Extrapulmonary Coccidioidomycosis Among Children in Central California: A Retrospective Review.
The Pediatric infectious disease journal
2019; 38 (12): 1189?94
Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children and Adolescents Aged 6-17 Years.
The American journal of tropical medicine and hygiene
BACKGROUND: The literature on pediatric extrapulmonary coccidioidomycosis is limited. We reviewed the clinical course, diagnostic studies, treatment and outcomes of children with extrapulmonary coccidioidomycosis followed at a tertiary care center in central California.METHODS: Retrospective study of 78 patients ?21 years old with extrapulmonary coccidioidomycosis diagnosed over 10 years (1/1/07-12/31/16).RESULTS: The median age was 9.7 years (interquartile range, 4.5-14.8). The majority of patients were males (55%), Hispanic (65%) and without comorbid conditions (85%). Over two-thirds (68%) had concurrent pulmonary disease. Organ involvements included bones and joints (33%), mediastinum (19%), central nervous system (19%), cervical lymph nodes (15%), larynx (6%) and skin (5%). Most cases (84%) resolved and/or became stable on maintenance therapy, 14% experienced relapse and/or progressive disease, and 2% were fatal. Children ?10 years of age tended to have >1 site of involvement (47% vs. 25%, P = 0.06), and more relapsed/progressive/fatal disease (21% vs. 5%, P = 0.06) compared with those <10 years. They also required longer durations of treatment (median, 611 vs. 349 days, P = 0.02). Non-Hispanics were more likely to require >1 drug therapy (85% vs. 70%, P = 0.04) and tended to have Coccidioides complement fixation titers ?1:32 (89% vs. 72%, P = 0.04) compared with Hispanics.CONCLUSIONS: Extrapulmonary coccidioidomycosis in children can be severe and spread to multiple sites and requires prolonged treatment. Non-Hispanics and those ?10 years of age are more likely to experience severe disease, suggesting a need for early recognition and intervention in these populations.
View details for DOI 10.1097/INF.0000000000002470
View details for PubMedID 31738333
Age-related immunogenicity and reactogenicity of live oral cholera vaccine CVD 103-HgR in a randomized, controlled clinical trial.
2019; 37 (11): 1389?97
The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, redeveloped as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera-induced diarrhea in adult volunteer challenge trials but has not been studied in children in developed countries. We performed a phase 4, placebo-controlled, double-blind, multicenter study to assess the safety, immunogenicity, and tolerability of a single, oral dose of PXVX0200 in children and adolescents aged 6-17 years in the United States and bridged immunogenicity to adults aged 18-45 years from a separate lot consistency study. Volunteers were randomized to receive a single dose of 1 * 109 CFU of PXVX0200 or placebo. Immunogenicity endpoints included SVA levels on days 1, 11, and 29 in volunteers aged 6-17 years and also on days 91 and 181 in volunteers aged 12-17 years. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events (AEs) through day 29, and serious AEs through day 181. A total of 374 participants were enrolled, comprising 321 vaccine and 53 placebo recipients. The SVA seroconversion rates 10 days after immunization were 98.6% and 2.1% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in adults aged 18-45 years. Most reactogenicity was mild to moderate, and there were no vaccine-related serious AEs. The complete dose was consumed in 95.3% and 98.1% of vaccine and placebo recipients, respectively. PXVX0200 appears safe, immunogenic, and well tolerated in children and adolescents aged 6-17 years.
View details for DOI 10.4269/ajtmh.19-0241
View details for PubMedID 31769402
Age-related immunogenicity and reactogenicity of live oral cholera vaccine CVD 103-HgR in a randomized, controlled clinical trial
2019; 37 (11): 1389?97
Pediatric Coccidioidomycosis Case Series From a California Pediatric Infectious Diseases Clinic
PEDIATRIC INFECTIOUS DISEASE JOURNAL
2019; 38 (2): 115?21
Aging is accompanied by a decline in immune function which can lead to decreased responses to vaccines. Attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies but has not been studied in older adults. We evaluated CVD 103-HgR (PXVX0200) in adults age 46-64, compared them to previously studied adults age 18-45, and studied age-related immunogenicity across adults 18-64?years of age. Volunteers were randomized to receive a single dose of 1?*?109?CFU of PXVX0200 or placebo. Immunogenicity endpoints included SVA and anti-cholera toxin (CT) antibody levels on days 1, 11, 29, 91 and 181 and lipopolysaccharide (LPS) and CT-specific IgA and IgG memory B cells on days 1, 91 and 181. Safety was assessed by comparing solicited signs and symptoms on days 1-8 and other adverse events through day 181. 2979 volunteers received vaccine, including 291 age 45-64. Day 11 seroconversion occurred in 90.4% of older adults vs 93.5%% of younger adults and met the endpoint of demonstrating non-inferiority between the two groups. Significant increases in LPS-specific IgG and IgA and CT-specific memory IgG memory B cells were seen at days 91 and 181. There appeared to be a continuous age-related decline in SVA seroconversion and geometric mean titers, but not memory B cell responses, across the 18-64?year age range. Most reactogenicity was mild and was more common in the placebo group. PXVX0200 appears safe and immunogenic in older adults. Clinical Trials Registration: clinicaltrials.gov NCT02100631.
