Publications by authors named "Tahaniyat Lalani"

66 Publications

Risk Factors Associated With Chronic Liver Enzyme Elevation in Persons With HIV Without Hepatitis B or C Coinfection in the Combination Antiretroviral Therapy Era.

Open Forum Infect Dis 2021 Mar 24;8(3):ofab076. Epub 2021 Feb 24.

Division of Infectious Diseases, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.

Background: As morbidity due to viral coinfections declines among HIV-infected persons, changes in liver-related morbidity are anticipated. We examined data from the US Military HIV Natural History Study (NHS), a cohort of military beneficiaries, to evaluate incidence and risk factors associated with chronic liver enzyme elevation (cLEE) in HIV-monoinfected patients in the combination antiretroviral therapy (cART) era.

Methods: Participants who were hepatitis B virus and hepatitis C virus seronegative with follow-up after 1996 were included. We defined chronic liver enzyme elevation (cLEE) as alanine aminotransferase elevations ≥1.25 times the upper limit of normal on at least 2 visits, for a duration of ≥6 months within 2 years. We used multivariate Cox proportional hazards models to examine risk factors for cLEE.

Results: Of 2779 participants, 309 (11%) met criteria for cLEE for an incidence of 1.28/100 PYFU (1.28-1.29/100 PYFU). In an adjusted model, cLEE was associated with Hispanic/other ethnicity (reference Caucasian: hazard ratio [HR], 1.744; 95% CI, 1.270-2.395), non-nucleoside reverse transcriptase inhibitor-based cART (reference boosted protease inhibitors: HR, 2.232; 95% CI, 1.378-3.616), being cART naïve (HR, 6.046; 95% CI, 3.686-9.915), or having cART interruptions (HR, 8.671; 95% CI, 4.651-16.164). African American race (HR, 0.669; 95% CI, 0.510-0.877) and integrase strand transfer inhibitor (INSTI)-based cART (HR, 0.222; 95% CI, 0.104-0.474) were protective.

Conclusions: Our findings demonstrate that initiation and continued use of cART are protective against cLEE and support the hypothesis that HIV infection directly impacts the liver. INSTI-based regimens were protective and could be considered in persons with cLEE.
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http://dx.doi.org/10.1093/ofid/ofab076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953661PMC
March 2021

Travel-associated multidrug-resistant organism acquisition and risk factors among US military personnel.

J Travel Med 2021 Mar 2. Epub 2021 Mar 2.

Brooke Army Medical Center, JBSA Fort Sam Houston, TX, USA.

Background: International travel is a risk factor for incident colonization with extended spectrum beta-lactamase (ESBL)-producing organisms. These and other multidrug-resistant (MDR) bacteria are major pathogens in combat casualties. We evaluated risk factors for colonization with MDR bacteria in US military personnel traveling internationally for official duty.

Methods: TravMil is a prospective observational study enrolling subjects presenting to military travel clinics. We analyzed surveys, antimicrobial use data, and pre- and post-travel perirectal swabs in military travelers to regions outside the continental United States, Canada, Western or Northern Europe, or New Zealand, presenting to one clinic from 12/2015-12/2017. Recovered Gram-negative isolates underwent identification and susceptibility testing (BD Phoenix). Characteristics of trip and traveler were analyzed to determine risk factors for MDR organism colonization.

Results: 110 trips were planned by 99 travelers (74% male, median age 38 years [IQR 31, 47.25]); 72 trips with returned pre- and post-travel swabs were completed by 64 travelers. Median duration was 21 days (IQR 12.75, 79.5). 17% traveled to Mexico/Caribbean/Central America, 15% to Asia, 57% to Africa, and 10% to South America; 56% stayed in hotels and 50% in dormitories/barracks. Travelers used doxycycline (15%) for malaria prophylaxis, 11% took an antibiotic for travelers' diarrhea (TD) treatment (fluoroquinolone 7%, azithromycin 4%). Incident MDR organism colonization occurred in 8 travelers (incidence density 3.5/1000 travel days; cumulative incidence 11% of trips [95% CI: 4%-19%]), all ESBL-producing E. coli. A higher incidence of ESBL-producing E. coli acquisition was associated with travel to Asia (36% vs 7%, P = 0.02) but not with travel to other regions, TD, or use of antimicrobials. No relationship was seen between fluoroquinolone or doxycycline exposure and resistance to those antimicrobials.

Conclusions: Incident colonization with MDR organisms occurs at a lower rate in this military population compared to civilian travelers, with no identified modifiable risk factors, with highest incidence of ESBL acquisition observed after South Asia travel.
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http://dx.doi.org/10.1093/jtm/taab028DOI Listing
March 2021

SARS-CoV-2 Infections and Serologic Responses Among Military Personnel Deployed on the USNS COMFORT to New York City During the COVID-19 Pandemic.

Open Forum Infect Dis 2021 Feb 23;8(2):ofaa654. Epub 2021 Jan 23.

Naval Medical Center Portsmouth, Portsmouth, Virginia, USA.

Background: Coronavirus disease 2019 (COVID-19) presents a unique challenge to United States Navy hospital ships. The aim of this study was to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among US Navy personnel deployed on the USNS COMFORT to augment the inpatient health care capacity in New York City.

Methods: This was a cross-sectional study conducted on USNS COMFORT crewmembers returning to Norfolk, Virginia, following deployment. Participants completed an electronic questionnaire and provided a serum sample at Day 14 post-deployment. Polymerase chain reaction (PCR) results from testing of symptomatic crewmembers during deployment and Day 0 and Day 14 post-deployment screening swabs conducted on all crewmembers, per military order, were abstracted. SARS-CoV-2 infection was defined as a positive SARS-CoV-2 spike glycoprotein immunoglobulin G antibody or PCR result.

