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1.  Mohn et al (J Infect Dis 2016; 214:722–31) 
doi:10.1093/infdis/jiw424
PMCID: PMC5144659  PMID: 27697891
2.  Armah et al (J Infect Dis 2016; 213:1678–85) 
doi:10.1093/infdis/jiw265
PMCID: PMC5144671  PMID: 27485358
3.  Matsumiya et al (J Infect Dis 2015; 211:1499–509) 
doi:10.1093/infdis/jiw339
PMCID: PMC5144672  PMID: 27503368
4.  Payne et al (J Infect Dis 2016; 213:1743–51) 
doi:10.1093/infdis/jiw202
PMCID: PMC5144673  PMID: 27357343
5.  Kamau et al (J Infect Dis 2015; 211:1352–5) 
doi:10.1093/infdis/jiv595
PMCID: PMC4826904  PMID: 26705199
6.  Dent et al (J Infect Dis 2015; 212:1429–38) 
doi:10.1093/infdis/jiv559
PMCID: PMC5144669  PMID: 26657090
7.  Grabowski et al (J Infect Dis 2015; 212:1613–7) 
doi:10.1093/infdis/jiv560
PMCID: PMC5144670  PMID: 26657091
8.  Suarez et al (J Infect Dis 2015; 212:213–22) 
doi:10.1093/infdis/jiv514
PMCID: PMC4838205  PMID: 26598315
9.  Gut Colonization of Healthy Children and Their Mothers With Pathogenic Ciprofloxacin-Resistant Escherichia coli 
The Journal of Infectious Diseases  2015;212(12):1862-1868.
Background. The reservoir of pathogenic ciprofloxacin-resistant Escherichia coli remains unknown.
Methods. We conducted a prospective cohort study of 80 healthy twins and their mothers to determine the frequency of excretion of ciprofloxacin-resistant, potentially pathogenic E. coli. Stool specimens were cultured selectively for ciprofloxacin-resistant gram-negative bacteria. Isolates were categorized on the basis of additional resistance and virulence profiles. We also prospectively collected clinical metadata.
Results. Fifteen children (19%) and 8 mothers (20%) excreted ciprofloxacin-resistant E. coli at least once. Overall, 33% of 40 families had at least 1 member whose stool specimen yielded ciprofloxacin-resistant E. coli on culture. Fifty-seven submitted stool specimens (2.8%) contained such organisms; clones ST131-H30 and ST405 accounted for 52 and 5 of the positive specimens, respectively. Length of hospital stay after birth (P = .002) and maternal colonization (P = .0001) were associated with subsequent childhood carriage of ciprofloxacin-resistant E. coli; antibiotic use, acid suppression, sex, mode of delivery, and maternal perinatal antibiotic use were not. Ciprofloxacin-resistant E. coli were usually resistant to additional antibiotic classes, and all had virulence genotypes typical of extraintestinal pathogenic E. coli.
Conclusions. Healthy children and their mothers commonly harbor ciprofloxacin-resistant E. coli with pathogenic potential.
doi:10.1093/infdis/jiv278
PMCID: PMC4655851  PMID: 25969564
ciprofloxacin-resistant E. coli; extra-intestinal pathogenic E. coli; E. coli ST131-H30; E. coli ST405; urinary tract infections
10.  The Rise of Fluoroquinolone-Resistant Escherichia coli in the Community: Scarier Than We Thought 
The Journal of Infectious Diseases  2015;212(12):1853-1855.
doi:10.1093/infdis/jiv279
PMCID: PMC4655852  PMID: 25969562
E. coli; fluoroquinolone; antibiotic resistance; transmission
11.  Induction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production 
The Journal of Infectious Diseases  2015;212(12):1999-2010.
