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Avian colibacillosis is an infectious disease of birds caused by Escherichia coli, which is considered as one of the principal causes of morbidity and mortality, associated with heavy economic losses to the poultry industry by its association with various disease conditions, either as primary pathogen or as a secondary pathogen. It causes a variety of disease manifestations in poultry including yolk sac infection, omphalitis, respiratory tract infection, swollen head syndrome, septicemia, polyserositis, coligranuloma, enteritis, cellulitis and salpingitis. Colibacillosis of poultry is characterized in its acute form by septicemia resulting in death and in its subacute form by peri-carditis, airsacculitis and peri-hepatitis. On the other hand, Salmonella infection caused by a variety of Salmonella species is one of the most important bacterial diseases in poultry causing heavy economic losses through mortality and reduced production. Avian salmonella infection may occur in poultry either acute or chronic form by one or more member of genus Salmonella, under the family Enterobacteriaceae. Besides, motile Salmonellae (paratyphoid group) infection cause salmonellosis in chickens and have zoonotic significance.
Avian colibacillosis has been noticed to be a major infectious disease in birds of all ages. This disease has an important economic impact on poultry production worldwide. The majority of economic losses results from mortality and decrease in productivity of the affected birds. Infectious bursal disease (IBD), mycoplasmosis, coccidiosis, Newcastle disease or infectious bronchitis, as well as nutritional deficiencies all predispose the birds to this disease. However, faecal contamination of egg may result in the penetration of E. coli through the shell and may spread to the chickens during hatching and is often associated with high mortality rates, or it may give rise to yolk sac infection. On the other hand, with the great expansion of poultry rearing and farming, avian salmonellosis is the most devastating disease worldwide. The epidemiology of fowl typhoid and pullorum disease in poultry, particularly with regard to transmission from one generation to the next is known to be closely associated with infected eggs. The birds that survive from clinical disease when infected at a young stage may show few signs of infection but can become carriers.
At slaughter, resistant strains from the gut readily soil poultry carcasses and as a result poultry meats are often contaminated with multiresistant E. coli [ 8–14]; likewise eggs become contaminated during laying. Hence, resistant faecal E. coli from poultry can infect humans both directly and via food. These resistant bacteria may colonize the human intestinal tract and may also contribute resistance genes to human endogenous flora. Similarly, the emergence of multidrug resistance among Salmonella spp. is an increasing concern. Salmonella serovar Hadar has been reported as one of the most resistant Salmonella serotypes [17–19].
Microbial food safety is an increasing public health concern worldwide. Epidemiological reports suggest that poultry meat is still the primary cause of human food poisoning. Poultry meat is more popular in the consumer market because of advantages such as easy digestibility and acceptance by the majority of people. However, the presence of pathogenic and spoilage microorganisms in poultry meat and its by-products remains a significant concern for suppliers, consumers and public health officials worldwide. E. coli and Salmonella has been consistently associated with foodborne illnesses in most countries of the world.
There are many poultry diseases transmissible to human, among them avian colibacillosis and avian salmonellosis are the prime concerns. But the detailed information about avian colibacillosis and avian salmonellosis in connection to the public health concerns are not available yet in one place. So, I intend to write this review article focusing on the various aspects of avian colibacillosis and avain salmonellosis in connection to the public health concerns.
In recent years the human microbiota is more and more recognized to play a crucial role in pathogenesis of many diseases (Weinstock, 2012). The upper respiratory tract is a natural niche for potentially pathogenic bacteria embedded in commensal communities forming the nasopharyngeal microbiome. In particular, the microbial communities of the nasopharynx (Hilty et al., 2012) are associated with respiratory diseases, i.e., severe pneumonia, which are responsible for substantial mortality and morbidity in humans worldwide (Prina et al., 2016). The composition of the nasopharyngeal microbiome is highly dynamic (Biesbroek et al., 2014a,b,c) and many factors, including environmental and host factors, can affect microbial colonization (Koppen et al., 2015). Recent studies on neonates have shown that the respiratory microbiota develops from initially maternally transmitted mixed flora with predominance of Streptococcus viridans species to niche-specific bacterial profiles containing mostly Staphylococcus aureus at around 1 week of age (Bosch et al., 2016a). Between 2 weeks and 6 months after birth, the staphylococcal predominance declines and colonization with Streptococcus pneumoniae (pneumococci) as a predominant pathobiont emerges (Miller et al., 2011; Bosch et al., 2016a,b). The dynamic microbiome composition is guaranteed through the interplay between bacterial species, other microbes, and changing environmental conditions, as well as host–bacteria interactions (Blaser and Falkow, 2009). Most of the time, the microbiome and its interplay with the human host are believed to be beneficial for both (Pettigrew et al., 2008; Murphy et al., 2009). However, imbalances in microbial composition can lead to acquisition of new viral or bacterial species and invasion of potential pathogens, which in turn can become detrimental, especially in elderly people and children with an exhausted or immature immune system (Pettigrew et al., 2008; Blaser and Falkow, 2009; Murphy et al., 2009).
One particular example showing imbalances introduced by single dosage of antibiotics was demonstrated by Ichinohe and colleagues (Ichinohe et al., 2011). While commensal respiratory microbiota facilitated immune-support against Influenza A virus infection (IAV), oral treatment with antibiotics resulted not only in a shift of bacterial composition, but also in impaired CD4 T-, CD8 T-, and B-cell immunity following infection with IAV in mice (Ichinohe et al., 2011). Analyses of human oropharyngeal microbiomes during the 2009 H1N1 IAV pandemic revealed that at the phylum level, the abundance of Fermicutes and Proteobacteria was augmented in pneumonia patients as compared to healthy controls (Leung et al., 2013). However, another study published in the same year contradicted these results (Chaban et al., 2013). Chaban and colleagues analyzed microbiomes of 65 patients from H1N1 IAV outbreak in 2009. Although the phylogenetic composition of pneumonia patients was dominated by Fermicutes, Proteobacteria, and Actinobacteria, no significant differences between the patients and healthy controls or any other variables tested, including age and gender, were observed (Chaban et al., 2013).
In this review we discuss secondary bacterial infections of the respiratory tract after primary infection by IAV with a focus on mechanisms by which these interactions are potentially mediated, and we will provide insight into the host contribution and immunological consequences. We further focus on potential animal models suitable for mimicking asymptomatic bacterial colonization and disease progression and thus, enabling to study adaptation strategies, viral-bacterial interactions, and immune responses in these highly lethal co-infections.
The mechanisms by which avian pathogenic E. coli cause infection are largely unknown. The virulence factors contributing to the pathogenesis of avian colibacillosis are summarized in Table 3.
Recently, Hughes et al. described a cross-sectional study of wild birds in northern England to determine the prevalence of E. coli-containing genes that encoded Shiga toxins (stx1 and stx2) and intimin (eae), important virulence determinants of STEC associated with human disease and they stated that while wild birds were unlikely to be direct sources of STEC infections, they did represent a potential reservoir of virulence genes.
