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At the beginning of April 2019, China National Health Commission (NHC) and China Center for Disease Control and Prevention (China CDC) received reports of a cluster of febrile illness involving about ten Chinese workers in a manganese ore in Cooperative Republic of Guyana. The enterprise applied to NHC for permission for evacuating the patients back to China for further treatment. A special Chinese medical team composed of the experts of epidemiology, medical bacteriology, clinical and emergency medicines was deployed to Georgetown, Guyana on April 6, 2019 to provide the support in clinical and public health, to identify the potential etiology and to assess the potential threat, especially the risk of international transmission.
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Various tissue specimens from the two fatal cases and blood samples from surviving patients were transferred to the laboratories of China CDC. Next-generation sequencing (NGS) technology based on Illumina MiSeq platform identified different lengths of specific gene sequences of Histoplasma capsulatum in seven different samples of two fatal cases and one severe case, including lung and blood samples. Up to April 15, 7 cases were laboratory confirmed as being infected with Histoplasma capsulatum. Therefore, 7 of 15 patients were laboratory confirmed cases and the remaining 8 patients were clinically diagnosed cases (Table 1).
Case No. Age (years) Date of Onset Type of diagnosis Clinical Outcome Clinical evaluation score† Details of exposure in the four old mines Date of first entry Date of last entry Times of entry No. of mines Type of work Place of work Hours of stay per time Other miner's working§ Exposure intensity¶ 1 47 Mar 22 Laboratory confirmed Dead 100 Mar 16 Mar 22 7 4 Shovel Bottom 2 Yes 189 2 44 Mar 26 Laboratory confirmed Dead 100 Mar 16 Mar 25 7 4 Shovel Bottom 2 Yes 270 3 42 Mar 27 Laboratory confirmed Coma, ICU 90 Mar 16 Mar 27 5 4 Shovel, crush Bottom, middle 2 Yes 175 4 51 Mar 25 Laboratory confirmed ICU 90 Mar 17 Mar 23 5 4 Shovel Bottom 2 Yes 171 5 49 Mar 29 Laboratory confirmed Hospitalization 70 Mar 16 Mar 27 7 4 Shovel, crush Bottom, middle 2 Yes 249 6 33 Mar 29 Clinical diagnosis Hospitalization 1 Mar 18 Mar 18 1 1 Check around Bottom 0.1 Yes 0.113 7 44 Mar 28 Laboratory confirmed Hospitalization 1 Mar 24 Mar 27 4 4 Crush, check around Bottom 1.5 No 9.6 8 56 Mar 30 Clinical diagnosis Hospitalization 20 Mar 16 Mar 24 2 4 Check around Bottom 0.1 No 0.525 9 34 Mar 30 Clinical diagnosis Hospitalization 30 Mar 18 Mar 28 1 2 Crush Bottom 1.5 Yes 5.625 10 48 Mar 30 Clinical diagnosis Hospitalization 1 Mar 16 Mar 16 2 1 Check around Bottom 0.1 Yes 0.225 11 43 Mar 30 Clinical diagnosis Hospitalization 5 Mar 17 Mar 27 1 2 Check around Bottom 0.1 Yes 0.3 12 38 Mar 31 Clinical diagnosis Discharge 0.5 Mar 16 Mar 16 1 1 Check around Entrance 0.5 No 0.094 13 50 Mar 26 Laboratory confirmed ICU 80 Mar 16 Mar 24 7 4 Shovel Bottom, middle 2 Yes 198 14 41 Apr 11 Clinical diagnosis Hospitalization 30 Mar 28 Mar 28 1 1 Crush Middle 1.5 Yes 2.25 15 23 Apr 11 Clinical diagnosis Hospitalization 30 Mar 28 Mar 29 2 2 Crush Entrance 6 Yes 12 Abbreviation: ICU = intensive care unit. All 15 cases were male. Next-generation sequencing (NGS) technology based on Illumina MiSeq platform identified different lengths of specific gene sequences of Histoplasma capsulatum in 7 different samples of 2 fatal cases and one severe case, including lung and blood samples. Up to April 15, 2019, 7 cases were laboratory confirmed being infected with Histoplasma capsulatum.
* All data were updated as of April 15, 2019 when the special Chinese medical team departed from Guyana back to China.† A clinical evaluation score (range: 0.5 to 100) was assigned to each of the 15 Chinese cases by clinical experts according to their illness severity. The more severe the illness was, the higher score was. § Were other miners working close by? ¶ The exposure intensity was a score representing the exposure degree and risk of infection according to the detailed exposure information of the case-patients. It was calculated by using the equation of $\sum\nolimits_{F = 1}^n {\left( {{{twTLE}}} \right)} $; n was the number of the abandoned tunnels (range: 1-4), F was the times of entry, t was hours of stay per entry, w was the type of work including shovel (score=1.5), crush (score=1) and inspection (score=0.5), T was the date of entry including Period 1 (score=1.5) from March 13 to 22, 2019 and Period 2 (score=1) from March 23 to 29, 2019, L was the place of work including the bottom (score=1.5), middle (score=1) and entrance (score=0.5) of the tunnels, and E indicated whether other work was performed during the stay (Yes scoring 1, No scoring 0.5).Table 1. The epidemiological and clinical characteristics of the 15 Chinese manganese-miner male case-patients in the outbreak of febrile illness in Matthews Ridge, Cooperative Republic of Guyana in 2019*
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As shown in Table 1, the frequency of entry and duration of stay inside of the tunnels among the 15 Chinese patients varied largely. To evaluate the exposure intensity of cases, an equation was used as below:
$$\mathop \sum \nolimits_{F = 1}^n \left( {{{twTLE}}} \right)$$ Of note, n was the number of abandoned tunnels (range: 1-4), F was the times of entry, t was hours of stay per entry, w was the type of work including shovel (score=1.5), crush (score=1), and inspection (score=0.5), T was the date of entry including Period 1 (score=1.5) from March 13 to 22 and Period 2 (score=1) from March 23 to 29, L was the place of work including the bottom (score=1.5), middle (score=1) and entrance (score=0.5) of the tunnels, and E indicated whether other work was performed during the stay (Yes scoring 1, No scoring 0.5).
Two distinct profiles of exposure intensity among the patients were clearly noticed. One was above 170 and the other was below 15. A logistic regression model [y=11.882ln(x)+18.405] was established by combining the exposure intensity scores of the cases with the individual clinical scores. The distribution of the 15 patients were distinctly divided in two separate areas (Figure 2). Patients with severe clinical manifestations and poor prognosis harbored significantly higher exposure intensity scores, in which 2 fatal cases showed exposure intensity scores of 189 and 270. Patients with low exposure intensity scores underwent mild clinical processes (Table 1). These data indicate a close relationship between the exposure intensity and disease severity.
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