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      Notes from the Field: Increase in Coccidioidomycosis — Arizona, October 2017–March 2018

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          Abstract

          Beginning in October 2017, the Arizona Department of Health Services (ADHS) noted an increase in the number of reported cases of coccidioidomycosis (Figure). According to provisional data (not finalized), the incidence in December 2017 (17.2 per 100,000 population) represented the highest monthly rate in the last 5 years, surpassing the previous peak of 14.2 cases per 100,000 population in September 2015. In total, 4,827 cases of coccidioidomycosis were reported to ADHS during October 2017–March 2018. Whereas case counts typically increase during these months, this particular period represented a 58.3% increase over the 3,050 cases reported during the same months the previous year and a 50.3% increase over the 6-month average of 3,211 cases reported during October–March for the years 2013–2017. FIGURE Monthly incidence of coccidioidomycosis — Arizona, April 2013–March 2018 The figure is a line chart showing the monthly incidence of coccidioidomycosis in Arizona during April 2013–March 2018. Coccidioidomycosis (Valley fever) is an infectious disease caused by inhalation of Coccidioides spores; approximately 40% of infected persons experience signs and symptoms including fever, cough, fatigue, chest pain, shortness of breath, and rash. Coccidioides is endemic in soil in the southwestern United States ( 1 ). The majority of reported U.S. coccidioidomycosis cases occur in Arizona ( 2 ), and incidence is seasonal: the highest number of reported cases in Arizona typically occurs during the fall and winter months.* Because of the high number of cases in Arizona and the high predictive value of a positive laboratory result, Arizona’s coccidioidomycosis case definition requires only laboratory evidence to confirm a case ( 3 ). Laboratory evidence can include detection of anticoccidioidal immunoglobulin M (IgM) or immunoglobulin G (IgG) antibodies; culture, histopathologic, or molecular evidence of Coccidioides spp.; or coccidioidal skin test conversion after illness onset. During October 2017–March 2018, the median age of persons with reported coccidioidomycosis was 56 years (interquartile range [IQR] = 39–69 years); approximately half (50.5%) of patients were male. Age and sex distributions were similar to those observed during October 2016–March 2017, with a median age of 57 years, (IQR = 40–69); 51.2% of patients were male. Approximately 90% of persons with reported coccidioidomycosis in Arizona reside in the three most populous counties (Maricopa, Pima, and Pinal). During October 2017–March 2018, 3,674 cases were reported in Maricopa County (87.0 cases per 100,000 population), a 70.5% increase over the 2,157 cases (52.0 per 100,000 population) reported during the same period the preceding year. The number of reported cases and incidence also increased, but less sharply, in Pima County (31.5% increase, 601 cases, 58.6 per 100,000 population versus 457 cases, 45.1 per 100,000 population the preceding year) and Pinal County (29.5% increase, 329 cases, 76.9 per 100,000 population versus 254 cases, 61.5 per 100,000 population). To evaluate the possibility of laboratory or reporting artifact, data were reviewed to assess the proportion of cases that were coccidioidomycosis-positive by enzyme immunoassay (EIA) for IgM antibodies alone. EIA IgM alone has been reported to have lower specificity in some circumstances compared with other testing methods ( 4 ). There were 4,638 cases reported during October 2017–March 2018 where the type of laboratory test used could be classified; 602 (13.0%) tested positive by EIA IgM alone, compared with 316 of 2973 (10.6%) during the same months 1 year before. This slightly higher proportion of cases testing positive by EIA IgM alone is insufficient to explain the magnitude of the increase in cases during October 2017–March 2018. No known changes in provider or laboratory reporting occurred during this time. Reasons for the current increase in reported coccidioidomycosis are unknown but might include weather and environmental factors, including precipitation, which can facilitate growth of Coccidioides, followed by high temperatures and drought, which can facilitate distribution ( 5 ). Preliminary data suggest that 2017 was uncharacteristically warm and dry in central Arizona. † In addition, during 2016–2017, Maricopa County experienced the largest population gain of any county in the United States. § An increase in the number of susceptible persons and dust disturbance, resulting from increased residential construction, might have contributed to the increased incidence of coccidioidomycosis. Further investigation of the causes of increased coccidioidomycosis in areas with endemic transmission is crucial to informing strategies to prevent disease and educate providers and the public regarding the importance of appropriate diagnosis and management of coccidioidomycosis.

