Investigation of an mpox outbreak affecting many vaccinated persons in Chicago, IL-March 2023-June 2023.

BACKGROUND: After months of few mpox cases, an increased number of cases were reported in Chicago during May 2023; predominantly among fully vaccinated patients. We investigated the outbreak scope, differences between vaccinated and unvaccinated patients, and hypotheses for monkeypox virus (MPXV) infection after vaccination. METHODS: We interviewed patients and reviewed medical records to assess demographic, behavioral, and clinical characteristics, mpox vaccine status, and vaccine administration routes. We evaluated serum antibody levels after infection and compared patient viral genomes with MPXV sequences in available databases. We discussed potential vaccine compromise with partners who manufactured, handled, and administered vaccine associated with breakthrough infections. RESULTS: During March 18-June 27, 2023, we identified 49 mpox cases; 57% of these mpox patients were fully vaccinated (FV). FV patients received both JYNNEOS doses subcutaneously (57%), intradermally (7%), or via heterologous administration (36%). FV patients had more median sex partners (3, IQR=1-4) versus not fully vaccinated (NFV) patients (1, IQR=1-2). Thirty-six of 37 sequenced specimens belonged to lineage B.1.20 of clade IIb MPXV, which did not demonstrate any amino acid changes relative to B.1, the predominant lineage from May 2022. Vaccinated patients demonstrated expected humoral antibody responses; none were hospitalized. No vaccine storage excursions were identified. Approximately 63% of people at risk for mpox in Chicago were FV during this period. CONCLUSIONS: Our investigation indicated cases were likely due to frequent behaviors associated with mpox transmission, even with relatively high vaccine effectiveness and vaccine coverage. Cases after vaccination might occur in similar populations.

Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae.

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

The Management of Gonorrhea in the Era of Emerging Antimicrobial Resistance: What Primary Care Clinicians Should Know.

Gonorrhea rates continue to rise in the United States and Neisseria gonorrhoeae's propensity to develop resistance to all therapies used for treatment has complicated the management of gonorrhea. Ceftriaxone is the only remaining highly effective recommended regimen for gonococcal treatment and few new anti-gonococcal antimicrobials are being developed. The 2021 CDC STI Treatment Guidelines increased the dose of ceftriaxone to 500 mg (1 g if ≥ 150 kg) for uncomplicated infections. It is recommended that all clinicians should be aware of antimicrobial resistant gonorrhea and be able to appropriately manage any suspected gonorrhea treatment failure case.

How the Orthodox Features of Orthopoxviruses Led to an Unorthodox Mpox Outbreak: What We've Learned, and What We Still Need to Understand.

Orthopoxviruses have repeatedly confounded expectations in terms of the clinical illness they cause and their patterns of spread. Monkeypox virus (MPXV), originally characterized in the late 1950s during outbreaks among captive primates, has been recognized since the 1970s to cause human disease (mpox) in West and Central Africa, where interhuman transmission has largely been associated with nonsexual, close physical contact. In May 2022, a focus of MPXV transmission was detected, spreading among international networks of gay, bisexual, and other men who have sex with men. The outbreak grew in both size and geographic scope, testing the strength of preparedness tools and public health science alike. In this article we consider what was known about mpox before the 2022 outbreak, what we learned about mpox during the outbreak, and what continued research is needed to ensure that the global public health community can detect, and halt further spread of this disease threat.

Understanding the Impact of Mpox on Sexual Health Clinical Services: A National Knowledge, Attitudes, and Practices Survey-United States, 2022.

