2019 Lung Infection Symposium - Libke 10/26/2019 58 YO ♂ • 1974 PRESENTED WITH HEADACHE – DX = COCCI MENINGITIS WITH HYDROCEPHALUS – Rx = IV AMPHOTERICIN X 6 WKS – VP SHUNT – INTRACISTERNAL AMPHO B X 2.5 YRS (>200 PUNCTURES) • 1978 – 2011 VP SHUNT REVISIONS X 5 • 1974 – 2019 GAINFULLY EMPLOYED, RAISED FAMILY, RETIRED AND CALLS OCCASIONALLY TO SEE HOW I’M DOING. VALLEY FEVER A K A COCCIDIOIDOMYCOSIS COCCIDIOIDOSIS COCCIDIODAL GRANULOMA SAN JOAQUIN VALLEY FEVER DESERT RHEUMATISM VALLEY BUMPS COCCI COX C 1 2019 Lung Infection Symposium - Libke 10/26/2019 COCCIDIOIDOMYCOSIS • DISEASE FIRST DESCRIBED IN 1892 – POSADAS –ARGENTINA – RIXFORD & GILCHRIST - CALIFORNIA – INITIALLY THOUGHT PARASITE – RESEMBLED COCCIDIA “COCCIDIOIDES” – “IMMITIS” = NOT MINOR COCCIDIOIDOMYCOSIS • 1900 ORGANISM IDENTIFIED AS FUNGUS – OPHULS AND MOFFITT – ORGANISM CULTURED FROM TISSUES OF PATIENT – LIFE CYCLE DEFINED – FULFULLED KOCH’S POSTULATES 2 2019 Lung Infection Symposium - Libke 10/26/2019 COCCIDIOIDOMYCOSIS • 1932 ORGANISM IN SOIL SAMPLE FROM DELANO – UNDER BUNKHOUSE OF 4 PATIENTS – DISEASE FATAL • 1937 DICKSON & GIFFORD CONNECTED “VALLEY FEVER” TO C. IMMITIS – USUALLY SELF LIMITED – FREQUENTLY SEEN IN SAN JOAQUIN VALLEY – RESPIRATORY TRACT THE PORTAL OF ENTRY The usual cause for coccidioidomycosis in Arizona is C. immitis A. True B. False 3 2019 Lung Infection Symposium - Libke 10/26/2019 COCCIDIOIDAL SPECIES • COCCIDIOIDES IMMITIS – CALIFORNIA • COCCIDIOIDES POSADASII – NON-CALIFORNIA • ARIZONA, MEXICO • OVERLAP IN SAN DIEGO AREA THE MICROBIAL WORLD • PRIONS • VIRUSES • BACTERIA • FUNGI • PARASITES 4 2019 Lung Infection Symposium - Libke 10/26/2019 VIRUSES • SMALLEST INFECTIOUS PARTICLES • 18-300 NM – (< 200 NOT SEEN WITH LIGHT MICROSCOPE) • RNA OR DNA PLUS PROTEINS • TRUE PARASITES (REQUIRE HOST CELLS) • COLDS, FLU (PNEUMONIA), GASTROENTERITIS, RABIES, SMALL POX, AIDS BACTERIA • SIMPLE UNICELLULAR ORGANISMS – NO NUCLEAR MEMBRANE – NO MITOCHONDRIA • REPRODUCE BY ASEXUAL DIVISION • CELL WALL – 2 TYPES (SOME LACK) • SPHERES, RODS, SPIRALS • SINGLES, CHAINS, CLUSTERS • PNEUMONIA, GASTROENTERITIS, CELLULITIS, URINE INFECTIONS, LYME DISEASE, MENINGITIS 5 2019 Lung Infection Symposium - Libke 10/26/2019 FUNGI • CELLULAR STRUCTURE MORE COMPLEX – MITOCHONDRIA – GOLGI BODIES – ENDOPLASMIC RETICULUM • MAY REPRODUCE SEXUALLY OR ASEXUALLY • UNICELLULAR FORMS = YEAST • FILAMENTOUS FORMS = MOLD • DIMORPHOUS = BOTH FORMS • MUSHROOMS • VALLEY FEVER, THRUSH, SKIN INFECTIONS, PNEUMONIA FUNGAL DISEASES • BROWN PATCH, • PINK PATCH, • SUMMER PATCH, • RED THREAD, • BLACK SPOT, • LEAF SPOT, • DOWNY MILDEW, • POWDERY MILDEW, • ANTHRACNOSE, • SNOW MOLD, • SCAB, • RUST, 6 2019 Lung Infection Symposium - Libke 10/26/2019 PARASITES • MOST COMPLEX • UNICELLULAR AND MULTICELLULAR • TINY PROTOZOA 1-2 NM • VISIBLE ORGANISMS – TAPEWORMS, ARTHROPODS • COMPLEX LIFE CYCLES • MALARIA, INTESTINAL INFECTIONS, BRAIN LESIONS Lifecycle phases Coccidioides immitis posadasii 7 2019 Lung Infection Symposium - Libke 10/26/2019 Life Cycle THE AGENT CAUSING COCCIDIOIDOMYCOSIS IS NOT TRANSMITTED BY? A. ARTHROCONIDIA B. AIRBOURNE ROUTE C. SKIN INOCULATION D. PERSON TO PERSON SPREAD 8 2019 Lung Infection Symposium - Libke 10/26/2019 Sabouraud’s dextrose agar culture of Coccidioides immitis CDC/Dr. Lenore Haley 9 2019 Lung Infection Symposium - Libke 10/26/2019 Spherule of Coccidioides immitis with endospores. Calcofluor stain. 