Adam W. Armstrong

Comparisons of causes of death and mortality rates among HIV-infected persons : Analysis of the pre-, early, and late HAART (Highly active antiretroviral therapy) eras

Methods:Comparisons of death-related variables during the 3 eras were performed. Results:The number of deaths declined over the study period, with 987 deaths in the pre-HAART era, 159 deaths in the early HAART era (1997-1999), and 78 deaths in the late HAART era (2000-2003) (P < 0.01). The annual death rate peaked in 1995 (10.3 per 100 patients) and then declined to <2 deaths per 100 persons in the late HAART era (P < 0.01). The proportion of deaths attributable to infection decreased, but infection remained the leading cause of death in our cohort, followed by cancer. Of those who died, there was an increasing proportion of non-HIV-related deaths (32% vs. 9%; P < 0.01), including cardiac disease (22% vs. 8%; P < 0.01) and trauma (8% vs. 2%; P = 0.01) in the post-HAART versus pre-HAART era. Despite the absence of intravenous drug use and the low prevalence of hepatitis C coinfection in our cohort, an increasing proportion of deaths in the HAART era were attributable to liver disease, although the numbers are small. Conclusions:Despite increasing concerns regarding antiretroviral resistance, the death rate among HIV-infected persons in our cohort continues to decline. Our data show a lower death rate than that reported among many other US HIV-infected populations; this may be the result of open access to health care. A shift in the causes of death toward non-HIV-related causes suggests that a more comprehensive health care approach may be needed for optimal life expectancy; this may include enhanced screening for malignancy and heart disease as well as preventive measures for liver disease and accidents.

Traveler's Diarrhea in Thailand: Randomized, Double-Blind Trial Comparing Single-Dose and 3-Day Azithromycin-Based Regimens with a 3-Day Levofloxacin Regimen

BACKGROUND Travelers diarrhea in Thailand is frequently caused by Campylobacter jejuni. Rates of fluoroquinolone (FQ) resistance in Campylobacter organisms have exceeded 85% in recent years, and reduced fluoroquinolone efficacy has been observed. METHODS Azithromycin regimens were evaluated in a randomized, double-blind trial of azithromycin, given as a single 1-g dose or a 3-day regimen (500 mg daily), versus a 3-day regimen of levofloxacin (500 mg daily) in military field clinics in Thailand. Outcomes included clinical end points (time to the last unformed stool [TLUS] and cure rates) and microbiological end points (pathogen eradication). RESULTS A total of 156 patients with acute diarrhea were enrolled in the trial. Campylobacter organisms predominated (in 64% of patients), with levofloxacin resistance noted in 50% of Campylobacter organisms and with no azithromycin resistance noted. The cure rate at 72 h after treatment initiation was highest (96%) with single-dose azithromycin, compared with the cure rates of 85% noted with 3-day azithromycin and 71% noted with levofloxacin (P=.002). Single-dose azithromycin was also associated with the shortest median TLUS (35 h; P=.03, by log-rank test). Levofloxacins efficacy was inferior to azithromycins efficacy, except in patients with no pathogen identified during the first 24 h of treatment or in patients with levofloxacin-susceptible Campylobacter isolates, in whom it appeared to be equal to azithromycin. The rate of microbiological eradication was significantly better with azithromycin-based regimens (96%-100%), compared with levofloxacin (38%) (P=.001); however, this finding was poorly correlated with clinical outcome. A higher rate of posttreatment nausea in the 30 min after receipt of the first dose (14% vs. <6%; P=.06) was observed as a mild, self-limited complaint associated with single-dose azithromycin. CONCLUSIONS Single-dose azithromycin is recommended for empirical therapy of travelers diarrhea acquired in Thailand and is a reasonable first-line option for empirical management in general.

Past Trends and Current Status of Self-Reported Incidence and Impact of Disease and Nonbattle Injury in Military Operations in Southwest Asia and the Middle East

OBJECTIVES To evaluate the evolutional changes in disease and nonbattle injury in a long-term deployment setting, we investigated trends of selected disease and nonbattle injury (NBI) incidence among US military personnel deployed in ongoing military operations in Southwest Asia and the Middle East. METHODS Participants completed an anonymous questionnaire concerning diarrhea, acute respiratory illness (ARI), and NBIs. We compared incidence, morbidity, and risk associations of disease and NBI incidence with historical data. We analyzed a clinic screening form to describe trends in diarrhea incidence over a 3-year period. RESULTS Between April 2006 and March 2007, 3374 troops completed deployment questionnaires. Incidence of diarrhea was higher than that of ARI and NBI (12.1, 7.1, and 2.5 episodes per 100 person-months, respectively), but ARI and NBI resulted in more-frequent health system utilization (both P < .001) and decreased work performance (P < .001 and P = .05, respectively) than did diarrhea. Compared with historical disease and NBI incidence rates, diarrhea and NBI incidence declined over a 4-year period, whereas ARI remained relatively constant. CONCLUSIONS Diarrhea, ARI, and NBI are important health concerns among deployed military personnel. Public health and preventive measures are needed to mitigate this burden.