Results: Of the ship's total complement of 1200 crewmembers, 450 were enrolled: 432 (96.0%) completed the questionnaire and provided a serum sample. The median age of participants (interquartile range) was 30 (24-39) years, 50.8% were female, 58.6% were White, and 14.0% were Black; 80.1% had a clinical role during deployment. The cumulative prevalence of SARS-CoV-2 infection was 3.01% (13/432; 95% CI, 1.61%-5.09%). Twelve of 13 infections occurred in health care providers, and 8 of 13 were asymptomatic. The antibody profile of infected crewmembers varied by suspected timing of infection.

Conclusions: We observed a low prevalence of SARS-CoV-2 infection among USNS COMFORT crewmembers despite the inherent risk of a shipboard deployment to an area with high rates of community transmission. Our findings suggest that early infection control measures mitigated the spread of SARS-CoV-2 among crewmembers.
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http://dx.doi.org/10.1093/ofid/ofaa654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856331PMC
February 2021

Sexual Risk Behaviors Associated with Sexually Transmitted Infections in a US Military Population Living with HIV After the Repeal of "Don't Ask, Don't Tell".

AIDS Patient Care STDS 2020 12;34(12):523-533

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Risk behaviors associated with sexually transmitted infections (STIs) among people living with HIV (PLWH) have not been well characterized in the US military. We identified risk behaviors associated with a new STI in this population after the repeal of "Don't Ask, Don't Tell." US Military HIV Natural History Study participants who completed the risk behavior questionnaire (RBQ) between 2014 and 2017 and had at least 1 year of follow-up were included ( = 1589). Logistic regression identified behaviors associated with incident STI in the year following RBQ completion. Overall, 18.9% acquired an STI and 52.7% reported condom use at last sexual encounter. Compared with those with no new sex partners, participants with between one and four or five or more new partners were 1.71 [1.25-2.35] and 6.12 [3.47-10.79] times more likely to get an STI, respectively. Individuals reporting low or medium/high perceived risk of STI were 1.83 [1.23-2.72] and 2.65 [1.70-4.15] times more likely to acquire a new STI than those reporting no perceived risk, respectively. Participants who preferred not to answer about sexual preference, number of new partners, or perceived STI risk were also more likely to acquire a new STI. Our study illustrates that despite regular access to health care and accurate perceptions of risk, rates of STI among PLWH remain high in the US military setting, as in others. Given the potential individual and public health consequences of STI coinfection after HIV, more work is needed to assess interventions aimed at sexual behavior change for PLWH.
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http://dx.doi.org/10.1089/apc.2020.0095DOI Listing
December 2020

Performance characteristics of a quantitative PCR assay on repository stool specimens and smeared filter-paper cards.

BMC Res Notes 2020 Oct 30;13(1):500. Epub 2020 Oct 30.

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Objective: Stool repositories are a valuable resource for retrospective analyses including quantitative PCR assays to distinguish between asymptomatic shedding and clinical disease. The suitability of archival specimens for this purpose is unclear and requires assessment. We conducted a pilot study to evaluate pathogen detection by TaqMan Array Card (TAC) in travelers' diarrhea (TD) stool specimens stored for 1-13 years, as well as the impact of transporting specimens on Whatman FTA Elute cards (FTA Cards) on detection.

Results: The positive percent agreement (PPA) for TAC on stool vs. microbiologic testing was lower than our a priori PPA estimate of 80% for most pathogens: Shigella spp. (100% [95%CI 69-100%]), enterotoxigenic E coli (ETEC) (63% [95%CI 49-75%]), Campylobacter spp. (66% [95%CI 43-85%]) and Norovirus (37% [95%CI 16-61%]). Use of the FTA card resulted in a further reduction of PPA. Our findings suggest that archival specimens may lead to insensitive detection on quantitative PCR assays due to degradation of nucleic acid with prolonged storage, although our limited sample size precluded us from evaluating the impact of storage duration on nucleic acid yield. Additional studies are needed to understand the impact of storage duration on quantitative PCR data.
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http://dx.doi.org/10.1186/s13104-020-05340-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597010PMC
October 2020

Comparison of A(H3N2) neutralizing antibody responses elicited by 2018-2019 season quadrivalent influenza vaccines derived from eggs, cells, and recombinant hemagglutinin.

Clin Infect Dis 2020 Sep 8. Epub 2020 Sep 8.

Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.

Background: Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity.

Methods: Neutralization titers in pre- and post-immunization sera from 133 adults immunized with one of three types of influenza vaccines in a randomized, open-label trial during the 2018-2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA-pseudoviruses.

Results: All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Pre-immunization titers against H3 HA-pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA-pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA-pseudoviruses with egg-adaptive substitutions, but poorly neutralized wildtype 2019-2020 A/Kansas/14/2017 (H3N2) HA-pseudoviruses.

Conclusion: Egg- and cell-derived 2018-2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.
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http://dx.doi.org/10.1093/cid/ciaa1352DOI Listing
September 2020

Doxycycline Malaria Prophylaxis Impact on Risk of Travelers' Diarrhea among International Travelers.

Am J Trop Med Hyg 2020 11;103(5):1864-1870

Uniformed Services University of the Health Sciences, Bethesda, Maryland.

