Costs and cost-effectiveness of influenza illness and vaccination in low- and middle-income countries: A systematic review from 2012 to 2022.

BACKGROUND: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness; (2) costs of influenza vaccination programs; and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist that could hinder global implementation of influenza vaccination programs. METHODS AND FINDINGS: We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus in January 2022 and October 2023 using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2022. Studies were eligible if they (1) presented original, peer-reviewed findings on cost of illness, cost of vaccination program, or cost-effectiveness of vaccination for seasonal influenza; and (2) included data for at least 1 low- or middle-income country. We abstracted general study characteristics and data specific to each of the 3 study types. Of 54 included studies, 26 presented data on cost-effectiveness, 24 on cost-of-illness, and 5 on program costs. Represented countries were classified as upper-middle income (UMIC; n = 12), lower-middle income (LMIC; n = 7), and low-income (LIC; n = 3). The most evaluated target groups were children (n = 26 studies), older adults (n = 17), and persons with chronic medical conditions (n = 12); fewer studies evaluated pregnant persons (n = 9), healthcare workers (n = 5), and persons in congregate living settings (n = 1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest national economic burden, as a percent of gross domestic product and national health expenditure, was reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (88%) interpreted at least 1 scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Key limitations of this work included (1) heterogeneity across included studies; (2) restrictiveness of the inclusion criteria used; and (3) potential for missed influenza burden from use of sentinel surveillance systems. CONCLUSIONS: The 54 studies identified in this review suggest an increased momentum to generate economic evidence about influenza illness and vaccination from low- and middle-income countries during 2012 to 2022. However, given that we observed substantial heterogeneity, continued evaluation of the economic burden of influenza illness and costs/cost-effectiveness of influenza vaccination, particularly in LICs and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed. Use of standardized methodology could facilitate pooling across settings and knowledge sharing to strengthen global influenza vaccination programs.

Vaccine Effectiveness of CanSino (Adv5-nCoV) Coronavirus Disease 2019 (COVID-19) Vaccine Among Childcare Workers-Mexico, March-December 2021.

BACKGROUND: Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) coronavirus disease 2019 (COVID-19) vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE). METHODS: We evaluated CanSino VE within a childcare worker cohort that included 1408 childcare facilities. Participants were followed during March-December 2021 and tested through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% × (1 - hazard ratio for SARS-CoV-2 infection in fully vaccinated vs unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation. RESULTS: The cohort included 43 925 persons who were mostly (96%) female with a median age of 32 years; 37 646 (86%) were vaccinated with CanSino. During March-December 2021, 2250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% confidence interval [CI], 10%-29%) against illness, 76% (95% CI, 42%-90%) against hospitalization, and 94% (95% CI, 66%-99%) against death. VE against illness declined from 48% (95% CI, 33%-61%) after 14-60 days following full vaccination to 20% (95% CI, 9%-31%) after 61-120 days. CONCLUSIONS: CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes.

Azithromycin and Ciprofloxacin Treatment Outcomes During an Outbreak of Multidrug-Resistant Shigella sonnei Infections in a Retirement Community-Vermont, 2018.

BACKGROUND: In 2018, the Centers for Disease Control and Prevention and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin. METHODS: To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms. RESULTS: Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, 4 were treated with azithromycin; all had clinical treatment failure and 2 also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; 2 patients failed treatment with ciprofloxacin. CONCLUSIONS: These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations.

Multistate Outbreak of SARS-CoV-2 Infections, Including Vaccine Breakthrough Infections, Associated with Large Public Gatherings, United States.

During July 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 variant infections, including vaccine breakthrough infections, occurred after large public gatherings in Provincetown, Massachusetts, USA, prompting a multistate investigation. Public health departments identified primary and secondary cases by using coronavirus disease surveillance data, case investigations, and contact tracing. A primary case was defined as SARS-CoV-2 detected <14 days after travel to or residence in Provincetown during July 3-17. A secondary case was defined as SARS-CoV-2 detected <14 days after close contact with a person who had a primary case but without travel to or residence in Provincetown during July 3-August 10. We identified 1,098 primary cases and 30 secondary cases associated with 26 primary cases among fully and non-fully vaccinated persons. Large gatherings can have widespread effects on SARS-CoV-2 transmission, and fully vaccinated persons should take precautions, such as masking, to prevent SARS-CoV-2 transmission, particularly during substantial or high transmission.

Epidemiology and Clinical Characteristics of Primary Amebic Meningoencephalitis Caused by Naegleria fowleri: A Global Review.

