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Invasive group A streptococcal infection in pregnancy
Journal of Infection (2010) 60, 417e424
www.elsevierhealth.com/journals/jinf
REVIEW
Invasive group A streptococcal infection in pregnancy Takahiro Yamada a,*, Takashi Yamada a, Mie K. Yamamura a, Kenichi Katabami b, Mineji Hayakawa b, Utano Tomaru c, Shigeki Shimada a, Mamoru Morikawa a, Toshio Seki d, Satoshi Ariga e, Kaoru Ishikawa f, Tadayoshi Ikebe g, Satoshi Gando b, Hisanori Minakami a a Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan b Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan c Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan d Department of Obstetrics and Gynecology, Sapporo Tokushuukai Hospital, Shiroishi-ku, Sapporo 003-0021, Japan e Department of Obstetrics and Gynecology, Hokkaido Shakaihoken Hospital, Toyohira-ku, Sapporo 062-8618, Japan f Department of Obstetrics and Gynecology, Japanese Red Cross Nagoya Daiich Hospital, Nakamura-ku, Nagoya 453-8511, Japan g Department of Bacteriology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Accepted 18 March 2010 Available online 30 March 2010
KEYWORDS Group A streptococcus; Pregnancy; Delivery; Toxic shock syndrome (TSS); Toxic shock like syndrome (TSLS)
Summary We conducted a literature review of 55 pregnancies with symptomatic Group A streptococcus (Streptococcus pyogenes) infection reported in English (20 cases), French (2 cases) and Japanese (33 cases) to seek ways of improving prognosis. Multiparous women (83% [39/47]) in the third trimester (90% [47/52]) were prone to infection from winter to spring (75% [21/28]). Onset was heralded by flu-like symptoms, such as high fever (94% [46/49]), with upper respiratory (40% [22/55]) and/or gastrointestinal symptoms (49% [27/55]). Characteristic findings were early onset of shock (91% [50/55]) and infection-induced strong uterine contraction (73% [40/55]) suggestive of placental abruption. The clinical course was too acute and severe to rescue the mother (58% [32/55] died) and/or infant (66% [39/59] died). However, outcome has improved over the last decade, with rescue of 68% (15/22) of the mothers since 2000, and early use of antibiotics (71% [22/31] survived) and use of intravenous immunoglobulin (91% [10/11] survived) were associated with favourable outcome. Early use of antibiotics
* Corresponding author. Tel.: þ81 11 706 5941; fax: þ81 11 706 7711. E-mail address: [email protected] (T. Yamada). 0163-4453/$36 ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2010.03.011
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T. Yamada et al. and intravenous immunoglobulin may improve outcome of pregnant women suffering from flulike symptoms, shock and strong uterine contractions suggestive of placental abruption. ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction Group A streptococcus (GAS: Streptococcus pyogenes) may cause a variety of illnesses ranging from very common, usually clinically mild conditions, such as pharyngitis and impetigo, to less common severe infections, including septicaemia and pneumonia. GAS is isolated from 18% of throat swabs from patients with peritonsillar abscess (median age 22 years; range, 13e83 years) that occurs with an incidence of 19e37/100,000 per year1 and from 0.03% of vaginal and/or rectal swabs from pregnant women in the third trimester.2 Prior to the 20th century, GAS infection was a common cause of serious and sometimes fatal puerperal problems. However, the prevalence of symptomatic GAS infection in pregnancy decreased and became uncommon in the 20th century. Over the past three decades, however, a number of cases of GAS infection with clinical features similar to staphylococcal toxic shock syndrome, designated as streptococcal toxic shock syndrome (TSS), have been reported.3,4 A striking characteristic of streptococcal TSS is the early onset of shock and organ failure, with no site of infection being apparent at presentation in some cases. As this dramatic clinical presentation is not typically associated with GAS infection, there is concern regarding delay in diagnostic workup and institution of definitive therapy. Accordingly, case definitions for streptococcal TSS and classification of GAS infection were proposed by an informal working group of clinicians, microbiologists and epidemiologists in 1993 to assist clinicians by improving awareness and diagnosis of these infections, leading to early therapy4 (Tables 1 and 2). Although streptococcal TSS during pregnancy is rare, the outcome in these cases is poor.5 It may be important to improve awareness and early initiation of therapy to rescue these pregnant women with streptococcal TSS. However, physicians in western countries are often not familiar with this condition, perhaps due to the limited number of case reports published in English. This review presents the clinical features of 55 cases with symptomatic GAS infection during pregnancy published in English (20 cases), French (2 cases) or Japanese (33 cases).
Methods, results and discussion Cases included in this review We identified a total of 58 cases of pregnant women with symptomatic GAS infection that manifested within 12 h after delivery and were reported in English, French or Japanese using PubMed (1966eJune 2009), Japana Centra Revuo Medicina (1983eJune 2009) and the reference lists of previous reports. The search terms ‘‘Streptococcus’’, ‘‘S. pyogenes’’, ‘‘pregnancy’’, ‘‘delivery’’, ‘‘toxic shock’’, ‘‘shock’’, ‘‘sepsis’’ and ‘‘group A streptococcus’’ were used. As GAS infection acquired after delivery was suggested to have a different clinical course from that manifested soon after
delivery in a previous report,5 we used the following selection criterion: ‘‘GAS infection manifested within 12 h after delivery’’. Three cases6,7 were excluded from the present analysis as isolation of GAS was not clearly stated in these 3 case reports. Thus, a total of 55 cases (Table 3)8e52 were analyzed in this study. Of these, 49 cases fulfilled the criteria for streptococcal TSS shown in Table 1, and the remaining 6 cases (Cases 13, 17, 19 and 47e49) were classified as ‘‘other invasive GAS infection’’ according to the criteria shown in Table 2. Thirty-seven (67%) of the 55 patients were Japanese (Cases 19e55) and 33 (60%) cases (Cases 19e21, 24e31 and 34e55) were reported in Japanese only (Table 3). Sixteen of the 55 cases (Cases 3, 5e8, 10, 11, 22e29 and 33) and 2 other cases (Cases 16 and 32) were already discussed in reviews by Udagawa et al. in 19995 and by Crum et al. in 2002,21 respectively. Thus, 37 other cases were added to this review, including 27 cases (Cases 19e21, 30, 31 and 34e55) reported in Japanese only, 8 cases (Cases 1, 2, 4, 9, 12, 14, 15 and 18) reported in English and 2 cases (Cases 13 and 17) reported in French.
Statistics For categorical data, Fisher’s exact test was applied. To compare median values, the Student’s t test or ManneWhitney U-test was applied.
Backgrounds of patients and seasonal prevalence of infection Parity was specified in 47 cases (Table 3). Nulliparous women accounted for only 17% of cases (8/47). Nulliparous women accounted for 15% (5/34) of Japanese patients, while births by nulliparous women accounted for approximately 44%e47% of 1.1e1.2 million births that occurred each year in the last two decades in Japan [Tabulation information released annually from the Ministry of Health and Welfare of Japan]. Thus, nulliparous pregnant women are apparently less likely to acquire severe GAS infection than multiparous pregnant women. A relatively large number of subjects included in this review first showed this new characteristic of GAS infection. Gestational age when infection occurred was specified in 52 cases (Table 3, Fig. 1a). Ninety percent of the cases (47/52) were infected at 30 weeks of gestation or later (Mean SD, 33.5 6.0), indicating that women in the third trimester are more likely to acquire severe GAS infection than those in the first or second trimester. The month of the year in which infection occurred was specified in 27 cases (Table 3, Fig. 1b). Infection occurred most often in spring (March to May), accounting for 56% (15/27) of cases, followed by winter (December to February) in 22% (6/27) of cases. Twin pregnancy accounted for 7.3% (4/55) of the patients. Although the incidence of twin pregnancy has
Invasive GAS infection in pregnancy Table 1
419
Proposed case definition for streptococcal toxic shock syndrome.a,4
I. Isolation of group A Streptococci (Streptococcus pyogenes) A. From a normally sterile site (e.g., blood, cerebrospinal, pleural, or peritoneal fluid, tissue biopsy, surgical wound, etc.) B. From a non-sterile site (e.g., throat, sputum, vagina, superficial skin lesion, etc.) II. Clinical signs of severity A. Hypotension: systolic blood pressure 90 mmHg in adults or < 5th percentile for age in children and B. 2 of the following signs 1. Renal impairment: creatinine 177 mmol/L (2 mg/dL) for adults or 2 the upper limit of normal for age. In patients with pre-existing renal disease, a 2-fold elevation over the baseline level. 2. Coagulopathy: platelets 100 109/L (100,000/mm3) or disseminated intravascular coagulation defined by prolonged clotting times, low fibrinogen level and the presence of fibrin degradation products. 3. Liver involvement: alanine aminotransferase (SGOT), aspartate aminotransferase (SGPT) or total bilirubin levels 2 the upper limit of normal for age. In patients with pre-existing liver disease, a 2-fold elevation over the baseline level. 4. Adult respiratory distress syndrome infiltrates and hypoxaemia in the absence of cardiac failure, or evidence of diffuse capillary leak manifested by acute onset of generalised oedema, or pleural or peritoneal effusions with hypoalbuminaemia 5. A generalised erythematous macular rash that may desquamate. 6. Soft-tissue necrosis, including necrotising fasciitis or myositis, or gangrene. a NOTE. An illness fulfilling criteria IA and II (A and B) can be defined as a definite case. An illness fulfilling criteria IB and II (A and B) can be defined as a probable case if no other aetiology for the illness is identified.
increased worldwide over the past two decades, largely as a consequence of the delay in pregnancy until older ages and the increased use of assisted reproductive technologies,53 twin pregnancy accounts for only 1.5% of all pregnancies in many developed countries. This suggests that women with twin pregnancies were more likely to acquire severe GAS infection.
