Consecutive Negative Tests Research Articles

Modeling relaxed policies for discontinuation of methicillin-resistant Staphylococcus aureus contact precautions.

To evaluate the economic costs of reducing the University of Virginia Hospital's present "3-negative" policy, which continues methicillin-resistant Staphylococcus aureus (MRSA) contact precautions until patients receive 3 consecutive negative test results, to either 2 or 1 negative. Cost-effective analysis. The University of Virginia Hospital. The study included data from 41,216 patients from 2015 to 2019. We developed a model for MRSA transmission in the University of Virginia Hospital, accounting for both environmental contamination and interactions between patients and providers, which were derived from electronic health record (EHR) data. The model was fit to MRSA incidence over the study period under the current 3-negative clearance policy. A counterfactual simulation was used to estimate outcomes and costs for 2- and 1-negative policies compared with the current 3-negative policy. Our findings suggest that 2-negative and 1-negative policies would have led to 6 (95% CI, -30 to 44; P < .001) and 17 (95% CI, -23 to 59; -10.1% to 25.8%; P < .001) more MRSA cases, respectively, at the hospital over the study period. Overall, the 1-negative policy has statistically significantly lower costs ($628,452; 95% CI, $513,592-$752,148) annually (P < .001) in US dollars, inflation-adjusted for 2023) than the 2-negative policy ($687,946; 95% CI, $562,522-$812,662) and 3-negative ($702,823; 95% CI, $577,277-$846,605). A single negative MRSA nares PCR test may provide sufficient evidence to discontinue MRSA contact precautions, and it may be the most cost-effective option.

Persistent colonization of Candida auris among inpatients rescreened as part of a weekly surveillance program.

We established a surveillance program to evaluate persistence of C. auris colonization among hospitalized patients. Overall, 17 patients (34%) had ≥1 negative result followed by a positive test, and 7 (41%) of these patients had ≥2 consecutive negative tests.

Optimising follow-up strategy based on cytology and human papillomavirus after fertility-sparing surgery for early stage cervical cancer: a nationwide, population-based, retrospective cohort study

The optimal follow-up strategy to detect recurrence after fertility-sparing surgery for early stage cervical cancer is unknown. Tailored surveillance based on individual risks could contribute to improved efficiency and, subsequently, reduce costs in health care. The aim of this study was to establish the predictive value of cervical cytology and high-risk human papillomavirus (HPV) testing to detect recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+; including recurrent cervical cancer) after fertility-sparing surgery. In this nationwide, population-based, retrospective cohort study, we used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank. All patients aged 18-40 years with cervical cancer of any histology who received fertility-sparing surgery (ie, large loop excision of the transformation zone, conisation, or trachelectomy) between Jan 1, 2000, and Dec 31, 2020, were included. Pathology data from diagnosis, treatment, and during follow-up were analysed. The primary and secondary outcomes were the cumulative incidence of recurrent CIN2+ and recurrence-free survival, overall and stratified by results for cytology and high-risk HPV. 1548 patients were identified, of whom 1462 met the inclusion criteria. Of these included patients, 19 568 pathology reports were available. The median age at diagnosis was 31 years (IQR 30-35). After a median follow-up of 6·1 years (IQR 3·3-10·8), recurrent CIN2+ was diagnosed in 128 patients (cumulative incidence 15·0%, 95% CI 11·5-18·2), including 52 patients (cumulative incidence 5·4%, 95% CI 3·7-7·0) with recurrent cervical cancer. The overall 10-year recurrence-free survival for CIN2+ was 89·3% (95% CI 87·4-91·3). By cytology at first follow-up visit within 12 months after fertility-sparing surgery, 10-year recurrence-free survival for CIN2+ was 92·1% (90·2-94·1) in patients with normal cytology, 84·6% (77·4-92·3) in those with low-grade cytology, and 43·1% (26·4-70·2) in those with high-grade cytology. By high-risk HPV status at first follow-up visit within 12 months after surgery, 10-year recurrence-free survival for CIN2+ was 91·1% (85·3-97·3) in patients who were negative for high-risk HPV and 73·6% (58·4-92·8) in those who were positive for high-risk HPV. Cumulative incidence of recurrent CIN2+ within 6 months after any follow-up visit (6-24 months) in patients negative for high-risk HPV with normal or low-grade cytology was 0·0-0·7% and with high-grade cytology was 0·0-33·3%. Cumulative incidence of recurrence in patients positive for high-risk HPV with normal or low-grade cytology were 0·0-15·4% and with high-grade cytology were 50·0-100·0%. None of the patients who were negative for high-risk HPV without high-grade cytology, at 6 months and 12 months, developed recurrence. Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery, could be offered a prolonged follow-up interval of 6 months. This group comprises 80% of all patients receiving fertility-sparing surgery. An interval of 12 months seems to be safe after two consecutive negative tests for high-risk HPV with an absence of high-grade cytology, which accounts for nearly 75% of all patients who receive fertility-sparing surgery. KWF Dutch Cancer Society.

