Estimating False-Recent Classification for the Limiting-Antigen Avidity EIA and BED-Capture Enzyme Immunoassay in Vietnam: Implications for HIV-1 Incidence Estimates.

Laboratory tests that can distinguish recent from long-term HIV infection are used to estimate HIV incidence in a population, but can potentially misclassify a proportion of long-term HIV infections as recent. Correct application of an assay requires determination of the proportion false recents (PFRs) as part of the assay characterization and for calculating HIV incidence in a local population using a HIV incidence assay. From April 2009 to December 2010, blood specimens were collected from HIV-infected individuals attending nine outpatient clinics (OPCs) in Vietnam (four from northern and five from southern Vietnam). Participants were living with HIV for ≥1 year and reported no antiretroviral (ARV) drug treatment. Basic demographic data and clinical information were collected. Specimens were tested with the BED capture enzyme immunoassay (BED-CEIA) and the Limiting-antigen (LAg)-Avidity EIA. PFR was estimated by dividing the number of specimens classified as recent by the total number of specimens; 95% confidence intervals (CI) were calculated. Specimens that tested recent had viral load testing performed. Among 1,813 specimens (north, n = 942 and south, n = 871), the LAg-Avidity EIA PFR was 1.7% (CI: 1.2-2.4) and differed by region [north 2.7% (CI: 1.8-3.9) versus south 0.7% (CI: 0.3-1.5); p = .002]. The BED-CEIA PFR was 2.3% (CI: 1.7-3.0) and varied by region [north 3.4% (CI: 2.4-4.7) versus south 1.0% (CI: 0.5-1.2), p < .001]. Excluding specimens with an undetectable VL, the LAg-Avidity EIA PFR was 1.2% (CI: 0.8-1.9) and the BED-CEIA PFR was 1.7% (CI: 1.2-2.4). The LAg-Avidity EIA PFR was lower than the BED-CEIA PFR. After excluding specimens with an undetectable VL, the PFR for both assays was similar. A low PFR should facilitate the implementation of the LAg-Avidity EIA for cross-sectional incidence estimates in Vietnam.

Uptake of early infant diagnosis in Thailand's national program for preventing mother-to-child HIV transmission and linkage to care, 2008-2011.

INTRODUCTION: Early infant diagnosis (EID) has been a component of Thailand's prevention of mother-to-child HIV transmission (PMTCT) programme since 2007. This study assessed the uptake, EID coverage, proportion of HIV-exposed infants receiving a definitive HIV diagnosis, mother-to-child transmission (MTCT) rates and linkage to HIV care and treatment. METHODS: Infant polymerase chain reaction (PCR) testing data from the National AIDS Program database were analyzed. EID coverage was calculated as the percentage of number of HIV-exposed infants receiving ≥ 1 HIV PCR test divided by the number of HIV-exposed infants estimated from HIV prevalence and live-birth registry data. Definitive HIV diagnosis was defined as having two concordant PCR results. MTCT rates were calculated based on infants tested with PCR and applied as a best-case scenario, and a sensitivity analysis was used to adjust these rates in average and worst scenarios. We defined linkage to HIV care as infants with at least one PCR-positive test who were registered with Thailand's National AIDS Program. Chi-squared tests for linear trend were used to analyze changes in programme coverage. RESULTS: For 2008 to 2011, the average EID coverage rate increased from 54 to 76% (p < 0.001), with 65% coverage (13,761/21,099) overall. The number of hospitals submitting EID samples increased from 458 to 645, and the percentage of community hospitals submitting samples increased from 75 to 78% (p = 0.044). A definitive HIV diagnosis was made for 10,854 (79%) infants during this period. The adjusted MTCT rates had significantly decreasing trends in all scenarios. Overall, an estimated 53% (429/804) of HIV-infected infants were identified through the EID programme, and 80% (341/429) of infants testing positive were linked to care. The overall rate of antiretroviral treatment (ART) initiation within one year of age was 37% (157/429), with an increasing trend from 28 to 52% (p < 0.001). CONCLUSIONS: EID coverage increased and MTCT rates decreased during 2008 to 2011; however, about half of HIV-infected infants still did not receive EID. Most HIV-infected infants were linked to care but less than half initiated ART within one year of age. Active follow-up of HIV-exposed infants to increase early detection of HIV infection and early initiation of ART should be more widely implemented.

Diverse HIV epidemics among people who inject drugs in Thailand: evidence from respondent-driven sampling surveys in Bangkok and Chiang Mai.

