descriptive investigation of a cluster of 5 sfts cases following exposure to an index patient who died from the disease was performed . a 77-year - old male farmer who died from sfts
five other cases in the cluster included a 32-year - old male intensive care unit ( icu ) physician ( case 1 ) , a 48-year - old male icu consultation physician ( case 2 ) , a 42-year - old younger son of the index patient ( case 3 ) , and a 45-year - old older son of the index patient ( case 4 ) , as well as a 43-year - old male mortuary beautician ( case 5 ) .
the investigation included a review of circumstances and medical records , specimen collection , virus isolation , real - time polymerase chain reaction for viral rna detection , and sequencing and serological tests ( capture enzyme - linked immunosorbent assay [ elisa ] for immunoglobin [ ig ] m antibody , antigen sandwich elisa for igg antibody , and microneutralization tests [ mnt ] ) .
as for risk assessment of transmission factors , all contactors of the index patient during the period from the beginning ( 25 september 2010 ) to the end ( 8 october 2010 ) were classified through 3 types of contacts , including blood , droplet , and possible airborne contacts . the investigation was reviewed and approved by the ethics committee of china center for disease control and prevention ( cdc ) , which uses international guidelines to ensure confidentiality , anonymity , and informed consent .
the index patient was from an sfts - endemic region and first had onset of illness on 25 september 2010 ; was admitted to a local hospital on 28 september with a high fever of 39.5c and vomiting ; and the infection was identified through initial laboratory testing of thrombocytopenia , leukocytopenia , and elevated aspartate aminotransferase level .
the patient was diagnosed as a suspected sfts case , and transferred to the intensive care unit the next day , where he received ribavirin , dexamethasone , omeprazole , and cryoprecipitation for therapy . on 2 october 2010 ,
his condition deteriorated with hypersomnia , shortness of breath , and mouth mucosal bleeding . on 3 october
, he appeared confused and showed dyspnea , then was intubated and mechanical ventilated . on 4 october ,
the patient was in shock and comatose , developed disseminated intravascular coagulation and multiple organ dysfunction syndrome , and died the next day .
an important observation was that the index patient had unique hemorrhagic symptoms , including bleeding from mouth mucosa , gastrointestinal lumen , and lungs , which was rare in previously identified sfts patients .
the patient s fever remained high ( 39c40c ) until death , although lowered somewhat by giving dexamethasone .
clinical laboratory values ( table 1 ) showed unusually high level of tissue enzymes , blood urea nitrogen , and creatinine , which might indicate impaired liver , heart , and kidney functions .
consistent with the largely reduced platelet count , the index patient had a significantly elongated activated partial thromboplastin time , which represented a largely impaired coagulation function .
immediately after death , the corpse was transferred to the patient s home in a local village for a funeral ceremony , then transferred to a crematorium 3 days later .
laboratory analysis of a cluster of severe fever with thrombocytopenia syndrome patients in china alt , alanine aminotransferase ; ast , aspartate aminotransferase ; ldh , lactate dehydrogenase ; aptt , activated partial thromboplastin time .
 , negative ; + , weak positive ; + + + , strong positive .
viral rna copies were calculated according to standard reaction curves , which were established using serially diluted in vitro rna transcripts as standard samples .
virus load was determined based on an average conversion coefficient between virus copies and virus titer presented as 50% tissue culture infective dose ( tcid50/ml ) .
serum samples collected in the acute phase were subjected to immunoglobin ( ig ) m detection with igm antibody capture enzyme - linked immunosorbent assay ( elisa ) , with horseradish peroxidase  conjugated recombinant severe fever with thrombocytopenia syndrome bunyavirus ( sftsv ) nucleoprotein as the detection agent .
serum samples collected in the convalescent phase were subjected to igg detection with sandwich elisa by using recombinant sftsv nucleoprotein as the detection agent .
values for igm antibodies , igg antibodies , and mnt are the reciprocals of the serum dilution .
risk factors were assessed using logistic regression analysis ; p  <  .05 was considered to be statistically different .
epidemiologic investigations began with interviews with 5 secondary sfts patients and 58 other individuals who had exposure to the index patient from onset of the illness until cremation .
we found that all 5 secondary cases had possible blood contact through skin or mucosa .
case 1 , the local icu doctor , performed the intubation for the index patient , resuscitating the patient before his death .
case 2 , the consultant doctor , traveled from a nonendemic area to the local hospital for a medical consult with the patient , and the patient s blood dropped on his hand when he was helping an icu nurse draw blood without wearing gloves .
case 3 , the younger son of the index patient , was a long - distance truck driver not living in the same village , and directly touched the blood flowing from the deceased patient s mouth and nose when he cried on the corpse .
