research advances in polymerase chain reaction technology have resulted in methods that provide rapid, first-line detection and prospective identification of H capsulatum in clinical samples. ^(24–30)

Serologic tests

Serologic evidence is often the prime factor in the diagnosis of histoplasmosis. ⁽³¹⁾ Rapid and accurate determination of serologic test results depends on the proper collection, storage, and shipment of serum specimens. Thus, following guidelines established for these activities is essential. ^(31–33)

Because of their convenience, availability, and utility, the most widely accepted serologic tests are the immunodiffusion test and the complement-fixation test. ^(8,25–27) Serologic test results are useful when positive. However, sometimes test results are negative even when a person is sick with histoplasmosis, a situation that arises especially in patients with weakened immune systems. ^(6,14,26)

The immunodiffusion test qualitatively measures precipitating antibodies (H and M precipitin lines or bands) to concentrated histoplasmin. ^(8,14,34) While this test is more specific for histoplasmosis (i.e., a person who is not infected with H. capsulatum is unlikely to have a positive test result) than the complement-fixation test, it is less sensitive (i.e., someone who is acutely infected can have a negative test result). ^(8,14,25) Because the H band of the immuno-diffusion test is usually present for only 4 to 6 weeks after exposure, it indicates active infection. ^(6,8,25) The M band is observed more frequently, appears soon after infection, and may persist up to 3 years after a patient recovers. ^(8,14)

The complement-fixation test, which measures antibodies to the intact yeast form and mycelial (histoplasmin) antigen, is more sensitive but less specific than the immunodiffusion test. ⁽¹⁴⁾ Complement-fixing antibodies may appear in 3 to 6 weeks (sometimes as early as 2 weeks ⁽³⁴⁾) following infection by H. capsulatum, and repeated tests will give positive results for months. ^(6,34) The results of complement-fixation tests are of greatest diagnostic usefulness when both acute and convalescent serum specimens can be obtained. A high titer (1:32 or higher) or a fourfold increase is indicative of active histoplasmosis. ^(8,26,27,34) Lower titers (1:8 or 1:16), although less specific, may also provide presumptive evidence of infection, ^(7,25) but they can also be measured in the serum of healthy persons from regions where histoplasmosis is endemic. (27) Antibody titers will gradually decline and eventually disappear months to years after a patient recovers. ^(6,8,25,34)

Detection of H. capsulatum antigen

A radioimmunoassay method can be used to measure H. capsulatum polysaccharide antigen (HPA) levels in samples of a patient’s urine, serum, and other body fluids. ^{(12,25,35,36)} The test appears to meet the important need for a rapid and accurate method for early diagnosis of disseminated histoplasmosis, especially in patients with AIDS. ^(12,25,36) HPA is detected in body fluid samples of most patients with disseminated infection and in the urine and serum of 25% to 50% of those with less severe infections. ⁽²⁵⁾

Histoplasmin skin test

The manufacturing of diluted histoplasmin for skin testing was stopped in January, 2000. The skin testing reagents were still unavailable when these guidelines were updated in 2004. A person could learn from a histoplasmin skin test whether he or she had been previously infected by H. capsulatum. This test, similar to a tuberculin skin test, had been available at many physicians’ offices and medical clinics. A histoplasmin skin test became positive 2 to 4 weeks after a person was infected by H. capsulatum, and repeated tests usually gave positive results for the rest of the person’s life. ⁽²⁶⁾ While histoplasmin skin test information was useful to epidemiologists, a positive skin test did not help diagnose acute histoplasmosis, unless a previous skin test was known to have been negative. ^(6,8,14) A previous infection by H. capsulatum can provide partial protection against ill effects if a person is reinfected. ⁽³⁴⁾ Since a positive skin test does not mean that a person is completely protected against ill effects, ⁽³⁴⁾ appropriate exposure precautions should be taken regardless of a worker’s skin-test status in the past.

Where are H. capsulatum spores found?