APEC are responsible for a considerable number of various diseases at different ages. Neonatal infection of chicks can occur horizontally, from the environment, or vertically, from the hen. A laying hen suffering from E. coli-induced oophoritis or salpingitis may infect the internal egg before shell formation. Faecal contamination of the eggshell is possible during the passage of the egg through the cloaca and after laying. The latter possibility is considered as the main route of infection for the egg. Before hatching, APEC causes yolk sac infections and embryo mortality. The chick can also be infected during or shortly after hatching. In these cases, retained infected yolk, omphalitis, septicemia and mortality of the young chicks up to an age of three weeks is seen. Broilers may be affected by necrotic dermatitis, also known as cellulitis, characterized by a chronic inflammation of the subcutis on abdomen and thighs.
Swollen head syndrome (SHS), mainly a problem in broilers, causes oedema of the cranial and periorbital skin. SHS can cause a reduction in egg production of 2 to 3%, and a mortality of 3 to 4%. Data on this disease are contradictory. Picault et al. and Hafez & Löhren considered SHS as a disease caused by avian pneumovirus (APV), usually followed by an opportunistic E. coli infection. Nakamura et al. however reported that APEC were probably playing a significant part in the disease, but that the role of APV was not at all clear. This had been confirmed by Georgiades et al., who did not detect APV in any of the flocks affected by SHS during a field study, but instead detected infectious bronchitis virus (IBV), avian adenovirus, avian reovirus, and Newcastle disease virus (NDV), as well as Mycoplasma synoviae and M. gallisepticum (MG).
APEC probably do not cause intestinal diseases. Nevertheless, enterotoxigenic E. coli (ETEC) are occasionally isolated from poultry suffering from diarrhoea [161–163] and diarrhoea was experimentally induced after intramuscular inoculation of APEC. On the other hand, enteropathogenic E. coli (EPEC) were isolated from clinically healthy chickens. In turkeys, experimentally inoculated EPEC can only cause enteritis in combination with coronavirus.
Layers as well as broilers may suffer from acute or chronic salpingitis. Salpingitis can be the result of an ascending infection from the cloaca or an infection of the left abdominal airsac, although Bisgaard and Dam considered the latter possibility less likely than an ascending infection. Salpingitis can lead to the loss of egg-laying capacity. In the case of chronic salpingitis, the oviduct has a yellowish-gray, cheese-like content, with a concentric structure. In layers, salpingitis can cause egg peritonitis if yolk material has been deposited in the peritoneal cavity, characterised by a sero-fibrinous inflammation of the surrounding tissues.
Airsacculitis is observed at all ages. The bird is infected by inhalation of dust contaminated with faecal material, which may contain 106 CFU of E. coli per gram. This aerogenic route of infection is considered as the main origin of systemic colibacillosis or colisepticemia.
Septicemia also affects chickens of all ages, and is mainly described in broilers. It is the most prevalent form of colibacillosis, characterised by polyserositis. It causes depression, fever and often high mortality. Although its pathogenesis has not been elucidated, several routes of infection are possible: neonatal infections, infections through skin lesions, infection of the reproductive organs, of the respiratory tract and even infection per os. When E. coli reaches the vascular system, the internal organs and the heart are infected. The infection of the myocard causes heart failure. Septicemia occasionally also leads to synovitis and osteomyelitis and on rare occasions to panophthalmia. Coligranuloma or Hjarre’s disease is characterised by granulomas in liver, caeca, duodenum and mesenterium, but not in the spleen. It is a rare form of colibacillosis, but in affected flocks it may cause up to 75% mortality.
Further studies are needed to determine the role of newly identified putative virulence genes and genes with unknown functions as virulence markers of APEC to strengthen the current understanding of mechanisms underlying the pathogenesis of avian colibacillosis.
Contagious upper airway infections in dogs occur regularly and are most commonly caused by canine parainfluenza virus (CPIV) or Bordetella bronchiseptica, amongst other agents. This clinical syndrome has also been named infectious tracheobronchitis (ITB), canine infectious respiratory disease (CIRD), “kennel cough” or “kennel croup”, so named due to its occurrence in environments where many dogs live or stay close together for shorter periods of time. Characteristic clinical signs include a self-limiting paroxysmal cough lasting for up to two weeks, which usually resolves without treatment. In Norway, immunisation against CIRD is performed using live attenuated viruses, annually with CPIV and every third year against canine adenovirus type 2 (CAV-2). However, in spite of vaccination, outbreaks of CIRD remain common. Some dogs with CIRD will develop serious pneumonia due to an immature immune system or other causes of immunodeficiency. Occasionally, bacteria such as Streptococcus equi subsp. zooepidemicus can cause fatal pneumonia.
This case-report describes the first canine outbreak of haemorrhagic pneumonia in the Nordic countries caused by S. equi subsp. zooepidemicus. Most of the animals in the pack of athletic sled dogs showed symptoms of CIRD with three dogs demonstrating symptoms of severe peracute infection. One sled dog died while two were successfully treated, rehabilitated and returned to competition. To the author’s knowledge, this is the first report documenting the chronology from onset of clinical signs, through convalescence to complete recovery for peracute haemorrhagic pneumonia in dogs. The vaccination regimen related to season and extreme training will also be discussed.
Streptococcus suis serotype 2 (S. suis 2, SS2) is an important zoonotic pathogen that causes severe porcine infectious diseases, including arthritis, meningitis, and pneumonia. Virulent strains of SS2 can also be transmitted to humans (especially abattoir workers and pork handlers) by direct contact, causing meningitis, permanent hearing loss, septic shock, and even death. Two large-scale outbreaks of severe SS2 epidemics occurred in China in 1998 and 2005, causing great economic losses in the swine industry. These two outbreaks also posed serious public health risks from the newly emerging streptococcal toxin shock syndrome (STSS), which claimed 52 lives. Over the past decade, considerable attention has been given to the study of virulence factors (e.g., CPS, MRP, EF, and suilysin) and the pathogen-host interaction in this emerging pathogen. However, comparative studies at the whole-genome level had little done to decipher the evolutionary aspects by which the virulence and environmental adaptation of SS2 are shaped.
To shed light on the evolution of pathogenicity and potential genomic polymorphisms of SS2, several virulent strains were subjected to whole-genome sequencing and comparative genomic studies. Comparative analysis of the whole-genomic DNA sequence of the European S. suis strain P1/7 (by the Sanger Institute) and two representative highly virulent strains (98HAH12 and 05ZYH33) isolated from STSS patients during the two epidemic outbreaks in China uncovered a candidate pathogenicity island (PAI) named 89K, which has been confirmed to undergo horizontal gene transfer (HGT) by our recent work. Further analysis based on PCR amplification revealed that 89K exclusively present in the epidemic strains in these two Chinese SS2 outbreaks but not in other domestic clinical isolates or international virulent strains. However, analysis of the unfinished genomic sequence of SS2 strain 89/1591 (by the DOE Joint Genome Institute) revealed that a partial 89K sequence (~30 kb) is present in this typical North American virulent strain. Similarly, results from a recently published work suggest that S. suis strain BM407, which was isolated from a human meningitis case in Vietnam in 2004, contains two regions with extended similarity to 89K. These findings led us to hypothesize that the genome of SS2 would be highly polymorphic among different strains.
