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Running head: THE EPIDEMIOLOGY OF HISTOPLASMOSIS
The Epidemiology of Histoplasmosis
Katelyn Strasser
September 26, 2013
Applied Epidemiology MPH 510
Concordia University Nebraska
THE EPIDEMIOLOGY OF HISTOPLASMOSIS
Histoplasmosis is a fungal infection that in humans is caused by one of two
subspecies of Histoplasma capsulatum. Although this infection can be acquired
many places throughout the world, it is endemic in parts of Africa, Asia, in Central
and South America, and in North America in the Mississippi and Ohio River Valley
(Luo et al., 2012). In the United States, histoplasmosis is the most common endemic
fungal infection found in humans, infected around 250,000 people each year.
Histoplasmosis is often asymptomatic in people with the illness, presenting
symptoms in just 5% of those infected (Fayyaz, 2013). However, it is becoming an
increasing significant public health concern as healthy individuals and those
immunocompromised are being treated for the illness in a growing number of
countries.
H. capsulatum is usually found in soil, and most often in soil that is
contaminated with bird or bat droppings. The microorganism may harbor in soil for
years (Luo et al., 2012). Humans acquire the illness when they inhale the H.
capsulatum spores from soil (MMWR, 2012). Areas endemic for the infection share
a characteristic humid and temperate climate, which allow for the microorganism’s
growth. Places with high rates of infection are usually associated with activities that
disturb the soil or that have bird or bat droppings. Activities such as archaeology,
ploughing, and construction work can overturn soil and allow the fungal spores to
spread (Norman et al., 2009). Bat and bird droppings actually bolster the growth of
the microorganism by increasing the rate of sporulation (Baddley et al., 2011).
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
In areas where histoplasmosis is endemic, 50-80% of people who live there
show proof, through laboratory testing, of having had the infection at one point. It is
difficult for epidemiologists to calculate morbidity and mortality rates for this
infection because many people remain asymptomatic. Furthermore, symptoms
similar to pneumonia often mask the true identity of the illness (CDC, 2012). The
incubation period is anywhere from three to seventeen days and symptoms may
include, fever, chest pain, a dry or nonproductive cough, joint pain, and anorexia.
More life threatening symptoms can occur if the disease disseminates throughout
the body. Luo et al. (2012) writes that the infection is diagnosed through the
“detection of the fungus in organic fluids or tissues, culture of biological samples,
and serologic assays.” Treatment is usually a type of anti-fungal antibiotic. (Luo et
al, 2012).
H. capsulatum skin tests have provided positive results for similar numbers
of men and women. Women with the disease seem to develop more rheumatologic
complications. Anyone can contract histoplasmosis, but it occurs more often in
immunocompromised people and others with weaker immune system such as
young children and the elderly (CDC, 2012). Progressive disseminated
histoplasmosis is more common in the immunosuppressed patients, resulting in 1
case per 2000 adults from this group (Loulergue, et al., 2007).
Although it is difficult to identify the incidence and prevalence of the disease
in the United States, one study found the cumulative incidence of cases of the illness
that required hospitalization. The study found the cumulative incidences for both
children and adults, according to regions of the country. Figure 1 shows that the
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
highest incidences were in the Southern and Midwestern parts of the United States.
For example, the cumulative incidence of the number of children that needed to be
hospitalized because of histoplasmosis in the Southern part of the United States was
3.05. The cumulative incidence in the Midwestern part of the United States was
27.08 in 2002. Table 1 highlights the demographic and clinical features of children
and adults hospitalized for histoplasmosis and other endemic mycosis in 2002.
According to this data, adults are affected more often than children, and the number
of cases affecting white adults more than doubled the cases of other ethnicities. As
expected, many of these patients were already immunocompromised (Chu, Feudtner,
Heydon, Walsh, & Zaoutis, 2006). Other epidemiological studies of the illness have
focused on specific populations such as the elderly, HIV positive individuals,
travelers and immigrants, those who work in occupationally hazardous, and others
living in endemic areas (Loulergue, 2007).
The weakened immune systems of many elderly people cause them to be
more susceptible to histoplasmosis and other fungal infections. A retrospective
cohort study was conducted to find statistics on three fungal infections in elderly.
