James McCarty

All Publications

• Immunogenicity of partial doses of live oral cholera vaccine CVD 103-HgR in children in the United States. Vaccine McCarty, J. M., Cassie, D., Bedell, L. 2023

  Abstract

  In a phase 4, placebo-controlled, double-blind, multi-center study performed to assess the immunogenicity of a single oral dose of live, attenuated cholera vaccine, volunteers aged 2-17 years were randomized 6:1 to receive 1 × 109 colony forming units of PXVX0200 or placebo. In the subset of subjects who consumed < 80 % of the vaccine dose, seroconversion rates were calculated and stratified by amount consumed. Of 468 subjects dosed, a subset of 33 (7 %) received < 80 % of the vaccine dose. SVA seroconversion occurred in 75.8 % of these subjects, including 100 % (7/7) of those who took 50-80 % and 69.2 % (18/26) of those who took < 50 %, versus 98.5 % of those who consumed 80 % or more. Vaccination with PXVX0200 produced an immune response in most children who received partial dosing. Since SVA seroconversion is a strong correlate of protection, PXVX0200 may protect against cholera infection in children who ingest only part of the vaccine dose.

  View details for DOI 10.1016/j.vaccine.2023.03.013

  View details for PubMedID 36959054

• Central Nervous System Coccidioidomycosis in Children: A Retrospective Case Series. The Pediatric infectious disease journal Naeem, F., Laningham, F., Giglio, L., Sharma, J., Clerkin, P. Q., McCarty, J. M. 2022

  Abstract

  BACKGROUND: Published literature on central nervous system (CNS) coccidioidomycosis in children is limited. Here we describe a large case series of pediatric CNS coccidioidomycosis from a tertiary care center in an endemic region.METHOD: This is a retrospective case review of patients ≤21 years old with a diagnosis of CNS coccidioidomycosis from January 1, 2000, to December 31, 2018.RESULTS: Thirty patients (median age 10.8 years) were identified and most (93%) were previously healthy. Fever (90%), headache (70%), vomiting (53%), and fatigue (57%) were the most common presenting clinical manifestations, with focal neurological signs/symptoms present in 14 (47%). The initial serum Coccidioides compliment fixation (CF) titer was ≤ 1:8 in 33%. Most patients had extra-axial brain involvement (83%) and seven (23%) had associated spinal cord disease. Shunt placement was required in 70% and 62% required revision. Fluconazole was the initial treatment in 22 (73%), with treatment failure occurring in 50%. Most patients (77%) stabilized and were maintained on suppressive therapy, 4 (13%) experienced relapses and/or progressive disease, and one (3%) died, while long-term neurological complications occurred in 17%.CONCLUSIONS: CNS coccidioidomycosis is an uncommon and sometimes devastating complication of disseminated coccidioidomycosis. Many patients present with relatively low CF titers and hydrocephalus is common. Fluconazole treatment failures are common, and management remains difficult despite recent advances in therapy. Most patients do well once the disease is stabilized and require lifelong therapy. Newer therapeutic agents are needed.

  View details for DOI 10.1097/INF.0000000000003813

  View details for PubMedID 36728889

• Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial. The Lancet. Infectious diseases Bennett, S. R., McCarty, J. M., Ramanathan, R., Mendy, J., Richardson, J. S., Smith, J., Alexander, J., Ledgerwood, J. E., de Lame, P., Royalty Tredo, S., Warfield, K. L., Bedell, L. 2022

