Papers by Cristhiam Cerpas
Open Forum Infectious Diseases, Nov 28, 2022
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In the first two years of the COVID-19 pandemic, influenza transmission decreased substantially w... more In the first two years of the COVID-19 pandemic, influenza transmission decreased substantially worldwide meaning that health systems were not faced with simultaneous respiratory epidemics. In 2022, however, substantial influenza transmission returned to Nicaragua where it co-circulated with SARS-CoV-2 causing substantial disease burden.
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Journal of the International AIDS Society, 2010
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BackgroundAn immune correlate of protection from SARS-CoV-2 infection is urgently needed.MethodsW... more BackgroundAn immune correlate of protection from SARS-CoV-2 infection is urgently needed.MethodsWe used an ongoing household cohort with an embedded transmission study that closely monitors participants regardless of symptom status. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Enzyme-linked immunosorbent assays (ELISAs) were used to measure infections and seropositivity. Sequencing was performed to determine circulating strains of SARS-CoV-2. We investigated the protection associated with seropositivity resulting from prior infection, the anti-spike antibody titers needed for protection, and we compared the severity of first and second infections.ResultsIn March 2021, 62.3% of the cohort was seropositive. After March 2021, gamma and delta variants predominated. Seropositivity was associated with 69.2% protection from any infection (95% CI: 60.7%-75.9%), with higher protection against moderate or severe infection (79.4%, 95% CI: 64.9%-87.9%). Anti-spike tite...
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New England Journal of Medicine
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ImportanceThe impact of the SARS-CoV-2 pandemic on children remains unclear. Better understanding... more ImportanceThe impact of the SARS-CoV-2 pandemic on children remains unclear. Better understanding of the burden of COVID-19 among children and their protection against re-infection is crucial as they will be among the last groups vaccinated.ObjectiveTo characterize the burden of COVID-19 and assess how protection from symptomatic re-infection among children may vary by age.DesignA prospective, community-based pediatric cohort study conducted from March 1, 2020 through October 15, 2021.SettingThe Nicaraguan Pediatric Influenza Cohort is a community-based cohort in District 2 of Managua, Nicaragua.ParticipantsA total of 1964 children aged 0-14 years participated in the cohort. Non-immunocompromised children were enrolled by random selection from a previous pediatric influenza cohort. Additional newborn infants aged ≤4 weeks were randomly selected and enrolled monthly, via home visits.ExposuresPrior COVID-19 infection as confirmed by positive anti SARS-CoV-2 antibodies (receptor bindin...
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Journal of clinical microbiology, Mar 5, 2018
Zika virus (ZIKV) is a mosquito-borne flavivirus that is responsible for recent explosive epidemi... more Zika virus (ZIKV) is a mosquito-borne flavivirus that is responsible for recent explosive epidemics in the Americas. Notably, ZIKV infection during pregnancy has been found to cause congenital birth defects, including microcephaly, and ZIKV has been associated with Guillain Barré Syndrome in adults. Diagnosis and surveillance of Zika in the Americas have been challenging due to similar clinical manifestations and extensive antibody cross-reactivity with endemic flaviviral diseases, like dengue. We evaluated four serological and two RT-PCR methods in acute (mean day 1.8), early convalescent (mean day 16.7), and late convalescent (∼7 months) samples from the same individuals in a long-term pediatric cohort study in Nicaragua. Well-characterized samples from 301 cases of Zika, dengue, or non-Zika, non-dengue febrile illnesses were tested. Compared to a composite reference, an in-house MAC-ELISA and the NIAID-BEI MAC-ELISA measuring IgM yielded sensitivities of 94.5% and 70.1% and speci...
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Frontiers in immunology, 2017
Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important t... more Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4(+) T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4(+) T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4(+) T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen-presenting cells, followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a "megapool" (MP) consisting of 180 peptides specifically designed to achieve bala...
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Human immunology, Jan 6, 2017
DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1 loci was performed... more DNA sequence-based typing at the HLA-A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1 loci was performed on anonymized samples provided by 339 healthy adult blood bank donors in Managua, Nicaragua. The purpose of the study was to characterize allele frequencies in the local population to support studies of T cell immunity against pathogens, including Dengue virus. Deviations from Hardy Weinberg proportions were detected for all class II loci (HLA-DPB1, -DQA1, -DQB1 and -DRB1), and at the class I C locus, but not at the class I A and B loci. The genotype data will be available in the Allele Frequencies Net Database.
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Journal of virology, Jan 4, 2017
While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, l... more While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the fr...
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Journal of virology, Jan 24, 2016
Dengue disease is a large public health problem that mainly afflicts tropical and subtropical reg... more Dengue disease is a large public health problem that mainly afflicts tropical and subtropical regions. Understanding of the correlates of protection against dengue virus (DENV) is poor and hinders the development of a successful human vaccine. The present study aims to define DENV-specific CD8(+) T cell responses in general, and those of HLA alleles associated with dominant responses in particular. In human blood donors in Nicaragua, we observed a striking dominance of HLA B-restricted responses in general, and of B*35:01 in particular. Comparing these patterns to those in the general population of Sri Lanka, we found a strong correlation between restricting HLA allele and breadth and magnitude of CD8(+) T cell responses, suggesting that HLA genes profoundly influence the nature of responses. The majority of IFNγ responses were associated with effector memory phenotypes, which were also detected in non-B*35:01-expressing T cells. However, only the B*35:01 DENV-specific T cells were ...
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Journal of Infectious Diseases, 2015
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JAMA Network Open
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Papers by Cristhiam Cerpas