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

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 76th POD in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th 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-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.

Distribution pattern of Crimean–Congo Hemorrhagic Fever in Asia and the Middle East

“…From 2010 to 2019, 34 outbreaks were reported from the region of Uttar Pradesh, Rajasthan, and Gujarat ( 55 ). Eight secondary cases of CCHF were reported out of the 34 cases ( 56 ). In another study, CCHF cases were detected in four states of India ( 57 ).…”

Analysis of highly frequent point mutations in glycoprotein C, glycoprotein N, and nucleoprotein of CCHFV

“…12,13 Recently, 34 cases of CCHF disease were notified, and among them 17 patients died in 2019 in Gujarat, India. 14 Out of 34 cases, eight patients were tested positive for CCHF disease due to exposure of infected body fluid and taking care of CCHF-infected patients. 14 This report described that CCHFV is highly contagious and can be transmitted from infected patient to healthy individual, 14 and moreover CCHFV has been listed as a high-priority pathogen by World Health Organization.…”

A fatal case of Crimean‐Congo hemorrhagic fever from Kutch, Gujarat, India 2023

“…2 Since the year 2011, sporadic cases and outbreaks of CCHF have been reported from 15 districts of Gujarat and four districts of Rajasthan state. [3][4][5][6][7][8][9][10] These cases were mainly associated with individuals who have had close contact with livestock, such as farmers, slaughterhouse workers, or healthcare professionals involved in treating infected individuals. 1 Apparently, the majority of the cases and outbreaks have been known to occur while handling livestock.…”

“…1 Apparently, the majority of the cases and outbreaks have been known to occur while handling livestock. [3][4][5][6][7][8][9][10] The initial symptoms of CCHF can be nonspecific including fever, headache, myalgia, and fatigue. As the disease progresses, patients may experience more severe symptoms such as bleeding, bruising, and multiorgan dysfunction.…”

“…All the acute phase markers were elevated including C-reactive protein amongst CCHF survivors and fatal cases in 2019. 9 Subsequently, the Hyalomma tick pools (n = 2) and cattle blood specimens (n = 17) were collected from the household of the case (Figure 1). Of the tick pools, one tick pool was found to be positive for CCHF viral RNA [1.4 × 10 4 copies/mL], while anti-CCHFV IgG antibodies were detected in the serum of only one cattle.…”