Streptococcus pyogenes: Comparison
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Streptococcus pyogenes, (colloquially named “group A streptococcus” (GAS)), is a Gram-positive bacterial pathogen that can cause both non-invasive and invasive disease (iGAS), as well as nonsuppurative sequelae. This includes pharyngitis, scarlet fever, impetigo, cellulitis, type II necrotizing fasciitis, streptococcal toxic shock syndrome, acute rheumatic fever and post-streptococcal glomerulonephritis.

  • group A strep
  • group A streptococcus
  • Strep A
  • GAS
  • streptococcus pyogenes
  • risk assessment
  • infection control
  • management
  • policy

1. Areas of Prevalence

Despite being in existence for hundreds of years, GAS still creates a substantial burden of disease and death on a global scale, mainly in children and young adults in less developed countries [122]. In low- and middle-income countries, and in disadvantaged populations in high-income countries such as the United States and Australia, GAS diseases remain endemic [9,14]. GAS diseases also remain relatively important in more developed countries. According to this review, the broad diversity of GAS genotypes has led to the persistence of these infections globally [12]. Strain variations also exist for GAS between developed and developing countries. Low-income settings report high GAS strain diversity compared with high-income settings. The reason as to why this is so is not clear [123]. However, Tartof et al. [18] argue that local factors, such as crowding, may enhance the frequency of GAS transmission and horizontal gene transfers that contribute to the increased strain diversity in such settings. A study carried out in South Africa showed that there were similarities in the GAS strains when they were compared with the ones in Tunisia and Kenya, but they were different when compared with those of developed countries [107]. Similarities in strain diversity were also reported in settings with similar living conditions, which include indigenous populations in developed countries [9,56]. This review also found that socially disadvantaged communities are heavily burdened by these diseases due to their low socioeconomic status, characterized by poor housing conditions and inability to afford medical care, among other factors [15,20,21,26,118,124]. According to a study performed in the United Kingdom, interviews conducted with the patients, teachers and parents of children affected with rheumatic fever revealed that low socioeconomic status was common among most of the respondents [51]. In Australia, records indicate that GAS infections and their sequalae among Indigenous Australians continue to persist at equal or higher levels when compared with cases in developing countries [14]. Tropical regions of northern Queensland and the Northern Territory, the only states that report GAS infections as notifiable diseases, have the highest reported rates, with the incidence in indigenous populations ranging from 23.9 to 82.5 cases per 100,000 persons, and in non-indigenous populations from 4.7 to 10.3 cases per 100,000 persons. This has been linked to the higher proportion of indigenous people in northern Australia who experience high levels of socioeconomic disadvantage and household overcrowding [27]. In Alaska in the United States, a region where indigenous Americans live, the incidence rate of GAS infections in 2015 was 12.3 cases per 100,000 persons, a rate that was more than twice that of the rest of the United States [9].

Despite being in existence for hundreds of years, GAS still creates a substantial burden of disease and death on a global scale, mainly in children and young adults in less developed countries [1]. In low- and middle-income countries, and in disadvantaged populations in high-income countries such as the United States and Australia, GAS diseases remain endemic [2][3]. GAS diseases also remain relatively important in more developed countries. According to this review, the broad diversity of GAS genotypes has led to the persistence of these infections globally [4]. Strain variations also exist for GAS between developed and developing countries. Low-income settings report high GAS strain diversity compared with high-income settings. The reason as to why this is so is not clear [5]. However, Tartof et al. [6] argue that local factors, such as crowding, may enhance the frequency of GAS transmission and horizontal gene transfers that contribute to the increased strain diversity in such settings. A study carried out in South Africa showed that there were similarities in the GAS strains when they were compared with the ones in Tunisia and Kenya, but they were different when compared with those of developed countries [7]. Similarities in strain diversity were also reported in settings with similar living conditions, which include indigenous populations in developed countries [2][8]. This review also found that socially disadvantaged communities are heavily burdened by these diseases due to their low socioeconomic status, characterized by poor housing conditions and inability to afford medical care, among other factors [9][10][11][12][13][14]. According to a study performed in the United Kingdom, interviews conducted with the patients, teachers and parents of children affected with rheumatic fever revealed that low socioeconomic status was common among most of the respondents [15]. In Australia, records indicate that GAS infections and their sequalae among Indigenous Australians continue to persist at equal or higher levels when compared with cases in developing countries [3]. Tropical regions of northern Queensland and the Northern Territory, the only states that report GAS infections as notifiable diseases, have the highest reported rates, with the incidence in indigenous populations ranging from 23.9 to 82.5 cases per 100,000 persons, and in non-indigenous populations from 4.7 to 10.3 cases per 100,000 persons. This has been linked to the higher proportion of indigenous people in northern Australia who experience high levels of socioeconomic disadvantage and household overcrowding [16]. In Alaska in the United States, a region where indigenous Americans live, the incidence rate of GAS infections in 2015 was 12.3 cases per 100,000 persons, a rate that was more than twice that of the rest of the United States [2].

A limitation in identifying the areas of highest prevalence is the fact that GAS diseases are not always notifiable. A few countries, such as England, Wales, Japan, Canada, Norway, China and the United States, report specific GAS diseases, but not all clinical manifestations. For example, in Japan and the United States, only streptococcal TSS is notifiable [6,125], in Canada and Norway all iGAS diseases are notifiable [10,57], and in China only scarlet fever is notifiable [96]. In other countries, the disease is only notifiable in specific regions. For example, in Australia, GAS diseases are notifiable in the Northern Territory and Queensland only [15]. Another limitation with this review is that only articles published from 2010 to 2020 were included. This may have introduced a bias towards publications from Asia and Australasia, since an increasing number of publications on this subject have originated from these regions during the last few years.

A limitation in identifying the areas of highest prevalence is the fact that GAS diseases are not always notifiable. A few countries, such as England, Wales, Japan, Canada, Norway, China and the United States, report specific GAS diseases, but not all clinical manifestations. For example, in Japan and the United States, only streptococcal TSS is notifiable [17][18], in Canada and Norway all iGAS diseases are notifiable [19][20], and in China only scarlet fever is notifiable [21]. In other countries, the disease is only notifiable in specific regions. For example, in Australia, GAS diseases are notifiable in the Northern Territory and Queensland only [9]. Another limitation with this review is that only articles published from 2010 to 2020 were included. This may have introduced a bias towards publications from Asia and Australasia, since an increasing number of publications on this subject have originated from these regions during the last few years.

2. Transmission

Understanding the transmission routes is essential for identifying appropriate control interventions. The individual transmission routes for each GAS disease are shown in Table 2. Humans are the only natural reservoir for GAS, and it is commonly found in the carrier state on the anus, vagina, pharynx and skin of human hosts without causing disease [126].

Transmission of GAS primarily occurs through respiratory droplets, or skin contact with broken skin that has secretions from infected sores on it [23][24][25]. The environment is also a potential reservoir, and facilitates transmission through contaminated equipment, surfaces, dust and fomites [26][23][27][28][29]; however, very few current studies have explored this area, hence it is an area for further research. The foodborne transmission of GAS infections is also possible [30]. GAS has been shown to survive in ice cream (18 days), raw and pasteurized milk at 15–37 °C (96 h), room temperature butter (48 h) and neutralized butter (12–17 days) [31]. Additionally, GAS has been found to last several days in salads at room temperature [32]. An investigation of a GAS outbreak in China in 2014 among a film crew demonstrated that foodborne outbreaks due to GAS infections exist, although they are very rare. However, these outbreaks are always difficult to recognize at early stages, and thus are usually ignored by healthcare workers [33]. From the literature reviewed, very few studies have been done with regards to foodborne GAS transmission, and therefore more research needs to be done on the same.

Table 2. Transmission routes for diseases caused by Streptococcus pyogenes.
 
 
Transmission of GAS primarily occurs through respiratory droplets, or skin contact with broken skin that has secretions from infected sores on it [31,127,128]. The environment is also a potential reservoir, and facilitates transmission through contaminated equipment, surfaces, dust and fomites [16,31,32,33,34]; however, very few current studies have explored this area, hence it is an area for further research. The foodborne transmission of GAS infections is also possible [35]. GAS has been shown to survive in ice cream (18 days), raw and pasteurized milk at 15–37 °C (96 h), room temperature butter (48 h) and neutralized butter (12–17 days) [129]. Additionally, GAS has been found to last several days in salads at room temperature [130]. An investigation of a GAS outbreak in China in 2014 among a film crew demonstrated that foodborne outbreaks due to GAS infections exist, although they are very rare. However, these outbreaks are always difficult to recognize at early stages, and thus are usually ignored by healthcare workers [131]. From the literature reviewed, very few studies have been done with regards to foodborne GAS transmission, and therefore more research needs to be done on the same.

3. Common Areas of Infection

GAS infections are commonly spread in schools, nurseries and kindergartens, hospitals, care homes, military camps and homeless shelters [8,22,33,34,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50]. A review of epidemiological data for scarlet fever for the period 2005–2015 conducted by Zhang et al. [8] in Hong Kong showed that the infections were higher during the months when schools were open. Additionally, more cases were reported among children who attended nurseries and kindergartens. This was attributed to low immunity in this population group and high populations in these settings [8].

GAS infections are commonly spread in schools, nurseries and kindergartens, hospitals, care homes, military camps and homeless shelters [34][35][28][29][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. A review of epidemiological data for scarlet fever for the period 2005–2015 conducted by Zhang et al. [34] in Hong Kong showed that the infections were higher during the months when schools were open. Additionally, more cases were reported among children who attended nurseries and kindergartens. This was attributed to low immunity in this population group and high populations in these settings [34].

Cummins et al.’s [42] review of 20 outbreaks in care homes showed high infection rates existed as a result of cross-infection from infected care home residents to the healthy residents, as well as infections from home care staff to residents. However, cross-infection from care staff was slightly lower compared with cross-infection among residents. This is supported by Dooling et al. [47] and Deutscher et al. [65]. The incidence of GAS diseases in residents of long-term care facilities is also higher (3-8-fold) than among community residents of the same age [43].