Symptoms Concurrent or preceding high fever (>38 C) and respiratory symptoms, such as a sore throat, were described in almost all cases (94%, 46/49) and in 40% (22/55) of cases, respectively (Table 3). Gastrointestinal symptoms, such as diarrhoea, nausea and vomiting, were also noted in 49% (27/55) of cases. Thus, life-threatening GAS infection in pregnancy began with flu-like symptoms. Early onset of shock (hypotension) and unusually strong uterine contractions, which are often seen in cases with placental abruption, were striking characteristics of severe GAS infection during pregnancy and occurred in 91% (50/55) and 73% (40/55) of cases, respectively. Strong labour pain may
Table 2
have been associated with purulent uterine myometritis,5 and was noted more frequently in the 33 women in whom GAS was isolated from the genital tract, including the uterus, amniotic fluid, vagina and neonate, than in the remaining 22 women (85% [28/33] vs. 55% [12/22], P Z 0.0284). Cocci concentrated in the vessels and the myometrium were reported (Fig. 2B, C). Non-reassuring foetal heart rate pattern (Fig. 2A) and acute deterioration of foetal condition, which led to foetal/neonatal death in 66% (39/59) of cases, may have been due to uteroplacental circulatory insufficiency because of strong uterine contraction and hypotension. Decreased consciousness level and skin rash were described in 31% (17/55) and 15% (8/ 55) of cases, respectively.
Relationships between maternal outcome and various symptoms, treatments and demographic characteristics Only 42% (23/55) of the mothers and 34% (20/59) of the infants (including four sets of twins) survived the disease (Table 3).
Classification of group A streptococcal infection.a,4.
I. Streptococcal toxic shock syndrome (streptococcal TSS): Defined by criteria in Table 1. II. Other invasive infections: Defined by isolation of group A streptococci from a normally sterile site in patients not meeting criteria for streptococcal TSS. A. Bacteraemia with no identified focus. B. Focal infections with or without bacteraemia. Includes meningitis, pneumonia, peritonitis, puerperal sepsis, osteomyelitis, septic arthritis, necrotising fasciitis, surgical wound infections, erysipelas and cellulitis. III. Scarlet fever: Defined by a scarlatina rash with evidence of group A streptococcal infection, most commonly pharyngotonsillitis. IV. Noninvasive infections: Defined by the isolation of group A streptococci from a non-sterile site. A. Mucous membrane: includes pharyngitis, tonsillitis, otitis media, sinusitis, vaginitis. B. Cutaneous: includes impetigo. V. Nonsuppurative sequelae: Defined by specific clinical findings with evidence of a recent group A streptococcal infection. A. Acute rheumatic fever. B. Acute glomerulonephritis. a
NOTE. Examples of conditions in each category are not inclusive.
420
District, Country
year
Month
age
para
GW
fever
RS
GS
SL
UC
R
G
FI
S
TSS
AB
IG
DM
PF
PM
UK London, UK Portsmouth, UK Portsmouth, UK Birmingham, UK Gloucester, UK Gloucester, UK France North Carolina, US Australia Toronto, Canada Indiana, US France North Yorkshire, UK Wales, UK San Diego, US France Veldhoven, Netherland Nagano, Japan* Aichi, Japan* Japan* Chiba, Japan Chiba, Japan Shimane, Japan* Hyogo, Japan* Fukushima, Japan* Fukuoka, Japan* Tottori, Japan* Chiba, Japan* Ibaraki, Japan* Okinawa, Japan* Aichi, Japan Niigata, Japan Aichi, Japan* Hyogo, Japan* Oita, Japan* Iwate, Japan* Aichi, Japan* Kanagawa, Japan* Aichi, Japan* Tokyo, Japan* Tokyo, Japan*
1969 1987 1988 1988 1988 1988 1988 1988 1991 1995 1995 1995 1996 1996 1998 2002 2005 2007 1986 1991 1992 1993 1994 1994 1994 1994 1994 1995 1996 1997 1997 1997 1997 1998 1999 1999 2001 2001 2002 2002 2002 2002
UN UN UN UN UN UN UN UN UN summer UN UN UN 5 UN 1 UN UN 12 5 UN 3 4 1 5 6 9 3 4 3 7 UN 1 3 2 UN 3 6 UN 2 4 3
27 33 32 24 33 27 24 33 40 31 32 29 30 36 30 31 43 33 29 31 27 29 42 34 33 35 39 35 28 31 30 43 37 27 34 25 34 36 32 36 33 24
7 UN 3 0 UN UN UN UN 0 2 1 3 2 2 2 0 2 4 UN 1 1 1 3 2 1 2 2 2 3 1 1 UN 1 1 2 1 1 2 3 1 2 0
UN term 34 18 39 37 39 UN 7 37 36 32 34 36 25 34 32 34 37 40 39 34 34 39 39 33 30 34 37 31 36 34 30 32 39 31 40 30 33 40 33 36
UN þ UN þ þ þ þ þ þ þ þ UN þ þ þ þ þ þ þ þ þ þ þ þ þ þ UN þ UN þ þ þ þ þ þ þ þ þ þ
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þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ
V V V V V C C V V C C V V C C C V V C C V C V C C V V V C C C C V V V V V C C C
A A SB SB SB A A A abortion SB 1:SB, 2:SB A A SB SB ND (day15) A A A SB ND 1:SB, 2:SB SB A SB SB SB SB SB SB A SB A A SB ND ND A SB SB SB SB
D D D D D D A D A D D A A D A A A A A D D D D D D D D D D D D D D A D A A D D D D A
8
to fulfil the criteria for streptococcal TSS (Table 1). Of the 50
1 29 310 410 511 612 712 813 914 1015 1116 1217 1318 1419 1520 1621 1722 1823 1924 2025 2125 2226 2326 2427 2528 2627 2729 2827 2930 3031 3127 3232 3333 3434 3527 3635 3736 3837 3938 4039 4140 4241
T. Yamada et al.
Reported cases of group A streptococcal infection in pregnancy.
Case [#]
Early onset of shock was the chief symptom and is required
Table 3
421 *NOTE. [#]: Reference no., Year : when episode occurred, Japan*: Case reported in Japanese only, GW: gestational weeks, UN: unknown, RS: respiratory symptom, GS: gastrointestinal symptom, SL: unusual strong labour, UC: unconsciousness and/or coma, R: rash and/or erythema, G: group A streptococcus was isolated from the uterus, placenta, amniotic fluid, vagina, or neonate, FI; focal infection site other than genital tract was identified early, S: early onset shock, TSS: case definition4 for streptococcal toxic shock syndrome was fulfilled, AB: antibiotics, IG: immunoglobulin, DM: delivery mode, C: cesarean delivery, V: vaginal delivery, PF: prognosis of fetus, PM: prognosis of mother; SB: Still birth, ND: neonatal death, A: alive, D: dead.
