Neurological manifestations of ehrlichiosis among a cohort of patients: prevalence and clinical symptoms.

BACKGROUND: Ehrlichiosis is a potentially fatal tick-borne disease that can progress to involve the central nervous system (CNS) (i.e., neuro-ehrlichiosis), particularly in cases where diagnosis and treatment are delayed. Despite a six-fold national increase in the incidence of ehrlichiosis over the past 20 years, recent data on the prevalence and manifestations of neuro-ehrlichiosis are lacking. METHODS: We conducted a retrospective chart review of all patients tested for ehrlichiosis at University of North Carolina Health facilities between 2018 and 2021 and identified patients who met epidemiological criteria for ehrlichiosis as established by the Council of State and Territorial Epidemiologists and employed by the Centers for Disease Control and Prevention. We estimated the prevalence of neurological symptoms and described the spectrum of neurological manifestations in acute ehrlichiosis, documenting select patient cases in more detail in a case series. RESULTS: Out of 55 patients with confirmed or probable ehrlichiosis, five patients (9.1%) had neurologic symptoms, which is notably lower than previous estimates. Neurological presentations were highly variable and included confusion, amnesia, seizures, focal neurological deficits mimicking ischemic vascular events, and an isolated cranial nerve palsy, though all patients had unremarkable neuroimaging at time of presentation. All but one patient had risk factors for severe ehrlichiosis (i.e., older age, immunosuppression). CONCLUSIONS: Neuro-ehrlichiosis may lack unifying patterns in clinical presentation that would otherwise aid in diagnosis. Clinicians should maintain a high index of suspicion for neuro-ehrlichiosis in patients with acute febrile illness, diverse neurological symptoms, and negative neuroimaging in lone star tick endemic regions.

Impact of Sulfadoxine-Pyrimethamine and Dihydroartemisinin-Piperaquine as Intermittent Preventive Treatment in Pregnancy on Stool Antimicrobial Resistance Gene Abundance.

Increasing antimicrobial resistance (AMR) is a global public health emergency. Although chemoprevention has improved malaria-related pregnancy outcomes, the downstream effects on AMR have not been characterized. We compared the abundance of 10 AMR genes in stool samples from pregnant women receiving sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment against malaria in pregnancy (IPTp) to that in samples from women receiving dihydroartemisinin-piperaquine (DP) for IPTp. All participants had at least one AMR gene at baseline. Mean quantities of the antifolate gene dfrA17 were increased after two or more doses of SP (mean difference = 1.6, 95% CI: 0.4-2.7, P = 0.008). Antimicrobial resistance gene abundance tended to increase from baseline in SP recipients compared with a downward trend in the DP group. Overall, IPTp-SP had minimal effects on the abundance of antifolate resistance genes (except for dfrA17), potentially owing to a high starting prevalence. However, the trend toward increasing AMR in SP recipients warrants further studies.

Comprehensive assessment of pediatric acute and inpatient care at a tertiary referral hospital in Malawi: opportunities for quality improvement.

BACKGROUND: Despite the reduction in global under-5 mortality over the last decade, childhood deaths remain high. To combat this, there has been a shift in focus from disease-specific interventions to use of healthcare data for resource allocation, evaluation of performance and impact, and accountability. This is a descriptive analysis of data derived from a prospective cohort study describing paediatric admissions to a tertiary referral hospital in Malawi for the purpose of process evaluation and quality improvement. METHODS: Using a REDCap database, we collected data for patients admitted acutely to Kamuzu Central Hospital, a tertiary referral centre in the central region. Data were collected from 17 123 paediatric inpatients from 2017 to 2020. RESULTS: Approximately 6% of patients presented with either two or more danger signs or severely abnormal vital signs. Infants less than 6 months, who had the highest mortality rate, were also the most critically ill on arrival to the hospital. Sepsis was diagnosed in about 20% of children across all age groups. Protocols for the management of high-volume, lower-acuity conditions such as uncomplicated malaria and pneumonia were generally well adhered to, but there was a low rate of completion for labs, radiology studies and subspecialty consultations required to provide care for high acuity or complex conditions. The overall mortality rate was 4%, and 60% of deaths occurred within the first 48 hours of admission. CONCLUSION: Our data highlight the need to improve the quality of care provided at this tertiary-level centre by focusing on the initial stabilisation of high-acuity patients and augmenting resources to provide comprehensive care. This may include capacity building through the training of specialists, implementation of clinical processes, provision of specialised equipment and increasing access to and reliability of ancillary services. Data collection, analysis and routine use in policy and decision-making must be a pillar on which improvement is built.

