Multiplex Reverse Transcription Polymerase Chain Reaction Combined with a Microwell Hybridization Assay Screening for Arbovirus and Parasitic Infections in Febrile Patients Living in Endemic Regions of Colombia
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Sample Collection and Procedures
2.3. Multiplex RT-PCR-ELISA
2.4. Single-Primer RT-PCR
2.5. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Arroyave, E.; Londoño, A.F.; Quintero, J.C.; Agudelo-Florez, P.; Arboleda, M.; Díaz, F.J.; Rodas, J.D. Etiología y caracterización epidemiológica del síndrome febril no malárico en tres municipios del Urabá antioqueño, Colombia. Biomédica 2012, 33 (Suppl. 1), 99–107. [Google Scholar] [CrossRef]
- Ovalle, M.V.; Bello, S.; Rico, A.; Pardo, L.; Beltrán, M.; Duarte, C.; Páez, A. Caracterización epidemiológica de síndrome febril en pacientes fallecidos en Colombia, 2011–2013. Inf. Epidemiol. Nac. 2016, 21, 266–277. [Google Scholar] [CrossRef]
- Colford, J.M.; Kalantri, S.; Joshi, R.; Reingold, A.L. Nonmalarial Acute Undifferentiated Fever in a Rural Hospital in Central India: Diagnostic Uncertainty and Overtreatment with Antimalarial Agents. Am. J. Trop. Med. Hyg. 2008, 78, 393–399. [Google Scholar] [CrossRef]
- Cortés, L.J.; Guerra, Á.P. Análisis de concordancia de tres pruebas para el diagnóstico de malaria en la población sintomática de los municipios endémicos de Colombia. Biomédica 2020, 40, 117–128. [Google Scholar] [CrossRef] [PubMed]
- Betancur, C.; Ferro, S.; Obregón, J.; Torres, H. Síndrome febril de difícil diagnóstico. Acta Med. Colomb. 1990, 15, 194–203. [Google Scholar]
- Braack, L.; Gouveia de Almeida, A.P.; Cornel, A.J.; Swanepoel, R.; de Jager, C. Mosquito-borne arboviruses of African origin: Review of key viruses and vectors. Parasites Vectors 2018, 11, 29. [Google Scholar] [CrossRef]
- García-Henao, J.P.; Alzate-Piedrahita, J.A.; Guevara, M.P.; Forero-Gómez, J.E.; Suárez-Brochero, Ó.F.; Medina-Morales, A. Acute Febrile Syndrome in an endemic region of Colombia: What is there beyond Dengue? Iatreia 2023, 36, 147–157. [Google Scholar]
- González-Macea, O.; Martínez-Ávila, M.C.; Pérez, M.; Tibocha Gordon, I.; Arroyo Salgado, B. Concurrent Dengue-Malaria Infection: The Importance of Acute Febrile Illness in Endemic Zones. Clin. Med. Insights Case Rep. 2023, 16, 117954762211445. [Google Scholar] [CrossRef]
- Cortés, J.A.; Romero Moreno, L.F.; Aguirre León, C.A.; Pinzón Lozano, L.; Cuervo, S.I. Enfoque clínico del síndrome febril agudo en Colombia. Infectio 2017, 21, 39–50. [Google Scholar] [CrossRef][Green Version]
- Villamil-Gómez, W. Protocolo Diagnóstico Del Síndrome Febril Sin Focalidad En Áreas Geográficas de Riesgo Endémico de Infecciones Tropicales. Med. Programa Form. Méd. Contin. Acreditado 2022, 13, 3426–3431. [Google Scholar] [CrossRef]
- Kigozi, B.K.; Kharod, G.A.; Bukenya, H.; Shadomy, S.V.; Haberling, D.L.; Stoddard, R.A.; Galloway, R.L.; Tushabe, P.; Nankya, A.; Nsibambi, T.; et al. Investigating the etiology of acute febrile illness: A prospective clinic-based study in Uganda. BMC Infect. Dis. 2023, 23, 411. [Google Scholar] [CrossRef] [PubMed]
- Guía de Práctica Clínica Diagnóstico y Tratamiento de la Malaria; Ministerio de Salud y Protección Social: Bogotá, Colombia, 2022.
