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Combat extremity wounds are highly susceptible to contamination from surrounding environmental material. This bioburden could be partially transferred from materials in immediate proximity to the wound, including fragments of the uniform and gear. However, the assessment of the microbial bioburden present on military gear during operational conditions of deployment or training is relatively unexplored. Opportunistic pathogens that can survive on gear represent risk factors for infection following injury, especially following combat blasts, where fibers and other materials are embedded in wounded tissue. We utilized 16S rRNA sequencing to assess the microbiome composition of different military gear types (boot, trouser, coat, and canteen) from two operational environments (training in Hawai'i and deployed in Indonesia) across time (days 0 and 14). We found that microbiome diversity, stability, and composition were dependent on gear type, training location, and sampling timepoint. At day 14, species diversity was significantly higher in Hawai'i samples compared to Indonesia samples for boot, coat, and trouser swabs. In addition, we observed the presence of potential microbial risk factors, as opportunistic pathogenic species, such as Acinetobacter, Pseudomonas, and Staphylococcus, were found to be present in all sample types and in both study sites. These study outcomes will be used to guide the design of antimicrobial materials and uniforms and for infection control efforts following combat blasts and other injuries, thereby improving treatment guidance during military training and deployment.IMPORTANCECombat extremity wounds are vulnerable to contamination from environments of proximity to the warfighter, leading to potential detrimental outcomes such as infection and delayed wound healing. Therefore, microbial surveillance of such environments is necessary to aid the advancement of military safety and preparedness through clinical diagnostics, treatment protocols, and uniform material design.
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Militares , Humanos , RNA Ribossômico 16S , Fatores de Risco , Havaí , IndonésiaRESUMO
Background: We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara-Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device. Methods: Healthy, HIV-uninfected adults were randomized to receive 4 mg of PENNVAX-G DNA delivered intramuscularly by Biojector or electroporation at baseline and week 4 followed by intramuscular injection of 108 plaque forming units of MVA-CMDR at weeks 12 and 24. The open-label part A was conducted in the United States, followed by a double-blind, placebo-controlled part B in East Africa. Solicited and unsolicited adverse events were recorded, and immune responses were measured. Results: Eighty-eight of 100 enrolled participants completed all study injections, which were generally safe and well tolerated, with more immediate, but transient, pain in the electroporation group. Cellular responses were observed in 57% of vaccine recipients tested and were CD4 predominant. High rates of binding antibody responses to CRF01_AE antigens, including gp70 V1V2 scaffold, were observed. Neutralizing antibodies were detected in a peripheral blood mononuclear cell assay, and moderate antibody-dependent, cell-mediated cytotoxicity activity was demonstrated. Discussion: The PVG/MVA-CMDR HIV-1 vaccine regimen is safe and immunogenic. Substantial differences in safety or immunogenicity between modes of DNA delivery were not observed. Clinical Trials Registration: NCT01260727.
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Vacinas contra a AIDS/administração & dosagem , Vacinas contra a AIDS/imunologia , Anticorpos Anti-HIV/sangue , Infecções por HIV/prevenção & controle , Imunidade Celular/efeitos dos fármacos , Vaccinia virus/imunologia , Adulto , África Oriental , Método Duplo-Cego , Eletroporação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , VacinaçãoRESUMO
Background: The RV144 ALVAC-HIV prime, AIDSVAX B/E boost afforded 60% efficacy against human immunodeficiency virus (HIV) acquisition at 1 year, waning to 31.2% after 3.5 years. We hypothesized that additional vaccinations might augment immune correlates of protection. Methods: In a randomized placebo-controlled double-blind study of 162 HIV-negative RV144 vaccine recipients, we evaluated 2 additional boosts, given 6-8 years since RV144 vaccination, for safety and immunogenicity, at weeks 0 and 24. Study groups 1-3 received ALVAC-HIV+AIDSVAX B/E, AIDSVAX B/E, and ALVAC-HIV, respectively, or placebo. Results: Vaccines were well tolerated. For groups 1 and 2, plasma immunoglobulin (Ig) G, IgA, and neutralizing antibody responses at week 2 were all significantly higher than 2 weeks after the last RV144 vaccination. IgG titers against glycoprotein (gp) 70V1V2 92TH023 increased 14-fold compared with 2 weeks after the last RV144 vaccination (14069 vs 999; P < .001). Groups 1 and 2 did not differ significantly from each other, whereas group 3 was similar to placebo recipients. Responses in groups 1 and 2 declined by week 24 but were boosted by the second vaccination, albeit at lower magnitude than for week 2. Conclusions: In RV144 vaccinees, AIDSVAX B/E with or without ALVAC-HIV 6-8 years after initial vaccination generated higher humoral responses than after RV144, but these responses were short-lived, and their magnitude did not increase with subsequent boost. Clinical Trials Registration: NCT01435135.