In this study, we employed the comparative genome re-sequencing (CGS) approach developed by Roche NimbleGen Systems to investigate genomic diversity in a collection of 18 SS2 strains, including isolates from the two outbreaks in China, other virulent strains from China (isolated before these outbreaks), virulent strains from European countries, and several avirulent strains. Although CGS cannot identify recently gained genes due to technical limitations, the DNA microarray-based comparative genome sequencing technique allows high resolution detection of sequence polymorphisms based on a reference genome. Using this technology, we identified a number of novel genetic polymorphisms in SS2 strains and several candidate virulence factors that may contribute to STSS. Our results provide new insight into the virulence mechanisms and genome dynamics of SS2, which will help to elucidate the evolution of SS2 strains and better monitor the incidence and spread of epidemic strains.
Sore throat is a common presentation to primary care internationally, including Thailand. Approximately 40–80% of throat infections are caused by viruses, most commonly influenza, parainfluenza, coronavirus, rhinovirus, adenovirus, and enteroviruses, and antibiotics are ineffective for these infections. Bacterial pathogens are identified in 5–40% of cases, and group A Streptococcus (GAS) is the most common.1,2 A study of 290 Thai adults presenting to ambulatory care with acute upper respiratory tract infections (URTIs) found the presence of the following bacteria: 7.9% GAS, 9.2% non–group A β-hemolytic Streptococcus (BHS), 9.6% Klebsiella pneumoniae, 1.7% Streptococcus pneumoniae, 1.4% coagulase-negative Staphylococcus, 0.7% Staphylococcus aureus, 0.3% Hemophilus influenzae, 0.3% Enterobacter spp., and 0.3% Proteus mirabilis.3
In Chiang Rai, northern Thailand, pharyngitis or tonsillitis makes up over 30% of the respiratory tract infections presenting to government primary care units.4 National guidelines recommend the use of the Centor score to determine the need for antibiotics. When required, penicillin V and amoxicillin are recommended, or macrolides in the case of penicillin allergy.5 Antibiotics, typically amoxicillin, were prescribed to 88.4% of cases (14,621/16,539) from 2015 to 2016.4 Antibiotic resistance is an important problem in both the developed and developing world. In Thailand, an estimated 19,122 deaths were thought to be caused by multidrug-resistant hospital-acquired infections in 2010.6 Given that antibiotic use, even with narrow-spectrum agents, drives antimicrobial resistance (AMR), interventions that achieve safe reductions in antibiotic use are needed.
A 2016 Cochrane review compared antibiotic treatment against placebo for sore throats and found some reduction in symptom severity. However, average symptom duration was reduced by only 16 hours.7 Reducing the risk of complications is often used as a justification for antibiotic treatment, but a large cohort study from 2006 to 2009, albeit from a high-income setting (UK), found the risk of suppurative complications (otitis media, sinusitis, quinsy, and cellulitis) to be around 1% with or without antibiotic treatment. There were no cases of acute rheumatic fever or post-streptococcal glomerulonephritis.8 Nonetheless, these findings may not be applicable in low- and middle-income countries (LMICs) where prevalence of rheumatic heart disease is higher. The 2015 global burden of disease study found a high burden of rheumatic heart disease in Oceania, South Asia, and central sub-Saharan Africa. The burden is lower in Southeast Asia, and Thailand is considered non-endemic for rheumatic heart disease.9 Current guidelines recommend antibiotics for pharyngitis caused by GAS and that narrow-spectrum penicillins are most suitable.10,11 Concern is growing about increasing levels of GAS resistance to macrolide antibiotics.12,13
It is important to identify those most likely to benefit from antibiotic use and to reduce unnecessary antibiotic use to limit AMR; to achieve this, a variety of methods have been used, but with limited success. The best current reference standard for diagnosis of GAS is culture, although the length of time required to generate results limits its use to affect management decisions in primary care. Alternatives for use in primary care include rapid antigen testing, clinical scores such as Centor and FeverPAIN, and biomarkers of inflammation such as C-reactive protein (CRP). Studies assessing CRP’s performance in identifying the presence of GAS in patients presenting to primary care with sore throats or pharyngitis have produced mixed results, with some studies finding CRP predictive,14–16 whereas others have not.2,17–20 Rapid molecular tests for GAS are also being developed and have proved valuable in settings such as northern Australia, where a high burden of GAS, acute post-streptococcal glomerulonephritis, and acute rheumatic fever is evident.21
Our main objective was to evaluate the performance of CRP in identifying the presence of GAS among people consulting with sore throat and fever in Chiang Rai’s government-run primary care units. The secondary objectives were to estimate the prevalence of GAS and other key pathogens, study the antibiotic susceptibility of GAS isolates, and compare the performance of CRP against the Centor and FeverPAIN clinical scores.
Group A Streptococcus (GAS) is a bacterial pathogen responsible for a wide spectrum of clinical manifestations. Mild common infections include pharyngitis and impetigo, while more-serious infections such as streptococcal toxic shock syndrome, necrotizing fasciitis, and sepsis are relatively rare and yet life-threatening conditions. Poststreptococcal sequelae can manifest following repeated mild infections in the form of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). The global burden of streptococcal diseases has been long neglected despite being responsible for an estimated 500,000 deaths annually (1). Recent advocacy efforts have highlighted the urgent need for the development of a vaccine that prevents GAS-related infections (2–4). M protein-based vaccines have been considered strong candidates, despite concerns over insufficient serotype coverage (N-terminal-based vaccines) and the association of M protein with the generation of cross-reactive antibodies linked to ARF and RHD (5). On the other hand, non-M protein-based vaccines have emerged as alternative candidates that overcome such concerns. Regardless of the choice of GAS antigen used as a vaccine candidate, the choice of adjuvant, a significant element of the final vaccine formulation, has generally been overlooked. Aluminum salts (alum) have represented the most common adjuvant used to test GAS vaccine candidates (6–9). For M-protein based vaccines, alum has proven effective for the generation of opsonizing antibodies, which are associated with protection against infection in animal models (10, 11).
