By Carol Kemper, MD, FACP
Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center
Dr. Kemper reports no financial relationships relevant to this field of study.
California Inmates With Cocci Lose Appeal
SOURCES: United States Court of Appeals for the Ninth Circuit, Feb. 1, 2019; ; California Department of Public Health. Coccidioidomycosis in California Provisional Monthly Report, January-April 2019. Available at: . Accessed May 6, 2019.
In February 2019, in response to four consolidated appeals, the United States Court of Appeals for the Ninth Circuit reversed, in part, earlier district court rulings stating that inmates at several California state prisons were exposed to an increased risk of coccidioidomycosis, constituting a violation of their Eighth Amendment rights. African-American inmates also sued under the 14th Amendment, alleging unequal protection based on an increased risk of acquiring coccidioidomycosis because of race. Recall that the Eighth Amendment is the right to be free from cruel and unusual punishment; whereas the Equal Protection Clause of the 14th Amendment says prisoners are protected against discrimination or unequal treatment based on race, sex, age, national origin, and creed. The original court filings alleged the increased risk of coccidioidomycosis in prison facilities located near Coalinga, in Fresno County, and in Avenal, in Kings County, had resulted in the deaths of 40 inmates, and more than 100 others required long-term medical care for chronic infection.
The Appeals Court for the Ninth Circuit stated that specific state and prison officials were entitled to qualified immunity against such claims they had acted with deliberate intent, as the right to be free from exposure to Valley Fever had not been established at the time the officials acted. Further, there was no evidence that society shared the attitude that involuntary exposure violated current standards of decency, since millions of people voluntarily choose to live in endemic areas in California, despite a recognized risk, and that coccidioidomycosis occurs in areas outside of California (i.e., Arizona). The Appeals Court also stated that African Americans did not clearly have an established right to be segregated to avoid the risk of exposure.
The history behind these district appeals and current decision is of interest. Beginning in 2005, an increase in coccidioidomycosis infection in prisoners in certain facilities located in the California Central Valley prompted investigation by the California Department of Public Health (CDPH) of an increased number of cases at Pleasant Valley State Prison (PVSP) located in Coalinga, CA. In January 2007, CDPH reported that 166 cocci infections had occurred in prisoners at PVSP, including 29 hospitalizations and four deaths. This infection rate was approximately 38 times higher than the rate among residents of Coalinga and 600 times higher than that of Fresno County at the time. It was recommended that removing immunosuppressed patients from the facility would help reduce the risk. In response, in November 2007, a statewide prison policy was established to remove — or not house in the first place — individuals at risk for cocci, based on six different criteria. These included HIV infection, a history of solid organ transplant or other immunosuppression, current chemotherapy, a history of lymphoma, or moderate to severe chronic obstructive pulmonary disease (COPD). This policy was amended and broadened in 2010.
Despite these policy changes, the risk of cocci infection in inmates at certain California facilities remained high. From 2006 to 2010, the risk of cocci infection was 7% at PVSP and 1.3% at Avenal State Prison, both significantly higher than the rate of infection in those communities. From 2006 to 2011, 36 inmates in Central Valley prisons died from cocci infection. Notably, 71% of these were African American, more than double the percentage of African American prisoners at the time. Following this report, in 2012, a district court overrode state objections and suspended the transfer of African Americans and prisoners with diabetes to Central Valley facilities.
The reasons for the apparent higher rates of infection in inmates are not entirely clear. PVSP was next door to a large construction project at the time of the original outbreak. Undoubtedly, individuals who lack immunity to cocci and move into a hyperendemic area are at greater risk for acquiring infection compared with residents who have lived in the area for years and who may have acquired immunity. It would be helpful, therefore, to compare the rates of infection in inmates to residents moving into these endemic areas, rather than to overall county statistics. A colleague of mine once examined the risk of acquiring cocci infection in individuals who lived in western Washington state in the summer and wintered in Arizona, finding that approximately 3% acquired cocci annually.
