Sequential determination of viral load, humoral responses and phylogenetic analysis in fatal and non-fatal cases of Crimean-Congo hemorrhagic fever patients from Gujarat, India, 2019
Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. Methods Thirty four cases were included in t...
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| Published in | PLoS neglected tropical diseases Vol. 15; no. 8; p. e0009718 |
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| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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01.08.2021
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| Abstract | Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. Methods Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tickpools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. Results CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76.sup.th POD in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2.sup.nd and 20.sup.th POD (post onset date) respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-[gamma] during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. Conclusions The persistence of CCHF viral RNA was detected till 76.sup.th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India. |
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| AbstractList | Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. Methods Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tickpools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. Results CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76.sup.th POD in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2.sup.nd and 20.sup.th POD (post onset date) respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-[gamma] during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. Conclusions The persistence of CCHF viral RNA was detected till 76.sup.th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India. BackgroundThirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases.MethodsThirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences.ResultsCCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks.ConclusionsThe persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India. Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases.BACKGROUNDThirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases.Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences.METHODSThirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences.CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks.RESULTSCCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks.The persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India.CONCLUSIONSThe persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India. Crimean Congo hemorrhagic fever is a zoonotic tick-borne viral hemorrhagic disease. This disease is reported from Europe, Mediterranean, north-western China, central Asia, Africa, and the Middle East. Several outbreaks of CCHF were reported from Gujarat and Rajasthan states, India from 2011 to 2019. In this study, we discuss the clinical, molecular, serological, and the cytokine data of 34 CCHF cases (17 fatal and 17 survived) which were detected from Gujarat state in the year 2019. A sequential weekly follow up of the CCHF survivors was performed to understand the viral kinetics and the antibody profile. Interestingly, the presence of persistence CCHF viral RNA was observed till 76 th POD in one of the survivors. To our knowledge, we are reporting this long term persistence of viremia for the first time. We also observed that the anti-CCHFV IgM detection in the serum samples starts as soon as 2 nd POD but anti-CCHFV IgG antibody could be detected in the majority of the cases only after the 28 th POD. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. We did the phylogenetic analysis and concluded the circulation of the Asian-West African re-assortment genotype in humans, which has not been reported from India prior to this study. Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. Methods Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. Results CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19–45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. Conclusions The persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India. Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tickpools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76.sup.th POD in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2.sup.nd and 20.sup.th POD (post onset date) respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-[gamma] during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. The persistence of CCHF viral RNA was detected till 76.sup.th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India. Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. Methods Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. Results CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19–45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. Conclusions The persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India. |