International travelers are frequently at risk for travelers' diarrhea (TD) and malaria. Doxycycline was one of the earliest antibiotics shown to have efficacy in TD prevention. With increasing resistance and recommendations against antibiotic chemoprophylaxis, doxycycline fell out of use. We evaluated TD incidence and risk factors in a prospective cohort of travelers, specifically in regard to malaria prophylaxis. Travelers' diarrhea was defined as ≥ 3 loose stools in 24 hours or two loose stools in 24 hours associated with other gastrointestinal symptoms. The Poisson regression model with robust error variance was used to estimate the RR of TD. Three thousand two hundred twenty-seven trips were enrolled: 62.1% of participants were male, with a median age of 39 years (interquartile range [IQR] 27,59) and a median travel duration of 19 days (IQR 12,49); 17.4% developed TD; 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America; and 20% took doxycycline for malaria chemoprophylaxis, 50% took other antimalarials, and 30% took none. Decreased RR of TD was associated with doxycycline (RR 0.62 [0.47-0.82], < 0.01) and military travel (RR 0.57 [0.47-0.70], < 0.01). Increased risk of TD was associated with female gender (RR 1.28 [1.09-1.50], < 0.01), hotel accommodations (RR 1.30 [1.10-1.53], < 0.01), travel to tropical South America (RR 1.34 [1.09-1.64], < 0.01), and duration of travel (RR 1.00 [1.00-1.01], < 0.01). The use of doxycycline for malaria prophylaxis is associated with lower TD risk, suggesting increasing bacterial enteropathogen susceptibility similar to previous observations. Doxycycline selection for antimalarial chemoprophylaxis may provide additional traveler benefit in infection prevention.
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http://dx.doi.org/10.4269/ajtmh.20-0241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646764PMC
November 2020

Comparable Disease Severity by Influenza Virus Subtype in the Acute Respiratory Infection Consortium Natural History Study.

Mil Med 2020 08;185(7-8):e1008-e1015

Infectious Diseases Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 2088.

Introduction: Since the influenza A/H1N1 pandemic of 2009 to 2010, numerous studies have described the clinical course and outcome of the different subtypes of influenza (A/H1N1, A/H3N2, and B). A recent systematic literature review concluded that there were no appreciable differences in either clinical presentation or disease severity among these subtypes, but study parameters limit the applicability of these results to military populations. We sought to evaluate differences in disease severity among influenza subtypes in a cohort of healthy, primarily outpatient adult U.S. Department of Defense beneficiaries.

Materials And Methods: From 2009 to 2014, we enrolled otherwise healthy adults age 18 to 65 years with influenza-like illness in an observational cohort study based in 5 U.S. military medical centers. Serial nasopharyngeal swabs were collected for determination of etiology and viral shedding by polymerase chain reaction. The presence and severity of symptoms was assessed by interview and patient diary.

Results: Over a 5-year period, a total of 157 adults with laboratory-confirmed influenza and influenza subtype were enrolled. Of these, 69 (44%) were positive for influenza A(H1N1), 69 (44%) for influenza A(H3N2), and 19 (12%) for influenza B. About 61% were male, 64% were active duty military personnel, and 72% had received influenza vaccine in the past 8 months. Almost 10% were hospitalized with influenza. Seasonal influenza virus distribution among enrollees mirrored that of nationwide trends each year of study. Individuals with A/H1N1 had upper respiratory composite scores that were lower than those with A/H3N2. Multivariate models indicated that individuals with A(H1N1) and B had increased lower respiratory symptom scores when compared to influenza A(H3N2) (A[H1N1]: 1.51 [95% CI 0.47, 2.55]; B: 1.46 [95% CI 0.09, 2.83]), whereas no other differences in symptom severity scores among influenza A(H1N1), influenza A(H3N2), and influenza B infection were observed. Overall, influenza season (maximum in 2012-2013 season) and female sex of the participant were found to be associated with increased influenza symptom severity.

Conclusions: Our study of influenza in a cohort of otherwise healthy, outpatient adult Department of Defense beneficiaries over 5 influenza seasons revealed few differences between influenza A(H1N1), influenza A(H3N2), and influenza B infection with respect to self-reported disease severity or clinical outcomes. This study highlights the importance of routine, active, and laboratory-based surveillance to monitor ongoing trends and severity of influenza in various populations to inform prevention measures.
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http://dx.doi.org/10.1093/milmed/usaa120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427663PMC
August 2020

HIV Care Continuum and Meeting 90-90-90 Targets: Cascade of Care Analyses of a U.S. Military Cohort.

Mil Med 2020 08;185(7-8):e1147-e1154

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20852, USA.

Introduction: The new initiative by the Department of Health and Human Services (DHHS) aims to decrease new HIV infections in the U.S. by 75% within 5 years and 90% within 10 years. Our objective was to evaluate whether the U.S. military provides a good example of the benefits of such policies.

Materials And Methods: We conducted an analysis of a cohort of 1,405 active duty military personnel with HIV enrolled in the Natural History Study who were diagnosed between 2003 and 2015 at six U.S. military medical centers. The study was approved by institutional review boards at the Uniformed Services University of the Health Sciences and each of the sites. We evaluated the impact of Department of Defense (DoD) HIV care policies, including screening, linkage to care, treatment eligibility, and combined antiretroviral therapy (cART) initiation on achieving viral suppression (VS) within 3 years of diagnosis. As a secondary outcome, we evaluated the DoD's achievement of UNAIDS 90-90-90 targets.

Results: Nearly all (99%) were linked to care within 60 days. Among patients diagnosed in 2003-2009, 77.5% (95% confidence intervals (CI) 73.9-80.6%) became eligible for cART within 3 years of diagnosis, 70.6% (95% CI 66.6-74.1%) overall initiated cART, and 64.2% (95% CI 60.1-68.0%) overall achieved VS. Among patients diagnosed in 2010-2015, 98.7% (95% CI 96.7-99.5%) became eligible for cART within 3 years of diagnosis, 98.5% (95% CI 96.4-99.4%) overall initiated cART, and 89.8% (95% CI 86.0-92.5%) overall achieved VS.