Cummins et al.’s [42] review of 20 outbreaks in care homes showed high infection rates existed as a result of cross-infection from infected care home residents to the healthy residents, as well as infections from home care staff to residents. However, cross-infection from care staff was slightly lower compared with cross-infection among residents. This is supported by Dooling et al. [47] and Deutscher et al. [51]. The incidence of GAS diseases in residents of long-term care facilities is also higher (3-8-fold) than among community residents of the same age [43].

This review identified hospitals as high-risk areas for infections [33,34,38,39,40,41]. This was attributed to poor surgical procedures, contaminated medical instruments or hospital environments, and cross-infection from other patients and healthcare workers [33,38,39,44,74,75].

This review identified hospitals as high-risk areas for infections [28][29][38][39][40][41]. This was attributed to poor surgical procedures, contaminated medical instruments or hospital environments, and cross-infection from other patients and healthcare workers [28][38][39][44][52][53].

According to Engelthaler et al. [22], evidence from a study conducted on clients from homeless shelters and jails in the United States showed that conditions in these settings favored the transmission of GAS infections. A comparable study conducted in Canada also reported similar findings [62]. Hammond-Collins et al. [49] also conducted a study on GAS-infected cases between August 2016 to January 2018 in Belgium. The results showed incidence rates of 2333/100,000 persons in homeless groups and 25/100,000 persons in non-homeless groups, showing a higher incidence (100 times higher) for homeless persons compared to non-homeless persons. An outbreak investigation in homeless shelters done in Canada in 2019 supported the same findings [50].

According to Engelthaler et al. [35], evidence from a study conducted on clients from homeless shelters and jails in the United States showed that conditions in these settings favored the transmission of GAS infections. A comparable study conducted in Canada also reported similar findings [54]. Hammond-Collins et al. [49] also conducted a study on GAS-infected cases between August 2016 to January 2018 in Belgium. The results showed incidence rates of 2333/100,000 persons in homeless groups and 25/100,000 persons in non-homeless groups, showing a higher incidence (100 times higher) for homeless persons compared to non-homeless persons. An outbreak investigation in homeless shelters done in Canada in 2019 supported the same findings [50].

4. At Risk Groups

GAS affects anyone in any population [132,133]. However, GAS diseases are more common in children and the elderly [8,10,11,36,43,51,52,53,54,55,56,57,58], as demonstrated in this review. School-aged children were consistently identified as high-risk for GAS diseases. A population-based case control study undertaken in New Zealand between 2010 and 2014 showed that 79.1% of new cases were reported in children 5–17 years old, and cases were rare in children 4 years old and below [121]. This was also reported in studies from the United Kingdom in 2013, where most cases were children 5 to 14 years old [51]. Additionally, a review of scarlet fever cases for the period 2005–2015 in Hong Kong revealed a high incidence among children 5–15 years old, although those at most risk were children 3–5 years of age. This age group includes children just entering kindergarten [36]. Even though any person of any age group can be an asymptomatic case of a GAS disease, most asymptomatic cases are seen in children. An asymptomatic person can act as a reservoir for GAS, and therefore pose a greater risk of transmission [80].

GAS affects anyone in any population [55][56]. However, GAS diseases are more common in children and the elderly [34][19][57][36][43][15][58][59][60][61][8][20][62], as demonstrated in this review. School-aged children were consistently identified as high-risk for GAS diseases. A population-based case control study undertaken in New Zealand between 2010 and 2014 showed that 79.1% of new cases were reported in children 5–17 years old, and cases were rare in children 4 years old and below [63]. This was also reported in studies from the United Kingdom in 2013, where most cases were children 5 to 14 years old [15]. Additionally, a review of scarlet fever cases for the period 2005–2015 in Hong Kong revealed a high incidence among children 5–15 years old, although those at most risk were children 3–5 years of age. This age group includes children just entering kindergarten [36]. Even though any person of any age group can be an asymptomatic case of a GAS disease, most asymptomatic cases are seen in children. An asymptomatic person can act as a reservoir for GAS, and therefore pose a greater risk of transmission [64].

In addition to children, the elderly population are high-risk for GAS diseases [10,43,57,58]. A study of the review of outbreaks of GAS diseases in Europe conducted by Cummins et al. [42] established that 20 out of 31 outbreaks that occurred between 1992 and 2008 were related to residential care homes. Chalker et al.’s [38] study also showed that many cases of GAS infections were common in the elderly population, especially those over 70 years. Mearkle et al. [64] demonstrated an increased risk of GAS transmission within a household when one family member is positive. This risk was greatest in couples aged 75 years and older, and in mother–neonate pairs.

In addition to children, the elderly population are high-risk for GAS diseases [19][43][20][62]. A study of the review of outbreaks of GAS diseases in Europe conducted by Cummins et al. [42] established that 20 out of 31 outbreaks that occurred between 1992 and 2008 were related to residential care homes. Chalker et al.’s [38] study also showed that many cases of GAS infections were common in the elderly population, especially those over 70 years. Mearkle et al. [65] demonstrated an increased risk of GAS transmission within a household when one family member is positive. This risk was greatest in couples aged 75 years and older, and in mother–neonate pairs.

People with underlying medical conditions are also more vulnerable to GAS infections, as seen in the reviewed articles [10,17,27,59,60,61,62]. This review also showed that previous skin conditions and recent wounds were also some of the medical conditions that favored the transmission of GAS infections [50,71]. Pre-existing medical conditions and co-infections such as influenza, malnutrition, diabetes mellitus, HIV and malaria also expose people to GAS infections, due to a reduced immunity for fighting infections [10,17,27,59,60,61,62,78], as seen in the reviewed articles. Sosa [127] argues that pre-existing medical conditions in pregnancy can cause GAS infections to progress to toxic shock syndrome or necrotizing fasciitis, severe types of GAS diseases. This review also reported changes in host immunity, especially during pregnancy, as a risk factor for GAS infections [39,41,63,64,65,66,67,68,69]. The results of a study carried out by Rottenstreich et al. [67] reported that pregnant women were 20 times more at risk of GAS infections than non-pregnant women. This has been attributed to changes in host immunity due to pregnancy or postpartum status [103,119]. Studies carried out on pregnant women also reveal that GAS infections can cause still births and neonatal deaths [65]. Additionally, caesarean sections undertaken with contaminated medical instruments expose pregnant women to GAS infections [127]. Lactation also reduces the availability of protective vaginal flora such as lactobacillus, and thus increases the chances of the growth of other microorganisms such as GAS [134]. Increased incidence has also been reported in infants mainly through exposure to asymptomatic persons in the households, or mother to neonate cross-infection [64].

People with underlying medical conditions are also more vulnerable to GAS infections, as seen in the reviewed articles [19][66][16][67][68][69][54]. This review also showed that previous skin conditions and recent wounds were also some of the medical conditions that favored the transmission of GAS infections [50][70]. Pre-existing medical conditions and co-infections such as influenza, malnutrition, diabetes mellitus, HIV and malaria also expose people to GAS infections, due to a reduced immunity for fighting infections [19][66][16][67][68][69][54][71], as seen in the reviewed articles. Sosa [24] argues that pre-existing medical conditions in pregnancy can cause GAS infections to progress to toxic shock syndrome or necrotizing fasciitis, severe types of GAS diseases. This review also reported changes in host immunity, especially during pregnancy, as a risk factor for GAS infections [39][41][72][65][51][73][74][75][76]. The results of a study carried out by Rottenstreich et al. [74] reported that pregnant women were 20 times more at risk of GAS infections than non-pregnant women. This has been attributed to changes in host immunity due to pregnancy or postpartum status [77][78]. Studies carried out on pregnant women also reveal that GAS infections can cause still births and neonatal deaths [51]. Additionally, caesarean sections undertaken with contaminated medical instruments expose pregnant women to GAS infections [24]. Lactation also reduces the availability of protective vaginal flora such as lactobacillus, and thus increases the chances of the growth of other microorganisms such as GAS [79]. Increased incidence has also been reported in infants mainly through exposure to asymptomatic persons in the households, or mother to neonate cross-infection [65].

In terms of gender, the review showed that higher incidence rates of GAS infections are reported in men compared with women [22,23,36,52,57,70]. According to a study carried out in China, the incidence of scarlet fever cases from 2004 to 2016 was 1.54 times greater among boys compared with girls and women [52]. Lee, Cowling and Lau [36] attribute this high risk to more physical interactions and poorer personal hygiene among boys. In the United Kingdom, however, there is an even distribution of cases across all genders [43]. Very little is known about why the incidence is higher in men than in women.

In terms of gender, the review showed that higher incidence rates of GAS infections are reported in men compared with women [35][80][36][58][20][81]. According to a study carried out in China, the incidence of scarlet fever cases from 2004 to 2016 was 1.54 times greater among boys compared with girls and women [58]. Lee, Cowling and Lau [36] attribute this high risk to more physical interactions and poorer personal hygiene among boys. In the United Kingdom, however, there is an even distribution of cases across all genders [43]. Very little is known about why the incidence is higher in men than in women.

5. Risk Factors for GAS Infections

The transmission of GAS is determined by a number of factors. GAS is chiefly a disease of poverty [3]. Housing conditions characterized by overcrowding, dampness, poor ventilation and/or lack of temperature control encourage the transmission of these infections [18,20,51]. Overcrowding, especially in households, in military camps and in other institutions such as care homes, is a significant environmental factor for the spread of GAS infections [18,51,64], as seen in the reviewed articles. In overcrowded conditions, coughing or sneezing from one infected person in the household or institution can easily infect others [135]. Since these bacteria are believed to survive on dry surfaces and materials for up to 6.5 months, there is an increased likelihood of their transmission in overcrowded settings [136].

The transmission of GAS is determined by a number of factors. GAS is chiefly a disease of poverty [82]. Housing conditions characterized by overcrowding, dampness, poor ventilation and/or lack of temperature control encourage the transmission of these infections [6][10][15]. Overcrowding, especially in households, in military camps and in other institutions such as care homes, is a significant environmental factor for the spread of GAS infections [6][15][65], as seen in the reviewed articles. In overcrowded conditions, coughing or sneezing from one infected person in the household or institution can easily infect others [83]. Since these bacteria are believed to survive on dry surfaces and materials for up to 6.5 months, there is an increased likelihood of their transmission in overcrowded settings [84].

