Malignancy in U.S. Air Force fighter pilots and other officers, 1986-2017: A retrospective cohort study.

OBJECTIVE: This study sought to determine the incidence rates of cancer, overall and by site, among active component U.S. Air Force fighter pilots, and to compare the rates with those in other active component Air Force officers. METHODS: Using a matched retrospective cohort design, U.S. Air Force fighter pilots were compared with other commissioned officers who entered active component service between 1 January 1986 and 31 December 2006. The cohort was followed for cancer diagnoses in TRICARE and the Veterans Health Administration from 1 October 1995 through 31 December 2017. Fighter pilots and non-fighter pilot officers were compared after matching on sex, age at first observation (15 age groups), and age at last observation (15 age groups). Sex-stratified overall and site-specific cancer rates were compared with matched Poisson regression to determine incidence rate ratios with 95% confidence intervals. RESULTS: During 1,412,590 person-years of follow-up, among the study population of 88,432 service members (4,949 fighter pilots and 83,483 matched officers), 977 incident cancer cases were diagnosed (86 in fighter pilots and 891 in matched officers). Male fighter pilots and matched officers had similar rates of all malignant cancers (RR = 1.04; 95% CI: 0.83-1.31) and of each cancer site. Female fighter pilots and matched officers also had similar rates of all malignant cancers (RR = 0.99; 95% CI: 0.25-4.04). DISCUSSION: In the active component U.S. Air Force, fighter pilots and their officer peers had similar overall and site-specific cancer rates.

Positive predictive value of an algorithm used for cancer surveillance in the U.S. Armed Forces.

Recent large-scale epidemiologic studies of cancer incidence in the U.S. Armed Forces have used International Classification of Disease, 9th and 10th Revision (ICD-9 and ICD-10, respectively) diagnostic codes from administrative medical encounter data archived in the Defense Medical Surveillance System. Cancer cases are identified and captured according to an algorithm published by the Armed Forces Health Surveillance Branch. Standardized chart reviews were performed to provide a gold standard by which to validate the case definition algorithm. In a cohort of active component U.S. Air Force, Navy, and Marine Corps officers followed from 1 October 1995 through 31 December 2017, a total of 2,422 individuals contributed 3,104 algorithm-derived cancer cases. Of these cases, 2,108 (67.9%) were classified as confirmed cancers, 568 (18.3%) as confirmed not cancers, and 428 (13.8%) as unclear. The overall positive predictive value (PPV) of the algorithm was 78.8% (95% confidence interval [CI]: 77.2-80.3). For the 12 cancer sites with at least 50 cases identified by the algorithm, the PPV ranged from a high of 99.6% for breast and testicular cancers (95% CI: 97.8-100.0 and 97.7-100.0, respectively) to a low of 78.1% (95% CI: 71.3-83.9) for non-Hodgkin lymphoma. Of the 568 cases confirmed as not cancer, 527 (92.7%) occurred in individuals with at least 1 other confirmed cancer, suggesting algorithmic capture of metastases as additional primary cancers.

Evaluation of serological testing for Lyme disease in Military Health System beneficiaries in Germany, 2013-2017.

Lyme disease diagnostic workups conducted on active and retired U.S. service members and their dependents at U.S. Air Force military treatment facilities (MTFs) in Germany between 2013 and 2017 were assessed to determine the appropriateness of laboratory testing and antibiotic prescriptions. Of the 1,176 first-tier immunoassays, 1,114 (94.7%) were negative, and of the 285 immunoglobulin M (IgM) immunoblots, 242 (84.9%) followed a negative first-tier assay or were performed without an antecedent first-tier assay. Eighty-three positive IgM immunoblot tests were adjudicated using modified published criteria, of which 40 (48.2%) were deemed false positives. Thirtytwo patients with false-positive tests were treated with an antibiotic. Additionally, 30 patients with uncomplicated erythema migrans could have been treated without laboratory confirmation. Understanding the use and limitations of 2-tier diagnostic criteria, as well as the common pitfalls in diagnosing Lyme disease, may help prevent overdiagnosis, reduce unnecessary testing, and promote antibiotic stewardship.