However, less is known about potential correlates of protection for non-M protein-based vaccines and the role that different adjuvants may play in the protection afforded by these vaccines. Our research has focused on the development of Combo5 vaccine, a combination of 5 GAS protein antigens (arginine deiminase, [ADI], C5a peptidase [SCPA], streptolysin O [SLO], interleukin-8 protease [SpyCEP], and trigger factor [TF]). We previously tested Combo5 formulated with alum in murine and nonhuman primate (NHP) models of infection with various results. While immunization with Combo5/alum decreased the severity of clinical signs but did not reduce colonization in a NHP pharyngitis model of infection (12) and provided protection in a murine superficial skin infection model, the same formulation failed to protect in a murine invasive model of disease (13). In this study, taking advantage of the opportunity presented by these findings, we examined the protective capacity of Combo5 formulated with a panel of different adjuvants (Table 1) using the invasive GAS disease model. The level of protection from lethal challenge ranged from 20% to 90% survival among the different formulations. We further characterized the protective immune response elicited by Combo5 formulated with SMQ adjuvant and compared this to the nonprotective response elicited by Combo5/alum and to the protective response elicited by the “gold standard” homologous M1 protein formulated with alum.
Post-mortem examination revealed epistaxis and haemorrhagic frothy fluids in the trachea and bronchial airways on cut sections. Haemorrhages were present in the thymus, epicardium, intercostally, and in the pleural space 200 mL of uncoagulated blood were present. The lungs were congested, wet, consolidated and diffusely to cavernous haemorrhagic, these changes being more severe in the left lung lobes (Figure 1).
Histopathology of the lungs revealed a subacute necrotising suppurative pneumonia, with haemorrhagic, often cavernous areas in the lungs and intra-lesional gram-positive cocci. A large number of macrophages with phagocytosed erythrocytes were present (Figures 2 and 3). A subacute pleuritis was also seen.
Streptococcus equi subsp. zooepidemicus was isolated in pure culture from the lung tissue with identification based on morphology, microscopy, Lancefield grouping (Streptococcal grouping kit, Oxoid, Basingstoke, Hampshire, England) and biochemical testing. Properties included β-haemolytic colonies on bovine blood agar, gram-positive, katalase negative cocci belonging to Lancefield group C. Glucose, lactose, and sorbitol were fermented, trehalose was not. The isolate was also tested by using API20STREP (bioMérieux®, Lyon, France) with the same conclusion.
Toxicological diagnostic screening of the liver tissue showed no evidence of anticoagulant poisons.
Respiratory tract infections are a major cause of morbidity and mortality globally1,2. In 2015, acute lower respiratory infections (ALRI) due to respiratory syncytial virus (RSV) resulted in an estimated 33.1 million disease episodes, 3.2 million hospitalisations and 118,200 deaths in children younger than the age of 5 years3. A common complication of respiratory virus infection is secondary bacterial infection; viruses such as influenza, RSV and parainfluenza often predispose the host to secondary respiratory disease caused by pathobionts, such as Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus4–8, leading to serious, potentially life-threatening sequelae9. Secondary bacterial complications are thought to have been the major cause of the fatalities that occurred in the wake of the major influenza pandemics of the 20th and early 21st century8,10,11. In the case of RSV, there is a strong link between virus infection and secondary bacterial infections, particularly otitis media caused by S. pneumoniae and H. influenzae12–14. Although the molecular and cellular basis for this co-pathogenesis is not fully understood, evidence from in vitro studies suggests that RSV infection of respiratory epithelial cell lines, such as HEp-2 and A549 facilitates increased adhesion of bacteria such as S. pneumoniae and H influenzae15–18, and suggests that RSV infection in vivo increases the capacity of these bacteria to colonise the airway. These observations are supported by results from clinical studies which show that the upper airway microbiota of children with RSV infection is significantly enriched for H. influenzae and Streptococcus19,20. The host response to RSV infection is characterised by the recruitment of innate immune cells21 and the release of inflammatory cytokines, such as IL-17A and other soluble mediators22. To date, no studies have examined whether the immune response triggered by replication of RSV in the airway has simultaneous antibacterial activity, aimed at controlling increased bacterial colonisation resulting from viral infection. Here we report the simultaneous analysis of the upper airway proteomes and microbiota of infants and children with and without RSV infection to determine whether elements of the innate immune response to RSV infection in the human airway has incidental antibacterial activity. Using shotgun proteomics, we find that the local airway response that followed RSV infection is characterised by a strong neutrophil response, which has direct antibacterial properties.
Overuse and inappropriate use of antibiotics drive the emergence and spread of antimicrobial resistance [1, 2]. In the Republic of Korea, the number of antibiotic prescriptions is relatively higher (31.7 defined daily dose [DDD] per 1000 inhabitants per day) than in other member countries of the Organization for Economic Co-operation and Development (mean, 23.7 DDD per 1000 inhabitants per day). In Korea, the majority of antibiotics (ca. 90%) are prescribed in primary care and mainly for acute respiratory tract infections (ARTIs; ca. 57%). ARTIs are mainly viral in origin, are generally self-limiting, and do not require antibiotics [5, 6]. Secondary bacterial pneumonia is the most important clinical complication of respiratory viral infections. However, previous studies have shown that antibiotics do not improve outcomes for patients with ARTIs [7–10].
To prevent overuse and inappropriate use of antibiotics, it is essential to identify and understand antibiotic prescribing patterns and determining factors, however, little is known about antibiotic prescribing patterns in the Republic of Korea. The purpose of this study was to describe antibiotic prescription patterns in primary care clinics over a 6-year period and to identify its temporal relationship with respiratory viruses and ARTIs.