BACKGROUND: Thailand's long-standing HIV sero-sentinel surveillance system for people who inject drugs (PWID) is confined to those in methadone-based drug treatment clinics and representative data are scarce, especially outside of Bangkok. METHODS: We conducted probability-based respondent-driven sampling (RDS) surveys in Bangkok (n=738) and Chiang Mai (n=309) to increase understanding of local HIV epidemics and to better inform the planning of evidence-based interventions. RESULTS: PWID had different epidemiological profiles in these two cities. Overall HIV prevalence was higher in Bangkok (23.6% vs. 10.9%, p<0.001) but PWID in Bangkok are older and appear to have long-standing HIV infections. In Chiang Mai, HIV infections appear to be more recently acquired and PWID were younger and had higher levels of recent injecting and sexual risk behaviors with lower levels of intervention exposure. Methamphetamine was the predominant drug injected in both sites and polydrug use was common although levels and patterns of the specific drugs injected varied significantly between the sites. In multivariate analysis, recent midazolam injection was significantly associated with HIV infection in Chiang Mai (adjusted odds ratio=8.1; 95% confidence interval: 1.2-54.5) whereas in Bangkok HIV status was not associated with recent risk behaviors as infections had likely been acquired in the past. CONCLUSION: PWID epidemics in Thailand are heterogeneous and driven by local factors. There is a need to customize intervention strategies for PWID in different settings and to integrate population-based survey methods such as RDS into routine surveillance to monitor the national response.

Assessment of a couples HIV counseling and testing program for pregnant women and their partners in antenatal care (ANC) in 7 provinces, Thailand.

BACKGROUND: Couples HIV testing and counseling (CHTC) at antenatal care (ANC) settings allows pregnant women to learn the HIV status of themselves and their partners. Couples can make decisions together to prevent HIV transmission. In Thailand, men were tested at ANC settings only if their pregnant partners were HIV positive. A CHTC program based in ANC settings was developed and implemented at 16 pilot hospitals in 7 provinces during 2009-2010. METHODS: Cross-sectional data were collected using standard data collection forms from all pregnant women and accompanying partners who presented at first ANC visit at 16 hospitals. CHTC data for women and partners were analyzed to determine service uptake and HIV test results among couples. In-depth interviews were conducted among hospital staff of participating hospitals during field supervision visits to assess feasibility and acceptability of CHTC services. RESULTS: During October 2009-April 2010, 4,524 women initiating ANC were enrolled. Of these, 2,435 (54%) women came for ANC alone; 2,089 (46%) came with partners. Among men presenting with partners, 2,003 (96%) received couples counseling. Of these, 1,723 (86%) men and all pregnant women accepted HIV testing. Among 1,723 couples testing for HIV, 1,604 (93%) returned for test results. Of these, 1,567 (98%) were concordant negative, 6 (0.4%) were concordant positive and 17 (1%) were HIV discordant (7 male+/female- and 10 male-/female+). Nine of ten (90%) executive hospital staff reported high acceptability of CHTC services. CONCLUSIONS: CHTC implemented in ANC settings helps identify more HIV-positive men whose partners were negative than previous practice, with high acceptability among hospital staff.

'Getting to zero' in Asia and the Pacific through more strategic use of antiretrovirals for HIV prevention.

Encouraged by experimental trials demonstrating the efficacy of antiretrovirals (ARVs) in preventing HIV infection, countries across the Asia-Pacific region have committed to the achievement of ambitious targets tantamount to ending AIDS. The available data suggest that some countries still can make progress through targeted condom promotion and the expansion of harm-reduction interventions, but that none may realise its vision of 'zero new HIV infections' without more strategic use of ARVs as part of a combination of HIV prevention efforts targeting key populations. Low rates of HIV testing among men who have sex with men, people who inject drugs, sex workers and other key populations evidence low treatment coverage where treatment could have the greatest impact on curbing local epidemics. Studies have demonstrated the promise of adding ARV treatment and pre-exposure prophylaxis to the existing HIV prevention toolkit, but achieving population-level impact will require service-delivery approaches that overcome traditional prevention, care and treatment program distinctions. Priorities include: (1) innovative strategies to reach, test, treat and retain in services the individuals most likely to acquire or transmit HIV; (2) task shifting and enhanced partnerships between the public sector and civil society; (3) improved 'cascade' data systems to assess and promote service uptake and retention; and (4) policy and financing reform to enhance HIV testing and treatment access among key populations.

