Identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge, Guyana

Here, we report the identification of Histoplasma causing an unexplained disease cluster in Matthews Ridge, Guyana. In March 2019, 14 employees of Chongqing Bosai Mining Company, China, working in a manganese mining of Guyana, had unexplained fever, and two of them died. We obtained lung and brain tissues as well as the blood samples from the two deceased cases (patient No. 1 and 2), and bronchoscopy lavages and cerebrospinal fluid samples from one severe case (patient No. 3), respectively. All samples were tested by pathological examination, high-throughput sequencing, and real-time PCR. Pathological detection showed the presence of spore-like structures in the lung tissue of patient No. 1, indicating a fungal infection in this patient. Nanopore sequencing identified the existing of H. capsulatum in the lung tissue sample within 13 h. Next-generation sequencing identified specific fragments of H. capsulatum in all of the samples tested (lung, brain and blood serum from the deceased cases, and plasma from the severe case). Real-time PCR assays did not reveal any viral infection related to transmission from bat feces. We conclude that H. capsulatum was the causative pathogen of this disease cluster based on epidemiologic, clinical, pathological and nucleic acid evidence. •Scientific questionThis study reported the identification of Histoplasma as the cause of an unexplained disease cluster in Matthews Ridge, Guyana.•Evidence before this studyIn March 2019, 14 Chinese employees from Chongqing Bosai Mining Company, China, were engaged in manganese mining in Guyana and presented with unexplained fever. Two of them died. After preliminary examination by the local hospital, some potential infectious pathogens were excluded, including Leptospira, HIV, influenza H1N1, Zika virus, Chikungunya virus, Dengue virus, and Influenza A and B viruses. Histoplasmosis is a fungal disease caused by members of the genus Histoplasma and is mainly prevalent in the American continents. Histoplasma is capable of survival in moist soils and can often be isolated from soils containing decaying feces of bats and birds. Human activities in the surface soil produce aerosols, which in turn are inhaled to cause infection.•New findingsIn response to the unexplained disease cluster, pathological examination, high through-put sequencing and real-time PCR were implemented. A TGS platform found Histoplasma within 13 hours. NGS was also successfully applied in response to this event. Compared