Contamination in hospitals and nursing facilities is also a risk factor that the review highlighted, and this needs to be addressed if infections are to be prevented or controlled. This contamination includes shared hospital equipment, surroundings such as curtains, furniture, walls and floors and devices, or implants [33,74,75]. Contamination from healthcare workers due to poor infection control practices can also occur [38,39,44,45].

Contamination in hospitals and nursing facilities is also a risk factor that the review highlighted, and this needs to be addressed if infections are to be prevented or controlled. This contamination includes shared hospital equipment, surroundings such as curtains, furniture, walls and floors and devices, or implants [28][52][53]. Contamination from healthcare workers due to poor infection control practices can also occur [38][39][44][45].

Substandard infection control practices, including errors in equipment sterilization, lack of cleaning and disinfection of shared hospital equipment, lack of proper use of personal protective equipment, poor waste management and disposal and poor wound care practices, are also major contributors to the transmission of GAS infections [32,48,74,88]. For example, in a study performed by Mahida et al. [33] in an ear, nose and throat ward in a hospital in the United Kingdom, ward curtains sampled and tested for GAS during an outbreak in a hospital showed that 10 out of 34 curtains tested positive for GAS.

Substandard infection control practices, including errors in equipment sterilization, lack of cleaning and disinfection of shared hospital equipment, lack of proper use of personal protective equipment, poor waste management and disposal and poor wound care practices, are also major contributors to the transmission of GAS infections [27][48][52][85]. For example, in a study performed by Mahida et al. [28] in an ear, nose and throat ward in a hospital in the United Kingdom, ward curtains sampled and tested for GAS during an outbreak in a hospital showed that 10 out of 34 curtains tested positive for GAS.

Cross-infection by health workers colonized with GAS to patients was reported to occur in hospitals [77]. Exposure to asymptomatic persons or cases of GAS infections can also occur at the household level. Such exposure is high in overcrowded households, as discussed earlier. In addition, limited household resources, such as those for washing and laundry, contribute to an increase in bacterial load on the skin of household members, or objects in the house, resulting in increased transmission. Moreover, sharing bedding and personal items like towels is also a predisposing factor for the transmission of GAS infections [121]. High numbers of social contacts, a key environmental factor, which is common in schools, hospitals and other enclosed social places, increase the chances of the transmission of GAS infections [49,137]

Cross-infection by health workers colonized with GAS to patients was reported to occur in hospitals [86]. Exposure to asymptomatic persons or cases of GAS infections can also occur at the household level. Such exposure is high in overcrowded households, as discussed earlier. In addition, limited household resources, such as those for washing and laundry, contribute to an increase in bacterial load on the skin of household members, or objects in the house, resulting in increased transmission. Moreover, sharing bedding and personal items like towels is also a predisposing factor for the transmission of GAS infections [63]. High numbers of social contacts, a key environmental factor, which is common in schools, hospitals and other enclosed social places, increase the chances of the transmission of GAS infections [49][87]

Personal hygiene and hand hygiene are key to the control and prevention of communicable diseases like common cold, diphtheria, rubella and GAS infections [33,48]. Poor personal and hand hygiene have been proven to be risk factors for GAS infections in all age groups [15,42]. However, school-going children, especially boys, have been reported to be highly susceptible. This has been attributed to lower hygiene standards among the boys [36]. Poor hygiene practices like infrequent tooth brushing among people living in homeless shelters also contributes to an increased risk of GAS spread among these population groups [71]. Broken skin was also identified as a risk factor for GAS transmission. Healthy skin provides a barrier of protection against infections, and when broken, it provides a good growth environment for GAS, hence the high chances of infection [23,117]. GAS biofilms can also form on human tissues, especially in necrotizing soft tissue infections [138].

Personal hygiene and hand hygiene are key to the control and prevention of communicable diseases like common cold, diphtheria, rubella and GAS infections [28][48]. Poor personal and hand hygiene have been proven to be risk factors for GAS infections in all age groups [9][42]. However, school-going children, especially boys, have been reported to be highly susceptible. This has been attributed to lower hygiene standards among the boys [36]. Poor hygiene practices like infrequent tooth brushing among people living in homeless shelters also contributes to an increased risk of GAS spread among these population groups [70]. Broken skin was also identified as a risk factor for GAS transmission. Healthy skin provides a barrier of protection against infections, and when broken, it provides a good growth environment for GAS, hence the high chances of infection [80][88]. GAS biofilms can also form on human tissues, especially in necrotizing soft tissue infections [89].

Exposures to tobacco smoke and other air pollutants are risk factors for GAS infections [53,111] that compromise the immune system, thus increasing the risk of infection.

Exposures to tobacco smoke and other air pollutants are risk factors for GAS infections [59][90] that compromise the immune system, thus increasing the risk of infection.

Knowledge gaps on the proper diagnosis and management of GAS infections among health workers still exist. For example, a study carried out in Italy in 2017–2018 on pediatricians’ knowledge of the diagnosis and management of GAS infections showed that only 8% of 154 pediatricians correctly answered all of the questions on GAS diagnosis and management. Understanding diagnosis and management is particularly important in reducing the incidence of GAS sequelae [101].

Knowledge gaps on the proper diagnosis and management of GAS infections among health workers still exist. For example, a study carried out in Italy in 2017–2018 on pediatricians’ knowledge of the diagnosis and management of GAS infections showed that only 8% of 154 pediatricians correctly answered all of the questions on GAS diagnosis and management. Understanding diagnosis and management is particularly important in reducing the incidence of GAS sequelae [91].

Seasonal variation was also reported as a factor that influenced the transmission of GAS infections. Higher case numbers have been reported during winter and the early spring months [8,53,57].

Seasonal variation was also reported as a factor that influenced the transmission of GAS infections. Higher case numbers have been reported during winter and the early spring months [34][59][20].

Alcohol abuse and intravenous drug use are also risk factors for GAS infections [62,72,73]. However, not all GAS disease cases found in populations that inject drugs or abuse alcohol are directly linked to these factors. An outbreak investigation carried out in England among cases of GAS infection who were injecting-drug users showed that the transmission of these infections was not associated with the alcohol or drug use [73]; however, very few studies have explored this factor, and this therefore presents an area for future research.

Alcohol abuse and intravenous drug use are also risk factors for GAS infections [54][92][93]. However, not all GAS disease cases found in populations that inject drugs or abuse alcohol are directly linked to these factors. An outbreak investigation carried out in England among cases of GAS infection who were injecting-drug users showed that the transmission of these infections was not associated with the alcohol or drug use [93]; however, very few studies have explored this factor, and this therefore presents an area for future research.

6. Prevention and Control Measures/Strategies

Strategies aiming to prevent or treat GAS infections should be feasible, accessible and affordable, especially in low-resource settings [3]. The prevention and control of GAS infections has been approached from the public and environmental health and clinical perspectives; however, most of the intervention programs available focus more on clinical intervention, and there are limited data on possible infection prevention strategies in the community [114]. The available public health strategies focus on minimizing transmission and the protection of the people most vulnerable to GAS infections in all areas with increased potential for infection. Primary preventive strategies are also necessary, since they prevent irreversible health conditions that may arise from complications due to GAS infections [118]. These strategies include epidemiological investigations and improved surveillance systems [94,95,96,97,98,99,111,112,113,114,115,116], improved quality of housing [18,20], good hand hygiene, which includes regular proper hand washing with soap and water, or use of alcohol hand rub [15,42], and avoiding overcrowding [15]. Improved personal hygiene is also key in controlling transmission, especially in boys, who tend to be more at-risk than girls [36]. Limited or no sharing of personal items like towels and even beddings should be encouraged to reduce the spread of GAS infections [15]. The sharing of items that could be contaminated with saliva, such as water bottles, drinking glasses, utensils, etc., should also be avoided [71].

Strategies aiming to prevent or treat GAS infections should be feasible, accessible and affordable, especially in low-resource settings [82]. The prevention and control of GAS infections has been approached from the public and environmental health and clinical perspectives; however, most of the intervention programs available focus more on clinical intervention, and there are limited data on possible infection prevention strategies in the community [94]. The available public health strategies focus on minimizing transmission and the protection of the people most vulnerable to GAS infections in all areas with increased potential for infection. Primary preventive strategies are also necessary, since they prevent irreversible health conditions that may arise from complications due to GAS infections [13]. These strategies include epidemiological investigations and improved surveillance systems [95][96][21][97][98][99][90][100][101][94][102][103], improved quality of housing [6][10], good hand hygiene, which includes regular proper hand washing with soap and water, or use of alcohol hand rub [9][42], and avoiding overcrowding [9]. Improved personal hygiene is also key in controlling transmission, especially in boys, who tend to be more at-risk than girls [36]. Limited or no sharing of personal items like towels and even beddings should be encouraged to reduce the spread of GAS infections [9]. The sharing of items that could be contaminated with saliva, such as water bottles, drinking glasses, utensils, etc., should also be avoided [70].

Environmental sanitation, including the cleaning and sanitation of surfaces and common touch areas, should be maintained in all areas considered risky transmission zones [34,139]. GAS diseases have been reported to be susceptible to moist heat of 121 °C for at least 15 min, and dry heat of 170 °C for at least 1 h. In addition, the bacteria are also susceptible to 1% sodium hypochlorite, 4% formaldehyde, 2% glutaraldehyde, 70% ethanol, 70% propanol, 2% peracetic acid, 3–6% hydrogen peroxide and 16% iodine [140]. The constant disinfection and cleaning of shared equipment, especially in hospitals, should be encouraged [47,74]. This review also highlights decontamination and the thorough cleaning of curtains and communal facilities, such as bathrooms and toilets, as key measures in the prevention of infections such as GAS infections [39,141]. Curtains in high-risk areas such as hospital settings should also be changed frequently. This should be done once a month in high-risk areas and in low-risk areas twice a year. Hospitals should also consider using disposable curtains or plastic screens instead of washable curtains [33].