HIV incidence in Asia: a review of available data and assessment of the epidemic.

Rates of new HIV infections in Asia are poorly characterized, likely resulting in knowledge gaps about infection trends and the most important areas to target for interventions. We conducted a systematic review of peer-reviewed English language publications and conference abstracts on HIV incidence in thirteen countries - Bangladesh, Cambodia, China, India, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Taiwan, Thailand, and Vietnam. We obtained data on HIV incidence rate, incidence estimation method, population, and risk factors for incident infection. Our search yielded 338 unique incidence estimates from 70 published articles and 41 conference abstracts for eight countries. A total of 138 (41%) were obtained from prospective cohort studies and 106 (31%) were from antibody-based tests for recent infection. High HIV incidence rates were observed among commercial sex workers (0.4-27.8 per 100 person-years), people who inject drugs (0.0-43.6 per 100 person-years) and men who have sex with men (0.7-15.0 per 100 person-years). Risk factors for incident HIV infection include brothel-based sex work and cervicitis among commercial sex workers; young age, frequent injection use and sharing needles or syringes among people who inject drugs; multiple male sexual partners, receptive anal intercourse and syphilis infection among men who have sex with men. In the countries with available data, incidence rates were highest in key populations and varied widely by incidence estimation method. Established surveillance systems that routinely monitor trends in HIV incidence are needed to inform prevention planning, prioritize resources, measure impact, and improve the HIV response in Asia.

Surveillance of transmitted HIV drug resistance using matched plasma and dried blood spot specimens from voluntary counseling and testing sites in Ho Chi Minh City, Vietnam, 2007-2008.

During 2007-2008, surveillance of transmitted human immunodeficiency virus (HIV) drug resistance (TDR) was performed following World Health Organization guidance among clients with newly diagnosed HIV infection attending voluntary counseling and testing (VCT) sites in Ho Chi Minh City (HCMC), Vietnam. Moderate (5%-15%) TDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was observed among VCT clients aged 18-21 years. Follow-up surveillance of TDR in HCMC and other geographic regions of Vietnam is warranted. Data generated will guide the national HIV drug resistance surveillance strategy and support selection of current and future first-line antiretroviral therapy and HIV prevention programs.

Utilization of HIV voluntary counseling and testing in Vietnam: an evaluation of 5 years of routine program data for national response.

This study evaluated the utilization of HIV voluntary counseling-and-testing (VCT) services targeting high-risk populations in Vietnam in order to inform decisions on program improvement and expansion. A total of 158,888 records collected from 55 VCT sites supported by the U.S. Centers for Disease Control and Prevention's Global AIDS Program in the period of 2002 to 2007 were used to analyze sociodemographic characteristics, risk exposures, seropositivity, test refusal, and failure to return for test results among VCT clients. High-risk exposures, such as injection drug use, commercial sex work, homosexual contacts or heterosexual contacts with high-risk sex partners, were reported in 126,815 (81%) records. Among high-risk clients, any condom use in the past month ranged from 34% to 71%. During the study period, 19% of the VCT encounters resulted in a positive HIV test; of those persons tested, 23% of men and 13% of women were HIV-positive. High HIV positivity rates were associated with injection drug use, being ill/recommended by health care provider, and having an HIV-infected sex partner. Of all records, 6.1% documented refusal of HIV testing. Failure to return for results was reported in 3.5% of records for clients who were tested. Previously testing positive was the strongest predictor of test refusal, and being referred by peer educators was associated with failure to return for results. The VCT program in Vietnam successfully targeted high-risk populations, and clients had high return rates using a standard testing strategy. Interventions to increase consistent condom use and promote access to prevention services among sex partners of high-risk individuals should be implemented and evaluated.

Effectiveness of 23-valent polysaccharide pneumococcal vaccine on pneumonia in HIV-infected adults in the United States, 1998--2003.

Pneumococcal polysaccharide vaccine (PPV-23) has been recommended for HIV-infected adults. We investigated factors that could influence PPV-23 effectiveness against all-cause pneumonia in a longitudinal cohort of 23,255 HIV-infected adults receiving care during 1998--2003. Patients who received PPV-23 had a lower rate of pneumonia (IRR = 0.8; 95% CI: 0.8-0.9) than patients who had never been vaccinated, independent of recent CD4 count, HIV viral load, antiretroviral therapy, and history of pneumonia. However, PPV-23 provided no benefit when patients were vaccinated at HIV viral load > 100,000 copies/ml, irrespective of CD4 count at vaccination. Receipt of PPV-23 was associated with lower incidence of all-cause pneumonia.

HIV drug resistance threshold survey using specimens from voluntary counselling and testing sites in Hanoi, Vietnam.

BACKGROUND: In countries where antiretroviral therapy has been available or is being rapidly expanded, the World Health Organization (WHO) recommends surveillance for transmitted HIV drug resistance (HIVDR) by threshold surveillance methods using specimens from antenatal clinics or voluntary counselling and testing (VCT) sites. The aim of this study was to implement the HIVDR threshold survey in VCT sites in Vietnam, where HIV prevalence is high. Estimating transmitted resistance in the infected population will enable the appropriateness of current antiretroviral drug regimens to be assessed and will inform plans for future HIVDR surveillance. METHODS: Consecutive blood specimens were collected from 70 newly diagnosed HIV-positive clients 18-24 years of age at two sites in Hanoi, Vietnam. Informed consent and serum specimens were obtained from each eligible client, with serum frozen at -70 degrees C until shipping to Thailand for resistance testing using the TruGene system. RESULTS: From February until August 2006, 559 clients were eligible to participate in this survey. Of the 535 clients (95.7%) who agreed to participate, 70 (13%) were HIV-positive and were included in the survey. Of the 70 specimens sent for genotyping, 52 consecutive samples were amplified, 49 of which could be genotyped. Only 1 of 49 genotyped specimens had mutations associated with drug resistance (L74V and Y181C) in the reverse transcriptase gene, indicating that the prevalence of transmitted HIVDR to all drugs and drug classes evaluated was <5%. CONCLUSION: The prevalence of transmitted HIVDR was low in Hanoi as determined using threshold surveillance methods. The Ministry of Health plans to repeat this survey methodology in one more province and to confirm these findings by expanded HIVDR surveillance.

Trends in perimortal conditions and mortality rates among HIV-infected patients.

OBJECTIVES: To describe trends in perimortal conditions (pathological conditions causing death or present at death but not necessarily the reported cause of death) during three periods related to the availability of HAART, pre-HAART (1992-1995), early HAART (1996-1999), and contemporary HAART (2000-2003); annual mortality rates; and antiretroviral therapy (ART) prevalence during 1992-2003. DESIGN: Multicenter observational clinical cohort in the United States (Adult/Adolescent Spectrum of HIV Disease [ASD] project). METHODS: Proportionate mortality for selected perimortal conditions, annual mortality rates, and ART prevalence were standardized by sex, race/ethnicity, age at death, HIV transmission category, and lowest CD4 cell count of ASD decedents. Multivariable generalized linear regression was used to estimate trends in proportionate mortality, as linear trends through all three HAART periods, mortality rates, and ART prevalence. RESULTS: Of 9225 deaths, 58.6% occurred during 1992-1995, 29.5% during 1996-1999, and 11.9% during 2000-2003. Linear trends in proportionate mortality for noninfectious diseases (e.g., liver disease, hypertension, and alcohol abuse) increased significantly; proportionate mortality for AIDS-defining infectious diseases (e.g., pneumocystosis, nontuberculous mycobacterial disease, and cytomegalovirus disease) decreased significantly. Mortality rates decreased from 487.5/1000 person-years in 1995 to 100.6 in 2002. Of 36 256 patients from ASD, 75.7% (standardized average) were prescribed ART annually. CONCLUSIONS: Among HIV-infected patients, the majority of whom were prescribed ART, the increasing trend in common noninfectious perimortal conditions support screening and treatment for these conditions in order to sustain the trend in declining mortality rates.

Improving the representativeness of behavioral and clinical surveillance for persons with HIV in the United States: the rationale for developing a population-based approach.

The need for a new surveillance approach to understand the clinical outcomes and behaviors of people in care for HIV evolved from the new challenges for monitoring clinical outcomes in the HAART era, the impact of the epidemic on an increasing number of areas in the US, and the need for representative data to describe the epidemic and related resource utilization and needs. The Institute of Medicine recommended that the Centers for Disease Control and Prevention and the Heath Resources and Services Administration coordinate efforts to survey a random sample of HIV-infected persons in care, in order to more accurately measure the need for prevention and care services. The Medical Monitoring Project (MMP) was created to meet these needs. This manuscript describes the evolution and design of MMP, a new nationally representative clinical outcomes and behavioral surveillance system, and describes how MMP data will be used locally and nationally to identify care and treatment utilization needs, and to plan for prevention interventions and services.

