Risk of sexually transmitted infections among U.S. military service members in the setting of HIV pre-exposure prophylaxis use.

BACKGROUND: The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP. METHODS: Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model. RESULTS: Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11-0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82-4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60-2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46-11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81-2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance. CONCLUSIONS: The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

Screening tools for predicting mortality of adults with suspected sepsis: an international sepsis cohort validation study.

OBJECTIVES: We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana. DESIGN: Prospective cohort studies. SETTING AND PARTICIPANTS: From 2014 to 2021, participants with two or more SIRS (Systemic Inflammatory Response Syndrome) criteria and suspected infection were enrolled in emergency departments and medical wards at hospitals in Cambodia and Ghana and hospitalised participants with suspected infection were enrolled in the USA. Cox proportional hazards regression was performed, and Harrell's C-statistic calculated to determine 28-day mortality prediction performance of the quick Sequential Organ Failure Assessment (qSOFA) score ≥2, SIRS score ≥3, National Early Warning Score (NEWS) ≥5, Modified Early Warning Score (MEWS) ≥5 or Universal Vital Assessment (UVA) score ≥2. Screening tools were compared with baseline risk (age and sex) with the Wald test. RESULTS: The cohorts included 567 participants (42.9% women) including 187 participants from Kumasi, Ghana, 200 participants from Takeo, Cambodia and 180 participants from Durham, North Carolina in the USA. The pooled mortality was 16.4% at 28 days. The mortality prediction accuracy increased from baseline risk with the MEWS (C-statistic: 0.63, 95% CI 0.58 to 0.68; p=0.002), NEWS (C-statistic: 0.68; 95% CI 0.64 to 0.73; p<0.001), qSOFA (C-statistic: 0.70, 95% CI 0.64 to 0.75; p<0.001), UVA score (C-statistic: 0.73, 95% CI 0.69 to 0.78; p<0.001), but not with SIRS (0.60; 95% CI 0.54 to 0.65; p=0.13). Within individual cohorts, only the UVA score in Ghana performed better than baseline risk (C-statistic: 0.77; 95% CI 0.71 to 0.83; p<0.001). CONCLUSIONS: Among the cohorts, MEWS, NEWS, qSOFA and UVA scores performed better than baseline risk, largely driven by accuracy improvements in Ghana, while SIRS scores did not improve prognostication accuracy. Prognostication scores should be validated within the target population prior to clinical use.

Serum Fc-Mediated Monocyte Phagocytosis Activity Is Stable for Several Months after SARS-CoV-2 Asymptomatic and Mildly Symptomatic Infection.

We investigated the temporal profile of multiple components of the serological response after asymptomatic or mildly symptomatic SARS-CoV-2 infection, in a cohort of 67 previously SARS-CoV-2 naive young adults, up to 8.5 months after infection. We found a significant decrease of spike IgG and neutralization antibody titers from early (11 to 56 days) to late (4 to 8.5 months) time points postinfection. Over the study period, S1-specific IgG levels declined significantly faster than that of the S2-specific IgG. Further, serum antibodies from PCR-confirmed participants cross-recognized S2, but not S1, of the betacoronaviruses HKU1 and OC43, suggesting a greater degree of cross-reactivity of S2 among betacoronaviruses. Antibody-Dependent Natural Killer cell Activation (ADNKA) was detected at the early time point but significantly decreased at the late time point. Induction of serum Antibody-Dependent Monocyte Phagocytosis (ADMP) was detected in all the infected participants, and its levels remained stable over time. Additionally, a reduced percentage of participants had detectable neutralizing activity against the Beta (50%), Gamma (61 to 67%), and Delta (90 to 94%) variants, both early and late postinfection, compared to the ancestral strain (100%). Antibody binding to S1 and RBD of Beta, Gamma, Delta (1.7 to 2.3-fold decrease), and Omicron (10 to 16-fold decrease) variants was also significantly reduced compared to the ancestral SARS-CoV-2 strain. Overall, we found variable temporal profiles of specific components and functionality of the serological response to SARS-CoV-2 in young adults, which is characterized by lasting, but decreased, neutralizing activity and antibody binding to S1, stable ADMP activity, and relatively stable S2-specific IgG levels. IMPORTANCE Adaptive immunity mediated by antibodies is important for controlling SARS-CoV-2 infection. While vaccines against COVID-19 are currently widely distributed, a high proportion of the global population is still unvaccinated. Therefore, understanding the dynamics and maintenance of the naive humoral immune response to SARS-CoV-2 is of great importance. In addition, long-term responses after asymptomatic infection are not well-characterized, given the challenges in identifying such cases. Here, we investigated the longitudinal humoral profile in a well-characterized cohort of young adults with documented asymptomatic or mildly symptomatic SARS-CoV-2 infection. By analyzing samples collected preinfection, early after infection and during late convalescence, we found that, while neutralizing activity decreased over time, high levels of serum S2 IgG and Antibody-Dependent Monocyte Phagocytosis (ADMP) activity were maintained up to 8.5 months after infection. This suggests that a subset of antibodies with specific functions could contribute to long-term protection against SARS-CoV-2 in convalescent unvaccinated individuals.

