Routine Surveillance Research Articles

Assessment of the efficiency of the routine epidemiological surveillance system for malaria at the Tambacounda Health District, Senegal.

as part of the fight against malaria, epidemiological surveillance (ES) is one of the key pillars of the global technical strategy 2016-2030 to combat this disease. However, in the south-east of Senegal, where malaria poses a major public health problem, epidemiological surveillance has until recently been very neglected. To help reduce malaria-related morbidity and mortality in Senegal, an evaluation of the routine malaria ES system was conducted in the Tambacounda Health District in 2021. we conducted a cross-sectional, descriptive survey of 27 health structures in Tambacounda district from 20th February to 1st March 2022. overall, the routine ES system in the district was acceptable according to its users, with satisfactory tool filling time in 96.3% of the structures in our study, a cumulative completeness of reports at 92% despite a 77% promptness. The data collected at the services delivery points (SDP) level allowed a representativeness of the ES system in 100% of health facilities. The ES system was also rated as simple by 74.1% of SDP managers even though only 55.6% of them were trained. However, the stability of the system was low because 55.6% of SDP had staff to ensure the continuity of ES service despite the availability of management tools (100%) and the telephone network (96.3%). The same was true for the usefulness of the ES because only 25.9% of SDP managers analyzed their produced data. The reported ES and malaria morbidity data were not adequate. On the other hand, the ES system was reactive with a speed of transmission of information at 96.3% and a possibility of rapid diagnosis and management of cases at 100%. the routine malaria ES system at the level of health facilities in Tambacounda District was acceptable, simple, flexible, representative, and responsive. However, an increase in qualified staff at the health posts, capacity strengthening of the ES staff and regular supervision of SDP are needed essentials to make the district's malaria surveillance system more efficient.

Multiplex Bead Assay for the Serological Surveillance of Measles and Rubella.

There is increasing interest in evaluating antibody responses to multiple antigen targets in a single assay. Immunity to measles and rubella are often evaluated together because immunity is provided through combined vaccines and because routine immunization efforts and surveillance for measles and rubella pathogens are combined in many countries. The multiplex bead assay (MBA) also known as the multiplex immunoassay (MIA) described here combines the measurement of measles- and rubella-specific IgG antibodies in serum quantitatively according to international serum standards and has been successfully utilized in integrated serological surveillance.

When is vancomycin prophylaxis necessary? Risk factors for MRSA surgical site infection.

The 2022 SHEA/IDSA/APIC guidance for surgical site infection (SSI) prevention recommends reserving vancomycin prophylaxis to patients who are methicillin-resistant Staphylococcus aureus (MRSA) colonized. Unfortunately, vancomycin prophylaxis remains common due to the overestimation of MRSA risk and the desire to cover MRSA in patients with certain healthcare-associated characteristics. To optimize vancomycin prophylaxis, we sought to identify risk factors for MRSA SSI. This was a single-center, case-control study of patients with a postoperative SSI after undergoing a National Healthcare Safety Network operative procedure over eight years. MRSA SSI cases were compared to non-MRSA SSI controls. Forty-two demographic, medical, and surgical characteristics were evaluated. Of the 441 patients included, 23 developed MRSA SSIs (rate = 5.2 per 100 SSIs). In the multivariable model, we identified two independent risk factors for MRSA SSI: a history of MRSA colonization or infection (OR, 9.0 [95% CI, 1.9-29.6]) and hip or knee replacement surgery (OR, 3.8 [95% CI, 1.3-9.9]). Hemodialysis, previous hospitalization, and prolonged hospitalization prior to the procedure had no measurable association with odds of MRSA SSI. Patients with prior MRSA colonization or infection had 9-10 times greater odds of MRSA SSI and patients undergoing hip and knee replacement had 3-4 times greater odds of MRSA SSI. Healthcare-associated characteristics, such as previous hospitalization or hemodialysis, were not associated with MRSA SSI. Our findings support national recommendations to reserve vancomycin prophylaxis for patients who are MRSA colonized, as well as those undergoing hip and knee replacement, in the absence of routine MRSA colonization surveillance.