Nonbattle injury among deployed troops: an epidemiologic study.

(n = 150) Nonbattle injury (NBI) continues to be a leading cause of morbidity among troops currently deployed to Iraq and Afghanistan. To assess NBI incidence, impact, and risk factors, a survey was given to soldiers during mid- or postdeployment from Iraq, Afghanistan, and surrounding region, from January 2005 through May 2006. Among 3,367 troops completing a survey, 19.5% reported at least one NBI, and 85% sought care at least once for their symptoms. Service component, rank, and unit type were among factors associated with differential NBI risk. Twenty percent stated that NBI resulted in back-up personnel being called or shift change to cover impacted duties, and among those reported having been grounded from flight status, a third were the result of NBI. NBI continues to be a problem in recent deployments, and given the findings on individual and potential operational impact indicators, NBI should be viewed as a primary force health protection problem.

Discovery and phylogenetic analysis of novel members of class b enterotoxigenic Escherichia coli adhesive fimbriae

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is recognized to be a common cause of acute watery diarrhea in children from developing countries. Colonization factors (CFAs) have been identified predominantly in ETEC isolates secreting heat-stable enterotoxin (ST) or cosecreting ST with a heat-labile toxin (LT). We hypothesized that LT-only-secreting ETEC produces unique colonization factors not previously described in ST and LTST-secreting ETEC. A set of degenerate primers based on nucleotide sequence similarities between the major structural genes of CS20 (csnA), CS18 (fotA), CS12 (cswA), and porcine antigen 987 (fasA) was developed and used to screen a collection of 266 LT-secreting ETEC isolates in which no known CFA was detected. PCR-amplified products of different molecular masses were obtained from 49 (18.4%) isolates. Nucleotide sequence analysis of the PCR amplicons followed by GenBank nucleotide BLASTn analysis revealed five novel DNA sequences; translated amino acid BLASTx analysis confirmed sequence similarity to class 1b major structural proteins encoded by csnA, fotA, and fasA. Strains expressing the novel CFAs were phylotyped and analyzed using multilocus sequence typing (MLST; Achtman scheme), and the types detected were compared to those of a collection of archived global E. coli strains. In conclusion, application of the degenerate primer sets to ETEC isolates from surveillance studies increased the total number of ETEC isolates with detectable CFAs by almost 20%. Additionally, MLST analysis suggests that for many CFAs, there may be a requirement for certain genetic backgrounds to acquire and maintain plasmids carrying genes encoding CFAs.

Design and validation of a multiplex polymerase chain reaction for the identification of enterotoxigenic Escherichia coli and associated colonization factor antigens.

Development of a genetic tool for the detection of genes encoding enterotoxins and colonization factors would greatly enhance enterotoxigenic Escherichia coli (ETEC) surveillance. Oligonucleotide primers were designed to amplify genes encoding human ST, porcine ST, LT and the structural genes of colonization factor antigen (CFA)/I, CS1 to CS8, CS12 to CS15, CS17 to CS22, and PCFO71. Screening 89 ETEC isolates phenotypically expressing a known CFA showed that, without exception, the multiplex polymerase chain reaction (mPCR) detected the structural gene of the expressed CFA, in addition to CS21 in 22.5% of isolates. Silent genes such as cssB (CS6) were also detected in 9.0%. Additionally, we screened 71 CFA phenotypically negative isolates and detected a CFA in more than 50% of tested isolates. In conclusion, we have designed a simple 4-step mPCR for the rapid detection of ETEC virulence factors. The assay is rapid, reproducible, relatively inexpensive, and has the potential to be field applicable.

Diagnostic Approach to Acute Diarrheal Illness in a Military Population on Training Exercises in Thailand, a Region of Campylobacter Hyperendemicity