Streptococcosis is regarded as a leading infectious disease in the swine industry, that clinically features with meningitis, septicemia, or arthritis and annually results in significant economic loss worldwide.1
Streptococcus suis (S. suis) that was initially reported in 19542 has been demonstrated as an etiological agent for this kind of frequently-occurring bacterial infection.1,3 Indeed, S. suis, a complex population consisting of heterogeneous strains,4 can be classified into 35 serotypes (1–34, 1/2) based on the differentiation of capsule antigens.1,3 Based on the varied virulence of these bacteria, they may be categorized into highly-pathogenic, weakly-pathogenic (hypo-virulent), and nonpathogenic (avirulent) strains.1 Generally, serotype 2 of S. suis (SS2) is considered to be the most virulent, and is frequently isolated from clinically-diseased piglets.1 In fact, serotype 9 of S. suis is also one of the most important serotypes in several countries. Of particular note, SS2 seems to be a previously neglected but recently emerging human pathogen,5 whose infection has become increasingly potent, especially in the southeast Asian countries like Thailand,6 Vietnam,7 and China.8,9
As the primary agent of meningitis, septicemia, arthritis and as an opportunistic pathogen in the case of pneumonia,1,5
S. suis have been reported to have spread over 30 countries and/or regions (Fig. 1) and has claimed no less than 1600 human cases, some of which were fatal.2 Also, similar clinical symptoms including bacterial meningitis, septicemia, and arthritis are frequently observed in human SS2 infections.2,3 Occasionally, serotypes other than SS2, including SS1,10 SS4,10 SS5,11,12 SS14,13,14 SS16,15,16 and SS2411 can also be found to function as the causative agents responsible for sporadic cases of human S. suis infection.3 Of note, two big outbreaks of human SS2 endemics which occurred in China, in 1998 and 2005, respectively,9,17,18 have raised serious concerns in public health and have challenged the conventional opinion that human SS2 infections are only present in sporadic cases.2,8,19 Unfortunately, no specific/effective human therapeutics or vaccine against SS2 infections is available thus far. Considering the severity (high mortality and modality) of SS2 infection in humans,5,8 it is important to develop a method for convenient and quick diagnosis, which can be applied toward local SS2 detection.4,18
Over the past four decades, significant progress has been made toward better understanding the highly infectious clones of S. suis. At the time of formulating this review, 1104 articles were available in PubMed regarding S. suis (http://www.ncbi.nlm.nih.gov/pubmed/?term=Streptococcus+suis).Totally, over 20 bacterial virulence-associated factors have been identified that include capsular polysaccharides (CPS),20 Muramidase-released protein (MRP),21 and Suilysin (SLY).22 To date, genomic sequences of a collection of S. suis strains are available (Fig. 2), the majority of which are derived from SS2 species,23,24 except two newly-released genomes which correspond to SS325 and SS14,26 respectively. Genomic mining combined with bacterial genetics have elucidated that Chinese epidemic strains of highly pathogenic S. suis 2 carry a specific 89K PAI (pathogenicity island).23,27 Further studies suggested that 89K PAI with a transposon-like essence can undergo GI-type T4SS-mediated horizontal transfer in epidemic SS2 species.28 The systematic elucidation of the of S. suis pathogenesis in the Omics Era was illustrated by functional definition of a collection of other new genes or putative orthologs (such as Zur, a zinc uptake regulator,29 CovR, an orphan response regulator,30 and Rgg-like transcription factor31) following the release of the genome sequence of SS2 (e.g., 05ZYH33).23 Although we have gained a partial glimpse of the molecular mechanism underlying the high pathogenicity of SS2 itself, we are still lacking further insights into the interface between the SS2 pathogen and the host it infects.3,8
In this review, we aim to describe an updated but partial picture of SS2 as an emerging infectious agent, which centers on five aspects: global epidemiology/distribution, clinical diagnostics/typing, pathogenesis, protective antigen/candidate vaccine, and zoonotic potential.
Both viruses and bacteria may colonize the nasopharynx (NP) and oropharynx (OP) without causing infection. Advances in molecular testing and microbial antigen detection with enhanced sensitivity may allow detection of colonization or postinfectious shedding of respiratory pathogens without clinical significance. Respiratory viruses, such as the herpes viruses, including Epstein-Barr (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV), are associated with chronic intermittent asymptomatic nucleic acid shedding.
Streptococcal carriers are at low risk to spread GABHS to close contacts. They do not require antibiotic treatment and are at minimal risk for development of rheumatic fever. Streptococcal carriage may persist for many months and frequently poses diagnostic challenges when a symptomatic viral URI develops in carriers. The low predictive value of throat swabs relates to the prevalence of carrier rates, and neither the blood agar plate culture nor the rapid antigen tests can accurately differentiate individuals with true GABHS pharyngitis from GABHS carriers. Studies have shown that only 40%–50% of the children with GABHS isolated from the upper respiratory tract who presented with symptoms of tonsillitis or pharyngitis demonstrated a systemic immune response [16–18].
When Group A strep is cultured from the OP and associated with an antibody response characteristic of a true infection, CRP will elevate 80%–90% of the time [15, 17]. Conversely, patients with a negative initial CRP test seldom show a rise in antibody titer, and 96% have CRP <10 mg/mL. The high carrier rate of GABHS and false-positive diagnoses may contribute to the apparent “failure” rate of approximately 20% with penicillin therapy. Valkenburg et al. have shown that an antistreptococcal antibody titer is more accurate than a throat culture in predicting therapeutic outcome.
Differentiation of infection from colonization requires the demonstration of an antibody response. However, proving this immune response is time-consuming and may lead to false-negative results following appropriate antibiotic therapy. A study by Ivaska et al. showed that in 83 patients presenting with pharyngitis, there was no significant difference in the mean initial serum antistreptolysin O (ASO) levels between the GABHS and non-GABHS patients and only 5 patients showed a 2-fold ASO increase in paired serum samples. Of the 5 patients with an antibody response, 3 of them were GABHS positive, 1 of them was GCBHS positive, and 1 was negative for streptococci by throat culture. Conversely, blood MxA levels were found to be elevated in 79% of patients with viral pharyngitis and remained low in 90% of patients with GABHS without virus detection.
Serum and plasma samples were collected from patients with fever of >38 °C and symptoms of respiratory infections and from asymptomatic healthy subjects.
Infected patients were classified as having a bacterial, mycoplasma or viral cause of their disease. The primary study group included patients with confirmed etiology of respiratory infections. The study group consisted of 279 subjects (144 asymptomatic healthy controls, 71 with bacterial infections, 24 with mycoplasma infections and 40 with viral infections) (Table 1).
Acute pharyngotonsillitis constitutes one fifth of all visits for respiratory tract infections in Swedish primary healthcare. The most common causative agent is Streptococcus pyogenes (Group A streptococcus, GAS) but several other bacteria and viruses have also been associated with the condition [2, 3], among these Streptococcus group C and G, Mycoplasma pneumoniae and Arcanobacterium haemolyticum. Furthermore, Fusobacterium necrophorum has been suggested as a possible pathogen in tonsillitis [4–8] and reported to be the second most common bacterial finding. However, no one has so far studied the course of these patients, and studies on the course of patients with pharyngotonsillitis where modern diagnostic approaches and treatment recommendations have been used are also lacking.
Pharyngotonsillitis is associated with short-term complications such as sinusitis, otitis and peritonsillar abscess in a small percentage of patients. Historically, post-streptococcal acute rheumatic fever and glomerulonephritis were dreaded conditions, but these are now uncommon in industrialized countries. In some cases, recurrent infections lead to tonsillectomy [10, 11], but the long-term complications of an episode of pharyngotonsillitis have very rarely been studied, especially in relation to the aetiology of the condition.
Recently, we performed a case-control study on the aetiology of pharyngotonsillitis in young Swedish adults with a special focus on the importance of F. necrophorum as a possible pathogen. The present study is a follow-up on that study with the purpose of observing patients over a 2-year period after a pharyngotonsillitis episode together with a cohort of non-infected patients. Specifically, our objective was to quantify the proportion of patients who would have a new doctor’s appointment for a sore throat within 2 years; have a complication of pharyngotonsillitis within 30 days; undergo or be planned for tonsillectomy within 2 years. These outcomes were studied in relation to the identified microorganism at inclusion.
