Transmission of respiratory tract infections at mass gathering events.

PURPOSE OF REVIEW: Mass gathering events bring people from across all continents increasing the risk of spread of aerosol transmissible respiratory tract infections. Respiratory tract infections for instance in pilgrims attending the world's largest recurring annual pilgrimage, the Hajj are common. We review recent literature on viral and bacterial infectious diseases with special focus on the Hajj. RECENT FINDINGS: The prevalence of bacterial and viral infections continue to increase, because of the acquisition of rhinovirus, coronaviruses (229E, HKU1, OC43), influenza A H1N1, Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus during Hajj. Whilst MERS-CoV continues to circulate in the Middle East, no cases of MERS-CoV have yet been identified in pilgrims during Hajj. SUMMARY: Respiratory tract infections are a major cause of morbidity in pilgrims attending mass gathering events. The management of severe respiratory infections should consider investigation and empirical coverage for the most likely agents based on syndromic surveillance data from hosting country and /or other relevant exposure history during events. Pneumococcal and Pertussis vaccines should be recommended for Hajj pilgrims.

Pneumococcal pneumonia and carriage in Africa before and after introduction of pneumococcal conjugate vaccines, 2000-2019: protocol for systematic review.

INTRODUCTION: Africa harbours a high burden of pneumococcal disease, with associated high mortality rates. Despite 34 countries introducing the pneumococcal conjugate vaccine, which reduces the risk of pneumococcal carriage (a prerequisite for disease) of some of the most pathogenic pneumococcal serotypes, it remains uncertain whether they will achieve the sustained direct or indirect protection necessary to reduce pneumococcal carriage to levels sufficient to interrupt transmission and disease. We will therefore summarise the available data on the impact of the pneumococcal conjugate vaccine in reducing vaccine serotype carriage and pneumococcal pneumonia in Africa between 2000 and 2019. METHODS AND ANALYSIS: Using a predetermined search strategy, we will conduct a comprehensive search of PubMed, MEDLINE database, the Excerpta Medica Database, the ISI Web of Science (Science Citation Index), Scopus and the African Index Medicus to identify published studies reporting the prevalence of Streptococcus pneumoniae carriage (vaccine type and non-vaccine type), incidence rates of pneumococcal pneumonia and mortality among children, adults and HIV-infected (all-ages) pre-pneumococcal conjugate vaccine (PCV) and post-PCV introduction (published between 1st January 2000 and 31st December 2019) in African countries that have introduced PCVs (PCV7/PCV10/PCV13) in their routine national immunisation programme. The studies retained and data extracted will be assessed for bias using prevalidated tools and checklists. Heterogeneity across studies will be assessed using the χ2 test on Cochrane Q statistic. A random effect meta-analysis will be used to estimate the overall prevalence of pneumococcal carriage and incidence of pneumococcal pneumonia across studies with similar characteristics. Results will be reported in compliance with the Meta-Analysis Of Observational Studies in Epidemiology guidelines. The protocol has been prepared in accordance to the 2015 guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses. ETHICS AND DISSEMINATION: This systematic review will not require ethical approval as we will be using already published data. The final manuscript will be submitted for publication in a peer-reviewed journal and presented at conferences. PROSPERO REGISTRATION NUMBER: CRD42019130976.

Epidemiology and Transmission of Respiratory Infections in Thai Army Recruits: A Prospective Cohort Study.

Military recruits are at high risk of respiratory infections. However, limited data exist on military populations in tropical settings, where the epidemiology of respiratory infections differs substantially from temperate settings. We enrolled recruits undertaking a 10-week military training at two Royal Thai Army barracks between May 2014 and July 2015. We used a multiplex respiratory panel to analyze nose and throat swabs collected at the start and end of the training period, and from participants experiencing respiratory symptoms during follow-up. Paired sera were tested for influenza seroconversion using a hemagglutinin inhibition assay. Overall rates of upper respiratory illness and influenza-like illness were 3.1 and 2.0 episodes per 100 person-weeks, respectively. A pathogen was detected in 96% of samples. The most commonly detected microbes were Haemophilus influenzae type B (62.7%) or non-type B (58.2%) and rhinovirus (22.4%). At baseline, bacterial colonization was high and included H. influenzae type B (82.3%), H. influenzae non-type B (31.5%), Klebsiella pneumoniae (14.6%), Staphylococcus aureus (8.5%), and Streptococcus pneumoniae (8.5%). At the end of follow-up, colonization with H. influenzae non-type B had increased to 74.1%, and S. pneumoniae to 33.6%. In the serology subset, the rate of influenza infection was 3.4 per 100 person-months; 58% of influenza infections resulted in clinical disease. Our study provides key data on the epidemiology and transmission of respiratory pathogens in tropical settings. Our results emphasize the need for improved infection prevention and control in military environments, given the high burden of illness and potential for intense transmission of respiratory pathogens.