ABSTRACT High rates of Campylobacter fluoroquinolone resistance highlight the need to evaluate diagnostic strategies that can be used to assist with clinical management. Diagnostic tests were evaluated with U.S. soldiers presenting with acute diarrhea during deployment in Thailand. The results of bedside and field laboratory diagnostic tests were compared to stool microbiology findings for 182 enrolled patients. Campylobacter jejuni was isolated from 62% of the cases. Clinical and laboratory findings at the time of presentation were evaluated to determine their impact on the posttest probability, defined as the likelihood of a diagnosis of Campylobacter infection. Clinical findings, the results of tests for inflammation (stool occult blood testing [Hemoccult], fecal leukocytes, fecal lactoferrin, plasma C-reactive protein), and the numbers of Campylobacter-specific antibody-secreting cells in peripheral blood failed to increase the posttest probability above 90% in this setting of Campylobacter hyperendemicity when these findings were present. Positive results by a Campylobacter-specific commercial enzyme immunoassay (EIA) and, less so, a research PCR were strong positive predictors. The negative predictive value for ruling out Campylobacter infection, defined as a posttest probability of less than 10%, was similarly observed with these Campylobacter-specific stool-based tests as well the fecal leukocyte test. Compared to the other tests evaluated, the Campylobacter EIA is a sensitive and specific rapid diagnostic test that may assist with diagnostic evaluation, with consideration of the epidemiological setting, logistics, and cost.

D-Dimer Levels before HIV Seroconversion Remain Elevated Even after Viral Suppression and Are Associated with an Increased Risk of Non-AIDS Events

The mechanism underlying the excess risk of non-AIDS diseases among HIV infected people is unclear. HIV associated inflammation/hypercoagulability likely plays a role. While antiretroviral therapy (ART) may return this process to pre-HIV levels, this has not been directly demonstrated. We analyzed data/specimens on 249 HIV+ participants from the US Military HIV Natural History Study, a prospective, multicenter observational cohort of >5600 active duty military personnel and beneficiaries living with HIV. We used stored blood specimens to measure D-dimer and Interleukin-6 (IL-6) at three time points: pre-HIV seroconversion, ≥6 months post-HIV seroconversion but prior to ART initiation, and ≥6 months post-ART with documented HIV viral suppression on two successive evaluations. We evaluated the changes in biomarker levels between time points, and the association between these biomarker changes and future non-AIDS events. During a median follow-up of 3.7 years, there were 28 incident non-AIDS diseases. At ART initiation, the median CD4 count was 361cells/mm3; median duration of documented HIV infection 392 days; median time on ART was 354 days. Adjusted mean percent increase in D-dimer levels from pre-seroconversion to post-ART was 75.1% (95% confidence interval 24.6–148.0, p = 0.002). This increase in D-dimer was associated with a significant 22% increase risk of future non-AIDS events (p = 0.03). Changes in IL-6 levels across time points were small and not associated with future non-AIDS events. In conclusion, ART initiation and HIV viral suppression does not eliminate HIV associated elevation in D-dimer levels. This residual pathology is associated with an increased risk of future non-AIDS diseases.

Factors Associated with the Use of Protective Measures against Vector-Borne Diseases among Troops Deployed to Iraq and Afghanistan

BACKGROUND AND METHODS Vector-borne diseases are known threats to deployed troops. We performed a cross-sectional study of troops deployed to Southwest Asia between January 2005 and February 2007 to evaluate practices of personal protective measures and their relationship to self-report of Old World cutaneous leishmaniasis (CL), a marker of vector-borne disease threat. RESULTS Regular or always N, N-diethyl-m-toluamide (DEET) use was low (2-5%). Associations for DEET use were command emphasis, branch of service, uniform treatment with permethrin, and duty station. Uniform treatment with permethrin was associated with branch of service, command emphasis, and use of DEET. We identified 22 cases of CL (incidence density of 1.8-3.7 per 100 person-years) with increased risk among Reserve/National Guard components, Air Force and Marine personnel. CONCLUSIONS Commanders can influence the use of the military insect repellent system. Unit-based treatment of uniforms improves prevalence. CL incidence may be higher than previously reported.

Outcomes of diarrhea management in operations Iraqi Freedom and Enduring Freedom

INTRODUCTION Among deployed U.S. military personnel, a sub-population of international travelers, acute infectious diarrhea continues to be a leading cause of morbidity and a potential threat to military effectiveness. METHODS To assess outcomes and satisfaction of diarrhea management in the field, a systematic survey was given to military personnel during mid- or post-deployment from Iraq or Afghanistan, from January through August 2004. RESULTS Sixty-three percent of those surveyed reported at least one episode of diarrhea, while less than half sought care for their symptoms. Overall, trends of decreased post-treatment duration were noted as travelers diarrhea therapy modalities grew more complex, controlling for severity of illness at presentation. Among those reporting diarrhea, the greatest level of satisfaction was seen in treatment with IV fluids (59%) followed by antibiotics (46%) and loperamide (40%). The greatest amount of dissatisfaction was seen in treatments with oral fluids only. CONCLUSION While current standard of care is self-treatment of diarrhea in civilian travelers, the U.S. military lacks standards outlining self-treatment of personnel at the individual level. Further research is needed to develop treatment guidelines on diarrhea management during military deployment.