Reported Attack Rates Research Articles

RAPID AND SUSTAINED REDUCTIONS IN HEREDITARY ANGIOEDEMA ATTACK RATES WITH LONG-TERM BEROTRALSTAT: REAL-WORLD OUTCOMES

<h3>Introduction</h3> Berotralstat, an oral once-daily prophylactic treatment for hereditary angioedema (HAE), has demonstrated sustained reduction in HAE attack rates and improvements in patient-reported quality of life in clinical trials. Here we present the preliminary efficacy data of patients in the United States receiving berotralstat in the real-world clinical setting. <h3>Methods</h3> This analysis is data collected through the sole-source pharmacy and included patients with confirmed HAE Type I/II based on laboratory tests and actively received berotralstat 110 or 150mg from 12/16/2020 to 5/20/22 for >270 days. Baseline attack rates were reported for the 90 days prior to berotralstat initiation. While on therapy, median attacks/month (25^th,75^th percentile) were calculated over each 90-day period by averaging each patient's monthly reported attack rate (1 month=∼28 days). Some patients did not report attack rates at each refill. <h3>Results</h3> In the patients who actively received berotralstat for >270 days (n=128) the median baseline attack rate was 1.7 attacks/month. A rapid reduction in median monthly attack rates was observed after starting berotralstat. During the first 90 days on therapy (days 1-90) the median monthly attack rate decreased to 0.3 (0,1.50) attacks/month; 0.5 (0,1.00) attacks/month from days 91-180; 0.3 (0,1.25) attacks/month from days 181-270; and 0.3 (0,1.25) attacks/month from days 271-360. The most common adverse events reported were consistent with clinical trials. <h3>Conclusions</h3> This data shows that berotralstat provided a rapid and sustained reduction in HAE attack rates within the first months of starting therapy making oral berotralstat an effective treatment option for patients with HAE.

CONSISTENTLY LOW HEREDITARY ANGIOEDEMA ATTACK RATES OBSERVED WITH BEROTRALSTAT REGARDLESS OF PREVIOUS PROPHYLAXIS: REAL-WORLD OUTCOMES

<h3>Introduction</h3> Clinical trial data showed patients who switched to oral berotralstat monotherapy reported consistently low hereditary angioedema (HAE) attack rates. Here we present preliminary efficacy data of patients in the United States who initiated berotralstat treatment in the real-world clinical setting and were previously on another prophylactic therapy. <h3>Methods</h3> Data was collected through the sole-source pharmacy and included patients with confirmed HAE Type I/II who actively received berotralstat 110 or 150mg from 12/16/2020-5/20/22 and were stratified by previous prophylaxis. Baseline attack rates were reported for the 90 days prior to berotralstat initiation. While on therapy, median attacks/month(25^th,75^th percentile) were calculated over each 90-day period by averaging each patient's monthly reported attack rate (1 month=∼28 days). Some patients did not report attack rates at each refill. <h3>Results</h3> In patients treated with prior prophylaxis(n=129) the median baseline attack rate was 1.7 attacks/month which decreased to 0.3(0,1.31) from days 1-90; 0.6(0,1.00) from days 91-180; 0.5(0.25,1.00) from days 181-270; and 0.5(0,1.50) from days 271-360. Specifically, in the lanadelumab group(n=53), the baseline attack rate of 1.0 attack/month decreased to 0(0,0.50) from days 1-90; 0.3(0,0.75) from 91-180; 0.5(0,1.00) from 181-270; and 0.5(0,1.38) from 271-360. In the subcutaneous C1-inhibitor group(n=31), the baseline attack rate of 1.7 attacks/month decreased to 0.8(0,2.00) from days 1-90; 0.7(0,2.08) from 91-180; 1.0(0.54,1.50) from 181-270; and 1.0(0.29,2.17) from 271-360. Patients without prior prophylaxis(n=112) had similar attack rate reductions. The most common adverse events reported were consistent with clinical trials. <h3>Conclusions</h3> Patients previously treated with another prophylactic therapy reported consistently low HAE attack rates when treated with once daily berotralstat.