Comparison of commercially available, rapid, point-of-care C-reactive protein assays among children with febrile illness in southwestern Uganda.

In Uganda, children with febrile illness are often treated with antibiotics even though most have self-limiting, likely viral, infections. C-reactive protein (CRP) measurement can help identify those who are more likely to have a bacterial infection and therefore need antibiotic treatment. Implementation of a CRP rapid diagnostic test (RDT) at the point-of-care in resource-constrained settings with minimal laboratory infrastructure could reduce unnecessary antibiotic use. In this study, we evaluated the performance of three semi-quantitative CRP RDTs (Actim, BTNX, Duo) against a reference CRP assay requiring an electrically powered analyzer (Afinion). While both tests demonstrated substantial agreement with Afinion, Actim had slightly higher agreement than BTNX. The sensitivity was higher for the BTNX test, whereas the Actim test had a higher specificity, at cut-offs of 40 mg/L and 80 mg/L. At a cut-off of 20 mg/L, Duo demonstrated substantial agreement with the Afinion test as well. Our results demonstrate the reliability of CRP RDTs when compared to a reference standard. CRP RDTs without the need for a laboratory-based analyzer are promising tools for optimizing antibiotic use in low-resource settings.

Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel.

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection.

Infection precaution adherence varies by potential exposure risks to SARS-CoV-2 and job role: Findings from a US medical center.

BACKGROUND: Infection precautions (IP) facilitate standardized and safe patient care. Research has demonstrated several barriers to IP adherence among health care personnel (HCP) but potential exposure risk to SARS-CoV-2 and job role has not been considered. METHODS: Researchers used self-reported baseline surveys with 191 HCPs at a university medical center to examine factors that may have affected IP adherence (eg, personal protective equipment [PPE] and hand hygiene errors) over the 2 weeks prior to the survey. Chi-square tests were used to determine if differences existed first, among job role and IP adherence, and second, the potential risk of exposure to SARS-CoV-2 and IP adherence. A binary logistic regression estimated if PPE nonadherence was associated with COVID-19 stress, job role, and potential exposure risk to SARS-CoV-2. RESULTS: PPE nonadherence varied by job role. Those in the Other group (ie, nonphysician/non-nursing HCP) reported significantly fewer errors (9.6%) compared to Physicians (26.5%) and Registered Nurses (33.3%). Hand/glove hygiene errors between COVID-19 patient rooms varied by job role. Respondents who had higher risks of exposure to SARS-CoV-2 were 5.74 times more likely to experience errors. CONCLUSIONS: The results provide implications for adopting systems-level approaches to support worker knowledge and engagement across job roles to improve IP adherence.

Using microbiological data to improve the use of antibiotics for respiratory tract infections: A protocol for an individual patient data meta-analysis.

BACKGROUND: Resistance to antibiotics is rising and threatens future antibiotic effectiveness. 'Antibiotic targeting' ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence. AIM: To undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs. METHODS: A systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs. TRIAL REGISTRATION: PROSPERO Registration number: CRD42023376769.

Comparison of capillary blood self-collection using the Tasso-SST device with venous phlebotomy for anti-SARS-CoV-2 antibody measurement.

Measuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous total Ig and IgG specific antibody quantitative levels was high (Total Ig: Spearman ρ = 0.72, 95% CI (0.39,0.90); IgG: Spearman ρ = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing.