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Vacinas contra a AIDS/administração & dosagem , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , Imunidade Humoral , Imunização Secundária , Adulto , Anticorpos Neutralizantes/sangue , Citocinas/imunologia , Método Duplo-Cego , Feminino , Anticorpos Anti-HIV/sangue , HIV-1 , Voluntários Saudáveis , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , TailândiaRESUMO
Mucosal Th17 cells play an important role in maintaining gut epithelium integrity and thus prevent microbial translocation. Chronic HIV infection is characterized by mucosal Th17 cell depletion, microbial translocation and subsequent immune-activation, which remain elevated despite antiretroviral therapy (ART) correlating with increased mortality. However, when Th17 depletion occurs following HIV infection is unknown. We analyzed mucosal Th17 cells in 42 acute HIV infection (AHI) subjects (Fiebig (F) stage I-V) with a median duration of infection of 16 days and the short-term impact of early initiation of ART. Th17 cells were defined as IL-17+ CD4+ T cells and their function was assessed by the co-expression of IL-22, IL-2 and IFNγ. While intact during FI/II, depletion of mucosal Th17 cell numbers and function was observed during FIII correlating with local and systemic markers of immune-activation. ART initiated at FI/II prevented loss of Th17 cell numbers and function, while initiation at FIII restored Th17 cell numbers but not their polyfunctionality. Furthermore, early initiation of ART in FI/II fully reversed the initially observed mucosal and systemic immune-activation. In contrast, patients treated later during AHI maintained elevated mucosal and systemic CD8+ T-cell activation post initiation of ART. These data support a loss of Th17 cells at early stages of acute HIV infection, and highlight that studies of ART initiation during early AHI should be further explored to assess the underlying mechanism of mucosal Th17 function preservation.
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Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Imunidade nas Mucosas/fisiologia , Mucosa Intestinal/fisiologia , Células Th17/fisiologia , Doença Aguda , Adulto , Antirretrovirais/farmacologia , Biomarcadores/sangue , Biópsia , Colo Sigmoide/patologia , Citocinas/sangue , Feminino , Infecções por HIV/patologia , Infecções por HIV/fisiopatologia , Humanos , Imunidade nas Mucosas/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Células Th17/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case-control analysis to identify antibody and cellular immune correlates of infection risk. METHODS: In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up. RESULTS: Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds ratio, 0.57 per 1-SD increase; P=0.02; q=0.08), and the binding of plasma IgA antibodies to Env correlated directly with the rate of infection (estimated odds ratio, 1.54 per 1-SD increase; P=0.03; q=0.08). Neither low levels of V1V2 antibodies nor high levels of Env-specific IgA antibodies were associated with higher rates of infection than were found in the placebo group. Secondary analyses suggested that Env-specific IgA antibodies may mitigate the effects of potentially protective antibodies. CONCLUSIONS: This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific IgA antibodies may have mitigated the effects of protective antibodies. Vaccines that are designed to induce higher levels of V1V2 antibodies and lower levels of Env-specific IgA antibodies than are induced by the RV144 vaccine may have improved efficacy against HIV-1 infection.