  Abstract

  BACKGROUND: Chikungunya virus (CHIKV) disease is an ongoing public health threat. We aimed to evaluate the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV virus-like particle (VLP) vaccine.METHODS: This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA. Eligible participants were healthy CHIKV-naive adults aged 18-45 years. Participants were stratified by site and randomly assigned (1:1:1:1:1:1:1:1) to one of the eight vaccination groups using a block size of 16. Group 1 received two doses of unadjuvanted PXVX0317 28 days apart (2 * 20 mug; standard); all other groups received adjuvanted PXVX0317: groups 2-4 received two doses 28 days apart (2 * 6 mug [group 2], 2 * 10 mug [group 3], or 2 * 20 mug [group 4]; standard); group 4 also received a booster dose 18 months after the first active injection (40 mug; standard plus booster); groups 5-7 received two doses 14 days apart (2 * 6 mug [group 5], 2 * 10 mug [group 6], or 2 * 20 mug [group 7]; accelerated); and group 8 received one dose (1 * 40 mug; single). The primary endpoint was the geometric mean titre of anti-CHIKV neutralising antibody on day 57 (28 days after the last vaccination), assessed in the immunogenicity-evaluable population. Additionally, we assessed safety. This trial is registered at ClinicalTrials.gov, NCT03483961.FINDINGS: This trial was conducted from April 18, 2018, to Sept 21, 2020; 468 participants were assessed for eligibility. Of these, 415 participants were randomly assigned to eight groups (n=53 in groups 1, 5, and 6; n=52 in groups 2 and 8; n=51 in groups 3 and 7; and n=50 in group 4) and 373 were evaluable for immunogenicity. On day 57, serum neutralising antibody geometric mean titres were 2057·0 (95% CI 1584·8-2670·0) in group 1, 1116·2 (852·5-1461·4; p=0·0015 vs group 1 used as a reference) in group 2, 1465·3 (1119·1-1918·4; p=0·076) in group 3, 2023·8 (1550·5-2641·7; p=0·93) in group 4, 920·1 (710·9-1190·9; p<0·0001) in group 5, 1206·9 (932·4-1562·2; p=0·0045) in group 6, 1562·8 (1204·1-2028·3; p=0·14) in group 7, and 1712·5 (1330·0-2205·0; p=0·32) in group 8. In group 4, a booster dose increased serum neutralising antibody geometric mean titres from 215·7 (95% CI 160·9-289·1) on day 547 to 10 941·1 (7378·0-16 225·1) on day 575. Durability of the immune response (evaluated in groups 1, 4, and 8) was shown up to 2 years. The most common solicited adverse event was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported.INTERPRETATION: PXVX0317 was well tolerated and induced a robust and durable serum neutralising antibody immune response against CHIKV up to 2 years. A single 40 mug injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials (NCT05072080 and NCT05349617).FUNDING: Emergent BioSolutions.

  View details for DOI 10.1016/S1473-3099(22)00226-2

  View details for PubMedID 35709798

• Pediatric Musculoskeletal Coccidioidomycosis in Central California: A Single Center Experience. The Pediatric infectious disease journal Naeem, F., Gerardi, J., Gholve, P., Merriott, D., Hassan, R., McCarty, J. 2022

  Abstract

  BACKGROUND: Published literature on musculoskeletal coccidioidomycosis is sparse and limited to case reports and case series. This is one of the largest case series to describe the clinical presentation, diagnosis, medical and surgical management and outcomes of pediatric musculoskeletal coccidioidomycosis at a tertiary care hospital.METHOD: A retrospective case review was performed on patients ≤ 21 years old who were followed at a tertiary care center with a diagnosis of musculoskeletal coccidioidomycosis from January 1, 2007, to December 31, 2020. Descriptive data are expressed as medians and interquartile range (IQR) for continuous variables or as frequency and percentage for categorical variables. Categorical values were compared using the chi2 test.RESULTS: Forty-one patients were identified. The median age was 12.8 years, and most were male (71%), Latinx (66%) and healthy (71%). Limb swelling (66%), bone pain (54%) and joint pain (46%) were the most common presenting symptoms. Multiple bone involvement was present in 29% while 12% had the joint disease, and craniofacial (n = 10) and metacarpal/metatarsal bones (n=9) were the most commonly involved sites. Elevated Coccidioides complement fixation (CF) titers ≥1:32 were seen in 90% of the patients. Thirty-three patients (81%) required surgical interventions and of these 16 (48%) required additional surgical procedures. Eleven patients (27%) had disease relapse. Children >13 years of age were more likely to have > 1 organ involvement (16 vs. 7, P = 0.04), multiple bone involvement (10 vs. 2, P = 0.004) and maximum Coccidioides CF titers >1:128 (13 vs. 6, P = 0.02).CONCLUSIONS: In endemic areas, musculoskeletal coccidioidomycosis causes a substantial disease burden in children and should be considered in the differential diagnosis of those presenting with bone and joint pain or swelling. Early diagnosis and treatment are essential to minimize long-term morbidity and mortality.