H. capsulatum grows in soils throughout the world. ^(2,14) In the United States, the fungus is endemic and the proportion of people infected by H. capsulatum is higher in central and eastern states, especially along the Ohio and Mississippi River valleys. ^(3,8,37) The fungus seems to grow best in soils having a high nitrogen content, especially those enriched with bird manure or bat droppings. The organism can be carried on the wings, feet, and beaks of birds and infect soil under roosting sites or manure accumulations inside or outside buildings. Active and inactive roosts of blackbirds (e.g., starlings, grackles, red-winged blackbirds, and cowbirds) have been found heavily contaminated by H. capsulatum. ^(34,38,50) Therefore, the soil in a stand of trees where blackbirds have roosted for 3 or more years should be suspected of being contaminated by the fungus. ^(42,51) Habitats of pigeons ^{(38–40,52–54)} and bats, ^(38,55–72) and poultry houses with dirt floors ^(38,73–78) have also been found contaminated by H. capsulatum.

On the other hand, fresh bird droppings on surfaces such as sidewalks and windowsills have not been shown to present a health risk for histoplasmosis because birds themselves do not appear to be infected by H. capsulatum. ^(34,79) Rather, bird manure is primarily a nutrient source for the growth of H. capsulatum already present in soil. ⁽²⁷⁾ Unlike birds, bats can become infected with H. capsulatum and consequently can excrete the organism in their droppings. ^{(27,62,65,80)}

Increasing numbers of resident Canada geese in urban and suburban areas have caused concern about whether droppings and water contaminated by their droppings are possible sources of disease transmission to humans. As with exposures to the fresh droppings of other birds, exposures to goose droppings have not been shown to be a health risk for histoplasmosis. However, the human pathogens Cryptosporidium, Giardia, and Campylobacter have been found in Canada goose droppings.^(81–83) The fecal-oral route is the primary route of ingesting pathogens that could cause infection and disease, notably diarrhea and gastroenteritis. ⁽⁸²⁾ Thus, people working in areas frequented by Canada geese, such as ground maintenance workers at golf courses and parks, should take precautions to prevent hand-to-mouth contact with droppings. ⁽⁸¹⁾

T o learn whether soil or droppings are contaminated with H. capsulatum spores, samples must be collected and cultured. The culturing process involves inoculating mice with small portions of a sample, sacrificing the mice after 4 weeks, and streaking agar plates with portions of each mouse’s liver and spleen. ⁽³⁸⁾ Then for four more weeks, the plates are watched for the growth of H. capsulatum. Enough samples must be collected so that small but highly contaminated areas are not overlooked. On several occasions, H. capsulatum has not been recovered from any of the samples collected from material believed responsible for causing illness in people diagnosed from the results of clinical tests as having histoplasmosis. ^{(39,40,61,74,84–86)} Molecular techniques, such as polymerase chain reaction methods that produce results in days instead of weeks, may provide less costly and quicker methods of analyzing soil samples for H. capsulatum. ⁽⁸⁷⁾

Until a less expensive and more rapid method is available, testing field samples for H. capsulatum will be impractical in most situations. Consequently, when thorough testing is not done, the safest approach is to assume that the soil in regions where H. capsulatum is endemic and any accumulations of bat droppings or bird manure are contaminated with H. capsulatum and to take appropriate exposure precautions.

Authors and Acknowledgments

This booklet was written by Mr. Steven W. Lenhart, Dr. Millie P. Schafer, and Dr. Mitchell Singal, National Institute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Prevention (CDC), and Dr. Rana A. Hajjeh, National Center for Infectious Diseases (NCID), also of CDC. Secretarial support was provided by Ms. Ellen Blythe. Ms. Priscilla Wopat, Spokane Research Laboratory, NIOSH, was the document’s editor. Ms. Pauline Elliott of NIOSH, formatted the document. The cover design and respirator drawings were created by Mr. Richard A. Carlson. The histoplasmosis fact sheet was translated to Spanish by Dr. Veronica Herrera-Moreno and Dr. Tania Carreon-Valencia. The authors also extend gratitude to Dr. Donald L. Campbell, Ms. Teresa A. Seitz, Mr. Kenneth F. Martinez, and Ms. Dawn G. Tharr of NIOSH; Dr. Ted Pass II of Morehead State University; and Dr. Myat Htoo Razak for their encouragement and invaluable contributions to this work.

Disclaimer

Mention of company names or products does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH) or the National Center for Infectious Diseases (NCID), Centers for Disease Control and Prevention (CDC).