Conclusions: U.S. military HIV policies have been highly successful in achieving VS goals, exceeding the UNAIDS 90-90-90 targets. In spite of limitations, including generalizability, this example demonstrates the feasibility of the DHHS initiative to decrease new infections through testing, early treatment, and retention in care.
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http://dx.doi.org/10.1093/milmed/usaa021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429920PMC
August 2020

Impact of Doxycycline as Malaria Prophylaxis on Risk of Influenza-Like Illness among International Travelers.

Am J Trop Med Hyg 2020 04;102(4):821-826

Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Travelers are often at risk for both influenza-like illness (ILI) and malaria. Doxycycline is active against pathogens causing ILI and is used for malaria prophylaxis. We evaluated the risk factors for ILI, and whether the choice of malaria prophylaxis was associated with ILI. TravMil is a prospective observational study enrolling subjects presenting to military travel clinics. Influenza-like illness was defined as subjective fever with either a sore throat or cough. Characteristics of trip and use of malaria prophylaxis were analyzed to determine association with development of ILI. Poisson regression models with robust error variance were used to estimate relative risk (RR) of ILI. A total of 3,227 trips were enrolled: 62.1% male, median age of 39 years (interquartile range [IQR] 27,59), median travel duration 19 days (IQR 12, 49); 32% traveled to Africa, 40% to Asia, and 27% to the Caribbean and Latin America. Military travel (46%) and vacation (40%) were most common reasons for travel. Among them, 20% took doxycycline, 50% other prophylaxis, and 30% took none; 8.7% developed ILI. Decreased RR of ILI was associated with doxycycline (RR 0.65 [0.43-0.99], = 0.046) and military travel (RR 0.30 [0.21-0.43], < 0.01). Increased risk of ILI was associated with female gender (RR 1.57 [1.24-1.98], < 0.01), travel to Asia (RR 1.37 [1.08-1.75], = 0.01), and cruises (RR 2.21 [1.73-2.83], < 0.01). Use of doxycycline malaria prophylaxis is associated with a decreased risk of ILI. Possible reasons include anti-inflammatory or antimicrobial effects, or other unmeasured factors. With few strategies for decreasing ILI in travelers, these findings bear further investigation.
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http://dx.doi.org/10.4269/ajtmh.19-0648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124920PMC
April 2020

The US Military HIV Natural History Study: Informing Military HIV Care and Policy for Over 30 Years.

Mil Med 2019 11;184(Suppl 2):6-17

National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5601 Fishers Lane, Bethesda, MD 20892.

Introduction: In October 1985, 4 years after the initial descriptions of the acquired immunodeficiency syndrome (AIDS), the U.S. Department of Defense (DoD) began routine screening for human immunodeficiency virus (HIV) infection to prevent infected recruits from exposure to live virus vaccines, implemented routine active-duty force screening to ensure timely care and help protect the walking blood bank, and initiated the U.S. Military HIV Natural History Study (NHS) to develop epidemiologic, clinical, and basic science evidence to inform military HIV policy and establish a repository of data and specimens for future research. Here, we have reviewed accomplishments of the NHS over the past 30 years and sought to describe relevant trends among NHS subjects over this time, with emphasis on combination antiretroviral therapy (cART) use and non-AIDS comorbidities.

Methods: Subjects who were prospectively enrolled in the NHS from 1986 through 2015 were included in this analysis. Time periods were classified by decade of study conduct, 1986-1995, 1996-2005, and 2006-2015, which also correlate approximately with pre-, early-, and late-combination ART (cART) eras. Analyses included descriptive statistics and comparisons among decades. We also evaluated mean community log10 HIV viral load (CVL) and CD4 counts for each year.

Results: A total of 5,758 subjects were enrolled between 1986 and 2015, of whom 92% were male with a median age of 28 years, and 45% were African-American, 42% Caucasian, and 13% Hispanic/other. The proportion of African-Americans remained stable over the decades (45%, 47%, and 42%, respectively), while the proportion of Hispanic/other increased (10%, 13%, and 24%, respectively). The CD4 count at HIV diagnosis has remained high (median 496 cells/uL), while the occurrence of AIDS-defining conditions (excluding low CD4 count) has decreased by decade (36.7%, 5.4%, and 2.9%, respectively). Following the introduction of effective cART in 1996, CVL declined through 2000 as use increased and then plateaued until guidelines changed. After 2004, cART use again increased and CVL declined further until 2012-15 when the vast majority of subjects achieved viral suppression. Non-AIDS comorbidities have remained common, with approximately half of subjects experiencing one or more new diagnoses overall and nearly half of subjects diagnosed between 2006 and 2015, in spite of their relatively young age, shorter median follow-up, and wide use of cART.

Conclusions: The US Military HIV NHS has been critical to understanding the impact of HIV infection among active-duty service members and military beneficiaries, as well as producing insights that are broadly relevant. In addition, the rich repository of NHS data and specimens serves as a resource to investigators in the DoD, NIH, and academic community, markedly increasing scientific yield and identifying novel associations. Looking forward, the NHS remains relevant to understanding host factor correlates of virologic and immunologic control, biologic pathways of HIV pathogenesis, causes and consequences of residual inflammation in spite of effective cART, identifying predictors of and potential approaches to mitigation of excess non-AIDS comorbidities, and helping to understand the latent reservoir.
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http://dx.doi.org/10.1093/milmed/usy430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886375PMC
November 2019

Deployment Infectious Disease Threats: IDCRP Initiatives and Vision Forward.

Mil Med 2019 11;184(Suppl 2):26-34

Infectious Disease Clinical Research Program, Preventive Medicine & Biostatistics Department, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814.

Background: Infectious diseases pose a significant threat to health and readiness of military personnel deployed globally during wartime and peacekeeping activities. Surveillance and improvement in mitigation through research of infectious disease threats remain an integral part of Force Health Protection. Herein, we review research efforts of the Infectious Disease Clinical Research Program related to deployment and travel-related infections.