Environmental sanitation, including the cleaning and sanitation of surfaces and common touch areas, should be maintained in all areas considered risky transmission zones [29][104]. GAS diseases have been reported to be susceptible to moist heat of 121 °C for at least 15 min, and dry heat of 170 °C for at least 1 h. In addition, the bacteria are also susceptible to 1% sodium hypochlorite, 4% formaldehyde, 2% glutaraldehyde, 70% ethanol, 70% propanol, 2% peracetic acid, 3–6% hydrogen peroxide and 16% iodine [105]. The constant disinfection and cleaning of shared equipment, especially in hospitals, should be encouraged [47][52]. This review also highlights decontamination and the thorough cleaning of curtains and communal facilities, such as bathrooms and toilets, as key measures in the prevention of infections such as GAS infections [39][106]. Curtains in high-risk areas such as hospital settings should also be changed frequently. This should be done once a month in high-risk areas and in low-risk areas twice a year. Hospitals should also consider using disposable curtains or plastic screens instead of washable curtains [28].

Appropriate infection control practice was also identified as critical to preventing GAS infections in hospital and healthcare settings. This includes the proper use of personal protective equipment, aseptic management of wounds and proper disposal of medical waste [31,32,39,88,89,90,91,92,93]. Patients or residents infected with GAS in hospitals or care homes should also be isolated as a prevention measure to stop further GAS transmission [93,104]. The support of antisepsis measures during delivery and neonatal cord care was also identified as important to the prevention strategy to reduce GAS transmission among birthing women and neonates [17]. Medical practitioners are also required to adhere to the diagnosis and treatment guidelines to effectively control GAS infections [35,101,124]. This review also advocates for the proper management of co-infections, such as influenza [78], and patients who have undergone surgical interventions, such as tonsillectomy and other similar operations [40,142], so as to reduce the risk of the development of GAS infections.

Appropriate infection control practice was also identified as critical to preventing GAS infections in hospital and healthcare settings. This includes the proper use of personal protective equipment, aseptic management of wounds and proper disposal of medical waste [23][27][39][85][107][108][109][110][111]. Patients or residents infected with GAS in hospitals or care homes should also be isolated as a prevention measure to stop further GAS transmission [111][112]. The support of antisepsis measures during delivery and neonatal cord care was also identified as important to the prevention strategy to reduce GAS transmission among birthing women and neonates [66]. Medical practitioners are also required to adhere to the diagnosis and treatment guidelines to effectively control GAS infections [30][91][14]. This review also advocates for the proper management of co-infections, such as influenza [71], and patients who have undergone surgical interventions, such as tonsillectomy and other similar operations [40][113], so as to reduce the risk of the development of GAS infections.

The screening of health workers, asymptomatic cases including social contacts and family members of infected persons, and post-exposure prophylaxis for vulnerable groups is encouraged [11,32,37,64,77]. Successful screening should include both the throat and perianal sites [75]. However, the lack of official guidelines concerning the prevention of secondary disease using contact prophylaxis remains a challenge in many countries [111]. In addition, chemoprophylaxis can sometimes be ineffective, especially in controlling outbreaks due to the introduction of new strains as a result of the mutating nature of GAS [48].

The screening of health workers, asymptomatic cases including social contacts and family members of infected persons, and post-exposure prophylaxis for vulnerable groups is encouraged [57][27][37][65][86]. Successful screening should include both the throat and perianal sites [53]. However, the lack of official guidelines concerning the prevention of secondary disease using contact prophylaxis remains a challenge in many countries [90]. In addition, chemoprophylaxis can sometimes be ineffective, especially in controlling outbreaks due to the introduction of new strains as a result of the mutating nature of GAS [48].

Health education for healthcare providers, patients and communities is key for the prevention of GAS infections [15,45,85,100,101,102,103,104]. This should include messages that encourage people to cover coughs or sneezes with a tissue or a forearm, which is effective in the prevention of most infections transmitted through respiratory droplets [49,143]. Messages on proper health-seeking behavior should also be emphasized, since this also helps to reduce disease spread through treatment success [19,49,100]. The capacity building of health workers as regards GAS infections and their control will also help to provide targeted advice to clients, and thus break the transmission chain [3,14,26,85]. This will reduce existing knowledge gaps in GAS infections prevention and management. After training is completed, facilities should try to avoid high staff turnover, which is likely to contribute to knowledge gaps in the control and management of these infections [47].

Health education for healthcare providers, patients and communities is key for the prevention of GAS infections [9][45][114][115][91][116][77][112]. This should include messages that encourage people to cover coughs or sneezes with a tissue or a forearm, which is effective in the prevention of most infections transmitted through respiratory droplets [49][117]. Messages on proper health-seeking behavior should also be emphasized, since this also helps to reduce disease spread through treatment success [118][49][115]. The capacity building of health workers as regards GAS infections and their control will also help to provide targeted advice to clients, and thus break the transmission chain [82][3][12][114]. This will reduce existing knowledge gaps in GAS infections prevention and management. After training is completed, facilities should try to avoid high staff turnover, which is likely to contribute to knowledge gaps in the control and management of these infections [47].

Clinical interventions, such as early accurate diagnosis and treatment as an effective preventive measure for GAS infections, were highly advocated for [15,19,69,79,80,81,82,83,84,85,86,87]. Early treatment with antibiotics is essential for reducing the transmission window. It also prevents the development of complications, including associated sequelae. For example, with antibiotics, GAS is typically communicable for 24–48 h; however, without antibiotics, communicability can last for 10–21 days, and even longer in complicated cases [144]. This is illustrated by an outbreak of GAS pharyngitis in a Canadian military camp between December 2016 and April 2017. The outbreak investigation found that reluctance to seek medical care and low compliance with antibiotics were reported factors that hindered treatment success and led to the increased spread of the GAS disease [49]. Patients are therefore advised to adhere to the treatment advice to avoid treatment failure, and therefore reduce disease spread. In addition, the early and improved treatment of skin infections and burns has been encouraged as a prevention measure [14,28,71,145]. Safe injection practices should also be encouraged among people who inject drugs [146] to reduce GAS transmission rates in these populations.

Clinical interventions, such as early accurate diagnosis and treatment as an effective preventive measure for GAS infections, were highly advocated for [9][118][76][119][64][120][121][122][123][114][124][125]. Early treatment with antibiotics is essential for reducing the transmission window. It also prevents the development of complications, including associated sequelae. For example, with antibiotics, GAS is typically communicable for 24–48 h; however, without antibiotics, communicability can last for 10–21 days, and even longer in complicated cases [126]. This is illustrated by an outbreak of GAS pharyngitis in a Canadian military camp between December 2016 and April 2017. The outbreak investigation found that reluctance to seek medical care and low compliance with antibiotics were reported factors that hindered treatment success and led to the increased spread of the GAS disease [49]. Patients are therefore advised to adhere to the treatment advice to avoid treatment failure, and therefore reduce disease spread. In addition, the early and improved treatment of skin infections and burns has been encouraged as a prevention measure [3][127][70][128]. Safe injection practices should also be encouraged among people who inject drugs [129] to reduce GAS transmission rates in these populations.

Improved detection methods and outbreak investigation tools, such as whole genome sequencing, can enable the early detection of GAS infections and the identification of outbreaks. This can facilitate the rapid administration of treatment, and reduce the transmission rate [105,106]. Governments should also ensure the availability of affordable and accessible healthcare services to all citizens to prevent and control all infections. Equitable resource distribution is key in reducing social disadvantage, which highly influences GAS transmission [3,9,20,30].

Improved detection methods and outbreak investigation tools, such as whole genome sequencing, can enable the early detection of GAS infections and the identification of outbreaks. This can facilitate the rapid administration of treatment, and reduce the transmission rate [130][131]. Governments should also ensure the availability of affordable and accessible healthcare services to all citizens to prevent and control all infections. Equitable resource distribution is key in reducing social disadvantage, which highly influences GAS transmission [82][2][10][132].

Currently, there is no licensed vaccine for the control of GAS infections; however, the development of a vaccine is underway [2]. This process has been hindered by factors like the availability of various unique GAS serotypes, antigenic variations within the same serotype, safety concerns, and a lack of consensus on clinical endpoints for the establishment of proof of concept [108,110,147,148]. Studies in this review, however, indicate that vaccination could help reduce these diseases, and therefore highly recommend its development and use [89,102,107,108,109,110]. Rivera-Hernandez et al. [109] suggest that vaccination can reduce antibiotic use and therefore reduce antibiotic resistance. Reducing antibiotic resistance will further reduce the transmission of GAS infections through increased treatment success, as discussed earlier. Studies have also proposed screening for invasive GAS during pregnancy so as to prevent transmission to pregnant women who are a high-risk group for GAS infections [41,63,67,97,119].

Currently, there is no licensed vaccine for the control of GAS infections; however, the development of a vaccine is underway [133]. This process has been hindered by factors like the availability of various unique GAS serotypes, antigenic variations within the same serotype, safety concerns, and a lack of consensus on clinical endpoints for the establishment of proof of concept [134][135][136][137]. Studies in this review, however, indicate that vaccination could help reduce these diseases, and therefore highly recommend its development and use [107][116][7][134][138][135]. Rivera-Hernandez et al. [138] suggest that vaccination can reduce antibiotic use and therefore reduce antibiotic resistance. Reducing antibiotic resistance will further reduce the transmission of GAS infections through increased treatment success, as discussed earlier. Studies have also proposed screening for invasive GAS during pregnancy so as to prevent transmission to pregnant women who are a high-risk group for GAS infections [41][72][74][97][78].

GAS is an important global pathogen with diverse clinical manifestations and limited epidemiological data [3,122]. Currently, a lack of mandatory patient notification in most countries limits the ability of public health programs to effectively target, prevent and control GAS diseases [111,112,113,114,115,116]. Most studies and countries focus more on the clinical management of the diseases than on prevention at the community level. Since GAS diseases are not notifiable worldwide, conducting informed public health and research initiatives aimed at reducing the impact of GAS diseases remains a challenge. Efforts to improve reporting systems, and scaling up public and environmental health interventions at the community level coupled with the effective treatment of cases, will help reduce the transmission rate [46,94,111,113,122]. Future strategies must use a multi-disciplinary approach to the prevention and control of GAS diseases in both the community and clinical settings.