BACKGROUND: During the 2022 mpox outbreak, most cases were associated with sexual contact, and many people with mpox sought care from sexual health clinics and programs. The National Network of STD Clinical Prevention Training Centers, in partnership with the Centers for Disease Control and Prevention, conducted a survey of US sexual health clinics and programs to assess knowledge, practices, and experiences around mpox to inform a future public health response. METHODS: Between August 31 and September 13, 2022, the National Network of STD Clinical Prevention Training Centers facilitated a web-based survey. Descriptive statistics were generated in R. RESULTS: Among 168 responses by clinicians (n = 131, 78%) and program staff (n = 37, 22%), more than half (51%) reported at least somewhat significant mpox-related clinical disruptions including burdensome paperwork requirements for mpox testing (40%) and tecovirimat use (88%). Long clinic visits (51%) added additional burden, and the median mpox-related visit lasted 1 hour. Few clinicians felt comfortable with advanced pain management, and clinicians felt most uninformed about preexposure (19%) and postexposure (24%) prophylaxis. Of 89 respondents involved in vaccination, 61% reported using equity strategies; however, accounts of these strategies revealed a focus on guideline or risk factor-based screenings instead of equity activities. CONCLUSIONS: These findings highlight the substantial impact of the 2022 mpox outbreak on sexual health care in the United States. Critical gaps and barriers were identified that may inform additional mpox training and technical assistance, including challenges with testing, diagnosis, and management as well as a disconnect between programs' stated goal of equity and operationalization of strategies to achieve equity.

The CDC Domestic Mpox Response - United States, 2022-2023.

Monkeypox (mpox) is a serious viral zoonosis endemic in west and central Africa. An unprecedented global outbreak was first detected in May 2022. CDC activated its emergency outbreak response on May 23, 2022, and the outbreak was declared a Public Health Emergency of International Concern on July 23, 2022, by the World Health Organization (WHO),* and a U.S. Public Health Emergency on August 4, 2022, by the U.S. Department of Health and Human Services.† A U.S. government response was initiated, and CDC coordinated activities with the White House, the U.S. Department of Health and Human Services, and many other federal, state, and local partners. CDC quickly adapted surveillance systems, diagnostic tests, vaccines, therapeutics, grants, and communication systems originally developed for U.S. smallpox preparedness and other infectious diseases to fit the unique needs of the outbreak. In 1 year, more than 30,000 U.S. mpox cases were reported, more than 140,000 specimens were tested, >1.2 million doses of vaccine were administered, and more than 6,900 patients were treated with tecovirimat, an antiviral medication with activity against orthopoxviruses such as Variola virus and Monkeypox virus. Non-Hispanic Black (Black) and Hispanic or Latino (Hispanic) persons represented 33% and 31% of mpox cases, respectively; 87% of 42 fatal cases occurred in Black persons. Sexual contact among gay, bisexual, and other men who have sex with men (MSM) was rapidly identified as the primary risk for infection, resulting in profound changes in our scientific understanding of mpox clinical presentation, pathogenesis, and transmission dynamics. This report provides an overview of the first year of the response to the U.S. mpox outbreak by CDC, reviews lessons learned to improve response and future readiness, and previews continued mpox response and prevention activities as local viral transmission continues in multiple U.S. jurisdictions (Figure).

Potential for Recurrent Mpox Outbreaks Among Gay, Bisexual, and Other Men Who Have Sex with Men - United States, 2023.

More than 30,000 monkeypox (mpox) cases have been diagnosed in the United States since May 2022, primarily among gay, bisexual, and other men who have sex with men (MSM) (1,2). In recent months, diagnoses have declined to one case per day on average. However, mpox vaccination coverage varies regionally, suggesting variable potential risk for mpox outbreak recurrence (3). CDC simulated dynamic network models representing sexual behavior among MSM to estimate the risk for and potential size of recurrent mpox outbreaks at the jurisdiction level for 2023 and to evaluate the benefits of vaccination for preparedness against mpox reintroduction. The risk for outbreak recurrence after mpox reintroduction is linearly (inversely) related to the proportion of MSM who have some form of protective immunity: the higher the population prevalence of immunity (from vaccination or natural infection), the lower the likelihood of recurrence in that jurisdiction across all immunity levels modeled. In contrast, the size of a potential recurrent outbreak might have thresholds: very small recurrences are predicted for jurisdictions with mpox immunity of 50%-100%; exponentially increasing sizes of recurrences are predicted for jurisdictions with 25%-50% immunity; and linearly increasing sizes of recurrences are predicted for jurisdictions with <25% immunity. Among the 50 jurisdictions examined, 15 are predicted to be at minimal risk for recurrence because of their high levels of population immunity. This analysis underscores the ongoing need for accessible and sustained mpox vaccination to decrease the risk for and potential size of future mpox recurrences.

A Sore Subject? An Examination of National Case-Based Chancroid Surveillance.