- Reyes, A.J.R.; Ruge, D.G.; Herrera, L.C.P. Informe de Evento Dengue; Instituto Nacional de Salud: Bogotá, Colombia, 2019. [Google Scholar]
- Ramírez, V.G.; García, M.A.B.; Limas, C.A.S. Guía de Atención de la Fiebre Amarilla; Ministerio de Salud y Protección Social: Bogotá, Colombia, 2003. [Google Scholar]
- Gómez, F.R.; Saldarriaga, E.O.; Londoño, D.A.G.; Lozano, F.E.L. Lineamientos Para la Atención Clínica Integral de Pacientes con Zika en Colombia; Ministerio de Salud y Protección Social: Bogotá, Colombia, 2016. [Google Scholar]
- Monsalve, L.C.O.; Valderrama, J.F. Chikunguña, Memorias Para el Personal en Bacteriología; Ministerio de Salud y Protección Social: Bogotá, Colombia, 2015. [Google Scholar]
- Koliopoulos, P.; Kayange, N.M.; Daniel, T.; Huth, F.; Gröndahl, B.; Medina-Montaño, G.C.; Pretsch, L.; Klüber, J.; Schmidt, C.; Züchner, A.; et al. Multiplex-RT-PCR-ELISA panel for detecting mosquito-borne pathogens: Plasmodium sp. preserved and eluted from dried blood spots on sample cards. Malar. J. 2021, 20, 66. [Google Scholar] [CrossRef]
- Puppe, W.; Weigl, J.; Gröndahl, B.; Knuf, M.; Rockahr, S.; von Bismarck, P.; Aron, G.; Niesters, H.G.M.; Osterhaus, A.D.M.E.; Schmitt, H.-J. Validation of a multiplex reverse transcriptase PCR ELISA for the detection of 19 respiratory tract pathogens. Infection 2013, 41, 77–91. [Google Scholar] [CrossRef] [PubMed]
- Instituto Nacional de Salud. Boletín Epidemiológico Semanal. Semana Epidemiológica 52. 2022. Available online: https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2022_Boletin_epidemiologico_semana_52.pdf (accessed on 25 September 2023).
- Padilla, J.C.; Lizarazo, F.E.; Murillo, O.L.; Mendigaña, F.A.; Pachón, E.; Vera, M.J. Epidemiología de las principales enfermedades transmitidas por vectores en Colombia, 1990–2016. Biomédica 2017, 37, 27. [Google Scholar] [CrossRef] [PubMed]
- Gröndahl, B.; Puppe, W.; Hoppe, A.; Kühne, I.; Weigl, J.A.I.; Schmitt, H.-J. Rapid Identification of Nine Microorganisms Causing Acute Respiratory Tract Infections by Single-Tube Multiplex Reverse Transcription-PCR: Feasibility Study. J. Clin. Microbiol. 1999, 37, 1–7. [Google Scholar] [CrossRef]
- Chappuis, F.; Alirol, E.; d’Acremont, V.; Bottieau, E.; Yansouni, C.P. Rapid diagnostic tests for non-malarial febrile illness in the tropics. Clin. Microbiol. Infect. 2013, 19, 422–431. [Google Scholar] [CrossRef]
- Paixão, E.S.; Teixeira, M.G.; Rodrigues, L.C. Zika, chikungunya and dengue: The causes and threats of new and re-emerging arboviral diseases. BMJ Glob. Health 2018, 3, e000530. [Google Scholar] [CrossRef]
- Weaver, S.C.; Charlier, C.; Vasilakis, N.; Lecuit, M. Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases. Annu. Rev. Med. 2018, 69, 395–408. [Google Scholar] [CrossRef]
- Simmons, C.P.; Farrar, J.J.; Nguyen, V.V.; Wills, B. Dengue. N. Engl. J. Med. 2012, 366, 1423–1432. [Google Scholar] [CrossRef]
- Girard, M.; Nelson, C.B.; Picot, V.; Gubler, D.J. Arboviruses: A global public health threat. Vaccine 2020, 38, 3989–3994. [Google Scholar] [CrossRef]
- Klüber, J. Etablierung Einer Multiplex-PCR zur Detektierung von Chikungunya, West Nil und Dengue. Master’s Thesis, Johannes-Gutenberg-Universität Mainz, Mainz, Germany, 2016. [Google Scholar]