Transmission of SARS-CoV-2 Associated with Cruise Ship Travel: A Systematic Review.

Background: Maritime and river travel may be associated with respiratory viral spread via infected passengers and/or crew and potentially through other transmission routes. The transmission models of SARS-CoV-2 associated with cruise ship travel are based on transmission dynamics of other respiratory viruses. We aimed to provide a summary and evaluation of relevant data on SARS-CoV-2 transmission aboard cruise ships, report policy implications, and highlight research gaps. Methods: We searched four electronic databases (up to 26 May 2022) and included studies on SARS-CoV-2 transmission aboard cruise ships. The quality of the studies was assessed based on five criteria, and relevant findings were reported. Results: We included 23 papers on onboard SARS-CoV-2 transmission (with 15 reports on different aspects of the outbreak on Diamond Princess and nine reports on other international cruises), 2 environmental studies, and 1 systematic review. Three articles presented data on both international cruises and the Diamond Princess. The quality of evidence from most studies was low to very low. Index case definitions were heterogeneous. The proportion of traced contacts ranged from 0.19 to 100%. Studies that followed up >80% of passengers and crew reported attack rates (AR) up to 59%. The presence of a distinct dose–response relationship was demonstrated by findings of increased ARs in multi-person cabins. Two studies performed viral cultures with eight positive results. Genomic sequencing and phylogenetic analyses were performed in individuals from three cruises. Two environmental studies reported PCR-positive samples (cycle threshold range 26.21–39.00). In one study, no infectious virus was isolated from any of the 76 environmental samples. Conclusion: Our review suggests that crowding and multiple persons per cabin were associated with an increased risk of transmission on cruise ships. Variations in design, methodology, and case ascertainment limit comparisons across studies and quantification of transmission risk. Standardized guidelines for conducting and reporting studies on cruise ships of acute respiratory infection transmission should be developed.

Modes of transmission and attack rates of group A Streptococcal infection: a protocol for a systematic review and meta-analysis

BackgroundGroup A Streptococcus (Strep A) is an important cause of mortality and morbidity globally. This bacterium is responsible for a range of different infections and post-infectious sequelae. Summarising the current knowledge of Strep A transmission to humans will address gaps in the evidence and inform prevention and control strategies. The objective of this study is to evaluate the modes of transmission and attack rates of group A streptococcal infection in human populations.MethodsThis systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-analysis Protocols (PRISMA-P) 2015 Statement. Using a comprehensive search strategy to identify any transmission studies that have been published in English since 1980, full-text articles will be identified and considered for inclusion against predefined criteria. We will include all studies reporting on Strep A transmission, who have identified a mode of transmission, and who reported attack rates. Risk of bias will be appraised using an appropriate tool. Our results will be described narratively and where feasible and appropriate, a meta-analysis utilizing the random-effects model will be used to aggregate the incidence proportions (attack rates) for each mode of transmission. In addition, we will also evaluate the emm genotype variants of the M protein causing Strep A infection and the association with transmission routes and attack rates, if any, by setting, socioeconomic background and geographical regions.DiscussionWe anticipate that this review will contribute to elucidating Strep A modes of transmission which in turn, will serve to inform evidence-based strategies including environmental health activities to reduce the transmission of Strep A in populations at risk of severe disease.Trial registrationSystematic review registration: PROSPERO (CRD42019138472).

Epidemiology and burden of illness of seasonal influenza among the elderly in Japan: A systematic literature review and vaccine effectiveness meta-analysis.

BackgroundElderly populations are particularly vulnerable to influenza and often require extensive clinical support. In Japan, nationwide passive surveillance monitors seasonal influenza but does not capture the full disease burden. We synthesized existing evidence on the epidemiology, vaccine effectiveness (VE), and economic burden of seasonal influenza in the elderly population.MethodsPubMed, EMBASE, and ICHUSHI were searched for articles on seasonal influenza in Japan, published between 1997 and 2018, in English or Japanese. Grey literature was also assessed. A random‐effects meta‐analysis characterized VE of influenza vaccines among studies reporting this information.ResultsOf 1,147 identified articles, 143 met inclusion criteria. Reported incidence rates varied considerably depending on study design, season, study setting and, most importantly, case definition. In nursing homes, the maximum reported attack rate was 55.2% and in the 16 articles reporting mortality rates, case fatality rates varied from 0.009% to 14.3%. Most hospitalizations were in people aged >60; healthcare costs were partially mitigated by vaccine administration. Meta‐analysis estimated overall VE of 19.1% (95% CI: 2.3% ‐ 33.0%) with a high proportion of heterogeneity (I2: 89.1%). There was a trend of lower VE in older people (40.1% [−57.3‐77.2] in the <65 group; 12.9% [−8.0‐29.8] in those 65; P = .21).ConclusionsDespite differences between studies that make comparisons challenging, the influenza burden in elderly Japanese is significant. While vaccines are effective, current vaccination programs offer suboptimal protection. Health economic data and cost‐effectiveness analyses were limited and represent areas for policy‐relevant future research.

Airborne or Fomite Transmission for Norovirus? A Case Study Revisited.

Norovirus infection, a highly prevalent condition associated with a high rate of morbidity, comprises a significant health issue. Although norovirus transmission mainly occurs via the fecal-oral and vomit-oral routes, airborne transmission has been proposed in recent decades. This paper re-examines a previously described norovirus outbreak in a hotel restaurant wherein airborne transmission was originally inferred. Specifically, the original evidence that suggested airborne transmission was re-analyzed by exploring an alternative hypothesis: could this outbreak instead have occurred via fomite transmission? This re-analysis was based on whether fomite transmission could have yielded similar attack rate distribution patterns. Seven representative serving pathways used by waiters were considered, and the infection risk distributions of the alternative fomite transmission routes were predicted using a multi-agent model. These distributions were compared to the reported attack rate distribution in the original study using a least square methods approach. The results show that with some reasonable assumptions of human behavior patterns and parameter values, the attack rate distribution corresponded well with that of the infection risk via the fomite route. This finding offers an alternative interpretation of the transmission routes that underlay this particular norovirus outbreak and an important consideration in the development of infection control guidelines and the investigation of similar norovirus outbreaks in future.

A study of the probable transmission routes of MERS-CoV during the first hospital outbreak in the Republic of Korea.

Infections caused by the Middle East respiratory syndrome coronavirus (MERS‐CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS‐CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi‐agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long‐range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi‐agent modeling framework. Least‐squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super‐spreader, our model simulations suggested that MERS‐CoV probably spread via the long‐range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long‐range airborne and close contact route.

Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong.

The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission.

Influenza control in Australian prison settings: Cost ‐ benefit analysis of major strategies

Repeated influenza outbreaks are surprisingly rare in prison settings worldwide, a factor that has made it superfluous, to date, to develop contingency plans for responding to prison‐based influenza epidemics. However, the influenza outbreak that occurred in an Australian prison in 2000 has highlighted the appropriateness of developing an outbreak plan, not least because of the security implications of a widespread prison influenza epidemic. Using reported attack rates and morbidity profiles of the 2000 Australian prison influenza outbreak to develop scenarios, the authors estimated the cost ‐ benefit of mass vaccination and antiviral chemotherapy approaches for the control of hypothetical widespread influenza outbreaks in New South Wales prisons, occurring at an average frequency of once every 10 years. It was concluded that, from the perspectives of maintaining prison security as well as health care services’ provision to prisoners, early antiviral chemotherapy for symptomatic individuals will have more favourable cost ‐ benefit ratios than a mass vaccination approach for controlling prison‐based influenza outbreaks that occur in line with this model.