The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T-lymphocyte attenuator-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed death-1 (PD-1) are involved in the functional impairment of T cells during infection. Our goal was to define the role of these molecules during P. vivax malaria. We demonstrate that infection triggers the expression of regulatory molecules on T cells. The pattern of expression differs in CD4+ and CD8+ T cells. Higher frequencies of CD4+ express more than 1 regulatory molecule compared to CD8+ T cells. Moreover, lower proportions of CD4+ T cells coexpress regulatory molecules, but are still able to proliferate. Importantly, simultaneously blockade of the CLTA-4, PD-1, and T-cell immunoglobulin and mucin–3 signaling restores the cytokine production by antigen-specific cells. These data support the hypothesis that upregulation of inhibitory receptors on T cells during P. vivax malaria impairs parasite-specific T-cell effector function.
doi:10.1093/infdis/jiv306
PMCID: PMC4655853  PMID: 26019284
malaria; Plasmodium vivax; regulatory molecules; T cells
12.  Persistence of Antibodies to Influenza Hemagglutinin and Neuraminidase Following One or Two Years of Influenza Vaccination 
The Journal of Infectious Diseases  2015;212(12):1914-1922.
Background. Antibody titers to influenza hemagglutinin (HA) and neuraminidase (NA) surface antigens increase in the weeks after infection or vaccination, and decrease over time thereafter. However, the rate of decline has been debated.
Methods. Healthy adults participating in a randomized placebo-controlled trial of inactivated (IIV) and live-attenuated (LAIV) influenza vaccines provided blood specimens immediately prior to vaccination and at 1, 6, 12, and 18 months postvaccination. Approximately half had also been vaccinated in the prior year. Rates of hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titer decline in the absence of infection were estimated.
Results. HAI and NAI titers decreased slowly over 18 months; overall, a 2-fold decrease in antibody titer was estimated to take >600 days for all HA and NA targets. Rates of decline were fastest among IIV recipients, explained in part by faster declines with higher peak postvaccination titer. IIV and LAIV recipients vaccinated 2 consecutive years exhibited significantly lower HAI titers following vaccination in the second year, but rates of persistence were similar.
Conclusions. Antibody titers to influenza HA and NA antigens may persist over multiple seasons; however, antigenic drift of circulating viruses may still necessitate annual vaccination. Vaccine seroresponse may be impaired with repeated vaccination.
doi:10.1093/infdis/jiv313
PMCID: PMC4655854  PMID: 26014800
antibody persistence; hemagglutinin; immune correlates; influenza; influenza vaccine; longevity of antibody; neuraminidase; serologic assays; waning
13.  Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial 
The Journal of Infectious Diseases  2015;212(12):1949-1956.
Background. Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear.
Methods. We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates.
Results. 64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by −0.50 (−0.86–0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL.
Conclusions. Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions.
Clinical Trials Registration. NCT01448616
doi:10.1093/infdis/jiv317
PMCID: PMC4655855  PMID: 26044291
herpes simplex virus-2 (HSV-2); tenofovir; vaginal microbicide; HSV-2 transmission; HIV acquisition; genital herpes
14.  Parallel Epidemics of Community-Associated Methicillin-Resistant Staphylococcus aureus USA300 Infection in North and South America 
The Journal of Infectious Diseases  2015;212(12):1874-1882.
Background. The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) epidemic in the United States is attributed to the spread of the USA300 clone. An epidemic of CA-MRSA closely related to USA300 has occurred in northern South America (USA300 Latin-American variant, USA300-LV). Using phylogenomic analysis, we aimed to understand the relationships between these 2 epidemics.
Methods. We sequenced the genomes of 51 MRSA clinical isolates collected between 1999 and 2012 from the United States, Colombia, Venezuela, and Ecuador. Phylogenetic analysis was used to infer the relationships and times since the divergence of the major clades.
Results. Phylogenetic analyses revealed 2 dominant clades that segregated by geographical region, had a putative common ancestor in 1975, and originated in 1989, in North America, and in 1985, in South America. Emergence of these parallel epidemics coincides with the independent acquisition of the arginine catabolic mobile element (ACME) in North American isolates and a novel copper and mercury resistance (COMER) mobile element in South American isolates.