BACKGROUND: Chancroid has been a nationally notifiable condition in the United States since 1944, with cases reported to Centers Disease Control and Prevention through the National Notifiable Diseases Surveillance System. Although frequently reported during the 1940s, <20 cases have been reported annually since 2011. We assessed the performance and utility of national case-based chancroid surveillance. METHODS: We reviewed the literature to contextualize chancroid surveillance through National Notifiable Diseases Surveillance System. We then assessed 4 system attributes, including data quality, sensitivity, usefulness, and representativeness: we reviewed chancroid cases reported during 2011-2020, conducted interviews with (a) sexually transmitted disease programs reporting ≥1 case in 2019 or 2020 (n = 9) and (b) Centers Disease Control and Prevention subject matter experts (n = 10), and reviewed published communicable disease reporting laws. RESULTS: Chancroid diagnostic testing is limited, which affects the surveillance case definition. National case-based surveillance has poor data quality; of the 2019 and preliminary 2020 cases (n = 14), only 3 were verified by jurisdictions as chancroid cases. Sexually transmitted disease programs report the system has low sensitivity given limited clinician knowledge and resources; experts report the system is not useful in guiding national control efforts. Review of reporting laws revealed it is not representative, as chancroid is not a reportable condition nationwide. CONCLUSIONS: Critical review of system attributes suggest that national case-based chancroid surveillance data have limited ability to help describe and monitor national trends, and chancroid's inclusion on the national notifiable list might need to be reconsidered. Alternative strategies might be needed to monitor national chancroid burden.

Mpox virus and transmission through sexual contact: Defining the research agenda.

In a Policy Forum piece, Dr. Nicola Low and colleagues define the research agenda for Mpox virus and transmission through sexual contact.

COVID-19 on the Nile: a cross-sectional investigation of COVID-19 among Nile River cruise travellers returning to the United States, February-March 2020.

BACKGROUND: Early in the pandemic, cruise travel exacerbated the global spread of SARS-CoV-2. We report epidemiologic and molecular findings from an investigation of a cluster of travellers with confirmed COVID-19 returning to the USA from Nile River cruises in Egypt. METHODS: State health departments reported data on real-time reverse transcription-polymerase chain reaction-confirmed COVID-19 cases with a history of Nile River cruise travel during February-March 2020 to the Centers for Disease Control and Prevention (CDC). Demographic and epidemiologic data were collected through routine surveillance channels. Sequences were obtained either from state health departments or from the Global Initiative on Sharing Avian Flu Data (GISAID). We conducted descriptive analyses of epidemiologic data and explored phylogenetic relationships between sequences. RESULTS: We identified 149 Nile River cruise travellers with confirmed COVID-19 who returned to 67 different US counties in 27 states: among those with complete data, 4.7% (6/128) died and 28.1% (38/135) were hospitalized. These individuals travelled on 20 different Nile River cruise voyages (12 unique vessels). Fifteen community transmission events were identified in four states, with 73.3% (11/15) of these occurring in Wisconsin (as the result of a more detailed contact investigation in that state). Phylogenetic analyses supported the hypothesis that travellers were most likely infected in Egypt, with most sequences in Nextstrain clade 20A 93% (87/94). We observed genetic clustering by Nile River cruise voyage and vessel. CONCLUSIONS: Nile River cruise travellers with COVID-19 introduced SARS-CoV-2 over a very large geographic range, facilitating transmission across the USA early in the pandemic. Travellers who participate in cruises, even on small river vessels as investigated in this study, are at increased risk of SARS-CoV-2 exposure. Therefore, history of river cruise travel should be considered in contact tracing and outbreak investigations.

Reported Neurologic, Ocular, and Otic Manifestations Among Syphilis Cases-16 States, 2019.