Methods: The objectives of the Deployment and Travel-Related Infections Research Area are to (1) provide epidemiologic and clinical data, including pathogen-specific estimates of disease incidence among deployed troops, (2) execute clinical trials and effectiveness studies to improve recommendations regarding prevention and treatment of infections during deployment, and (3) evaluate the knowledge and practice patterns of health care providers engaged in deployment/travel medicine and the impact on outcomes. The centerpiece protocol of the research area is the Deployment and Travel-Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies cohort study (TravMil), which was initiated in 2010 and collects data on a broad range of deployment-related infections.

Results: To date, 4,154 deployed military personnel and traveling Department of Defense (DoD) beneficiaries have been enrolled in TravMil. Surveillance data collected through the TravMil study provide assessment of deployment and travel-related infectious disease threats, and the effectiveness of mitigation strategies. The incidence of travelers' diarrhea, influenza-like illness, and undifferentiated febrile illness is 20.48%, 9.34%, and 6.16%, respectively. The cohort study also provides necessary infrastructure to execute clinical trials. The TrEAT TD clinical trial evaluated the effectiveness of single-dose antibiotic therapy for travelers' diarrhea in the deployed setting. When compared to levofloxacin, azithromycin was not inferior; however, inferiority was not demonstrated with use of single dose of rifaximin. The trial findings supported the development of a deployment-related health guideline for the management of acute diarrheal disease. A clinical trial evaluating the effectiveness of rifaximin for prevention for travelers' diarrhea (Prevent TD) is underway.

Conclusions: The research area has proven its ability to conduct impactful research, including the development of field-expedient diagnostics, the largest DoD multi-site travelers' diarrhea randomized control trial in peacetime and combat settings, and informed Force Health Protection guidance. The research area continues to provide surveillance data to military commands via an established collaborative network of military treatment facilities, DoD laboratories (both within and outside the continental United States), foreign militaries, and academia. The conduct of clinical and translational research in a deployment setting presents significant challenges, most notably in recruitment/enrollment and compliance with study-related procedures during deployment.
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http://dx.doi.org/10.1093/milmed/usz182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886669PMC
November 2019

A Comparison of Stool Enteropathogen Detection by Semiquantitative PCR in Adults With Acute Travelers' Diarrhea Before and 3 Weeks After Successful Antibiotic Treatment.

Open Forum Infect Dis 2019 May 26;6(5):ofz187. Epub 2019 Apr 26.

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Rockville, Maryland.

We evaluated stool enteropathogen detection by semiquantitative polymerase chain reaction (PCR) in 108 subjects with travelers' diarrhea before and 3 weeks after treatment. Stool samples from 21 subjects were positive for the same pathogen species at both visits. We discuss factors that should be considered when interpreting stool PCR data after treatment.
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http://dx.doi.org/10.1093/ofid/ofz187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524828PMC
May 2019

A Comparison of Pretravel Health Care, Travel-Related Exposures, and Illnesses among Pediatric and Adult U.S. Military Beneficiaries.

Am J Trop Med Hyg 2019 05;100(5):1285-1289

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

We evaluated differences in pretravel care, exposures, and illnesses among pediatric and adult travelers, using a prospective, observational cohort. Eighty-one pediatric travelers were matched 1:1 with adult military dependents by travel region, destination's malaria risk, and travel duration. Pediatric travelers were more likely to have coverage for hepatitis A and B (90% versus 67% of adults; 85% versus 44%), visit friends and relatives (36% versus 16%), report mosquito bites (69% versus 44%), and have close contact with wild or domesticated animals (40% versus 20%) than adults ( < 0.05). Subjects < 10 years of age were less likely to be prescribed antibiotics (28% versus 95%; RR = 0.63; 95% CI: 0.46-0.85) and antidiarrheals (9% versus 100%; RR = 0.10; 95% CI: 0.03-0.29) for travelers' diarrhea (TD) self-treatment than adults. Travel medicine providers should emphasize strategies for vector avoidance, prevention of animal bites and scratches, and TD self-treatment in pediatric pretravel consultations.
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http://dx.doi.org/10.4269/ajtmh.18-0353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493949PMC
May 2019

Persistent Low-level Viremia While on Antiretroviral Therapy Is an Independent Risk Factor for Virologic Failure.

Clin Infect Dis 2019 11;69(12):2145-2152

Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Background: Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF.

Methods: NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50-199 copies/mL on <25% of measurements), pLLV (VL of 50-199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200-1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented.

Results: Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42-4.93]), and hLV (2.29 [1.78-2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06-1.68]) and antiretroviral use prior to ART (1.79 [1.34-2.38]). Older age at ART initiation (0.71 [0.61-0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51-0.90]) or integrase strand transfer inhibitor use (0.26 [0.13-0.53]) were protective.

Conclusion: Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.
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http://dx.doi.org/10.1093/cid/ciz129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880328PMC
November 2019

Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir.

Open Forum Infect Dis 2018 Oct 8;5(10):ofy221. Epub 2018 Sep 8.

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

HIV integrase mutation T97A emerges after suboptimal therapy with integrase strand transfer inhibitors (INSTIs), but the contribution of T97A to dolutegravir resistance remains uncertain. Here we report >10-fold increase in dolutegravir resistance after the single addition of T97A in 2 individuals with prior INSTI resistance receiving dolutegravir salvage therapy.
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http://dx.doi.org/10.1093/ofid/ofy221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172925PMC
October 2018

Breast Implant Infections: An Update.

Authors:
Tahaniyat Lalani

Infect Dis Clin North Am 2018 Dec 18;32(4):877-884. Epub 2018 Sep 18.

