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.

中文翻译：

---

2019 年印度古吉拉特邦克里米亚-刚果出血热患者致死和非致死病例的病毒载量、体液反应和系统发育分析的顺序测定。

背景 2019 年，印度古吉拉特邦确认了 34 例 CCHF 病例（17 例死亡；17 例幸存）。我们旨在找出致命和非致命病例之间的病毒载量、抗体动力学、细胞因子谱和系统发育分析。方法本研究共纳入34例病例。所有病例均于入院当天采集血样和尿样。每周对非致命病例进行跟踪，以了解病毒动力学、抗 CCHFV IgM 和 IgG 抗体的特征。我们还量化了致命和非致命病例中的细胞因子。对于流行病学相关性，对牲畜进行抗 CCHF IgG 抗体筛查，并通过实时 RT-PCR 检测蜱池标本。尝试对蜱池和人类标本进行病毒分离，并对人类和蜱的完整基因组序列进行系统发育分析。结果 2019 年全年均发现 CCHF 病例，以 8 月为高峰。在 34 个病例中，报告了 8 个继发性 CCHF 病例。病例主要发生在男性和 19-45 岁年龄组中 (55.88%)。在一个病例中观察到病毒血症持续到第 76 天（发病后日期），而在这些病例中分别从第 2 天和第 20 天起检测到抗 CCHFV IgM 和 IgG。在牲畜和蜱池中观察到的阳性率分别为 21.57% 和 7.4%。细胞因子分析显示，在感染的急性期，血清 IL-6、IL-10 和 IFN-γ 水平显着升高，但有趣的是，在临床康复病例中，病毒清除后 IL-10 降至正常。致命病例具有高病毒 RNA 拷贝数。一个或两个粘膜部位的出血与死亡率显着相关（OR-16.47；p-0.0034，95% CI）。我们可以从两个案例中进行 CCHF 病毒分离。系统发育分析揭示了亚洲-西非基因型在人类和蜱中重新分类的循环。结论 在一名幸存者中检测到 CCHF 病毒 RNA 持续存在到第 76 天。印度也首次报道了 CCHF 病例中重新分类的亚洲-西非基因型的传播。我们可以从两个案例中进行 CCHF 病毒分离。系统发育分析揭示了亚洲-西非基因型在人类和蜱中重新分类的循环。结论 在一名幸存者中检测到 CCHF 病毒 RNA 持续存在到第 76 天。印度也首次报道了 CCHF 病例中重新分类的亚洲-西非基因型的传播。我们可以从两个案例中进行 CCHF 病毒分离。系统发育分析揭示了亚洲-西非基因型在人类和蜱中重新分类的循环。结论 在一名幸存者中检测到 CCHF 病毒 RNA 持续存在到第 76 天。印度也首次报道了 CCHF 病例中重新分类的亚洲-西非基因型的传播。