case 4 , the older son of the index patient , was also a long - distance truck driver , and took care of the dead body and was wiping off the blood from the face of the corpse .
case 5 , a local mortuary beautician , did the make - up for the corpse with gloves and mask , but took them off twice during the procedure . the above 5 cases all developed the disease 715 days after exposure , with only 3 of them having contact with blood after death . in comparison with the index patient
, all 5 secondary cases had minor clinical features ( table 1 ) , without obvious hemorrhagic manifestations , so they did not receive dexamethasone therapy . except for the major risk factor of blood contact , droplet contact ( n  =  4 ) , which included 3 medical staff who were involved in the intubation and the index patient s daughter who cared for him before death ,
in addition , the risk factor of possible airborne transmission ( being in the icu room or funeral room without mask protection ) was also assessed among all 63 exposed individuals . of them , the medical doctors and nurses ( n  =  16 ) were with protection ; and the others were without ( n  =  47 ) , including icu patients who were staying in the same room ( n  =  8) , family members (
n  =  3 ) , and visitors to the funeral room where the corpse was kept ( n  =  35 ) .
the multivariate analysis ( logistic regression analysis ) showed that blood contact was the most likely mode of transmission ( p  <  .001 ; table 1 ) .
it is noticeable that the serum collected from the index patient on the day he died contained a relatively high amount of sftsv , which reached about 3.55    10 viral rna copies / ml ( calculated as 9.67    10 50% tissue culture infective dose [ tcid50]/ml ) .
this number was about 100  000-fold higher than viral copies detected in the serum samples of the 5 secondary patients , which ranged from 10 to 10 copies / ml ( table 1 ) .
all 5 patients had virus - specific igm antibodies in the acute phase , and elevated virus - specific immunoglobin g ( igg ) antibodies in the convalescent phase . the index patient , however , had minimal or undetectable levels of virus specific igm antibodies on day 11 after onset of fever ( table 1 ) . compared with the entire genomic sequence of the virus strain isolated from the index patient ,
cases 2 and 3 were nearly 100% identical , and provided genetic evidence for the epidemic findings on the possible transmission of sftsv from the index patient to secondary patients .
here , we reported the person - to - person transmission of sftsv with a cluster of 6 sfts patients that occurred in shandong province of eastern china .
investigation studies revealed that all 5 secondary infected patients had possible contact with the index patient s blood .
of them , only case 1 ( icu doctor ) had evidence of droplet contact contamination ( during intubation ) but not blood contact , but we included him also as a blood contactor because he performed intubation without protective face shield and goggles , therefore he had an extremely high risk of blood contact through unprotected skin and mucosa .
the risk assessment revealed that blood contact was the major risk factor for the human - to - human transmission of sftsv .
additionally , 3 secondary patients who only had contact with the index patient after death were still infected , which indicated that sftsv - infected blood may remain infectious for a long time , even after patient death .
it is notable that the level of virus copies in the index patient s serum was extremely high , but with no detectable igm or igg antibodies , which suggested that his immune responses to limit the replication of sftsv were severely impaired .
the patient had no immune system disease , thus the minimal immune responses might be due to the early and sustained application of glucocorticoid , which has a side effect of repressing immune functions ; clinical physicians should take note of this finding .
clinically , sfts is easily confused with hemorrhagic fever with renal syndrome caused by hantavirus   and human anaplasmosis .
the hantavirus - specific igm antibodies were not detected in the sfts patients serum samples ( data not show ) . due to the limitation of our study , we were not able to detect rickettsia infection , which was previously reported in outbreaks of nosocomial infections
. however , the methods we used for diagnosis of sfts patients were well validated , and the human - to - human transmission of sftsv we described in this study could not simply be classified as being nosocomial transmission ; specially , 3 of the 5 secondary cases that occurred in the household .
additionally , the lessons of person - to - person transmission of sftsv we learned from this study highlighted the necessity of establishing standard precautions for avoiding direct contact and blood - based transmission .
this work was supported by the china mega - project for infectious diseases ( 2008zx10004 - 001 , 2009zx10004 ) from the ministry of science and technology and ministry of health of the people s republic of china .
conflicts that the editors consider relevant to the content of the manuscript have been disclosed .
 severe fever with thrombocytopenia syndrome bunyavirus is a newly discovered bunyavirus with high pathogenicity to human . 
 the transmission model has been largely uncharacterized . 
 investigation on a cluster of severe fever with thrombocytopenia syndrome cases provided evidence of person - to - person transmission through blood contact to the index patient with high serum virus load . 
METHODS
RESULTS
DISCUSSION
Financial support.
Potential conflicts of interest.