Pneumococcal serotypes in adult non-invasive and invasive pneumonia in relation to child contact and child vaccination status.

BACKGROUND: On a population level, pneumococcal conjugate vaccination in children has reduced the incidence of vaccine-type disease in all age groups, including older adults. Few individual level studies have been performed describing the pneumococcal serotypes associated with adult community acquired pneumonia (CAP) and quantifying associations with child contact and child vaccination status. METHODS: Pneumococcal serotypes were determined using a validated multiplex immunoassay (Bio-Plex) in a large prospective cohort of adults hospitalised with CAP. Child (<16 years old) contact history and child pneumococcal vaccination status were obtained from patients and public health records, respectively. RESULTS: Of 1130 participants, 329 (29.1%) reported child contact, and pneumococcal infection was identified in 410 (36.3%). Pneumococcal CAP was commoner in adults with child contact (148/329 (45.0%) vs 262/801 (32.7%); adjusted OR 1.63, CI 1.25 to 2.14; p<0.001). A serotype was determined in 263 of 410 (64.1%) adults with pneumococcal CAP; 112 (42.6%) reported child contact, 38 (33.9%) with a vaccinated child. Adults in contact with a vaccinated child were significantly less likely to have vaccine-type CAP compared with adults in contact with an unvaccinated child (6 of 38 (15.8%) vs 25 of 74 (33.8%), respectively; OR 0.37, 95% CI 0.14 to 0.99; p=0.044). CONCLUSIONS: Pneumococcal aetiology in adult CAP is independently associated with child contact and implicated serotypes are influenced by child vaccination status. This is the first study to demonstrate these associations at an individual rather than population level; it affirms that 'herd protection' from childhood vaccination extends beyond adult invasive disease to pneumococcal CAP.

Influenza and community-acquired pneumonia interactions: the impact of order and time of infection on population patterns.

Discoveries made during the 1918 influenza A pandemic and reports of severe disease associated with coinfection during the 2009 hemagglutinin type 1 and neuraminidase type 1 (commonly known as H1N1 or swine flu) pandemic have renewed interest in the role of coinfection in disease pathogenesis. The authors assessed how various timings of coinfection with influenza virus and pneumonia-causing bacteria could affect the severity of illness at multiple levels of interaction, including the biologic and population levels. Animal studies most strongly support a single pathway of coinfection with influenza inoculation occurring approximately 7 days before inoculation with Streptococcus pneumoniae, but less-examined pathways of infection also may be important for human disease. The authors discussed the implications of each pathway for disease prevention and what they would expect to see at the population level if there were sufficient data available. Lastly, the authors identified crucial gaps in the study of timing of coinfection and proposed related research questions.

[Vaccination against pneumococci and influenza. How good is the evidence?]. / Impfungen gegen Pneumokokken und Influenza. Wie groß ist die Evidenz?

Diseases caused by pneumococci and influenza viruses can lead to severe complications in children, in older, chronically ill and immunosuppressed patients. In an aging population in western countries they present an important cause of morbidity and mortality. Additionally, antibiotic resistance may complicate a therapy. Consequently, the need of an effective vaccine is obvious. The 23-valent polysaccharide pneumococcal vaccine has been discussed critically. New meta-analyses do not show an efficacy in preventing invasive pneumococcal disease or death of all cause. However, a very recent study has shown a significant reduction of pneumonias and death due to pneumococcal disease in nursing-home residents. The 7-valent conjugated vaccine is more immunogenic and efficient in children and first studies demonstrate its efficacy in immunosuppressed persons. In Switzerland this latter vaccine is used in children, in Germany the 7-valent vaccine has been replaced by the 13-valent conjugated vaccine since December 2009. Influenza-vaccines are effective, while vaccines with an adjuvance seem more immunogenic, in particular in older persons. The 2010/2011 influenza vaccine has been adapted and includes the pandemic influenza H1N1 2009 strain. The influenza vaccine often does not provide protection against infection, however, it does provide good efficacy against severe complications related to influenza.