Physical and Mental Health of US Air Force Military Training Instructors.

INTRODUCTION: Many epidemiologic studies have been performed in military recruit populations, but little is known about the health of those who conduct the training. This study aims to characterize the physical and mental health of a military trainer cohort. MATERIALS AND METHODS: All US Air Force military training instructors (MTIs) who served between 1 October 2011 and 30 September 2016 were included in this retrospective descriptive study. All International Classification of Diseases, Ninth or Tenth Revision codes received by MTIs as inpatients or outpatients in the TRICARE system were obtained and mapped to Clinical Classifications Software levels. After excluding routine and administrative codes, the relative burden of disease by diagnostic category and subcategory was calculated, with further classification of musculoskeletal conditions by anatomic site. For all conditions accounting for at least 1.0% of the burden of care, incidence density rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated to compare males and females. RESULTS: A total of 1,269 MTIs received 32,601 non-administrative, non-routine diagnoses while accumulating 50,376 person-months of exposure during the surveillance period. Musculoskeletal conditions were the greatest contributor to overall disease burden, accounting for 39.1% of all diagnoses, followed by mental health (10.4%), respiratory (10.1%), and neurologic and sensory (9.8%). The burden attributed to mental health conditions decreased by 54% over the 5-year period. Twenty-three conditions accounted for at least 1.0% of the healthcare burden. The highest incidence conditions were connective tissue disease (27.18 per 1,000 person-months), non-traumatic joint disorders (25.74), upper respiratory infections (25.14), and back pain (23.70). As compared to males, females had a higher incidence of several conditions, including adjustment disorders (IRR: 2.57; 95% CI: 1.61, 4.11) and anxiety disorders (IRR: 2.24; 95% CI: 1.33, 3.77). CONCLUSIONS: Musculoskeletal conditions are the leading contributor to burden of care among US Air Force MTIs, followed by mental health, respiratory, and neurologic and sensory conditions. The burden of healthcare among US Air Force MTIs more closely resembles active component service members than recruit trainees.

Diagnoses and ordering practices driving blood demand for treatment of anemia in Tanzania.

BACKGROUND: Resource-limited countries in Africa experience blood shortages. Understanding clinical drivers of blood demand can inform strategies to increase blood availability. STUDY DESIGN AND METHODS: From a national representative sample of 42 hospitals in Tanzania, patient records and requests for whole blood (WB) and red blood cells (RBCs) to treat anemia were analyzed using data collected prospectively from June through September 2013. Abstracted data included cause of anemia, number of requested units, clinical signs, and pretransfusion hemoglobin (Hb) levels. Weighted projections of nationwide drivers of blood demand for the year, 2013, were calculated. Mean posttransfusion Hb levels were estimated, and blood requests were assessed for clinical appropriateness. RESULTS: Malaria was the leading driver of blood demand for anemia among children, accounting for 67% (55,949 units; standard deviation [SD], 1911 units) of projected units requested for children in 2013. Maternal hemorrhage was the leading driver of blood demand for anemia among adults, accounting for 21% (31,321 units; SD, 963 units) of projected units requested. Seventeen percent (26,133 units; SD, 1013 units) of projected requested units were deemed inappropriate. Adults with severe anemia had a mean Hb level of 3.7 g/dL and a mean of 1.6 WB or RBC units per request, resulting in an estimated mean posttransfusion Hb level of 5.3 g/dL. CONCLUSIONS: Strategies to prevent and treat underlying causes of anemia and decrease inappropriate blood requests will likely increase blood availability. Restrictive blood ordering practices seen in adults with severe anemia suggests undertreatment of anemia and may result in an underestimation of the national blood demand.

Estimating Tanzania's National Met and Unmet Blood Demand From a Survey of a Representative Sample of Hospitals.