Conclusions. Our results reveal the existence of 2 parallel USA300 epidemics that shared a recent common ancestor. The simultaneous rapid dissemination of these 2 epidemic clades suggests the presence of shared, potentially convergent adaptations that enhance fitness and ability to spread.
doi:10.1093/infdis/jiv320
PMCID: PMC4655856  PMID: 26048971
USA300; USA300-LV; MRSA; epidemics
15.  Protective Effect of Intranasal Regimens Containing Peptidic Middle East Respiratory Syndrome Coronavirus Fusion Inhibitor Against MERS-CoV Infection 
The Journal of Infectious Diseases  2015;212(12):1894-1903.
To gain entry into the target cell, Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) uses its spike (S) protein S2 subunit to fuse with the plasma or endosomal membrane. Previous work identified a peptide derived from the heptad repeat (HR) 2 domain in S2 subunit, HR2P, which potently blocked MERS-CoV S protein–mediated membrane fusion. Here, we tested an HR2P analogue with improved pharmaceutical property, HR2P-M2, for its inhibitory activity against MERS-CoV infection in vitro and in vivo. HR2P-M2 was highly effective in inhibiting MERS-CoV S protein–mediated cell-cell fusion and infection by pseudoviruses expressing MERS-CoV S protein with or without mutation in the HR1 region. It interacted with the HR1 peptide to form stable α-helical complex and blocked six-helix bundle formation between the HR1 and HR2 domains in the viral S protein. Intranasally administered HR2P-M2 effectively protected adenovirus serotype-5–human dipeptidyl peptidase 4–transduced mice from infection by MERS-CoV strains with or without mutations in the HR1 region of S protein, with >1000-fold reduction of viral titers in lung, and the protection was enhanced by combining HR2P-M2 with interferon β. These results indicate that this combination regimen merits further development to prevent MERS in high-risk populations, including healthcare workers and patient family members, and to treat MERS-CoV–infected patients.
doi:10.1093/infdis/jiv325
PMCID: PMC4655857  PMID: 26164863
MERS-CoV; fusion inhibitor; peptide; interferon
16.  Protection Against Rectal Chimeric Simian/Human Immunodeficiency Virus Transmission in Macaques by Rectal-Specific Gel Formulations of Maraviroc and Tenofovir 
The Journal of Infectious Diseases  2015;212(12):1988-1995.
Background. Rectal human immunodeficiency virus (HIV) transmission is an important driver of the HIV epidemic. Optimally formulated gels of antiretroviral drugs are under development for preventing rectally acquired HIV. We investigated in a macaque model the pharmacokinetics and efficacy of 3 rectal gel formulations
Methods. Single-dose pharmacokinetics of low-osmolar 1% maraviroc (MVC), 1% tenofovir (TFV), or 1% MVC/1% TFV combination gel were evaluated in blood, rectal fluids, colorectal biopsy specimens, and rectal lymphocytes. Efficacy was evaluated over 10 twice-weekly rectal SHIV162p3 challenges in rhesus macaques that received either placebo (n = 7), MVC (n = 6), TFV (n = 6), or MVC/TFV (n = 6) gel 30 minutes before each challenge.
Results. MVC and TFV were detected in plasma 30 minutes after gel application and remained above 95% inhibitory concentrations in rectal fluids at 24 hours. MVC, TFV, and TFV diphosphate (TFV-DP) concentrations in colorectal tissues collected up to 30 cm from the anal margin were all high at 2 hours, demonstrating rapid and extended tissue dosing. TFV-DP concentrations in tissue homogenates and rectal lymphocytes were highly correlated (r2 = 0.82). All 3 gel formulations were highly protective (82% efficacy; P ≤ .02 by the log-rank test).