Mortality by Admission Diagnosis in Children 1-60 Months of Age Admitted to a Tertiary Care Government Hospital in Malawi.

Diagnosis-specific mortality is a measure of pediatric healthcare quality that has been incompletely studied in sub-Saharan African hospitals. Identifying the mortality rates of multiple conditions at the same hospital may allow leaders to better target areas for intervention. In this secondary analysis of routinely collected data, we investigated hospital mortality by admission diagnosis in children aged 1-60 months admitted to a tertiary care government referral hospital in Malawi between October 2017 and June 2020. The mortality rate by diagnosis was calculated as the number of deaths among children admitted with a diagnosis divided by the number of children admitted with the same diagnosis. There were 24,452 admitted children eligible for analysis. Discharge disposition was recorded in 94.2% of patients, and 4.0% (N = 977) died in the hospital. The most frequent diagnoses among admissions and deaths were pneumonia/bronchiolitis, malaria, and sepsis. The highest mortality rates by diagnosis were found in surgical conditions (16.1%; 95% CI: 12.0-20.3), malnutrition (15.8%; 95% CI: 13.6-18.0), and congenital heart disease (14.5%; 95% CI: 9.9-19.2). Diagnoses with the highest mortality rates were alike in their need for significant human and material resources for medical care. Improving mortality in this population will require sustained capacity building in conjunction with targeted quality improvement initiatives against both common and deadly diseases.

Comparison of Capillary Blood Self-Collection using the Tasso-SST Device with Venous Phlebotomy for anti-SARS-CoV-2 Antibody Measurement.

Measuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous total Ig and IgG specific antibody quantitative levels was high (Total Ig: ρ = 0.72, 95% CI (0.39- 0.90); IgG: ρ = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing.

Longitudinal study of glomerular hyperfiltration in adults with sickle cell anemia: a multicenter pooled analysis.

Glomerular hyperfiltration is common in young sickle cell anemia patients and precedes development of overt kidney disease. In this multicenter pooled cohort, we characterized hyperfiltration and its decline to normal range in adult patients. Glomerular filtration rate (GFR) was estimated using the creatinine-based 2009 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation omitting race adjustment and the 2021 CKD-EPI equation. Using CKD-EPI-2009, 506 patients had baseline estimated GFR (eGFR) ≥90 mL/min per 1.73 m2, median age of 24 (interquartile range [IQR], 19-34) years and 5.17 years of follow-up. The prevalence of hyperfiltration (eGFR ≥140 and ≥130 mL/min per 1.73 m2 for men and women, respectively) was 38.3%. Using CKD-EPI-2009, baseline hyperfiltration was less likely with older age (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.73-0.83; P < .0001), male sex (OR, 0.32; 95% CI, 0.18-0.58; P = .0002), and higher weight (OR, 0.96; 95% CI, 0.94-0.99; P = .001). Using CKD-EPI-2021, hyperfiltration was similarly less likely with older age (OR, 0.75; 95% CI, 0.70-0.81; P < .0001), male sex (OR, 0.24; 95% CI, 0.13-0.44; P < .0001), and higher weight (OR, 0.97; 95% CI, 0.95-0.99; P = .004). In patients with baseline hyperfiltration, eGFR declined to normal values at a median age of 26.2 years. Using CKD-EPI-2009, this decline was associated with male sex (HR, 2.20; 95% CI, 1.26-3.87; P = .006), systolic blood pressure (hazard ratio [HR], 1.02; 95% CI, 1.01-1.04; P = .01), and hydroxyurea use (HR, 1.74; 95% CI, 1.002-3.03; P = .05). Using CKD-EPI-2021, decline of eGFR to normal was only associated with male sex (HR, 3.39; 95% CI, 2.01-5.69; P < .0001). Decline to normal eGFR range from hyperfiltration occurs earlier in males, those on hydroxyurea, and with higher systolic blood pressure.