Spatial Analysis of Drought Vulnerability Related to Climate Change and Under Five Children’s Nutritional Status

Drought vulnerability which more prevalent due to climate change reduce public health quality. This research aims to map areas that are vulnerable to drought and correlate them with under five children nutritional status. This was a cross-sectional study using spatial analysis in Borobudur District. Drought vulnerabilities were overlayed using three drought-prone indicators of Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), and Land Surface Temperature (LST). The spatial analysis found 8 villages (40%) had high, 6 villages (30%) had medium, and 6 villages (30%) had low drought vulnerability. Stunting prevalence derived from the routine community-based nutritional surveillance of the Magelang District Health Office. Analysis of Variance (ANOVA) were used to assess the risk of stunting among different level of spatial indicators related to drought. The average prevalence of stunting was higher in the areas with high (12.57%), compared to medium (8.93%), and low (8.73%) drought vulnerability, but not statistically significant (F=1.763; p>0.05). Stunting was significantly related to water availability (NDWI). A lower NDWI index increased the risk of stunting in children (F=4.620; p<0.05). NDWI spatial analysis can be used as a reference to support preventive efforts to mitigate drought and the nutritional status of children in rural areas.

Public health surveillance perspectives from provincial COVID-19 experiences, South Africa 2021.

The review identified opportunities to advance the existing routine public health surveillance system and improve public health surveillance and response. This qualitative review articulates local knowledge that should be translated into strategies and actions to bolster public health preparedness.

Clinical isolate characteristics and demographics of patients with C.jejuni and C.coli infections in Northern Israel, 2015-2021.

C.coli is a significant cause of foodborne gastroenteritis worldwide, with the majority of cases attributed to C.jejuni. Although most clinical laboratories do not typically conduct antimicrobial susceptibility testing for C.coli, the rise in resistant strains has underscored the necessity for such testing and epidemiological surveillance. The current study presents clinical isolate characteristics and demographics of 221 patients with C.coli (coli and jejuni) infections in Northern Israel, between 2015 and 2021. Clinical and demographic data were collected from patient medical records. Susceptibility to erythromycin, tetracycline, ciprofloxacin, and gentamicin was assessed using the standard E-test. No significant correlations were found between bacterial species and patient ethnicity, patient gender, or duration of hospitalization. In contrast, significant differences were found between infecting species and patient age and age subgroup (P<0.001). Furthermore, erythromycin resistance was observed in only 0.5% of the study population, while resistance to ciprofloxacin, tetracycline, and gentamicin was observed in 95%, 93%, and 2.3% of the population, respectively. The presented study underscores the need for routine surveillance of C.coli antibiotic resistance.

Occurrence, antimicrobial resistance and genomic features of Klebsiella pneumoniae from broiler chicken in Faisalabad, Pakistan.

The dissemination of antimicrobial resistance (AMR) in critical priority pathogens is a significant threat. Non-clinical reservoirs of AMR, such as agriculture and food production facilities, may contribute to the transmission of clinically relevant pathogens such as multidrug-resistant (MDR) Klebsiella pneumoniae. There is currently very limited knowledge regarding the population structure and genomic diversity of K. pneumoniae in poultry production in Pakistan. We explored healthy broilers in a commercial farm from Faisalabad, Pakistan, and identified six K. pneumoniae strains from 100 broiler birds. We characterized the strains, determining clonality, virulence and antimicrobial resistance genes using next generation sequencing. The evaluation of antimicrobial susceptibility revealed that all the strains were MDR. Genomic analysis showed that 3/6 strains belonged to ST152, harbouring acquired resistance aminoglycosides [aadA2, aph(4')-Ia], β-lactams (blaSHV-187 , blaLAP2 ), fosfomycin (fosA6), tetracycline (tetA), trimethoprim (dfrA12), quinolone (qnrS1), sulphonamides (sul2) and phenicol (floR). All the strains harboured the efflux pump genes oqxA, oqxB, emrR, kpnG, kpnH, kpnF, baeR, mtdB and mtdC. All six strains encoded identical virulence profiles possessing six genes, i.e., ureA, iutA, entB, allS, fimH and mrkD. Phylogenomic analysis of the dominant sequence type (ST152) present in our dataset with publicly available genomes showed that the isolates clustered to strains mainly from human sources and could pose a potential threat to food safety and public health. The combination of these findings with antimicrobial use data would allow a better understanding of the selective pressures that may be driving the spread of AMR. This is the first report of MDR K. pneumoniae isolated from broiler hens in Pakistan, and the finding suggests that routine surveillance of WHO critical priority pathogens in such settings would be beneficial to the development of effective control strategies to reduce AMR.