Conclusions. Desirable pharmacokinetic profiles and high efficacy in this macaque model support the clinical development of these gel formulations for preventing rectal HIV infection.
doi:10.1093/infdis/jiv334
PMCID: PMC4655858  PMID: 26071566
HIV prevention; rectal microbicides; maraviroc; tenofovir; macaque model; repeat-challenge
17.  Kinetics of Hemagglutination-Inhibiting Antibodies Following Maternal Influenza Vaccination Among Mothers With and Those Without HIV Infection and Their Infants 
The Journal of Infectious Diseases  2015;212(12):1976-1987.
Background. We evaluated the immunogenicity of trivalent inactivated influenza vaccine (IIV3) in pregnant women with and those without human immunodeficiency virus (HIV) infection and the persistence of hemagglutination-inhibiting antibodies in mothers and infants.
Methods. Antibodies were measured before vaccination, 1 month after vaccination, at delivery, and at postpartum week 24 in mothers and within 1 week of birth and at 8, 16, and 24 weeks of age in infants.
Results. We enrolled 98 HIV-uninfected and 100 HIV-infected pregnant women, including 93% with a CD4+ T-cell count of ≥200 cells/µL. Compared with HIV-uninfected women, HIV-infected women had lower seroconversion rates (ranging from 63%–92% vs 36%–40%), lower antibody titers through postpartum week 24, and overlapping antibody half-lives (ranging from 106–121 vs 87–153 days). Infant titers were lower than the maternal titers within 1 week of delivery, regardless of vaccine strain and HIV exposure status. Compared with HIV-unexposed infants, HIV-exposed infants had a similar transplacental influenza virus antibody transfer ratio, lower titers, and a lower frequency of titers ≥1:40 (ranging from 82%–95% vs 43%–79%) at birth and higher antibody half-lives (ranging from 43–45 vs 56–65 days).
Conclusions. Compared with HIV-uninfected pregnant women, HIV-infected pregnant women had lower antibody responses and persistence. Compared with HIV-unexposed infants, HIV-exposed infants had lower antibody levels at birth but similar antibody levels after 8 weeks of life. Early IIV3 administration during pregnancy did not decrease antibody titers among infants at birth.
doi:10.1093/infdis/jiv339
PMCID: PMC4655859  PMID: 26080370
influenza vaccine; HIV; immunogenicity; pregnancy; transplacental antibody transfer
18.  A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia 
The Journal of Infectious Diseases  2015;212(12):1939-1948.
Background. Secondary bacterial infections after influenza can be a serious problem, especially in young children and the elderly, yet the efficacy of current vaccines is limited. Earlier work demonstrated that a replication-incompetent PB2-knockout (PB2-KO) influenza virus possessing a foreign gene in the coding region of its PB2 segment can serve as a platform for a bivalent vaccine.
Methods. In the current study, we generated the PB2-KO virus expressing pneumococcal surface protein A (PspA), PB2-KO-PspA virus, the replication of which is restricted to PB2-expressing cells. We then examined the protective efficacy of intranasal immunization with this virus as a bivalent vaccine in a mouse model.
Results. High levels of influenza virus–specific and PspA-specific antibodies were induced in the serum and airways of immunized mice. The intranasally immunized mice were protected from lethal doses of influenza virus or Streptococcus pneumoniae. These mice were also completely protected from secondary pneumococcal pneumonia after influenza virus infection.
Conclusions. These findings indicate that our recombinant influenza virus serves as a novel and powerful bivalent vaccine against primary and secondary pneumococcal pneumonia as well as influenza.
doi:10.1093/infdis/jiv341
PMCID: PMC4655860  PMID: 26123562
secondary pneumococcal pneumonia; replication-incompetent influenza virus; bivalent vaccine
19.  Reply to Nalin 
The Journal of Infectious Diseases  2015;212(12):2021-2022.
doi:10.1093/infdis/jiv394
PMCID: PMC4668769  PMID: 26272934
20.  Epidemiology of Chikungunya in the Americas 
The Journal of Infectious Diseases  2016;214(Suppl 5):S441-S445.
Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya.
doi:10.1093/infdis/jiw390
PMCID: PMC5137246  PMID: 27920170
chikungunya; epidemiology; arbovirus; emerging disease; Americas
21.  Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial 
The Journal of Infectious Diseases  2016;214(12):1831-1839.
Background. Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir.
Methods. A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence.
Results. All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02–.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06–1.49; P = .14) and 58% lower (0.42; .18–.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point.
Conclusions. Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas.
Clinical Trials Registration. NCT02329301.
doi:10.1093/infdis/jiw416
PMCID: PMC5142084  PMID: 27923947
malaria; elimination; mass drug administration
22.  Serum Procalcitonin Measurement and Viral Testing to Guide Antibiotic Use for Respiratory Infections in Hospitalized Adults: A Randomized Controlled Trial 
The Journal of Infectious Diseases  2015;212(11):1692-1700.
Background. Viral lower respiratory tract illness (LRTI) frequently causes adult hospitalization and is linked to antibiotic overuse. European studies suggest that the serum procalcitonin (PCT) level may be used to guide antibiotic therapy. We conducted a trial assessing the feasibility of using PCT algorithms with viral testing to guide antibiotic use in a US hospital.
Methods. Three hundred patients hospitalized with nonpneumonic LRTI during October 2013–April 2014 were randomly assigned at a ratio of 1:1 to receive standard care or PCT-guided care and viral PCR testing. The primary outcome was antibiotic exposure, and safety was assessed at 1 and 3 months.
Results. Among the 151 patients in the intervention group, viruses were identified in 42% (63), and 83% (126) had PCT values of <0.25 µg/mL. There were no significant differences in antibiotic use or adverse events between intervention patients and those in the nonintervention group. Subgroup analyses revealed fewer subjects with positive results of viral testing and low PCT values who were discharged receiving antibiotics (20% vs 45%; P = .002) and shorter antibiotic durations among algorithm-adherent intervention patients versus nonintervention patients (2.0 vs 4.0 days; P = .004). Compared with historical controls (from 2008–2011), antibiotic duration in nonintervention patients decreased by 2 days (6.0 vs 4.0 days; P < .001), suggesting a study effect.
Conclusions. Although antibiotic use was similar in the 2 arms, subgroup analyses of intervention patients suggest that physicians responded to viral and biomarker data. These data can inform the design of future US studies.
Clinical Trials Registration. NCT01907659.
doi:10.1093/infdis/jiv252
PMCID: PMC4633755  PMID: 25910632
procalcitonin; viral testing; antibiotic use; respiratory infections
23.  E119D Neuraminidase Mutation Conferring Pan-Resistance to Neuraminidase Inhibitors in an A(H1N1)pdm09 Isolate From a Stem-Cell Transplant Recipient 
The Journal of Infectious Diseases  2015;212(11):1726-1734.
Background. An influenza A(H1N1)pdm09 infection was diagnosed in a hematopoietic stem cell transplant recipient during conditioning regimen. He was treated with oral oseltamivir, later combined with intravenous zanamivir. The H275Y neuraminidase (NA) mutation was first detected, and an E119D NA mutation was identified during zanamivir therapy.
Methods. Recombinant wild-type (WT) E119D and E119D/H275Y A(H1N1)pdm09 NA variants were generated by reverse genetics. Susceptibility to NA inhibitors (NAIs) was evaluated with a fluorometric assay using the 2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA) substrate. Susceptibility to favipiravir (T-705) was assessed using plaque reduction assays. The NA affinity and velocity values were determined with NA enzymatic studies.
Results. We identified an influenza A(H1N1)pdm09 E119D mutant that exhibited a marked increase in the 50% inhibitory concentrations against all tested NAIs (827-, 25-, 286-, and 702-fold for zanamivir, oseltamivir, peramivir, and laninamivir, respectively). The double E119D/H275Y mutation further increased oseltamivir and peramivir 50% inhibitory concentrations by 790- and >5000-fold, respectively, compared with the WT. The mutant viruses remained susceptible to favipiravir. The NA affinity and velocity values of the E119D variant decreased by 8.1-fold and 4.5-fold, respectively, compared with the WT.