4342 4443 4544 4645 4746 4846 4947 5048 5149 5250 5351 5452 5537
Shiga, Japan* Chiba, Japan* Hyogo, Japan* Tokyo, Japan* Okayama, Japan* Okayama, Japan* Aichi, Japan* Shizuoka, Japan* Wakayama, Japan* Okayama, Japan* Mie, Japan* Hokkaido, Japan* Aichi, Japan*
2002 2003 2004 2004 2005 2005 2006 2006 2007 2008 2008 2008 2009
7 UN UN UN UN UN 5 6 UN UN UN 4 4
29 34 38 35 23 22 34 33 28 UN 16 33 31
3 4 1 1 0 0 UN 1 0 multi 0 2 1
35 UN 38 20 36 38 34 34 33 32 37 30 25
þ UN þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ
þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ
þ þ
þ þ þ þ þ þ þ þ þ þ þ þ
þ
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þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ
þ þ þ þ
C V V V V V C C C V C V
1: A, 2: SB SB A SB SB A SB 1: A, 2: A SB SB SB SB SB
A A A A A A A A A A D D D
Invasive GAS infection in pregnancy cases a 25 20 15 10 5 0
<21
21-25
26-30
12 1
2
4
31-35
36-40
>40
weeks
Cases b 7 6 5 4 3 2 1 0
3
5
6
7
8
9
10 11 Month
Figure 1 Histogram of numbers of cases of GAS infection occurring in each gestational week (a) and seasonal trends (b).
women in whom early onset of shock was observed, 49 (98%) fulfilled the criteria for streptococcal TSS. Five of the remaining six women, who were classified as having ‘‘other invasive infections’’ according to the criteria shown in Table 2, did not develop shock (Table 3). All women without shock or with ‘‘other invasive infections’’ survived the disease, suggesting that absence of shock is a key factor predicting favourable outcome (Table 4). In addition, all seven women whose sites of focal infection, such as peritonitis (Case 9), fasciitis (Case 12), gastritis (Case 17), meningitis (Cases 13, 18 and 19) and arthritis (Case 50), survived the disease, although early onset of shock was observed in 57% (4/7) of these women (Tables 3 and 4). Nulliparous women were more resistant to GAS infection than multiparous women; nulliparous women acquired severe GAS infection less frequently than multiparous women (Table 3) and nulliparous women appeared to succumb to this disease less frequently than multiparous women (Table 4). Administration of antibiotics was described in 31 women, of whom 71% (22/31) survived the disease, while only 4.2% (1/24) of those with no description of antibiotic use survived (Table 4). Thus, at least 22 (96%) of 23 surviving patients received antibiotics. Ten (91%) of 11 patients who received intravenous immunoglobulin (IVIG) therapy survived, while 30% (13/44) of the cases without such treatment survived. These findings suggest that administration of antibiotics and intravenous immunoglobulin help patients with severe GAS infection to overcome this life-threatening disease. However, it is possible that the effectiveness of antibiotics and IVIG have been overestimated due to the rapidity of disease progression and
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T. Yamada et al.
Figure 2 A: Cardiotocogram of the Case 54. Prolonged deceleration and foetal bradycardia were seen. B: Microscopic findings of the lung with haematoxylin-eosin staining (upper panel) and gram staining (lower panel) (Case 54). Emboli of gram-positive cocci in the pulmonary vessels and alveoli are shown. C: Microscopic view of the myometrium of the uterus (Case 54). Hypertrophic or degenerated smooth muscle cells and gram-positive coccal colonies were observed.
publication bias. Some patients may have been suspected initially as having viral infection and may have had very little time to receive antibiotics and IVIG before death. In fact, we reported a patient who died 20 h after the onset of illness before commencement of such specific treatment.52 In contrast, patients with relatively slow progression were likely to receive various treatments, such as antibiotics and IVIG, which may therefore have led to a better outcome. Reports describing severe cases or cases that responded positively to treatment may be more likely to be submitted for publication. Thus, further studies are clearly needed to confirm the efficacy of early administration of IVIG, although administration of antibiotics may have been necessary to rescue patients with severe GAS infection.
Outcome has shown improvement over the last decade, although the reasons for this are unknown (Table 4). However, as Japanese patients accounted for 67% (37/55) of all pregnant women with symptomatic GAS infection, Japanese physicians may have paid greater attention to this disease after publication of the criteria for diagnosis of perinatal GAS infection by the Ministry of Health and Welfare of Japan in 1996.4,54 The use of the sensational term ‘‘flesh-eating bacteria’’ by the Japanese media has also played an important role in attracting the attention of physicians. It is possible that information about GAS infection in pregnancy may have contributed to the survival of 14 Japanese patients treated since 1998, at least 13 (93%) and 7 (50%) of whom received antibiotics and IVIG, respectively (Table 3).
Invasive GAS infection in pregnancy
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Table 4 Maternal survival rate according to various symptoms, treatment, and factors.
Fever Respiratory symptoms GI tract symptomsa Strong labour pain Unconsciousness Skin rash Genital tract infectionb Focal infectionc Early onset of shock TSSd Nulliparous Twin pregnancy Cesarean delivery Use of antibiotics Use of immunoglobulin Japanese Infection at/after 2000
Absent/No
Present/Yes
p-value
1/3 (33%) 15/33 (45%)
21/46 (46%) 8/22 (36%)
>0.9999 0.5832
14/28 5/15 17/38 19/47 10/22
(50%) (33%) (45%) (40%) (45%)
9/27 18/40 6/17 4/8 13/33
(33%) (45%) (35%) (50%) (39%)
16/48 5/5 6/6 14/39 21/51 12/28 1/24 13/44
(33%) (100%) (100%) (36%) (41%) (43%) (4.2%) (30%)
7/7 18/50 17/49 6/8 2/4 11/24 22/31 10/11
(100%) 0.0012 (36%) 0.0097 (35%) 0.0035 (75%) 0.0574 (50%) >0.9999 (46%) >0.9999 (71%) <0.0001 (91%) 0.0003
8/18 (44%) 8/33 (24%)
15/37 (41%) 15/22 (68%)
0.2772 0.5454 0.5668 0.7071 0.7818
0.7805 0.0020
a
NOTE. gastrointestinal tract symptoms. GAS was isolated from the uterus, placenta, amniotic fluid, vagina, or newborns. c Focal infection site other than genital tract including peritonitis (Case 9), fasciitis (Case 12), phlegmonous gastritis (Case 17), meningitis (Cases 13, 18, and 19) and arthritis (Case 50) was determined early. d Case definition for streptococcal TSS4 is fulfilled. b
In conclusion, the outcome of pregnant women with symptomatic Group A streptococcus infection remains to be improved. Multiparous women are suggested to be more likely to acquire severe GAS infection during pregnancy. Early use of antibiotics and intravenous immunoglobulin may help patients with severe GAS infection to overcome this life-threatening disease. Initial signs of this disease mimic those of influenza, followed by strong labour pains. It is important to be aware of these characteristics of this infection to initiate early treatment with antibiotics and immunoglobulin.
References 1. Sunnergren O, Swanberg J, Mo ¨lstad S. Incidence, microbiology and clinical history of peritonsillar abscesses. Scand J Infect Dis 2008;40:752e5. 2. Mead PB, Winn WC. Vaginal-rectal colonization with group A streptococci in late pregnancy. Infect Dis Obstet Gynecol 2000;8:217e9. 3. Stevens DL, Tanner MH, Winship J, Swarts R, Ries KM, Schlievert PM, et al. Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. N Eng J Med 1989;321:1e7. 4. The working group on severe streptococcal infections. Defining the group A streptococcal toxic shock syndrome. JAMA 1993; 269:390e1.
5. Udagawa H, Oshio Y, Shimizu Y. Serious group A streptococcal infection around delivery. Obstet Gynecol 1999;94:153e7. 6. Chimura T, Numazaki M. Septic shock (maternal death) related to group A hemolytic streptococcus during pregnancy. Sanfujinka Chiryo 1997;75:329e34 [in Japanese]. 7. Udagawa H. Fulminant streptococcal infection and maternal death. Shusanki-Igaku 1999;29:1347e51 [in Japanese]. 8. Puerperal streptococcal infection. Br Med J 1969;27:788. 9. Teall A, Visuvanthan S, Payne A, Silverstone A. Unsuspected streptococcal infection presenting with diarrhoea in late pregnancy. J Infect 1987;14:185e6. 10. Acharya U, Lamont CAR. Group A beta-haemolytic streptococcus causing disseminated intravascular coagulation and maternal death. Lancet 1988;1:595. 11. Kavi J, Wise R. Group A beta-haemolytic streptococcus causing disseminated intravascular coagulation and maternal death. Lancet 1988;1:993e4. 12. Swingler GR, Bigrigg MA, Hewitt BG, Nulty Mc. Disseminated intravascular coagulation associated with group A streptococcal infection in pregnancy. Lancet 1988;1:1456e7. 13. Bollaert PE, Bauer Ph, Lambert H, Laprevote-Heully MC, Burdin JC, Larcan A. Septice ´mie fulminante a ´ streptocoque du groupe A en fin de grossesse. La Presse Medicale 1988;17: 1816 [in French]. 14. Dotters DJ, Katz VL. Streptococcal toxic shock associated with septic abortion. Obstet Gynecol 1991;78:549e51. 15. Margin CJ. Streptococcus group A maternal death. An important message for readers. Aust N Z J Obstet Gynaecol 1995; 35:227. 16. Morgan PJ. Maternal death following epidural anaesthesia for caesarean section delivery in a patient with unsuspected sepsis. Can J Anesth 1995;42:330e4. 17. Nyberg SL, Schlievert PM, Saul W, Johnson JR, Ferrieri P, Watkins VS. Successful management of a serious group A streptococcal infection during the third trimester of pregnancy. Clin Infect Dis 1995;21:1058e9. 18. Ferrazzini G, Peduzzi R, Balestra B. Group A beta-hemolytic streptococcal meningitis in a pregnant woman. Schweiz Med Wochenschr 1996;126:1842e4. 19. Barnham MRD, Weightman NC. Bacteraemic Streptococcus pyogenes infection in the peri-partum period: now a rare disease and prior carriage by the patient may be important. J Infect 2001;43:173e6. 20. Simmonds M. Necrotising fasciitis and group A streptococcus toxic shock-like syndrome in pregnancy: treatment with plasmapheresis and immunoglobulin. Int J Obstet Anesth 1999;8:125e30. 21. Crum NF, Helen MC, Thomas GG, Braden RH. Group A streptococcal toxic shock syndrome developing in the third trimester of pregnancy. Infect Dis Obstet Gynecol 2002;10:209e16. 22. Hommel S, Savoye G, Lorenceau-Savale C, Costaglioli B, Baron F, Le Pessot F, et al. Phlegmonous gastritis in a 32week pregnant woman managed by conservative surgical treatment and antibiotics. Dig Dis Sci 2007;52:1042e6. 23. Verhulsdonk MT, Hassell DR, Oei SG. Septic shock as a result of group A beta-hemolytic streptococcal meningitis with empyema in pregnancy. Int J Gynaecol Obstet 2007;97:197e8. 24. Kikkawa T, Ikeda S, Takeda S, Yanagisawa N, Inoue K. A case report of a pregnant woman with severe bacterial meningitis caused by group A beta-hemolytic Streptococcus. Rinsho Shinkeigaku 1986;26:343e7 [in Japanese]. 25. Nagaya K. Maternal death of Japan (Case reports of maternal death) Sanpo-sha. Tokyo; 1998 [in Japanese]. 26. Ooe K, Udagawa H. A new type of fulminant group A streptococcal infection in obstetric patients: report of two cases. Hum Pathol 1997;28:509e12. 27. Udagawa H, Oshio Y, Shimizu Y. Clinical characteristics of streptococcal toxic shock syndrome: perinatal type. Acta Obst Gynaecol Jpn 1999;51:1141e9 [in Japanese].