There is increasing evidence that the nasopharyngeal microbiota plays an important role in the pathogenesis of acute viral respiratory infections (Teo et al., 2015; de Steenhuijsen Piters et al., 2016; Rosas-Salazar et al., 2016a,b). Respiratory viruses, including IAV, have been shown to alter bacterial adherence and colonization leading to an increased risk of secondary bacterial infections (Tregoning and Schwarze, 2010). Pneumococci, S. aureus, and GAS are important human Gram-positive pathogens. All of them are frequent colonizers of the human nasopharynx and they share many features including pathogenic mechanisms and clinical aspects (Figure 1). However, they also have unique properties.
Staphylococcus aureus colonizes persistently about 30% of the human population and typical niches include nares, axillae, and skin (Peacock et al., 2001; von Eiff et al., 2001; van Belkum et al., 2009). They cause a variety of clinical manifestations ranging from mild skin infections to fatal necrotizing pneumonia. In the last decades, the pathogen became resistant to an increasing number of antibiotics and methicillin-resistant S. aureus (MRSA) is now a major cause of hospital acquired infections (Hartman and Tomasz, 1984; Ubukata et al., 1989; Zetola et al., 2005). Also the rise of community-acquired S. aureus strains is of special concern, because certain clones are associated with very severe infections (Rasigade et al., 2010). Recent prospective studies demonstrated an increase in proportion of community-acquired methicillin-sensitive S. aureus in severe pneumonia cases (McCaskill et al., 2007; Sicot et al., 2013).
The pneumococcus is a typical colonizer of the human nasopharynx. About 20–50% of healthy children and 8–30% of healthy adults are asymptomatically colonized (McCullers, 2006). Pneumococci cause diseases ranging from mild, i.e., sinusitis, conjunctivitis, and otitis media, to more severe and potentially life-threatening infections, including community-acquired pneumonia, bacteraemia, and meningitis (Bogaert et al., 2004; Valles et al., 2016). This bacterium is associated with high morbidity and mortality rates in risk groups such as immunocompromised individuals, children, and elderly (Black et al., 2010; Valles et al., 2016).
Group A streptococci colonize the mouth and upper respiratory tract in about 2–5% of world’s population (Okumura and Nizet, 2014). The most common, non-invasive and mild infections caused by GAS are tonsillitis and pharyngitis with estimated 600 million cases per year (Carapetis et al., 2005). Listed as number nine in the list of global killers with around 500,000 deaths annually (Carapetis et al., 2005), it is obvious that this pathogen can cause severe invasive infections, including pneumonia, sepsis, streptococcal toxic shock syndrome, and necrotizing skin infections (Cunningham, 2000; Carapetis et al., 2005).
Although all three pathogens are able to cause highly lethal diseases, the most fatal remains the pneumococcus, estimated to cause ca. 10% of all deaths in children below 5 years of age (O’Brien et al., 2009), in the elderly (Marrie et al., 2017), and in immuno-compromised individuals (Baxter et al., 2016).
The range of implicated pathogens in paediatric community-acquired pneumonia (CAP) is wide and includes viruses, bacteria and co-infection with both [1, 2]. Studies of pneumonia frequently report low levels of pathogen identification, although improved knowledge of pneumonia aetiology is essential for the development of targeted management and effective public health strategies such as vaccination [3, 4]. In the UK, the 7-valent pneumococcal conjugate vaccine (PCV) was introduced routinely in September 2006 and replaced by PCV13 from April 2010. The vaccine schedule is three doses administered at 2, 4 and 13 months of age. When first introduced, those over and under 1 year of age received one and two doses, respectively, as part of a catch-up programme for children aged <2 years.
Identifying the aetiology of paediatric CAP is challenging, with a large number of potential pathogens, some of which may also be carried as commensal organisms, which can complicate the interpretation of the results of testing nasopharyngeal samples. Conventional methods such as blood culture and serology often have limited sensitivity due to inadequate sample volume or lack of convalescent sera. Molecular diagnostics are now routinely used in the assessment of viral respiratory infections and similar techniques have been developed for the detection of bacterial respiratory infections [6, 7]. Resti
et al. demonstrated a significant improvement in the identification of pneumococcal pneumonia in children by PCR on blood samples (15.4%) when applied simultaneously with blood culture (3.8%). In a recent study of Italian children aged <5 years, overall bacteraemic pneumococcal pneumonia was identified in 14.3%, which was established by PCR in 92%, blood culture in 1% and both in 7% of subjects.
The introduction of PCV was expected to decrease the incidence of pneumonia in children, and this was supported by a region-wide epidemiological prospective survey. We present data from studies conducted over two periods, before (2001–2002) and after (2009–2011) the addition of PCV. These were designed to describe the proportion of causative pathogens in paediatric CAP and describe how the identification of causative pathogens could be improved with the application of more PCR-based assays. As disease incidence declined, a longer recruitment period in the post-vaccine study was therefore planned, in order to have a larger cohort with representative aetiological data.
Throat swabs were collected and placed in Amies transport medium with charcoal and stored at 0–4°C until processed at the Shoklo Malaria Research Unit (SMRU) laboratory, Tak Province, Thailand. Samples were plated onto blood agar and incubated at 35 ± 2°C in 5–10% CO2 for 20–24 hours. The presence of BHS was confirmed by Gram stain, catalase, and Lancefield grouping. GAS isolates were then tested for antimicrobial susceptibility by disk diffusion according to the Clinical and Laboratory Standards Institute criteria.26 The SMRU laboratory is not accredited but participates in external quality assurance (EQA) including the EQA program from the Department of Medical Sciences, Ministry of Public Health, Thailand, for bacterial identification and antimicrobial susceptibility testing.
Patients within the control group also had a nasopharyngeal swab taken, which was tested using TaqMan® Array Card (TAC; Life TechnologiesTM, Waltham, MA).27,28 The assay was screened for 32 pathogens in a single run of multiplex reverse transcriptase real-time polymerase chain reaction (see Supplementary Material). This article fulfills the Microbiology Investigation Criteria for Reporting Objectively (MICRO) framework checklist requirements for standardized reporting of clinical microbiology data.29
Worldwide, the use of vaccines is seen as critical for the prevention and control of many economically damaging outbreaks of poultry diseases. In Caribbean countries, the use of vaccination to prevent poultry diseases is variable and is mainly influenced by the size of the poultry industry in the various countries. Many of the larger poultry-producing CARICOM countries (for example, T & T, Jamaica, Belize, Barbados, and Guyana) with large poultry (broiler and layer) operations have structured and rigid regimes of vaccination in place, while smaller island states (for example, Grenada and St. Lucia), with smaller poultry and egg production operations, often do not vaccinate their poultry. The larger intensive broiler and layer production units in the Caribbean routinely vaccinate their birds against IBV, NDV, and IBDV, whereas some smaller semi-intensive and backyard operations often do not carry out vaccination against these three viral pathogens. Routine vaccination is not carried out in the region against other viral pathogens (AIV, ILTV, APV, FADV Gp1, and EDSV) included in this review, although occasional vaccination against FADV Gp1 has been carried out in the face of disease outbreaks. All reports/publications describing the detection of viruses and outbreaks of disease in both vaccinated and unvaccinated poultry were reviewed. When information pertaining to vaccination history was given in the relevant report/publication, this information was included.