Conclusions. The actual emergence of a single NA mutation conferring pan-NAI resistance in the clinical setting reinforces the pressing need to develop new anti-influenza strategies.
doi:10.1093/infdis/jiv288
PMCID: PMC4633758  PMID: 25985905
H1N1 influenza; zanamivir; oseltamivir; resistance; immunosuppression
24.  Human CD8+ T-Cell Responses Against the 4 Dengue Virus Serotypes Are Associated With Distinct Patterns of Protein Targets 
The Journal of Infectious Diseases  2015;212(11):1743-1751.
Background. All 4 dengue virus (DENV) serotypes are now simultaneously circulating worldwide and responsible for up to 400 million human infections each year. Previous studies of CD8+ T-cell responses in HLA-transgenic mice and human vaccinees demonstrated that the hierarchy of immunodominance among structural versus nonstructural proteins differs as a function of the infecting serotype. This led to the hypothesis that there are intrinsic differences in the serotype-specific reactivity of CD8+ T-cell responses.
Methods. We tested this hypothesis by analyzing serotype-specific CD8+ T-cell reactivity in naturally infected human donors from Sri Lanka and Nicaragua, using ex vivo interferon γ–specific enzyme-linked immunosorbent spot assays.
Results. Remarkably similar and clear serotype-specific patterns of immunodominance in both cohorts were identified. Pooling of epitopes that accounted for 90% of the interferon γ response in both cohorts resulted in a global epitope pool. Its reactivity was confirmed in naturally infected donors from Brazil, demonstrating its global applicability.
Conclusions. This study provides new insight into differential serotype-specific immunogenicity of DENV proteins. It further provides a potentially valuable tool for future investigations of CD8+ T-cell responses in the typically small sample volumes available from patients with acute fever and children without requiring prior knowledge of either infecting DENV serotype or HLA type.
doi:10.1093/infdis/jiv289
PMCID: PMC4633759  PMID: 25980035
dengue virus; serotype specific; CD8+ T cells; Nicaragua; Sri Lanka; Brazil
25.  Breast Milk as a Potential Source of Epstein-Barr Virus Transmission Among Infants Living in a Malaria-Endemic Region of Kenya 
The Journal of Infectious Diseases  2015;212(11):1735-1742.
Background. We previously reported that infants in Kenya were infected with Epstein-Barr virus (EBV) at <6 months of age, suggesting that mothers were the likely source of transmissible virus to the infant. In this study, we investigated whether breast milk contained infectious EBV and the role of malaria in EBV shedding in breast milk.
Methods. Breast milk samples were obtained from Kenyan mothers at postpartum weeks 6, 10, 14, and 18 and analyzed for presence of infectious EBV.
Results. We found that the prevalence of EBV DNA and the mean EBV load were significantly higher at 6 weeks and decreased through postpartum week 18 (P < .0001). High EBV load in breast milk correlated with mothers who had Plasmodium falciparum malaria at delivery. To determine whether viral DNA was encapsidated, breast milk samples were treated with DNAse before DNA extraction. Sixty percent of samples were DNAse resistant, suggesting that the viral DNA in breast milk was encapsidated. Next, we exposed peripheral blood mononuclear cells to breast milk supernatant, which resulted in the generation of EBV-positive lymphoblastoid cell lines, indicating that the virus in breast milk was infectious.
Conclusions. Our data suggest that breast milk contains infectious EBV and is a potential source of viral transmission to infants living in malaria-endemic regions.
doi:10.1093/infdis/jiv290
PMCID: PMC4633760  PMID: 25985902
breast milk; EBV transmission; malaria; Kenya

Results 1-25 (1750)