424 28. Takekida S, Tanaka A, Hayakawa Y, Matsuo H, Bo M, Yamazaki M, et al. A case report of Toxic Shock Like Syndrome (TSLS) by group A streptococcus in pregnancy. Sanfujinkano Shinpo 1994;46:823 [in Japanese]. 29. Sato M, Tsukimori S, Hirakawa T, Koyanagi T, Nakano H. A case report of streptococcal toxic shock syndrome (STSS) during pregnancy. Kyushu Journal Obstetrics Gynecol; 1995; Dec: 111e2 [in Japanese]. 30. Udagawa H, Shimizu K, Nakata H, Inayoshi C, Miyashita S, Kobayashi K, et al. Fulminant streptococcal infection and sudden death in a pregnant woman: a case report. Acta Obst Gynaec Jpn 1997;49:125e8 [in Japanese]. 31. Inoue K, Saito M, Toyama S, Tsukahara T, Kubo T. Maternal death due to severe infection by group A streptococcus (A case report). Kanto Journal Obstetrics Gynecol 1998;35:33e7 [in Japanese]. 32. Ichiyama S, Nakashima K, Shimokata K, Ohta M, Shimizu Y, Ooe K, et al. Transmission of streptococcus pyogenes causing toxic shock-like syndrome among family members and confirmation by DNA macrorestriction analysis. J Infect Dis 1997; 175:723e6. 33. Hirose Y, Shibuya H, Okazaki E, Aono K, Tokunaga A, Taguchi S, et al. Toxic shock-like syndrome with flu-like prodrome: a possible role of ‘enhancing tissue focus’ for streptococcal toxic shock. J Infect 2001;42:195e200. 34. Ito T, Ishikawa K, Ikoma Y, Miwa T, Oonuma M, Kuno N, et al. A case report of serious group A streptococcal infection during pregnancy. Acta Obst Gynaec Jpn 1998;50:1016e20 [in Japanese]. 35. Terawaki S, Taniguchi I, Baba M. A case report of fulminant group A streptococcal infection. J Jpn Soc Perin Neon Med 1999;35:259 [in Japanese]. 36. Kubo T, Oikawa N. A case report of suspected fulminant group A streptococcal infection at 40 weeks of gestation. Iwate Kenritsu Byoin Igakkai Zasshi 2001;41:123e6 [in Japanese]. 37. Sakado M, Yoshida K, Yokoi A, Gunjima S, Hamashima Y, Nakatsu M, et al. Two cases of perinatal type Streptoccal toxic shock syndrome. The proceeding of the 89th Aichi District Conference of the Japanese Obstetrical and Gynecological Society; 2009 [in Japanese]. 38. Yamaguchi S, Takae K, Hashimoto K, Fujisawa S. A case report of a maternal death of woman with gestational diabetes due to fulminant group A streptococcal infection. Kanto J Obstetrics Gynecol 2002;39:163 [in Japanese]. 39. Noguchi M, Matsushita S, Sawaguchi K, Noguchi M. A case report of maternal fetal death due to fulminant group A streptococcal infection in late pregnancy. Proc Conf Obstetrical Gynecol Infect 2003;20:104e6 [in Japanese]. 40. Mita S, Okuda N, Yokota A, Sasaki S, Koshino T, Nakai A, et al. A case report of streptococcal toxic shock syndrome led to maternal death. Tokyo District J Jpn Obstetrical Gynecol Soc 2002;51:454e9 [in Japanese]. 41. Hanada R, Takagi T, Iijima T, Iwao Y. A case report of acute respiratory failure after intra uterine fetal death due to
T. Yamada et al.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53. 54.
fulminant group A streptococcal infection. Kokyu 2004;23: 430e2 [in Japanese]. Tsuji S, Takebayashi K, Ono T, Akiyama M, Kimura T, Hirose M, et al. A case report of fulminant group A streptococcal infection in 35 weeks of gestation: A survival case of twin pregnancy. Shiga District J Jpn Obstetrical Gynecol Soc 2003;2: 27e9 [in Japanese]. Sato M, Noguchi C, Ando N, Kanazawa T, Tsukada Y, Isomine S, et al. A survival case of fulminant group A streptococcal infection (perinatal type). J Jpn Soc Intensive Care Medicine 2003; 10(Suppl. 206) [in Japanese]. Amano M, Tanaka A, Makihara N, Yamada T, Bo M. A case of puerperal septic pelvic thrombophlebitis caused by group A streptococcal infection. Sanfujinkano Shinpo 2005;57:297e 300 [in Japanese]. Kohmoto Y, Hamada T, Motohara M, Amamiya S, Honma S, Yokoyama K, et al. A case report of fulminant group A streptococcal infection in 20 weeks of gestation. Kanagawa District J Jpn Obstetrical Gynecol Soc 2004;41:166 [in Japanese]. Nakahori T, Takata H, Sai R, Kanamoto N, Uchida T, Beppu M, et al. Kurashiki Chuo-byoin Nenpo 2005;68:99e104 [in Japanese]. Tanemura Y, Kamei J, Horie K, Ubukawa M, Tatsumi N, Naito J, et al. A case of intrauterine fetal death because of the infection of streptococcus pyogenes. Igaku Kensa 2007;56:428 [in Japanese]. Serizawa M, Matsui H, Asano H, Yamashita M, Maeda M. A case report of perinatal type fulminant group A streptococcal infection: A survival case of twin neonates and the mother. J Jpn Soc Perin Neon Med 2007;43:417 [in Japanese]. Minami S, Ikeshima M, Boushi E, Yagi S. A survival case of fulminant group A streptococcal infection. J Jpn Soc Perin Neon Med 2007;43:546 [in Japanese]. Maeda A, Morimoto A, Horikawa N, Usami T, Kawasaki K, Uchida T, et al. A rescued case of fulminant group A streptococcal infection (perinatal type). Mod Trends Obstetrics Gynecol 2008;57:49 [in Japanese]. Kobayashi T, Sugiyama T, Yamasaki A, Inoue A, Nagao K, Umekawa T, et al. A case report of fulminant group A streptococcal infection during pregnancy: the patient died 12 hours after admission. Acta Obst Gynaec Jpn 2009;61:612 [in Japanese]. Yamamura KM, Yamada T, Tanaka R, Koyama T, Araki N, Shimada S, et al. A case report of fulminant group A streptococcal infection in pregnancy. The proceeding of the 56th North Japan District Conference of the Japanese Obstetrical and Gynecological Society 2008;95 [in Japanese]. Barret JF, Ritchie WK. Twin delivery. Best Pract Res Clin Obstet Gynaecol 2002;16:43e56. Shimizu Y, Igarashi H, Murai T, Ohkuni H, Watanabe H, Uchiyama T, et al. Report of surveillance on streptococcal toxic shock syndrome in Japan and presentation of the criteria. Kansenshogaku Zasshi 1998;72:258e65 [in Japanese].