Asymptomatic or symptomatic SARS-CoV-2 infection plus vaccination confers increased adaptive immunity to variants of concern.

The ongoing evolution of SARS-CoV-2 requires monitoring the capability of immune responses to cross-recognize Variants of Concern (VOC). In this cross-sectional study, we examined serological and cell-mediated immune memory to SARS-CoV-2 variants, including Omicron, among a cohort of 18-21-year-old Marines with a history of either asymptomatic or mild SARS-CoV-2 infection 6 to 14 months earlier. Among the 210 participants in the study, 169 were unvaccinated while 41 received 2 doses of mRNA-based COVID-19 vaccines. Vaccination of previously infected participants strongly boosted neutralizing and binding activity and memory B and T cell responses including the recognition of Omicron, compared to infected but unvaccinated participants. Additionally, no measurable differences were observed in immune memory in healthy young adults with previous symptomatic or asymptomatic infections, for ancestral or variant strains. These results provide mechanistic immunological insights into population-based differences observed in immunity against Omicron and other variants among individuals with different clinical histories.

Hepatitis B seroprevalence in the U.S. military and its impact on potential screening strategies.

INTRODUCTION: Knowledge of the contemporary epidemiology of hepatitis B virus (HBV) infection among military personnel can inform potential Department of Defense (DoD) screening policy and infection and disease control strategies. MATERIALS AND METHODS: HBV infection status at accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period from 2007 to 2010. A cost model was developed from the perspective of the Department of Defense for a program to integrate HBV infection screening of applicants for military service into the existing screening program of screening new accessions for vaccine-preventable infections. RESULTS: The prevalence of chronic HBV infection at accession was 2.3/1,000 (95% CI: 1.4, 3.2); most cases (16/21, 76%) identified after deployment were present at accession. There were 110 military service-related HBV infections identified. Screening accessions who are identified as HBV susceptible with HBV surface antigen followed by HBV surface antigen neutralization for confirmation offered no cost advantage over not screening and resulted in a net annual increase in cost of $5.78 million. However, screening would exclude as many as 514 HBV cases each year from accession. CONCLUSIONS: Screening for HBV infection at service entry would potentially reduce chronic HBV infection in the force, decrease the threat of transfusion-transmitted HBV infection in the battlefield blood supply, and lead to earlier diagnosis and linkage to care; however, applicant screening is not cost saving. Service-related incident infections indicate a durable threat, the need for improved laboratory-based surveillance tools, and mandate review of immunization policy and practice.

Pre-positioned Outbreak Research: The Joint Medical Emerging Diseases Intervention Clinical Capability Experience in Uganda.