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Vacinas contra a AIDS/imunologia , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , HIV-1/imunologia , Adulto , Estudos de Casos e Controles , Seguimentos , Infecções por HIV/prevenção & controle , Humanos , Imunoglobulina A/sangue , Análise Multivariada , Razão de Chances , Análise de Regressão , Risco , Resultado do TratamentoRESUMO
BACKGROUND: The Thai Phase III Trial of ALVAC-HIV and AIDSVAX B/E showed an estimated vaccine efficacy (VE) of 31% to prevent acquisition of human immunodeficiency virus (HIV). Here we evaluated the effect of vaccination on disease progression after infection. METHODS: CD4(+) T-cell counts and HIV viral load (VL) were measured serially. The primary analysis evaluated vaccine efficacy (VEP) as the percent reduction (vaccine vs placebo) in cumulative probability of a primary composite endpoint of clinical and CD4(+) count components at prespecified time points after infection. Secondary analyses of biomarker-based endpoints were assessed using marginal mean and linear mixed models. RESULTS: There were 61 endpoints in the modified intent-to-treat cohort (mITT; n = 114). There was no evidence for efficacy at 30, 42, 54, and 60 months in the mITT and per protocol (n = 90) cohorts. Estimated VEP (mITT) was15.8% (-21.9, 41.8) at 60 months postinfection. There was weak evidence of lower VL and higher CD4(+) count at 60 and 66 months in the vaccine group. Lower mucosal VL was observed among vaccine recipients, primarily in semen (P = .04). CONCLUSIONS: Vaccination did not affect the clinical course of HIV disease after infection. A potential vaccine effect on the genital mucosa warrants further study.
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Vacinas contra a AIDS/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Vacinas Virais/imunologia , Vacinas contra a AIDS/administração & dosagem , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/patologia , Infecções por HIV/prevenção & controle , HIV-1/patogenicidade , Humanos , Modelos Lineares , Masculino , Estudos Prospectivos , Assunção de Riscos , Sêmen/virologia , Tailândia , Fatores de Tempo , Vacinação , Vagina/virologia , Carga Viral , Vacinas Virais/administração & dosagem , Adulto JovemRESUMO
Identified in December 2019, SARS-CoV-2 quickly spread worldwide with a resultant increase in global morbidity, mortality, and economic disruption on a scale not seen since the 1918 Spanish flu. Health officials recommended universal masking to further reduce human-to-human spread of SARS-CoV-2. The state of Hawaii and the Department of Defense (DOD) adopted strict mask policies early in the pandemic and is shown to be effective at reducing transmission. We report a case of Staphylococcus aureus bacteremia in an immunocompetent 21-year-old man attributed to local skin irritation with resultant infection in the setting of continuous reuse of a mask that resulted in bilateral cavernous venous thrombosis and septic pulmonary embolism.
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Reliably assessing exposure to mosquitoes carrying malaria parasites continues to be a challenge due to the lack of reliable, highly sensitive diagnostics with high-throughput potential. Here, we describe an approach that meets these requirements by simultaneously measuring immune responses to both disease vector and pathogen, using an electro-chemiluminescence-based multiplex assay platform. While using the same logistical steps as a classic ELISA, this platform allows for the multiplexing of up to ten antigens in a single well. This simple, reproducible, quantitative readout reports the magnitude, incidence, and prevalence of malaria infections in residents of malaria-endemic areas. By reporting exposure to both insect vectors and pathogen, the approach also provides insights into the efficacy of drugs and/or other countermeasures deployed against insect vectors aimed at reducing or eliminating arthropod-borne diseases. The high throughput of the assay enables the quick and efficient screening of sera from individuals for exposure to Plasmodium even if they are taking drug prophylaxis. We applied this assay to samples collected from controlled malaria infection studies, as well as those collected in field studies in malaria-endemic regions in Uganda and Kenya. The assay was sensitive to vector exposure, malaria infection, and endemicity, demonstrating its potential for use in malaria serosurveillance.