10 2019 Lung Infection Symposium - Libke 10/26/2019 COCCIDIOIDOMYCOSIS EPIDEMIOLOGY • INFECTIOUS AGENT: • ARTHROCONIDIA (ARTHROSPORES) • SOURCE: • SOIL • TRANSMISSION: • USUAL: AIRBOURNE • RARE: CUTANEOUS INOCULATION • NO PERSON TO PERSON TRANSMISSION • APPARENT EPIDEMICS: • ARCHEOLOGIC DIGS PRISON • WINDSTORMS SOLAR FARMS • CONSTRUCTION DUST STORM 1991 11 2019 Lung Infection Symposium - Libke 10/26/2019 EPIDEMIOLOGY • FOUND ONLY IN WESTERN HEMISPHERE – BETWEEN 400 NORTH AND SOUTH LATITUDES • LOWER SONORAN LIFE ZONE – ARID CLIMATE – 5-20 INCHES OF RAIN – HOT SUMMERS – WINTERS WITH FEW FREEZES – ALKALINE SOIL 12 2019 Lung Infection Symposium - Libke 10/26/2019 What time of year is primary cocci most prevalent in the San Joaquin Valley? A. Summer B. Fall C. Winter D. Spring 13 2019 Lung Infection Symposium - Libke 10/26/2019 IN HOW MANY STATES IS COCCI ENDEMIC A. 4 B. 5 C. 6 D. 7 ENDEMIC AREAS FOR COCCI 14 2019 Lung Infection Symposium - Libke 10/26/2019 Nearly 130,000 valley fever cases were reported to CDC during 1998 to 2012.1,4 Over 17,000 cases were reported in the U.S. in 2012, more than 70% of which were from Arizona.4 CDC: Final 2012 Reports of Nationally Notifiable Infectious Diseases, MMWR 62(33);669-682. • The reasons for the overall increase in the number of reported valley fever cases are not entirely known, but could be due to: • Higher numbers of people exposed to the fungus Coccidioides because of increased travel or relocation to endemic areas • Changes in environmental factors such as temperature and rainfall, which can affect the growth of the fungus and how much of it is circulating • Changes in the way cases are being detected and reported 15 2019 Lung Infection Symposium - Libke 10/26/2019 A costly problem • • In 2011, more than 20,000 cases were reported in the US, twice as many cases as tuberculosis. • • Nearly 75% of valley fever victims miss work or school for about two weeks. • • More than 40% of valley fever victims are hospitalized. The average cost of a hospital stay for valley fever is almost $50,000. Tsang CA, et al. Emerg Infect Dis. 2010 Nov;16(11):1738-44. Number of deaths due to valley fever • A recent study found that 3,089 coccidioidomycosis-associated deaths occurred in the US during 1990 to 2008, which is an average of fewer than 200 deaths per year.5 The number of coccidioidomycosis-associated deaths each year has been fairly stable since 1997.5 Huang. Emerg Infect Dis. 2012 Nov;18(11):1723-8. 16 2019 Lung Infection Symposium - Libke 10/26/2019 Valley fever outbreaks • Although most cases of valley fever are not associated with outbreaks, valley fever outbreaks linked to a common source do occasionally occur. Past outbreaks have occurred in military trainees,6,7 archeological workers,8-11 and in people exposed to earthquakes12 and dust storms.13 How common is coccidioidomycosis? • In states where valley fever is endemic and reportable (Arizona, California, Nevada, New Mexico, and Utah), incidence