The West Africa Ebola virus disease outbreak of 2014-2016 demonstrated that responses to viral hemorrhagic fever epidemics must go beyond emergency stopgap measures and should incorporate high-quality medical care and clinical research. Optimal patient management is essential to improving outcomes, and it must be implemented regardless of geographical location or patient socioeconomic status. Coupling clinical research with improved care has a significant added benefit: Improved data quality and management can guide the development of more effective supportive care algorithms and can support regulatory approvals of investigational medical countermeasures (MCMs), which can alter the cycle of emergency response to reemerging pathogens. However, executing clinical research during outbreaks of high-consequence pathogens is complicated and comes with ethical and research regulatory challenges. Aggressive care and excellent quality control must be balanced by the requirements of an appropriate infection prevention and control posture for healthcare workers and by overcoming the resource limitations inherent in many outbreak settings. The Joint Mobile Emerging Disease Intervention Clinical Capability was established in 2015 to develop a high-quality clinical trial capability in Uganda to support rigorous evaluation of MCMs targeting high-consequence pathogens like Ebola virus. This capability assembles clinicians, laboratorians, clinical researchers, logisticians, and regulatory professionals trained in infection prevention and control and in good clinical and good clinical laboratory practices. The resulting team is prepared to provide high-quality medical care and clinical research during high-consequence outbreaks.

Virologic Suppression in U.S. Navy Personnel Living with HIV Infection and Serving in Operational Assignments.

INTRODUCTION: Current United States Navy policy supports the continuation of duty for active duty (AD) service members living with HIV infection. The creation of this policy is instrumental to prevent exclusion and to promote career expansion and promotional opportunities for AD service members infected with HIV. The established instruction parallels the HIV care continuum, a widely accepted public health model. No studies have been done to determine whether allowing service members to fill operational and Outside the Continental United States (OCONUS) assignments disrupts this continuum of care. This retrospective study aims to evaluate how an operational or OCONUS assignment impacts the ability of an HIV AD service members to receive the standard of care HIV medical treatment and maintain viral suppression. MATERIALS/METHODS: A retrospective chart review was performed on the health records of 20 United States AD Navy service members with HIV who were placed in OCONUS or large ship assignments per current U.S. Navy policy. Health records were reviewed during the service member's assignment. Viral loads were documented immediately prior and at 6 months after starting their new assignment. Changes to anti-retroviral medications and the medical treatment facility, including the specialty of the treating provider were recorded. RESULTS: The results demonstrate no significant change in the service member's viral load during the first 6 months in an operational or OCONUS assignment. Members still had access to care including medications and specialty providers based on the locality. CONCLUSION: All service members within this review were able to maintain viral suppression despite the location of their assignments. This limited study suggests that care is accessible and the standard HIV care continuum is maintained while deployed or stationed overseas.

Provider Knowledge Gaps in HIV PrEP Affect Practice Patterns in the US Navy.

INTRODUCTION: Although HIV pre-exposure prophylaxis (PrEP) is available at no cost to personnel in the United States (U.S.) military, uptake has been lower than expected. An online survey was conducted assessing current knowledge, perceptions, and attitudes of primary care providers in the U.S. Navy. MATERIALS AND METHODS: A cross-sectional anonymous online survey was conducted among U.S. Navy healthcare providers in active service. Providers' demographics, medical practice and PrEP experience, and attitudes regarding PrEP were assessed by self-rated PrEP knowledge. RESULTS: Greater than half of respondents reported being knowledgeable about PrEP and a majority (78%) supported the provision of PrEP in the military health system. However, only 19% had ever prescribed PrEP. Self-reports of having been questioned by a patient about PrEP, having high levels of comfort discussing sexual risk behaviors, and being in a specialty of infectious disease, occupational health, or preventive medicine were associated with increased knowledge about PrEP. The more knowledgeable a provider was about PrEP, the more likely they were to prescribe it (29% vs. 6%). CONCLUSIONS: Although Navy providers were supportive of the provision of PrEP by the military, knowledge gaps remain. Training to address the knowledge deficit as well as improving sexual history taking are potential areas to target in implementing PrEP in primary care specialties.