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Health inequalities based on race are well-documented, and the COVID-19 pandemic is no exception. Despite the advances in modern medicine, access to health care remains a primary determinant of health outcomes, especially for communities of color. African-Americans and other minorities are disproportionately at risk for infection with COVID-19, but this problem extends beyond access alone. This study sought to identify trends in race-based disparities in COVID-19 in the setting of universal access to care. Tripler Army Medical Center (TAMC) is a Department of Defense Military Treatment Facility (DoD-MTF) that provides full access to healthcare to active duty military members, beneficiaries, and veterans. We evaluated the characteristics of individuals diagnosed with SARS-CoV-2 infection at TAMC in a retrospective, case-controlled (1:1) study. Most patients (69%) had received a COVID-19 test within 3 days of symptom onset. Multivariable logistic regression analyses were used to identify factors associated with testing positive and to estimate adjusted odds ratios. African-American patients and patients who identified as "Other" ethnicities were two times more likely to test positive for SARS-CoV-2 relative to Caucasian patients. Other factors associated with testing positive include: younger age, male gender, previous positive test, presenting with >3 symptoms, close contact with a COVID-19 positive patient, and being a member of the US Navy. African-Americans and patients who identify as "Other" ethnicities had disproportionately higher rates of positivity of COVID-19. Although other factors contribute to increased test positivity across all patient populations, access to care does not appear to itself explain this discrepancy with COVID-19.
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Teste para COVID-19/métodos , COVID-19/diagnóstico , Etnicidade/estatística & dados numéricos , Militares/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , COVID-19/epidemiologia , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Havaí/epidemiologia , Humanos , Masculino , Estudos RetrospectivosRESUMO
The global burden of malaria remains substantial. Circumsporozoite protein (CSP) has been demonstrated to be an effective target antigen, however, improvements that offer more efficacious and more durable protection are still needed. In support of research and development of next-generation malaria vaccines, Walter Reed Army Institute of Research (WRAIR) has developed a CSP-based antigen (FMP013) and a novel adjuvant ALFQ (Army Liposome Formulation containing QS-21). We present a single center, open-label, dose-escalation Phase 1 clinical trial to evaluate the safety and immunogenicity of the FMP013/ALFQ malaria vaccine candidate. In this first-in-human evaluation of both the antigen and adjuvant, we enrolled ten subjects; five received 20 µg FMP013 / 0.5 mL ALFQ (Low dose group), and five received 40 µg FMP013 / 1.0 mL ALFQ (High dose group) on study days 1, 29, and 57. Adverse events and immune responses were assessed during the study period. The clinical safety profile was acceptable and there were no serious adverse events. Both groups exhibited robust humoral and cellular immunological responses, and compared favorably with historical responses reported for RTS,S/AS01. Based on a lower reactogenicity profile, the 20 µg FMP013 / 0.5 mL ALFQ (Low dose) was selected for follow-on efficacy testing by controlled human malaria infection (CHMI) with a separate cohort. Trial Registration:Clinicaltrials.gov Identifier NCT04268420 (Registered February 13, 2020).
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Vacinas Antimaláricas , Malária Falciparum , Adjuvantes Imunológicos/efeitos adversos , Adulto , Anticorpos Antiprotozoários , Humanos , Malária Falciparum/prevenção & controle , Plasmodium falciparum , Proteínas de ProtozoáriosRESUMO
BACKGROUND: We previously demonstrated that RTS,S/AS01B and RTS,S/AS01E vaccination regimens including at least one delayed fractional dose can protect against Plasmodium falciparum malaria in a controlled human malaria infection (CHMI) model, and showed inferiority of a two-dose versus three-dose regimen. In this follow-on trial, we evaluated whether fractional booster vaccination extended or induced protection in previously protected (P-Fx) or non-protected (NP-Fx) participants. METHODS: 49 participants (P-Fx: 25; NP-Fx: 24) received a fractional (1/5th dose-volume) RTS,S/AS01E booster 12 months post-primary regimen. They underwent P. falciparum CHMI three weeks later and were then followed for six months for safety and immunogenicity. RESULTS: Overall vaccine efficacy against re-challenge was 53% (95% CI: 37-65%), and similar for P-Fx (52% [95% CI: 28-68%]) and NP-Fx (54% [95% CI: 29-70%]). Efficacy appeared unaffected by primary regimen or previous protection status. Anti-CS (repeat region) antibody geometric mean concentrations (GMCs) increased post-booster vaccination. GMCs were maintained over time in primary three-dose groups but declined in the two-dose group. Protection after re-challenge was associated with higher anti-CS antibody responses. The booster was well-tolerated. CONCLUSIONS: A fractional RTS,S/AS01E booster given one year after completion of a primary two- or three-dose RTS,S/AS01 delayed fractional dose regimen can extend or induce protection against CHMI. CLINICAL TRIAL REGISTRATION: NCT03824236. linked to this article can be found on the Research Data as well as Figshare https://figshare.com/s/ee025150f9d1ac739361.