  View details for DOI 10.1097/INF.0000000000003540

  View details for PubMedID 35389943

• MODELING THE KINETICS AND DURABILITY OF THE HUMORAL RESPONSE TO A CHIKUNGUNYA VIRUS-LIKE PARTICLE VACCINE Stoddard, S., Bedell, L., Richardson, J., Mendy, J., Stonier, S., Metz, S., Vang, L., Anantha, R., McCarty, J., Fernando, S., Prithviraj, R., Ramanathan, R. AMER SOC TROP MED & HYGIENE. 2021: 272

  View details for Web of Science ID 000778105602540

• Neonatal Coccidioidomycosis: A Single-center Experience and Review of the Literature. The Pediatric infectious disease journal Vaughn, J., Tablizo, M. A., Zayed, Z., Hepple, R. R., McCarty, J. M., Naeem, F. 2021

  Abstract

  BACKGROUND: Coccidioidomycosis is common in adult and pediatric populations living in endemic areas of the United States but has rarely been reported in neonates. We reviewed recent cases of neonatal coccidioidomycosis treated at a tertiary care children's hospital in an endemic area and compared them with previously reported cases in the literature.METHODS: We performed a retrospective chart review of infants 1 month old or less hospitalized with a diagnosis of coccidioidomycosis from January 1, 2014, to December 31, 2019. Additionally, we performed a literature review of all reported cases of neonatal coccidioidomycosis over the past 7 decades through PubMed. Infants born to mothers with confirmed or suspected active coccidioidomycosis were excluded.RESULTS: Three cases of neonatal coccidioidomycosis were identified at our institution. Each presented in a unique manner and had an alternative diagnosis at the time of initial presentation. Two patients had negative coccidioidal screening tests upon admission but later seroconverted. All patients had extrapulmonary involvement, and all recovered after appropriate treatment. A review of the literature reveals that the presentations and outcomes of neonatal coccidioidomycosis vary widely.CONCLUSIONS: There is significant variability in the presentation of coccidioidomycosis in the neonatal period, and diagnosis may be challenging. In endemic regions, healthcare providers should consider coccidioidomycosis in their differential diagnoses of ill-appearing neonates that do not respond to treatment.

  View details for DOI 10.1097/INF.0000000000003281

  View details for PubMedID 34310505

• Congenital Coccidioidomycosis: A Case Report and Review of the Literature. Journal of the Pediatric Infectious Diseases Society Naeem, F., Vijayan, V., Kim, B. Y., Rahmati, E., McCarty, J. 2021

  Abstract

  Coccidioidomycosis in neonates is rare and the acquisition of disease in this age group is not well understood. Congenital coccidioidomycosis is very rare, usually associated with coccidioidal placentitis. Only a handful of cases of congenital coccidioidomycosis have been described in the literature. We describe an infant with congenital coccidioidomycosis delivered by cesarean section to a mother who was diagnosed with disseminated disease in the second trimester and summarize the available literature on congenital coccidioidomycosis.

  View details for DOI 10.1093/jpids/piab019

  View details for PubMedID 33969875

• Long-Term Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Adolescents Aged 12-17 Years in the United States. The American journal of tropical medicine and hygiene McCarty, J. M., Cassie, D., Bedell, L., Lock, M. D., Bennett, S. 2021

  Abstract

  As part of a phase 4, randomized, double-blind, placebo-controlled trial to assess the immunogenicity and safety of PXVX0200 in children and adolescents aged 2-17 years, a subset of 73 adolescent subjects aged 12-17 years was followed up for 2 years after vaccination and had blood collected for antibody assays on days 1, 11, 29, 91, 181, 365, 547, and 730. Endpoints included serum vibriocidal antibody (SVA) seroconversion, defined as a 4-fold or greater rise in antibody titer over baseline; geometric mean titers (GMTs); and geometric mean fold increase (GMFI) over baseline. Serum vibriocidal antibody seroconversion persisted in most subjects, with a rate of 64.5% noted at day 730. Geometric mean titers and GMFI both peaked at day 11 and remained greater than baseline at all time points, including day 730. Vaccination with PXVX0200 produces an immune response which persists for at least 2 years in adolescents aged 12-17 years.