Preventive Medicine and Biostatistics, Uniformed Services University of the Health Science, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address:

Prosthetic breast implantation is a common surgical procedure for augmentation and reconstruction after mastectomy. The incidence of implant infection is 1% to 2.5% and is higher for reconstruction following mastectomy compared with augmentation. Most infections are caused by gram-positive pathogens, such as coagulase-negative staphylococci, Cutibacterium species, Staphylococcus aureus, and streptococci. Acute infections are usually associated with fever and breast pain, erythema, and drainage. Subacute infections may present with chronic pain, persistent drainage, failed healing of the incision site, or migration of the implant. Depending on severity of infection, patients are started on empiric intravenous or oral antibiotics and closely monitored.
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http://dx.doi.org/10.1016/j.idc.2018.06.007DOI Listing
December 2018

Influenza-Like Illness in Travelers to the Developing World.

Am J Trop Med Hyg 2018 11;99(5):1269-1274

San Antonio Military Medical Center, Joint Base San Antonio, Fort Sam Houston, Texas.

Travelers to developing regions are at risk for development of influenza-like illness (ILI). Little is known of traveler and trip characteristics associated with the development of ILI. TravMil is a prospective observational study, enrolling subjects presenting to six military travel clinics or predeployment-screening sites. We analyzed pre- and post-travel surveys from travelers visiting regions outside of the continental United States, Western or Northern Europe, Canada, Australia, or New Zealand between January 2010 and March 2016. Influenza-like illness was defined as a self-reported fever associated with either sore throat or cough. Trip and traveler characteristics were analyzed to determine risk factors for the development of ILI. Two thousand nine hundred and thirty-two trips were recorded (55% male, median age 45 years, 69% white, 51% on vacation, median travel duration 17 days). The 2,337 trips included the number of self-reported influenza vaccinations in the preceding 5 years (median 5). Eleven percent of the trips were complicated by an ILI lasting a median of 5 days; 70% and 17% of these reported upper and lower respiratory tract infection, respectively, and 12% reported both. On multivariate analysis, increased risk of ILI was associated with female gender (odds ratio [OR]: 1.60 [confidence interval (CI): 1.25-2.05], < 0.01), age (years) (OR: 1.01 [CI: 1.01-1.02], < 0.01); and duration of travel (days) (OR: 1.01 [CI: 1.00-1.01], < 0.01). Influenza-like illness is common in travelers, regardless of traveler characteristics, purpose of travel, destination, or season of year. Female gender, older age, and longer duration of travel were associated with an increased risk of ILI. Additional tools and strategies are needed to prevent ILI in international travelers.
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http://dx.doi.org/10.4269/ajtmh.17-0884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221204PMC
November 2018

Comparison of stool collection and storage on Whatman FTA Elute cards versus frozen stool for enteropathogen detection using the TaqMan Array Card PCR assay.

PLoS One 2018 30;13(8):e0202178. Epub 2018 Aug 30.

F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, MD, United States of America.

The use of Polymerase Chain Reaction (PCR) assays for pathogen detection in travelers' diarrhea (TD) field studies is limited by the on-site processing and storage requirements for fecal specimens. The objectives of this investigation were to i) characterize the pathogen distribution in deployed military personnel with TD using the TaqMan® Array Card PCR (TAC) on frozen stool and diarrheal smears on Whatman FTA Elute cards (FTA cards), and to ii) compare TAC detection of enteropathogen targets using smeared FTA cards and frozen stool, using TAC on frozen stool as the 'reference standard'. Stool samples, obtained from active duty personnel with acute TD enrolled in a field trial, were smeared onto FTA cards and stored at room temperature. A corresponding aliquot of stool was frozen in a cryovial. FTA cards and frozen stool samples were tested at a central lab, using a customized TAC for detection of TD pathogens. 187 paired frozen stool samples and smeared FTA cards were stored for a median of 712 days (IQR 396-750) before testing. Overall detection rates were 78.6% for frozen stool and 73.2% for FTA cards. Diarrheagenic Escherichia coli were the most common bacteria identified. Using the TAC results on frozen stool as the reference, the overall sensitivity and specificity of TAC on FTA cards was 72.9% and 98.0% respectively. TAC on FTA cards demonstrated a decrease in sensitivity with increasing frozen stool quantification cycle (Cq) (90.0% in FTA cards with a corresponding frozen stool Cq < 30, and 72.9% in samples with a corresponding frozen stool Cq < 35). Our findings support the use and further development of FTA cards in combination with a quantitative PCR assay for enteropathogen detection in TD field studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0202178PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117160PMC
February 2019

Human Serum With High Neutralizing Antibody Titers Against Both Zika and Dengue Virus Shows Delayed In Vitro Antibody-Dependent Enhancement of Dengue Virus Infection.

Open Forum Infect Dis 2018 Jul 22;5(7):ofy151. Epub 2018 Jun 22.

F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland.

Zika virus infection in a dengue virus-naïve subject was associated with the induction of high levels of cross-reactive binding antibodies. These responses were, however, largely non-neutralizing and displayed a capacity to enhance dengue infection in vitro at significantly low dilution (1:10). In contrast, a subject who had high levels of neutralizing antibodies against both dengue and Zika viruses enhanced infection at a dilution of 1:10 000. These results suggest that high levels of dengue cross-neutralizing antibodies could potentially prevent the enhancement of dengue infection in Zika virus-convalescent individuals.
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http://dx.doi.org/10.1093/ofid/ofy151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041987PMC
July 2018

Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI).

PLoS One 2018 22;13(3):e0194180. Epub 2018 Mar 22.

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Background: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza.

Objectives: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI).

Methods: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7).

Results: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes).

Conclusions: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194180PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863969PMC
July 2018

Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) Scores in Influenza-Positive Patients.

Value Health 2018 02 7;21(2):210-218. Epub 2017 Jun 7.

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

Objectives: To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms.

Methods: An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health.

Results: Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness.