[Household transmission of pneumococcal pneumonia associated with pandemic influenza (H1N1) 2009].

We report 2 cases of household transmission of pneumococcal pneumonia in isolation, associated with pandemic influenza (H1N1) 2009. A Chinese-American family consisting of a 47-year-old woman and her 16- and 9-year-old sons came to Japan at the beginning of July 2009. The day after their arrival, the woman noticed a high fever in the eldest son. The following day, the other family members also developed high fevers. Real-time reverse transcription polymerase chain reaction (RRT-PCR) analysis confirmed pandemic influenza A (H1N1) 2009 infection in all family members. After diagnosis, all patients were given oseltamivir at another hospital. Subsequently, they were admitted to our hospital and placed in isolation in accordance with the Japanese Infectious Disease Law. At the time of admission, all family members were in a stable condition. However, on the day after admission, the mother complained of a productive cough. Upon further investigation, a CT scan showed a consolidation shadow in the right middle lung lobe. After isolating Streptococcus pneumoniae from her sputum culture, we diagnosed bacterial pneumonia due to S. pneumoniae. In addition, both of her sons also developed fever and cough, and sputum obtained from her elder son indicated S. pneumoniae infection. All 3 were treated with ampicillin and their symptoms improved over a period of a few days. Although the role of Streptococcus pneumoniae in cases of novel influenza A (H1N1) remains unclear, these bacteria may have been responsible for many complications during past pandemic and non-pandemic influenza cases. Use of the 23-valent pneumococcal polysaccharide vaccine should be considered as a potential way to prevent pneumococcal pneumonia during future influenza pandemics.

[Pneumococcal pneumonia highly probable in immunized children cared for in-group settings]. / Pneumonies à pneumocoque hautement probables chez les enfants vaccinés gardés en collectivité.

Invasive pneumococcal diseases were reduced after introduction of pneumococcal conjugate vaccine, but infections due to non-vaccine serotypes persisted. The pneumococcal origin of community-acquired pneumonia remains difficult to affirm, but high procalcitonin and C-reactive protein blood levels and duration of fever 48 h or less after initial antibiotic treatment are excellent predictors of pneumococci. Among 259 patients under 7 years of age hospitalized from 2003 to 2008 for community-acquired pneumonia, 47 met these criteria, including 27 of 141 hospitalized between 2006 (date of vaccine generalization) and 2008. Of these 27, 21 had previously received pneumococcal conjugate vaccine and 19 of 21 were attendees of nursery school or day care centers versus only 2 in 2003-2006. These data show that pneumococcal pneumonias are possible in immunized children cared for in-group settings.

Influenza A virus facilitates Streptococcus pneumoniae transmission and disease.

Streptococcus pneumoniae (the pneumococcus) kills approximately 1.6 million people annually. Pneumococcal infections predominantly manifest as pneumonia, sepsis, meningitis, and otitis media. S. pneumoniae is also a member of the normal nasopharyngeal flora, colonizing up to 80% of children. Infection with influenza A virus (IAV) has been associated with both pneumococcal disease and transmission. However, to date no animal model has been available to investigate the role of IAV in the spread of S. pneumoniae. Here we investigate pneumococcal-influenza synergism with a particular focus on the role of IAV on pneumococcal transmission. Infant mice were colonized with S. pneumoniae and subsequently infected with IAV 3 d later. Using this novel model we show increased pneumococcal colonization and disease in the presence of IAV. Notably, in vivo imaging showed that IAV was essential for the transmission of S. pneumoniae from colonized ("index") mice to their naive cohoused littermates ("contacts"). Transmission occurred only when all mice were infected with IAV and was prevented when an IAV-neutralizing antibody was used to inhibit IAV replication in either index mice or contact mice. Together, these data provide novel insights into pneumococcal-influenza synergism and may indicate a previously unappreciated role of IAV in the spread of S. pneumoniae.

Streptococcus pneumoniae forms surface-attached communities in the middle ear of experimentally infected chinchillas.