  View details for DOI 10.4269/ajtmh.20-1576

  View details for PubMedID 33819178

• Hydrocephalus in Mexican children with Coccidioidal Meningitis: Clinical, serological, and neuroimaging findings. Surgical neurology international De la Cerda-Vargas, M. F., Sandoval-Bonilla, B. A., McCarty, J. M., De Leon, F. C., Candelas-Rangel, J. A., Rodriguez-Rodriguez, J. D., Navarro-Dominguez, P., Munoz-Hernandez, M. A., Meza-Mata, E., Fernandez-Gonzalez, E. M., Samano-Avina, M. G. 2021; 12: 119

  Abstract

  Background: Coccidioidal meningitis (CM) is a fungal infectious disease that rarely affects children. Even in endemic areas, coccidiomycosis rarely affects the pediatric population. However, 40% of affected children develop hydrocephalus. Here, we describe the clinical, serological, and neuroimaging findings in a series of Mexican children admitted to our neurosurgical service with hydrocephalus and subsequently diagnosed with CM.Methods: We report a prospective series of pediatric patients with hydrocephalus secondary to CM in an endemic area at the north of Mexico. Our report includes children with CM who were hospitalized from 2015 to 2019 in a regional hospital in Torreon, Coahuila. Clinical evolution was monitored for 1 year after hospital discharge.Results: Our series include five children with CM (2-17-years-old, three female), who were hospitalized for hydrocephalus and developed intracranial hypertension. The most frequent neuroimaging findings were leptomeningeal enhancement (5/5) and basal arachnoiditis (4/5), followed by asymmetric hydrocephalus (3/5), abnormalities in fourth ventricle morphology (3/5), and cerebral vasculitis (2/5). CM was diagnosed by positive serology or pathology studies. All children were initially managed with fluconazole and a shunt was placed for management of hydrocephalus. Four patients recovered without permanent neurological deficits and one subject developed persistent vegetative state. One year after hospital discharge, none of the subjects died.Conclusion: This series contributes to the limited number of pediatric CM cases reported in the literature, and describes neuroimaging findings in the pediatric population. The cases here presented show that the identification of Coccidioides as causal agent in pediatric meningitis is crucial for targeted treatment and can affect dramatically neurological prognosis. Furthermore, our report stresses that even in endemic areas pediatric coccidiomycosis represents a diagnostic challenge, which is further exacerbated by the limited availability of resources in these regions. Therefore, a positive immunoglobulin G by enzyme immunoassay is enough for diagnosis of CM in endemic areas without access to CF.

  View details for DOI 10.25259/SNI_895_2020

  View details for PubMedID 33880224

• Update on CVD 103-HgR single-dose, live oral cholera vaccine. Expert review of vaccines McCarty, J., Bedell, L., de Lame, P. A., Cassie, D., Lock, M., Bennett, S., Haney, D. 2021

  Abstract

  Cholera remains endemic in >50 countries, putting millions at risk, especially young children for whom killed vaccines offer limited protection. An oral, live attenuated vaccine - CVD 103-HgR (Vaxchora vaccine) - was licensed by the US FDA in 2016 for adults aged 18-64 years traveling to endemic regions, based on clinical trials in human volunteers showing the vaccine was well-tolerated and conferred 90% efficacy within 10 days.The evidence base for Vaxchora vaccine has expanded with additional clinical trial data, in older adults (aged 46-64 years) and children (aged 2-17 years), demonstrating that the vaccine is well-tolerated and produces a cross-strain vibriocidal antibody response and seroconversion rates associated with protection from cholera diarrhea. Over 68,000 doses have been administered in the USA, with no new safety signals. The dose volume has been reduced in children to improve acceptability, and cold chain requirements are less stringent, at +2°C─+8°C. The vaccine has recently been licensed in the USA for children aged 2-17 years, in Europe for individuals aged ≥2 years, and for home administration in Europe.Next steps include a Phase 4 study in infants (6-23 months). Additional information is needed regarding duration of immunity, the need for and timing of revaccination, and efficacy data from lower-middle-income countries.