- Medina-Montaño, G.C. Establishment of A m-RT-PCR for the Diagnosis of Arboviral Etiologies of Malaria-Like Acute Febrile Illnesses. Master’s Thesis, Johannes-Gutenberg-Universität Mainz, Mainz, Germany, 2017. [Google Scholar]
- Daniel, T.W. Etablierung einer Multiplex-PCR zur Diagnostik von Arboviralen Infektionen und Malaria. Master’s Thesis, Johannes Gutenberg-Universität Mainz, Mainz, Germany, 2019. [Google Scholar]
- Ramanan, P.; Bryson, A.L.; Binnicker, M.J.; Pritt, B.S.; Patel, R. Syndromic Panel-Based Testing in Clinical Microbiology. Clin. Microbiol. Rev. 2018, 31, e00024-17. [Google Scholar] [CrossRef] [PubMed]
- Tansarli, G.S.; Chapin, K.C. Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: A systematic review and meta-analysis. Clin. Microbiol. Infect. 2020, 26, 281–290. [Google Scholar] [CrossRef] [PubMed]
- Gutierrez-Barbosa, H.; Medina-Moreno, S.; Zapata, J.C.; Chua, J.V. Dengue Infections in Colombia: Epidemiological Trends of a Hyperendemic Country. Trop. Med. Infect. Dis. 2020, 5, 156. [Google Scholar] [CrossRef]
- Restrepo, B.N.; Piedrahita, L.D.; Agudelo, I.Y.; Marín, K.; Ramírez, R.E. Infección por dengue una causa frecuente de síndrome febril en pacientes de Quibdó, Chocó, Colombia. Biomédica 2014, 35, 2345. [Google Scholar] [CrossRef][Green Version]
- Vilela, A.P.P.; Miranda, D.P.J.; Andrade, E.H.P.; Abrahão, J.S.; Araújo, V.E.M.; Zibaoui, H.M.; Oliveira, J.G.; Rosa, J.C.C.; Figueiredo, L.B.; Kroon, E.G.; et al. Spatial–Temporal Co-Circulation of Dengue Virus 1, 2, 3, and 4 Associated with Coinfection Cases in a Hyperendemic Area of Brazil: A 4-Week Survey. Am. J. Trop. Med. Hyg. 2016, 94, 1080–1084. [Google Scholar] [CrossRef]
- Mamani, E.; Figueroa, D.; García, M.P.; Pozo, E.J. Infecciones Concurrentes Por dos Serotipos del Virus Dengue Durante un Brote en el Noroeste de Perú. Rev. Peru Med. Exp. Salud Publica 2010, 27, 16–21. [Google Scholar] [CrossRef] [PubMed]
- Masyeni, S.; Yohan, B.; Sasmono, R.T. Concurrent infections of dengue virus serotypes in Bali, Indonesia. BMC Res. Notes 2019, 12, 129. [Google Scholar] [CrossRef] [PubMed]
- Simo Tchetgna, H.; Sado Yousseu, F.; Kamgang, B.; Tedjou, A.; McCall, P.J.; Wondji, C.S. Concurrent circulation of dengue serotype 1, 2 and 3 among acute febrile patients in Cameroon. PLoS Negl. Trop. Dis. 2021, 15, e0009860. [Google Scholar] [CrossRef]
- Ramos-Castañeda, J.; Barreto dos Santos, F.; Martínez-Vega, R.; Galvão de Araujo, J.M.; Joint, G.; Sarti, E. Dengue in Latin America: Systematic Review of Molecular Epidemiological Trends. PLoS Negl. Trop. Dis. 2017, 11, e0005224. [Google Scholar] [CrossRef]
- Senaratne, U.T.N.; Murugananthan, K.; Sirisena, P.D.N.N.; Carr, J.M.; Noordeen, F. Dengue virus co-infections with multiple serotypes do not result in a different clinical outcome compared to mono-infections. Epidemiol. Infect. 2020, 148, e119. [Google Scholar] [CrossRef]
- Dhanoa, A.; Hassan, S.S.; Ngim, C.F.; Lau, C.F.; Chan, T.S.; Adnan, N.A.A.; Eng, W.W.H.; Gan, H.M.; Rajasekaram, G. Impact of dengue virus (DENV) co-infection on clinical manifestations, disease severity and laboratory parameters. BMC Infect. Dis. 2016, 16, 406. [Google Scholar] [CrossRef] [PubMed]