GAS is an important global pathogen with diverse clinical manifestations and limited epidemiological data [82][1]. Currently, a lack of mandatory patient notification in most countries limits the ability of public health programs to effectively target, prevent and control GAS diseases [90][100][101][94][102][103]. Most studies and countries focus more on the clinical management of the diseases than on prevention at the community level. Since GAS diseases are not notifiable worldwide, conducting informed public health and research initiatives aimed at reducing the impact of GAS diseases remains a challenge. Efforts to improve reporting systems, and scaling up public and environmental health interventions at the community level coupled with the effective treatment of cases, will help reduce the transmission rate [46][95][90][101][1]. Future strategies must use a multi-disciplinary approach to the prevention and control of GAS diseases in both the community and clinical settings.

References

  1. Sanyahumbi, A.S.; Colquhoun, S.; Wyber, R.; Carapetis, J.R. Global disease burden of group A Streptococcus. In Streptococcus pyogenes: Basic Biology to Clinical Manifestations [Internet]; University of Oklahoma Health Sciences Center: Oklahoma City, OK, USA, 2016.
  2. Mosites, E.; Frick, A.; Gounder, P.; Castrodale, L.; Li, Y.; Rudolph, K.; Hurlburt, D.; Lecy, K.D.; Zulz, T.; Adebanjo, T. Outbreak of invasive infections from subtype emm26. 3 group A streptococcus among homeless adults—Anchorage, Alaska, 2016–2017. Clin. Infect. Dis. 2018, 66, 1068–1074.
  3. May, P.J.; Bowen, A.C.; Carapetis, J.R. The inequitable burden of group A streptococcal diseases in Indigenous Australians. Med. J. Aust. 2016, 205, 201–203.
  4. Barnett, T.; Bowen, A.; Carapetis, J.R. The fall and rise of group A streptococcus diseases. Epidemiol. Infect. 2019, 147, e4.
  5. Steer, A.C.; Law, I.; Matatolu, L.; Beall, B.W.; Carapetis, J.R. Global emm type distribution of group A streptococci: Systematic review and implications for vaccine development. Lancet Infect. Dis. 2009, 9, 611–616.
  6. Tartof, S.Y.; Reis, J.N.; Andrade, A.N.; Ramos, R.T.; Reis, M.G.; Riley, L.W. Factors associated with Group A streptococcus emm type diversification in a large urban setting in Brazil: A cross-sectional study. BMC Infect. Dis. 2010, 10, 327. Available online: (accessed on 20 July 2020).
  7. Barth, D.; Naicker, P.; Engel, K.; Muhamed, B.; Basera, W.; Mayosi, B.; Dale, J.; Engel, M. Molecular epidemiology of noninvasive and invasive group A streptococcal infections in Cape Town. mSphere 2019, 4.
  8. De Almeida Torres, R.S.L.; Fedalto, L.E.; de Almeida Torres, R.F.; Steer, A.C.; Smeesters, P.R. Group A streptococcus meningitis in children. Pediatric Infect. Dis. J. 2013, 32, 110–114.
  9. Francis, J.R.; Gargan, C.; Remenyi, B.; Ralph, A.P.; Draper, A.; Holt, D.; Krause, V.; Hardie, K. A cluster of acute rheumatic fever cases among Aboriginal Australians in a remote community with high baseline incidence. Aust. N. Z. J. Public Health 2019, 43, 288–293.
  10. Oliver, J.R.; Pierse, N.; Stefanogiannis, N.; Jackson, C.; Baker, M.G. Acute rheumatic fever and exposure to poor housing conditions in New Zealand: A descriptive study. Paediatr. Child Health 2017, 53, 358–364.
  11. Shetty, A.; Mills, C.; Eggleton, K. Primary care management of group A streptococcal pharyngitis in Northland. J. Prim. Health Care 2014, 6, 189–194.
  12. Gray, L.-A.; D’Antoine, H.A.; Tong, S.Y.; McKinnon, M.; Bessarab, D.; Brown, N.; Reményi, B.; Steer, A.; Syn, G.; Blackwell, J.M. Genome-wide analysis of genetic risk factors for rheumatic heart disease in aboriginal Australians provides support for pathogenic molecular mimicry. J. Infect. Dis. 2017, 216, 1460–1470.
  13. Kumar, R.; Sharma, Y.P.; Thakur, J.S.; Patro, B.K.; Bhatia, A.; Singh, I.P.; Rana, S.K.; Chakraborti, A.; Dhanda, V.; Sapru, S. Streptococcal pharyngitis, rheumatic fever and rheumatic heart disease: Eight-year prospective surveillance in Rupnagar district of Punjab, India. Natl. Med. J. India 2014, 27, 2.
  14. Mathan, J.J.; Erkart, J.; Houlding, A. Clinical management and patient persistence with antibiotic course in suspected group A streptococcal pharyngitis for primary prevention of rheumatic fever: The perspective from a New Zealand emergency department. N. Z. Med. J. 2017, 130, 58–68.
  15. Cannon, J.; Abouzeid, M.; de Klerk, N.; Dibben, C.; Carapetis, J.; Katzenellenbogen, J. Environmental and social determinants of acute rheumatic fever: A longitudinal cohort study. Epidemiol. Infect. 2019, 147.
  16. Boyd, R.; Patel, M.; Currie, B.; Holt, D.; Harris, T.; Krause, V. High burden of invasive group A streptococcal disease in the Northern Territory of Australia. Epidemiol. Infect. 2016, 144, 1018–1027.
  17. Ikebe, T.; Tominaga, K.; Shima, T.; Okuno, R.; Kubota, H.; Ogata, K.; Chiba, K.; Katsukawa, C.; Ohya, H.; Tada, Y. Increased prevalence of group A streptococcus isolates in streptococcal toxic shock syndrome cases in Japan from 2010 to 2012. Epidemiol. Infect. 2015, 143, 864–872.
  18. Centers for Disease Control and Prevention. Group A Streptococcal (GAS) Disease; U.S. Department of Health and Human Services: Atlanta, GE, USA, 2020.
  19. Tyrrell, G.J.; Fathima, S.; Kakulphimp, J.; Bell, C. Increasing rates of invasive group A streptococcal disease in Alberta, Canada; 2003–2017. In Open Forum Infectious Diseases; Oxford University Press: New York, NY, USA, 2018; p. ofy177.
  20. Oppegaard, O.; Mylvaganam, H.; Kittang, B. Beta-haemolytic group A, C and G streptococcal infections in Western Norway: A 15-year retrospective survey. Clin. Microbiol. Infect. 2015, 21, 171–178.
  21. Yang, P.; Peng, X.; Zhang, D.; Wu, S.; Liu, Y.; Cui, S.; Lu, G.; Duan, W.; Shi, W.; Liu, S. Characteristics of group A Streptococcus strains circulating during scarlet fever epidemic, Beijing, China, 2011. Emerg. Infect. Dis. 2013, 19, 909.
  22. DeMuri, G.P.; Wald, E.R. The Group A Streptococcal Carrier State Reviewed: Still an Enigma. J. Pediatric Infect. Dis. Soc. 2014, 3, 336–342.
  23. Al-ajmi, J.A.; Hill, P.; O’Boyle, C.; Garcia, M.L.B.; Malkawi, M.; George, A.; Saleh, F.; Lukose, B.; Al Ali, B.; Elsheikh, M. Group A streptococcus toxic shock syndrome: An outbreak report and review of the literature. J. Infect. Public Health 2012, 5, 388–393.
  24. Sosa, M.E.B. Group A streptococcal infection in pregnancy and the puerperium. J. Perinat. Neonatal Nurs. 2016, 30, 124–130.
  25. Walker, M.J.; Barnett, T.C.; McArthur, J.D.; Cole, J.N.; Gillen, C.M.; Henningham, A.; Sriprakash, K.; Sanderson-Smith, M.L.; Nizet, V. Disease manifestations and pathogenic mechanisms of group A Streptococcus. Clin. Microbiol. Rev. 2014, 27, 264–301.
  26. Chen, M.; Wang, W.; Tu, L.; Zheng, Y.; Pan, H.; Wang, G.; Chen, Y.; Zhang, X.; Zhu, L.; Chen, J. An emm5 group A streptococcal outbreak among workers in a factory manufacturing telephone accessories. Front. Microbiol. 2017, 8, 1156.
  27. Sharma, H.; Ong, M.; Ready, D.; Coelho, J.; Groves, N.; Chalker, V.; Warren, S. Real-time whole genome sequencing to control a Streptococcus pyogenes outbreak at a national orthopaedic hospital. J. Hosp. Infect. 2019, 103, 21–26.
  28. Mahida, N.; Beal, A.; Trigg, D.; Vaughan, N.; Boswell, T. Outbreak of invasive group A streptococcus infection: Contaminated patient curtains and cross-infection on an ear, nose and throat ward. J. Hosp. Infect. 2014, 87, 141–144.
  29. Winter, G. Curtains hide risks to health and hygiene. Nurs. Stand. 2014, 28, 27.
  30. Kemble, S.K.; Westbrook, A.; Lynfield, R.; Bogard, A.; Koktavy, N.; Gall, K.; Lappi, V.; DeVries, A.S.; Kaplan, E.; Smith, K.E. Foodborne outbreak of group A streptococcus pharyngitis associated with a high school dance team banquet—Minnesota, 2012. Clin. Infect. Dis. 2013, 57, 648–654.
  31. International Commission on Microbiological Specifications for Foods. Microorganisms in Foods 5: Characteristics of Microbial Pathogens; Springer Science & Business Media: Berlin/Heidelberg, Germany, 1996; Volume 5.
  32. Katzenell, U.; Shemer, J.; Bar-Dayan, Y. Streptococcal contamination of food: An unusual cause of epidemic pharyngitis. Epidemiol. Infect. 2001, 127, 179–184.