www.elsevierhealth.com/journals/jinf
REVIEW
Invasive group A streptococcal infection in pregnancy Takahiro Yamada a,*, Takashi Yamada a, Mie K. Yamamura a, Kenichi Katabami b, Mineji Hayakawa b, Utano Tomaru c, Shigeki Shimada a, Mamoru Morikawa a, Toshio Seki d, Satoshi Ariga e, Kaoru Ishikawa f, Tadayoshi Ikebe g, Satoshi Gando b, Hisanori Minakami a a Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan b Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan c Department of Pathology, Hokkaido University Graduate School of Medicine, N15W7, Kita-ku, Sapporo 060-8638, Japan d Department of Obstetrics and Gynecology, Sapporo Tokushuukai Hospital, Shiroishi-ku, Sapporo 003-0021, Japan e Department of Obstetrics and Gynecology, Hokkaido Shakaihoken Hospital, Toyohira-ku, Sapporo 062-8618, Japan f Department of Obstetrics and Gynecology, Japanese Red Cross Nagoya Daiich Hospital, Nakamura-ku, Nagoya 453-8511, Japan g Department of Bacteriology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Accepted 18 March 2010 Available online 30 March 2010
KEYWORDS Group A streptococcus; Pregnancy; Delivery; Toxic shock syndrome (TSS); Toxic shock like syndrome (TSLS)
Summary We conducted a literature review of 55 pregnancies with symptomatic Group A streptococcus (Streptococcus pyogenes) infection reported in English (20 cases), French (2 cases) and Japanese (33 cases) to seek ways of improving prognosis. Multiparous women (83% [39/47]) in the third trimester (90% [47/52]) were prone to infection from winter to spring (75% [21/28]). Onset was heralded by flu-like symptoms, such as high fever (94% [46/49]), with upper respiratory (40% [22/55]) and/or gastrointestinal symptoms (49% [27/55]). Characteristic findings were early onset of shock (91% [50/55]) and infection-induced strong uterine contraction (73% [40/55]) suggestive of placental abruption. The clinical course was too acute and severe to rescue the mother (58% [32/55] died) and/or infant (66% [39/59] died). However, outcome has improved over the last decade, with rescue of 68% (15/22) of the mothers since 2000, and early use of antibiotics (71% [22/31] survived) and use of intravenous immunoglobulin (91% [10/11] survived) were associated with favourable outcome. Early use of antibiotics
* Corresponding author. Tel.: þ81 11 706 5941; fax: þ81 11 706 7711. E-mail address: [email protected] (T. Yamada). 0163-4453/$36 ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2010.03.011
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T. Yamada et al. and intravenous immunoglobulin may improve outcome of pregnant women suffering from flulike symptoms, shock and strong uterine contractions suggestive of placental abruption. ª 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction Group A streptococcus (GAS: Streptococcus pyogenes) may cause a variety of illnesses ranging from very common, usually clinically mild conditions, such as pharyngitis and impetigo, to less common severe infections, including septicaemia and pneumonia. GAS is isolated from 18% of throat swabs from patients with peritonsillar abscess (median age 22 years; range, 13e83 years) that occurs with an incidence of 19e37/100,000 per year1 and from 0.03% of vaginal and/or rectal swabs from pregnant women in the third trimester.2 Prior to the 20th century, GAS infection was a common cause of serious and sometimes fatal puerperal problems. However, the prevalence of symptomatic GAS infection in pregnancy decreased and became uncommon in the 20th century. Over the past three decades, however, a number of cases of GAS infection with clinical features similar to staphylococcal toxic shock syndrome, designated as streptococcal toxic shock syndrome (TSS), have been reported.3,4 A striking characteristic of streptococcal TSS is the early onset of shock and organ failure, with no site of infection being apparent at presentation in some cases. As this dramatic clinical presentation is not typically associated with GAS infection, there is concern regarding delay in diagnostic workup and institution of definitive therapy. Accordingly, case definitions for streptococcal TSS and classification of GAS infection were proposed by an informal working group of clinicians, microbiologists and epidemiologists in 1993 to assist clinicians by improving awareness and diagnosis of these infections, leading to early therapy4 (Tables 1 and 2). Although streptococcal TSS during pregnancy is rare, the outcome in these cases is poor.5 It may be important to improve awareness and early initiation of therapy to rescue these pregnant women with streptococcal TSS. However, physicians in western countries are often not familiar with this condition, perhaps due to the limited number of case reports published in English. This review presents the clinical features of 55 cases with symptomatic GAS infection during pregnancy published in English (20 cases), French (2 cases) or Japanese (33 cases).
Methods, results and discussion Cases included in this review We identified a total of 58 cases of pregnant women with symptomatic GAS infection that manifested within 12 h after delivery and were reported in English, French or Japanese using PubMed (1966eJune 2009), Japana Centra Revuo Medicina (1983eJune 2009) and the reference lists of previous reports. The search terms ‘‘Streptococcus’’, ‘‘S. pyogenes’’, ‘‘pregnancy’’, ‘‘delivery’’, ‘‘toxic shock’’, ‘‘shock’’, ‘‘sepsis’’ and ‘‘group A streptococcus’’ were used. As GAS infection acquired after delivery was suggested to have a different clinical course from that manifested soon after
delivery in a previous report,5 we used the following selection criterion: ‘‘GAS infection manifested within 12 h after delivery’’. Three cases6,7 were excluded from the present analysis as isolation of GAS was not clearly stated in these 3 case reports. Thus, a total of 55 cases (Table 3)8e52 were analyzed in this study. Of these, 49 cases fulfilled the criteria for streptococcal TSS shown in Table 1, and the remaining 6 cases (Cases 13, 17, 19 and 47e49) were classified as ‘‘other invasive GAS infection’’ according to the criteria shown in Table 2. Thirty-seven (67%) of the 55 patients were Japanese (Cases 19e55) and 33 (60%) cases (Cases 19e21, 24e31 and 34e55) were reported in Japanese only (Table 3). Sixteen of the 55 cases (Cases 3, 5e8, 10, 11, 22e29 and 33) and 2 other cases (Cases 16 and 32) were already discussed in reviews by Udagawa et al. in 19995 and by Crum et al. in 2002,21 respectively. Thus, 37 other cases were added to this review, including 27 cases (Cases 19e21, 30, 31 and 34e55) reported in Japanese only, 8 cases (Cases 1, 2, 4, 9, 12, 14, 15 and 18) reported in English and 2 cases (Cases 13 and 17) reported in French.
Statistics For categorical data, Fisher’s exact test was applied. To compare median values, the Student’s t test or ManneWhitney U-test was applied.
Backgrounds of patients and seasonal prevalence of infection Parity was specified in 47 cases (Table 3). Nulliparous women accounted for only 17% of cases (8/47). Nulliparous women accounted for 15% (5/34) of Japanese patients, while births by nulliparous women accounted for approximately 44%e47% of 1.1e1.2 million births that occurred each year in the last two decades in Japan [Tabulation information released annually from the Ministry of Health and Welfare of Japan]. Thus, nulliparous pregnant women are apparently less likely to acquire severe GAS infection than multiparous pregnant women. A relatively large number of subjects included in this review first showed this new characteristic of GAS infection. Gestational age when infection occurred was specified in 52 cases (Table 3, Fig. 1a). Ninety percent of the cases (47/52) were infected at 30 weeks of gestation or later (Mean SD, 33.5 6.0), indicating that women in the third trimester are more likely to acquire severe GAS infection than those in the first or second trimester. The month of the year in which infection occurred was specified in 27 cases (Table 3, Fig. 1b). Infection occurred most often in spring (March to May), accounting for 56% (15/27) of cases, followed by winter (December to February) in 22% (6/27) of cases. Twin pregnancy accounted for 7.3% (4/55) of the patients. Although the incidence of twin pregnancy has
Invasive GAS infection in pregnancy Table 1
419
Proposed case definition for streptococcal toxic shock syndrome.a,4
I. Isolation of group A Streptococci (Streptococcus pyogenes) A. From a normally sterile site (e.g., blood, cerebrospinal, pleural, or peritoneal fluid, tissue biopsy, surgical wound, etc.) B. From a non-sterile site (e.g., throat, sputum, vagina, superficial skin lesion, etc.) II. Clinical signs of severity A. Hypotension: systolic blood pressure 90 mmHg in adults or < 5th percentile for age in children and B. 2 of the following signs 1. Renal impairment: creatinine 177 mmol/L (2 mg/dL) for adults or 2 the upper limit of normal for age. In patients with pre-existing renal disease, a 2-fold elevation over the baseline level. 2. Coagulopathy: platelets 100 109/L (100,000/mm3) or disseminated intravascular coagulation defined by prolonged clotting times, low fibrinogen level and the presence of fibrin degradation products. 3. Liver involvement: alanine aminotransferase (SGOT), aspartate aminotransferase (SGPT) or total bilirubin levels 2 the upper limit of normal for age. In patients with pre-existing liver disease, a 2-fold elevation over the baseline level. 4. Adult respiratory distress syndrome infiltrates and hypoxaemia in the absence of cardiac failure, or evidence of diffuse capillary leak manifested by acute onset of generalised oedema, or pleural or peritoneal effusions with hypoalbuminaemia 5. A generalised erythematous macular rash that may desquamate. 6. Soft-tissue necrosis, including necrotising fasciitis or myositis, or gangrene. a NOTE. An illness fulfilling criteria IA and II (A and B) can be defined as a definite case. An illness fulfilling criteria IB and II (A and B) can be defined as a probable case if no other aetiology for the illness is identified.
increased worldwide over the past two decades, largely as a consequence of the delay in pregnancy until older ages and the increased use of assisted reproductive technologies,53 twin pregnancy accounts for only 1.5% of all pregnancies in many developed countries. This suggests that women with twin pregnancies were more likely to acquire severe GAS infection.