- De Alwis, R.; Williams, K.L.; Schmid, M.A.; Lai, C.-Y.; Patel, B.; Smith, S.A.; Crowe, J.E.; Wang, W.-K.; Harris, E.; De Silva, A.M. Dengue Viruses Are Enhanced by Distinct Populations of Serotype Cross-Reactive Antibodies in Human Immune Sera. PLoS Pathog. 2014, 10, e1004386. [Google Scholar] [CrossRef] [PubMed]
- Aguas, R.; Dorigatti, I.; Coudeville, L.; Luxemburger, C.; Ferguson, N.M. Cross-serotype interactions and disease outcome prediction of dengue infections in Vietnam. Sci. Rep. 2019, 9, 9395. [Google Scholar] [CrossRef] [PubMed]
- Shukla, M.K.; Singh, N.; Sharma, R.K.; Barde, P.V. Utility of dengue NS1 antigen rapid diagnostic test for use in difficult to reach areas and its comparison with dengue NS1 ELISA and qRT-PCR. J. Med. Virol. 2017, 89, 1146–1150. [Google Scholar] [CrossRef]
- Oboh, M.A.; Oriero, E.C.; Ndiaye, T.; Badiane, A.S.; Ndiaye, D.; Amambua-Ngwa, A. Comparative analysis of four malaria diagnostic tools and implications for malaria treatment in southwestern Nigeria. Int. J. Infect. Dis. 2021, 108, 377–381. [Google Scholar] [CrossRef]
- John, E.H. Unidad III: El corazón Guyton & Hall. Tratado de Fisiología Médica, 13th ed.; Elsevier: Amsterdam, The Netherlands, 2016. [Google Scholar]
- Parchani, A.; Krishnan, V.G.; Kumar, V.S. Electrocardiographic Changes in Dengue Fever: A Review of Literature. Int. J. Gen. Med. 2021, 14, 5607–5614. [Google Scholar] [CrossRef]
- Organización Panamericana de la Salud. Dengue: Guías para la Atención de Enfermos en la Región de las Américas, 2nd ed.; Oficina Sanitaria Panamericana—Oficina Regional de la Organización Mundial de la Salud: Washington, DC, USA, 2016; ISBN 978-92-75-31890-4. [Google Scholar]
- Epelboin, L.; Boullé, C.; Ouar-Epelboin, S.; Hanf, M.; Dussart, P.; Djossou, F.; Nacher, M.; Carme, B. Discriminating Malaria from Dengue Fever in Endemic Areas: Clinical and Biological Criteria, Prognostic Score and Utility of the C-Reactive Protein: A Retrospective Matched-Pair Study in French Guiana. PLoS Negl. Trop. Dis. 2013, 7, e2420. [Google Scholar] [CrossRef]
- Kaagaard, M.D.; Matos, L.O.; Holm, A.E.; Gomes, L.C.; Wegener, A.; Lima, K.O.; Vieira, I.V.M.; de Souza, R.M.; Marinho, C.R.F.; Hviid, L.; et al. Frequency of Electrocardiographic Alterations and Pericardial Effusion in Patients with Uncomplicated Malaria. Am. J. Cardiol. 2022, 165, 116–123. [Google Scholar] [CrossRef]
- Silva, M.M.O.; Tauro, L.B.; Kikuti, M.; Anjos, R.O.; Santos, V.C.; Gonçalves, T.S.F.; Paploski, I.A.D.; Moreira, P.S.S.; Nascimento, L.C.J.; Campos, G.S.; et al. Concomitant Transmission of Dengue, Chikungunya, and Zika Viruses in Brazil: Clinical and Epidemiological Findings from Surveillance for Acute Febrile Illness. Clin. Infect. Dis. 2019, 69, 1353–1359. [Google Scholar] [CrossRef]
- World Health Organization. Laboratory Testing for Zika Virus and Dengue Virus Infections. 2022. Available online: https://iris.who.int/bitstream/handle/10665/359857/WHO-ZIKV-DENV-LAB-2022.1-eng.pdf?sequence=1 (accessed on 25 September 2023).
