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2. Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study

Author

Peñataro Yori, Pablo, Paredes Olórtegui, Maribel, Schiaffino, Francesca, Colston, Josh M., Pinedo Vasquez, Tackeshy, Garcia Bardales, Paul F., Shapiama Lopez, Valentino, Zegarra Paredes, Loyda Fiorella, Perez, Karin, Curico, Greisi, Flynn, Thomas, Zhang, Jixian, Ramal Asayag, Cesar, Meza Sanchez, Graciela, Silva Delgado, Hermann, Casapia Morales, Martin, Casanova, Wilma, Jiu, Bruce, Oberhelman, Richard, Munayco Escate, Cesar, Silver, Rachel, Henao, Olga, Cooper, Kerry K., Liu, Jie, Houpt, Eric R., and Kosek, Margaret N.

Published
2023
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4. Efficacy of Single-Dose Albendazole and Albendazole Plus Ivermectin for Soil-Transmitted Helminth Infection in Children in the Peruvian Amazon

Author

Curico, Greisi, primary, Garcia Bardales, Paul F., additional, Pinedo Vasquez, Tackeshy N., additional, Shapiama Lopez, Wagner Valentino, additional, Paredes Olortegui, Maribel, additional, Schiaffino, Francesca, additional, Peñataro Yori, Pablo, additional, Colston, Josh M., additional, Flynn, Thomas G., additional, Meza Sánchez, Graciela, additional, Silva Delgado, Hermann, additional, Oberhelman, Richard A., additional, and Kosek, Margaret N., additional

Published
2024
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5. The Enterics for Global Health (EFGH) Shigella Surveillance Study in Peru

Author

Manzanares Villanueva, Katia, primary, Pinedo Vasquez, Tackeshy, additional, Peñataro Yori, Pablo, additional, Romaina Cacique, Lucero, additional, Garcia Bardales, Paul F, additional, Shapiama Lopez, Wagner V, additional, Zegarra Paredes, Fiorella, additional, Perez, Karin F, additional, Rengifo Pinedo, Silvia, additional, Silva Delgado, Hermann, additional, Flynn, Thomas, additional, Schiaffino, Francesca, additional, Colston, Josh M, additional, Paredes Olortegui, Maribel Paredes, additional, and Kosek, Margaret N, additional

Published
2024
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6. Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study

Author

Benedicto-Matambo, Prisca, primary, Avolio, Lindsay N, additional, Badji, Henry, additional, Batool, Rabab, additional, Khanam, Farhana, additional, Munga, Stephen, additional, Tapia, Milagritos D, additional, Peñataro Yori, Pablo, additional, Awuor, Alex O, additional, Ceesay, Bubacarr E, additional, Cornick, Jennifer, additional, Cunliffe, Nigel A, additional, Garcia Bardales, Paul F, additional, Heaney, Christopher D, additional, Hotwani, Aneeta, additional, Ireen, Mahzabeen, additional, Taufiqul Islam, Md, additional, Jallow, Ousman, additional, Kaminski, Robert W, additional, Shapiama Lopez, Wagner V, additional, Maiden, Victor, additional, Ikumapayi, Usman Nurudeen, additional, Nyirenda, Ruth, additional, Ochieng, John Benjamin, additional, Omore, Richard, additional, Paredes Olortegui, Maribel, additional, Pavlinac, Patricia B, additional, Pisanic, Nora, additional, Qadri, Firdausi, additional, Qureshi, Sonia, additional, Rahman, Nazia, additional, Rogawski McQuade, Elizabeth T, additional, Schiaffino, Francesca, additional, Secka, Ousman, additional, Sonye, Catherine, additional, Sultana, Shazia, additional, Timite, Drissa, additional, Traore, Awa, additional, Yousafzai, Mohammad Tahir, additional, Taufiqur Rahman Bhuiyan, Md, additional, Jahangir Hossain, M, additional, Jere, Khuzwayo C, additional, Kosek, Margaret N, additional, Kotloff, Karen L, additional, Qamar, Farah Naz, additional, Sow, Samba O, additional, and Platts-Mills, James A, additional

Published
2024
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7. Population Enumeration and Household Utilization Survey Methods in the Enterics for Global Health (EFGH): Shigella Surveillance Study