Estimating blood demand to determine collection goals challenges many low-income countries. We sampled Tanzanian hospitals to estimate national blood demand. A representative sample based on probability proportional to size sampling of 42 of 273 (15%) Tanzanian transfusing hospitals was selected. Blood bank registers, patient medical records, and blood component disposition records were reviewed prospectively from June to September 2013 to determine the number of components requested and the number and proportion issued, not issued due to nonavailability, and not issued for other reasons. Data were estimated for an annual national estimate. Of an estimated 278 371 components requested in 2013, 6648 (2.4%) were not issued due to nonavailability, 34 591 (12.4%) were not issued for other reasons, and 244 535 (87.8%) were issued. Of these 278 371 components, 86 753 (31.2%) were requested by adult medical, 74 499 (26.8%) by pediatric medical, and 57 312 (20.6%) by obstetric units. In these 3 units, the proportion of units not issued due to nonavailability was 1.8%. Private (4.1%) and large (6%) hospitals had the largest proportion of units not issued because of nonavailability. Of 244 535 issued components, 91 690 (37.5%) were collected, tested, and issued from blood banks that are not part of the Tanzania National Blood Transfusion Services (TNBTS). Nearly 98% of blood component demand was met. However, a large portion of the blood supply for the hospitals came from non-TNBTS blood banks. TNBTS could increase availability of safe blood through assuring the quality of donor selection and donation testing at non-TNBTS blood banks.

HIV and alcohol knowledge, self-perceived risk for HIV, and risky sexual behavior among young HIV-negative men identified as harmful or hazardous drinkers in Katutura, Namibia.

BACKGROUND: Namibia's HIV prevalence is 13.3%. Alcohol is associated with sexual risk-taking, leading to increased HIV risk. Baseline sexual behaviors, HIV and alcohol knowledge, and self-perceived HIV risk were examined among men reporting high-risk drinking in Katutura, Namibia. METHODS: HIV negative men, ≥ 18 years, were screened for harmful or hazardous levels of drinking and >1 recent sex partner prior to randomization into control or intervention arm. SAS 9.3 and R 3.01 were used for descriptive baseline cohort analyses. RESULTS: A total of 501 participants who met criteria were included in analysis (mean Alcohol Use Disorders Identification Test [AUDIT] =12.4). HIV and alcohol knowledge were high with the majority (>85 and 89.8-98%, respectively) of respondents correctly answering assessment questions. Despite high knowledge levels, 66.7% of men felt they were at some or high risk of HIV acquisition. Among those respondents, 56.5% stated often wanting to have sex after drinking and 40.3% stated sex was better when drunk. Among respondents with non-steady partners [n = 188], 44.1% of last sexual encounters occurred while the participant was drunk and condoms were not used 32.5% of those times. Among persons who were not drunk condoms were not used 13.3% of those times. CONCLUSIONS: Sex with casual partners was high. Inconsistent condom use and alcohol use before sex were frequently reported. Increased emphasis on alcohol risk-reduction strategies, including drinking due to peer pressure and unsafe sexual behaviors, is needed.

Qualitative Assessment of Speech Perception Performance of Early and Late Cochlear Implantees.

The present study aims to provide a qualitative description and comparison of speech perception performance using model based tests like multisyllabic lexical neighborhood test (MLNT) and lexical neighborhood test (LNT), in early and late implanted (prelingual) hearing impaired children using cochlear implants. The subjects comprised of cochlear implantees; Group I (early implantees)-n = 15, 3-6 years of age; mean age at implantation-3½ years. Group II (late implantees)-n = 15, 7-13 years of age; mean age at implantation-5 years. The tests were presented in a sound treated room at 70 dBSPL. The children were instructed to repeat the words on hearing them. Responses were scored as percentage of words correctly repeated. Their means were computed. The late implantees achieved higher scores for words on MLNT than those on LNT. This may imply that late implantees are making use of length cues in order to aid them in speech perception. The major phonological process used by early implantees was deletion and by the late implantees was substitution. One needs to wait until the child achieves a score of 20 % on LNT before assessing other aspects of his/her speech perception abilities. There appears to be a need to use speech perception tests which are based on theoretical empirical models, in order to enable us to give a descriptive analysis of post implant speech perception performance.