The study used claims data from 1999-2008 that was taken from a “random 5%
national sample of Medicare beneficiaries” (Baddley et al., 2011). All of the
participants had certain selection criteria, including being age 65 or older at the
beginning of the study. Along with histoplasmosis, coccidoidomycosis and
blastomycosis were also studied in this research. 357 of the 1,913,247 people
studied were found to have histoplasmosis. Out of the almost two million people,
the mean age was 75.7 years and a little over half of the patients were male.
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
Common co-morbidities of this disease included COPD, diabetes mellitus, solid
malignancy, and rheumatoid arthritis (Baddley et al., 2011).
Among this cohort, the incidence rate of histoplasmosis was 3.3. This was
the highest incidence rate among the three mycosis. Geographic distribution maps
showed definitive areas of higher rates of histoplasmosis (Figure 2). The Midwest
had the highest incidence rate at 6.1, with rates of 13.0 and 12.0 in Indiana and
Arkansas, respectively. Although many of the cases occurred in traditional
histoplasmosis endemic areas, some of the cases were reported in non-endemic
areas. This suggests that additional research is needed to understand why people
living in non-endemic areas are contracting the illness. Another conclusion from
this study is that immunosuppression plays a major role in this patient population.
Since people are living longer, the elderly are more likely to be immunosuppressed
because of pending transplantation or from receiving chemotherapy or
immunosuppressive drugs due to other conditions (Baddley et al., 2011).
Increased longevity may also allow older people to travel to areas where they
are exposed to H. capsulatum. Travel to an endemic area is certainly a risk factor for
acquiring the illness. One outbreak of histoplasmosis in a group of travelers in
Nicaragua illustrated that the illness can occur in young, healthy individuals as well.
In this case, a group of travelers contracted histoplasmosis while visiting a small
cave that had live bats and bat guano on the ground. The infection rate of this group
was 100%, as 14 of the 14 travelers tested positive for the illness. Contrary to other
studies, the majority of those infected showed symptoms (12 out of 14). Half of the
symptomatic persons developed mild to moderate respiratory distress, measured
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
by the patient’s oxygen saturation. Interestingly, the two people who were
asymptomatic had prior exposure to bats or caving (Weinberg et al., 2003). Other
research has suggested that exposure provides partial immunity later in life
(Baddley et al., 2011). No substantial differences in symptoms were attributed to
sex, previous spelunking, residence in areas endemic to histoplasmosis, or activities
while in the cave. This outbreak demonstrates the risk of histoplasmosis as a travelrelated illness. It shows that when exposed to high concentrations of H. capsulatum
spores, even groups of healthy travelers from areas of low histoplasmosis
prevalence can have high attack rates of the illness and develop symptoms
(Weinberg et al, 2003).
Increased travel due to tourism and immigration has brought histoplasmosis
to areas that were not formerly endemic. Europe in particular has found many
recent cases of the disease in people traveling to the continent. In fact, histoplasmin
skin tests have given evidence that the incidence of Europeans who have traveled to
Latin American countries may have an infection rate of as high as 20%. Clinical
manifestations of the disease vary from patients being asymptomatic, to the disease
spreading and causing systemic problems. Most Europeans with the illness can be
placed into one of two categories. Some are people who have traveled to endemic
areas, were exposed to spores, and develop short-term effects of the illness from
which they recover. The second group is comprised of immigrants or expatriates
from endemic regions who are immunosuppressed. Much of the
immunosuppression occurs because the same person also has HIV. The illness is
particularly dangerous for these patients, as these people are more likely to develop
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
disseminated forms of the infection with mortality rates up to 50%. (Norman et al.,
2009).
Because symptoms of histoplasmosis are commonly seen in HIV patients, this
infection is actually an AIDS-defining opportunistic infection. Before HIV positive
patients received the highly-active antiretroviral therapy (HAART), the prevalence
of histoplasmosis in HIV infected individuals was around 30%. Histoplasmosis is
more common in patients with CD4 counts below 50/mm3, and it usually spreads
throughout the body, even appearing on the skin as lesions (Loulergue et al., 2007).