A prospective, single center, blinded, clinical feasibility trial was performed at Beth Israel Deaconess Medical Center (a Harvard Medical School teaching tertiary care hospital) from December 2012 to August 2013. The feasibility trial planned an estimated minimum sample size enrollment of 20 negative patients, 10 confirmed viral patients, and 10 confirmed bacterial patients. The study enrolled 60 patients (34 males and 26 females) with an acute febrile respiratory infection. All subjects older than 17 years of age who presented with fever with acute respiratory symptoms consistent with infection, or reported having a body temperature of ≥100.5°F in the last 48 h, were considered eligible for the study (Supplementary file). At enrollment, the 36 case subjects were separated into two groups: 12 with presumed pharyngitis and 24 with presumed LRTI (Supplementary file). If a patient did not have a fever and was asymptomatic (as described in the inclusion criteria), the patient was considered for inclusion as a control subject (Supplementary file). Twenty-four patients were enrolled into the control group.
The study was approved by the Beth Israel Deaconess Medical Center Committee for Clinical Investigations with a written consent. Study personnel collected up to seven samples from all patients including one venous blood sample, four oropharyngeal samples, a urine sample, and a fingerstick blood sample that was applied to a rapid, POC immunoassay, according to the manufacturer's instructions for use. In addition to the preceding tests, subjects suspected of having an LRTI had sputum and blood cultures as well as a chest X-ray. Participation of subjects required one visit with one follow-up visit. The follow-up visit, 4–6 weeks after the initial visit, was necessary to collect a venous blood sample for follow-up serology testing.
The immunoassay was interpreted by identifying the presence of the control lines or result lines according to Fig. 1. Two of the oropharyngeal samples were sent for a viral respiratory PCR panel (Luminex xTAG, Austin, TX) and other viral PCR testing, whereas the other two oropharyngeal samples were sent for routine bacterial cell culture. A 5 mL peripheral venous blood sample, collected in a purple top tube (ethylenediaminetetraacetic acid [EDTA]), was sent for quantitative MxA enzyme–linked immunosorbent assays (ELISA) testing using the MxA Protein ELISA Test Kit (Kyowa Medex Co., Ltd., Tokyo, Japan) and WBC measurement. A second sample, collected in a red top tube, was used for CRP testing with the High Sensitivity CRP Enzyme Immunoassay Test Kit (Biocheck, Inc., Foster City, CA).
Diagnosis of Chlamydia pneumoniae and Mycoplasma pneumoniae was determined by PCR and performed by means of paired serology at the time of enrollment and at 4–6 weeks thereafter. Commercially available ELISA tests (Ani Labsystems Ltd. Oy., Vantaa, Finland) were used according to the manufacturer's instructions for the detection of immunoglobulin M (IgM) and IgG antibodies to M. pneumoniae and C. pneumoniae. Atypical bacterial infection was confirmed if M. pneumoniae and C. pneumoniae were identified by PCR, M. pneumoniae and C. pneumoniae IgM antibodies were detected, or a twofold increase in IgG antibodies between acute and convalescent phase samples was found.
A definitive typical bacterial infection was considered when a bacterium was cultured from blood, sputum, or if the urine antigen assay for Legionella or Streptococcus was found to be positive. All subjects suspected of an LRTI had peripheral venous blood collected and sent for plating on routine bacterial blood cultures. Upon reaching the clinical laboratory, the specimens were divided into samples for plating on blood and chocolate agar. All specimens were processed within 24 h of collection, and a single colony-forming unit (CFU)/mL of a single bacterial species indicated an infection and not colonization.
Expectorated sputum was collected from subjects with a productive cough and a presumptive LRTI. Only samples that had more than 25 polymorphonuclear leukocytes and less than 25 squamous cells per microscope high-power field were plated for culture (32). The quality of sputum samples was evaluated by assessing the number of inflammatory and epithelial cells. A definitive bacterial infection was considered when any Group A beta hemolytic strep growth occurred or any other bacterial growth greater than 1×105 CFU/mL occurred in oropharyngeal samples or sputum samples.
Urine samples were collected and assayed for Streptococcal pneumoniae and Legionella pneumophila antigen. Immunochromatographic membrane tests (Alere BinaxNOW S. pneumoniae and BinaxNOW Legionella, Waltham, MA) were performed on urine samples for detection of S. pneumoniae and L. pneumophila antigens. Identification of L. pneumophila by PCR also confirmed the diagnosis of Legionella.
Definitive viral infection was confirmed if the oropharyngeal PCR respiratory panel (Luminex xTAG; Austin, TX) or other viral PCR was positive for viral nucleic acid.
Subjects who did not have a definitive microbiological confirmation of disease were characterized according to an algorithm incorporating additional radiological and laboratory findings (Fig. 2). The presence of radiologic evidence of diffuse infiltrates by chest X-ray suggested a viral infection while the presence of radiologic evidence of a focal lobar process or infiltrate by chest X-ray suggested a bacterial infection. In addition, significantly elevated WBC count over 12,000 mm3 was interpreted to suggest bacterial infection.
Finding an organism is only one step in establishing a causal relationship or understanding how it causes disease. Many have wrestled with the challenge of codifying the process of proving causation. Based on the germ theory of disease of Pasteur, Koch and Loeffler proposed criteria that define a causative relationship between agent and disease: the agent is present in every case of a disease; it is specific for that disease; and it can be propagated in culture and inoculated into a naïve host to cause the same disease. Known as Koch's postulates, these criteria were modified by Rivers for viruses, and by Fredericks and Relman to reflect the introduction of molecular methods. Although fulfillment of Koch's postulates remains the most persuasive evidence of causation, there are problems with holding to this standard. Overlap in signs and symptoms due to infection with different agents is common. Results of infection may vary with genetic background, age, nutrition, and previous exposure to similar agents. Many agents cannot be cultured; furthermore, there may be no animal model. Proving causation is particularly challenging where agents have remote effects or require co-factors for expression. In many acute infectious diseases, the responsible agent is readily implicated because it replicates at high levels in the affected tissue at the time the disease is manifest, morphological changes consistent with infection are evident, the agent is readily identified with classical or molecular methods, and there is evidence of an adaptive immune response. However, implication is more difficult when classical hallmarks of infection are absent or mechanisms of pathogenesis are indirect or subtle. Here, one may resort to a statistical assessment of the strength of epidemiological association based on the presence of the agent or its footprints (nucleic acid, antigen, and preferably, an immune response), and biological plausibility as indicated by analogy to diseases with other organisms where linkage is persuasive.