BACKGROUND: Primary amebic meningoencephalitis (PAM) is a rapidly progressive and often fatal condition caused by the free-living ameba Naegleria fowleri. To estimate the global occurrence, characterize the epidemiology, and describe the clinical features of PAM, we report a series of PAM cases published in the international literature and reported to the Centers for Disease Control and Prevention (CDC). METHODS: We performed a literature search of PAM case reports published through 2018. Additionally, we included cases reported through the CDC's Free-Living Ameba surveillance or diagnosed via CDC's Free-Living and Intestinal Amebas Laboratory. Cases were classified as confirmed, probable, or suspect on the basis of confirmatory testing, presentation, exposure, and disease course. RESULTS: A total of 381 PAM cases were identified. Seven reported survivors were classified as confirmed. The most commonly reported exposure associated with PAM was swimming/diving, and the most common class of water source was lakes/ponds/reservoirs. Patients were predominantly male (75%), with a median age of 14 years. Confirmed and probable cases were similar in their survival, course of illness, and cerebrospinal fluid (CSF) findings. CONCLUSIONS: PAM is a rare but deadly disease with worldwide occurrence. Improved clinician awareness, resulting in earlier diagnosis and treatment, may contribute to increased survival among PAM patients. The case definition of probable used in this study appears to capture cases of PAM, as evidenced by similarities in outcomes, clinical course, and CSF profile to confirmed cases. In the absence of confirmatory testing, clinicians could use this case definition to identify cases of PAM.

Loss of Taste and Smell as Distinguishing Symptoms of Coronavirus Disease 2019.

In a household study, loss of taste and/or smell was the fourth most reported symptom (26/42 [62%]) among coronavirus disease 2019 (COVID-19) case patients and had the highest positive predictive value (83% [95% confidence interval [CI], 55%-95%) among household contacts. Olfactory and taste dysfunctions should be considered for COVID-19 case identification and testing prioritization.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 in the United States.

BACKGROUND: The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. METHODS: We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020-25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. RESULTS: Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%-36%) overall, 42% among children (aged <18 years) of the COVID-19 patient and 33% among spouses/partners. Household contacts to COVID-19 patients with immunocompromised conditions and household contacts who themselves had diabetes mellitus had increased odds of infection with ORs 15.9 (95% CI, 2.4-106.9) and 7.1 (95% CI: 1.2-42.5), respectively. CONCLUSIONS: We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.

A Prospective Cohort Study in Nonhospitalized Household Contacts With Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Symptom Profiles and Symptom Change Over Time.

BACKGROUND: Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection. METHODS: From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time. RESULTS: We identified 47 contacts, median age 24 (3-75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 [68%]) and neurologic (n = 30 [64%]); fever was not commonly reported (n = 9 [19%]). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for <18, 18-49, and ≥50 years of age, respectively; P = .03). CONCLUSIONS: Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.

Geographic Range of Recreational Water-Associated Primary Amebic Meningoencephalitis, United States, 1978-2018.

Naegleria fowleri is a free-living ameba that causes primary amebic meningoencephalitis (PAM), a rare but usually fatal disease. We analyzed trends in recreational water exposures associated with PAM cases reported during 1978-2018 in the United States. Although PAM incidence remained stable, the geographic range of exposure locations expanded northward.

Early COVID-19 First-Dose Vaccination Coverage Among Residents and Staff Members of Skilled Nursing Facilities Participating in the Pharmacy Partnership for Long-Term Care Program - United States, December 2020-January 2021.

Residents and staff members of long-term care facilities (LTCFs), because they live and work in congregate settings, are at increased risk for infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1,2). In particular, skilled nursing facilities (SNFs), LTCFs that provide skilled nursing care and rehabilitation services for persons with complex medical needs, have been documented settings of COVID-19 outbreaks (3). In addition, residents of LTCFs might be at increased risk for severe outcomes because of their advanced age or the presence of underlying chronic medical conditions (4). As a result, the Advisory Committee on Immunization Practices has recommended that residents and staff members of LTCFs be offered vaccination in the initial COVID-19 vaccine allocation phase (Phase 1a) in the United States (5). In December 2020, CDC launched the Pharmacy Partnership for Long-Term Care Program* to facilitate on-site vaccination of residents and staff members at enrolled LTCFs. To evaluate early receipt of vaccine during the first month of the program, the number of eligible residents and staff members in enrolled SNFs was estimated using resident census data from the National Healthcare Safety Network (NHSN†) and staffing data from the Centers for Medicare & Medicaid Services (CMS) Payroll-Based Journal.§ Among 11,460 SNFs with at least one vaccination clinic during the first month of the program (December 18, 2020-January 17, 2021), an estimated median of 77.8% of residents (interquartile range [IQR] = 61.3%- 93.1%) and a median of 37.5% (IQR = 23.2%- 56.8%) of staff members per facility received ≥1 dose of COVID-19 vaccine through the Pharmacy Partnership for Long-Term Care Program. The program achieved moderately high coverage among residents; however, continued development and implementation of focused communication and outreach strategies are needed to improve vaccination coverage among staff members in SNFs and other long-term care settings.

Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings - Barnstable County, Massachusetts, July 2021.

During July 2021, 469 cases of COVID-19 associated with multiple summer events and large public gatherings in a town in Barnstable County, Massachusetts, were identified among Massachusetts residents; vaccination coverage among eligible Massachusetts residents was 69%. Approximately three quarters (346; 74%) of cases occurred in fully vaccinated persons (those who had completed a 2-dose course of mRNA vaccine [Pfizer-BioNTech or Moderna] or had received a single dose of Janssen [Johnson & Johnson] vaccine ≥14 days before exposure). Genomic sequencing of specimens from 133 patients identified the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, in 119 (89%) and the Delta AY.3 sublineage in one (1%). Overall, 274 (79%) vaccinated patients with breakthrough infection were symptomatic. Among five COVID-19 patients who were hospitalized, four were fully vaccinated; no deaths were reported. Real-time reverse transcription-polymerase chain reaction (RT-PCR) cycle threshold (Ct) values in specimens from 127 vaccinated persons with breakthrough cases were similar to those from 84 persons who were unvaccinated, not fully vaccinated, or whose vaccination status was unknown (median = 22.77 and 21.54, respectively). The Delta variant of SARS-CoV-2 is highly transmissible (1); vaccination is the most important strategy to prevent severe illness and death. On July 27, CDC recommended that all persons, including those who are fully vaccinated, should wear masks in indoor public settings in areas where COVID-19 transmission is high or substantial.* Findings from this investigation suggest that even jurisdictions without substantial or high COVID-19 transmission might consider expanding prevention strategies, including masking in indoor public settings regardless of vaccination status, given the potential risk of infection during attendance at large public gatherings that include travelers from many areas with differing levels of transmission.

Demographic and Social Factors Associated with COVID-19 Vaccination Initiation Among Adults Aged ≥65 Years - United States, December 14, 2020-April 10, 2021.

Compared with other age groups, older adults (defined here as persons aged ≥65 years) are at higher risk for COVID-19-associated morbidity and mortality and have therefore been prioritized for COVID-19 vaccination (1,2). Ensuring access to vaccines for older adults has been a focus of federal, state, and local response efforts, and CDC has been monitoring vaccination coverage to identify and address disparities among subpopulations of older adults (2). Vaccine administration data submitted to CDC were analyzed to determine the prevalence of COVID-19 vaccination initiation among adults aged ≥65 years by demographic characteristics and overall. Characteristics of counties with low vaccination initiation rates were quantified using indicators of social vulnerability data from the 2019 American Community Survey.* During December 14, 2020-April 10, 2021, nationwide, a total of 42,736,710 (79.1%) older adults had initiated vaccination. The initiation rate was higher among men than among women and varied by state. On average, counties with low vaccination initiation rates (<50% of older adults having received at least 1 vaccine dose), compared with those with high rates (≥75%), had higher percentages of older adults without a computer, living in poverty, without Internet access, and living alone. CDC, state, and local jurisdictions in partnerships with communities should continue to identify and implement strategies to improve access to COVID-19 vaccination for older adults, such as assistance with scheduling vaccination appointments and transportation to vaccination sites, or vaccination at home if needed for persons who are homebound.† Monitoring demographic and social factors affecting COVID-19 vaccine access for older adults and prioritizing efforts to ensure equitable access to COVID-19 vaccine are needed to ensure high coverage among this group.

Injection Drug Use-Associated Candidemia: Incidence, Clinical Features, and Outcomes, East Tennessee, 2014-2018.

BACKGROUND: Injection drug use (IDU) is an established but uncommon risk factor for candidemia. Surveillance for candidemia is conducted in East Tennessee, an area heavily impacted by the opioid crisis and IDU. We evaluated IDU-associated candidemia to characterize the epidemiology and estimate the burden. METHODS: We assessed the proportion of candidemia cases related to IDU during January 1, 2014-September 30, 2018, estimated candidemia incidence in the overall population and among persons who inject drugs (PWID), and reviewed medical records to compare clinical features and outcomes among IDU-associated and non-IDU candidemia cases. RESULTS: The proportion of IDU-associated candidemia cases in East Tennessee increased from 6.1% in 2014 to 14.5% in 2018. Overall candidemia incidence in East Tennessee was 13.5/100 000, and incidence among PWID was 402-1895/100 000. Injection drug use-associated cases were younger (median age, 34.5 vs 60 years) and more frequently had endocarditis (39% vs 3%). All-cause 30-day mortality was 8% among IDU-associated cases versus 25% among non-IDU cases. CONCLUSIONS: A growing proportion of candidemia in East Tennessee is associated with IDU, posing an additional burden from the opioid crisis. The lower mortality among IDU-associated cases likely reflects in part the younger demographic; however, Candida endocarditis seen among approximately 40% underscores the seriousness of the infection and need for prevention.