Next-generation sequencing of HIV-1 single genome amplicons.

The analysis of HIV-1 sequences has helped understand the viral molecular epidemiology, monitor the development of antiretroviral drug resistance, and design candidate vaccines. The introduction of single genome amplification (SGA) has been a major advancement in the field, allowing for the characterization of multiple sequences per patient while preserving linkage among polymorphisms in the same viral genome copy. Sequencing of SGA amplicons is performed by capillary Sanger sequencing, which presents low throughput, requires a high amount of template, and is highly sensitive to template/primer mismatching. In order to meet the increasing demand for HIV-1 SGA amplicon sequencing, we have developed a platform based on benchtop next-generation sequencing (NGS) (IonTorrent) accompanied by a bioinformatics pipeline capable of running on computer resources commonly available at research laboratories. During assay validation, the NGS-based sequencing of 10 HIV-1 env SGA amplicons was fully concordant with Sanger sequencing. The field test was conducted on plasma samples from 10 US Navy and Marine service members with recent HIV-1 infection (sampling interval: 2005-2010; plasma viral load: 5,884-194,984 copies/ml). The NGS analysis of 101 SGA amplicons (median: 10 amplicons/individual) showed within-individual viral sequence profiles expected in individuals at this disease stage, including individuals with highly homogeneous quasispecies, individuals with two highly homogeneous viral lineages, and individuals with heterogeneous viral populations. In a scalability assessment using the Ion Chef automated system, 41/43 tested env SGA amplicons (95%) multiplexed on a single Ion 318 chip showed consistent gene-wide coverage >50×. With lower sample requirements and higher throughput, this approach is suitable to support the increasing demand for high-quality and cost-effective HIV-1 sequences in fields such as molecular epidemiology, and development of preventive and therapeutic strategies.

HIV Preexposure Prophylaxis in the U.S. Military Services - 2014-2016.

Human immunodeficiency virus (HIV) infection is a substantial health concern for the U.S. Department of Defense (DoD) and for service members stationed throughout the world. Each year, approximately 350 new HIV infections are diagnosed in members of the U.S. military services, with most infections acquired within the United States (1). The DoD populations most affected by HIV mirror those in the U.S. civilian population; the highest rates of new military diagnoses are in men and blacks or African Americans (blacks) (1). Blacks are disproportionally affected, and most new diagnoses occur among men who have sex with men (MSM). HIV preexposure prophylaxis (PrEP) is approximately 90% effective in preventing HIV infection when used properly (2), and an increasing number of active duty personnel have used HIV prevention services and PrEP in the military health system since the repeal of "Don't Ask, Don't Tell"* in 2011 (3). Military health system and service records were reviewed to describe HIV PrEP use among military personnel, and military health care providers were surveyed to assess HIV PrEP knowledge and attitudes. Among 769 service members prescribed PrEP during February 1, 2014-June 10, 2016, 60% received prescriptions from an infectious disease provider, 19% were black men, and 42% were aged >28 years. Half of surveyed military health care providers self-rated their PrEP knowledge as poor. DoD is developing new policy to address access to care challenges by defining requirements and establishing pathways for universal patient access to PrEP.

HIV PrEP in the Military: Experience at a Tertiary Care Military Medical Center.

Objectives: We evaluated human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) administration at the Walter Reed National Military Medical Center (WRNMMC), which serves a geographic area at high risk of HIV infection. Methods: Medical records were reviewed for all patients initiating PrEP at WRNMMC from November 1, 2013, to March 30, 2016. Demographic, laboratory, clinical, and risk exposure characteristics and outcomes were described. Results: One hundred fifty-nine patients received PrEP; 133 (84%) patients were active duty, 95 (60%) patients were over 28 yr old. The majority were non-Hispanic Whites (n = 87, 55%). The median men who have sex with men (MSM) risk index score was 18.0 (IQR 12.0-22.0); 20 patients scored less than 10. One hundred and thirty-one (82%) patients remained on PrEP through the evaluation period. Patients mainly discontinued PrEP for service-related or toxicity reasons. Incident STIs occurred in 31 (19%) patients. No cases of HIV seroconversion were observed. Conclusions: In this first description of PrEP utilization in a U.S. military health care system, a significant number of patients were non-Hispanic Whites, well-educated, were older, or were otherwise at low risk for HIV acquisition. Further effort is needed to enhance PrEP use among the higher risk young African-American MSM population, and further studies are needed to determine the cost-effectiveness of PrEP in individuals who are not categorized as high risk.