Heat-Associated Death Surveillance in Maricopa County During the 2023 Heat Wave

Abstract Since 2006, the Maricopa County Department of Public Health (MCDPH) has conducted routine surveillance of heat-associated deaths in the county. During that time, the number of deaths each year has been on the rise with 2022 numbers showing a 25% increase over 2021. Risk factors such as homelessness and alcohol and drug use have been shown to increase the risk of heat-associated death. During the summer of 2023, record-breaking heat in the metro-Phoenix area was widely reported. The MCDPH heat-associated death surveillance data was widely reported and used by policy makers to address extreme heat as a regional disaster. In this presentation participants will learn how heat-associated death surveillance has evolved over time to inform public health leaders and policy makers to the risk factors associated with poor outcomes from extreme heat. Participants will also understand how the data is shared at the local, national and international levels to inform extreme heat response activities. Learning Objectives Participants will learn how heat-associated death surveillance has evolved over time to inform public health leaders and policy makers of the risk factors associated with poor outcomes from extreme heat. Participants will also understand how the data is shared at the local, national and international levels to inform extreme heat response activities.

Implementation of Glucose-6-Phosphate Dehydrogenase (G6PD) testing for Plasmodium vivax case management, a mixed method study from Cambodia.

Plasmodium vivax remains a challenge for malaria elimination since it forms dormant liver stages (hypnozoites) that can reactivate after initial infection. 8-aminoquinolone drugs kill hypnozoites but can cause severe hemolysis in individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. The STANDARD G6PD test (Biosensor) is a novel point-of-care diagnostic capable of identifying G6PD deficiency prior to treatment. In 2021, Cambodia implemented the Biosensor to facilitate radical cure treatment for vivax malaria. To assess the Biosensor's implementation after its national rollout, a mixed-methods study was conducted in eight districts across three provinces in Cambodia. Interviews, focus group discussions, and observations explored stakeholders' experiences with G6PD testing and factors influencing its implementation. Quantitative data illustrative of test implementation were gathered from routine surveillance forms and key proportions derived. Qualitative data were analyzed thematically. The main challenge to implementing G6PD testing was that only 49.2% (437/888) of eligible patients reached health centers for G6PD testing following malaria diagnosis by community health workers. Factors influencing this included road conditions and long distances to the health center, compounded by the cost of seeking further care and patients' perceptions of vivax malaria and its treatment. 93.9% (790/841) of eligible vivax malaria patients who successfully completed referral (429/434) and directly presented to the health center (360/407) were G6PD tested. Key enabling factors included the test's acceptability among health workers and their understanding of the rationale for testing. Only 36.5% (443/1213) of eligible vivax episodes appropriately received primaquine. 70.5% (165/234) of female patients and all children under 20 kilograms never received primaquine. Our findings suggest that access to radical cure requires robust infrastructure and income security, which would likely improve referral rates to health centers enabling access. Bringing treatment closer to patients, through community health workers and nuanced community engagement, would improve access to curative treatment of vivax malaria.