Author

Dodd, Ryan, primary, Awuor, Alex O, additional, Garcia Bardales, Paul F, additional, Khanam, Farhana, additional, Mategula, Donnie, additional, Onwuchekwa, Uma, additional, Sarwar, Golam, additional, Yousafzai, Mohammad Tahir, additional, Ahmed, Naveed, additional, Atlas, Hannah E, additional, Amirul Islam Bhuiyan, Md, additional, Colston, Josh M, additional, Conteh, Bakary, additional, Diawara, Manan, additional, Dilruba, Nasrin, additional, Elwood, Sarah, additional, Fatima, Irum, additional, Feutz, Erika, additional, Galagan, Sean R, additional, Haque, Shahinur, additional, Taufiqul Islam, Md, additional, Karim, Mehrab, additional, Keita, Belali, additional, Kosek, Margaret N, additional, Kotloff, Karen L, additional, Lefu, Clement, additional, Mballow, Mamadou, additional, Ndalama, Maureen, additional, Ndeketa, Latif, additional, Ogwel, Billy, additional, Okonji, Caleb, additional, Paredes Olortegui, Maribel, additional, Pavlinac, Patricia B, additional, Pinedo Vasquez, Tackeshy, additional, Platts-Mills, James A, additional, Qadri, Firdausi, additional, Qureshi, Sonia, additional, Rogawski McQuade, Elizabeth T, additional, Sultana, Shazia, additional, Traore, Moussa Oumar, additional, Cunliffe, Nigel A, additional, Jahangir Hossain, M, additional, Omore, Richard, additional, Qamar, Farah Naz, additional, Tapia, Milagritos D, additional, Peñataro Yori, Pablo, additional, Zaman, K, additional, and McGrath, Christine J, additional

Published
2024
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8. Shigella Detection and Molecular Serotyping With a Customized TaqMan Array Card in the Enterics for Global Health (EFGH): Shigella Surveillance Study

Author

Liu, Jie, primary, Garcia Bardales, Paul F, additional, Islam, Kamrul, additional, Jarju, Sheikh, additional, Juma, Jane, additional, Mhango, Chimwemwe, additional, Naumanga, Queen, additional, Qureshi, Sonia, additional, Sonye, Catherine, additional, Ahmed, Naveed, additional, Aziz, Fatima, additional, Bhuiyan, Md Taufiqur Rahman, additional, Charles, Mary, additional, Cunliffe, Nigel A, additional, Abdou, Mahamadou, additional, Galagan, Sean R, additional, Gitteh, Ensa, additional, Guindo, Ibrehima, additional, Jahangir Hossain, M, additional, Jabang, Abdoulie M J, additional, Jere, Khuzwayo C, additional, Kawonga, Flywell, additional, Keita, Mariama, additional, Keita, Noumou Yakhouba, additional, Kotloff, Karen L, additional, Shapiama Lopez, Wagner V, additional, Munga, Stephen, additional, Paredes Olortegui, Maribel, additional, Omore, Richard, additional, Pavlinac, Patricia B, additional, Qadri, Firdausi, additional, Qamar, Farah Naz, additional, Azadul Alam Raz, S M, additional, Riziki, Laura, additional, Schiaffino, Francesca, additional, Stroup, Suzanne, additional, Traore, Sarata Nassoun, additional, Pinedo Vasquez, Tackeshy, additional, Yousafzai, Mohammad Tahir, additional, Antonio, Martin, additional, Cornick, Jennifer E, additional, Kabir, Furqan, additional, Khanam, Farhana, additional, Kosek, Margaret N, additional, Ochieng, John Benjamin, additional, Platts-Mills, James A, additional, Tennant, Sharon M, additional, and Houpt, Eric R, additional

Published
2024
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9. Evaluation of Fecal Inflammatory Biomarkers to Identify Bacterial Diarrhea Episodes: Systematic Review and Protocol for the Enterics for Global Health Shigella Surveillance Study