Alcohol use and its association with HIV risk behaviors among a cohort of patients attending HIV clinical care in Tanzania, Kenya, and Namibia.

This article describes the frequency of alcohol use among HIV-positive patients attending clinical care in sub-Saharan Africa and explores the association between alcohol use, medication adherence, and sexual risk behavior. Data from 3538 patients attending an HIV clinic in Kenya, Tanzania, or Namibia were captured through interview and medical record abstraction. Participants were categorized into three drinking categories: nondrinkers, nonharmful drinkers, and harmful/likely dependent drinkers. A proportional odds model was used to identify correlates associated with categories of alcohol use. Overall, 20% of participants reported alcohol use in the past 6 months; 15% were categorized as nonharmful drinkers and 5% as harmful/likely dependent drinkers. Participants who reported missing a dose of their HIV medications [adjusted odds ratio (AOR): 2.04, 95% confidence interval (CI): 1.67, 2.49]; inconsistent condom use (AOR: 1.49, 95% CI: 1.23, 1.79); exchanging sex for food, money, gifts, or a place to stay (AOR: 1.57, 95% CI: 1.06, 2.32); and having a sexually transmitted infection symptom (AOR: 1.40, 95% CI: 1.10, 1.77) were more likely to be categorized in the higher risk drinking categories. This research highlights the need to integrate alcohol screening and counseling into the adherence and risk reduction counseling offered to HIV-positive patients as part of their routine care. Moreover, given the numerous intersections between alcohol and HIV, policies that focus on reducing alcohol consumption and alcohol-related risk behavior should be integrated into HIV prevention, care, and treatment strategies.

Sexual risk behavior among HIV-uninfected men who have sex with men participating in a tenofovir preexposure prophylaxis randomized trial in the United States.

OBJECTIVE: To evaluate for changes in sexual behaviors associated with daily pill use among men who have sex with men (MSM) participating in a preexposure prophylaxis trial. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to receive tenofovir disoproxil fumarate or placebo at enrollment or after a 9-month delay and followed for 24 months. METHODS: Four hundred HIV-negative MSM reporting anal sex with a man in the past 12 months and meeting other eligibility criteria enrolled in San Francisco, Atlanta, and Boston. Sexual risk was assessed at baseline and quarterly visits using Audio Computer-Assisted Self-Interview. The association of pill taking with sexual behavior was evaluated using logistic and negative-binomial regressions for repeated measures. RESULTS: Overall indices of behavioral risk declined or remained stable during follow-up. Mean number of partners and proportion reporting unprotected anal sex declined during follow-up (P < 0.05), and mean unprotected anal sex episodes remained stable. During the initial 9 months, changes in risk practices were similar in the group that began pills immediately vs. those in the delayed arm. These indices of risk did not differ significantly after initiation of pill use in the delayed arm or continuation of study medication in the immediate arm. Use of poppers, amphetamines, and sexual performance-enhancing drugs were independently associated with one or more indices of sexual risk. CONCLUSIONS: There was no evidence of risk compensation among HIV-uninfected MSM in this clinical trial. Monitoring for risk compensation should continue now that preexposure prophylaxis has been shown to be efficacious in MSM and other populations and will be provided in open-label trials and other contexts.

Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.

OBJECTIVES: To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo). METHODS: Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities. RESULTS: Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade ≥3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug. CONCLUSIONS: Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.

Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

BACKGROUND: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

HIV/AIDS knowledge scores and perceptions of risk among African American students attending historically black colleges and universities.