Since the rates of coccidioidomycosis continue to increase in California, the risk to inmates in high-risk areas also is likely to increase. In 2017, more than 14,343 cases of Valley Fever were reported to the Centers for Disease Control and Prevention — approximately half of these cases were from California. Provisional data for 2018 suggest cases have increased 36% over 2016 figures, including approximately 3,000 cases in Kern County, followed by Los Angeles (1,046), Fresno (633), and Tulare (507).
Tuberculosis Testing in Small Children
SOURCE: Velasco-Arnaiz E, Soriano-Arandes A, Latorre I, et al. Performance of tuberculin skin tests and interferon-gamma release assays in children younger than 5 years. Pediatr Infect Dis 2018;37:1235-1241.
Tuberculosis (TB) screening in small children remains controversial. Although Interferon-gamma release assays (IGRA) largely have replaced TST skin testing in many healthcare facilities, at least in first-world countries, current guidelines in the United States, Canada, and Europe still advocate for skin testing over IGRA as the preferred screening tool in children younger than 5 years of age, regardless of a history of BCG vaccination. However, in some countries, such as Spain, IGRA testing is recommended as an adjunct, especially in those at risk for TB with a negative skin test or those with a history of BCG vaccination and a positive skin test. Investigators in Spain examined the use of skin testing vs. IGRA testing (Quantiferon-TB Gold In-Tube) in children younger than 5 years of age at risk for TB who were evaluated at two tertiary pediatric TB units in Barcelona. The study was conducted from 2005 to 2015.
A total of 383 children younger than 5 years of age were included in the study, all of whom received both skin testing and IGRA testing. Children with immune suppression or steroid use were excluded from analysis. The children were undergoing evaluation for latent TB infection (LTBI) as either part of contact tracing or as a new immigrant exam, or were being assessed for suspected active TB. Children with a history of BCG vaccination were statistically older and more likely to be screened for a new entrance exam.
A total of 304 children were considered uninfected. During a median of 47 months of follow-up, one of these children, a 3-year-old Pakistani boy, developed active TB. He had a history of BCG vaccination, a positive skin test at 8 mm, and a negative IGRA test. The skin test had been attributed to his BCG testing and he had not received treatment for latent TB.
Forty children were diagnosed with latent TB and treated with either isoniazid for six to nine months or isoniazid and rifampin for three months, per current guidelines in Spain. With a median of 42 months of follow-up after completion of anti-TB medications, none of them developed TB.
Thirty-nine were diagnosed with active TB, including 15 with confirmed TB and 23 with suspected TB. The sensitivity in children with confirmed TB was 100% for skin testing and 93.7% for IGRA testing. Test results in the 23 children with suspected TB were more variable, and included five children (22%) with concordant negative skin and IGRA testing. All five of these children had symptoms and radiographic evidence consistent with active TB and responded to therapy. Two others had positive skin tests and negative IGRA, and one child with suspected TB had a positive skin test and an indeterminate IGRA. This suggests that IGRA was negative or indeterminate in 53% of those children with suspected TB.
In those without active TB, discordance between the two tests was 16.8% (similar to screening test results in U.S. adults at low risk for TB). All of this was attributed to positive skin testing and negative IGRA results. However, if those children with BCG vaccination were excluded, the agreement between the two tests was much better (94.6%). Only 3.6% of the children had indeterminate IGRA test results. Most of these were in children younger than 2 years of age (8.7%) compared with older children (0.8%), P < 0.001.
For those children with a history of BCG vaccination and a positive skin test/negative IGRA, it is still not possible to determine whether they have latent TB. Some argue that because discordance is so much more common in BCG-vaccinated children, the negative IGRA test should be believed. Others argue that the risk of a positive skin test in such children is only 8% to 20% depending on the age of BCG vaccination and age of testing, so a history of BCG vaccination should be disregarded. In the end, pre-test probability should be taken into account, similar to the decision-making for adults with a history of BCG in the United States. If such children are from a country endemic for TB, then the history of BCG should be disregarded.