Different Clinical Manifestations of Human Brucellosis in Pregnant Women: A Systematic Scoping Review of 521 Cases from 10 Countries

Figures & data

Figure 1 Flow diagram of selection of studies included in the review.

Table 1 Overview of the Included Seven Case Series Studies and 20 Case Reports of Brucellosis in Pregnant Women

First Author, Publication Year	From Seven Case Series Studies (%)							Case Reports^Citation25,Citation30-48
	Madkour MM (2001)^Citation49	Kurdoglu M (2010)^Citation23	Gulsun S (2011)^Citation16	Roushan MR (2011)^Citation20	Vilchez G (2015)^Citation12	Ali S (2016)^Citation50	Inan A (2019)^Citation51
Country, time of study	Saudi Arabia (before 2001)	Turkey 2003–2008	Turkey 2003–2010	Iran 2000–2010	Peru 1970–2012	Pakistan 2013	Turkey 2002–2015	^†
Number of patients involved	29	33	39	19	101	25	242	33
Mean/median age (range of age, years)	29.2±6.2 (16–41)	26.8±5.1 (16–42)	28.07 (20–40)	25±4.6 (18–36)	26.1 (15–45)	27 (18–41+)	28.8±6.3 (17–50)	28.2±5.8 (16–39)
Trimester (%)	First (41.4) Second (24.1) Third (34.5)	First (39.4) Second (33.3) Third (27.3)	Not mentioned	First (57.9)	First (45.5) Second (22.2) Third (32.3)	Not mentioned	First (24.8) Second (39.3) Third (32.2)	First (12.9) Second (51.6) Third (35.2)
Diagnostic methods	SAT, blood culture	SAT, Coomb’s test	SAT, Coomb’s, blood culture	SAT, 2ME, blood culture	SAT, BAB, blood/bone marrow culture	RBPT	SAT, RBPT, blood culture, Coomb’s	^†
Incidence of brucellosis in pregnancy (%)	5.8	Not mentioned	Not mentioned	1.5	Not mentioned	5.8	2.1	Not applicable
Adverse outcomes (%)	Abortion (41.0), Preterm delivery (3.4) IUFD (3.4)	Abortion (24.1) Preterm delivery (6.9) IUFD (3.5)	Abortion (2.5%) Preterm deliveries (17.9%);	Abortion (53.0)	Preterm delivery (13.9) Spontaneous abortion (12.8) IUFD (8.1)	Not mentioned	Preterm delivery (1.2) Abortion (6.2) IUFD (2.1)	Preterm delivery (31.3) Abortion (37.5) IUFD (9.8)
Epidemiological history (%)	Not mentioned	A (92.3) B (58.8) C (63.2) D (50.0) E (80.0) F (60.0)	C (76.9) E (46.1)	A (63.2) B (15.8)	A (90.8)	A (52.0) B (36.0) E (68.0)		A (18.5) C/D (22.2) E (44.4)

Notes: A, consumption of unpasteurized or infected dairy products or meat; B, stockbreeding or contact with animals; C, previous diagnosis in family members; D, previous diagnosis in neighbors; E, low socioeconomic class or rural areas; F, not literate. ^†Detailed in Table 2.

Abbreviations: 2ME, 2-mercaptoethanol; BAB, blocking antibody titer; Coomb’s test, anti-human immunoglobulin test; IUFD, intrauterine fetal death; RBPT, rose bengal plate agglutination test; SAT, serum agglutination test.

Table 2 Clinical Manifestations of Individual Case Reports of Brucellosis in Pregnant Women

