Dengue Virus (DENV) Neutralizing Antibody Kinetics in Children After Symptomatic Primary and Postprimary DENV Infection

Clapham, Hannah E.,Rodriguez-Barraquer, Isabel,Azman, Andrew S.,Althouse, Benjamin M.,Salje, Henrik,Gibbons, Robert V.,Rothman, Alan L.,Jarman, Richard G.,Nisalak, Ananda,Thaisomboonsuk, Butsaya,Kalay Oxford University Press 2016 The Journal of Infectious Diseases Vol.213 No.9

<P>The immune response to dengue virus (DENV) infection is complex and not fully understood. Using longitudinal data from 181 children with dengue in Thailand who were followed for up to 3 years, we describe neutralizing antibody kinetics following symptomatic DENV infection. We observed that antibody titers varied by serotype, homotypic vs heterotypic responses, and primary versus postprimary infections. The rates of change in antibody titers over time varied between primary and postprimary responses. For primary infections, titers increased from convalescence to 6 months. By comparing homotypic and heterotypic antibody titers, we saw an increase in type specificity from convalescence to 6 months for primary DENV3 infections but not primary DENV1 infections. In postprimary cases, there was a decrease in titers from convalescence up until 6 months after infection. Beginning 1 year after both primary and postprimary infections, there was evidence of increasing antibody titers, with greater increases in children with lower titers, suggesting that antibody titers were boosted due to infection and that higher levels of neutralizing antibody may be more likely to confer a sterilizing immune response. These findings may help to model virus transmission dynamics and provide baseline data to support the development of vaccines and therapeutics.</P>

Epidemiology of Infant Dengue Cases Illuminates Serotype-Specificity in the Interaction between Immunity and Disease, and Changes in Transmission Dynamics

Clapham, Hannah,Cummings, Derek A. T.,Nisalak, Ananda,Kalayanarooj, Siripen,Thaisomboonsuk, Butsaya,Klungthong, Chonticha,Fernandez, Stefan,Srikiatkhachorn, Anon,Macareo, Louis R.,Lessler, Justin,Reis Public Library of Science 2015 PLoS neglected tropical diseases Vol.9 No.12

<▼1><P><B>Background</B></P><P>Infants born to dengue immune mothers acquire maternal antibodies to dengue. These antibodies, though initially protective, decline during the first year of life to levels thought to be disease enhancing, before reaching undetectable levels. Infants have long been studied to understand the interaction between infection and disease on an individual level.</P><P><B>Methods/Findings</B></P><P>Considering infants (cases <1 year old) as a unique group, we analyzed serotype specific dengue case data from patients admitted to a pediatric hospital in Bangkok, Thailand. We show differences in the propensity of serotypes to cause disease in individuals with dengue antibodies (infants and post-primary cases) and in individuals without dengue antibodies (primary cases). The mean age of infant cases differed among serotypes, consistent with previously observed differential waning of maternal antibody titers by serotype. We show that trends over time in epidemiology of infant cases are consistent with those observed in the whole population, and therefore with trends in the force of infection.</P><P><B>Conclusions/Significance</B></P><P>Infants with dengue are informative about the interaction between antibody and the dengue serotypes, confirming that in this population DENV-2 and DENV-4 almost exclusively cause disease in the presence of dengue antibody despite infections occurring in others. We also observe differences between the serotypes in the mean age in infant cases, informative about the interaction between waning immunity and disease for the different serotypes in infants. In addition, we show that the mean age of infant cases over time is informative about transmission in the whole population. Therefore, ongoing surveillance for dengue in infants could provide useful insights into dengue epidemiology, particularly after the introduction of a dengue vaccine targeting adults and older children.</P></▼1><▼2><P><B>Author Summary</B></P><P>Infants born to dengue immune mothers acquire maternal dengue antibodies. These antibodies, though initially protective, decline during the first year of life to levels thought to be disease enhancing, before reaching undetectable levels. We show that in this population, DENV-2 and DENV-4 almost exclusively cause disease in the presence of dengue antibody, despite infections occurring in others. We also observe serotype-specificity in the mean age of infant cases, consistent with differential waning of antibody to each serotype. These results highlight serotype-specificity in the way the immune response interacts with infection to cause disease. In addition, we show that the mean age of infant cases over time is informative about transmission in the whole population. Therefore, ongoing surveillance for dengue in infants could provide useful insights into dengue epidemiology, particularly after the introduction of a dengue vaccine targeting adults and older children.</P></▼2>