Symptoms Concurrent or preceding high fever (>38 C) and respiratory symptoms, such as a sore throat, were described in almost all cases (94%, 46/49) and in 40% (22/55) of cases, respectively (Table 3). Gastrointestinal symptoms, such as diarrhoea, nausea and vomiting, were also noted in 49% (27/55) of cases. Thus, life-threatening GAS infection in pregnancy began with flu-like symptoms. Early onset of shock (hypotension) and unusually strong uterine contractions, which are often seen in cases with placental abruption, were striking characteristics of severe GAS infection during pregnancy and occurred in 91% (50/55) and 73% (40/55) of cases, respectively. Strong labour pain may
Table 2
have been associated with purulent uterine myometritis,5 and was noted more frequently in the 33 women in whom GAS was isolated from the genital tract, including the uterus, amniotic fluid, vagina and neonate, than in the remaining 22 women (85% [28/33] vs. 55% [12/22], P Z 0.0284). Cocci concentrated in the vessels and the myometrium were reported (Fig. 2B, C). Non-reassuring foetal heart rate pattern (Fig. 2A) and acute deterioration of foetal condition, which led to foetal/neonatal death in 66% (39/59) of cases, may have been due to uteroplacental circulatory insufficiency because of strong uterine contraction and hypotension. Decreased consciousness level and skin rash were described in 31% (17/55) and 15% (8/ 55) of cases, respectively.
Relationships between maternal outcome and various symptoms, treatments and demographic characteristics Only 42% (23/55) of the mothers and 34% (20/59) of the infants (including four sets of twins) survived the disease (Table 3).
Classification of group A streptococcal infection.a,4.
I. Streptococcal toxic shock syndrome (streptococcal TSS): Defined by criteria in Table 1. II. Other invasive infections: Defined by isolation of group A streptococci from a normally sterile site in patients not meeting criteria for streptococcal TSS. A. Bacteraemia with no identified focus. B. Focal infections with or without bacteraemia. Includes meningitis, pneumonia, peritonitis, puerperal sepsis, osteomyelitis, septic arthritis, necrotising fasciitis, surgical wound infections, erysipelas and cellulitis. III. Scarlet fever: Defined by a scarlatina rash with evidence of group A streptococcal infection, most commonly pharyngotonsillitis. IV. Noninvasive infections: Defined by the isolation of group A streptococci from a non-sterile site. A. Mucous membrane: includes pharyngitis, tonsillitis, otitis media, sinusitis, vaginitis. B. Cutaneous: includes impetigo. V. Nonsuppurative sequelae: Defined by specific clinical findings with evidence of a recent group A streptococcal infection. A. Acute rheumatic fever. B. Acute glomerulonephritis. a
NOTE. Examples of conditions in each category are not inclusive.
420
District, Country
year
Month
age
para
GW
fever
RS
GS
SL
UC
R
G
FI
S
TSS
AB
IG
DM
PF
PM
UK London, UK Portsmouth, UK Portsmouth, UK Birmingham, UK Gloucester, UK Gloucester, UK France North Carolina, US Australia Toronto, Canada Indiana, US France North Yorkshire, UK Wales, UK San Diego, US France Veldhoven, Netherland Nagano, Japan* Aichi, Japan* Japan* Chiba, Japan Chiba, Japan Shimane, Japan* Hyogo, Japan* Fukushima, Japan* Fukuoka, Japan* Tottori, Japan* Chiba, Japan* Ibaraki, Japan* Okinawa, Japan* Aichi, Japan Niigata, Japan Aichi, Japan* Hyogo, Japan* Oita, Japan* Iwate, Japan* Aichi, Japan* Kanagawa, Japan* Aichi, Japan* Tokyo, Japan* Tokyo, Japan*
1969 1987 1988 1988 1988 1988 1988 1988 1991 1995 1995 1995 1996 1996 1998 2002 2005 2007 1986 1991 1992 1993 1994 1994 1994 1994 1994 1995 1996 1997 1997 1997 1997 1998 1999 1999 2001 2001 2002 2002 2002 2002
UN UN UN UN UN UN UN UN UN summer UN UN UN 5 UN 1 UN UN 12 5 UN 3 4 1 5 6 9 3 4 3 7 UN 1 3 2 UN 3 6 UN 2 4 3
27 33 32 24 33 27 24 33 40 31 32 29 30 36 30 31 43 33 29 31 27 29 42 34 33 35 39 35 28 31 30 43 37 27 34 25 34 36 32 36 33 24
7 UN 3 0 UN UN UN UN 0 2 1 3 2 2 2 0 2 4 UN 1 1 1 3 2 1 2 2 2 3 1 1 UN 1 1 2 1 1 2 3 1 2 0
UN term 34 18 39 37 39 UN 7 37 36 32 34 36 25 34 32 34 37 40 39 34 34 39 39 33 30 34 37 31 36 34 30 32 39 31 40 30 33 40 33 36
UN þ UN þ þ þ þ þ þ þ þ UN þ þ þ þ þ þ þ þ þ þ þ þ þ þ UN þ UN þ þ þ þ þ þ þ þ þ þ
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þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ
V V V V V C C V V C C V V C C C V V C C V C V C C V V V C C C C V V V V V C C C
A A SB SB SB A A A abortion SB 1:SB, 2:SB A A SB SB ND (day15) A A A SB ND 1:SB, 2:SB SB A SB SB SB SB SB SB A SB A A SB ND ND A SB SB SB SB
D D D D D D A D A D D A A D A A A A A D D D D D D D D D D D D D D A D A A D D D D A
8
to fulfil the criteria for streptococcal TSS (Table 1). Of the 50
1 29 310 410 511 612 712 813 914 1015 1116 1217 1318 1419 1520 1621 1722 1823 1924 2025 2125 2226 2326 2427 2528 2627 2729 2827 2930 3031 3127 3232 3333 3434 3527 3635 3736 3837 3938 4039 4140 4241
T. Yamada et al.
Reported cases of group A streptococcal infection in pregnancy.
Case [#]
Early onset of shock was the chief symptom and is required
Table 3
421 *NOTE. [#]: Reference no., Year : when episode occurred, Japan*: Case reported in Japanese only, GW: gestational weeks, UN: unknown, RS: respiratory symptom, GS: gastrointestinal symptom, SL: unusual strong labour, UC: unconsciousness and/or coma, R: rash and/or erythema, G: group A streptococcus was isolated from the uterus, placenta, amniotic fluid, vagina, or neonate, FI; focal infection site other than genital tract was identified early, S: early onset shock, TSS: case definition4 for streptococcal toxic shock syndrome was fulfilled, AB: antibiotics, IG: immunoglobulin, DM: delivery mode, C: cesarean delivery, V: vaginal delivery, PF: prognosis of fetus, PM: prognosis of mother; SB: Still birth, ND: neonatal death, A: alive, D: dead.