Updated COVID-19 clearance time among patients with cancer in the Delta and Omicron waves.

COVID-19 infection delays therapy and in-person evaluation for oncology patients, but clinic clearance criteria are not clearly defined. We conducted a retrospective review of oncology patients with COVID-19 at a tertiary care center during the Delta and Omicron waves and compared clearance strategies. Median clearance by two consecutive negative tests was 32.0 days (Interquartile Range [IQR] 22.0-42.5, n = 153) and was prolonged in hematologic malignancy versus solid tumors (35.0 days for hematologic malignancy, 27.5 days for solid tumors, p = 0.01) and in patients receiving B-cell depletion versus other therapies. Median clearance by single negative test was reduced to 23.0 days (IQR 16.0-33.0), with recurrent positive rate 25.4% in hematologic malignancy versus 10.6% in solid tumors (p = 0.02). Clearance by a predefined waiting period required 41 days until an 80% negative rate. COVID-19 clearance remains prolonged in oncology patients. Single-negative test clearance can balance delays in care with risk of infection in patients with solid tumors.

High positive rate after consecutive negative tests of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a global public health event since 2019. Real-time reverse transcription polymerase chain reaction (RT-PCR) assays of upper respiratory tract specimens were used as the most common method for confirmation of SARS-CoV-2. Patients diagnosed with coronavirus disease 2019 and hospitalized in Cancer Center of Wuhan Union Hospital were retrospectively enrolled. Epidemiological, clinical, and laboratory records were analyzed with highlights on the pattern of results of repeated RT-PCR tests. Nine hundred eighty-four patients admitted to hospital between February 13, 2020 to March 10, 2020 were enrolled. The median age was 62.0 years (interquartile range 49.0-68.0) and 44.5% was male. Three thousand-three hundred eleven specimens were collected for RT-PCR tests with a median of 3 tests (interquartile range 2.0-4.0) per patient. Three hundred sixty-two (36.8%) patients showed positive records from repeated RT-PCR tests. For the 362 confirmed patients, 147 cases received further RT-PCR tests after 2 consecutive negative records of SARS-CoV-2 and 38 (26%) of them obtained a positive result. Ten (23%) of 43 patients showed positive results after 3 consecutive negative tests and 4 (24%) of 17 patients were positive after 4 negative tests. Consecutive negative RT-PCR tests with respiratory specimens could not guarantee a viral clearance.

An open, retrospective study on the duration of virus shedding for Shanghai patients infected with SARS-CoV-2 omicron variants.

An open, retrospective study on the duration of virus shedding for Shanghai patients infected with SARS-CoV-2 omicron variants.

