Health care workers and researchers traveling to developing-world clinical settings: disease transmission risk and mitigation.

With the recent emphasis on funding and training opportunities for global health and humanitarian aid and the increased interest in the field, many health care workers and medical researchers are traveling from resource-replete to resource-limited settings. This type of travel brings unique disease risks not routinely considered for the business or vacationing traveler. This review provides practical advice for this special population of travelers, targeted to specific health care-related risks (needlestick, hemorrhagic fever viruses, severe viral respiratory disease, and tuberculosis), with suggestions for risk mitigation.

An outbreak of Plasmodium falciparum malaria in U.S. Marines deployed to Liberia.

In 2003, 44 U.S. Marines were evacuated from Liberia with either confirmed or presumed Plasmodium falciparum malaria. An outbreak investigation showed that only 19 (45%) used insect repellent, 5 (12%) used permethrin-treated clothing, and none used bed netting. Adherence with weekly mefloquine (MQ) was reported by 23 (55%). However, only 4 (10%) had serum MQ levels high enough to correlate with protection (> 794 ng/mL), and 9 (22%) had evidence of steady-state kinetics (MQ carboxy metabolite/MQ > 3.79). Tablets collected from Marines met USP identity and dissolution specifications for MQ. Testing failed to identify P. falciparum isolates with MQ resistance. This outbreak resulted from under use of personal protective measures and inadequate adherence with chemophrophylaxis. It is essential that all international travelers make malaria prevention measures a priority, especially when embarking to regions of the world with high transmission intensity such as west Africa..

Guidelines for the prevention of infection after combat-related injuries.

Management of combat-related trauma is derived from skills and data collected in past conflicts and civilian trauma, and from information and experience obtained during ongoing conflicts. The best methods to prevent infections associated with injuries observed in military combat are not fully established. Current methods to prevent infections in these types of injuries are derived primarily from controlled trials of elective surgery and civilian trauma as well as retrospective studies of civilian and military trauma interventions. The following guidelines integrate available evidence and expert opinion, from within and outside of the US military medical community, to provide guidance to US military health care providers (deployed and in permanent medical treatment facilities) in the diagnosis, treatment, and prevention of infections in those individuals wounded in combat. These guidelines may be applicable to noncombat traumatic injuries under certain circumstances. Early wound cleansing and surgical debridement, antibiotics, bony stabilization, and maintenance of infection control measures are the essential components to diminish or prevent these infections. Future research should be directed at ideal treatment strategies for prevention of combat-related injury infections, including investigation of unique infection control techniques, more rapid diagnostic strategies for infection, and better defining the role of antimicrobial agents, including the appropriate spectrum of activity and duration.

Trauma-related infections in battlefield casualties from Iraq.

OBJECTIVE: To describe risks for, and microbiology and antimicrobial resistance patterns of, war trauma associated infections from Operation Iraqi Freedom. BACKGROUND: : The invasion of Iraq resulted in casualties from high-velocity gunshot, shrapnel, and blunt trauma injuries as well as burns. Infectious complications of these unique war trauma injuries have not been described since the 1970s. METHODS: Retrospective record review of all trauma casualties 5 to 65 years of age evacuated from the Iraqi theatre to U.S. Navy hospital ship, USNS Comfort, March to May 2003.War trauma-associated infection was defined by positive culture from a wound or sterile body fluid (ie, blood, cerebrospinal fluid) and at least two of the following infection-associated signs/symptoms: fever, dehiscence, foul smell, peri-wound erythema, hypotension, and leukocytosis. A comparison of mechanisms of injury, demographics, and clinical variables was done using multivariate analysis. RESULTS: Of 211 patients, 56 met criteria for infection. Infections were more common in blast injuries, soft tissue injuries, >3 wound sites, loss of limb, abdominal trauma, and higher Injury Severity Score (ISS). Wound infections accounted for 84% of cases, followed by bloodstream infections (38%). Infected were more likely to have had fever prior to arrival, and had higher probability of ICU admission and more surgical procedures. Acinetobacter species (36%) were the predominant organisms followed by Escherichia coli and Pseudomonas species (14% each). CONCLUSIONS: Similar to the Vietnam War experience, gram-negative rods, particularly Acinetobacter species, accounted for the majority of wound infections cared for on USNS Comfort during Operation Iraqi Freedom. Multidrug resistance was common, with the exception of the carbapenem class, limiting antibiotic therapy options.