| Audience | Academic |
| Author | Patil, Savita Shete, Anita M. Nyayanit, Dimpal A. Kaushal, Himanshu Gangakhedkar, Raman R. Panjwani, Sunil J. Yadav, Pragya D. Majumdar, Triparna Sahay, Rima R. Vora, Alpesh Varevadiya, Chetan L. Kanani, Amit Jain, Rajlaxmi Upadhyay, Kamlesh J. |
| AuthorAffiliation | 1 Indian Council of Medical Research-National Institute of Virology, Maximum Containment Facility, Pune, Maharashtra, India 4 Health Department, District Panchayat, Morbi, Gujarat, India 6 Epidemiology and Communicable Diseases (ECD) Division, Indian Council of Medical Research, New Delhi, India 2 Government Medical College and Sir-T Hospital Bhavnagar, Gujarat, India 3 BJ Medical College and Civil Hospital, Ahmedabad, Gujarat, India 5 Animal Husbandry Department, Foot and Mouth Disease Scheme, Ahmedabad, Gujarat, India Lowell General Hospital, UNITED STATES |
| AuthorAffiliation_xml | – name: Lowell General Hospital, UNITED STATES – name: 6 Epidemiology and Communicable Diseases (ECD) Division, Indian Council of Medical Research, New Delhi, India – name: 4 Health Department, District Panchayat, Morbi, Gujarat, India – name: 5 Animal Husbandry Department, Foot and Mouth Disease Scheme, Ahmedabad, Gujarat, India – name: 3 BJ Medical College and Civil Hospital, Ahmedabad, Gujarat, India – name: 1 Indian Council of Medical Research-National Institute of Virology, Maximum Containment Facility, Pune, Maharashtra, India – name: 2 Government Medical College and Sir-T Hospital Bhavnagar, Gujarat, India |
| Author_xml | – sequence: 1 givenname: Rima R. orcidid: 0000-0003-1492-5568 surname: Sahay fullname: Sahay, Rima R. – sequence: 2 givenname: Anita M. orcidid: 0000-0003-2625-3703 surname: Shete fullname: Shete, Anita M. – sequence: 3 givenname: Pragya D. orcidid: 0000-0002-0861-7166 surname: Yadav fullname: Yadav, Pragya D. – sequence: 4 givenname: Savita orcidid: 0000-0002-8358-1271 surname: Patil fullname: Patil, Savita – sequence: 5 givenname: Triparna surname: Majumdar fullname: Majumdar, Triparna – sequence: 6 givenname: Rajlaxmi surname: Jain fullname: Jain, Rajlaxmi – sequence: 7 givenname: Dimpal A. surname: Nyayanit fullname: Nyayanit, Dimpal A. – sequence: 8 givenname: Himanshu orcidid: 0000-0003-0935-9039 surname: Kaushal fullname: Kaushal, Himanshu – sequence: 9 givenname: Sunil J. orcidid: 0000-0003-2267-2804 surname: Panjwani fullname: Panjwani, Sunil J. – sequence: 10 givenname: Kamlesh J. orcidid: 0000-0002-2413-6530 surname: Upadhyay fullname: Upadhyay, Kamlesh J. – sequence: 11 givenname: Chetan L. surname: Varevadiya fullname: Varevadiya, Chetan L. – sequence: 12 givenname: Alpesh surname: Vora fullname: Vora, Alpesh – sequence: 13 givenname: Amit orcidid: 0000-0002-0202-1177 surname: Kanani fullname: Kanani, Amit – sequence: 14 givenname: Raman R. orcidid: 0000-0002-9641-7366 surname: Gangakhedkar fullname: Gangakhedkar, Raman R. |
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| CitedBy_id | crossref_primary_10_2174_0118715265281694240223113930 crossref_primary_10_1002_hsr2_70053 crossref_primary_10_1016_j_micpath_2022_105657 crossref_primary_10_1002_bab_2679 crossref_primary_10_1002_jmv_29218 crossref_primary_10_1093_infdis_jiae395 crossref_primary_10_3389_fviro_2024_1498672 crossref_primary_10_1002_bab_2540 crossref_primary_10_3389_fpubh_2023_1093817 |
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| Copyright | COPYRIGHT 2021 Public Library of Science 2021 Sahay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2021 Sahay et al 2021 Sahay et al |
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| DOI | 10.1371/journal.pntd.0009718 |
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| References_xml | – volume: 13 start-page: 1769 issue: 11 year: 2007 ident: pntd.0009718.ref024 article-title: Viral load as predictor of Crimean-Congo hemorrhagic fever outcome publication-title: Emerg Infect Dis doi: 10.3201/eid1311.070222 – ident: pntd.0009718.ref009 – volume: 142 start-page: 489 year: 2015 ident: pntd.0009718.ref004 article-title: First confirmed case of Crimean-Congo haemorrhagic fever from Sirohi district in Rajasthan State, India publication-title: Indian J. Med. 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| Snippet | Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load,... Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody... Crimean Congo hemorrhagic fever is a zoonotic tick-borne viral hemorrhagic disease. This disease is reported from Europe, Mediterranean, north-western China,... BackgroundThirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load,... Background Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load,... |
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| Title | Sequential determination of viral load, humoral responses and phylogenetic analysis in fatal and non-fatal cases of Crimean-Congo hemorrhagic fever patients from Gujarat, India, 2019 |
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