Conclusions: Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.
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http://dx.doi.org/10.1016/j.jval.2017.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831548PMC
February 2018

Species-specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults.

Influenza Other Respir Viruses 2018 03 2;12(2):299-303. Epub 2018 Feb 2.

Department of Preventive Medicine and Biostatistics, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Human coronavirus (HCoV) is a known cause of influenza-like illness (ILI). In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR-positive for HCoV. The distribution of species was as follows: HCoV-OC43 (34%), HCoV-229E (28%), HCoV-NL63 (22%), and HCoV-HKU1 (16%). We did not observe species-specific differences in the clinical characteristics of HCoV infection, with the exception of HCoV-HKU1, for which the severity of gastrointestinal symptoms trended higher on the fourth day of illness.
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http://dx.doi.org/10.1111/irv.12538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820427PMC
March 2018

Brief Report: Racial Comparison of D-Dimer Levels in US Male Military Personnel Before and After HIV Infection and Viral Suppression.

J Acquir Immune Defic Syndr 2018 04;77(5):502-506

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.

Background: D-dimer blood levels in persons with HIV infection are associated with risk of serious non-AIDS conditions and death. Black race has been correlated with higher D-dimer levels in several studies. We examined the effects of race and HIV on D-dimer over time and the impact of viral load suppression by longitudinally comparing changes in levels among healthy young adult male African Americans and whites before HIV seroconversion and before and after initiation of antiretroviral therapy (ART).

Methods: We analyzed D-dimer levels and clinical and laboratory data of 192 participants enrolled in the US Military HIV Natural History Study, a 30-year cohort of military personnel infected with HIV. D-dimer levels were measured on stored sera from each participant at 3 time points: (1) before HIV seroconversion (Pre-SC), (2) ≥6 months after HIV seroconversion but before ART initiation (Post-SC), and (3) ≥6 months after ART with documented viral suppression (Post-ART). Levels were compared at each time point using nonparametric and logistic regression analysis.

Results: Compared with whites (n = 106), African Americans (n = 86) had higher D-dimer levels post-SC (P = 0.007), but in the same individuals, pre-SC baseline and post-ART levels were similar (P = 0.40 and P = 0.99, respectively). There were no racial differences in CD4 cell counts, HIV RNA viral load, time from estimated seroconversion to ART initiation, and duration on ART.

Conclusions: Observed longitudinally, racial differences in D-dimer levels were seen only during HIV viremia. Higher levels of D-dimer commonly observed in African Americans are likely due to factors in addition to race.
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http://dx.doi.org/10.1097/QAI.0000000000001626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844843PMC
April 2018

Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide.

Clin Infect Dis 2017 Nov;65(12):2008-2017

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Background: Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations.

Methods: A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool.

Results: Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events.

Conclusions: Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea.

Clinical Trial Registration: NCT01618591.
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http://dx.doi.org/10.1093/cid/cix693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848251PMC
November 2017

Evaluation of T and B memory cell responses elicited by the pandemic H1N1 vaccine in HIV-infected and HIV-uninfected individuals.

Vaccine 2017 10 4;35(45):6103-6111. Epub 2017 Oct 4.

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, United States.

Background: This study was to compare B and T memory cells elicited by a single dose monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009 H1N1) in HIV and HIV groups, and to analyze the impact of the prior seasonal vaccines to the immunogenicity of this vaccine.

Methods: Blood samples were collected before vaccination (day 0) and at days 28 and 180. Participants were categorized into HIV/LAIV, HIV/TIV and HIV/TIV subgroups according to the trivalent live-attenuated or inactivated (LAIV or TIV) seasonal influenza vaccines they received previously. The IgG memory B cells (B) and IFNγ T cells were measured against antigens including the H1N1 vaccine, the hemagglutinin (HA) and neuraminidase (NA) proteins or peptide pools of the pandemic and the seasonal H1N1 strains, respectively.

Results: Overall B responses increased significantly at day 28 but returned to baseline by day 180 in all three subgroups. The average frequency of the H1N1-specific B at day 28 for the HIV/LAIV, HIV/TIV and HIV/TIV groups was 2.14%, 1.26% and 1.67%, respectively, and the average fold change was 14.39, 3.81 and 3.93, respectively. The differences of B between HIV/LAIV and the two TIV subgroups were significant. For the IFNγ response, the overall spot counts ranged widely between 0 and 958/10 PBMCs. The group average spot counts to H1N1 vaccine was 89, 102, and 30 at day 28 for HIV/LAIV, HIV/TIV and HIV/TIV subgroups, respectively. The average increase of IFNγ response at day 28 vs day 0 in all three subgroups did not reach 2-fold.

Conclusion: Participants with a prior LAIV seasonal vaccine, as compared to a TIV seasonal vaccine, responded significantly better to the monovalent H1N1 vaccine. Excluding LAIV participants, no difference was seen between the HIV and HIV subject groups in terms of B. The B response declined at 6months.
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http://dx.doi.org/10.1016/j.vaccine.2017.09.059DOI Listing
October 2017

Brief Report: Prevalence of Posttreatment Controller Phenotype Is Rare in HIV-Infected Persons After Stopping Antiretroviral Therapy.

J Acquir Immune Defic Syndr 2017 07;75(3):364-369

*Infectious Disease Service, Walter Reed National Military Medical Center, Bethesda, MD; †Infectious Disease Clinical Research Program, Rockville, MD; ‡Henry M Jackson Foundation for the Advancement of Military Medicine, Rockville, MD; §Infectious Disease Service, San Antonio Military Medical Center, San Antonio, TX; ‖Infectious Disease Service, Naval Medical Center Portsmouth, Portsmouth, VA; and ¶Infectious Disease Service, Tripler Army Medical Center, Honolulu, HI.