An overview of anthrax: a neglected zoonosis of the tropical region

Anthrax is a neglected bacterial zoonosis that can be highly contagious and potentially lethal. The disease, which mainly affects herbivorous ungulate animals, is caused by Bacillus anthracis, a rod-shaped, gram-positive bacterium. The pathogenicity depends on the production of toxins by Bacillus anthracis and the sensitivity of the host. The infection is transmitted to humans when they come in to contact with infected animals or their products. It is an important occupational risk to the abattoir workers. Clinical manifestations of disease in humans include different forms, including cutaneous, pulmonary and intestinal. The disease is widespread in African and Asian countries with frequent reports of cases. Lack of appropriate and effective control programs in these countries has led to increase in the number of human cases. Bacillus anthracis spores are extremely resistant to environmental conditions, and can persist for several decades in nature and, thus making the control or eradication of the disease difficult. Disease control involves managing contaminated animal products, avoiding contact with infected animals, livestock vaccination in endemic regions and routine surveillance of animals. The most effective and dependable way to control zoonotic diseases like anthrax is through collaborative monitoring programs including the "One Health" approach.

Estimating the true number of people with acute rheumatic fever and rheumatic heart disease from two data sources using capture-recapture methodology.

ObjectiveIn Australia, accurate case ascertainment of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) diagnoses for disease surveillance and control purposes requires the use of multiple data sources, including RHD registers and hospitalisation records. Despite drawing on multiple data sources, the true burden of ARF/RHD is likely to be underestimated.MethodsThis study used capture-recapture methods to quantify the missing number of ARF/RHD cases in data from hospitals and jurisdictional RHD registers. Linked datasets comprised reported cases of ARF/RHD in register records and administrative hospital data.ResultsCapture-recapture analyses indicated the total number of new ARF/RHD cases in three Australian jurisdictions (Queensland, South Australia and Western Australia), among people aged 3-54years, was 3480 (95% CI=3366-3600) during 2011-2016. This included 894 (25.7%) individuals who were not listed in either the hospital or register datasets. Non-Indigenous, urban and older people with ARF/RHD were least likely to be identified in either the hospital or register data sources.ConclusionsThe 894 likely ARF/RHD cases our analyses detected that are not included in the routine surveillance datasets are concerning and quantify the magnitude and characteristics of under-notification to RHD registers in Australia, especially for groups that are not typically at high risk of ARF.

Impact of an ultrasensitive Cytomegalovirus quantitative nucleic acid test on Cytomegalovirus detection and therapy in renal transplant recipients.

Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR-based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decision-making and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on multiple clinical outcomes, including time to detection and duration of CMV DNAemia. We conducted a single-center cohort study contrasting RTRs monitored with a qNAT with a higher lower limit of quantification (LLOQ >300IU/mL) with those monitored with a more sensitive qNAT (LLOQ >35IU/mL). Patients were stratified by donor (D)/recipient (R) CMV serostatus (D+/R-: high risk; any R+: moderate risk). CMV viral load monitoring was performed monthly post transplantation, with the primary outcomes being time to CMV DNAemia and its duration. Total 1382 patients were analyzed from 2014 to 2016 and 2019 to 2021. Moderate-risk RTRs monitored with the more sensitive assay experienced a greater hazard for the development of a first episode of CMV DNAemia (aHR: 1.95, 95% confidence interval [CI]: 1.55-2.46) and an average of 24 (95% CI: 16.40-31.98) additional days of DNAemia. There was no difference in CMV end-organ disease or 1-year all-cause mortality between moderate-risk RTRs. The more sensitive assay was associated with earlier detection and extended durations of CMV DNAemia in moderate-risk RTRs, without altering clinical outcomes. These findings inform optimal use of these assays and antiviral stewardship in RTRs. The use of ultrasensitive CMV qNAT assays in moderate-risk CMV renal transplant recipients is associated with earlier detection and longer durations of CMV DNAemia without impacting CMV end-organ disease or 1-year mortality.

Bridging the Gap from Molecular Surveillance to Programmatic Decisions for Malaria Control and Elimination.