NK cell degranulation as a marker for measuring antibody-dependent cytotoxicity in neutralizing and non-neutralizing human sera from dengue patients.

The study assessed antibody-dependent NK cell degranulation, a biomarker relevant to antibody-dependent cell cytotoxicity (ADCC), to analyze dengue immune sera. We first determined binding intensity of patient sera to the surface of DENV-infected cells and examined the types of antigens expressed on infected cells. Antigens from pre-membrane (PreM) and envelope (E), but not from NS proteins were detected on the surface of infected cells. After adding NK cells to infected target cells previously treated with patient sera, rapid NK cell degranulation was observed. Non-neutralizing patient sera generated comparable NK cell degranulation as that of neutralizing sera, suggesting ADCC may be a protective mechanism apart from Ab neutralization. The level of NK cell degranulation varied dramatically among human individuals and was associated with the level of CD16 expression on NK cells, informing on the complexity of ADCC among human population.

Knowledge, attitudes, and beliefs about HIV pre-exposure prophylaxis among US Air Force Health Care Providers.

Providers are central to effective implementation of HIV pre-exposure prophylaxis (PrEP). Primary care providers (PCP) and infectious disease physicians (ID) in the US Air Force (USAF) participated in a cross-sectional survey regarding knowledge, attitudes, and beliefs toward HIV PrEP. Characteristics associated with PrEP knowledge were assessed in univariate and multivariate analyses.Among 403 (40% of 1015 providers) participants, 9% (PCP 383, ID 20) ever prescribed PrEP. In univariate analysis, years in practice, number of HIV-infected patients treated in the past 12 months, past prescription of antiretrovirals for HIV prevention, frequency of prescribing PrEP in the past 12 months, and ever being questioned by a patient about PrEP were associated with PrEP knowledge (P < 0.05). In multivariate analysis, providers who had ever prescribed antiretrovirals to prevent HIV (AOR: 2.37, 95% CI: 1.27-4.42) had greater odds of high PrEP knowledge. Despite concerns about medication side effects (overall 67%: PCP 68%, ID 85%) and prescribing PrEP without clear evidence (overall 60%: PCP 65%, ID 62%), 64% (PCP 65%, ID 85%) of participants indicated PrEP should be offered in the Military Health System and 68% (PCP 70%, ID 100%) disagreed with the statement that their patient population was not at risk for HIV infection.Successful PrEP implementation in the USAF will require continued education and training of primary care providers to improve knowledge and mitigate concerns about PrEP.

The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java.

BACKGROUND: Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000-2004 and 2006-2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. CONCLUSIONS/SIGNIFICANCE: Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with most infections resulting in asymptomatic disease. The circulation of all four serotypes of dengue virus was observed in most years of the study.

Costs and consequences: Hepatitis C seroprevalence in the military and its impact on potential screening strategies.