BACKGROUND: Syphilis can cause neurologic, ocular, or otic manifestations, possibly resulting in permanent disability or death. In 2018, the Centers for Disease Control and Prevention began collecting syphilis clinical manifestation data via the National Notifiable Diseases Surveillance System. We present the first reported US syphilis neurologic, ocular, and otic manifestation prevalence estimates. METHODS: We reviewed 2019 National Notifiable Diseases Surveillance System data to identify jurisdictions reporting 70% or greater of syphilis cases 15 years or older with clinical manifestation data (considered "complete reporting"). Among these jurisdictions, we determined reported neurologic, ocular, and otic manifestation prevalence, stratified by demographic, behavioral, and clinical characteristics. RESULTS: Among 41,187 syphilis cases in 16 jurisdictions with complete reporting, clinical manifestations were infrequently reported overall: neurologic (n = 445, 1.1%), ocular (n = 461, 1.1%), otic (n = 166, 0.4%), any (n = 807, 2.0%). Reported clinical manifestation prevalence was highest among cases 65 years or older (neurologic, 5.1%; ocular, 3.5%; otic, 1.2%) and those reporting injection drug use (neurologic: 2.8%; ocular: 3.4%; otic: 1.6%). Although reported neurologic and ocular manifestation prevalence was slightly higher among human immunodeficiency virus (HIV)-infected versus HIV-negative persons, approximately 40% of cases with manifestations were HIV-negative. Reported otic manifestation prevalence was similar regardless of HIV status. When stratifying by HIV status and syphilis stage, reported prevalence was highest among HIV-infected persons with unknown duration/late syphilis (neurologic, 3.0%; ocular, 2.3%; otic, 0.7%). CONCLUSIONS: Reported neurologic, ocular, and otic manifestation prevalence was low among syphilis cases, but these data are likely an underestimate given potential underreporting. Reported clinical manifestation frequency, including among HIV-negative persons, emphasizes the importance of evaluating all syphilis cases for signs/symptoms of neurosyphilis, ocular syphilis, and otosyphilis.

Cruise Ship Travel in the Era of Coronavirus Disease 2019 (COVID-19): A Summary of Outbreaks and a Model of Public Health Interventions.

BACKGROUND: Cruise travel contributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission when there were relatively few cases in the United States. By 14 March 2020, the Centers for Disease Control and Prevention (CDC) issued a No Sail Order suspending US cruise operations; the last US passenger ship docked on 16 April. METHODS: We analyzed SARS-CoV-2 outbreaks on cruises in US waters or carrying US citizens and used regression models to compare voyage characteristics. We used compartmental models to simulate the potential impact of 4 interventions (screening for coronavirus disease 2019 (COVID-19) symptoms; viral testing on 2 days and isolation of positive persons; reduction of passengers by 40%, crew by 20%, and reducing port visits to 1) for 7-day and 14-day voyages. RESULTS: During 19 January to 16 April 2020, 89 voyages on 70 ships had known SARS-CoV-2 outbreaks; 16 ships had recurrent outbreaks. There were 1669 reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections and 29 confirmed deaths. Longer voyages were associated with more cases (adjusted incidence rate ratio, 1.10, 95% confidence interval [CI]: 1.03-1.17, P < .003). Mathematical models showed that 7-day voyages had about 70% fewer cases than 14-day voyages. On 7-day voyages, the most effective interventions were reducing the number of individuals onboard (43.3% reduction in total infections) and testing passengers and crew (42% reduction in total infections). All four interventions reduced transmission by 80.1%, but no single intervention or combination eliminated transmission. Results were similar for 14-day voyages. CONCLUSIONS: SARS-CoV-2 outbreaks on cruises were common during January-April 2020. Despite all interventions modeled, cruise travel still poses a significant SARS-CoV-2 transmission risk.

Antimicrobial Susceptibility of Urogenital and Extragenital Neisseria gonorrhoeae Isolates Among Men Who Have Sex With Men: Strengthening the US Response to Resistant Gonorrhea and Enhanced Gonococcal Isolate Surveillance Project, 2018 to 2019.