  33. Liu, Y.-M.; Zhao, J.-Z.; Li, B.-B.; Yang, J.-Y.; Dong, X.-G.; Zhang, J.-J.; Cao, B. A report on the first outbreak of a single clone group A Streptococcus (emm-type 89) tonsillopharyngitis in China. J. Microbiol. Immunol. Infect. 2014, 47, 542–545.
  34. Zhang, Q.; Liu, W.; Ma, W.; Shi, Y.; Wu, Y.; Li, Y.; Liang, S.; Zhu, Y.; Zhou, M. Spatiotemporal epidemiology of scarlet fever in Jiangsu Province, China, 2005–2015. BMC Infect. Dis. 2017, 17, 596.
  35. Engelthaler, D.M.; Valentine, M.; Bowers, J.; Pistole, J.; Driebe, E.M.; Terriquez, J.; Nienstadt, L.; Carroll, M.; Schumacher, M.; Ormsby, M.E. Hypervirulent emm59 clone in invasive group A streptococcus outbreak, southwestern United States. Emerg. Infect. Dis. 2016, 22, 734.
  36. Lee, C.F.; Cowling, B.J.; Lau, E.H. Epidemiology of reemerging scarlet fever, Hong Kong, 2005–2015. Emerg. Infect. Dis. 2017, 23, 1707.
  37. Lamden, K. An outbreak of scarlet fever in a primary school. Arch. Dis. Child. 2011, 96, 394–397.
  38. Chalker, V.J.; Smith, A.; Al-Shahib, A.; Botchway, S.; Macdonald, E.; Daniel, R.; Phillips, S.; Platt, S.; Doumith, M.; Tewolde, R. Integration of genomic and other epidemiologic data to investigate and control a cross-institutional outbreak of Streptococcus pyogenes. Emerg. Infect. Dis. 2016, 22, 973.
  39. Dickinson, H.; Reacher, M.; Nazareth, B.; Eagle, H.; Fowler, D.; Underwood, A.; Chand, M.; Chalker, V.; Coelho, J.; Daniel, R. Whole-genome sequencing in the investigation of recurrent invasive group A streptococcus outbreaks in a maternity unit. J. Hosp. Infect. 2019, 101, 320–326.
  40. Hupp, J.A.; Kallstrom, G.; Myers, J.P. Streptococcus pyogenes bacteremia in adults in the 21st century: Review of 68 episodes over 10-year period in a large community teaching hospital. Infect. Dis. Clin. 2018, 26, 31–34.
  41. Shinar, S.; Fouks, Y.; Amit, S.; Pauzner, D.; Tarabeia, J.; Schechner, V.; Many, A. Clinical characteristics of and preventative strategies for peripartum group A streptococcal infections. Obstet. Gynecol. 2016, 127, 227–232.
  42. Cummins, A.; Millership, S.; Lamagni, T.; Foster, K. Control measures for invasive group A streptococci (iGAS) outbreaks in care homes. J. Infect. 2012, 64, 156–161.
  43. Saavedra-Campos, M.; Simone, B.; Balasegaram, S.; Wright, A.; Usdin, M.; Lamagni, T. Estimating the risk of invasive group A streptococcus infection in care home residents in England, 2009–2010. Epidemiol. Infect. 2017, 145, 2759–2765.
  44. Palladino, K.J.; Morrison, T.; Chochua, S.; Bowers, L.; MacFarquhar, J.K. Group A streptococcus outbreak among residents and employees of two skilled nursing facilities: North Carolina, 2017. Am. J. Infect. Control 2019, 47, 846–849.
  45. Kobayashi, M.; Lyman, M.M.; Francois Watkins, L.K.; Toews, K.A.; Bullard, L.; Radcliffe, R.A.; Beall, B.; Langley, G.; Beneden, C.V.; Stone, N.D. A cluster of group A streptococcal infections in a skilled nursing facility—the potential role of healthcare worker presenteeism. J. Am. Geriatr. Soc. 2016, 64, e279–e284.
  46. Worthing, K.A.; Werno, A.; Pink, R.; McIntyre, L.; Carter, G.P.; Williamson, D.A.; Davies, M.R. Biphasic outbreak of invasive group A Streptococcus disease in eldercare facility, New Zealand. Emerg. Infect. Dis. 2020, 26, 841.
  47. Dooling, K.L.; Crist, M.B.; Nguyen, D.B.; Bass, J.; Lorentzson, L.; Toews, K.-A.; Pondo, T.; Stone, N.D.; Beall, B.; Van Beneden, C. Investigation of a prolonged group A streptococcal outbreak among residents of a skilled nursing facility, Georgia, 2009–2012. J. Clin. Infect. Dis. 2013, 57, 1562–1567.
  48. Nanduri, S.; Metcalf, B.; Arwady, M.; Edens, C.; Lavin, M.; Morgan, J.; Clegg, W.; Beron, A.; Albertson, J.; Link-Gelles, R. Prolonged and large outbreak of invasive group A Streptococcus disease within a nursing home: Repeated intrafacility transmission of a single strain. Clin. Microbiol. Infect. 2019, 25, 248.e1–248.e7.
  49. Hammond-Collins, K.; Strauss, B.; Barnes, K.; Demczuk, W.; Domingo, M.-C.; Lamontagne, M.-C.; Lu, D.; Martin, I.; Tepper, M. Group A streptococcus outbreak in a canadian armed forces training facility. Mil. Med. 2019, 184, e197–e204.
  50. Dohoo, C.; Stuart, R.; Finkelstein, M.; Bradley, K.; Gournis, E. Risk factors associated with group A streptococcus acquisition in a large, urban homeless shelter outbreak. Can. J. Public Health 2020, 111, 117–124.
  51. Deutscher, M.; Lewis, M.; Zell, E.R.; Taylor Jr, T.H.; Van Beneden, C.; Schrag, S. Incidence and severity of invasive streptococcus pneumoniae, Group A streptococcus, and Group B streptococcus infections among pregnant and postpartum women. Clin. Infect. Dis. 2011, 53, 114–123.
  52. Ahmed, S.S.; Diebold, K.E.; Brandvold, J.M.; Ewaidah, S.S.; Black, S.; Ogundimu, A.; Li, Z.; Stone, N.D.; Van Beneden, C.A. The role of wound care in 2 group A streptococcal outbreaks in a Chicago skilled nursing facility, 2015‒2016. Open Forum Infect. Dis. 2018, 5, ofy145.
  53. Mahida, N.; Prescott, K.; Yates, C.; Spencer, F.; Weston, V.; Boswell, T. Outbreak of invasive group A streptococcus: Investigations using agar settle plates detect perineal shedding from a healthcare worker. J. Hosp. Infect. 2018, 100, e209–e215.
  54. Athey, T.B.; Teatero, S.; Sieswerda, L.E.; Gubbay, J.B.; Marchand-Austin, A.; Li, A.; Wasserscheid, J.; Dewar, K.; McGeer, A.; Williams, D. High incidence of invasive group A Streptococcus disease caused by strains of uncommon emm types in Thunder Bay, Ontario, Canada. J. Clin. Microbiol. 2016, 54, 83–92.
  55. Okuzono, S.; Ishimura, M.; Kanno, S.; Sonoda, M.; Kaku, N.; Motomura, Y.; Nishio, H.; Oba, U.; Hanada, M.; Fukushi, J.-i. Streptococcus pyogenes-Purpura fulminans as an invasive form of group A streptococcal infection. Ann. Clin. Microbiol. Antimicrob. 2018, 17, 31.
  56. Lanitis, S.; Khan, M.; Sgourakis, G.; Kontovounisios, C.; Papaconstandinou, T.; Karaliotas, C. Severe monobacterial necrotizing soft tissue infection by group A streptococcus: A surgical emergency. Asian Pac. J. Trop. Biomed. 2012, 2, 250–252.
  57. Watts, V.; Balasegaram, S.; Brown, C.S.; Mathew, S.; Mearkle, R.; Ready, D.; Saliba, V.; Lamagni, T. Increased risk for invasive group A streptococcus disease for household contacts of scarlet fever cases, England, 2011–2016. Emerg. Infect. Dis. 2019, 25, 529.
  58. Liu, Y.; Chan, T.-C.; Yap, L.-W.; Luo, Y.; Xu, W.; Qin, S.; Zhao, N.; Yu, Z.; Geng, X.; Liu, S.-L. Resurgence of scarlet fever in China: A 13-year population-based surveillance study. Lancet Infect. Dis. 2018, 18, 903–912.
  59. Marshall, H.S.; Richmond, P.; Nissen, M.; Lambert, S.; Booy, R.; Reynolds, G.; Sebastian, S.; Pride, M.; Jansen, K.U.; Anderson, A.S. Group A streptococcal carriage and seroepidemiology in children up to 10 years of age in Australia. Pediatric Infect. Dis. J. 2015, 34, 831–838.
  60. Wu, S.; Peng, X.; Yang, Z.; Ma, C.; Zhang, D.; Wang, Q.; Yang, P. Estimated burden of group A streptococcal pharyngitis among children in Beijing, China. BMC Infect. Dis. 2016, 16, 1–9.
  61. Turner, C.E.; Pyzio, M.; Song, B.; Lamagni, T.; Meltzer, M.; Chow, J.Y.; Efstratiou, A.; Curtis, S.; Sriskandan, S. Scarlet fever upsurge in England and molecular-genetic analysis in north-west London, 2014. Emerg. Infect. Dis. 2016, 22, 1075.
  62. Lin, J.-N.; Chang, L.-L.; Lai, C.-H.; Lin, H.-H.; Chen, Y.-H. Group A streptococcal necrotizing fasciitis in the emergency department. J. Emerg. Med. 2013, 45, 781–788.
  63. Baker, M.G.; Gurney, J.; Oliver, J.; Moreland, N.J.; Williamson, D.A.; Pierse, N.; Wilson, N.; Merriman, T.R.; Percival, T.; Murray, C. Risk factors for acute rheumatic fever: Literature review and protocol for a case-control study in New Zealand. Int. J. Environ. Res. Public Health 2019, 16, 4515.
  64. Vijaya, D.; Sathish, J.; Janakiram, K. The prevalence of group A streptococci carriers among asymptomatic school children. J. Clin. Diagn. Res. 2013, 7, 446.
  65. Mearkle, R.; Saavedra-Campos, M.; Lamagni, T.; Usdin, M.; Coelho, J.; Chalker, V.; Sriskandan, S.; Cordery, R.; Rawlings, C.; Balasegaram, S. Household transmission of invasive group A streptococcus infections in England: A population-based study, 2009, 2011 to 2013. Eurosurveillance 2017, 22.