An increasing number of molecular and genomic assays are available to study malaria parasite populations. However, so far they have played a marginal role in informing policy and programmatic decision-making. Currently, molecular data are mainly used for monitoring drug efficacy against Plasmodium falciparum; assessing molecular markers of drug and insecticide resistance; and assessing P. falciparum histidine-rich protein 2 and 3 genes (Pfhrp2/3) deletion. We argue that additional use cases for molecular routine surveillance could be implemented in the near future, especially in transmission settings approaching elimination. These would include using quantitative polymerase chain reaction to monitor the prevalence of sub-patent infections in asymptomatic carriers, monitoring parasite genetic diversity as transmission intensity is changing, using genomic data to determine the origin of imported infections and characterize transmission chains in settings with very low malaria transmission, and using serology to monitor recent and past exposures in low-transmission settings. Molecular surveillance could inform control programs on adapting novel strategies, such as reactive case detection or focal mass drug administration, and help evaluate the impact of interventions currently in place. To better integrate molecular and genomic data into control program decision-making, engagement of national malaria control experts is crucial. Local laboratory capacity needs to be strengthened, shortening the time from sample collection to data availability. Here, we discuss opportunities and challenges of the use of molecular and genomic data for supporting malaria control and elimination efforts, as well as the avenues to link molecular and genomic data with gold standard epidemiological measurements through mathematical modeling.

Screening for multidrug-resistant organisms in high-risk hospitalized patients with hematologic diseases.

Patients treated for hematologic malignancies are at higher risk for blood stream infections (BSI) and multidrug-resistant organisms (MDRO) are increasingly involved. Studies showed a significant association between rectal colonization status and a higher risk of subsequent MDRO BSI. The objective of our study was to probe the practice of surveillance cultures in Belgian hematology centers. A questionnaire was sent to the 13 hematology centers participating in the acute leukemia board of the Belgian Hematology Society. 21 questions probed for the method of surveillance cultures, MDRO screened, antimicrobial prophylaxis, and empirical therapy and their relationship with colonization status. All centers completed the questionnaire in full. Routine gastrointestinal surveillance cultures in hematologic patients are taken in 10 hospitals. Organisms tested for included mostly ESBL (n = 9) and carbapenem-resistant (n = 8) Enterobacterales. All centers with a screening strategy adapt empiric antibiotic therapy based on MDRO colonization. Prophylaxis strategies are variable, only two centers adapt prophylaxis upon documentation of fluoroquinolone resistance. The majority of the Belgian centers perform routine surveillance cultures and adapt empiric therapy for neutropenic fever accordingly. Other reasons for testing include to gain insight into local epidemiology and to prevent in-hospital transmission. In general, there was significant variability in surveillance dimensions.

Evaluation of Surveillance System Changes to Improve Detection of Disseminated Gonococcal Infections in Virginia, 2018 to 2021.

Disseminated gonococcal infection (DGI), a complication of untreated gonorrhea, is rarely reported through routine surveillance. We sought to improve local surveillance system capacity to estimate and monitor the incidence of DGI in Virginia. We modified surveillance protocols to identify possible DGI cases using information extracted from gonorrhea case reports and performed provider follow-up using standardized case report forms to confirm DGI diagnosis and collect clinical information. Suspect cases included those with a laboratory report indicating sterile site of specimen collection (e.g., blood, synovial fluid) and/or intravenous (IV) treatment. We performed descriptive analyses to summarize the characteristics of suspect and confirmed DGIs and estimated incidence. After piloting protocols in 2018 to 2019, we identified 405 suspect DGI cases from 29,294 gonorrhea cases reported in 2020 to 2021 (1.4%). We initiated investigations for 298 (73.6%) of the suspect cases, received provider responses for 105 (25.9%), and confirmed 19 DGI cases (4.7%). Positive laboratory reports from nonmucosal sites were the most reliable predictor of confirmed DGI status, but most were not confirmed as DGI even when provider follow-up was successful. The confirmed and estimated incidence of DGI were 0.06% and 0.22%, respectively. Sixteen (84%) of the confirmed cases were older than 25 years, 3 (16%) were HIV positive, and approximately half were male and non-Hispanic Black. Most (15 [74%]) were hospitalized, and common manifestations included septic arthritis and bacteremia. We improved surveillance for DGI in Virginia while incurring minor programmatic costs. Additional efforts to improve the completeness and quality of surveillance data for DGI are needed.