  View details for DOI 10.1080/14760584.2022.2003709

  View details for PubMedID 34775892

• Safety and Immunogenicity of Live Oral Cholera Vaccine CVD 103-HgR in Children Aged 2-5 Years in the United States. The American journal of tropical medicine and hygiene McCarty, J. M., Cassie, D., Bedell, L., Lock, M. D., Bennett, S. 2020

  Abstract

  In a phase 4, randomized, placebo-controlled, double-blind, multicenter study, to assess the safety and immunogenicity of live, attenuated cholera vaccine PXVX0200 in children aged 2-5 years in the United States, 172 volunteers were randomized 6:1 to receive a single dose of 1 * 109 CFU of PXVX0200 or placebo. Immunogenicity endpoints included serum vibriocidal antibody (SVA) levels on days 1, 11, and 29. Safety was assessed by comparing solicited signs and symptoms on days 1-8, unsolicited adverse events through day 29, and serious adverse events (SAEs) through day 181. The SVA seroconversion rates 10 days after immunization were 98.1% and 0% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in the bridging population of adults aged 18-45 years from a lot consistency study. Most reactogenicity was mild to moderate, and there were no study-related SAEs. PXVX0200 appears safe and immunogenic in children aged 2-5 years.

  View details for DOI 10.4269/ajtmh.20-0917

  View details for PubMedID 33319739

• Isavuconazole as Salvage Therapy for Refractory Pediatric Coccidioidal Meningitis. The Pediatric infectious disease journal Naeem, F., Laningham, F., Kuzmic, B., Clerkin, P., McCarty, J. 2020

  Abstract

  Coccidioidal meningitis remains difficult to treat. The newer triazole, isavuconazole, has demonstrated efficacy in invasive fungal disease with less side effects than other azoles. We describe a case of refractory pediatric coccidioidal meningitis with disease stabilization and improvement on isavuconazole after failing treatment with other antifungal agents.

  View details for DOI 10.1097/INF.0000000000003017

  View details for PubMedID 33315746

• Extrapulmonary Coccidioidomycosis Among Children in Central California: A Retrospective Review. The Pediatric infectious disease journal Naeem, F., McCarty, J., Mhaissen, M. N., Ha, S., Rongkavilit, C. 2019; 38 (12): 1189–94

  Abstract

  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

• 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 McCarty, J. M., Gierman, E. C., Bedell, L., Lock, M. D., Bennett, S. 2019

  Abstract

  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. Vaccine McCarty, J. M., Lock, M. D., Bennett, S., Hunt, K. M., Simon, J. K., Gurwith, M. 2019; 37 (11): 1389–97

  Abstract

  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

• Age-related immunogenicity and reactogenicity of live oral cholera vaccine CVD 103-HgR in a randomized, controlled clinical trial VACCINE McCarty, J. M., Lock, M. D., Bennett, S., Hunt, K. M., Simon, J. K., Gurwith, M. 2019; 37 (11): 1389–97

  View details for DOI 10.1016/j.vaccine.2019.01.077

  View details for Web of Science ID 000461405400003

• Pediatric Coccidioidomycosis Case Series From a California Pediatric Infectious Diseases Clinic PEDIATRIC INFECTIOUS DISEASE JOURNAL Lee, L. A., Cooksey, G., Kim, J. J., Kahal, A., Gilliss, D., Naeem, F., McCarty, J. M., Vugia, D. J. 2019; 38 (2): 115–21

  Abstract

  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

• Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients. The Journal of allergy and clinical immunology Davini, D., Naeem, F., Phong, A., Al-Kuhlani, M., Valentine, K. M., McCarty, J., Ojcius, D. M., Gravano, D. M., Hoyer, K. K. 2018; 142 (6): 1971

  View details for PubMedID 30539725

• Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Davini, D., Naeem, F., Phong, A., Al-Kuhlani, M., Valentine, K. M., McCarty, J., Ojcius, D. M., Gravano, D. M., Hoyer, K. K. 2018; 142 (6): 1971-+

  View details for DOI 10.1016/j.jaci.2018.10.022

  View details for Web of Science ID 000452315800030

• Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18-45 VACCINE McCarty, J. M., Lock, M. D., Hunt, K. M., Simon, J. K., Gurwith, M. 2018; 36 (6): 833–40

  Abstract

  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

• Epidemiology of Pediatric Coccidioidomycosis in California, 2000-2012. Pediatric infectious disease journal Sondermeyer, G. L., Lee, L. A., Gilliss, D., McCarty, J. M., Vugia, D. J. 2016; 35 (2): 166-171

  Abstract

  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