  66. Seale, A.C.; Davies, M.R.; Anampiu, K.; Morpeth, S.C.; Nyongesa, S.; Mwarumba, S.; Smeesters, P.R.; Efstratiou, A.; Karugutu, R.; Mturi, N. Invasive group A streptococcus infection among children, rural Kenya. Emerg. Infect. Dis. 2016, 22, 224.
  67. Langley, G.; Hao, Y.; Pondo, T.; Miller, L.; Petit, S.; Thomas, A.; Lindegren, M.L.; Farley, M.M.; Dumyati, G.; Como-Sabetti, K. The impact of obesity and diabetes on the risk of disease and death due to invasive group A Streptococcus infections in adults. Clin. Infect. Dis. 2016, 62, 845–852.
  68. Chadha, A.; Jamal, W.; Aziz, A.R.; Rotimi, V.O. Overwhelming Streptococcus pyogenes sepsis in an elderly patient with septic arthritis. J. Infect. Public Health 2018, 11, 434–435.
  69. Lin, J.-N.; Chang, L.-L.; Lai, C.-H.; Lin, H.-H.; Chen, Y.-H. Clinical and molecular characteristics of invasive and noninvasive skin and soft tissue infections caused by group A Streptococcus. J. Clin. Microbiol. 2011, 49, 3632–3637.
  70. Adebanjo, T.; Mosites, E.; Van Beneden, C.A.; Onukwube, J.; Blum, M.; Harper, M.; Rudolph, K.; Frick, A.; Castrodale, L.; McLaughlin, J. Risk factors for group A streptococcus colonization during an outbreak among people experiencing homelessness in Anchorage, Alaska, 2017. Clin. Infect. Dis. 2018, 67, 1784–1787.
  71. Abd El-Ghany, S.M.; Abdelmaksoud, A.A.; Saber, S.M.; Abd El Hamid, D.H. Group A beta-hemolytic streptococcal pharyngitis and carriage rate among Egyptian children: A case-control study. Ann. Saudi Med. 2015, 35, 377–382.
  72. Boie, S.; Krog, J.; Tørring, S.; Bor, I.P. Life-threatening necrotizing myometritis, due to group A streptococcus–still a life-threatening condition. Clin. Case Rep. 2015, 3, 291.
  73. Hamilton, S.M.; Stevens, D.L.; Bryant, A.E. Pregnancy-related group A streptococcal infections: Temporal relationships between bacterial acquisition, infection onset, clinical findings, and outcome. Clin. Infect. Dis. 2013, 57, 870–876.
  74. Rottenstreich, A.; Benenson, S.; Levin, G.; Kleinstern, G.; Moses, A.; Amit, S. Risk factors, clinical course and outcomes of pregnancy-related group A streptococcal infections: Retrospective 13-year cohort study. Clin. Microbiol. Infect. 2019, 25, 251.e251–251.e254.
  75. Alexander, A.J.; Myers, C.; Beres, S.B.; Olsen, R.J.; Musser, J.M.; Mangino, J.E. Postpartum group A streptococcus case series: Reach out to infection prevention! Open Forum Infect. Dis. 2018, 5, ofy159.
  76. Riad, M.; Thottacherry, E.; Crawley, C.; Phillip-Abraham, N.; Ibrahim, F. Invasive Group A streptococcal postpartum endometritis associated with multi-organ infarctions: An uncommon case presentation and literature review. Postgrad. Med. 2020, 132, 526–531.
  77. Anderson, B.L. Puerperal group A streptococcal infection: Beyond Semmelweis. Obstet. Gynecol. 2014, 123, 874–882.
  78. Olp, R.J.; Chamales, I.A.; Schmiedecke, S.S. A case study of puerperal Group A Streptococcal infection complicated by toxic shock syndrome. Am. J. Perinatol. Rep. 2020, 10, e1.
  79. Kawaguchi, K.; Mori, N.; Ejima, T.; Yamada, Y.; Takahashi, T. Streptococcal toxic shock syndrome following group A streptococcal vulvovaginitis in a breastfeeding woman. J. Infect. Chemother. 2019, 25, 1037–1039.
  80. Whitehead, B.; Smith, H.; Nourse, C. Invasive group A streptococcal disease in children in Queensland. Epidemiol. Infect. 2011, 139, 623–628.
  81. Teatero, S.; McGeer, A.; Tyrrell, G.J.; Hoang, L.; Smadi, H.; Domingo, M.-C.; Levett, P.N.; Finkelstein, M.; Dewar, K.; Plevneshi, A. Canada-wide epidemic of emm74 group A streptococcus invasive disease. In Open Forum Infectious Diseases; Oxford University Press: New York, NY, USA, 2018; p. ofy085.
  82. Ralph, A.P.; Carapetis, J.R. Group A streptococcal diseases and their global burden. In Host-Pathogen Interactions in Streptococcal Diseases; Springer: Berlin/Heidelberg, Germany, 2012; pp. 1–27.
  83. Gralton, J.; Tovey, E.; McLaws, M.-L.; Rawlinson, W.D. The role of particle size in aerosolised pathogen transmission: A review. J. Infect. 2011, 62, 1–13.
  84. Kramer, A.; Schwebke, I.; Kampf, G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect. Dis. 2006, 6, 130.
  85. Beaudoin, A.L.; Torso, L.; Richards, K.; Said, M.; Van Beneden, C.; Longenberger, A.; Ostroff, S.; Wendt, J.; Dooling, K.; Wise, M. Invasive group A streptococcus infections associated with liposuction surgery at outpatient facilities not subject to state or federal regulation. JAMA Intern. Med. 2014, 174, 1136–1142.
  86. Cohen, R.; Cohen, S.; Afraimov, M.; Finn, T.; Babushkin, F.; Geller, K.; Paikin, S.; Yoffe, I.; Valinsky, L.; Ron, M. Screening asymptomatic households for Streptococcus pyogenes pharyngeal carriage as a part of in-hospital investigation of puerperal sepsis. Am. J. Infect. Control 2019, 47, 1493–1499.
  87. Weiss, K.; Laverdiere, M.; Lovgren, M.; Delorme, J.; Poirier, L.; Beliveau, C. Group A Streptococcus carriage among close contacts of patients with invasive infections. Am. J. Epidemiol. 1999, 149, 863–868.
  88. Anderson, P.; King, J.; Moss, M.; Light, P.; McKee, T.; Farrell, E.; Stewart, J.; Lennon, D. Nurse-led school-based clinics for rheumatic fever prevention and skin infection management: Evaluation of Mana Kidz programme in Counties Manukau. N. Z. Med. J. 2016, 129, 36–45.
  89. Siemens, N.; Chakrakodi, B.; Shambat, S.M.; Morgan, M.; Bergsten, H.; Hyldegaard, O.; Skrede, S.; Arnell, P.; Madsen, M.B.; Johansson, L. Biofilm in group A streptococcal necrotizing soft tissue infections. JCI Insight 2016, 1, e87882.
  90. Oliver, J.; Thielemans, E.; McMinn, A.; Baker, C.; Britton, P.N.; Clark, J.E.; Marshall, H.S.; Blyth, C.C.; Francis, J.; Buttery, J. Invasive group A Streptococcus disease in Australian children: 2016 to 2018–a descriptive cohort study. BMC Public Health 2019, 19, 1–10.
  91. Di Muzio, I.; D’Angelo, D.M.; Di Battista, C.; Lapergola, G.; Zenobi, I.; Marzetti, V.; Breda, L.; Altobelli, E. Pediatrician’s approach to diagnosis and management of group A streptococcal pharyngitis. Eur. J. Clin. Microbiol. Infect. Dis. 2020, 39, 1103–1107.
  92. Cornick, J.E.; Kiran, A.M.; Vivancos, R.; Van Aartsen, J.; Clarke, J.; Bevan, E.; Alsahag, M.; Alaearts, M.; Moreno, L.B.; Jenkinson, H.F. Epidemiological and molecular characterization of an invasive group A streptococcus emm32. 2 outbreak. J. Clin. Microbiol. 2017, 55, 1837–1846.
  93. Bundle, N.; Bubba, L.; Coelho, J.; Kwiatkowska, R.; Cloke, R.; King, S.; Rajan-Iyer, J.; Courtney-Pillinger, M.; Beck, C.R.; Hope, V. Ongoing outbreak of invasive and non-invasive disease due to group A streptococcus (GAS) type emm66 among homeless and people who inject drugs in England and Wales, January to December 2016. Eurosurveillance 2017, 22, 30446.
  94. Turner, C.E.; Bedford, L.; Brown, N.M.; Judge, K.; Török, M.E.; Parkhill, J.; Peacock, S.J. Community outbreaks of group A streptococcus revealed by genome sequencing. Sci. Rep. 2017, 7, 1–9.
  95. Thielemans, E.; Oliver, J.; McMinn, A.; Baker, C.; Britton, P.N.; Clark, J.; Marshall, H.; Blyth, C.C.; Francis, J.; Buttery, J. Clinical description and outcomes of Australian children with invasive group A streptococcal disease. Pediatric Infect. Dis. J. 2020, 39, 379–384.
  96. Liu, M.; Lu, L.; Sun, R.; Zheng, Y.; Zhang, P. Rheumatic heart disease: Causes, symptoms, and treatments. Cell Biochem. Biophys. 2015, 72, 861–863.
  97. Lev-Sagie, A.; Hochner-Celnikier, D.; Stroumsa, D.; Khalaileh, A.; Daum, H.; Moses, A. Group A streptococcus: Is there a genital carrier state in women following infection? Eur. J. Clin. Microbiol. Infect. Dis. 2017, 36, 91–93.
  98. Smit, M.A.; Nyquist, A.-C.; Todd, J.K. Infectious shock and toxic shock syndrome diagnoses in hospitals, Colorado, USA. Emerg. Infect. Dis. 2013, 19, 1855.
  99. Fittipaldi, N.; Tyrrell, G.J.; Low, D.E.; Martin, I.; Lin, D.; Hari, K.L.; Musser, J.M. Integrated whole-genome sequencing and temporospatial analysis of a continuing group A streptococcus epidemic. Emerg. Microbes Infect. 2013, 2, 1–8.
  100. Sivagnanam, S.; Zhou, F.; Lee, A.S.; O’sullivan, M.V. Epidemiology of invasive group A Streptococcus infections in Sydney, Australia. Pathology 2015, 47, 365–371.