Vaccination in patients with HIV infection.

Although vaccine-preventable diseases are common in HIV, concerns about vaccine safety and lack of efficacy in this patient population often lead to missed opportunities for vaccination. In this article, we review the literature regarding vaccine risks and benefits and offer recommendations regarding their use and timing in patients with HIV infection.

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.

Use of bilirubin as a marker of adherence to atazanavir-based antiretroviral therapy.

We retrospectively reviewed 134 patients to evaluate atazanavir-related bilirubin elevation as an adherence marker. Using a 2 log reduction or undetectable viral load as a marker for suppression, the median bilirubin increase at first follow-up was 1.3 (0.7-2.2), versus 0.2 (-0.05-0.65) for those not suppressed. An increase in bilirubin of more than 0.4 mg/dl correctly classified 81% of patients as having successful treatment response (sensitivity 87%, specificity 63%), suggesting that bilirubin is a good adherence marker.

Safety and immunogenicity of an inactivated hepatitis A vaccine among HIV-infected subjects.

BACKGROUND: Hepatitis A is a major health risk for many human immunodeficiency virus (HIV)-infected individuals. Vaccination is a potentially attractive measure to reduce the incidence of hepatitis A among this population, but data on its safety and immunogenicity are incomplete. METHODS: Ninety HIV-uninfected adults received an inactivated hepatitis A vaccine (VAQTA; Merck), and 90 HIV-infected subjects were randomized, in double-blind fashion, to receive either the vaccine or placebo. The HIV-infected subjects were stratified by CD4 cell count, with 45 subjects having CD4 cell counts of > or =300 cells/mm3 and 45 subjects having CD4 cell counts of <300 cells/mm3. Vaccine was given at weeks 0 and 24 of the study.Results. Seroconversion rates at week 28 of the study were 94% among the HIV-infected subjects and 100% among the HIV-uninfected control subjects. HIV-infected subjects with CD4 cell counts of <300 cells/mm3 had a seroconversion rate of 87%, and HIV-infected subjects with CD4 cell counts of > or =300 cells/mm3 had a seroconversion rate of 100%. The vaccine was generally well tolerated, and no adverse effect on either HIV load or CD4 cell count was found. CONCLUSION: Hepatitis A vaccine was both immunogenic and safe among HIV-infected subjects.

Unintended smallpox vaccination of HIV-1-infected individuals in the United States military.

We identified 10 individuals who had undiagnosed human immunodeficiency virus type 1 (HIV-1) infection at the time of smallpox vaccination. Mean CD4 cell count was 483 cells/mm3 (range, 286-751 cells/mm3), and mean log10 plasma HIV-1 RNA load was 4.13 copies/cm3 (range, 2.54-5.16 copies/cm3). All vaccinees (3 primary and 7 repeat) had a normal, robust reaction without complications. Smallpox vaccine was well-tolerated in this small series of HIV-1-infected military personnel.

Long-term efficacy of routine access to antiretroviral-resistance testing in HIV type 1-infected patients: results of the clinical efficacy of resistance testing trial.

The long-term efficacy of making resistance testing routinely available to clinicians has not been established. We conducted a clinical trial at 6 US military hospitals in which volunteers infected with human immunodeficiency virus type-1 were randomized to have routine access to phenotype resistance testing (PT arm), access to genotype resistance testing (GT arm), or no access to either test (VB arm). The primary outcome measure was time to persistent treatment failure despite change(s) in antiretroviral therapy (ART) regimen. Overall, routine access to resistance testing did not significantly increase the time to end point. Time to end point was significantly prolonged in the PT arm for subjects with a history of treatment with > or =4 different ART regimens or a history of treatment with nonnucleoside reverse-transcriptase inhibitors before the study, compared with that in the VB arm. These results suggest that routine access to resistance testing can improve long-term virologic outcomes in HIV-infected patients who are treatment experienced but may not impact outcome in patients who are naive to or have had limited experience with ART.

Diverse HIV-1 subtypes and clinical, laboratory and behavioral factors in a recently infected US military cohort.