Author

Babb, Courtney, primary, Badji, Henry, additional, Bhuiyan, Md Taufiqur Rahman, additional, Cornick, Jennifer, additional, Qureshi, Sonia, additional, Sonye, Catherine, additional, Shapiama Lopez, Wagner V, additional, Adnan, Mehreen, additional, Atlas, Hannah E, additional, Begum, Kehkashan, additional, Brennhofer, Stephanie A, additional, Ceesay, Bubacarr E, additional, Ceesay, Abdoulie K, additional, Cunliffe, Nigel A, additional, Garcia Bardales, Paul F, additional, Haque, Shahinur, additional, Horne, Bri’Anna, additional, Hossain, M Jahangir, additional, Iqbal, Junaid, additional, Islam, Md Taufiqul, additional, Islam, Sadia, additional, Khanam, Farhana, additional, Kotloff, Karen L, additional, Malemia, Thandizo, additional, Manzanares Villanueva, Katia, additional, Million, Gertrude Malola, additional, Munthali, Vitumbiko, additional, Ochieng, John Benjamin, additional, Ogwel, Billy, additional, Paredes Olortegui, Maribel, additional, Omore, Richard, additional, Pavlinac, Patricia B, additional, Platts-Mills, James A, additional, Sears, Khandra T, additional, Secka, Ousman, additional, Tennant, Sharon M, additional, Peñataro Yori, Pablo, additional, Yousafzai, Mohammad Tahir, additional, Jere, Khuzwayo C, additional, Kosek, Margaret N, additional, Munga, Stephen, additional, Ikumapayi, Usman N, additional, Qadri, Firdausi, additional, Qamar, Farah Naz, additional, and Rogawski McQuade, Elizabeth T, additional

Published
2024
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10. Novel rpsK / rpsD primer-probe assay improves detection of Campylobacter jejuni and Campylobacter coli in human stool

Author

Schiaffino, Francesca, primary, Parker, Craig T., additional, Garcia Bardales, Paul F., additional, Huynh, Steven, additional, Manzanares Villanueva, Katia, additional, Mourkas, Evangelos, additional, Pascoe, Ben, additional, Peñataro Yori, Pablo, additional, Paredes Olortegui, Maribel, additional, Houpt, Eric R., additional, Liu, Jie, additional, Cooper, Kerry K., additional, and Kosek, Margaret N., additional

Published
2024
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11. Novel rpsK / rpsD primer-probe assay improves detection of Campylobacter jejuni and Campylobacter coli in human stool

Author

Schiaffino, Francesca, Parker, Craig T., Garcia Bardales, Paul F., Huynh, Steven, Manzanares Villanueva, Katia, Mourkas, Evangelos, Pascoe, Ben, Peñataro Yori, Pablo, Paredes Olortegui, Maribel, Houpt, Eric R., Liu, Jie, Cooper, Kerry K., Kosek, Margaret N., Schiaffino, Francesca, Parker, Craig T., Garcia Bardales, Paul F., Huynh, Steven, Manzanares Villanueva, Katia, Mourkas, Evangelos, Pascoe, Ben, Peñataro Yori, Pablo, Paredes Olortegui, Maribel, Houpt, Eric R., Liu, Jie, Cooper, Kerry K., and Kosek, Margaret N.

Abstract

Campylobacter causes bacterial enteritis, dysentery, and growth faltering in children in low- and middle-income countries (LMICs). Campylobacter spp. are fastidious organisms, and their detection often relies on culture independent diagnostic technologies, especially in LMICs. Campylobacter jejuni and Campylobacter coli are most often the infectious agents and in high income settings together account for 95% of Campylobacter infections. Several other Campylobacter species have been detected in LMIC children at an increased prevalence relative to high income settings. After doing extensive whole genome sequencing of isolates of C. jejuni and C. coli in Peru, we observed heterogeneity in the binding sites for the main species-specific PCR assay (cadF) and designed an alternative rpsKD-based qPCR assay to detect both C. jejuni and C. coli. The rpsKD-based qPCR assay identified 23% more C.jejuni/ C.coli samples than the cadF assay among 47 Campylobacter genus positive cadF negative samples verified to have C. jejuni and or C. coli with shotgun metagenomics. This assay can be expected to be useful in diagnostic studies of enteric infectious diseases and be useful in revising the attribution estimates of Campylobacter in LMICs.

Published
2024
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12. Genomic resistant determinants of multidrug-resistant Campylobacterspp. isolates in Peru

Author

Schiaffino, Francesca, Parker, Craig T., Paredes Olortegui, Maribel, Pascoe, Ben, Manzanares Villanueva, Katia, Garcia Bardales, Paul F., Mourkas, Evangelos, Huynh, Steven, Peñataro Yori, Pablo, Romaina Cachique, Lucero, Gray, Hannah K., Salvatierra, Guillermo, Silva Delgado, Hermann, Sheppard, Samuel K., Cooper, Kerry K., and Kosek, Margaret N.