View details for PubMedID 30772070
Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
2018; 142 (6): 1971-+
Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients.
The Journal of allergy and clinical immunology
2018; 142 (6): 1971
Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18-45
2018; 36 (6): 833?40
Coccidioidomycosis is not as well described in the pediatric population as it is in the adult population. We describe clinical findings, diagnosis and management of coccidioidomycosis in 108 pediatric patients seen in an outpatient clinic in the California Central Valley, an area endemic for coccidioidomycosis.We reviewed medical records of a convenience sample of pediatric patients (?17 years of age) diagnosed with coccidioidomycosis who visited an infectious diseases clinic in Madera, CA, during January 1 to October 1, 2012. We described demographic characteristics, symptoms, diagnostic testing, extent of infection (acute/pulmonary or disseminated), treatment and management.Of 108 patients, 90 (83%) had acute/pulmonary coccidioidomycosis and 18 (17%) had disseminated disease. The median age at diagnosis was 9 years (range, 5 months to 17 years). Only 3 (3%) patients were immunocompromised. Before coccidioidomycosis diagnosis, 72 (82%) patients received antibiotics, and 31 (29%) had at least 1 negative coccidioidomycosis serology at the time of or before diagnosis. Coccidioidomycosis was diagnosed significantly later after symptom onset among patients with disseminated (median, 57 days) than with acute/pulmonary (median, 16 days) disease (p < 0.01). A total of 104 (96%) patients received antifungal therapy, 51 (47%) visited an emergency room and 59 (55%) were hospitalized with a median stay of 44 days (range, 1-272 days).Substantial acute/pulmonary and disseminated coccidioidomycosis was seen among pediatric patients at this infectious disease clinic in California. In endemic areas, increased coccidioidomycosis awareness and vigilance among families and providers is necessary to facilitate early diagnosis and appropriate management.
View details for PubMedID 29620721
Epidemiology of Pediatric Coccidioidomycosis in California, 2000-2012.
Pediatric infectious disease journal
2016; 35 (2): 166-171
The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, re-developed as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies. We performed a phase 3, placebo controlled, double blind, multi-center study to further assess the safety, immunogenicity, and lot-to-lot consistency of PXVX0200. Adult volunteers 18-45?years of age were randomized 8:1 to receive a single dose of 1?×?109 CFU of PXVX0200 from three production lots or saline placebo. Immunogenicity endpoints included SVA and anti-cholera toxin (CT) antibody levels on days 1, 11, 29, 91 and 181. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events through day 29 and serious adverse events through day 181. A total of 3146 participants were enrolled, including 2795 vaccine and 351 placebo recipients. The SVA seroconversion rates at day 11 were 94% and 4% in the PXVX0200 and placebo recipients, respectively (P?.0001). Cumulative SVA seroconversion occurred among 96% of vaccine recipients. PXVX0200 SVA GMTs peaked on day 11 and remained significantly higher than placebo through day 181 while the fold-rise over baseline in PXVX0200 anti-CT antibody was significantly greater than placebo at every post-vaccination time point. Most reactogenicity was mild and resolved within 1-3?days with headache and diarrhea more frequently reported in PXVX0200 recipients. There were no differences in unsolicited adverse events and no study-related serious adverse events. Immunogenicity and safety endpoints were equivalent between the three production lots. PXVX0200 is immunogenic and well tolerated across multiple production lots.Clinicaltrials.gov NCT02094586.
View details for PubMedID 29317118
Reported coccidioidomycosis cases have increased in the southwestern US since 2000. However, there are few publications on pediatric coccidioidomycosis. We sought to describe the epidemiology of coccidioidomycosis in the California pediatric population during 2000-2012.We reviewed surveillance and hospitalization datasets for years 2000-2012 and death datasets for years 2000-2010 to identify coccidioidomycosis-associated cases, hospitalizations and deaths in pediatric (?17 years old) California residents. We calculated rates and described demographic characteristics of cases and hospitalized patients and, using Poisson regression, calculated bivariate relative risks to identify potential demographic risk factors. We identified immunocompromising conditions associated with hospitalization and death and calculated hospitalization charges.We identified 3453 cases, 1301 hospitalizations and 11 deaths associated with coccidioidomycosis in the California pediatric population. During 2000-2012, annual case and hospitalized patient rates increased and were highest in males, those in the 12-17 age group, and residents of the California endemic region. Compared with White children, African-American children were significantly more likely to be hospitalized (relative risk = 1.4, P = 0.01). Approximately 12.0% of those hospitalized and 27% of those who died had an immunocompromising condition. Hospitalized patients accrued $149 million in total hospital charges.Similar to recent increases among adults, reported pediatric coccidioidomycosis cases and hospitalizations have increased in California since 2000, disproportionately affecting certain demographic groups. The burden of coccidioidomycosis among California children emphasizes the need for more awareness and research into this reemerging fungal disease in endemic and nonendemic areas.
View details for DOI 10.1097/INF.0000000000000952
View details for PubMedID 26461228