BACKGROUND: We investigated differences in gonococcal antimicrobial susceptibility by anatomic site among cisgender men who have sex with men (MSM) using specimens collected through the Centers for Disease Control and Prevention's enhanced Gonococcal Isolate Surveillance Project and Strengthening the US Response to Resistant Gonorrhea. METHODS: During the period January 1, 2018-December 31, 2019, 12 enhanced Gonococcal Isolate Surveillance Project and 8 Strengthening the US Response to Resistant Gonorrhea sites collected urogenital, pharyngeal, and rectal isolates from cisgender MSM in sexually transmitted disease clinics. Gonococcal isolates were sent to regional laboratories for antimicrobial susceptibility testing by agar dilution. To account for correlated observations, linear mixed-effects models were used to calculate geometric mean minimum inhibitory concentrations (MICs), and mixed-effects logistic regression models were used to calculate the proportion of isolates with elevated or resistant MICs; comparisons were made across anatomic sites. RESULTS: Participating clinics collected 3974 urethral, 1553 rectal, and 1049 pharyngeal isolates from 5456 unique cisgender MSM. There were no significant differences in the geometric mean MICs for azithromycin, ciprofloxacin, penicillin, and tetracycline by anatomic site. For cefixime and ceftriaxone, geometric mean MICs for pharyngeal isolates were higher compared with anogenital isolates (P < 0.05). The proportion of isolates with elevated ceftriaxone MICs (≥0.125 µg/mL) at the pharynx (0.67%) was higher than at rectal (0.13%) and urethral (0.18%) sites (P < 0.05). CONCLUSIONS: Based on data collected from multijurisdictional sentinel surveillance projects, antimicrobial susceptibility patterns of Neisseria gonorrhoeae isolates may differ among MSM at extragenital sites, particularly at the pharynx. Continued investigation into gonococcal susceptibility patterns by anatomic site may be an important strategy to monitor and detect the emergence of antimicrobial resistant gonorrhea over time.

Genital Mycoplasma, Shigellosis, Zika, Pubic Lice, and Other Sexually Transmitted Infections: Neither Gone Nor Forgotten.

ABSTRACT: Most estimates of the combined burden and cost of sexually transmitted infections (STIs) in the United States have focused on 8 common STIs with established national surveillance strategies (chlamydia, gonorrhea, syphilis, trichomoniasis, genital herpes, human papillomavirus, and sexually transmitted human immunodeficiency virus and hepatitis B). However, over 30 STIs are primarily sexually transmitted or sexually transmissible. In this article, we review what is known about the burden of "other STIs" in the United States, including those where sexual transmission is not the primary transmission route of infection. Although the combined burden of these other STIs may be substantial, accurately estimating their burden due to sexual transmission is difficult due to diagnostic and surveillance challenges. Developing better estimates will require innovative strategies, such as leveraging existing surveillance systems, partnering with public health and academic researchers outside of the STI field, and developing methodology to estimate the frequency of sexual transmission, particularly for new and emerging STIs.

Prevalence of Self-reported Neurologic and Ocular Symptoms in Early Syphilis Cases.

BACKGROUND: Neurosyphilis, a complication of syphilis, can occur at any stage of infection. Measuring the prevalence of neurosyphilis is challenging, and there are limited data on the prevalence of neurologic or ocular symptoms among patients with syphilis. We sought to describe the prevalence of neurologic and/or ocular symptoms among early syphilis (ES) cases and the clinical management of symptomatic cases enrolled in the STD Surveillance Network (SSuN) Neuro/Ocular Syphilis Surveillance project. METHODS: Persons diagnosed with ES were selected for interviews based on current health department protocols in 5 participating SSuN jurisdictions from November 2016 through October 2017. All interviewed ES cases were screened for self-reported neurologic and/or ocular symptoms. Additional clinical information on diagnostic testing and treatment for cases concerning for neurosyphilis/ocular syphilis was obtained from providers. RESULTS: Among 9123 patients with ES who were interviewed, 151 (1.7%; 95% confidence interval [CI], 1.4%-1.9%) reported ≥ 1 neurologic or ocular symptom. Of the 53 (35%) who underwent lumbar puncture, 22 (42%) had documented abnormal cerebrospinal fluid, of which 21 (95%) were treated for neurosyphilis/ocular syphilis. Among the remaining 98 symptomatic patients with no documented lumbar puncture (65%), 12 (12%) were treated for and/or clinically diagnosed with neurosyphilis/ocular syphilis. CONCLUSIONS: We observed a low prevalence of self-reported neurologic and/or ocular symptoms in interviewed ES cases. Approximately one-third of ES cases who self-reported symptoms underwent further recommended diagnostic evaluation. Understanding barriers to appropriate clinical evaluation is important to ensuring appropriate management of patients with possible neurologic and/or ocular manifestations of syphilis.