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Vacinas Antimaláricas , Malária Falciparum , Malária , Anticorpos Antiprotozoários , Humanos , Malária Falciparum/prevenção & controle , Plasmodium falciparum , VacinaçãoRESUMO
Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.
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Anticorpos Monoclonais/imunologia , Anticorpos Antiprotozoários/imunologia , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Proteínas de Protozoários/imunologia , Esporozoítos/imunologia , Animais , Linhagem Celular , Feminino , Hepatócitos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de CélulasRESUMO
Sexual transmission is the principal driver of the human immunodeficiency virus (HIV) pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080) efficacy trial showed protection against HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and antigens including variable one and two loop scaffold antigens (gp70V1V2) previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE) and Case A2 (subtype B) in cervico-vaginal mucus (CVM), seminal plasma (SP) and rectal secretions (RS) from HIV-uninfected RV144 vaccine recipients, who were randomized to receive two late boosts of ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or ALVAC-HIV alone at 0 and 6 months. Late vaccine boosting increased IgG geometric mean titers (GMT) to gp120 A244gD in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively), followed by SP and RS. IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (11-17 fold) and SP (2 fold) two weeks post first boost. IgG to Case A2 was only detected in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal IgG to gp120 A244gD (CVM, SP, RS), gp70V1V2 92TH023 (CVM, SP), and Case A2 (CVM) correlated with plasma IgG levels (p<0.001). Although the magnitude of IgG responses declined after boosting, anti-gp120 A244gD IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific antibodies (IgG and dimeric IgA) in anogenital secretions will help determine their role in preventing mucosal HIV acquisition.
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Vacinas contra a AIDS/uso terapêutico , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , Imunidade nas Mucosas , Imunização Secundária , Adolescente , Adulto , Canal Anal/imunologia , Formação de Anticorpos , Especificidade de Anticorpos , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , HIV-1 , Humanos , Imunização , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Masculino , Proteínas Recombinantes/imunologia , Adulto JovemRESUMO
Hawaii has one of the highest incidences of Campylobacteriosis in the United States, but there remains little published data on circulating strains or antimicrobial resistance. We characterized 110 clinical Campylobacter isolates (106 C. jejuni, 4 C. coli) processed at Tripler Army Medical Center in Honolulu, HI from 2012-2016. Twenty-five percent of C. jejuni isolates exhibited fluoroquinolone (FQ) resistance, compared with 16% for tetracycline (TET), and 0% for macrolides. Two of the four C. coli isolates were resistant to FQ, TET, and macrolides. C. jejuni isolates further underwent multilocus sequence typing, pulsed-field gel electrophoresis, and molecular capsular typing. Nineteen capsule types were observed, with two capsule types (HS2 and HS9) being associated with FQ resistance (p < 0.001 and p = 0.006, respectively). HS2 FQ-resistant isolates associated with clonal complex 21, possibly indicating clonal spread in FQ resistance. Macrolides should be considered for treatment of suspect cases due to lack of observed resistance.
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Campylobacter/efeitos dos fármacos , Adulto , Antibacterianos/farmacologia , Campylobacter/genética , Infecções por Campylobacter/prevenção & controle , Farmacorresistência Bacteriana/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Fluoroquinolonas/farmacologia , Havaí , Humanos , Macrolídeos/farmacologia , Masculino , Tipagem de Sequências Multilocus , Estudos Retrospectivos , Tetraciclina/farmacologia , Adulto JovemRESUMO
Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity) may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb) responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT) of 250 to baseline (<20) after 10-20 years post vaccination. This contrasted with a comparator group of adults, ages 35-49, who were vaccinated with Dryvax® as children. In the childhood vaccinees, titers persisted for >30 years with a GMT of 210 (range 112-3234). This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.