Streptococcus pyogenes (Group A streptococcus) is a common pathogen responsible for a number of human suppurative infections, including pharyngitis, impetigo, pyoderma, erysipelas, cellulitis, necrotizing fasciitis, toxic streptococcal syndrome, scarlet fever, septicemia, pneumonia and meningitis. It also causes non-suppurative sequelae, including acute rheumatic fever, acute glomerulonephritis and acute arthritis. Scarlet fever, characterized by a sore throat, skin rash and strawberry tongue, is most prevalent in school children aged four to seven years old. This disease was listed as a notifiable disease in Taiwan until 2007; as such, all cases of scarlet fever had to be reported to the public heath department. According to our records, however, only 9% of the medical centers, regional hospitals and district hospitals in central Taiwan reported cases of scarlet fever to the health authorities between 1996 and 1999. The number of scarlet fever cases is therefore likely to be significantly underreported. Scarlet fever outbreaks frequently occur in young children at day-care centers, kindergartens and elementary schools and also occur in adults upon exposure to contaminated food.
Genotyping bacterial isolates with various methods is frequently used to compare the genetic relatedness of bacterial strains and provides useful information for epidemiological studies. In a previous study, we used emm (gene of M protein) sequencing, vir typing and pulsed-field gel electrophoresis (PFGE) typing to analyze a collection of streptococcal isolates from scarlet fever patients and used these data to build a DNA fingerprint and emm sequence database for long-term disease surveillance. Vir typing has since been abandoned in our lab because it has lower discriminatory power than PFGE and the protocol is difficult to standardize with conventional agarose gel electrophoresis. In contrast, the PFGE protocol for S. pyogenes has been standardized in our laboratory, and a second enzyme, SgrAI, has been found to replace SmaI for analysis of strains with DNA resistant to SmaI digestion. Since PFGE is highly discriminative and emm sequencing provides unambiguous sequence information regarding emm type, we adopted these two genotyping methods to characterize streptococcal isolates and build a Streptococcus pyogenes DNA fingerprint and sequence database for the long-term study of scarlet fever and other streptococcal diseases.
The number of scarlet fever cases in central Taiwan fluctuated greatly between 2000 and 2006. Relative to the number of scarlet fever occurrences in 2000, occurrences increased in 2001 and doubled in 2002, but dramatically dropped in 2003. The number of occurrences increased again since 2004. In this study, we characterized 1,218 isolates collected between 2000–2006 by emm sequencing and PFGE. The bacterial genotyping data and the epidemiological data collected via the Notifiable Disease Reporting System (established by Taiwan Centers for Disease Control (Taiwan CDC)) were used to examine the significant fluctuation in the number of scarlet fever cases between 2000 and 2006.
Acute respiratory infections (ARIs) significantly impact the health of children worldwide. Though the pathogens causing ARIs vary geographically and by season, globally viruses play a major role [1–3]. In a recent systematic review, the most common respiratory viruses causing acute lower respiratory tract infection (LRI) in children under five years of age were respiratory syncytial virus (RSV), influenza virus (IFV), parainfluenza virus (PIV) human metapneumovirus (hMPV), and rhinovirus (RV). Besides this, 10%–50% of children affected with ARI develop secondary bacterial infections, namely, acute otitis media, sinusitis, or pneumonia. Moreover, viruses are the most common pathogen associated with severe respiratory diseases (e.g., bronchiolitis), exacerbation of asthma, or pneumonia in early life and are leading cause of hospitalization in children under two [5–7]. Although viral etiology of ARIs and their impact on health care are much studied in developed countries, there is a gap in knowledge regarding the same in developing countries including India. From the public health point of view, it is important to know the most common viral agents causing ARIs, their manifestations, how often they cause severe disease, and how severe ARIs can be prevented. In this study, we aimed to characterize the viral spectrum and pattern of upper and lower ARIs in children under five from eastern part of India.
Two invalid tests occurred and four subjects were diagnostically indeterminant because of specimen leakage or rejection. Of the remaining 54 patients, the immunoassay correctly identified 92% (22/24) of subjects as negative for infection (95% CI: 74.2–97.7), 80% (16/20) of confirmed bacterial infections (95% CI: 56.3–94.1), and 70% (7/10) of confirmed viral infections (95% CI: 39.7–89.2). The percent negative and positive agreement of the test was calculated according to the charts in Table 1.
Of the 41 enrolled patients with LRTI, 26 were males and 15 were females with an age range of 22–89 and a mean age of 51 years. Of the 19 patients enrolled with pharyngitis, 8 were males and 11 were females with an age range of 18–69 and a mean age of 37 years. Viral pathogens detected by PCR included influenza A, influenza B, parainfluenza 2, parainfluenza 3, and HSV-1. Three asymptomatic controls had rhinovirus detected without an associated elevation in MxA; this was deemed likely colonization and was excluded from the microbiological confirmation. If both a viral and bacterial infection were confirmed microbiologically, this was characterized as a bacterial infection.
Pharyngitis is a common condition. It can last several days and is usually the result of self-limiting viral infections, such as the common cold, although occasionally, pharyngitis can be caused by a bacterial infection. The most commonly reported symptom is sore throat. Antibiotics do not work against the viruses that in most cases cause pharyngitis but are often prescribed anyway. This contributes to antimicrobial resistance, where bacteria become immune to antibiotics and treatment for infections becomes difficult. Alternative treatments could help reduce inappropriate prescriptions of antibiotics for pharyngitis, and previous studies have demonstrated the antiviral and pain-relieving qualities of some antiseptic lozenges. The authors conducted a laboratory- based study to assess the ability of antiseptic lozenges to kill a broad range of bacteria known to cause pharyngitis. They found that, when lozenges containing two antiseptic ingredients were dissolved in a solution similar to human saliva, the mixture killed 99.9% of all pharyngitis-associated bacteria that were tested within 10 minutes. These results suggest that patients with uncomplicated bacterial pharyngitis may benefit from the antibacterial and pain-relieving action of antiseptic lozenges, including those taking antibiotics. Additionally, antiseptic lozenges may be more relevant and appropriate than antibiotics for pharyngitis of a viral origin.
The number of acute respiratory virus diagnoses was collected from the Korea Influenza and Respiratory Virus Surveillance System (KINRESS) from the Korea Centers for Disease Control and Prevention. KINRESS collects nasopharyngeal specimens from patients with acute respiratory symptoms, including cough, rhinorrhea, and sore throat, from sentinel primary care clinics. This weekly laboratory-based surveillance system has been in operation since 2009 to measure respiratory virus activity at the community level, including adenovirus (ADV), influenza virus (IFV; A, B), human coronavirus (hCoV; 229E, OC43, NL63), human rhinovirus (hRV), and respiratory syncytial virus (RSV; A, B). Laboratory confirmation of respiratory pathogens was performed using multiplex polymerase chain reaction (PCR) or real-time reverse transcription PCR [13, 14].