A second type a organism that causes histoplasmosis is H. capsulatum var.
duboisii. All of the examples so far in this paper have been based on H. capsulatum
var. capsulatum. This second variety is much more rare, with Africa being the only
continent to produce the illness. For this reason, it is sometimes called the African
histoplasmosis. Although H. capsulatum var. capsulatum is often seen in patients
with HIV, the coinfection of African histoplasmosis and HIV is rare, even with the
overwhelming number of people infected with HIV in Africa. Literature has
documented less than 300 cases, and the prevalence of the variety duboisii has not
been researched in Africa in HIV-negative patients. The reason for this variety’s
rarity is unknown, but some speculate that AIDS victims die before the
histoplasmosis develops or that capsulatum is more potent than dubuoisii. Those
HIV positive people that do contract the disease usually present with manifestations
of the infection in other places besides the lungs. Locations of the infection for HIV
positive patients are lymph nodes, skin, bones, in the gastrointestinal tract, and
other places throughout the body, but none appear in the lungs. Those that contract
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
the illness but do not have HIV find the virus within their lungs, causing respiratory
symptoms (Loulergue et al., 2007).
No matter the variety of histoplasmosis that occurs in African nations, it is
undoubtedly a very risky illness for these people to acquire, with so many of them
also having HIV. The histoplasmosis skin test has shown a 3% prevalence in areas
endemic to he infection. Rural populations have shown an even higher prevalence
of around 35%, especially in people in work in occupations where environmental
exposure to the fungus is evident. The occurrence of both types of histoplasmosis in
Africa continues to be researched (Loulergue et al., 2007)).
As mentioned within the African population, contraction of histoplasmosis
can be an environmental occupational hazard. Any occupation that exposes
workers to soil contaminated with bird or bat droppings, especially in endemic
areas, can pose a greater risk of infection. These types of jobs include bridge
inspector, construction worker, farmer, pest control worker, spelunker, and many
more. The spores of H. capsulatum are not stagnant, and can actually be carried long
distances by the wind when dust is disturbed. Airborne travel of spores is blamed
for the three largest outbreaks of histoplasmosis ever noted in history. All three
outbreaks, occurring in 1979, 1980, and 1988, took place in Indianapolis, Indiana.
In 1979, 120,000 people were infected by the illness, resulting in 15 deaths. Half of
the victims in the third outbreak were AIDS patients. Workers are encouraged to
wear personal protective equipment as recommended by the National Institute for
Occupational Safety and Health (NIOSH) and avoid contaminated soil when possible
(Lenhart, Schafer, Singal & Hajjeh, 1997).
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
One population of workers exposed to histoplasmosis was a group of camp
counselors. In June 2012 in Nebraska, there was an outbreak of respiratory illness
among a group of 32 camp counselors. One of the counselors had a confirmed
laboratory diagnosis of histoplasmosis. 59% of the 32 counselors had symptoms
that fit the case definition of the infection, and 31% received medical care for their
symptoms. Some of the young campers also contracted the illness. Of the 153
children who allowed a laboratory sample or filled out a questionnaire, five had
confirmed cases of the infection and twelve more were suspected. Environmental
assessment of the area demonstrated that children assigned to a campsite with
guano had 2.4 times the odds of infection as children whose campsite was over 21
yards away from the droppings (MMWR, 2012). This outbreak demonstrated how
even recreational activities can cause exposure to the infection.
Although many small studies about this infection exist, there is not much
data available on national morbidity and mortality rates. One reason for this is that
the disease itself often difficult to detect because in most people it doesn’t produce
symptoms. Another issue with acquiring data on this topic is that the illness is only
reportable in a handful of states, and no national surveillance system exists (CDC,
2012). Instituting a national reporting system would be prudent because then
researchers could see where a majority of the cases are coming from. As the
population ages, more elderly people with weaker immune systems are likely to be
infected. Also, further epidemiological research into the duboisii variety would be
interesting, since this is so rare and is not usually seen in conjunction with HIV.
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
Since people with HIV are achieving longer life spans, data on opportunistic
infections may prove beneficial in knowing how to prevent and treat the illness.
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
Figure 1
Cumulative incidences of cases of histoplasmosis (HISTO), blastomycosis (BLASTO),
and coccidioidomycosis (COCCI) requiring hospitalization in the United States, 2002.
Data are the estimated number of hospitalized patients per 1 million US persons (Chu,
Feudtner, Heydon, Walsh, & Zaoutis, 2006).
Figure 2
Geographic distribution of histoplasmosis in persons >65 years of age, United States,
1999–2008. Values are no. cases/100,000 person-years (Baddley et al., 2011).
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
Table 1
Demographic and clinical features of hospitalized children and adults with endemic
mycoses in the United States during 2002 (Chu, Feudtner, Heydon, Walsh, & Zaoutis,
2006).
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THE EPIDEMIOLOGY OF HISTOPLASMOSIS
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