Prevalence and correlates of and a risk score to identify asymptomatic anorectal gonorrhoea and chlamydia infection among men who have sex with men in Kisumu, Kenya.

OBJECTIVES: In settings where laboratory capacity is limited, the WHO recommends presumptive treatment for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) in asymptomatic men who have sex with men (MSM) at high risk for these infections. However, little is known about how best to target this intervention. We aimed to identify correlates of anorectal NG/CT infection in Kenyan MSM with and without anorectal symptoms and evaluate the performance of an empirical, model-based risk score to identify cases in asymptomatic men. METHODS: Anorectal NG/CT infections were diagnosed by the Abbott RealTime NG/CT nucleic acid amplification testamong 698 MSM at enrolment into the Anza Mapema study. Multivariable logistic regression was used to identify correlates of anorectal NG/CT infection in men with and without anorectal symptoms. Using coefficients from the final multivariable model for asymptomatic men, we calculated a risk score for each participant. Risk score performance was determined by calculating the sensitivity, specificity and number needed to treat (NNT) to identify one NG/CT infection. RESULTS: Overall anorectal NG/CT infection prevalence was 5.2% (n=36), of which 58.3% (n=21) were asymptomatic. Factors associated with anorectal NG/CT infection in asymptomatic men were aged 18-24 years (aOR=7.6; 95% CI: 1.7 to 33.2), HIV positive serostatus (aOR=6.9; 95% CI: 2.2 to 21.6) and unprotected anal sex in the past 3 months (aOR=3.8; 95% CI: 1.2 to 11.9). Sensitivity and specificity were optimal (81.0% and 66.1%, respectively) at a model-derived risk score cut-point ≥3, and the NNT was 12. CONCLUSIONS: A model-derived risk score based on correlates of anorectal NG/CT infection in asymptomatic participants would be sensitive and efficient (i.e, low NNT) for targeting presumptive treatment. If validated in other settings, this risk score could improve on the WHO algorithm and help reduce the burden of asymptomatic anorectal NG/CT infections among MSM in settings where diagnostic testing is not available.

Adverse Birth Outcomes and Maternal Neisseria gonorrhoeae Infection: A Population-Based Cohort Study in Washington State.

BACKGROUND: Neisseria gonorrhoeae (gonorrhea) remains an important cause of reproductive and obstetric complications. There has been limited population-based research to evaluate the association between maternal gonorrhea and adverse birth outcomes. METHODS: A population-based retrospective cohort study was conducted of women with singleton pregnancies in Washington State from 2003 to 2014 using linked birth certificate and birth hospitalization discharge data. The exposed cohort consisted of women with gonorrhea diagnosed during pregnancy. The unexposed group, defined as pregnant women without gonorrhea, was selected by frequency-matching by birth year in a 4:1 ratio. Logistic regression was used to determine crude and adjusted odds ratios (OR) for the association of maternal gonorrhea and adverse birth outcomes. RESULTS: Women with gonorrhea during pregnancy (N = 819) were more likely to be younger, black, single, less educated, multiparous, and smokers compared with women without gonorrhea (N = 3276). Maternal gonorrhea was significantly associated with a 40% increased odds (adjusted OR, 1.4; 95% confidence interval [CI], 1.0-1.8) of low birth weight infants compared with women without gonorrhea when adjusted for marital and smoking status. Maternal gonorrhea was associated with a 60% increased odds (OR, 1.6; 95% CI, 1.3-2.0) of small for gestational age infants compared with women without gonorrhea. CONCLUSIONS: This analysis showed that pregnant women with gonorrhea were more likely to have low birth weight infants, consistent with prior literature, and provided new evidence that maternal gonorrhea is associated with small for gestational age infants. These findings support increased public health efforts to prevent, identify, and treat gonorrhea infection during pregnancy.

Disseminated histoplasmosis of infancy in one of the twins.

This report describes clinical manifestations of histoplasmosis in 6-month-old dizygotic twins, one of whom developed disseminated histoplasmosis of infancy while his sibling remained well, but developed serologic evidence of histoplasmosis. The report also documents histoplasma antigen concentrations in serum and urine before, during and after completing antifungal therapy.