Case A
Case A was a 47-year-old female. On June 4, 2016, she began to feel sick. Next day, she found herself with high fever of 39.9 °C, coughing, sore throat and malaise. She visited local hospitals A and B in Jiangsu Province. Then she was admitted by hospital B and treated with Ticarcillin/Clavulanate Potassium and levofloxacin. No sign of improvement was observed. Laboratory analysis of blood revealed leukopenia (white blood cells count 2.29 × 109/L) and thrombocytopenia (platelets count 97 × 109/L). Occult blood (25 + cell/u) and albumin (80 mg/L) were found in urine routine testing. In biochemistry testing, lower total protein (61.5 g/l), pre-albumin (126 mg/l), and elevated blood sugar was detected. Antibiotics, Oseltamivir and Insulin were administrated to control infection and lower the blood sugar. On June 11, blood testing still showed leukopenia (white blood cells count 2.42 × 109/L) and thrombocytopenia (platelets count 68 × 109/L). Mycobacterium tuberculosis (TB), EB virus, Cox A16 virus, EV71 virus, Chlamydia pneumoniae, syncytial virus, adenovirus, influenza virus and para-influenza virus were all detected as negative. The case was then transferred to hospital B in Shanghai on the same day. Presenting with the symptoms of coughing and malaise and with chest computerized tomography (CT) of “Left lung patchy shadow, bilateral small amount of pleural effusion, increased width of the longitudinal diaphragm” (Fig. 1), case A was admitted in hospital C. Thrombocytopenia (platelets count 81 × 109/L) continued and white cell counts were normal. Rapid testing for influenza A was negative. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated as 67.0 U/L and 59.0 U/L respectively. Ofloxacin Capsules, Methylprednisolone Sodium Succinate, Pantoprazole, Glutamine and Xiyanping (antiviral herbal medicine) were prescribed. Case A’s temperature got normal. Cough and muscle soreness were relieved after treatment.
Case B
Case B was case A’s elder brother. He was a 53-year-old and became sick since June 8, 2016. Symptoms including fever (38.5 °C), malaise and low lumber soreness appeared early during his illness. He visited hospital B in Jiangsu province on June 9, 2016. He was treated with Reduning (Antiviral herbal medicine), Oseltamivir, Levofloxacin, Ticarcillin/ Clavulanate Potassium and Insulin aspart. Blood routine testing upon admission showed leukopenia (white blood cells count 2.29 × 109/L), erythropenia (red cell count 4.10 × 1012/L), thrombocytopenia (platelets count 56 × 109/L), occult blood in fecal sample, elevated ALT (56.0 U/L) and AST (122.0 U/L), lowered total protein (59.4 g/L), lowered albumin (38.2 g/L), pre-albumin (163 mg/L), elevated lactate dehydrogenase (LDH) 240 U/L, and elevated blood sugar (12.84 mmol/L). X-ray detection showed increased bronchovascular shadows. He was also screened for other pathogens such as Mycobacterium TB, EB virus, Cox A16 virus, EV71 virus, Chlamydia pneumoniae, syncytial virus, adenovirus, influenza virus and para-influenza virus, but all tests were negative. Together with case A, he was transferred to hospital C in Shanghai and was admitted for viral pneumonia and type II diabetes. CT showed two nodular shadows in the left lung and pleural effusion in the right lung (Fig. 1). A Swab was collected and a test for Influenza A showed negative results. Blood routine testing still showed leukopenia (white blood cells count 3 × 109/L) and thrombocytopenia (platelets count 53 × 109/L). Blood gas analysis revealed lowered partial pressure of carbon dioxide (PCO2) (4.2kpa) and total carbon dioxide (TCO2) (22.3 mmol/L). Coagulopathy (activated partial thromboplastin time (APTT) 46.8 s) and elevated creatine phosphate kinase (260 IU/L) was also observed. Whole blood testing was done again on June 13. Leukopenia (white blood cells count 2.3 × 109/L) and thrombocytopenia (platelets count 28 × 109/L) had worsened.
Potential index case
The potential index case was a 72-year-old woman. She was the mother to cases A and B. Illness of potential index case began on May 21, 2016. She was sent to a local clinic by case A on the same day. Blood testing showed leukopenia (white blood cells count 3.83 × 109/L) and elevated blood sugar. She was treated for viral infection. On May 23, she had worse symptoms of fever (39 °C), bleeding gums, stomachache, diarrhea and malaise. Again, case A took her to a local community health center for treatment. Blood testing showed leucopenia (white blood cells count 2.38 × 109/L) and thrombocytopenia (platelets count 88 × 109/L). Dermal ecchymosis appeared on the index case’s chest and upper lumber. On May 25, she felt nausea and vomited. She visited hospital D in Jiangsu province. Blood testing showed leukopenia (white blood cells count 1.83 × 109/L), thrombocytopenia (platelets count 32 × 109/L), elevated liver-associated enzyme levels (AST 805.4 U/L; ALT 220.0 U/L, coagulopathy (Prothrombin Time 13.7 s and APTT 64.1 s). Urine testing showed abnormal sugar (++), protein (++), occult blood (+++). Heteropathy was applied. However, she got worse and began convulsing. She died of multiple-organ failure on May 28. According to the guideline for prevention and treatment of SFTS [17], she was confirmed as a probable case of SFTS.
Epidemiological findings
The potential index patient was sick from May 21 and died on May 28. Case A took care of index patient during all the 8 days. Case B had visited index case on May 23 and 27. On May 27, both case A and B found bleeding from the mouth, nostrils, and ears of the potential index case. After the death of potential index case, case A and B had cleaned the body and directly touched the blood of the potential index case without any protection.
The potential index patient lived in a village near Tai Lake in Jiangsu Province, which is located to the southeast of China. The village is on a downhill, and she used to climb the hill every day as she had planted some vegetables on the hill. It is unclear whether the patient was bitten by ticks or not. However, investigation on the surroundings of the patient showed that ticks could be found in the village and in other places that the patient came into contact with on the hill. Both case A and case B had their own houses and denied history of tick bite or outdoor activities within 2 weeks before illness onset (Fig. 2).
Altogether, 19 ticks were caught through flagging from the hill and grassland. Eight rodents were caught on the hill, around the village or indoor around the residency of potential index case. Ticks could be found on the surface of rodents. Three out of ten dogs were found to be infected with ticks and tick index was 0.4.
Close contacts
A total of 32 close contacts including case C were identified in this family cluster. They were mostly relatives from the family. Three close contacts became ill. One was Case C, a 30-year-old female. She was daughter to case B and became ill on June 1, 2016 with the symptoms of coughing and a slight fever. She took some self-prescribed drugs but she could not remember the drug’s name. On June 11, she accompanied her father (case B) and her aunt (case A) to hospital C in Shanghai. She had a fever of 37.8 °C. Blood testing was normal at the time of admission. Rapid testing for influenza A was negative. She was admitted in hospital C and treated with antiviral medicine. She was discharged on June 14 when serum detection for SFTSV was negative. Another relative who became sick was the husband to potential index case’s sister. He got fever on June 8, 2016 and recovered soon without any other symptoms. The third one who was an undertaker and had moved and cleaned the body of the potential index case. He had wiped the blood from the mouth of the potential index case. Other close contacts had no symptoms during the latent period after contact.
Laboratory testing
On June 13, serum samples were collected from case A and B. On June 14, Ct values of case A and B were 32 and 29 respectively in Real-Time PCR assay and both were positive to SFTSV. Sera of close contacts with fever or other symptoms were tested negative by Real Time RT-PCR including case C.