The Global and Regional Prevalence of Hospital-Acquired Carbapenem-Resistant Klebsiella pneumoniae Infection: A Systematic Review and Meta-analysis.

Due to scarce therapeutic options, hospital-acquired infections caused by Klebsiella pneumoniae (KP), particularly carbapenem-resistant KP (CRKP), pose enormous threat to patients' health worldwide. This study aimed to characterize the epidemiology and risk factors of CRKP among nosocomial KP infections. MEDLINE, Embase, PubMed, and Google Scholar were searched for studies reporting CRKP prevalence from inception to 30 March 2023. Data from eligible publications were extracted and subjected to meta-analysis to obtain global, regional, and country-specific estimates. To determine the cause of heterogeneity among the selected studies, prespecified subgroup analyses and meta-regression were also performed. Odds ratios of CRKP-associated risk factors were pooled by a DerSimonian and Laird random-effects method. We retained 61 articles across 14 countries and territories. The global prevalence of CRKP among patients with KP infections was 28.69% (95% CI, 26.53%-30.86%). South Asia had the highest CRKP prevalence at 66.04% (95% CI, 54.22%-77.85%), while high-income North America had the lowest prevalence at 14.29% (95% CI, 6.50%-22.0%). In the country/territory level, Greece had the highest prevalence at 70.61% (95% CI, 56.77%-84.45%), followed by India at 67.62% (95% CI, 53.74%-81.79%) and Taiwan at 67.54% (95% CI, 58.65%-76.14%). Hospital-acquired CRKP infections were associated with the following factors: hematologic malignancies, corticosteroid therapies, intensive care unit stays, mechanical ventilations, central venous catheter implantations, previous hospitalization, and antibiotic-related exposures (antifungals, carbapenems, quinolones, and cephalosporins). Study findings highlight the importance of routine surveillance to control carbapenem resistance and suggest that patients with nosocomial KP infection have a very high prevalence of CRKP.

Trends of measles in Tanzania: A 5-year review of case-based surveillance data, 2018-2022

ObjectivesTanzania observed a gradual increase in the number of measles cases since 2019 with a large outbreak recorded during 2022. This study describes the trend of measles in Tanzania over a 5-year period from 2018-2022. MethodsThis was a descriptive study conducted using routine measles case-based surveillance system including 195 councils of the United Republic of Tanzania. ResultsBetween 2018 and 2022 there were 12,253 measles cases reported. Out of 10,691 (87.25%) samples tested by enzyme-linked immunosorbent assay, 903 (8.4%) were measles immunoglobulin M positive. The highest number of laboratory-confirmed measles cases was in 2022 (64.8%), followed by 2020 (13.8%), and 2019 (13.5%). Out of 1279 unvaccinated cases, 213 (16.7%) were laboratory-confirmed measles cases compared to 77/723 (10.6%) who were partially vaccinated and 71/1121 (6.3%) who were fully vaccinated (P < 0.001). Children aged between 1-4 years constituted the most confirmed measles cases after laboratory testing, followed by those aged 5-9 years. There was a notable increase in the number of laboratory-confirmed measles cases in children <1 year and 10-14 years during 2022 compared to previous years. The vaccination coverage of the first dose of measles-containing vaccine (MCV1) was maintained >90% since 2013 while MCV2 increased gradually reaching 88% in 2022. ConclusionsAccumulation of susceptible children to measles due to suboptimal measles vaccination coverage over the years has resulted in an increase in the number of laboratory-confirmed measles cases in Tanzania with more cases recorded during the COVID-19 pandemic. Strengthening surveillance, routine immunization, and targeted strategies are key to achieving the immunity levels required to interrupt measles outbreaks.