  101. Oliver, J.; Wilmot, M.; Strachan, J.; St George, S.; Lane, C.R.; Ballard, S.A.; Sait, M.; Gibney, K.; Howden, B.P.; Williamson, D.A. Recent trends in invasive group A Streptococcus disease in Victoria. Commun. Dis. Intell. Q. Rep. 2019, 2018, 43.
  102. Bard, J.D.; Mongkolrattanothai, K.; Kachroo, P.; Beres, S.; Olsen, R.J. Case series description and genomic characterization of invasive group A streptococcal infections in pediatric patients. Pediatric Infect. Dis. J. 2017, 36, 618–620.
  103. Demoré, B.; Tebano, G.; Gravoulet, J.; Wilcke, C.; Ruspini, E.; Birgé, J.; Boivin, J.-M.; Hénard, S.; Dieterling, A.; Munerol, L. Rapid antigen test use for the management of group A streptococcal pharyngitis in community pharmacies. Eur. J. Clin. Microbiol. Infect. Dis. 2018, 37, 1637–1645.
  104. Sarangi, J.; Rowsell, R. A nursing home outbreak of group A streptococcal infection: Case control study of environmental contamination. J. Hosp. Infect. 1995, 30, 162–164.
  105. Block, S.S. Disinfection, Sterilization, and Preservation, 5th ed.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2001; p. 1481.
  106. Gordon, G.; Dale, B.A.; Lochhead, D. An outbreak of group A haemolytic streptococcal puerperal sepsis spread by the communal use of bidets. Br. J. Obstet. Gynaecol. 1994, 101, 447–448.
  107. Waddington, C.S.; Snelling, T.L.; Carapetis, J.R. Management of invasive group A streptococcal infections. J. Infect. 2014, 69, S63–S69.
  108. Qing-Zeng, C.; Yun-Bo, S.; Shi-Hai, L.; Li-Min, L.; Li-Juan, R.; Ying-Juan, S.; Pi-Chun, P. Outbreak of infections caused by Group A Streptococcus after modified radical mastectomy. Surg. Infect. 2013, 14, 385–388.
  109. Hancock-Allen, J.B.; Janelle, S.J.; Lujan, K.; Bamberg, W.M. Outbreak of group A streptococcus infections in an outpatient wound clinic—Colorado, 2014. Am. J. Infect. Control 2016, 44, 1133–1138.
  110. Rößler, S.; Berner, R.; Jacobs, E.; Toepfner, N. Prevalence and molecular diversity of invasive Streptococcus dysgalactiae and Streptococcus pyogenes in a German tertiary care medical centre. Eur. J. Clin. Microbiol. Infect. Dis. 2018, 37, 1325–1332.
  111. Inkster, T.; Wright, P.; Kane, H.; Paterson, E.; Dodd, S.; Slorach, J. Successive outbreaks of Group A streptococcus (GAS) in care of the elderly settings: Lessons learned. J. Infect. Prev. 2012, 13, 38–43.
  112. Deutscher, M.; Schillie, S.; Gould, C.; Baumbach, J.; Mueller, M.; Avery, C.; Van Beneden, C.A. Investigation of a group A streptococcal outbreak among residents of a long-term acute care hospital. Clin. Infect. Dis. 2011, 52, 988–994.
  113. Banigo, A.; Moinie, A.; Bleach, N.; Chand, M.; Chalker, V.; Lamagni, T. Have reducing tonsillectomy rates in England led to increasing incidence of invasive Group A Streptococcus infections in children? Clin. Otolaryngol. 2018, 43, 912–919.
  114. Bridges, M.A. A case study of surviving puerperal group A sepsis. J. Obstet. Gynecol. Neonatal Nurs. 2015, 44, S82–S83.
  115. Allen, L.B.; Allen, M.; Lesa, R.; Richardson, G.; Eggett, D. Rheumatic fever in Samoa: Education as prevention. Pac. Health Dialog 2011, 17, 107–118.
  116. Bono-Neri, F. Acute rheumatic fever: Global persistence of a preventable disease. J. Pediatric Health Care 2017, 31, 275–284.
  117. Centers for Disease Control and Prevention. Respiratory Hygiene/Cough Etiquette in Healthcare Settings. Available online: (accessed on 10 February 2020).
  118. Shakoor, S.; Khan, E.; Mir, F.; Malik, F.; Jamil, B. Secular trends of Streptococcus pyogenes sepsis in Pakistan and analysis of clinical features in ahospitalized cohort. Trop. Biomed. 2017, 34, 648–656.
  119. Giraldez-Garcia, C.; Rubio, B.; Gallegos-Braun, J.F.; Imaz, I.; Gonzalez-Enriquez, J.; Sarria-Santamera, A. Diagnosis and management of acute pharyngitis in a paediatric population: A cost–effectiveness analysis. Eur. J. Pediatrics 2011, 170, 1059–1067.
  120. Brennan, M.R.; LeFevre, F. Necrotizing fasciitis: Infection identification and management. Nurs. Crit. Care 2019, 14, 6–11.
  121. Malota, M.; Felbinger, T.W.; Ruppert, R.; Nüssler, N.C. Group A Streptococci: A rare and often misdiagnosed cause of spontaneous bacterial peritonitis in adults. Int. J. Surg. Case Rep. 2015, 6, 251–255.
  122. Follmann, D.; Huang, C.Y.; Gabriel, E. Who really gets strep sore throat? Confounding and effect modification of a time-varying exposure on recurrent events. Stat. Med. 2016, 35, 4398–4412.
  123. Yip, H.; Wong, O.; Lee, H.; Lam, S. Twelve-year experience with necrotising fasciitis in an intensive care unit of a local regional hospital. Hong Kong J. Emerg. Med. 2016, 23, 257–265.
  124. Hikone, M.; Kobayashi, K.-i.; Washino, T.; Ota, M.; Sakamoto, N.; Iwabuchi, S.; Ohnishi, K. Streptococcal toxic shock syndrome secondary to group A streptococcus vaginitis. J. Infect. Chemother. 2015, 21, 873–876.
  125. Krishna, V.; Sankaranarayan, S.; Sivaraman, R.P.; Prabaharan, K. Streptococcal toxic shock syndrome. Indian J. Pediatrics 2014, 81, 946–948.
  126. Vincent, M.T.; Celestin, N.; Hussain, A.N. Pharyngitis. Am. Fam. Physician 2004, 69, 1465–1470.
  127. Dauby, N.; Deyi, V.Y.M.; Delforge, V.; Martiny, D.; Mekkaoui, L.; Hallin, M.; Mahieu, R.; Bossuyt, N.; Botteaux, A.; Smeesters, P.R. Streptococcus pyogenes infections with limited emm-type diversity in the homeless population of Brussels, 2016–2018. Int. J. Infect. Dis. 2019, 81, 52–56.
  128. Cunningham, M.W. Pathogenesis of group A streptococcal infections. Clin. Microbiol. Rev. 2000, 13, 470–511.
  129. Kwiatkowska, R.M.; Manley, P.; Sims, B.; Lamagni, T.; Ready, D.; Coelho, J.; Alsaffar, L.; Beck, C.R.; Neely, F.; Team, O.C. Outbreak of group A streptococcus emm94. 0 affecting people who inject drugs in southwest England, April 2017. Am. J. Infect. Control 2018, 46, 238–240.
  130. Chochua, S.; Metcalf, B.J.; Li, Z.; Rivers, J.; Mathis, S.; Jackson, D.; Gertz, R.E.; Srinivasan, V.; Lynfield, R.; Van Beneden, C. Population and whole genome sequence based characterization of invasive group A streptococci recovered in the United States during 2015. mBio 2017, 8, e01417–e01422.
  131. Ralph, A.P.; Holt, D.C.; Islam, S.; Osowicki, J.; Carroll, D.E.; Tong, S.Y.; Bowen, A.C. Potential for molecular testing for group A streptococcus to improve diagnosis and management in a high-risk population: A prospective study. In Open Forum Infectious Diseases; Oxford University Press: New York, NY, USA, 2018; p. ofz097.
  132. Karaky, N.M.; Araj, G.F.; Tokajian, S.T. Molecular characterization of Streptococcus pyogenes group A isolates from a tertiary hospital in Lebanon. J. Med. Microbiol. 2014, 63, 1197–1204.
  133. World Health Organization. The Current Evidence for the Burden of Group A Streptococcal Diseases; World Health Organization: Geneva, Switzerland, 2005.
  134. Vekemans, J.; Gouvea-Reis, F.; Kim, J.H.; Excler, J.-L.; Smeesters, P.R.; O’Brien, K.L.; Van Beneden, C.A.; Steer, A.C.; Carapetis, J.R.; Kaslow, D.C. The path to group A streptococcus vaccines: World Health Organization research and development technology roadmap and preferred product characteristics. Clin. Infect. Dis. 2019, 69, 877–883.
  135. Seth, A.; Kong, I.G.; Lee, S.-H.; Yang, J.-Y.; Lee, Y.-S.; Kim, Y.; Wibowo, N.; Middelberg, A.P.; Lua, L.H.; Kweon, M.-N. Modular virus-like particles for sublingual vaccination against group A streptococcus. Vaccine 2016, 34, 6472–6480.
  136. Bi, S.; Xu, M.; Zhou, Y.; Xing, X.; Shen, A.; Wang, B. A multicomponent vaccine provides immunity against local and systemic infections by group A streptococcus across serotypes. mBio 2019, 10.
  137. Gupta, V.K.; Sekhar, S.; Dhanda, V.; Toor, D.; Kumar, R.; Chakraborti, A. Immune response against M protein-conserved region peptides from prevalent group A streptococcus in a North Indian population. J. Microbiol. Immunol. 2016, 49, 352–358.
  138. Rivera-Hernandez, T.; Rhyme, M.S.; Cork, A.J.; Jones, S.; Segui-Perez, C.; Brunner, L.; Richter, J.; Petrovsky, N.; Lawrenz, M.; Goldblatt, D. Vaccine-induced Th1-type response protects against invasive group A streptococcus infection in the absence of opsonizing antibodies. mBio 2020, 11.
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