YIELD OF SERIAL TESTING FOR TUBERCULOSIS EXPOSURE IN THE STUDY OF A PROSPECTIVE ADULT RESEARCH COHORT WITH INFLAMMATORY BOWEL DISEASES (SPARC IBD)

Abstract BACKGROUND More than 2 million Americans have Inflammatory Bowel Diseases (IBD), including Crohn’s Disease or Ulcerative Colitis. Although tuberculosis is uncommon in the United States, patients with IBD are at an increased risk for active tuberculosis infection due to the immunosuppressant therapies used to treat IBD. Due to this risk, testing for latent tuberculosis is recommended prior to and intermittently throughout administration of most IBD medications. The utility of this practice in a country with a low incidence and prevalence of tuberculosis is unknown. We aimed to determine the proportion of initial and subsequent tuberculosis tests that are positive, negative, or indeterminate. METHODS Data were acquired from SPARC IBD, a component of the Crohn’s &amp; Colitis Foundation’s IBD Plexus research platform. SPARC IBD is a prospective cohort study conducted at 18 centers throughout the USA and includes more than 4,000 patients. Data are collected from SPARC IBD case report forms and the IBD Smartform, diagnoses, test results and prescriptions within the linked electronic medical records. Patients with one or more interferon gamma release assay (IGRA) test for latent tuberculosis were included in this study. The outcome investigated was a positive, negative, or indeterminate lab result. The proportion of positive and indeterminate tests were computed with 95% confidence intervals (CI). Fisher’s exact test was used to detect a change in positive test proportions following a negative test compared to initial lab results. RESULTS A total of 687 patients with one or more IGRA test were identified. The median age was 37 (IQR 27-50) with 54% female patients. Of the initial lab results, 644 tests were negative (93.7%, 95% CI, 91.7, 95.4), 37 were indeterminate (5.4%, 95% CI, 3.8, 7.3), and six were positive (0.9%, 95% CI, 0.3, 1.9). Following an initial negative result, 269 patients received a second test, of which five were positive (1.9%, 95% CI, 0.6, 4.3). Following two consecutive negative results, 142 patients received an additional IGRA test, of which one was positive (0.7%, 95% CI, 0.02, 3.9). The proportion of positive tests was not significantly lower following one negative (p = 0.20) or two consecutive negative tests (p &amp;gt; 0.99). POTENTIAL LIMITATIONS Many patients only had one test for latent tuberculosis, and it is unclear if the initial IGRA labs in our dataset were their first latent tuberculosis tests. CONCLUSIONS Based on the findings of this study, there appears to be value in continued serial testing following a negative result even in the United States, despite the overall low incidence of tuberculosis.

First study on the efficacy of abamectin in a combined formulation with praziquantel against Aelurostrongylus abstrusus in cats

The information about abamectin efficacy in cases of feline aelurostrongylosis is scarce. Six naturally infected cats were treated with combination of abamectin and praziquantel every seven days until two consecutive negative faecal test results. Abamectin was administered at a dose rate of 0.1 mg/kg. For the evaluation of the efficacy, the number of larvae per gram (LPG) was assessed 30 and 60 days after the first treatment by the Baermann’s technique. After the first 4 administrations, a rapid decline in LPG was observed and after the 8th administration, all animals were free of A. abstrusus larvae. Although the results affirm that abamectin may be successfully used in cases of aelurostrogylosis in cats, further clinical studies are needed to validate this pilot investigation.

Can Chest CT be the first-line diagnostic test in COVID-19? A cross-sectional study