Abstract

•Multi drug resistant Campylobacterwere isolated from two pediatric cohorts in the Peruvian Amazon.•MDR variants were present in highly diverse Campylobacterstrains.•RE-cmeABCwas identified in clinical isolates and linked to a MDR phenotype and genotype.•Genomic variants in the promoter region that disrupt the CmeR-binding site of the cmeABCoperon were linked to a MDR phenotype and genotype.

Published
2024
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13. Etiology of Acute Febrile Illness in the Peruvian Amazon as determined by modular formatted quantitative PCR: A Protocol for RIVERA, a Health Facility-Based Case-Control Study

Author

Peñataro_Yori, Pablo, primary, Paredes_Olórtegui, Maribel, additional, Schiaffino, Francesca, additional, Perez, Karin, additional, Curico_Huansi, Greisi, additional, Flynn, Thomas, additional, Zhang, Jixian, additional, Ramal_Asayag, Cesar, additional, Meza_Sanchez, Graciela, additional, Silva_Delgado, Hermann, additional, Casapia_Morales, Martin, additional, Casanova, Wilma, additional, Jiu, Bruce, additional, Munayco_Escate, Cesar, additional, Silver, Rachel, additional, Henao, Olga, additional, Cooper, Kerry K., additional, Liu, Jie, additional, Houpt, Eric, additional, Kosek, Margaret N, additional, Colston, Josh M, additional, Oberhelman, Richard, additional, Pinedo_Vasquez, Tackeshy, additional, Garcia_Bardales, Paul F, additional, Shapiama_Lopez, Wagner Valentino, additional, and Zegarra_Paredes, Loyda Fiorella, additional

Published
2023
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14. Additional file 1 of Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study

Author

Peñataro Yori, Pablo, Paredes Olórtegui, Maribel, Schiaffino, Francesca, Colston, Josh M., Pinedo Vasquez, Tackeshy, Garcia Bardales, Paul F., Shapiama Lopez, Valentino, Zegarra Paredes, Loyda Fiorella, Perez, Karin, Curico, Greisi, Flynn, Thomas, Zhang, Jixian, Ramal Asayag, Cesar, Meza Sanchez, Graciela, Silva Delgado, Hermann, Casapia Morales, Martin, Casanova, Wilma, Jiu, Bruce, Oberhelman, Richard, Munayco Escate, Cesar, Silver, Rachel, Henao, Olga, Cooper, Kerry K., Liu, Jie, Houpt, Eric R., and Kosek, Margaret N.

Abstract

Supplementary Material 1

Published
2023
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15. “Candidatus Campylobacter infans” detection is not associated with diarrhea in children under the age of 2 in Peru

Author

Garcia Bardales, Paul F., primary, Schiaffino, Francesca, additional, Huynh, Steven, additional, Paredes Olortegui, Maribel, additional, Peñataro Yori, Pablo, additional, Pinedo Vasquez, Tackeshy, additional, Manzanares Villanueva, Katia, additional, Curico Huansi, Greisi E., additional, Shapiama Lopez, Wagner V., additional, Cooper, Kerry K., additional, Parker, Craig T., additional, and Kosek, Margaret N., additional

Published
2022
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16. Shotgun metagenomics of fecal samples from children in Peru reveals frequent complex co-infections with multiple Campylobacter species

Author

Parker, Craig T., primary, Schiaffino, Francesca, additional, Huynh, Steven, additional, Paredes Olortegui, Maribel, additional, Peñataro Yori, Pablo, additional, Garcia Bardales, Paul F., additional, Pinedo Vasquez, Tackeshy, additional, Curico Huansi, Greisi E., additional, Manzanares Villanueva, Katia, additional, Shapiama Lopez, Wagner V., additional, Cooper, Kerry K., additional, and Kosek, Margaret N., additional

Published
2022
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17. Associations among Household Animal Ownership, Infrastructure, and Hygiene Characteristics with Source Attribution of Household Fecal Contamination in Peri-Urban Communities of Iquitos, Peru

Author

Schiaffino, Francesca, primary, Rengifo Trigoso, Dixner, additional, Colston, Josh M., additional, Paredes Olortegui, Maribel, additional, Shapiama Lopez, Wagner V., additional, Garcia Bardales, Paul F., additional, Pisanic, Nora, additional, Davis, Meghan F., additional, Penataro Yori, Pablo, additional, and Kosek, Margaret N., additional

Published
2021
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18. Sharing of cmeRABC alleles between C. coli and C. jejuni associated with extensive drug resistance in Campylobacter isolates from infants and poultry in the Peruvian Amazon.