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Imunidade Humoral , Militares , Vacina Antivariólica/imunologia , Varíola/imunologia , Vacinação , Vaccinia virus/imunologia , Adulto , Criança , Células Dendríticas/imunologia , Ensaio de Imunoadsorção Enzimática , Proteínas de Fluorescência Verde/metabolismo , HIV/genética , Humanos , Imunização , Testes de Neutralização , TransgenesRESUMO
BACKGROUND: Campylobacter continues to be an important cause of diarrheal disease worldwide and a leading cause in Southeast Asia. Studies of US soldiers and marines deployed to Thailand for a 2 to 3 week field exercise provide a unique population in which to study traveler's diarrhea. METHODS: A case-control study of 217 deployed military personnel was conducted from 2002 through 2004. Of these, 155 subjects who presented to a field medical unit with acute diarrhea were enrolled as cases. These subjects referred an additional 62 diarrhea-free colleagues who served as controls. Frequencies of isolation of Campylobacter spp. and other enteric pathogens were compared in cases and controls, and antibiotic resistance of isolates was described. RESULTS: Of the 155 subjects with diarrhea, Campylobacter spp. was the most commonly identified pathogen, found in 54 (35%) of the subjects, followed by non-typhoidal Salmonella species found in 36 (23%) subjects. Of the 57 separate C. jejuni and C. coli isolates from these individuals, 51 (89%) were resistant to ciprofloxacin by the disc diffusion method. Nearly one-third of the Campylobacter species were resistant to ampicillin and trimethoprim-sulfamethoxazole. Resistance to azithromycin remained low at 2% (n = 1). CONCLUSIONS: The significant morbidity and marked fluoroquinolone resistance associated with Campylobacter infections in Thailand are important considerations for clinicians providing counseling on appropriate antibacterial regimens for civilian and military travelers.
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The Naval Health Research Center conducted laboratory-based surveillance for febrile respiratory infections at the 2003 Cobra Gold Exercise in Thailand. Seventeen individuals met the case definition for febrile respiratory illness, and diagnostic specimens were obtained from 16. Laboratory testing identified influenza A for 44%; sequence analysis demonstrated that these were Fujian-like influenza strains, which represented the predominant strain found globally in 2003/2004. Other pathogens identified included coronavirus OC43, respiratory syncytial virus, and rhinovirus. Logistical challenges were overcome as laboratory-supported febrile respiratory illness surveillance was conducted during a military training exercise. With heightened concern over the potential for another global influenza pandemic, such surveillance could prove critical for the detection of emerging influenza and respiratory pathogen strains with potential for importation to the United States.
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Vigilância da População , Infecções Respiratórias/epidemiologia , Adulto , Humanos , Masculino , Medicina Militar , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Tailândia/epidemiologiaRESUMO
Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy.
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Bactérias/isolamento & purificação , Coinfecção/complicações , Doença Imunoproliferativa do Intestino Delgado/complicações , Linfoma Difuso de Grandes Células B/complicações , Adulto , Bactérias/classificação , Coinfecção/microbiologia , Humanos , MasculinoRESUMO
Toothpicks are commonly used household items that rarely cause serious injury or infection. Toothpick-related injuries often occur due to ingestion with subsequent trauma/infection at distal sites within the gastrointestinal tract; however, cardiovascular, pleural, and soft tissue infections have been reported. Eikenella corrodens is a gram-negative, facultative anaerobic bacillus found in oral flora associated with bite wound infections. A few case reports describe E. corrodens osteomyelitis from toothpick puncture wounds. We report a case of foot cellulitis and abscess in an elderly diabetic after toothpick puncture injury that was unresponsive to empiric antibiotics. Wound cultures grew E. corrodens and rare Peptostreptococcus species. E. corrodens is resistant to first-generation cephalosporins, macrolides, aminoglycosides, clindamycin, and metronidazole. This case highlights the insidious nature of E. corrodens infections and the need to tailor empiric antibiotics for skin and soft tissue infections based on the mechanism of injury. In addition, this case stresses the importance of protective footwear in diabetics and serves as a cautionary tale regarding the use of seemingly innocuous toothpicks.