Management of acute diarrhea in children

Each year diarrheal disease causes an estimated 3.2 million deaths worldwide in children under 5 years of age. Reported attack rates in developing countries range from 1 to 12 episodes per child per year, with a global average of 3 episodes per child per year. Diarrhea is associated with 1/4 of all deaths in children under 5 years in developing countries. Oral rehydration therapy (ORT) is the cornerstone of global efforts to reduce mortality from acute diarrhea. The World Health Organization (WHO)/UNICEF ORS formula contains glucose and sodium in a molar ratio of 1.2:1. Potassium chloride is added to replace potassium lost in the stool. Trisodium citrate dihydrate (or sodium bicarbonate) corrects metabolic acidosis caused by fecal loss of bicarbonate. The WHO case management strategy for children with diarrhea consists of: prevention of dehydration through early administration of appropriate fluids available in the home; treatment of dehydration with ORS solution; treatment of severe dehydration with an intravenous electrolyte solution; continued feeding during, and increased feeding after the diarrheal episode; and selective use of antibiotics and nonuse of antidiarrheal drugs. The WHO/UNICEF formula is also suitable as a maintenance fluid when given with equal amounts of water, breast milk, or low carbohydrate juice. Despite the unquestioned success of ORT in developing countries, physicians in the United States, the United Kingdom, and other industrialized countries have been slow to adopt ORT. Guidelines for case management call for patient assessment. The physician evaluating a child with diarrhea should inquire about clinical features including its duration and the presence of blood in the stool. Thus, a reliable treatment plan can be made without need of laboratory tests. Most diarrheal episodes are self-limited and do not benefit from antimicrobial therapy. Children with bloody diarrhea should be treated for suspected shigellosis with an oral antibiotic.

Results of the First Pilot‐Scale Controlled Cohort Epidemiological Investigation into the Possible Health Effects of Bathing in Seawater at Langland Bay, Swansea

AbstractA pilot study was conducted to investigate the feasibility of using adult volunteers to examine the possible health effects of bathing in UK seawaters which passed the EC bathing waters Directive. Langland Bay, near Swansea, was chosen for this experiment, which was conducted on 2 September 1989. Adult volunteers were recruited from the City of Swansea and randomly divided into bather and non‐bather groups. All volunteers were given medical examinations and medical questionnaire interviews before and after 2 September.Water quality on the day of the test was relatively unpolluted, as indexed by the commonly‐employed bacterial and viral indicator species. The detailed medical questionnaire resulted in higher reported attack rates of perceived illness in both bather and non‐bather groups than those published in previous studies, which have commonly employed a single telephone interview to acquire disease perception data. Statistically‐significant differences in the bather and non‐bather cohorts were found for the following perceived symptoms: sore throat, ear symptom, eye symptom at 3 d after 2 September, and for diarrhoea at three weeks after the experiment. The clinical tests employed failed to confirm these significant perceived symptom attack rate differentials.The significance of these results is discussed in the context of previous research protocols to demonstrate the feasibility of this novel prospective controlled cohort approach for the acquisition of scientifically robust data on the health effect of recreational water use. If taken to a full‐scale study, it is argued that this research protocol could offer considerable advantages over past methods and lead to scientifically valid water‐quality standards for recreational waters.

