Successful Detection of Unrecognized Rickettsia typhi in Pregnancy Using Cell-Free Next-Generation Sequencing
Table 1
Patients with Rickettsiatyphi detection by NGS of plasma-based mcfDNA during pregnancy.
Parameter
Case 1
Case 2
Age (years)
34
29
Pregnancy details
G3P2, 31 3/7 wks GA
G1P0, 13 1/7 wks GA
Associated conditions
Initial suspected diagnosis
Viral syndrome
Viral syndrome, UTI
Fever
103.1 F→103.4 F
102.7 F→102.9 F
Septic shock
Yes
Yes
ICU admission
Hospital day 3
Hospital day 3
Headache
Yes
Yes
Confusion
No
No
Rash
Yes
No
Myalgia/arthralgia
Yes
No
Malaise
Yes
Yes
Respiratory symptoms
Dyspnea, hypoxia
Dyspnea, cough
GI symptoms
Yes
No
Hepatomegaly/splenomegaly
Imaging not performed
Hepatomegaly
Myocarditis
No
No
Laboratory analysis
Hgb (Ref: 9.6-12.4 g/dL)
9
12
WBC (Ref: 6.00-13.32 cells/mm3)
2.5
11.6
%PMNs (Ref: 10.9-76.0%)
33.1
61.4
%Bands
43.7
11.8
Platelet count (103/μL) (Ref: 244-580 103/μL)
91
354
Na (Ref: 133-142 mEq/L)
136
135
BUN (Ref: 2–23 mg/dL)
10
13
Cr (Ref: 0.15-0.4 mg/dL)
0.51
0.62
AST (Ref: 20-60 U/L)
651
95
ALT (Ref: 12-45 U/L)
429
146
Alk Phos (Ref: 60-330 U/L)
79
62
Lactate dehydrogenase (313-618 U/L)
860
774
Hematuria
Yes
No
Proteinuria
Yes
No
Lumbar puncture
Not performed
Not performed
Imaging
U/S: normal fetus CXR: bibasilar opacities
U/S: normal fetus CXR: bibasilar infiltrates Abd U/S: hepatomegaly
Karius® test result Rickettsia typhi cfDNA MPM (RR 0 MPM) EBV cfDNA MPM (RR 1.38 MPM)
147
6 242
Rickettsia typhi indirect immunofluorescence assay (IFA) serology IgG and IgM
Negative day 3 IgM (<1 : 64) Positive day 28 IgM 1 : 256 IgG 1 : 128
Negative day 3 IgM (<1 : 64) Positive day 10 IgM 1 : 128 IgG 1 : 1024
Blood, throat, stool, urine Cxs
Negative
Negative
Rapid plasma reagin
Negative
Negative
Hepatitis panel serology IgG and IgM
Negative
Negative
Human immunodeficiency virus 1/2 Ag/Ab 4th gen with reflex
Negative
Negative
Herpes simplex virus PCR direct assay
Negative
Negative
Epstein-Barr virus antibody panel IgM and IgG to EBV VCA
Negative
Positive—EBV VCA VCA IgG 1 : 544 EBNA
Cytomegalovirus IgG and IgM
Negative
Negative
Parvovirus IgM
Negative
Negative
Toxoplasma gondii IgG and IgM
Negative
Negative
Coccidioides IgM to DTP antigen
Negative
Negative
QuantiFERON®-TB
Negative
Negative
Histoplasma immunodiffusion of ant M/H
Negative
Negative
Brucella Ab (total) by agglutination
Negative
Negative
Legionella pneumophila urine antigen
Negative
Negative
Coxiella burnetii (Q fever) IgG
Negative
Negative
Empiric antibiotic coverage
Vancomycin, piperacillin/tazobactam, azithromycin
Vancomycin, meropenem, azithromycin
Hospital Day KT ordered
3
2
KT time to diagnosis
1 day from sample receipt 3 days from collection
1 day from sample receipt 2 days from collection
Impact of KT on therapy
Narrow to doxycycline
Narrow to doxycycline
Hospital day of doxycycline initiation
4
3
Outcome
Full recovery, delivery of a full-term male infant
Full recovery, currently 32 wks GA
wks = weeks; RP = rapid respiratory panel; CSF = cerebrospinal fluid; Cx = culture. MPM refers to molecules of microbial cell-free DNA/microliter (of a particular pathogen). RR refers to the reference range in MPM of a particular pathogen which is the 97.5%ile of the Karius® test result for that particular pathogen across a cohort of 609 asymptomatic healthy adults. indicates detection under the Karius® test commercial threshold.