Background: Posttreatment control of HIV infection is a rare phenomenon primarily described among those initiating treatment with antiretroviral therapy (ART) during early/acute HIV infection.

Methods: We examined a large, well-characterized cohort of HIV-infected Department of Defense beneficiaries for the presence of posttreatment controllers (PTCs) whom we defined as individuals with sustained viral suppression for ≥6 months after discontinuation of ART. We defined those who became viremic within 6 months of discontinuing ART as rapid viremics (RVs) and compared demographic and clinical characteristics, CD4 counts, and viral loads prior, during, and after ART discontinuation between the 2 groups.

Results: From a cohort of 6070 patients, we identified 95 who had been treated with ART for 2 years or more who subsequently discontinued ART and had viral load assessments available after discontinuation. Four (4.2%) of these 95 met our definition of PTC. The duration of viral suppression off of ART ranged from 267 to 1058 days with 1 of the 4 restarting ART without having redeveloped a significant viremia. All 4 patients initiated ART during chronic HIV infection. Demographic and clinical characteristics of PTCs were similar to RVs.

Conclusions: While posttreatment control has predominantly been described among individuals who initiated ART in early/acute HIV infection, we identified 4 PTCs who started ART during chronic infection suggesting that posttreatment control also occurs among such patients. The rarity of PTCs identified in our cohort is consistent with reports from previous studies.
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http://dx.doi.org/10.1097/QAI.0000000000001393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473334PMC
July 2017

Mosquito Exposure and Chikungunya and Dengue Infection Among Travelers During the Chikungunya Outbreak in the Americas.

Am J Trop Med Hyg 2017 Apr 23;96(4):903-912. Epub 2017 Jan 23.

San Antonio Military Medical Center, San Antonio, Texas.

AbstractTravelers are at risk for arbovirus infection. We prospectively enrolled 267 Department of Defense beneficiaries traveling to chikungunya-outbreak regions in the Americas between December 2013 and May 2015 and assessed travel characteristics and serologic exposure to chikungunya virus (CHIKV) and dengue virus (DENV). Ten ill-returning travelers were also assessed retrospectively. Self-reported mosquito exposure was common (64% of 198 evaluable travelers saw mosquitoes; 53% of 201 reported ≥ 1 bite). Increased exposure was associated with active-duty travelers (odds ratio [OR] = 2.6 [1.3-5.4] for seeing mosquitoes) or travelers visiting friends and relatives (VFR) (OR = 3.5 [1.0-10.0] for high-intensity bite exposure). Arbovirus infection was defined as seroconversion on plaque reduction neutralization testing (PRNT) of pre- and posttravel sera. For ill subjects enrolled posttravel, infection was defined by a positive convalescent PRNT and/or a positive reverse transcription polymerase chain reaction for CHIKV or DENV. We identified seven cases of arbovirus infection: four with CHIKV, five with DENV, and two with both. The composite attack rate for CHIKV and DENV infection was 3.7% of 108 evaluable, immunologically naïve, prospectively assessed travelers; there was serologic and/or polymerase chain reaction evidence of arbovirus infection in three of four evaluable (three of 10 total) ill-returning travelers. We identified both symptomatic and asymptomatic cases. Military purpose of travel and VFR travel accounted for five of seven cases. Pretravel counseling is important and should target higher risk groups. Given a shared vector between CHIKV, DENV, and Zika virus (ZIKV), this study can also help guide counseling for travelers to ZIKV-outbreak regions.
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http://dx.doi.org/10.4269/ajtmh.16-0635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392640PMC
April 2017

Safety and immunogenicity of a recombinant Staphylococcus aureus α-toxoid and a recombinant Panton-Valentine leukocidin subunit, in healthy adults.

Hum Vaccin Immunother 2017 04 23;13(4):791-801. Epub 2016 Dec 23.

a Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics , Uniformed Services University of the Health Sciences , Rockville , MD , USA.

We conducted a randomized, double-blind, placebo-controlled dose-escalation study in healthy adults to evaluate the safety and immunogenicity of recombinant Staphylococcus aureus candidate vaccine antigens, recombinant α-toxoid (rAT) and a sub-unit of Panton-Valentine leukocidin (rLukS-PV). 176 subjects were enrolled and randomized within 1 of 11 treatment cohorts: monovalent rAT or rLukS-PV dosages of 10, 25, 50, and 100 μg; bivalent rAT:rLukS dosages of 10:10, 25:25, and 50:50 μg; and alum or saline placebo. All subjects were assessed at Days 0, 7, 14, 28, and 84. Subjects in the 50:50 μg bivalent cohort received a second injection on Day 84 and were assessed on Days 98 and 112. Incidence and severity of reactogenicity and adverse events (AEs) were compared. Geometric mean serum concentrations (GMC) and neutralizing activity of anti-rAT and anti-rLukS-PV IgG were assessed. Reactogenicity incidence was significantly higher in vaccine than placebo recipients (77% versus 55%, respectively; p = 0.006). However, 77% of reactogenicity events were mild and 19% were moderate in severity. The AE incidence and severity were similar between the cohorts. All monovalent and bivalent rAT dosages resulted in a significant increase in the anti-rAT IgG and anti- rLukS-PV GMCs between day 0 and 28 compared with placebo, and persisted through Day 84. Exploratory subgroup analyses suggested a higher GMC and neutralizing antibody titers for the 50 μg monovalent or bivalent rAT and rLukS-PV dose as compared to the other doses. No booster effect was observed after administration of the second dose. We conclude that the rAT and rLukS-PV vaccine formulations were well-tolerated and had a favorable immunogenicity profile, producing antibody with neutralizing activity through day 84. There was no benefit observed with a booster dose of the vaccine.
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http://dx.doi.org/10.1080/21645515.2016.1248326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404372PMC
April 2017