Patient No.	Reference	Age (Years)	Country	Trimester	Clinical Manifestations	Diagnostic Methods	Duration of Delayed Diagnosis	Obstetric Outcomes
1	Sarram M (1974)^Citation30	35	Iran	Second	Fever, headache, sweating, malaise,	SAT Blood culture	Not mentioned	Abortion
2	Sarram M (1974)^Citation30	25	Iran	Second	Joint pains	SAT	Not mentioned	Abortion
3	Sarram M (1974)^Citation30	17	Iran	Second	Muscle and bone pains	SAT Blood culture	Not mentioned	Abortion
4	Sarram M (1974)^Citation30	25	Iran	Second	Joint pains	SAT Blood culture	Not mentioned	Abortion
5	Sarram M (1974)^Citation30	21	Iran	Second	Fever, sweating, joint pains	SAT Blood culture	Not mentioned	Abortion
6	Sarram M (1974)^Citation30	25	Iran	Second	Sweating, muscle, joint pains	SAT	Not mentioned	Abortion
7	Schreyer (1980)^Citation25	35	Israel	Second	Fever, chills, malaise, nausea, lower abdominal pains	Blood culture	Not mentioned	IUFD
8	Naveau (1983)^Citation31	34	USA	Second	Anorexia, fatigue, weight loss	CFT	Not mentioned	Term delivery
9	Gloeb (1994)^Citation32	24	USA	Third	Fever, shaking chills, night sweating, weakness, anorexia, nausea, vomiting, vague pain, upper abdominal pain, a non-productive cough, hand tremors, auditory hallucinations	SAT	8 days	Preterm delivery
10	Dan (2001)^Citation33	34	China	Third	Fever, sweating, general joint pain to knee joint clear, paroxysmal irregular abdominal pain	SAT	8 days	Preterm delivery
11	Dan (2001)^Citation33	27	China	Second	Fever, sweating, fatigue, general joints and muscles pain, insomnia	ELISA	Not mentioned	IUFD
12	Jensenius (2008)^Citation34	33	Norway	Third	Fever, both breasts pain	Blood culture ELISA	Not mentioned	Not mentioned
13	Cebesoy (2009)^Citation35	21	Turkey	First	Fever, back pain	SAT Blood culture	Not mentioned	Term delivery (caesarean)
14	Karcaaltincaba (2010)^Citation36	25	Turkey	Second	Fever, sweats, backache, malaise	Bone marrow culture	Not mentioned	Term delivery
15	Karcaaltincaba (2010)^Citation36	33	Turkey	Second	Fever, sweating, vaginal bleeding, rupture of the membranes	SAT Blood culture	Not mentioned	Abortion
16	Peker (2011)^Citation37	19	Turkey	Second	Fever, malaise, hematuria, nausea, membrane rupture	Blood culture	Not mentioned	Abortion
17	Ceylan (2012)^Citation38	18	Turkey	Third	Malaise, anorexia, intermittent vomiting, vaginal bleeding	SAT	2 months	Preterm delivery
18	Bi (2013)^Citation39	28	China	Third	Left lower limb pain, fever, sweating, paroxysmal abdominal pain	RBPT	11 days	Preterm delivery (caesarean section)
19	Aydın (2013)^Citation40	27	Turkey	Second	Sweating, arthralgia, oligohydramnios, premature rupture of membranes	SAT	Not mentioned	Preterm delivery
20	Li (2015)^Citation41	34	China	First	Fever, cough, vaginal bleeding	Blood culture	Not mentioned	Abortion
21	Fathassi (2016)^Citation42	30	Tunisia	Second	Fever, myalgia, arthralgia, asthenia, nausea, vomiting	SAT	Not mentioned	Term delivery
22	Fathassi (2016)^Citation42	39	Tunisia	Third	Fever, pelvic pain (uterine contractions), membrane rupture	SAT	Not mentioned	Preterm delivery
23	Agah (2016)^Citation43	29	Iran	First	Fever, chills, painless vaginal bleeding with symptoms of partial abortion	SAT 2ME	10 days	Abortion
24	Agah (2016)^Citation43	31	Iran	First	Fever, chills, night sweating, low back pain, vaginal bleeding	SAT 2ME	7 days	Abortion
25	Agah (2016)^Citation43	36	Iran	Second	Shaking chills, day time sweating, vaginal bleeding	SAT 2ME	Not mentioned	IUFD
26	Agah (2016)^Citation43	36	Iran	Third	Long-term backache, malaise, sweating	SAT 2ME	Not mentioned	Term delivery
27	Agah (2016)^Citation43	32	Iran	Third	Right shoulder pain, sweating	SAT 2ME	10 weeks	Term delivery
28	Zhou (2017)^Citation44	26	China	Third	Fever, chills, sweating, asthenia	BAB	Not mentioned	Preterm delivery (caesarean section)
29	Zhou (2017)^Citation44	25	China	Third	Fever, sweating, asthenia, vaginal bleeding with abdominal pain	BAB	Not mentioned	Preterm delivery (caesarean section)
30	Yang (2018)^Citation45	22	China	Not mentioned	Fever, vaginal bleeding, abdominal distension	SAT Blood culture	Not mentioned	Abortion
31	Sabzevari (2018)^Citation46	32	Iran	Not mentioned	Fever, severe arthralgia, chilling, sweating	Coomb’s test SAT BAB 2ME	Not mentioned	Term delivery (caesarean)
32	Zhao (2019)^Citation47	26	China	Third	Hepatosplenomegaly, weakness in lower extremities and hip joint pain, fever, shortness of breath	Blood culture PCR	Not mentioned	Preterm delivery
33	Tian (2019)^Citation48	26	China	Second	Intermittent fever, right thigh and hip pain	SAT	5 months	Preterm delivery

Abbreviations: 2ME, 2-mercaptoethanol; BAB, blocking antibody titer; CFT, complement fixation test; Coomb’s test, anti-human immunoglobulin test; ELISA, enzyme-linked immunosorbent assay; IUFD, intrauterine fetal death; PCR, polymerase chain reaction; RBPT, rose bengal plate agglutination test; SAT, serum agglutination test.