Author

Cooper KK, Mourkas E, Schiaffino F, Parker CT, Pinedo Vasquez TN, Garcia Bardales PF, Peñataro Yori P, Paredes Olortegui M, Manzanares Villanueva K, Romaina Cachique L, Silva Delgado H, Hitchings MD, Huynh S, Sheppard SK, Pascoe B, and Kosek MN

Subjects
Peru epidemiology, Animals, Humans, Infant, Bacterial Proteins genetics, Microbial Sensitivity Tests, Drug Resistance, Multiple, Bacterial genetics, Mutation, Drug Resistance, Bacterial genetics, Poultry Diseases microbiology, Poultry Diseases epidemiology, Operon, Child, Campylobacter jejuni genetics, Campylobacter jejuni drug effects, Campylobacter jejuni isolation & purification, Campylobacter coli genetics, Campylobacter coli drug effects, Campylobacter coli isolation & purification, Poultry microbiology, Anti-Bacterial Agents pharmacology, Campylobacter Infections microbiology, Campylobacter Infections veterinary, Campylobacter Infections epidemiology, Macrolides pharmacology, Fluoroquinolones pharmacology, Alleles
Abstract

Campylobacter is a serious health threat because of the rapid progressive evolution of antimicrobial resistance and efficient transmission from zoonotic as well as human sources. Resistance to fluoroquinolones and macrolides is particularly concerning as this compromises the two most effective oral antibiotic agents currently available for human campylobacteriosis. Here, we report on the prevalence and worldwide distribution of the operon cmeRABC , which encodes an efflux pump conferring high levels of combined resistance to fluoroquinolones and macrolides in Campylobacter strains isolated from poultry ( n = 75) and children ( n = 177). These mutations were found to be highly prevalent in isolates from poultry (62.7%) and children (29.4%) in Iquitos, Peru. We investigated the population structure of genes in the cmeRABC operon and identified a potential genetic bottleneck for the cmeA and cmeB genes. While most cmeB alleles segregate by species, alleles associated with high resistance to fluoroquinolones and macrolides were found in both Campylobacter jejuni and Campylobacter coli . We inferred that the likely ancestry of these alleles was from C. jejuni and was later acquired by C. coli through recombination. Publicly accessible global genomic data from 16,120 Campylobacter genomes identified these mutations in approximately 6% of C. jejuni and C. coli isolates globally, with higher prevalence in samples from poultry in many countries, including Peru. Our findings suggest that these extensively drug-resistant Campylobacter strains originated from C. jejuni in poultry.IMPORTANCEAntimicrobial resistance in Campylobacter is a growing public health concern, driven by the rapid evolution and zoonotic transmission of resistant strains. This study focuses on mutations in the cmeABC efflux pump, which confer high resistance to fluoroquinolones and macrolides, the two most effective oral antibiotics for human campylobacteriosis. By analyzing genomes from poultry and children in Iquitos, Peru, as well as global genomic data sets, we identified a significant prevalence of these resistance-associated mutations, particularly in poultry and children. Our findings suggest that these mutations originated in Campylobacter jejuni and spread to C. coli through recombination. Globally, these mutations are found in approximately 6% of isolates, with higher prevalence in poultry in multiple countries. This research underscores the critical role of genomic epidemiology in understanding the origins, evolution, and dissemination of antimicrobial resistance and highlights the need to address poultry as a reservoir for resistant Campylobacter ., Competing Interests: The authors declare no conflict of interest.

Published
2025
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19. Genomic Epidemiology of 2023-2024 Oropouche Outbreak in Iquitos, Peru reveals independent origin from a concurrent outbreak in Brazil.

