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]
- 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]
- 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 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
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