OBJECTIVE: To describe the demographics, risk behaviors, and HIV-1 subtypes in a large cohort of recently HIV-infected military personnel. DESIGN: Descriptive, cross-sectional study. METHODS: US military personnel with recent HIV seroconversion from six medical referral centers were enrolled with a self-administered questionnaire, CD4 cell counts, syphilis and hepatitis B serologies, plasma viral RNA levels, and HIV-1 subtype nucleic acid sequencing. RESULTS: Between February 1997 and May 2000, 520 patients were enrolled. Most [488 (94.3%)] were infected with HIV-1 subtype B. The most prevalent non-B subtype was a circulating recombinant form (CRF01_AE) [17 (61%)]; however, two pure subtypes (C and D), as well as CRF02_AG, CRF09_cpx and a BE recombinant were identified. The likely area of HIV-1 acquisition was the United States for 70% of the volunteers. At least three non-B subtype infections (two subtype C, one subtype CRF01_AE) were apparently acquired domestically. Risk behaviors and comorbid sexually transmitted diseases were reported during the seroconversion period. Volunteers with non-B subtype HIV infection were more likely to report heterosexual contacts [92% vs. 39%; odds ratio (OR), 10.0], including contacts with commercial sex workers (41% vs. 13%; OR, 4.9). The Roche Amplicor version 1.0 assay was less sensitive for non-B subtype infections than the Roche Amplicor version 1.5 assay. CONCLUSION: There is a high prevalence and diversity of non-B HIV subtypes in this large cohort. Efficient diagnosis of acute primary HIV-1 infection was identified as a goal for prevention programs. Modifiable risk behaviors and target populations for intervention were identified.

Correlates of human herpesvirus-8 seropositivity among U.S. military members recently infected with human immunodeficiency virus.

BACKGROUND: Human herpesvirus 8 (HHV-8), the cause of Kaposi's sarcoma, is common among HIV-infected persons. The exact route of transmission of HHV-8 in various populations is still debated. GOAL: The goal was to define the correlates of HHV-8 infection among men recently infected with human immunodeficiency virus. STUDY DESIGN: Three hundred forty-two HIV-infected U.S. military men were evaluated using a questionnaire regarding potential risk factors and laboratory data, including HHV-8, herpes simplex virus 2 (HSV-2), syphilis, hepatitis B, and hepatitis C serologies. RESULTS: The seroprevalence of HHV-8 was 32%. HHV-8 was significantly associated with hepatitis B seropositivity (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.5-4.1), and black ethnicity was negatively associated with HHV-8 (OR, 0.6; 95% CI, 0.3-0.9) in the multivariate analysis. HHV-8 was not associated with drug use or hepatitis C seropositivity. Among men who have sex with men (MSM), HHV-8 infection correlated with hepatitis B seropositivity (OR, 2.2; 95% CI, 1.1-4.3) and HSV-2 (OR, 2.6; 95% CI, 1.4-4.9). Among heterosexuals, the correlates of HHV-8 were different; blacks as compared with whites (OR, 0.3; 95% CI, 0.1-0.8) and married versus single status (OR, 0.4; 95% CI, 0.2-0.9) were associated with a lower rate of HHV-8 infection. Among heterosexuals, hepatitis B, HSV-2, and sexual behaviors were not associated with HHV-8. CONCLUSION: This study suggests that the seroprevalence of HHV-8 is increased in both MSM and heterosexual men with HIV infection, and that the route(s) of HHV-8 acquisition might be different between MSM and heterosexuals.

Reimmunization with 23-valent pneumococcal vaccine for patients infected with human immunodeficiency virus type 1: clinical, immunologic, and virologic responses.

We determined the immunogenicity and safety of reimmunization with the 23-valent polysaccharide pneumococcal vaccine in patients infected with human immunodeficiency virus type 1 (HIV-1). Patients immunized >5 years earlier (initially within 1 year of HIV-1 seroconversion) were randomized to receive vaccine (n=57) or placebo (n=30). Persons with recent HIV-1 seroconversion (n=14) were immunized for the first time. Preimmunization levels of capsule-specific immunoglobulin G were similar in all groups. Reimmunized patients showed a significantly lower frequency and magnitude of antibody responses compared with persons with recent HIV-1 seroconversion. Reimmunized patients did not show adverse virologic or immunologic changes, but some reported local discomfort (15%) or fever (8%). Thus, the limited responses after reimmunization of HIV-1-infected patients with the current 23-valent vaccine mandates the need for a more effective reimmunization schedule, more immunogenic vaccines, or other behavioral and therapeutic interventions.