Author

Olortegui MP, Schiaffino F, Peñataro Yori P, Colston JM, Shapiama Lopez V, Pinedo Vasquez T, Garcia Bardales PF, Flynn TG, Ramal-Asayag C, Hughes HR, Davis E, Russell BJ, Brault AC, Palomino YAA, Munayco C, Liu J, Houpt E, Cooper KK, Parker CT, and Kosek MN

Abstract

Oropouche virus is an arbovirus endemic to the Americas. Periodic outbreaks have occurred since its description in 1955. In late 2023, an outbreak occurred in Peru, centered in and around Iquitos in the Eastern Peruvian Amazon. An existing acute febrile illness (AFI) surveillance program was able to document its emergence and characterize arthralgia and dysuria and the absence of diarrhea as distinctive clinical features of Oropouche virus-associated febrile illness relative to other causes of AFI. Sequencing of isolates from the outbreak demonstrated that strains from this region were distinct from those causing disease in Brazil, despite the large-scale movement of people along the Amazon corridor, but highly similar to strains from Colombia and Ecuador. Our findings suggest that the current outbreak in South America is fundamentally multifocal in origin and not the result of geographic spread from Brazil, which experienced an outbreak between 2022 and 2024.

Published
2024
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20. Epstein-Barr Virus in the RIVERA Case-Control Study of Acute Febrile Illness: Acute Mononucleosis Nearly Absent as an Etiology in the Peruvian Amazon.

Author

Flynn TG, Paredes Olortegui M, Garcia Bardales PF, Schiaffino F, Pinedo Vasquez TN, Shapiama López WV, Peñataro Yori P, Ramal Asayag CJ, Meza Sánchez GR, Colston JM, and Kosek MN

Subjects
Humans, Peru epidemiology, Case-Control Studies, Female, Male, Child, Adolescent, Child, Preschool, Adult, DNA, Viral blood, Fever virology, Fever epidemiology, Young Adult, Infant, Acute Disease, Antibodies, Viral blood, Herpesvirus 4, Human genetics, Herpesvirus 4, Human isolation & purification, Infectious Mononucleosis epidemiology, Infectious Mononucleosis virology, Infectious Mononucleosis diagnosis, Epstein-Barr Virus Infections epidemiology, Epstein-Barr Virus Infections virology, Epstein-Barr Virus Infections complications, Epstein-Barr Virus Infections diagnosis
Abstract

Large diagnostic panels allow for pathogens with high or low likelihood of causing attributable illness to be tested simultaneously. Infectious mononucleosis (IM) due to primary infection with Epstein-Barr virus (EBV) is a common cause of acute febrile illness (AFI) in case series from high-income countries, though its contribution to AFI in tropical low-income settings is unclear. As part of a case-control study using multiplex quantitative polymerase chain reaction (qPCR) diagnostics, we set out to determine if primary EBV infection was an underrecognized cause of AFI in the Peruvian Amazon. Presence of EBV DNA in whole-blood samples was equally prevalent among febrile cases and afebrile controls (34.6% [247/714] versus 35.7% [248/695]) and was not correlated with classic IM symptoms. Given the clear lack of clinical significance of the whole-blood PCR results, additional testing was pursued to ascertain the true prevalence of IM among cases of AFI in this population. The presence of EBV DNA in plasma, a marker of active EBV-related processes, was detected in 7% (5/68). Anti-EBNA-1 IgG, a late marker of prior infection, was tested via ELISA and detected in 4/5 of the plasma-positive patients, thereby excluding an acute primary EBV infection in all but one patient. Infectious mononucleosis due to primary infection with EBV was not an important etiology of AFI in the Peruvian Amazon, despite high rates of initial test positivity.

Published
2024
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21. Etiology of Acute Febrile Illness in the Peruvian Amazon as determined by modular formatted quantitative PCR: A Protocol for RIVERA, a Health Facility-Based Case-Control Study.

Author

Peñataro Yori P, Paredes Olórtegui M, Schiaffino F, Perez K, Curico Huansi G, Flynn T, Zhang J, Ramal Asayag C, Meza Sanchez G, Silva Delgado H, Casapia Morales M, Casanova W, Jiu B, Munayco Escate C, Silver R, Henao O, Cooper KK, Liu J, Houpt E, Kosek MN, Colston JM, Oberhelman R, Pinedo Vasquez T, Garcia Bardales PF, Shapiama Lopez WV, and Zegarra Paredes LF

Abstract

Background: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI., Methods: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI., Discussion: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 hours and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific, prevalent pathogens as a cause of acute illness., Study Registration: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú., Competing Interests: Competing interests The authors declare that they have no competing interests or conflicts of interest.

Published
2023
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