Group B Streptococcal Infections in Neonates

β-Hemolytic streptococci of Lancefield group B have been causally linked to neonatal disease since 1938, but only in the last decade has the group B Streptococcus become the leading etiologic agent for bacteremia and/or meningitis occurring during the first two months of life. Neither the reasons for the emergence of this organism nor the shifts over the past 40 years in the prevalence of various bacteria responsible for neonatal infection has been adequately explained. However, the importance of the group B Streptococcus as a frequent cause of neonatal mortality and morbidity demands a thorough understanding of the epidemiology and pathogenesis, clinical features, diagnostic methods, and management of these infections by physicians caring for newborn infants.INCIDENCEThe common occurrence of neonatal group B streptococcal septicemia and meningitis in several geographically distant centers since 1970 has allowed the relatively precise determination of attack rates for early onset type (≤5 days) infection. Reported attack rates have been surprisingly uniform, varying from 1.3/1,000 to 4.0/1,000 live births (Table 1). Because the attack rates for serious neonatal infections associated with Escherichia coli and other maternally acquired coliform organisms have been constant since 1960, the appearance of the group B Streptococcus resulted in an absolute increase in the incidence of neonatal bacterial disease during the past decade in many hospitals in this country.

Group B Streptococcal Infections in Neonates

β-Hemolytic streptococci of Lancefield group B have been causally linked to neonatal disease since 1938, but only in the last decade has the group B Streptococcus become the leading etiologic agent for bacteremia and/or meningitis occurring during the first two months of life. Neither the reasons for the emergence of this organism nor the shifts over the past 40 years in the prevalence of various bacteria responsible for neonatal infection has been adequately explained. However, the importance of the group B Streptococcus as a frequent cause of neonatal mortality and morbidity demands a thorough understanding of the epidemiology and pathogenesis, clinical features, diagnostic methods, and management of these infections by physicians caring for newborn infants. INCIDENCE The common occurrence of neonatal group B streptococcal septicemia and meningitis in several geographically distant centers since 1970 has allowed the relatively precise determination of attack rates for early onset type (≤5 days) infection. Reported attack rates have been surprisingly uniform, varying from 1.3/1,000 to 4.0/1,000 live births (Table 1). Because the attack rates for serious neonatal infections associated with Escherichia coli and other maternally acquired coliform organisms have been constant since 1960, the appearance of the group B Streptococcus resulted in an absolute increase in the incidence of neonatal bacterial disease during the past decade in many hospitals in this country.

A Foodborne Outbreak of Shigellosis on an Indian Reservation

FOODBORNE OUTBREAKS of shigellosis are not often reported in the U.S. literature. In 1967 a total of 273 foodborne outbreaks from all causes was reported to the National Communicable Disease Center, Public Health Service (1). Of these, only seven (2.2 percent) were attributed to the Shigella species. Much more common were outbreaks due to Salmonella, Clostridiuam perfringenm, and Staphylococcus. In only two of the seven Shiqella outbreaks was the vehicle designated as food (unnamed), in two it was water, and in the remaining three it was unknown. Several reports in earlier literature specified food as the vehicle for Shigella outbreaks, including three in which potato salad was implicated (2-4). Shigellosis, via all modes of transmission, is prevalent on Indian reservations. During the last 6 months of 1967, the reported attack rate among Indians was 171.5 per 100,000 or 52 times the reported attack rate for the entire U.S. population, which was 3.3 per 100,000 (5). An outbreak of shigellosis occurred in April 1968 after a church dinner on the Yakima Indian Reservation. Potato salad was identified epidemiologically as the vehicle of infection and Shigella flqexneri as the etiological agent. The serotype responsible for the outbreak is unknown.

Susceptibility to serum hepatitis. Effect of time and temperature upon attack rates of iceterogenic plasma and serum.

Reported attack rates from different batches of icterogenic serum-containing material administered parenterally vary considerably one from another, as shown in Table 1. These data were selected because they represent essentially complete follow-up studies on all known individuals receiving units of icterogenic substances from the common lots indicated. Specificity of Attack Rates Are the above differences in attack rates due more to volume of icterogenic material administered than to concentration of virus particles (assuming no difference in the qualitative capacity of a viable virus particle to infect), or is there a wide variation in the natural or acquired immunity (or both) in an otherwise fairly homogeneous healthy population? The only existing body of data large enough to be usefully applied to these questions is contained in the carefully prepared follow-up studies of Sawyer et al. (1944) on the outbreaks of serum hepatitis following the administration of 2 batches of the serum-containing