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          Coccidioidomycosis: epidemiology

          Coccidioidomycosis consists of a spectrum of disease, ranging from a mild, self-limited, febrile illness to severe, life-threatening infection. It is caused by the soil-dwelling fungi, Coccidioides immitis and C. posadasii, which are present in diverse endemic areas. Climate changes and environmental factors affect the Coccidioides lifecycle and influence infection rates. The incidence of coccidioidomycosis has risen substantially over the past two decades. The vast majority of Coccidioides infections occur in the endemic zones, such as California, Arizona, Mexico, and Central America. Infections occurring outside those zones appear to be increasingly common, and pose unique clinical and public health challenges. It has long been known that elderly persons, pregnant women, and members of certain ethnic groups are at risk for severe or disseminated coccidioidomycosis. In recent years, it has become evident that persons with immunodeficiency diseases, diabetics, transplant recipients, and prisoners are also particularly vulnerable.
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            Increase in Reported Coccidioidomycosis — United States, 1998–2011

            Coccidioidomycosis, also known as valley fever, is an infection caused by inhalation of Coccidioides spp. spores. This soil-dwelling fungus is endemic to arid regions of Mexico, Central and South America, and the southwestern United States (1). Symptomatic patients typically experience a self-limited influenza-like illness, but some develop severe or chronic pulmonary disease, and less than 1% of patients experience disseminated disease (1). Coccidioidomycosis can be costly and debilitating, with nearly 75% of patients missing work or school because of their illness, and more than 40% requiring hospitalization (2). Previous publications have reported state-specific increases in coccidioidomycosis in Arizona and California during 1998–2001 and 2000–2007, respectively (3,4). To characterize long-term national trends, CDC analyzed data from the National Notifiable Diseases Surveillance System (NNDSS) for the period 1998–2011. This report describes the results of that analysis, which indicated that the incidence of reported coccidioidomycosis increased substantially during this period, from 5.3 per 100,000 population in the endemic area (Arizona, California, Nevada, New Mexico, and Utah) in 1998 to 42.6 per 100,000 in 2011. Health-care providers should be aware of this increasingly common infection when treating persons with influenza-like illness or pneumonia who live in or have traveled to endemic areas. In collaboration with the Council of State and Territorial Epidemiologists (CSTE), CDC compiles data on selected diseases through NNDSS. Data are reported to CDC from various state and territorial surveillance systems and reporting mechanisms. Coccidioidomycosis has been nationally notifiable since 1995; however, it was not nationally notifiable in 2010. Although the CSTE case definition includes both laboratory and clinical criteria, Arizona uses a laboratory-only case definition because of its large number of cases and the high predictive value of a positive laboratory result (2); since 2008, the laboratory component of the CSTE definition has included cases with a single positive serologic test. California uses the CSTE case definition, requiring both laboratory and clinical evidence of infection, but some counties with large numbers of cases use a laboratory-only definition. State and regional annual incidence rates were calculated by dividing the number of cases by U.S. Census Bureau population estimates for each year. Crude, sex-specific, age-specific, and age-adjusted incidence rates (aIR) were calculated for Arizona, California, and other endemic states where coccidioidomycosis is reportable (Nevada, New Mexico, and Utah, combined). Rates were age adjusted using the 2000 U.S. standard population. Negative binomial regression was performed to assess statistical significance of incidence trends during 1998–2011. This model adjusts for changes in population size and age and sex distribution over time. During 1998–2011, a total of 111,717 coccidioidomycosis cases were reported to CDC from 28 states and the District of Columbia: 66% from Arizona, 31% from California, 1% from other endemic states, and <1% from nonendemic states. In Arizona, California, Nevada, New Mexico, and Utah combined, the number of cases increased from 2,265 in 1998 (aIR: 5.3 per 100,000 population) to 8,806 in 2006 (18.0 per 100,000); a decrease occurred in 2007 and 2008 before an increase in 2009 (12,868 cases; 25.3 per 100,000), which continued into 2010 and 2011 (42.6 per 100,000) (Table 1). Incidence in endemic states increased among all age groups during 1998–2011 (Figure). During this period, incidence typically was highest among the 40–59 year age group in California but was consistently highest among persons aged ≥60 years in Arizona and other endemic states. Incidence during 2011 was 381.1 per 100,000 among persons aged 60–79 years and 385.2 per 100,000 among persons aged ≥80 years in Arizona (Table 2). During 1999–2008, most (56%) Arizona cases occurred among males, but beginning in 2009, a higher proportion (55%) of cases occurred among females. Incidence in 2011 in Arizona was substantially higher among females (286.9 per 100,000) than males (215.7 per 100,000). In contrast, only 35% of California cases occurred among females during 1998–2011, and 2011 incidence among California males (20.5 per 100,000) was more than double that among females (9.7 per 100,000). The increase in the number of Arizona cases, from 1,474 in 1998 to 16,467 in 2011, was statistically significant by negative binomial regression (aIR: 30.5 per 100,000 in 1998; 247.7 per 100,000 in 2011, p<0.001). Adjusting for changes in population demographics, this corresponds to an increase in coccidioidomycosis incidence of approximately 16% each year during the study period. The number of California cases increased from 719 in 1998 (aIR: 2.1 per 100,000) to 5,697 in 2011 (aIR: 14.9 per 100,000) (average annual increase of 13%, p<0.001). The number of cases reported in Nevada, New Mexico, and Utah combined increased from 72 in 1998 (aIR: 1.4 per 100,000) to 237 in 2011 (aIR: 3.1 per 100,000) (p<0.001). Cases reported in nonendemic states increased from six in 1998 to 240 in 2011. Editorial Note This report describes statistically significant increases in the incidence rate of reported coccidioidomycosis in endemic states during 1998–2011 after adjusting for changes in population size and in age and sex distribution. Although the number of cases decreased in Arizona during 2007–2008 and in California during 2007–2009, incidence dramatically increased in 2010 and 2011. In 2011, coccidioidomycosis was the second most commonly reported nationally notifiable condition in Arizona and the fourth most commonly reported in California (5). The reasons for the increases described in this report are unclear. Coccidioides exists in the soil and is sensitive to environmental changes; factors such as drought, rainfall, and temperature might have resulted in increased spore dispersal, and disruption of soil by human activity, such as construction, also might be a contributing factor. Changes in surveillance methodology might have resulted in artifactual increases. California transitioned to a laboratory-based reporting system during 2010, which facilitated reporting and might account for the increase in reported cases in 2011. However, some highly endemic counties, such as Kern County, already had been using laboratory-based systems, so this cannot fully explain the recent increase. The observed increase in Arizona might be partially attributable to a 2009 change by a major commercial laboratory to conform its reporting practices to the 2008 CSTE case definition, whereby positive enzyme immunoassay (EIA) results were reported as cases without confirmation by immunodiffusion. One commercially available EIA test (Meridian Bioscience) commonly used to diagnose coccidioidomycosis has been described to have false-positive results in some instances (6), but the contribution of this phenomenon, if any, to the overall increase in cases is unknown. Improved awareness of coccidioidomycosis might have resulted in increased diagnostic testing (and thus reporting) in endemic and nonendemic states. Coccidioides has been found to be the etiologic agent in an estimated 15%–29% of community-acquired pneumonias in highly endemic areas (7). However, a 2006 study demonstrated that only a small proportion (2%–13%) of patients with compatible illness in an endemic area were tested for coccidioidomycosis (7), suggesting that the disease is greatly underreported. Further study is needed to understand if testing practices have changed. Despite the increase in reported cases, overall U.S. coccidioidomycosis mortality rates have remained fairly stable at approximately 0.6 per 1 million person-years during 1990–2008 (8). What is already known on this topic? Coccidioidomycosis is an infection that results from inhalation of Coccidioides spp. fungal spores. It is endemic in the southwestern United States, with the highest number of cases occurring in Arizona and California, and constitutes a substantial public health burden in these areas, particularly among older persons. What is added by this report? Reported coccidioidomycosis cases have increased dramatically in recent years. The age-adjusted incidence was 5.3 cases per 100,000 population in the endemic area in 1998 and 42.6 per 100,000 in 2011. Among persons aged 60–79 years in the endemic area, incidence was 69.1 cases per 100,000 in 2011. What are the implications for public health practice? The number of reported cases of coccidioidomycosis is increasing. Health-care providers should be alert for this infection among persons with influenza-like illnesses who live in or have traveled to endemic areas. Further research on strategies to reduce the morbidity of coccidioidomycosis is needed. The findings in this report are subject to at least four limitations. First, NNDSS data might underrepresent the actual burden of disease because coccidioidomycosis is not reportable in every state, even in known endemic areas such as Texas, and because state reporting of cases to CDC is voluntary. In particular, the number of cases reported in 2010 might underestimate the actual number of infections because coccidioidomycosis was not notifiable in 2010 (but became notifiable again in 2011). Second, minor discrepancies between the findings in this report and those presented in MMWR’s annual Summary of Notifiable Diseases reports likely exist because the summary does not include cases from states where the disease was not reportable. Third, minor discrepancies might exist between this report and state-specific reports because of delays in case reporting. Finally, because nearly 70% of cases were missing race/ethnicity data, incidence rates by race and ethnicity were not calculated. This is an important consideration because high rates among Asians and blacks have been documented previously, and black race has been shown to be an independent risk factor for disseminated coccidioidomycosis (9). Further investigation is needed to determine how much of the observed increase in coccidioidomycosis incidence is artifactual. Nevertheless, health-care providers should be alert for coccidioidomycosis among patients of all ages who live in or have traveled to endemic areas. Persons in endemic areas should consider trying to reduce exposure to dusty air, which might contain Coccidioides spp. spores. However, because there are currently no proven preventive measures for coccidioidomycosis, additional research into strategies that reduce the incidence or morbidity of this infection is warranted. Specifically, the role of antifungal treatment for primary pulmonary disease remains controversial and deserves further exploration (10), although treatment is recommended in certain patient groups, particularly those at high risk for severe disease (1). Because the symptoms of coccidioidomycosis mimic those of other community-acquired respiratory illnesses, patients often experience delays in testing and diagnosis and receive unnecessary antibiotics; however, patients who know about coccidioidomycosis are more likely to request testing and receive a diagnosis sooner than those who are not familiar with the disease (2). Therefore, promoting increased community and health-care provider awareness of this infection continues to be an important role for public health officials.
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              Enhanced Surveillance of Coccidioidomycosis, Arizona, USA, 2007–2008

              Additional public and provider education are needed to reduce delays in diagnosis.
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                Author and article information

                Journal
                MMWR Morb Mortal Wkly Rep
                MMWR Morb. Mortal. Wkly. Rep
                WR
                Morbidity and Mortality Weekly Report
                Centers for Disease Control and Prevention
                0149-2195
                1545-861X
                09 November 2018
                09 November 2018
                : 67
                : 44
                : 1246-1247
                Affiliations
                Epidemic Intelligence Service, CDC; Arizona Department of Health Services, Phoenix, Arizona; Maricopa County Department of Public Health, Phoenix, Arizona; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia; Career Epidemiology Field Officer Program, CDC.
                Author notes
                Corresponding author: Carla P. Bezold, Carla.Bezold@ 123456azdhs.gov , 602-290-3514.
                Article
                mm6744a6
                10.15585/mmwr.mm6744a6
                6223958
                30408020
                fad26aae-df86-4f4e-9564-ca10efedaa46

                All material in the MMWR Series is in the public domain and may be used and reprinted without permission; citation as to source, however, is appreciated.

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