was highest among persons aged 60-79 years (69.1/100,000).1 In highly endemic areas such as the Phoenix and Tucson metropolitan areas of Arizona, valley fever causes an estimated 15% to 30% of community-acquired pneumonias, but low testing rates suggest that valley fever may be under- recognized.2,3 17 2019 Lung Infection Symposium - Libke 10/26/2019 18 2019 Lung Infection Symposium - Libke 10/26/2019 California Coccidioidomycosis cases and incidence rate 1995–2016 19 2019 Lung Infection Symposium - Libke 10/26/2019 FIGURE. Coccidioidomycosis incidence per 100,000 population, by age group — Arizona, California, Nevada, New Mexico, and Utah, 1998–2011 20 2019 Lung Infection Symposium - Libke 10/26/2019 EFFECT OF DROUGHT?? Coccidioidomycosis in S/W Fresno County Coalinga PVSP 21 2019 Lung Infection Symposium - Libke 10/26/2019 Total Cases of Coccidioidomycosis in Fresno County/Coalinga FRESNO COALINGA COUNTY (%) 2004 122 76(62%) 2005 290 142(49%) 2006 776 674(87%) 2007 450 342(76%) 2008 310 244(79%) County, Coalinga and PVSP Coccidioidomycosis Incidence 800 700 600 500 Total Cases 400 County 300 Coalinga 200 PVSP 100 0 2004 2006 2008 Year 22 2019 Lung Infection Symposium - Libke 10/26/2019 County, Coalinga and PVSP Coccidioidomycosis Incidence 12000 10000 8000 Cases per 6000 County 100,000 4000 Coalinga PVSP 2000 0 2004 2005 2006 2007 2008 Year EPIDEMIOLOGY • REEMERGING DISEASE – CHANGES IN DEMOGRAPHY • RISK OF EXPOSURE EXPANDING – GROWTH INTO SPARSELY POPULATED AREAS – INCREASED TOURISM – CHANGES IN MODERN MEDICINE • INCREASED NUMBERS WITH IMMUNE COMPROMISE 23 2019 Lung Infection Symposium - Libke 10/26/2019 EPIDEMIOLOGY • Risk of infection: – 3% per year in endemic areas – 150,000 cases annually in U.S. – Variable from year to year ACUTE 24 2019 Lung Infection Symposium - Libke 10/26/2019 CHRONIC CLASSIFICATION OF COCCIDIOIDOMYCOSIS • PRIMARY: – RESPIRATORY – CUTANEOUS INOCULATION • COMPLICATIONS OF PRIMARY INFECTION – PNEUMOTHORAX – EMPYEMA – PERICARDITIS – ATELECTASIS • CHRONIC RESIDUALS OF PRIMARY INFECTION – CAVITY – GRANULOMA – BRONCHIECTASIS • PROGRESSIVE PRIMARY COCCIDIOIDOMYCOSIS • DISSEMINATION 25 2019 Lung Infection Symposium - Libke 10/26/2019 COURSE OF COCCIDIOIDOMYCOSIS 1 PRIMARY INFECTION 1 4 3 2 5 DISSEMINATION COMPLETE RECOVERY COMLICATIONS PROGRESSIVE CHRONIC 10 RESIDUAL THICKNESS OF LINES AND ARROWS INDICATES FREQUENCY THICKEST - 1 = MOST FREQUENT FINEST - 5 = LEAST FREQUENT OUTCOME OF C. IMMITIS INFECTION 1000 INFECTIONS 600 400 ASYMPTOMATIC SYMPTOMATIC 50 5 PULMONARY DISSEMINATION RESIDUALS ? 26 2019 Lung Infection Symposium - Libke 10/26/2019 HOW MANY SYMPTOMATIC PATIENTS WITH VALLEY FEVER HAVE FEVER? A. 92% B. 56% C. 84% D. 76% MANIFESTATIONS PRIMARY COCCI(VALLEY FEVER) • FIRST SYMPTOMS 7-21 DAYS AFTER EXPOSURE • FEVER 76% • COUGH 73% • CHEST PAIN 44% • FATIGUE 39% • SHORTNESS OF BREATH 32% • WEIGHT LOSS 21% • FEVER, RASH, JOINT PAIN = “DESERT RHEUMATISM” 27 2019 Lung Infection Symposium - Libke 10/26/2019 CLUES TO THE DIAGNOSIS OF COCCIDIOIDOMYCOSIS ACUTE LOWER RESPIRATORY INFECTION WITH: • SKIN LESIONS: – ERYTHEMA NODOSUM – ERYTHEMA MULTIFORME – “TOXIC” MACULOPAPULAR ERUPTION • EOSINOPHILIA • UNILATERAL HILAR ADENOPATHY