ABSTRACT&#x0D; Background/aim: Early in the COVID-19 pandemic, chest computerized tomography (CCT) was shown to be more sensitive than real-time reverse transcription polymerase chain Reaction (rRT-PCR) in detecting the disease, especially in regions with high disease prevalence. In this study, we aimed to determine the sensitivity and specificity of chest CT in the diagnosis of COVID-19.&#x0D; Materials and methods: Between 17 March, 2020 and 25 April, 2020, 2170 patients who were admitted to the hospital for any reason and underwent chest CT scanning were retrospectively analyzed. Patients with a pre-diagnosis of COVID-19 and a positive rRT-PCR test, two consecutive negative rRT-PCR tests, or with a first negative rRT-PCR test and a positive follow-up rRT-PCR test were included. The day of the rRT-PCR test for these patients was counted as day “0,” and 200 patients whose CCT was performed within +/- three days were included in the study.&#x0D; Results: Of the 200 patients included in the study, 118 were rRT-PCR-positive, and 82 were rRT-PCR-negative. Of the 118 patients with positive rRT-PCR results, 62/118 (52.5%) had positive CCT scans. With the rRT-PCR results as the reference, the sensitivity, specificity, and accuracy of CCT in indicating COVID-19 infection were 52.5% (95% CI 43–61%), 67% (95% CI 56–77%), and 58.5% (95% CI 51-65%), respectively. The negative predictive value of CCT in diagnosing COVID-19 was greater for women than for men (p = 0.01).&#x0D; Conclusions: In regions where the prevalence of COVID-19 is not high, the use of CCT in the diagnosis of the disease is not an alternative to the rRT-PCR test due to its low sensitivity.

1943. Effect of Vaccination on Household Transmission of SARS-CoV-2

Abstract Background Understanding how COVID-19 vaccination affects transmission of SARS-CoV-2 within households may affect policy and healthcare decisions. We hypothesized that vaccination reduces transmission and viral load in vaccinated household members. Methods We prospectively enrolled participants during March 2020 – October 2021. Index cases (IC) were eligible if they tested positive for SARS-CoV-2 within the previous 10 days and did not have household contacts (HC) who had tested positive or had symptoms of COVID-19. Participants self-collected anterior nares swabs daily for SARS-CoV-2 RT-PCR for at least 21 days, or once every member of the household had 7 consecutive negative tests. Baseline data included demographics and self-reported vaccination status. Complete COVID-19 vaccination was defined as receiving 2 doses of Moderna/Pfizer or 1 dose of Johnson &amp; Johnson vaccine, and incomplete vaccination as receiving 1 dose of Moderna/Pfizer vaccine. Household transmission was analyzed via STATA 14.2 using logistic regression with robust standard error clustered by household, and SARS-CoV-2 cycle threshold was graphed by day of study enrollment using lowess smoothing. Results There were 60 households with positive ICs and 103 HCs for a total of 163 participants. ICs had median age 41.5 years (range 1–86) with 9 (18.0%) &amp;lt; 18 years. HCs had median age 34 years (range 0–87) with 32 (31.1%) HCs &amp;lt; 18 years. Overall, 33 (20.2%) participants received at least one COVID-19 vaccine dose. A total of 50 households had at least one HC (median 2, max 7). Transmission of SARS-CoV-2 occurred in 45 HCs (43.7%). Odds of SARS-CoV-2 transmission was lower in HCs who were vaccinated prior to study enrollment, though this finding was not statistically significant (Table 1). There were 507 positive SARS-CoV-2 tests collected among 74 participants (Figure 1). Table 1.Household Transmission By COVID-19 Vaccination Status Prior to Study Enrollment (among households with ≥ one household contact)*Using logistic regression with robust standard error, clustered by household. Reference is top group listed in each comparison (includes unvaccinated).CI: Confidence IntervalCompletely vaccinated: Received primary COVID-19 vaccination series (2 doses Pfizer or Moderna vaccine, or 1 dose Johnson &amp; Johnson vaccine) prior to enrollmentIncompletely vaccinated: Received of 1 dose of Pfizer or Moderna vaccine prior to enrollmentUnvaccinated: No COVID-19 vaccines prior to enrollmentFigure 1.SARS-CoV-2 Cycle Threshold Over Time by COVID-19 Vaccination Status Completely vaccinated: Received primary COVID-19 vaccination series (2 doses Pfizer or Moderna vaccine, or 1 dose Johnson &amp; Johnson vaccine) prior to enrollment Conclusion Vaccination of HCs may be protective against household SARS-CoV-2 transmission. However, analyses were limited due to low numbers of vaccinated study participants. Study enrollment is ongoing, and future analyses will include transmission during the 2022 Omicron surge, and daily symptom data which has been collected. Disclosures Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Member, DSMB, Pfizer Meningococcal Vaccine clinical trial.