강자성 배관 외ㆍ내부 벽의 racetrack형 결함깊이와 부피응력이 누설자속에 미치는 영향

유권상(K. S. Ryu),박영태(Y. T. Park),손대락(D. Son),D. L. Atherton(D. L. Atherton),L. Clapham(L. Clapham) 한국자기학회 2003 韓國磁氣學會誌 Vol.13 No.2

Non-linear anisotropic materials were used to simulate the effects of bulk tensile stress in 3D finite element analysis (FEA). FEA was used to calculate the effects of near and far-side racetrack pit depth and simulated bulk tensile stress on magnetic flux leakage (MFL) signals. The axial and radial MFL signals were depended on near and far-side racetrack pit depth and on the bulk stress, but the circumferential MFL signal was not depended on them. The axial and radial MFL signals increased with greater pit depth and applied bulk stress, but the circumferential MFL signal was scarcely changed.

강자성 배관 외ㆍ내부 면의 이중 원형 결함의 깊이와 응력이 누설자속에 미치는 영향

유권상(K. S. Ryu),박영태(Y. T. Park),손대락(D. Son),D. L. Atherton(D. L. Atherton),L. Clapham(L. Clapham) 한국자기학회 2003 韓國磁氣學會誌 Vol.13 No.2

Non-linear anisotropic materials were used to simulate the effects of tensile stress in 3D finite element analysis (FEA). FEA was used to calculate the effects of far and near-side pit depth and tensile stress on magnetic flux leakage (MFL) signals. The axial and radial MFL signals were depended on far and near-side double circular pit depth and on the stress, but the circumferential MFL signal was not depended on them. The axial and radial MFL signals increased with greater pit depth and applied stress, but the circumferential MFL signal was scarcely changed.

강자성 배관 외·내부 면의 단일 원형 홈의 깊이와 부피응력이 누설자속에 미치는 영향

유권상,박영태,Atherton, D.L.,Clapham, L. 한국비파괴검사학회 2003 한국비파괴검사학회지 Vol.23 No.3

누설자속(magnetic flux leakage: MFL) 신호는 매설된 송유관이나 가스관에 생성된 부식결함의 검사에 이용된다. 배관의 외내부 면의 단일 원형 홈(pit) 깊이와 부피응력(bulk stress)이 축(x) 방향, 원주(y) 방향 및 방사상(z) 방향의 누설자 속에 미치는 영향을 3차원 유한요소법을 이용하여 계산하였다. 자기이방성 물질을 이용하여 부피인장응력(bulk tensile stress)과 수직 응력에 의한 MFL 신호변화를 계산하였다. 배관의 축 및 방사상 방향의 MFL 신호는 배관 외내부의 결함 깊이가 깊어질수록, 부피인장응력이 커질수록 MFL 신호는 증가하였다. 그러나 원주 방향의 MFL 신호는 결함 깊이와 부피인장응력에 영향을 거의 받지 않았다. Magnetic flux leakage (MFL) signals were used for corrosion inspection of buried oil and gas pipeline. 3D finite element analysis was used to examine the effects of far and near-side depth and tensile stress on MFL signals. Anisotropic materials were used, and the effects of simulated tensile stress on MFL were investigated. The axial and radial MFL signals depended on far and near-side single pit depth and on the bulk stress, but the circumferential MFL signal did not depend on them. The axial and radial MFL signals increased with increasing pit depth and the bulk stress, but the circumferential MFL signal was scarcely changed.