- Muller, D.A.; Depelsenaire, A.C.I.; Young, P.R. Clinical and Laboratory Diagnosis of Dengue Virus Infection. J. Infect. Dis. 2017, 215, S89–S95. [Google Scholar] [CrossRef]
- Deng, J.; Ma, Z.; Huang, W.; Li, C.; Wang, H.; Zheng, Y.; Zhou, R.; Tang, Y.-W. Respiratory virus multiplex RT-PCR assay sensitivities and influence factors in hospitalized children with lower respiratory tract infections. Virol. Sin. 2013, 28, 97–102. [Google Scholar] [CrossRef] [PubMed]
Sociodemographic Data | Total | |
---|---|---|
n % | ||
Sex | ||
Male | 83 | 53.5 |
Female | 72 | 46.5 |
Age groups (years) a | ||
<5 | 17 | 11.0 |
5 to ≤15 | 37 | 23.9 |
≥15 | 86 | 55.5 |
Study location | ||
Antioquia | 81 | 52.3 |
Choco | 74 | 47.7 |
Residence a | ||
Urban area | 101 | 65.2 |
Rural area | 35 | 22.6 |
Village | 8 | 5.2 |
History of malaria a | ||
<1 month | 1 | 0.6 |
1 to 2 months | 3 | 1.9 |
3 to 6 months | 8 | 5.2 |
7 to 12 months | 3 | 1.9 |
>1 year | 33 | 21.3 |
Unsure | 2 | 1.3 |
Dengue-Positive Total (n = 16) | Malaria-Positive Total (n = 25) | Negative Total (n = 114) | ||||
---|---|---|---|---|---|---|
n | % | n | % | n | % | |
Vital signs a | ||||||
Heart rate (beats per min.) | 108 (92–130) | 98 (78–121) | 86 (75–102) | |||
Respiratory rate (breaths per min.) | 21 (19–22) | 21 (18–24) | 19 (16–22) | |||
Temperature °C | 37.5 (37.1–38.5) | 37.1 (36.6–37.9) | 36.9 (36.3–37.8) | |||
SpO2 (%) | 98 (98–99) | 98 (97–99) | 98 (97–98) | |||
Symptoms | ||||||
Headache | 13 | 81.3 | 22 | 88.0 | 104 | 92.2 |
Chills | 13 | 81.3 | 23 | 92.0 | 87 | 76.3 |
Sweats | 11 | 68.8 | 19 | 76.0 | 82 | 71.9 |
Arthralgia | 10 | 62.5 | 15 | 60.0 | 55 | 48.2 |
Nausea | 8 | 50.0 | 13 | 52.0 | 54 | 47.4 |
Myalgia | 9 | 56.3 | 13 | 52.0 | 52 | 45.6 |
Retro-orbital pain | 6 | 37.5 | 12 | 48.0 | 55 | 48.2 |
Abdominal pain | 7 | 43.8 | 12 | 48.0 | 36 | 31.6 |
Fever | 8 | 50,0 | 9 | 36.0 | 35 | 30.7 |
Vomiting | 7 | 43.8 | 7 | 28.0 | 25 | 21.9 |
Diarrhea | 0 | 0.0 | 4 | 16.0 | 9 | 7.9 |
Rash | 3 | 18.8 | 1 | 4.0 | 9 | 7.9 |
Hemoglobin (mg/dL) b | 12.5 ± 1.23 | 12.1 ± 2.44 | 12.9 ± 2.10 |
Rapid Test a | m-RT-PCR-ELISA | |||||
---|---|---|---|---|---|---|
Result | n | % | Result | n | % | |
Antioquia | Negative | 65 | 80.2 | Negative | 67 | 82.7 |
P. vivax | 9 | 11.2 | P. vivax | 8 | 9.9 | |
P. falciparum | 7 | 8.6 | P. falciparum | 5 b | 6.2 | |
Choco | Negative | 65 | 87.8 | Negative | 65 | 87.8 |
P. falciparum | 5 | 6.8 | P. falciparum | 5 | 6.8 | |
P. vivax | 4 | 5.4 | P. vivax | 4 | 5.4 |