BACKGROUND: Streptococcus pneumoniae (pneumococcus) causes respiratory and systemic infections that are a major public health problem worldwide. It has been postulated that pneumococci persist in vivo in biofilm communities. METHODS: In this study, we analyzed whether pneumococci form biofilms in vivo, and if so, whether biofilms correlated with bacterial persistence. Chinchillas were infected with S. pneumoniae TIGR4 and euthanized at varying times after infection, after which the superior ear bullae were excised and examined by culture and microscopy. RESULTS: Dense material, resembling the biofilms of other otitis media pathogens, was visible in the middle ear as late as 12 days after infection. Scanning electron microscopy revealed bacteria within an electron-dense matrix, similar to pneumococcal biofilms formed in vitro. Viability staining revealed groups of viable diplococci, as well as viable and nonviable host cells, attached to a fibrous matrix that was positive when stained with propidium iodide. Cryosections of biofilms were treated with polyclonal antibodies against the pneumococcal surface components pneumococcal surface protein A family 2, pneumococcal surface protein C, choline-binding protein, and neuraminidase, coupled with appropriate secondary antibody conjugates. Immunofluorescent staining showed the presence of pneumococcal communities within the material recovered from the middle ear chamber. CONCLUSIONS: On the basis of these data, we conclude that pneumococci form biofilms in vivo and that this process may be intertwined with the formation of neutrophil extracellular traps. These findings provide new insights into the potential causes of antibiotic treatment failure and bacterial persistence in chronic pneumococcal otitis media.

Introduction and proliferation of multidrug-resistant Streptococcus pneumoniae serotype 19A clones that cause acute otitis media in an unvaccinated population.

BACKGROUND: Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the United States in 2000 was temporally associated with an increase in the incidence of disease caused by Streptococcus pneumoniae serotype 19A (Sp19A) and with increasing drug resistance within this serotype. A causative role of PCV7 was speculated. We prospectively studied the dynamics of acute otitis media (AOM) caused by Sp19A in southern Israel before the introduction of PCV7. METHODS: AOM in children < 5 years old undergoing tympanocentesis during 1999-2006 was studied. Antibiotic prescriptions for approximately 20% of children < 5 years old were recorded. Sp19A isolates were studied for antibiotic-resistance and pulsed-field gel electrophoresis patterns; multilocus sequence typing of representative isolates was compared with that of international clones. RESULTS: Sp19A caused 438 (9.8%) of 4449 pneumococcal AOM episodes, increasing by 63.1% from 1999-2001 (mean +/- SD, 8.4% +/- 0.8%) to 2004-2006 (mean +/- SD, 13.7% +/- 0.9%) among Bedouin children, who were characterized by overcrowding and high antibiotic use. Penicillin, erythromycin, and multidrug resistance increased from < 10% to 78.6%, 50.0%, and 50.0%, respectively (P < .001), and was associated with the introduction and proliferation of 2 multidrug-resistant clones that were not previously associated with multidrug resistance. This was temporally associated with the introduction of and rapid increase in azithromycin use and the frequent use of oral cephalosporins. CONCLUSIONS: The introduction and proliferation of multidrug-resistant Sp19A occurred before the introduction of PCV7. The increasing proportion of antibiotic-resistant Sp19A suggests that antibiotic use plays an important role in the community.

[Nursing-home-acquired pneumococcal pneumonia--comparison of sputum cultures with Binax NOW Streptococcus pneumoniae urinary antigen assay].

To clarify the clinical significance of Pneumococcal pneumonia in nursing-home-acquired pneumonia, we examined the positive disease rate of using sputum cultures and the Binax NOW Streptococcus pneumoniae urinary antigen assay in 154 nursing-home patients with pneumonia. These included 54 males and 100 females with a mean age of 86.2 years. Bacteriological findings for sputum culture in 130 patients showed Streptococcus pneumoniae to be cultured in 11 cases (8%). In 72 in whom the Streptococcus pneumoniae-urinary antigen test (Binax NOW) was done, the urinary-antigen-positive rate (26/72 ; 36%) was higher than the culture positive rate for S. pneumoniae. Both examinations were done in 64 patients, among whom 5 in whom S. pneumoniae was cultured also had positive results for the urinary antigen test. Almost half of those undergoing percutaneous endoscopic gastroscopy (PEG) tube nutrition had positive results for the urinary antigen test, but not all such patients had positive cultures for S. pneumoniae. Although the culture-positive rate for S. pneumoniae in sputum was low, we concluded that S. pneumoniae was frequently linked to nursing-home-acquired pneumonia, especially in "total-care" patients.

Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study.

BACKGROUND: Natural immunity to Streptococcus pneumoniae is thought to be induced by exposure to S. pneumoniae or cross-reactive antigens. No longitudinal studies of carriage of and immune responses to S. pneumoniae have been conducted using sophisticated immunological laboratory techniques. METHODS: We enrolled 121 families with young children into this study. Nasopharyngeal (NP) swabs were collected monthly for 10 months from all family members and were cultured in a standard fashion. Cultured S. pneumoniae isolates were serotyped. At the beginning (month 0) and end (month 10) of the study, venous blood was collected from family members >18 years old. Serotype-specific antipolysaccharide immunoglobulin G (IgG) and functional antibody and antibodies to pneumolysin, pneumococcal surface protein A (PspA), and pneumococcal surface antigen A (PsaA) were measured in paired serum samples. RESULTS: Levels of anticapsular IgG increased significantly after carriage of serotypes 9V, 14, 18C, 19F, and 23F by an individual or family member. For serotype 14, a higher level of anticapsular IgG at the beginning of the study was associated with reduced odds of carriage (P = .006). There was a small (approximately 20%) but significant increase in titers of antibodies to PsaA and pneumolysin but no change in titers of antibody to PspA. CONCLUSIONS: Adults respond to NP carriage by mounting anticapsular and weak antiprotein antibody responses, and naturally induced anticapsular IgG can prevent carriage.

Seasonality of infectious diseases and severe acute respiratory syndrome-what we don't know can hurt us.

The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.

[Streptococcus pneumoniae transmission in a nursing home: analysis of an epidemic outbreak]. / Transmisión de Streptococcus pneumoniae en una residencia de ancianos: análisis de un brote epidémico.

BACKGROUND AND OBJECTIVE: On the basis of an outbreak of pneumococcal pneumonia in a nursing home, we analyze causes and patterns of transmission and discuss preventive interventions carried out on the target population. PATIENTS AND METHOD: A retrospective cohort study was designed on 232 residents to identify risk factors associated with the outbreak. A descriptive study of those nasopharyngeal carriers of pneumococcus among nursing home workers was also carried out. RESULTS: Twenty cases of pneumococcal pneumonia were detected with 4 deaths; 13 cases were confirmed. Cases occurred on a close temporal aggregation form but they were quite disseminated spatially. Among the factors investigated, an older age was the only factor significantly associated (p = 0.02) with the risk of disease. In 4 workers, strains of Streptococcus pneumoniae were isolated from nasopharyngeal swabs; two of them corresponded to the serotype 3, as it was the strain isolated from the blood of a nursing home case. The number of new cases decreased dramatically after vaccination and/or chemoprophylaxis. CONCLUSIONS: Vaccination and chemoprophylaxis administered to nursing home residents seemed effective measures to halt the spread of this outbreak. Detection of the S. pneumoniae antigen by immunochromatographic tests in urine samples is a valuable tool for detecting an outbreak.

Pneumonia due to resistant Streptococcus pneumoniae.

In the past 10 to 20 years the pneumococcus, the most common pathogen of community-acquired pneumonia, has developed resistance to most antibiotics used for its treatment. Classes with important resistance problems include the beta-lactams, the macrolides and lincosamides, trimethoprim-sulfamethoxazole, and the tetracyclines. Unfortunately, resistance to more than one class of antibiotics is common in pneumococci, and their treatment is thus becoming more difficult. Patients likely to harbour resistant organisms include young children, particularly those attending day care, older patients, and subjects who have received recent antibiotic therapy, suffer from underlying diseases including HIV, or have nosocomial or polymicrobial pneumonia. The consequences of resistance development are different for different classes of antibiotics. With beta-lactams, the increase in minimal inhibitory concentrations is usually moderate in resistant strains, and because of the high concentrations that can be achieved with this class of drugs resistance does not usually lead to treatment failure. Thus, beta-lactams continue to be important drugs for the treatment of pneumococcal pneumonia, even if the organism is resistant. In contrast, resistance to other classes of antibiotics must be assumed to render these drugs ineffective. Newer quinolones represent valuable alternatives for the treatment of pneumococcal pneumonia, since their efficacy is not affected by resistance to other classes of antibiotics and they cover almost all pathogens of community-acquired pneumonia, including the atypical pathogens. However, they should be used with restraint in order to preserve this valuable class of drugs.