Large Outbreak of Guillain-Barré Syndrome, Peru, 2019.

Outbreaks of Guillain-Barré syndrome (GBS) are uncommon. In May 2019, national surveillance in Peru detected an increase in GBS cases in excess of the expected incidence of 1.2 cases/100,000 population. Several clinical and epidemiologic findings call into question the suggested association between this GBS outbreak and Campylobacter.

Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020.

A recent report described a sharp increase in calls to poison centers related to exposures to cleaners and disinfectants since the onset of the coronavirus disease 2019 (COVID-19) pandemic (1). However, data describing cleaning and disinfection practices within household settings in the United States are limited, particularly concerning those practices intended to prevent transmission of SARS-CoV-2, the virus that causes COVID-19. To provide contextual and behavioral insight into the reported increase in poison center calls and to inform timely and relevant prevention strategies, an opt-in Internet panel survey of 502 U.S. adults was conducted in May 2020 to characterize knowledge and practices regarding household cleaning and disinfection during the COVID-19 pandemic. Knowledge gaps were identified in several areas, including safe preparation of cleaning and disinfectant solutions, use of recommended personal protective equipment when using cleaners and disinfectants, and safe storage of hand sanitizers, cleaners, and disinfectants. Thirty-nine percent of respondents reported engaging in nonrecommended high-risk practices with the intent of preventing SARS-CoV-2 transmission, such as washing food products with bleach, applying household cleaning or disinfectant products to bare skin, and intentionally inhaling or ingesting these products. Respondents who engaged in high-risk practices more frequently reported an adverse health effect that they believed was a result of using cleaners or disinfectants than did those who did not report engaging in these practices. Public messaging should continue to emphasize evidence-based, safe practices such as hand hygiene and recommended cleaning and disinfection of high-touch surfaces to prevent transmission of SARS-CoV-2 in household settings (2). Messaging should also emphasize avoidance of high-risk practices such as unsafe preparation of cleaning and disinfectant solutions, use of bleach on food products, application of household cleaning and disinfectant products to skin, and inhalation or ingestion of cleaners and disinfectants.

Demographic Characteristics, Experiences, and Beliefs Associated with Hand Hygiene Among Adults During the COVID-19 Pandemic - United States, June 24-30, 2020.

Frequent hand hygiene, including handwashing with soap and water or using a hand sanitizer containing ≥60% alcohol when soap and water are not readily available, is one of several critical prevention measures recommended to reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* Previous studies identified demographic factors associated with handwashing among U.S. adults during the COVID-19 pandemic (1,2); however, demographic factors associated with hand sanitizing and experiences and beliefs associated with hand hygiene have not been well characterized. To evaluate these factors, an Internet-based survey was conducted among U.S. adults aged ≥18 years during June 24-30, 2020. Overall, 85.2% of respondents reported always or often engaging in hand hygiene following contact with high-touch public surfaces such as shopping carts, gas pumps, and automatic teller machines (ATMs).† Respondents who were male (versus female) and of younger age reported lower handwashing and hand sanitizing rates, as did respondents who reported lower concern about their own infection with SARS-CoV-2§ and respondents without personal experience with COVID-19. Focused health promotion efforts to increase hand hygiene adherence should include increasing visibility and accessibility of handwashing and hand sanitizing materials in public settings, along with targeted communication to males and younger adults with focused messages that address COVID-19 risk perception.

Cryptosporidiosis Outbreaks - United States, 2009-2017.

Cryptosporidium is a parasite that causes cryptosporidiosis, a profuse, watery diarrhea that can last up to 3 weeks in immunocompetent patients and can lead to life-threatening malnutrition and wasting in immunocompromised patients.* Fecal-oral transmission can occur by ingestion of contaminated recreational water, drinking water, or food, or through contact with infected persons or animals. For the period 2009-2017, public health officials from 40 states and Puerto Rico voluntarily reported 444 cryptosporidiosis outbreaks resulting in 7,465 cases. Exposure to treated recreational water (e.g., in pools and water playgrounds) was associated with 156 (35.1%) outbreaks resulting in 4,232 (56.7%) cases. Other predominant outbreak exposures included contact with cattle (65 outbreaks; 14.6%) and contact with infected persons in child care settings (57; 12.8%). The annual number of reported cryptosporidiosis outbreaks overall increased an average of approximately 13% per year over time. Reversing this trend will require dissemination of prevention messages to discourage swimming or attending child care while ill with diarrhea and encourage hand washing after contact with animals. Prevention and control measures can be optimized by improving understanding of Cryptosporidium transmission through regular analysis of systematically collected epidemiologic and molecular characterization data.