Table 3 Clinical Manifestations of Brucellosis in Pregnant Women

Clinical Manifestations	Total Cases (%) (n=521)		From Seven Case Series Studies (%)						From Included 20 Publications of Case Reports (%)^Citation25,Citation30-48
		Madkour MM (2001)^Citation49 (n=29)	Kurdoglu M (2010)^Citation23 (n=33)	Gulsun S (2011)^Citation16 (n=39)	Roushan MR (2011)^Citation20 (n=19)	Vilchez G (2015)^Citation12 (n=101)	Ali S (2016)^Citation50 (n=25)	Inan A (2019)^Citation51 (n=242)	Cases from Case Reports (n=33)
Fever	400 (76.8)	29 (100.0)	–	30 (76.9)	7 (36.8)	98 (97.0)	12 (48.0)	202 (83.5)	22 (66.6)
Joint pain/swelling/arthralgia	389 (74.7)	11 (37.9)	30 (90.9)	36 (92.3)	11 (57.9)	57 (56.4)	16 (64.0)	215 (88.8)	13 (39.4)
Sweats	382 (73.3)	11 (37.9)	27 (81.8)	–	11 (57.9)	78 (77.2)	21 (84.0)	217 (89.7)	17 (51.5)
Fatigue/asthenia/weakness	262 (50.3)	–	25 (75.8)	–	1 (5.3)	–	–	231 (95.5)	5 (15.5)
Headache	227 (43.6)	3 (10.3)	–	–	–	77 (76.2)	1 (4.0)	145 (62.5)	1 (3.0)
Back pain	189 (36.3)	9 (31.0)	–		–	–	–	176 (72.7)	4 (12.2)
Nausea	111 (21.3)	–	–	–	–	39 (38.6)	–	68 (28.1)	4 (12.2)
Hepatomegaly	100 (19.2)	3 (10.3)	–	11 (28.2)	–	–	–	85 (35.1)	1 (3.0)
Splenomegaly	97 (18.6)	3 (10.3)		10 (25.6)				83 (34.3)	1 (3.0)
Myalgia	96 (18.4)	–	11 (33.3)	28 (71.7)	3 (15.8)	51 (50.5)	–	–	3 (9.1)
Weight loss	95 (18.2)	1 (3.4)	14 (42.4)		–	–	–	79 (32.6)	1 (3.0)
Malaise	92 (17.7)	–	–	–	–	86 (85.1)	–	–	6 (18.2)
Chills	69 (13.2)	13 (44.8)	–	–	–	49 (48.5)	–	–	7 (21.2)
Hypoxia	64 (12.3)	–	–	–	–	63 (62.4)	–	–	1(3.0)
Vaginal bleeding	47 (9.0)	1 (3.4)	–		–	16 (15.8)	–	22 (9.1)	8 (24.2)
Abdominal pain/distension/pelvic pain	39 (7.5)	2 (6.9)	–	–	–	22 (21.8)	–	8 (23.5)	7 (21.2)
Constipation	31 (5.6)	–	–	–	–	31 (30.7)	–	–	–
Anorexia	27 (5.2)	1 (3.4)	23 (69.7)	–	–	–	–	–	3 (9.1)
Vomiting	25 (4.8)	–	–		–	22 (21.8)	–	–	3 (9.1)
Cough	21 (4.0)	1 (3.4)	–		–	18 (17.8)	–	–	2 (6.1)
Epistaxis/Petechiae/brownish	19 (3.6)	–	–		–	11 (10. 9)	–	8 (3.3)	–
Diarrhea	9 (1.7)	–	–		–	9 (8.9)	–	–	–
Dysuria/urinary frequency/hematuria	8 (1.5)	1 (3.4)	–		–	6 (5.9)	–	–	1 (3.0)
Malodorous	8 (1.5)	–						8 (3.3)	–
Depression	7 (1.3)	–	–		–	7 (6.9)	–	–	–
Membrane rupture	5 (1.0)	–	–		–	–	–	–	5 (15.2)
General pain	5 (1.0)	1 (3.4)	–		2 (10.5)	–	–	–	2 (6.1)
Odynophagia	4 (0.8)	–	–		–	4 (4.0)	–	–	–
Dyspnea	3 (0.6)	–	–		–	2 (2.0)	–	–	1(3.0)
Rash	2 (0.4)	1 (3.4)	–		1 (5.3)	–	–	–	–
Oligohydramnios	1 (0.2)	–	–		–	–	–	–	1(3.0)
Breast pain	1 (0.2)	–	–		–	–	–	–	1(3.0)
Auditory hallucinations	1 (0.2)	–	–		–	–	–	–	1(3.0)
Dull/delirious	1 (0.2)	–	–		–	–	–	–	1(3.0)
Hand tremors	1 (0.2)		–		–	–	–		1(3.0)
Insomnia	1 (0.2)		–		–	–	–		1(3.0)

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