Rapid Test a | m-RT-PCR-ELISA | ||||||||
---|---|---|---|---|---|---|---|---|---|
Result | n | % | Result | n | % | Serotype | n | % | |
Antioquia | Negative | 71 | 87.7 | Negative | 71 | 87.7 | |||
Positive | 10 | 12.3 | Positive | 10 | 12.3 | DENV2 | 1 | 10.0 | |
DENV3 | 4 | 40.0 | |||||||
DENV1 & 4 b | 5 | 50.0 | |||||||
Choco | Negative | 68 | 91.9 | Negative | 68 | 91.9 | |||
Positive | 6 | 8.1 | Positive | 6 | 8.1 | DENV1 | 2 | 33.3 | |
DENV1 & 4 b | 4 | 66.7 |
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Calderon-Ruiz, P.; Haist, G.; Mascus, A.; Holguin-Rocha, A.F.; Koliopoulos, P.; Daniel, T.; Velez, G.; Londono-Renteria, B.; Gröndahl, B.; Tobon-Castano, A.; et al. Multiplex Reverse Transcription Polymerase Chain Reaction Combined with a Microwell Hybridization Assay Screening for Arbovirus and Parasitic Infections in Febrile Patients Living in Endemic Regions of Colombia. Trop. Med. Infect. Dis. 2023, 8, 466. https://doi.org/10.3390/tropicalmed8100466
Calderon-Ruiz P, Haist G, Mascus A, Holguin-Rocha AF, Koliopoulos P, Daniel T, Velez G, Londono-Renteria B, Gröndahl B, Tobon-Castano A, et al. Multiplex Reverse Transcription Polymerase Chain Reaction Combined with a Microwell Hybridization Assay Screening for Arbovirus and Parasitic Infections in Febrile Patients Living in Endemic Regions of Colombia. Tropical Medicine and Infectious Disease. 2023; 8(10):466. https://doi.org/10.3390/tropicalmed8100466
Chicago/Turabian StyleCalderon-Ruiz, Paula, Gregor Haist, Annina Mascus, Andres F. Holguin-Rocha, Philip Koliopoulos, Tim Daniel, Gabriel Velez, Berlin Londono-Renteria, Britta Gröndahl, Alberto Tobon-Castano, and et al. 2023. "Multiplex Reverse Transcription Polymerase Chain Reaction Combined with a Microwell Hybridization Assay Screening for Arbovirus and Parasitic Infections in Febrile Patients Living in Endemic Regions of Colombia" Tropical Medicine and Infectious Disease 8, no. 10: 466. https://doi.org/10.3390/tropicalmed8100466
APA StyleCalderon-Ruiz, P., Haist, G., Mascus, A., Holguin-Rocha, A. F., Koliopoulos, P., Daniel, T., Velez, G., Londono-Renteria, B., Gröndahl, B., Tobon-Castano, A., & Gehring, S. (2023). Multiplex Reverse Transcription Polymerase Chain Reaction Combined with a Microwell Hybridization Assay Screening for Arbovirus and Parasitic Infections in Febrile Patients Living in Endemic Regions of Colombia. Tropical Medicine and Infectious Disease, 8(10), 466. https://doi.org/10.3390/tropicalmed8100466