UNLABELLED: Knowledge of the contemporary epidemiology of hepatitis C viral (HCV) infection among military personnel can inform potential Department of Defense screening policy. HCV infection status at the time of accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period 2007-2010. A cost model was developed from the perspective of the Department of Defense for a military applicant screening program. Return on investment was based on comparison between screening program costs and potential treatment costs avoided. The prevalence of HCV antibody-positive and chronic HCV infection at accession among younger recently deployed military personnel born after 1965 was 0.98/1000 (95% confidence interval 0.45-1.85) and 0.43/1000 (95% confidence interval 0.12-1.11), respectively. Among these, service-related incidence was low; 64% of infections were present at the time of accession. With no screening, the cost to the Department of Defense of treating the estimated 93 cases of chronic HCV cases from a single year's accession cohort was $9.3 million. Screening with the HCV antibody test followed by the nucleic acid test for confirmation yielded a net annual savings and a $3.1 million dollar advantage over not screening. CONCLUSIONS: Applicant screening will reduce chronic HCV infection in the force, result in a small system costs savings, and decrease the threat of transfusion-transmitted HCV infection in the battlefield blood supply and may lead to earlier diagnosis and linkage to care; initiation of an applicant screening program will require ongoing evaluation that considers changes in the treatment cost and practice landscape, screening options, and the epidemiology of HCV in the applicant/accession and overall force populations.

Surveillance of influenza in Indonesia, 2003­2007.

BACKGROUND: Longitudinal data are limited about the circulating strains of influenza viruses and their public health impact in Indonesia. We conducted influenza surveillance among outpatients and hospitalized patients with influenza-like illness (ILI) across the Indonesian archipelago from 2003 through 2007. METHODOLOGY: Demographic, clinical data, and respiratory specimens were collected for 4236 ILI patients tested for influenza virus infection by RT-PCR and viral culture. PRINCIPAL FINDINGS: Influenza A and B viruses co-circulated year-round with seasonal peaks in influenza A virus activity during the rainy season (December­January). During 2003­2007, influenza viruses were identified in 20·1% (4236 / 21 030) of ILI patients, including 20·1% (4015 / 20 012) of outpatients, and 21·7% (221 / 1018) of inpatients. One H5N1 case was identified retrospectively in an outpatient with ILI. Antigenic drift in circulating influenza A and B virus strains was detected during the surveillance period in Indonesia. In a few instances, antigenically drifted viruses similar to the World Health Organization (WHO) vaccine strains were detected earlier than the date of their designation by WHO. CONCLUSIONS: Influenza A and B virus infections are an important cause of influenza-like illness among outpatients and hospitalized patients in Indonesia. While year-round circulation of influenza viruses occurs, prevention and control strategies should be focused upon the seasonal peak during rainy season months. Ongoing virologic surveillance and influenza disease burden studies in Indonesia are important priorities to better understand the public health impact of influenza in South-East Asia and the implications of influenza viral evolution and global spread.

Infection and activation of human peripheral blood monocytes by dengue viruses through the mechanism of antibody-dependent enhancement.

Human monocytes are susceptible to dengue virus (DV) infection through an FcR-dependent pathway known as antibody-dependent enhancement (ADE). In this study, infection enhancement was observed when purified monocytes were infected with DV serotypes in the presence of serially diluted immune serum antibodies. Analyzing binding of the DV-antibody immune complexes to monocytes by quantifying the amount of viruses attached to monocytes, we found that binding did not correlate with the input amount of antibodies; rather, it peaked at suboptimal antibody concentrations, correlating with the observed infection enhancement. These results suggested that immune complexes are involved in hindering DV from binding to FcR-bearing cells; when such a protective feature is weakened, enhancement of viral attachment and ADE are observed. Further, increased cytokine production (TNF-alpha and IFN-alpha), and costimulatory marker expression (CD86 and CD40), were found to be associated with infection enhancement, suggesting a pathological role of ADE-affected monocytes in dengue hemorrhagic diseases.

Development of dengue DNA vaccines.

Vaccination with plasmid DNA against infectious pathogens including dengue is an active area of investigation. By design, DNA vaccines are able to elicit both antibody responses and cellular immune responses capable of mediating long-term protection. Great technical improvements have been made in dengue DNA vaccine constructs and trials are underway to study these in the clinic. The scope of this review is to highlight the rich history of this vaccine platform and the work in dengue DNA vaccines accomplished by scientists at the Naval Medical Research Center. This work resulted in the only dengue DNA vaccine tested in a clinical trial to date. Additional advancements paving the road ahead in dengue DNA vaccine development are also discussed.