Encephalitis Caused by Jamestown Canyon Virus in a Liver Transplant Patient, North Carolina, USA, 2017.

We describe the first documented case of Jamestown Canyon virus (JCV) in North Carolina, which occurred in a liver transplant patient who presented acutely with headache, aphasia, and confusion. This is also the first report of recovery from JCV encephalitis following treatment with intravenous immune globulin.

At-home testing to mitigate community transmission of SARS-CoV-2: protocol for a public health intervention with a nested prospective cohort study.

BACKGROUND: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve as a global health crisis. Although highly effective vaccines have been developed, non-pharmaceutical interventions remain critical to controlling disease transmission. One such intervention-rapid, at-home antigen self-testing-can ease the burden associated with facility-based testing programs and improve testing access in high-risk communities. However, its impact on SARS-CoV-2 community transmission has yet to be definitively evaluated, and the socio-behavioral aspects of testing in underserved populations remain unknown. METHODS: As part of the Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program funded by the National Institutes of Health, we are implementing a public health intervention titled "Say Yes! COVID Test" (SYCT) involving at-home self-testing using a SARS-CoV-2 rapid antigen assay in North Carolina (Greenville, Pitt County) and Tennessee (Chattanooga City, Hamilton County). The intervention is supported by a multifaceted communication and community engagement strategy to ensure widespread awareness and uptake, particularly in marginalized communities. Participants receive test kits either through online orders or via local community distribution partners. To assess the impact of this intervention on SARS-CoV-2 transmission, we will conduct a non-randomized, ecological study using community-level outcomes. Specifically, we will evaluate trends in SARS-CoV-2 cases and hospitalizations, SARS-CoV-2 viral load in wastewater, and population mobility in each community before, during, and after the SYCT intervention. Individuals who choose to participate in SYCT will also have the option to enroll in an embedded prospective cohort substudy gathering participant-level data to evaluate behavioral determinants of at-home self-testing and socio-behavioral mechanisms of SARS-CoV-2 community transmission. DISCUSSION: This is the first large-scale, public health intervention implementing rapid, at-home SARS-CoV-2 self-testing in the United States. The program consists of a novel combination of an at-home testing program, a broad communications and community engagement strategy, an ecological study to assess impact, and a research substudy of the behavioral aspects of testing. The findings from the SYCT project will provide insights into innovative methods to mitigate viral transmission, advance the science of public health communications and community engagement, and evaluate emerging, novel assessments of community transmission of disease.

Rapid Diagnostic Tests to Guide Case Management of and Improve Antibiotic Stewardship for Pediatric Acute Respiratory Illnesses in Resource-Constrained Settings: a Prospective Cohort Study in Southwestern Uganda.

