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. 2020 Sep 14;14(9):e0008641. doi: 10.1371/journal.pntd.0008641

Table 1. Characteristics of included studies, sorted by year of study.

First author, Journal [Reference] Region, Study period Study design, characteristics No. untreated patients Age, Years (mean) Sex male (%) Duration of fever, days Diagnostic test used Complications Patients hospitalised
(%)
Untreated deaths %
(n)
Crofton, JRAMC
[9]
Middle East, countries not specified
1942–1943
Retrospective case series
Middle East Forces
28
(28/28)
- - - Rickettsial agglutination test with differentiation from R. prowazekii for all patients plus Weil-Felix. Five “severe” cases, of which one died (post-mortem—lung with haemorrhagic bronchopneumonia and abscess formation, brain with microscopic haemorrhages and scanty cellular nodes) all 3.6%
(1/28)
Calero, AJTMH
[10]
Panama City, Panama
1947
Prospective case series
Report of an outbreak
13
(13/13)
16–43 11/13 (85%) 12–17
(15)
Ten cases confirmed by complement or rickettsial agglutination test with differentiation from R. prowazekii plus Weil-Felix, three cases by Weil-Felix only Seven patients hospitalised
Pronounced “stuporous condition” in 30.7%
7/13
(54%)
0%
(0/13)
Diaz-Rivera, Am J Med Sci
[11]
San Juan, Puerto Rico
1947–1948?
Prospective case series
Drug trial, 33 treated
27
(27/60)
15–60
(30.6)
18/27
(67%)
12–22
(15)
Complement fixation test with conversion from negative to positive plus Weil-Felix with increasing titers up to ≥ 1:160 - all 0%
(0/27)
Shaked, Infection
[12]
Israel
1976–1985
Retrospective case series
Chart review
11
(11/45)
- - 12–19 Positive complement fixation test or immunofluorescent antibody test for murine typhus with differentiation from spotted fever (unspecified antigens/titer) One case of encephalitis
Two cases of pneumonia and one scrotal ulcer in treated patients
all 0%
(0/11)
34 treated - 34/45a
(76%)
Dumler, JAMA
[13]
Southern Texas, US
1980–1987
Retrospective case series
Chart review
8
(8/80)
- - - Indirect fluorescent antibody test (IFA) with 4-fold rise in typhus group antibody titer, single high titer ≥ 1:128 and lower titer to spotted fever group (R. rickettsii) antigen than to typhus group antigen
No differentiation from R. prowazekii, previous studies revealed no cases of R. prowazekii infection
No complications in the untreated
Neuropsychiatric complications (confusion, stupor, coma, hallucinations) in six, seizure in three, ataxia in one, renal insufficiency in five, jaundice in two, respiratory failure in three and hematemesis in one of the treated patients
Seven patients admitted to ICU, three (3.8%) died. Two deaths due to shock, renal and multisystem failure
77/80
(96%)
0%
(0/8)
72 treated
-
(46.3)a
-
(40%)a
-
Bernabeu-Wittel, Arch Intern Med
[14]
Sevilla, Spain
1979–1995
Prospective case series
1983–1995
62 cases
Retrospective case series
1979–1982
42 cases
Hospital in Spain
60
(60/104)
- - -
(12.7)
Immunofluorescence antibody assay R. typhi IgG ≥ 1:512 in 76 patients, 4-fold rise in titer in 28 patients, differentiation from Rickettsia conorii Organ complications in four untreated patients (6.7%)
Nine of all 104 patients (8.6%) with organ complications, including pneumonitis in six, cerebellitis in one and multiorgan failure in two patients
Complications classified as severe in four of 104 patients (3.8%)
all 0%
(0/60)
44 treated 12–81a
(37.9)
57/104a
(55%)
8–27a
(12.5)
Hernández-Cabrera, Emerg Infect Dis
[15]
Gran Canaria, Canary Islands, Spain
2000–2002
Not specified
in- and outpatients (>14 years) at University Hospital Las Palmas
8
(8/22)
- - - Direct immunofluorescence antibody test R. typhi IgM ≥ 1:40 or 4-fold rise in IgG titer and differentiation from Rickettsia conorii No complications in the untreated
One renopulmonary syndrome, one encephalitis and one meningitis with renal failure in the treated
Not specified 0%
(0/8)
14 treated 14–76a
(28)
21/22a
(95%)
7–20a
(10)
Shalev, Scand J Infect Dis
[16]
Rahat, Israel
2003–2005
Prospective case series
Bedouin children
47
(47/76)
- - - Micro immunofluorescence
R. typhi titer IgM or IgG ≥ 1:100 in acute and/or convalescent sample and stronger reaction to R. typhi antigen than to spotted fever group (R. conorii) antigen
No complications 1/76
(1.3%)
0%
(0/47)
29 treated -
(7.3)a
39/76a
(51%)
-
Gray,
N Z Med J
[17]
Waikato region, New Zealand
2006
Retrospective case series 5
(5/12)
- - - IFA with 4-fold R. typhi antibody titer rise in six patients and single high IgM ≥ 1:512 or IgG ≥ 1:1024 in six patients -
Nine patients hospitalised
9/12
(75%)
0%
(0/5)
Seven patients treated 19–69a
(46)
6/12a
(50%)
-
Adjemian, Emerg Infect Dis
[18]
Austin, Texas, US
2008
Retrospective case series
Outbreak investigation
16
(16/33)
- - - IFA with 4-fold antibody titer rise to R. typhi in all and detection of DNA in clinical specimen by PCR in one patient -
23 of all 33 patients hospitalised and 9 of them admitted to the ICU (pneumonia, coagulopathy, renal failure)
23/33
(70%)
0%
(0/16)
17 treated 7–64a
(39)
-
(56%)a
-
Znazen,
Med Mal Infect
[19]
Tunisia
2006–2008
Retrospective case series 8
(8/43)
- - - Micro immunofluorescence assay with IgM titer ≥ 1:32 to R. typhi in 32 and seroconversion or significant titer rise in 11 patients, sera showing cross-reactions between R. typhi and R. conorii or R. felis were excluded -
36 patients hospitalised
36/43
(84%)
0%
(0/8)
35 patients treated 8–83a
(41)
-
(51%)a
-
Afzal,
Emerg Infect Dis
[20]
Hidalgo County, Texas, US
2013–2016
Retrospective case series
Review of records from two hospitals
8
(8/90)
- - - IFA with IgM or IgG titer ≥ 1:128 to typhus group rickettsiae in 87, 4-fold IgG titer rise in three patients -
Complications in 25 patients, including bronchiolitis in two, pneumonia in eight, pancreatitis in three, cholecystitis in one, myositis in one, rhabdomyolysis in two, meningitis in two, sepsis with acute kidney injury in one, septic shock in four patients and septic shock plus pneumonia in one patient.
13 patients required ICU care
all 0%
(0/8)
82 patients treated - 45/90a
(50%)
-

“-”refers to missing information.

a entire study population, including treated patients.