강자성 배관의 racetrack 형 결함깊이와 응력이 누설자속에 미치는 영향

유권상,박영태,손대락,D.L. Atherton,L. Clapham 한국자기학회 2002 한국자기학회 학술연구발표회 논문개요집 Vol.12 No.2

Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines

Alera, Maria Theresa,Srikiatkhachorn, Anon,Velasco, John Mark,Tac-An, Ilya A.,Lago, Catherine B.,Clapham, Hannah E.,Fernandez, Stefan,Levy, Jens W.,Thaisomboonsuk, Butsaya,Klungthong, Chonticha,Macare Public Library of Science 2016 PLoS neglected tropical diseases Vol.10 No.2

<▼1><P><B>Background</B></P><P>The mean age of dengue has been increasing in some but not all countries. We sought to determine the incidence of dengue virus (DENV) infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic.</P><P><B>Methodology/Principal Findings</B></P><P>A prospective cohort of subjects ≥6 months old in Cebu City, Philippines, underwent active community-based surveillance for acute febrile illnesses by weekly contact. Fever history within the prior seven days was evaluated with an acute illness visit followed by 2, 5, and 8-day, and 3-week convalescent visits. Blood was collected at the acute and 3-week visits. Scheduled visits took place at enrolment and 12 months that included blood collections. Acute samples were tested by DENV PCR and acute/convalescent samples by DENV IgM/IgG ELISA to identify symptomatic infections. Enrolment and 12-month samples were tested by DENV hemagglutination inhibition (HAI) assay to identify subclinical infections. Of 1,008 enrolled subjects, 854 completed all study activities at 12 months per-protocol undergoing 868 person-years of surveillance. The incidence of symptomatic and subclinical infections was 1.62 and 7.03 per 100 person-years, respectively. However, in subjects >15 years old, only one symptomatic infection occurred whereas 27 subclinical infections were identified. DENV HAI seroprevalence increased sharply with age with baseline multitypic HAIs associated with fewer symptomatic infections. Using a catalytic model, the historical infection rate among dengue naïve individuals was estimated to be high at 11–22%/year.</P><P><B>Conclusions/Significance</B></P><P>In this hyperendemic area with high seroprevalence of multitypic DENV HAIs in adults, symptomatic dengue rarely occurred in individuals older than 15 years. Our findings demonstrate that dengue is primarily a pediatric disease in areas with high force of infection. However, the average age of dengue could increase if force of infection decreases over time, as is occurring in some hyperendemic countries such as Thailand.</P></▼1><▼2><P><B>Author Summary</B></P><P>The average age of dengue has been increasing in some but not all dengue endemic countries. To investigate the age pattern of dengue in people of all ages ≥6 months old, a prospective community-based cohort study was undertaken in Cebu City, Philippines where dengue virus has been circulating for many decades. Active surveillance for acute fevers was performed, and acute/convalescent blood samples were tested for evidence of symptomatic dengue. Blood was also collected at enrolment and one year later, and tested serologically to identify subclinical infections. Overall, 1.62 symptomatic and 7.03 subclinical infections per 100 person-years of surveillance were detected. Among people older than 15 years, only one symptomatic dengue case occurred while 27 subclinical infections were identified. By analyzing age-specific dengue serology data, the historical infection rate among people with no prior dengue virus infection was found to be high at around 11–22% per year. Our results show that dengue is primarily a childhood disease in endemic settings where the historical infection rate has been high. However, the average age of dengue could increase if the infection rate decreases over time as is happening in some endemic countries like Thailand.</P></▼2>

Structurally Distinct Ca²⁺ Signaling Domains of Sperm Flagella Orchestrate Tyrosine Phosphorylation and Motility

Chung, J.J.,Shim, S.H.,Everley, Robert A.,Gygi, Steven P.,Zhuang, X.,Clapham, David E. Cell Press ; MIT Press 2014 Cell Vol.157 No.4

Spermatozoa must leave one organism, navigate long distances, and deliver their paternal DNA into a mature egg. For successful navigation and delivery, a sperm-specific calcium channel is activated in the mammalian flagellum. The genes encoding this channel (CatSpers) appear first in ancient uniflagellates, suggesting that sperm use adaptive strategies developed long ago for single-cell navigation. Here, using genetics, super-resolution fluorescence microscopy, and phosphoproteomics, we investigate the CatSper-dependent mechanisms underlying this flagellar switch. We find that the CatSper channel is required for four linear calcium domains that organize signaling proteins along the flagella. This unique structure focuses tyrosine phosphorylation in time and space as sperm acquire the capacity to fertilize. In heterogeneous sperm populations, we find unique molecular phenotypes, but only sperm with intact CatSper domains that organize time-dependent and spatially specific protein tyrosine phosphorylation successfully migrate. These findings illuminate flagellar adaptation, signal transduction cascade organization, and fertility. PaperFlick: