Respiratory Disease Season Research Articles

Defining the South African Acute Respiratory Infectious Disease Season.

The acute respiratory infectious disease season, or colloquially the "flu season", is defined as the annually recurring period characterized by the prevalence of an outbreak of acute respiratory infectious diseases. It has been widely agreed that this season spans the winter period globally, but the precise timing or intensity of the season onset in South Africa is not well defined. This limits the efficacy of the public health sector to vaccinate for influenza timeously and for health facilities to synchronize efficiently for an increase in cases. This study explores the statistical intensity thresholds in defining this season to determine the start and finish date of the acute respiratory infectious disease season in South Africa. Two sets of data were utilized: public-sector hospitalization data that included laboratory-tested RSV and influenza cases and private-sector medical insurance claims under ICD 10 codes J111, J118, J110, and J00. Using the intensity threshold methodology proposed by the US CDC in 2017, various thresholds were tested for alignment with the nineteen-week flu season as proposed by the South African NICD. This resulted in varying thresholds for each province. The respiratory disease season commences in May and ends in September. These findings were seen in hospitalization cases and medical insurance claim cases, particularly with influenza-positive cases in Baragwanath hospital for the year 2019. These statistically determined intensity thresholds and timing of the acute respiratory infectious disease season allow for improved surveillance and preparedness among the public and private healthcare.

SHAR and effective SIR models: from dengue fever toy models to a COVID-19 fully parametrized SHARUCD framework

We review basic models of severe/hospitalized and mild/asymptomatic infection spreading (with classes of susceptibles S, hopsitalized H, asymptomatic A and recovered R, hence SHAR-models) and develop the notion of comparing different models on the same data set as exemplified in the comparison of SHAR models with effective SIR models, where only the H-class of the SHAR model is taken into account in the SIR model. This is done via the so-called Bayes factor. A simpler pair of models with analytical expressions up to the Bayes factor will be briefly mentioned as well. The notions developed with respect to dengue fever epidemiology will then be used to analyze recently becoming available data on coronavirus disease 2019, COVID-19, where models can be fully parametrized including hospital admission and more extensions like intensive care unit (ICU) admission and deceased, always with a close look on as simple as possible models but not simpler, as exercised in Ocham’s razor and analyzed by e.g. the Bayes factor. We present the resulting models of SHAR-type with additional classes of ICU admissions U, and deceased D, and for data analysis of cumulative disease data, also accounting the cumulative classes C, in the so-called SHARUCD framework. Besides a first basic version, SHARUCD model 1, we investigate also in detail a refined version, SHARUCD model 2, which could be achieved by a closer analysis of available data only obtained after the exponential growth phase of the epidemic, when lockdown control measures showed effects. Namely, the ICU admissions turned out to be more in synchrony with the hospitalized than with e.g. the deceased cases, such that we could adjust the transitions so that ICU admissions are modeled like hospitalizations in model 2, and not like recovery or disease induced death as assumed in model 1, explaining much better the empirical data, specially after the effects of the lockdown became visible. Special attention will be given here, for the first time, to the initial phase of the COVID-19 epidemics, before all variables entered into the exponential phase, and its interplay between asymptomatic and severe hospitalized cases, always in close check with the SIR-limiting case. Such improved understanding of the initial phase will help in the future analysis of re-emergent outbreaks of COVID-19, likely to happen in the next or a subsequent respiratory disease season in autumn or winter.

Hospital Utilization and the Respiratory Disease Season

In the United States, the respiratory disease season has challenged providers to care for populations at the community level. This study reviewed the utilization of inpatient hospitals in the metropolitan area of Syracuse, New York during the most recent twelve-month periods. It focused on the onset and duration of respiratory disease utilization. The study evaluated this utilization by identifying numbers of hospital patients admitted with respiratory diseases to the combined Syracuse hospitals by month. By focusing on twelve-month periods for July-June of each year, it was possible to identify changes in hospital utilization for respiratory disease season. The study demonstrated that, during the five-year period, inpatient respiratory diseases were concentrated between January and March. The highest levels of respiratory disease occurred during January. The study also demonstrated that the onset of the respiratory disease season was rapid, demonstrated by increases in census levels and discharges between October-December and January-March. The study suggested that the highest demands for inpatient care in Syracuse increased by a community wide average of 15 to 20 patients during January. The data show that increased levels of respiratory diseases extended from January-March into April and May. This approach to the utilization of health care could be employed by other providers to address the onset and duration of respiratory disease at the community level.

SARS Coronaviruses and Highly Pathogenic Influenza Viruses: Safety and Occupational Health for Laboratory Workers

SARS Coronaviruses and Highly Pathogenic Influenza Viruses: Safety and Occupational Health for Laboratory Workers

Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial isolates from hospitalized patients with pneumonia: I—results from the SENTRY Antimicrobial Surveillance Program (North America, 1998)

Pneumonia is the second most frequent cause of nosocomial infection, and hospitalization frequently is needed for community-acquired pneumonia. Knowledge of causative pathogens through periodic surveillance, and their prevailing antimicrobial susceptibility patterns becomes paramount in choosing appropriate empiric therapy. The SENTRY Antimicrobial Surveillance Program, tracks pathogen distribution worldwide since 1997 and documents emerging resistance to a wide range of antimicrobial agents. During the respiratory disease season in 1998, each of 30 medical centers (25 in the United States [US], and five in Canada [CAN]) contributed 100 consecutive isolates obtained from hospitalized patients with suspected pneumonia. The 2773 organisms, processed by the monitor consisted of a total of 35 species, with Staphylococcus aureus comprising 25.6% of all isolates and five other species ( Pseudomonas aeruginosa 18.7%, Haemophilus influenzae 9.4%, Streptococcus pneumoniae 7.8%, Klebsiella spp. 7.0%, and Enterobacter spp. 6.7%) making up almost 50% of the total. In the US, pneumococci (8.5%) were more prevalent than in CAN (4.1%; p = 0.001). The US isolates of S. pneumoniae were variably susceptible to penicillin (76.8%), with non-susceptible strains demonstrating greater levels of cross resistance to macrolides (31.8%), cefepime (9.0%) and cefotaxime (6.8%), but remaining susceptible to gatifloxacin and quinupristin/dalfopristin. H. influenzae and Moraxella catarrhalis were generally ampicillin-resistant, 40.4–44.4% and 93.7–95.7%, respectively. P. aeruginosa remained very susceptible to amikacin (91.3–93.8%) > tobramycin > meropenem > piperacillin/tazobactam > gentamicin > piperacillin > cefepime (80.0–81.8%). Extended spectrum β-lactamase phenotypes among the Klebsiella spp. were isolated from five medical centers in the US and were 4.8–6.0% overall; a rate similar to the previous year. Among the US isolates of Enterobacter spp., only 77.6% and 79.6% were susceptible to ceftazidime and cefotaxime, respectively, but >90% were inhibited by cefepime, imipenem, meropenem, aminoglycosides, and fluoroquinolones. Isolates from CAN were generally more susceptible, except for Pseudomonas isolates, where resistance to aminoglycosides, fluoroquinolones and imipenem was greater. The SENTRY Program results outline important national differences in the frequencies of pathogen occurrence, but more importantly, identify unstable patterns of resistance to available antimicrobial drugs, and serves as a reference for results of other local, national or international investigations.

Comparative antimicrobial activity of trovafloxacin tested against 3049 streptococcus pneumoniae isolates from the 1997–1998 respiratory infection season

Trovafloxacin is a new fluorinated naphthyridone having expanded activity against Gram-positive and anaerobic pathogens compared with ciprofloxacin or levofloxacin or ofloxacin. A multicenter in vitro trial (201 sites) was initiated in late 1997 to study the comparative activity of trovafloxacin against Streptococcus pneumoniae strains during the recently completed respiratory disease season. Each laboratory was asked to test 20 to 30 recent isolates (3049 strains) by the Etest (AB BIODISK, Solna, Sweden) method with observed phenotypes with elevated trovafloxacin results (MIC, >1 μg/mL) confirmed by the monitor laboratory (University of Iowa College of Medicine). Approximately one-third (34.0%) of isolates were penicillin nonsusceptible (12.8% high-level resistance at ≥2 μg/mL). Also 20.4% and 4.5% of strains were resistant to macrolides (erythromycin) and ceftriaxone, respectively. The macrolide resistance rate was lowered to 16.8% when the adverse effect of CO 2 incubation was considered. Only 0.3% of S. pneumoniae were vancomycin-nonsusceptible using the current National Committee for Clinical Laboratory Standards breakpoint (≤1 μg/mL) with nearly all results were at 1.5 μg/mL. Trovafloxacin (MIC 50 and MIC 90, 0.094 and 0.19 μg/mL, respectively) was eight fold more potent than levofloxacin (MIC 90, 0.75 and 1.5 μg/mL), and fewer strains (0.10%) were discovered with high-level resistance (MIC, ≥8 μg/mL). The four resistant isolates from different states had alterations in both par C and gyr A. Trovafloxacin had the best potency observed against contemporary pneumococcal isolates, and has a spectrum (>99.8% susceptible) for an orally administered agent that was comparable to the tested parenteral glycopeptide, vancomycin (>99.7%). Blood and spinal fluid culture isolates were generally more susceptible to penicillin (74.4 to 75.6%), other β-lactams, and erythromycin (84.4%); throat and sputum isolates were significantly more resistant ( p < 0.01). Increases in resistance among S. pneumoniae strains to β-lactams and erythromycin were documented in all geographic regions monitored, other resistances also continue to evolve, and high-level fluoroquinolone resistance remains very rare.

Adverse impact of infections on antibody responses to measles vaccination

Antibody titres were determined in 102 Thai infants who were vaccinated at 9-months of age during the respiratory disease season. The symptom densities of illnesses at or following vaccination, including rhinorrhea and diarrhea, were significantly lower among seroconverters, although the simple presence or absence of specific symptoms was not significantly related to seroconversions. Logistic regression indicated that neutralization test antibody titres below the median titre of 1:80 following vaccination were significantly more frequent among those with rhinorrhea when vaccinated and among those with diarrhea after vaccination. Compared with a referent group without these symptoms, titres were lower in those who had rhinorrhea when vaccinated, rhinorrhea during the first week post vaccination, and diarrhea in either of the two follow-up weeks. Illnesses concurrent or subsequent to measles vaccination adversely affected antibody responses in these study objects.

Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections.

Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.

Hyperimmune globulins in prevention and treatment of respiratory syncytial virus infections.

Respiratory syncytial virus (RSV) is an important community and nosocomial respiratory pathogen for infants and young children. RSV causes especially severe disease in the prematurely born or those with chronic cardiopulmonary diseases. Elderly persons and those with T-cell deficiencies, such as bone marrow transplant recipients, are also at high risk for serious lower respiratory tract infections. To date, prevention of RSV infections by vaccination has proven elusive and no preventive drugs exist. Studies in animals and humans have shown that the lower respiratory tract can be protected from RSV infection by sufficient circulating RSV neutralizing antibody levels. Recently, an RSV hyperimmune immune globulin (RSVIG) was developed and tested for the prevention of RSV infections or reduction of disease severity. Passive immunization of high-risk children with RSVIG during the respiratory disease season effected significant reductions in RSV infections, hospitalizations, days of hospitalization, intensive care unit admissions, days in the intensive care unit, and ribavirin use. Studies in cotton rats and owl monkeys show that RSV infections can also be treated with inhalation of immune globulin at doses substantially smaller than required for parenteral treatment. Therapeutic trials of parenteral RSVIG have been completed and are pending analysis. The use of polyclonal, hyperimmune globulins and perhaps human monoclonal antibodies provides an additional approach to the prevention and perhaps the treatment of certain viral lower respiratory tract infections such as those caused by RSV.

Age Distribution of Patients with Medically-Attended Illnesses Caused by Sequential Variants of Influenza A/H1N1: Comparison to Age-Specific Infection Rates, 1978–1989

Since influenza A/H1N1 viruses reappeared during the 1977-1978 season, this subtype has contributed 27% of 6,609 documented influenza infections of persons with acute respiratory disease presenting to clinics serving as surveillance sites of the Influenza Research Center in Houston for the 12-year period ending June 1989. Wide differences in the distribution of H1N1 viruses occurred by age group: more than 50% of H1N1 infections were detected among persons aged 10-34 years, compared with 28% for influenza A/H3N2 and 35% for influenza B. Over age 35 years, the contribution of H1N1 viruses dropped to only 4%, compared with 20% and 16% for influenza A/H3N2 and influenza B, respectively. When birth dates of persons with positive cultures were examined, it was found that most of the H1N1-positive persons were born after 1950. Concurrently, longitudinal studies of families and other adults under intensive surveillance for infection, including cultures of all respiratory illnesses and tests for serum antibody rise over the respiratory disease season, revealed appreciable infection rates for adults born before 1950. Furthermore, the annual peak of hospitalization of older persons with pneumonia and other acute respiratory illnesses was significantly correlated with the peak of H1N1 virus activity in 1978-1979, a year when H1N1 viruses were the only influenza viruses prevalent. These observations indicate that many persons infected with influenza A/H1N1 viruses that circulated from 1946 through 1953 have immunity which has persisted for more than 25 years but this immunity is not complete. Reinfection that may result in serious illness in older vulnerable adults does occur but with lower frequency than with influenza A/H3N2 infection. Currently prevalent H1N1 variants are antigenically different from those that circulated in the 1950s; however, older adults readily acquire immunity to these new variants--perhaps as a result of immunologic priming that occurred in childhood.

Duration of hospitalization in previously well infants with respiratory syncytial virus infection.

To describe the typical hospital course of infection in previously well infants hospitalized with respiratory syncytial virus (RSV) infection, we reviewed the charts of 196 patients with laboratory-proved respiratory syncytial virus infection in the 1987-1988 respiratory disease season. Eighty-seven of the children had been previously well. Their mean duration of hospitalization was 3.4 days. Previously well infants younger than 6 weeks of age experienced significantly longer hospitalizations and more days of supplemental oxygen and were more likely to require intensive care than were older children. Children older than 12 weeks of age were hospitalized for a mean of 2.5 days and did not require intensive care. Oxygen saturation was measured in the emergency room for 67 of the previously well infants; in 42 oxygen saturation was at least 90% whereas in 25 saturation was less than 90% or infants were receiving supplemental oxygen at the time of measurement. Decreased initial oxygen saturation was associated with a prolonged hospitalization (5.3 vs. 3.2 days, P less than 0.01) and with more days of supplemental oxygen (4.4 vs. 1.5 days, P less than 0.01). We conclude that among previously well infants admitted to the hospital with respiratory syncytial virus infection, infants younger than 6 weeks of age are at increased risk for a prolonged and more severe hospital course than are older children.

The influenza herald wave.

For three successive years (1976-1979), the community surveillance system of the Influenza Research Center identified a wave of influenza virus infections which occurred during the latter half of one epidemic period and which heralded the epidemic virus for the following year. Recognition of the herald waves required consistent and continuous sampling of respiratory illnesses occurring among persons who constituted a substantial proportion of the population of over two million people in Harris County, TX. The herald wave infections consisted of only 0.4-2.0% of the 2500 to 3000 respiratory illnesses examined for virus. During the first two epidemic periods, the herald wave was easily detected as a wave of influenza B virus infections occurring during an influenza A virus epidemic and then a wave of influenza A virus infections during an influenza B virus epidemic. The third herald wave was obscured because it consisted of a small number of infections caused by viruses antigenically like A/Brazil/11/78(H1N1) which occurred at the end of the outbreak caused by influenza A/USSR/90/77 (H1N1). The herald wave infections were detected among persons who lived in widely scattered areas of the county and who were representative of all age and socioeconomic groups. the herald wave phenomenon has the obvious benefit of providing information about the virus most likely to produce an epidemic during the next respiratory disease season. Under optimal conditions, this could allow six to nine months to prepare and administer control measures.

Mortality and influenza.

Systematic virologic surveillance in Houston over the past seven years has revealed that influenza virus infections have been epidemic during each respiratory disease season. The peak of the occurrence of acute respiratory illnesses that caused patients to seek medical care always coincided with the peak of influenza virus activity. The peak number of deaths attributed to pneumonia or influenza followed the peak of influenza virus activity by about two weeks. This relationship was constant even though the time of the epidemic peak ranged from as early as the third week of December to as late as the second week of March. No increase in deaths occurred in the absence of influenza virus activity. Therefore, the methods used to predict base-line mortality that show a seasonal rise in the absence of influenza activity may be inaccurate and, if so, lead to underestimation of mortality associated with influenza virus infections.

Influenza in children. Relationship to other respiratory agents.

During the 1975-1976 respiratory disease season, influenza A/Victoria virus exceeded respiratory syncytial (RS) virus as a cause of lower respiratory tract disease (LRD) in children admitted to the hospital. This was a reversal of their usual roles in the etiology of LRD; however, the importance of influenza viruses in causing serious disease in children has been underestimated because of failure to appreciate the full spectrum of disease associated with influenza virus infections. In addition to those with LRD, several children were hospitalized with nonspecific febrile illnesses or CNS involvement. Furthermore, in the ambulatory care setting, influenza viruses were the most important cause of illness that necessitated children's being brought for medical care during a three-year period. During the peak of epidemics, influenza viruses appeared to interfere with the spread of other major respiratory viruses--particularly RS virus.

Epidemiologic observations of influenza B virus infections in Houston, Texas, 1976-1977.

Influenza B virus infections were documented in Houston, Texas, in 726 patients with febrile respiratory illnesses who presented to representative primary care facilities during the 1976-1977 respiratory disease season. This epidemic followed a "herald wave" of illness associated with influenza B during the preceding spring. Over one-half the virus isolates were from children aged 5-19 years, and school absenteeism rates indicated that about 40 per cent of the students in the Houston area were ill enough to miss school during the epidemic. The rapid rise in the number of cases among students after the school holiday recess demonstrated the importance of school attendance for the rapid dissemination of influenza viruses. During the later phase of the epidemic, most of the cases were preschool children and adults. In addition to disease of the respiratory tract, the epidemic was accompanied by cases of Reye's syndrome at a rate expected for an urban area.

Influenza Prophylaxis for Children

During the last ten years most communities in the United States have experienced at least 11 outbreaks of influenza virus infections. Beginning with the last influenza A virus epidemic of the H2N2 (designates the major surface antigens of influenza A viruses, H for hemagglutinin and N for neuraminidase) (Asian) era in the winter of 1967-1968, we have been assaulted during almost every respiratory disease season with either influenza A or B viruses and on one or two occasions, depending on location, both viruses. Viruses of the influenza A/Hong Kong family (H3N2) first appeared in late 1968 and have produced epidemics with excess mortality on six occasions through the winter of 1976. Influenza B viruses have caused outbreaks in most localities during four different years, including the current one (1977). All of these epidemics produced notable morbidity in the pediatric age group and resulted in hospitalization of many children.

Influenza B in the spring of 1965.

SummaryStrains of influenza B virus recovered from children who had acute respiratory illnesses during the spring of 1965 showed antigenic deviation from the B/Md/ 1/59 strain of influenza virus. This finding was most evident in comparative hemagglu-tination-inhibition tests with chicken antisera but was also shown in the relatively poor antibody response against 1965 B strains compared with homologous virus in children who were given 3 doses of a heptavalent respiratory virus vaccine containing B/Md/1/59 antigen. Further evidence was given in the demonstration of less than expected efficacy of the vaccine in protecting children against influenza B in 1965 in a controlled field study. Sera from normal adults collected in June of 1965 often showed low antibody titers and this was consistent with the sporadic occurrence of influenza B which was recorded in the U.S.A. during the 1964-65 respiratory disease season. The findings in the study may be of value as a guideline for judging the significance of future...

Carrier Rates of Staphylococci in Preschool and School-Age Children-Reply

<h3>To the Editor:—</h3> 1. As the study took place over a 9-month period, not all children were treated with antibiotics at one time. At any one time, some children were in pretreatment status, some were undergoing treatment, and some were in post-treatment status. The largest number were under treatment during the height of the respiratory disease season. It was the fact of antibiotic therapy which led to "seasonal variation," as the carrier rates of staphylococci did not vary during the year among children not receiving antibiotics. 2. The data presented do show a greater number of persistent carriers among school-aged children than among preschool-aged children. It might be true, therefore, that antibiotics tend to produce greater or lesser effects upon one particular age group than upon another, but such could not be demonstrated in the present study. There did seem to be greater acquisition rates following the use of antibiotics

Effects of adenovirus vaccine on acute respiratory disease in U. S. Army recruits.

During the developmental period of the adenovirus vaccine, field trials of bivalent Types 4 and 7 vaccine conducted by the Army Medical Service in 1956 and 1957 resulted in 90% to 98% reduction in hospitalization due to adenovirus disease in recruits. During the respiratory disease season of 1960-1961, a standardized, commercially prepared, Types 4 and 7 vaccine was used at all recruit training stations. Preliminary results indicate that this vaccine was about 50% effective in reducing hospitalization resulting from adenovirus disease. It is evident from the earlier experience that, even though the commercial vaccine now being used is estimated to have saved the Army about $5,000,000 during the last respiratory disease season, there is an urgent requirement to make available adenovirus vaccine of greater antigenicity.

Clinical Trial of Gamma Globulin in the Prevention of Common Respiratory Diseases

SummaryConcentrated gamma globulin was administered at monthly intervals to one-half of a group of 70 medical students throughout a single respiratory disease season from early October to late May. The incidence of attacks of acute respiratory disease was reduced 40% in the experimental subjects as compared with the controls. The severity of the illnesses was significantly decreased in the experimental subjects as compared with their previous season experience.The reactions to the injections were mild and consisted primarily of local soreness at the site, lasting one day in the majority of the students. No jaundice of hepatitis was observed.The primary object of this small clinical trial of concentrated gamma globulin was not to discover a method of preventing colds, but to determine if possible, whether or not man is capable of forming neutralizing substances for some of the undifferentiated respiratory diseases. A cumulative effect of repeated injections was suggested by the results.A statistical evalua...