Evolution and ecology of Jeilongvirus among wild rodents and shrews in Singapore

BackgroundJeilongvirus was proposed as a new genus within the Paramyxoviridae in 2018. The advancement in metagenomic approaches has encouraged multiple reports of Jeilongvirus detection following the initial species discovery, enriching species diversity and host range within the genus. However, Jeilongvirus remains understudied in Singapore, where interfaces between humans and small mammals are plentiful.MethodsHere, we utilized metagenomic sequencing for the exploration of viral diversity in small mammal tissues. Upon discovery of Jeilongvirus, molecular screening and full genome sequencing was conducted, with the data used to conduct statistical modelling and phylogenetic analysis.ResultsWe report the presence of Jeilongvirus in four species of Singapore wild small mammals, detected in their spleen and kidney. We show that full genomes of three Singapore Jeilongvirus encode for eight ORFs including the small hydrophobic and transmembrane proteins. All generated genomes cluster phylogenetically within the small mammal subclade, but share low genetic similarity with representative Jeilongvirus species. Statistical modelling showed no spatial or temporal patterns and differences among species, life history traits and habitat types.ConclusionsThis study serves as a basis for understanding dynamics between Jeilongvirus and small mammal hosts in Singapore by displaying the virus generalist nature. In addition, the initial detection can help to invoke improved routine surveillance and detection of circulating pathogens in synanthropic hosts.

Genetic and potential antigenic evolution of influenza A(H1N1)pdm09 viruses circulating in Kenya during 2009–2018 influenza seasons

Influenza viruses undergo rapid evolutionary changes, which requires continuous surveillance to monitor for genetic and potential antigenic changes in circulating viruses that can guide control and prevention decision making. We sequenced and phylogenetically analyzed A(H1N1)pdm09 virus genome sequences obtained from specimens collected from hospitalized patients of all ages with or without pneumonia between 2009 and 2018 from seven sentinel surveillance sites across Kenya. We compared these sequences with recommended vaccine strains during the study period to infer genetic and potential antigenic changes in circulating viruses and associations of clinical outcome. We generated and analyzed a total of 383 A(H1N1)pdm09 virus genome sequences. Phylogenetic analyses of HA protein revealed that multiple genetic groups (clades, subclades, and subgroups) of A(H1N1)pdm09 virus circulated in Kenya over the study period; these evolved away from their vaccine strain, forming clades 7 and 6, subclades 6C, 6B, and 6B.1, and subgroups 6B.1A and 6B.1A1 through acquisition of additional substitutions. Several amino acid substitutions among circulating viruses were associated with continued evolution of the viruses, especially in antigenic epitopes and receptor binding sites (RBS) of circulating viruses. Disease severity declined with an increase in age among children aged < 5 years. Our study highlights the necessity of timely genomic surveillance to monitor the evolutionary changes of influenza viruses. Routine influenza surveillance with broad geographic representation and whole genome sequencing capacity to inform on prioritization of antigenic analysis and the severity of circulating strains are critical to improved selection of influenza strains for inclusion in vaccines.

Patterns of neurotoxicity among patients receiving chimeric antigen receptor T-cell therapy: A single-centre cohort study.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is an important complication of chimeric antigen receptor T-cell (CAR-T) therapy. This study aims to identify the patterns of neurotoxicity among patients with ICANS at a tertiary referral centre in Australia. This single-centre, prospective cohort study included all consecutively recruited patients who underwent CAR-T therapy for eligible haematological malignancies. All patients underwent a comprehensive neurological assessment and cognitive screening before CAR-T infusion, during the development of ICANS, and 1 month after treatment. Baseline demographic characteristics, incidence, and neurological patterns of neurotoxicity management were evaluated. Over a 19-month period, 23% (12) of the 53 eligible patients developed neurotoxicity (10/12 [83%] being grade 1). All patients showed changes in handwriting and tremor as their initial presentation. Changes in cognition were manifested in most of the patients, with a more substantial drop noted in their Montreal Cognitive Assessment compared to immune effector cell-associated encephalopathy scores. All manifestations of neurotoxicity were short-lived and resolved within a 1-month period, with a mean duration of 8.2 days (range = 1-33). The patterns of CAR-T-related neurotoxicity often include change in handwriting, tremor, and mild confusional state, especially early in their evolution. These may remain undetected by routine neurological surveillance. These features represent accessible clinical markers of incipient ICANS.