OBJECTIVE: African American young adults are disproportionately affected by the HIV/AIDS epidemic and often unaware of their personal risk for HIV. Historically black colleges and universities (HBCUs) enroll 25% of college-educated African American young adults and can play an important role in HIV prevention. We examined HIV/AIDS knowledge of students at HBCUs to inform and strengthen our HIV prevention efforts at HBCUs. METHODS: African American undergraduate HBCU students completed online surveys assessing HIV/AIDS knowledge and behaviors, and we analyzed data to assess their knowledge and behaviors. RESULTS: A total of 1,051 of 1,230 surveys completed (85.4%) were analyzable. Eighty-two percent of students had average/high HIV knowledge scores. Seventy-nine percent of students surveyed perceived themselves to be at low risk for HIV infection; 64% of those who had at least two or more sex partners had not used a condom at last sex encounter. In the final model, significant independent effects were identified for average/high knowledge of HIV risk, including agreeing with assessing a potential partner's HIV risk by all of the five actions listed (adjusted odds ratio [AOR] = 2.7, 95% confidence interval [CI] 1.7, 4.3) and never using a needle to inject drugs (AOR=5.6, 95% CI 3.2, 9.7). CONCLUSIONS: Educating students about effectively assessing sex partner risk will improve HIV knowledge and prevention efforts at HBCUs.

Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco.

BACKGROUND: Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco. METHODS/FINDINGS: We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13). CONCLUSIONS: Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00131677.

Behçet disease presenting with frosted branch angiitis.

The authors present a case of Behçet disease presenting with frosted branch angiitis. Frosted branch angiitis is a rare clinical finding and there are only two reported cases in the literature associated with Behçet disease.

Antimicrobial-resistant nocardia isolates, United States, 1995-2004.

We conducted a 10-year retrospective evaluation of the epidemiology and identification of Nocardia isolates submitted to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing. The species most commonly identified were N. nova (28%), N. brasiliensis (14%), and N. farcinica (14%). Of 765 isolates submitted, 61% were resistant to sulfamethoxazole and 42% were resistant to trimethoprim-sulfamethoxazole.

Effectiveness of non-nucleoside reverse-transcriptase inhibitor-based antiretroviral therapy in women previously exposed to a single intrapartum dose of nevirapine: a multi-country, prospective cohort study.

BACKGROUND: Intrapartum and neonatal single-dose nevirapine (NVP) reduces the risk of mother-to-child HIV transmission but also induces viral resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. This drug resistance largely fades over time. We hypothesized that women with a prior single-dose NVP exposure would have no more than a 10% higher cumulative prevalence of failure of their NNRTI-containing antiretroviral therapy (ART) over the first 48 wk of therapy than would women without a prior exposure. METHODS AND FINDINGS: We enrolled 355 NVP-exposed and 523 NVP-unexposed women at two sites in Zambia, one site in Kenya, and two sites in Thailand into a prospective, non-inferiority cohort study and followed them for 48 wk on ART. Those who died, discontinued NNRTI-containing ART, or had a plasma viral load >or=400 copies/ml at either the 24 wk or 48 wk study visits and confirmed on repeat testing were characterized as having failed therapy. Overall, 114 of 355 NVP-exposed women (32.1%) and 132 of 523 NVP-unexposed women (25.2%) met criteria for treatment failure. The difference in failure rates between the exposure groups was 6.9% (95% confidence interval [CI] 0.8%-13.0%). The failure rates of women stratified by our predefined exposure interval categories were as follows: 47 of 116 women in whom less than 6 mo elapsed between exposure and starting ART failed therapy (40%; p<0.001 compared to unexposed women); 25 of 67 women in whom 7-12 mo elapsed between exposure and starting ART failed therapy (37%; p = 0.04 compared to unexposed women); and 42 of 172 women in whom more than 12 mo elapsed between exposure and starting ART failed therapy (24%; p = 0.82 compared to unexposed women). Locally weighted regression analysis also indicated a clear inverse relationship between virologic failure and the exposure interval. CONCLUSIONS: Prior exposure to single-dose NVP was associated with an increased risk of treatment failure; however, this risk seems largely confined to women with a more recent exposure. Women requiring ART within 12 mo of NVP exposure should not be prescribed an NNRTI-containing regimen as first-line therapy.

Standardized, mathematical model-based and validated in vitro analysis of anthrax lethal toxin neutralization.

Quantification of anthrax lethal toxin (LTx) neutralization activity (TNA) is pivotal in assessing protective antibody responses to anthrax vaccines and for evaluation of immunotherapies for anthrax. We have adapted and redesigned the TNA assay to establish a unifying, standardized, quantitative and validated technology platform for LTx neutralization in the J774A.1 murine cell line. Critical design features of this platform are 1) the application of a free-form or constrained 4 parameter logistic (4-PL) function to model neutralization responses within and between boundary limits of 100% cell survival and 95% cell lysis and 2) to exploit innovative assay curve recognition algorithms for interpretive endpoints. The assay was validated using human serum ED50 (dilution of serum effecting 50% neutralization) as the primary reportable value (RV). Intra-operator and intermediate precision, expressed as the coefficient of variation (%CV), were high at 10.5-15.5%CV and 13.5-14.5%CV respectively. TNA assay dilutional linearity was demonstrated for human sera using linear regression analysis of log(10) transformed data with slope=0.99, intercept=-0.03 and r(2)=0.985. Assay accuracy, inferred from the precision and linearity data and using a spike-recovery approach, was high with a percent error (%E) range of only 3.4-20.5%E. The lower limit of detection (LLOD) was ED50=12 and the lower limit of quantification (LLOQ) was ED50=36. The cell-based assay was robust, tolerating incubation temperatures from 35 to 39 degrees C, CO(2) concentrations from 3% to 7% and reporter substrate (MTT) concentrations of 2.5-7.5 mg/ml. Strict assay quality control parameters were met for up to 25 cell culture passages. The long term (50 month) assay stability, determined using human reference standards AVR414 and AVR801, indicated high precision, consistent accuracy and no detectable assay drift. A customized software program provided two additional assay metrics, Quantification Titer (QT) and Threshold Titer (TT), both of which demonstrate acceptable accuracy, precision and dilutional linearity. The TT was also used to establish the assay reactivity threshold (RT). The application of the assay to sera from humans, Rhesus macaques and rabbits was demonstrated separately and by aggregate dilutional linearity analysis of the ED50 (slope=0.98, intercept=0.003, r(2)=0.989). We propose this TNA assay format with a qualified standard reference serum and customized interpretive software as a unifying platform technology for determination of functional serologic responses to anthrax vaccines and for evaluation of anthrax immunotherapeutics.

Risk factors for Buruli ulcer disease (Mycobacterium ulcerans Infection): results from a case-control study in Ghana.

BACKGROUND: Morbidity due to Buruli ulcer disease (BUD), a cutaneous infection caused by Mycobacterium ulcerans, has been increasingly recognized in rural West Africa. The source and mode of transmission remain unknown. METHODS: To identify BUD risk factors, we conducted a case-control study in 3 BUD-endemic districts in Ghana. We enrolled case patients with clinically diagnosed BUD and obtained skin biopsy specimens. M. ulcerans infection was confirmed by at least 1 of the following diagnostic methods: histopathologic analysis, culture, polymerase chain reaction, and Ziehl-Neelsen staining of a lesion smear. We compared characteristics of case patients with confirmed BUD with those of age- and community-matched control subjects using conditional logistic regression analysis. RESULTS: Among 121 case patients with confirmed BUD, leg lesions (49%) or arm lesions (36%) were common. Male case patients were significantly more likely than female case patients to have lesions on the trunk (25% vs. 6%; P = .009). Multivariable modeling among 116 matched case-control pairs identified wading in a river as a risk factor for BUD (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.27-5.68; P = .0096). Wearing a shirt while farming (OR, 0.27; 95% CI, 0.11-0.70; P = .0071), sharing indoor living space with livestock (OR, 0.36; 95% CI, 0.15-0.86; P = .022), and bathing with toilet soap (OR, 0.41; 95% CI, 0.19-0.90; P = .026) appeared to be protective. BUD was not significantly associated with penetrating injuries (P = .14), insect bites near water bodies (P = .84), bacille Calmette-Guerin vaccination (P = .33), or human immunodeficiency virus infection (P = .99). CONCLUSIONS: BUD is an environmentally acquired infection strongly associated with exposure to river areas. Exposed skin may facilitate transmission. Until transmission is better defined, control strategies in BUD-endemic areas could include covering exposed skin.