Pediatric acute respiratory illness (ARI) is one of the most common reasons for evaluation at peripheral health centers in sub-Saharan Africa and is frequently managed based on clinical syndrome alone. Although most ARI episodes are likely caused by self-limited viral infections, the majority are treated with antibiotics. This overuse contributes to the development of antimicrobial resistance. To evaluate the preliminary feasibility and potential impact of adding pathogen-specific and clinical biomarker diagnostic testing to existing clinical management algorithms, we conducted a prospective, observational cohort study of 225 children presenting with malaria-negative, febrile ARI to the outpatient department of a semi-urban peripheral health facility in southwestern Uganda from October 2019 to January 2020. In addition to routine clinical evaluation, we performed influenza and Streptococcus pneumoniae antigen testing and measured levels of C-reactive protein, procalcitonin, and lactate in the clinic's laboratory, and conducted a follow-up assessment by phone 7 days later. Almost one-fifth of participants (40/225) tested positive for influenza. Clinical biomarker measurements were low with C-reactive protein of >40 mg/L in only 11% (13/222) of participants and procalcitonin >0.25 ng/mL in only 13% (16/125). All but two children received antibiotic treatment; only 3% (7/225) were admitted. At follow-up, 59% (118/201) of caregivers reported at least one persistent symptom, but fever had resolved for all children. Positive influenza testing was associated with persistent symptoms. In summary, we demonstrate that simple, rapid pathogen-specific testing and biomarker measurement are possible in resource-limited settings and could improve syndromic management and, in turn, antibiotic stewardship. IMPORTANCE Globally, respiratory illness is one of the most common reasons that children seek care. It is often treated inappropriately with antibiotics, which can drive the development of antibiotic resistance. In resource-rich settings, testing for specific pathogens or measurement of clinical biomarkers, such as procalcitonin and C-reactive protein, is often employed to help determine which children should receive antibiotics. However, there are limited data on the use of these tests in resource-constrained, outpatient contexts in sub-Saharan Africa. We enrolled children with respiratory illness presenting to a clinic in southwestern Uganda and performed testing for influenza, Streptococcus pneumoniae, C-reactive protein, and procalcitonin on-site. Almost all children received antibiotics. We demonstrate that employing clinical algorithms that include influenza and clinical biomarker testing could significantly decrease antibiotic prescriptions. Our study therefore provides preliminary data to support the feasibility and potential utility of diagnostics to improve management of respiratory illness in resource-constrained settings.

SARS-CoV-2 infection in central North Carolina: Protocol for a population-based longitudinal cohort study and preliminary participant results.

Public health surveillance systems likely underestimate the true prevalence and incidence of SARS-CoV-2 infection due to limited access to testing and the high proportion of subclinical infections in community-based settings. This ongoing prospective, observational study aimed to generate accurate estimates of the prevalence and incidence of, and risk factors for, SARS-CoV-2 infection among residents of a central North Carolina county. From this cohort, we collected survey data and nasal swabs every two weeks and venous blood specimens every month. Nasal swabs were tested for the presence of SARS-CoV-2 virus (evidence of active infection), and serum specimens for SARS-CoV-2-specific antibodies (evidence of prior infection). As of June 23, 2021, we have enrolled a total of 153 participants from a county with an estimated 76,285 total residents. The anticipated study duration is at least 24 months, pending the evolution of the pandemic. Study data are being shared on a monthly basis with North Carolina state health authorities and future analyses aim to compare study data to state-wide metrics over time. Overall, the use of a probability-based sampling design and a well-characterized cohort will enable collection of critical data that can be used in planning and policy decisions for North Carolina and may be informative for other states with similar demographic characteristics.

Improving recognition and management of children with complicated severe acute malnutrition at a tertiary referral hospital in Malawi: a quality improvement initiative.

BACKGROUND: Severe acute malnutrition (SAM) is common in low-income countries and is associated with high mortality in young children. OBJECTIVE: To improve recognition and management of SAM in a tertiary hospital in Malawi. METHODS: The impact of multifaceted quality improvement interventions in process measures pertaining to the identification and management of SAM was assessed. Interventions included focused training for clinical staff, reporting process measures to staff, and mobile phone-based group messaging for enhanced communication. This initiative focused on children aged 6-36 months admitted to Kamuzu Central Hospital in Malawi from September 2019 to March 2020. Before-after comparisons were made with baseline data from the year before, and process measures within this intervention period which included three plan-do-study-act (PDSA) cycles were compared. RESULTS: During the intervention period, 418 children had SAM and in-hospital mortality was 10.8%, which was not significantly different from the baseline period. Compared with the baseline period, there was significant improvement in the documentation of full anthropometrics on admission, blood glucose test within 24 hours of admission and HIV testing results by discharge. During the intervention period, amidst increasing patient census with each PDSA cycle, three process measures were maintained (documentation of full anthropometrics, determination of nutritional status and HIV testing results), and there was significant improvement in blood glucose documentation. CONCLUSION: Significant improvement in key quality measures represents early progress towards the larger goal of improving patient outcomes, most notably mortality, in children admitted with SAM.