Discontinuation of primary prophylaxis against Mycobacterium avium complex infection in HIV-infected persons receiving antiretroviral therapy: observations from a large national cohort in the United States, 1992-2002.

In a large, diverse cohort of human immunodeficiency virus (HIV)-infected persons receiving routine care, the proportion of eligible persons who discontinued primary prophylaxis against Mycobacterium avium complex (MAC) infection, according to guidelines of the US Public Health Service and the Infectious Diseases Society of America, increased from 16.7% (in 1996) to 84.9% (in 2002). The discontinuation of primary prophylaxis was not associated with an increased risk of disseminated MAC infection.

Report from the CDC: mental health of women in postwar Afghanistan.

More than two decades of war and a culture that has denied women freedom of movement, access to healthcare, and education have affected the mental health status of Afghan women more than that of men. In 2002, the Centers for Disease Control and Prevention (CDC) conducted a national population-based mental health survey in Afghanistan. The prevalence of symptoms of depression was 73% (standard error [SE] 8.15) and 59% (SE 5.59), of symptoms of anxiety was 84% (SE 2.98) and 59% (SE 8.65), and of posttraumatic stress disorder (PTSD) was 48% (SE 6.19) and 32% (SE 4.22) for female and male respondents, respectively. Mean scores for social functioning were lower for women (52.00 [SE 2.77]) than for men (66.63 [SE 3.92]). Women had significantly lower mental health status and poorer social functioning than did men. Results of our survey underscore the need for financial donors and healthcare planners to address the current lack of mental healthcare resources, facilities, and trained mental healthcare professionals in Afghanistan and to establish mental health services directed at the specific needs of women. This study highlights the negative impact that war, restrictions in freedoms, and socioeconomic hardship have had on the mental health and social functioning of women in Afghanistan.

The validity of chief complaint and discharge diagnosis in emergency department-based syndromic surveillance.

OBJECTIVE: Emergency department (ED)-based syndromic surveillance systems are being used by public health departments to monitor for outbreaks of infectious diseases, including bioterrorism; however, few systems have been validated. The authors evaluated a "drop-in" syndromic surveillance system by comparing syndrome categorization in the ED with chief complaints and ED discharge diagnoses from medical record review. METHODS: A surveillance form was completed for each ED visit at 15 participating Arizona hospitals between October 27 and November 18, 2001. Each patient visit was assigned one of ten clinical syndromes or "none." For six of 15 EDs, kappa statistics were used to compare syndrome agreement between surveillance forms and syndrome categorization with chief complaint and ED discharge diagnosis from medical record review. RESULTS: Overall, agreement between surveillance forms and ED discharge diagnoses (kappa = 0.55; 95% confidence interval [CI] = 0.52 to 0.59) was significantly higher than between surveillance forms and chief complaints (kappa = 0.48; 95% CI = 0.44 to 0.52). Agreement between chief complaints and ED discharge diagnoses was poor for respiratory tract infection with fever (kappa = 0.33; 95% CI = 0.27 to 0.39). Furthermore, pediatric chief complaints showed lower agreement for respiratory tract infection with fever when compared with adults (kappa = 0.34 [95% CI = 0.20 to 0.47] vs. kappa = 0.44 [95% CI = 0.28 to 0.59], respectively). CONCLUSIONS: In general, this syndromic surveillance system classified patients into appropriate syndrome categories with fair to good agreement compared with chief complaints and discharge diagnoses. The present findings suggest that use of ED discharge diagnoses, in addition to or instead of chief complaints, may increase surveillance validity for both automated and drop-in syndromic surveillance systems.

Mental health, social functioning, and disability in postwar Afghanistan.