4342 4443 4544 4645 4746 4846 4947 5048 5149 5250 5351 5452 5537
Shiga, Japan* Chiba, Japan* Hyogo, Japan* Tokyo, Japan* Okayama, Japan* Okayama, Japan* Aichi, Japan* Shizuoka, Japan* Wakayama, Japan* Okayama, Japan* Mie, Japan* Hokkaido, Japan* Aichi, Japan*
2002 2003 2004 2004 2005 2005 2006 2006 2007 2008 2008 2008 2009
7 UN UN UN UN UN 5 6 UN UN UN 4 4
29 34 38 35 23 22 34 33 28 UN 16 33 31
3 4 1 1 0 0 UN 1 0 multi 0 2 1
35 UN 38 20 36 38 34 34 33 32 37 30 25
þ UN þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ
þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ þ
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þ
þ þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ
þ þ þ þ þ þ þ þ þ þ
þ þ þ þ
C V V V V V C C C V C V
1: A, 2: SB SB A SB SB A SB 1: A, 2: A SB SB SB SB SB
A A A A A A A A A A D D D
Invasive GAS infection in pregnancy cases a 25 20 15 10 5 0
<21
21-25
26-30
12 1
2
4
31-35
36-40
>40
weeks
Cases b 7 6 5 4 3 2 1 0
3
5
6
7
8
9
10 11 Month
Figure 1 Histogram of numbers of cases of GAS infection occurring in each gestational week (a) and seasonal trends (b).
women in whom early onset of shock was observed, 49 (98%) fulfilled the criteria for streptococcal TSS. Five of the remaining six women, who were classified as having ‘‘other invasive infections’’ according to the criteria shown in Table 2, did not develop shock (Table 3). All women without shock or with ‘‘other invasive infections’’ survived the disease, suggesting that absence of shock is a key factor predicting favourable outcome (Table 4). In addition, all seven women whose sites of focal infection, such as peritonitis (Case 9), fasciitis (Case 12), gastritis (Case 17), meningitis (Cases 13, 18 and 19) and arthritis (Case 50), survived the disease, although early onset of shock was observed in 57% (4/7) of these women (Tables 3 and 4). Nulliparous women were more resistant to GAS infection than multiparous women; nulliparous women acquired severe GAS infection less frequently than multiparous women (Table 3) and nulliparous women appeared to succumb to this disease less frequently than multiparous women (Table 4). Administration of antibiotics was described in 31 women, of whom 71% (22/31) survived the disease, while only 4.2% (1/24) of those with no description of antibiotic use survived (Table 4). Thus, at least 22 (96%) of 23 surviving patients received antibiotics. Ten (91%) of 11 patients who received intravenous immunoglobulin (IVIG) therapy survived, while 30% (13/44) of the cases without such treatment survived. These findings suggest that administration of antibiotics and intravenous immunoglobulin help patients with severe GAS infection to overcome this life-threatening disease. However, it is possible that the effectiveness of antibiotics and IVIG have been overestimated due to the rapidity of disease progression and
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Figure 2 A: Cardiotocogram of the Case 54. Prolonged deceleration and foetal bradycardia were seen. B: Microscopic findings of the lung with haematoxylin-eosin staining (upper panel) and gram staining (lower panel) (Case 54). Emboli of gram-positive cocci in the pulmonary vessels and alveoli are shown. C: Microscopic view of the myometrium of the uterus (Case 54). Hypertrophic or degenerated smooth muscle cells and gram-positive coccal colonies were observed.
publication bias. Some patients may have been suspected initially as having viral infection and may have had very little time to receive antibiotics and IVIG before death. In fact, we reported a patient who died 20 h after the onset of illness before commencement of such specific treatment.52 In contrast, patients with relatively slow progression were likely to receive various treatments, such as antibiotics and IVIG, which may therefore have led to a better outcome. Reports describing severe cases or cases that responded positively to treatment may be more likely to be submitted for publication. Thus, further studies are clearly needed to confirm the efficacy of early administration of IVIG, although administration of antibiotics may have been necessary to rescue patients with severe GAS infection.
Outcome has shown improvement over the last decade, although the reasons for this are unknown (Table 4). However, as Japanese patients accounted for 67% (37/55) of all pregnant women with symptomatic GAS infection, Japanese physicians may have paid greater attention to this disease after publication of the criteria for diagnosis of perinatal GAS infection by the Ministry of Health and Welfare of Japan in 1996.4,54 The use of the sensational term ‘‘flesh-eating bacteria’’ by the Japanese media has also played an important role in attracting the attention of physicians. It is possible that information about GAS infection in pregnancy may have contributed to the survival of 14 Japanese patients treated since 1998, at least 13 (93%) and 7 (50%) of whom received antibiotics and IVIG, respectively (Table 3).
Invasive GAS infection in pregnancy
423
Table 4 Maternal survival rate according to various symptoms, treatment, and factors.
Fever Respiratory symptoms GI tract symptomsa Strong labour pain Unconsciousness Skin rash Genital tract infectionb Focal infectionc Early onset of shock TSSd Nulliparous Twin pregnancy Cesarean delivery Use of antibiotics Use of immunoglobulin Japanese Infection at/after 2000
Absent/No
Present/Yes
p-value
1/3 (33%) 15/33 (45%)
21/46 (46%) 8/22 (36%)
>0.9999 0.5832
14/28 5/15 17/38 19/47 10/22
(50%) (33%) (45%) (40%) (45%)
9/27 18/40 6/17 4/8 13/33
(33%) (45%) (35%) (50%) (39%)
16/48 5/5 6/6 14/39 21/51 12/28 1/24 13/44
(33%) (100%) (100%) (36%) (41%) (43%) (4.2%) (30%)
7/7 18/50 17/49 6/8 2/4 11/24 22/31 10/11
(100%) 0.0012 (36%) 0.0097 (35%) 0.0035 (75%) 0.0574 (50%) >0.9999 (46%) >0.9999 (71%) <0.0001 (91%) 0.0003
8/18 (44%) 8/33 (24%)
15/37 (41%) 15/22 (68%)
0.2772 0.5454 0.5668 0.7071 0.7818
0.7805 0.0020
a
NOTE. gastrointestinal tract symptoms. GAS was isolated from the uterus, placenta, amniotic fluid, vagina, or newborns. c Focal infection site other than genital tract including peritonitis (Case 9), fasciitis (Case 12), phlegmonous gastritis (Case 17), meningitis (Cases 13, 18, and 19) and arthritis (Case 50) was determined early. d Case definition for streptococcal TSS4 is fulfilled. b
In conclusion, the outcome of pregnant women with symptomatic Group A streptococcus infection remains to be improved. Multiparous women are suggested to be more likely to acquire severe GAS infection during pregnancy. Early use of antibiotics and intravenous immunoglobulin may help patients with severe GAS infection to overcome this life-threatening disease. Initial signs of this disease mimic those of influenza, followed by strong labour pains. It is important to be aware of these characteristics of this infection to initiate early treatment with antibiotics and immunoglobulin.
References 1. Sunnergren O, Swanberg J, Mo ¨lstad S. Incidence, microbiology and clinical history of peritonsillar abscesses. Scand J Infect Dis 2008;40:752e5. 2. Mead PB, Winn WC. Vaginal-rectal colonization with group A streptococci in late pregnancy. Infect Dis Obstet Gynecol 2000;8:217e9. 3. Stevens DL, Tanner MH, Winship J, Swarts R, Ries KM, Schlievert PM, et al. Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A. N Eng J Med 1989;321:1e7. 4. The working group on severe streptococcal infections. Defining the group A streptococcal toxic shock syndrome. JAMA 1993; 269:390e1.
5. Udagawa H, Oshio Y, Shimizu Y. Serious group A streptococcal infection around delivery. Obstet Gynecol 1999;94:153e7. 6. Chimura T, Numazaki M. Septic shock (maternal death) related to group A hemolytic streptococcus during pregnancy. Sanfujinka Chiryo 1997;75:329e34 [in Japanese]. 7. Udagawa H. Fulminant streptococcal infection and maternal death. Shusanki-Igaku 1999;29:1347e51 [in Japanese]. 8. Puerperal streptococcal infection. Br Med J 1969;27:788. 9. Teall A, Visuvanthan S, Payne A, Silverstone A. Unsuspected streptococcal infection presenting with diarrhoea in late pregnancy. J Infect 1987;14:185e6. 10. Acharya U, Lamont CAR. Group A beta-haemolytic streptococcus causing disseminated intravascular coagulation and maternal death. Lancet 1988;1:595. 11. Kavi J, Wise R. Group A beta-haemolytic streptococcus causing disseminated intravascular coagulation and maternal death. Lancet 1988;1:993e4. 12. Swingler GR, Bigrigg MA, Hewitt BG, Nulty Mc. Disseminated intravascular coagulation associated with group A streptococcal infection in pregnancy. Lancet 1988;1:1456e7. 13. Bollaert PE, Bauer Ph, Lambert H, Laprevote-Heully MC, Burdin JC, Larcan A. Septice ´mie fulminante a ´ streptocoque du groupe A en fin de grossesse. La Presse Medicale 1988;17: 1816 [in French]. 14. Dotters DJ, Katz VL. Streptococcal toxic shock associated with septic abortion. Obstet Gynecol 1991;78:549e51. 15. Margin CJ. Streptococcus group A maternal death. An important message for readers. Aust N Z J Obstet Gynaecol 1995; 35:227. 16. Morgan PJ. Maternal death following epidural anaesthesia for caesarean section delivery in a patient with unsuspected sepsis. Can J Anesth 1995;42:330e4. 17. Nyberg SL, Schlievert PM, Saul W, Johnson JR, Ferrieri P, Watkins VS. Successful management of a serious group A streptococcal infection during the third trimester of pregnancy. Clin Infect Dis 1995;21:1058e9. 18. Ferrazzini G, Peduzzi R, Balestra B. Group A beta-hemolytic streptococcal meningitis in a pregnant woman. Schweiz Med Wochenschr 1996;126:1842e4. 19. Barnham MRD, Weightman NC. Bacteraemic Streptococcus pyogenes infection in the peri-partum period: now a rare disease and prior carriage by the patient may be important. J Infect 2001;43:173e6. 20. Simmonds M. Necrotising fasciitis and group A streptococcus toxic shock-like syndrome in pregnancy: treatment with plasmapheresis and immunoglobulin. Int J Obstet Anesth 1999;8:125e30. 21. Crum NF, Helen MC, Thomas GG, Braden RH. Group A streptococcal toxic shock syndrome developing in the third trimester of pregnancy. Infect Dis Obstet Gynecol 2002;10:209e16. 22. Hommel S, Savoye G, Lorenceau-Savale C, Costaglioli B, Baron F, Le Pessot F, et al. Phlegmonous gastritis in a 32week pregnant woman managed by conservative surgical treatment and antibiotics. Dig Dis Sci 2007;52:1042e6. 23. Verhulsdonk MT, Hassell DR, Oei SG. Septic shock as a result of group A beta-hemolytic streptococcal meningitis with empyema in pregnancy. Int J Gynaecol Obstet 2007;97:197e8. 24. Kikkawa T, Ikeda S, Takeda S, Yanagisawa N, Inoue K. A case report of a pregnant woman with severe bacterial meningitis caused by group A beta-hemolytic Streptococcus. Rinsho Shinkeigaku 1986;26:343e7 [in Japanese]. 25. Nagaya K. Maternal death of Japan (Case reports of maternal death) Sanpo-sha. Tokyo; 1998 [in Japanese]. 26. Ooe K, Udagawa H. A new type of fulminant group A streptococcal infection in obstetric patients: report of two cases. Hum Pathol 1997;28:509e12. 27. Udagawa H, Oshio Y, Shimizu Y. Clinical characteristics of streptococcal toxic shock syndrome: perinatal type. Acta Obst Gynaecol Jpn 1999;51:1141e9 [in Japanese].