CONTEXT: More than 2 decades of conflict have led to widespread human suffering and population displacement in Afghanistan. In 2002, the Centers for Disease Control and Prevention and other collaborating partners performed a national population-based mental health survey in Afghanistan. OBJECTIVE: To provide national estimates of mental health status of the disabled (any restriction or lack of ability to perform an activity in the manner considered normal for a human being) and nondisabled Afghan population aged at least 15 years. DESIGN, SETTING, AND PARTICIPANTS: A national multistage, cluster, population-based mental health survey of 799 adult household members (699 nondisabled and 100 disabled respondents) aged 15 years or older conducted from July to September 2002. Fifty district-level clusters were selected based on probability proportional to size sampling. One village was randomly selected in each cluster and 15 households were randomly selected in each village, yielding 750 households. MAIN OUTCOME MEASURES: Demographics, social functioning as measured by selected questions from the Medical Outcomes Study 36-Item Short-Form Health Survey, depressive symptoms measured by the Hopkins Symptoms Checklist-25, trauma events and symptoms of posttraumatic stress disorder (PTSD) measured by the Harvard Trauma Questionnaire, and culture-specific symptoms of mental illness and coping mechanisms. RESULTS: A total of 407 respondents (62.0%) reported experiencing at least 4 trauma events during the previous 10 years. The most common trauma events experienced by the respondents were lack of food and water (56.1%) for nondisabled persons and lack of shelter (69.7%) for disabled persons. The prevalence of respondents with symptoms of depression was 67.7% (95% confidence interval [CI], 54.6%-80.7%) and 71.7% (95% CI, 65.0%-78.4%), and symptoms of anxiety 72.2% (95% CI, 63.8%-80.7%) and 84.6% (95% CI, 74.1%-95.0%) for nondisabled and disabled respondents, respectively. The prevalence of symptoms of PTSD was similar for both groups (nondisabled, 42.1%; 95% CI, 34.2%-50.1%; and disabled, 42.2%; 95% CI, 29.2%-55.2%). Women had significantly poorer mental health status than men did. Respondents who were disabled had significantly lower social functioning and poorer mental health status than those who were nondisabled. Feelings of hatred were high (84% of nondisabled and 81% of disabled respondents). Coping mechanisms included religious and spiritual practices; focusing on basic needs, such as higher income, better housing, and more food; and seeking medical assistance. CONCLUSIONS: In this nationally representative survey of Afghans, prevalence rates of symptoms of depression, anxiety, and PTSD were high. These data underscore the need for donors and health care planners to address the current lack of mental health care resources, facilities, and trained mental health care professionals in Afghanistan.

Fatal infectious disease surveillance in a medical examiner database.

Increasing infectious disease deaths, the emergence of new infections, and bioterrorism have made surveillance for infectious diseases a public health concern. Medical examiners and coroners certify approximately 20% of all deaths that occur within the United States and can be a key source of information regarding infectious disease deaths. We hypothesized that a computer-assisted search tool (algorithm) could detect infectious disease deaths from a medical examiner database, thereby reducing the time and resources required to perform such surveillance manually. We developed two algorithms, applied them to a medical examiner database, and verified the cases identified against the opinion of a panel of experts. The algorithms detected deaths with infectious components with sensitivities from 67% to 94%, and predictive value positives ranging from 8% to 49%. Algorithms can be useful for surveillance in medical examiner offices that have limited resources or for conducting surveillance across medical examiner jurisdictions.

Assessment of urinary metals following exposure to a large vegetative fire, New Mexico, 2000.

INTRODUCTION: In May 2000, a vegetative fire burned 47,000 acres in northern New Mexico, including 7500 acres of land administered by the Los Alamos National Laboratory. We evaluated potential human exposures from the fire. METHODS: We surveyed two populations (firefighters and the general population) in four cities for urine heavy metal concentrations. Reference concentrations were based on the Third National Health and Nutrition Examination Survey (NHANES III). Multivariate linear regression assessed the association of urinary metal concentrations with smoke exposure. We also performed isotopic analysis of uranium and cesium on a subset of specimens. RESULTS: A total of 92 firefighters and 135 nonfirefighters participated. In both populations, urinary nickel, cesium, chromium, and uranium concentrations were greater than expected compared with NHANES III reference values. No values required immediate medical follow-up. Regression analysis demonstrated that for National Guard members, arsenic and cadmium levels were significantly related to smoke exposure, and for firefighters, cesium and arsenic levels were significantly related to exposure; however, only for cesium in National Guard members was this association in the positive direction. Isotopic analysis demonstrated that the cesium and uranium were naturally occurring. CONCLUSIONS: Some people had spot urine metal concentrations above nationally derived reference values, and values for some metals were associated with smoke exposure. These associations had little public health or clinical importance. Studies of exposures resulting from vegetative fires are difficult, and careful consideration should be given to the technical and communication processes at the outset of a fire exposure investigation. Recommendations for future investigations include testing as soon as possible during or after a fire, and early clinical consultation with a medical toxicologist.