424 28. Takekida S, Tanaka A, Hayakawa Y, Matsuo H, Bo M, Yamazaki M, et al. A case report of Toxic Shock Like Syndrome (TSLS) by group A streptococcus in pregnancy. Sanfujinkano Shinpo 1994;46:823 [in Japanese]. 29. Sato M, Tsukimori S, Hirakawa T, Koyanagi T, Nakano H. A case report of streptococcal toxic shock syndrome (STSS) during pregnancy. Kyushu Journal Obstetrics Gynecol; 1995; Dec: 111e2 [in Japanese]. 30. Udagawa H, Shimizu K, Nakata H, Inayoshi C, Miyashita S, Kobayashi K, et al. Fulminant streptococcal infection and sudden death in a pregnant woman: a case report. Acta Obst Gynaec Jpn 1997;49:125e8 [in Japanese]. 31. Inoue K, Saito M, Toyama S, Tsukahara T, Kubo T. Maternal death due to severe infection by group A streptococcus (A case report). Kanto Journal Obstetrics Gynecol 1998;35:33e7 [in Japanese]. 32. Ichiyama S, Nakashima K, Shimokata K, Ohta M, Shimizu Y, Ooe K, et al. Transmission of streptococcus pyogenes causing toxic shock-like syndrome among family members and confirmation by DNA macrorestriction analysis. J Infect Dis 1997; 175:723e6. 33. Hirose Y, Shibuya H, Okazaki E, Aono K, Tokunaga A, Taguchi S, et al. Toxic shock-like syndrome with flu-like prodrome: a possible role of ‘enhancing tissue focus’ for streptococcal toxic shock. J Infect 2001;42:195e200. 34. Ito T, Ishikawa K, Ikoma Y, Miwa T, Oonuma M, Kuno N, et al. A case report of serious group A streptococcal infection during pregnancy. Acta Obst Gynaec Jpn 1998;50:1016e20 [in Japanese]. 35. Terawaki S, Taniguchi I, Baba M. A case report of fulminant group A streptococcal infection. J Jpn Soc Perin Neon Med 1999;35:259 [in Japanese]. 36. Kubo T, Oikawa N. A case report of suspected fulminant group A streptococcal infection at 40 weeks of gestation. Iwate Kenritsu Byoin Igakkai Zasshi 2001;41:123e6 [in Japanese]. 37. Sakado M, Yoshida K, Yokoi A, Gunjima S, Hamashima Y, Nakatsu M, et al. Two cases of perinatal type Streptoccal toxic shock syndrome. The proceeding of the 89th Aichi District Conference of the Japanese Obstetrical and Gynecological Society; 2009 [in Japanese]. 38. Yamaguchi S, Takae K, Hashimoto K, Fujisawa S. A case report of a maternal death of woman with gestational diabetes due to fulminant group A streptococcal infection. Kanto J Obstetrics Gynecol 2002;39:163 [in Japanese]. 39. Noguchi M, Matsushita S, Sawaguchi K, Noguchi M. A case report of maternal fetal death due to fulminant group A streptococcal infection in late pregnancy. Proc Conf Obstetrical Gynecol Infect 2003;20:104e6 [in Japanese]. 40. Mita S, Okuda N, Yokota A, Sasaki S, Koshino T, Nakai A, et al. A case report of streptococcal toxic shock syndrome led to maternal death. Tokyo District J Jpn Obstetrical Gynecol Soc 2002;51:454e9 [in Japanese]. 41. Hanada R, Takagi T, Iijima T, Iwao Y. A case report of acute respiratory failure after intra uterine fetal death due to
T. Yamada et al.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53. 54.
fulminant group A streptococcal infection. Kokyu 2004;23: 430e2 [in Japanese]. Tsuji S, Takebayashi K, Ono T, Akiyama M, Kimura T, Hirose M, et al. A case report of fulminant group A streptococcal infection in 35 weeks of gestation: A survival case of twin pregnancy. Shiga District J Jpn Obstetrical Gynecol Soc 2003;2: 27e9 [in Japanese]. Sato M, Noguchi C, Ando N, Kanazawa T, Tsukada Y, Isomine S, et al. A survival case of fulminant group A streptococcal infection (perinatal type). J Jpn Soc Intensive Care Medicine 2003; 10(Suppl. 206) [in Japanese]. Amano M, Tanaka A, Makihara N, Yamada T, Bo M. A case of puerperal septic pelvic thrombophlebitis caused by group A streptococcal infection. Sanfujinkano Shinpo 2005;57:297e 300 [in Japanese]. Kohmoto Y, Hamada T, Motohara M, Amamiya S, Honma S, Yokoyama K, et al. A case report of fulminant group A streptococcal infection in 20 weeks of gestation. Kanagawa District J Jpn Obstetrical Gynecol Soc 2004;41:166 [in Japanese]. Nakahori T, Takata H, Sai R, Kanamoto N, Uchida T, Beppu M, et al. Kurashiki Chuo-byoin Nenpo 2005;68:99e104 [in Japanese]. Tanemura Y, Kamei J, Horie K, Ubukawa M, Tatsumi N, Naito J, et al. A case of intrauterine fetal death because of the infection of streptococcus pyogenes. Igaku Kensa 2007;56:428 [in Japanese]. Serizawa M, Matsui H, Asano H, Yamashita M, Maeda M. A case report of perinatal type fulminant group A streptococcal infection: A survival case of twin neonates and the mother. J Jpn Soc Perin Neon Med 2007;43:417 [in Japanese]. Minami S, Ikeshima M, Boushi E, Yagi S. A survival case of fulminant group A streptococcal infection. J Jpn Soc Perin Neon Med 2007;43:546 [in Japanese]. Maeda A, Morimoto A, Horikawa N, Usami T, Kawasaki K, Uchida T, et al. A rescued case of fulminant group A streptococcal infection (perinatal type). Mod Trends Obstetrics Gynecol 2008;57:49 [in Japanese]. Kobayashi T, Sugiyama T, Yamasaki A, Inoue A, Nagao K, Umekawa T, et al. A case report of fulminant group A streptococcal infection during pregnancy: the patient died 12 hours after admission. Acta Obst Gynaec Jpn 2009;61:612 [in Japanese]. Yamamura KM, Yamada T, Tanaka R, Koyama T, Araki N, Shimada S, et al. A case report of fulminant group A streptococcal infection in pregnancy. The proceeding of the 56th North Japan District Conference of the Japanese Obstetrical and Gynecological Society 2008;95 [in Japanese]. Barret JF, Ritchie WK. Twin delivery. Best Pract Res Clin Obstet Gynaecol 2002;16:43e56. Shimizu Y, Igarashi H, Murai T, Ohkuni H, Watanabe H, Uchiyama T, et al. Report of surveillance on streptococcal toxic shock syndrome in Japan and presentation of the criteria. Kansenshogaku Zasshi 1998;72:258e65 [in Japanese].