Getting Negative for COVID-19: Role of Ethnicity and Demographic Factors

Objective: To explore the relationship between ethnicity and demographic factors with the time taken by patients to get negative on PCR for COVID-19.&#x0D; Study Design: Prospective Comparative Study.&#x0D; Place and Duration of Study: Combined Military Hospital, Malir Pakistan, from Mar to May 2020.&#x0D; Methodology: All patients who tested positive for COVID-19 with less than one week of exposure time and were admitted to the COVID-19 ward of Combined Military Hospital, Malir without any complications were included in the study. They were tested after every seven days with PCR. Time taken to get two consecutive negative tests were noted for each patient.&#x0D; Results: Out of 84 patients included in the study, 12(14.3%) tested negative on the 7th day, 34(40.4%) on the 14th day and 38(45.3%) tested negative after 14 days. 17(20.2%) were Sindhi, 13(15.5%) were Muhajir, 19(22.6%) were Punjabi, 25(29.7%) were Pathan, and 10(11.9%) were Kashmiris. Chi-square revealed that ethnicity and advancing age have a statistically significant relationship (p-value&lt;0.05) with the time taken by patients to get negative on PCR for COVID-19.&#x0D; Conclusion: Ethnicity emerged as a significant factor in getting negative for COVID-19. Punjabis and Kashmiris required a shorter period to get negative than Sindhis and Pathans. Older age emerged as a factor requiring a longer period to get negative.

Vaccination, symptomatic infection and negative conversion of viral RNA by body mass index, diabetes, and age: An observational study

BackgroundThe associations of doses of vaccine received with symptomatic infection with SARS-CoV-2 and negative conversion rate of viral RNA by BMI, diabetes, and age are unclear. MethodsIncluded were adult cases of SARS-CoV-2 infection hospitalized at a makeshift hospital in Shanghai (N = 38,592). Each case received a real-time reverse transcriptase–polymerase chain reaction (RT-PCR) test every day until discharge. Symptomatic cases had ≥1 pre-specified symptoms. Negative conversion time (NCT) was the duration between the specimen collection date associated with the first positive RT-PCR test and the first test date of the two consecutive negative tests at least 24 h apart. BMI-, diabetes- and age-stratified multivariable logistic and Poisson regressions were applied. FindingsCoexistence of overweight/obesity and diabetes was associated with a higher risk of symptomatic infection and a longer NCT compared with coexistence of normal weight and without diabetes, but this association was primarily attributed to underlying comorbidities. Compared with absence of vaccination, booster vaccination, but not full vaccination, was consistently associated with a 42 %–56 % lower odds of symptomatic infection and ∼1.6–1.8 days of shorter NCT across different strata separately for weight and diabetes. Age-stratified analyses found that the effectiveness of booster vaccination did not attenuate with age, except for preventing symptomatic infection among adults with diabetes. InterpretationBMI and diabetes co-determined their associations with symptomatic infection and NCT. Booster vaccination but not full vaccination was associated a lower risk of symptomatic infection, a shorter NCT or both regardless of BMI, diabetes status and age.

COVID-19 clearance among patients with cancer during the Delta and Omicron waves.

42 Background: COVID-19 presents a particular challenge in oncology, as in-person visits and treatments can be delayed during infection and patients are at risk for prolonged viral shedding. Our center uses two consecutive negative PCR tests for patients to return to clinic. As vaccination rates increase, we questioned the need for this strategy vs a time-based clearance approach. Methods: We identified cancer patients who tested positive for COVID-19 from 10/1/2021 to 3/31/2022 at a single tertiary care center and performed chart review under an IRB-approved protocol. Subgroups were compared using the Welch’s t-test and Welch’s ANOVA for 2 or &gt; 2 groups, respectively. Results: 169 patients were identified. 153 had documented clearance defined as two consecutive negative PCR tests. The mean clearance time was 35.7 days (95% CI 32.3-39.0). There was a trend toward longer clearance time in patients with hematologic vs solid tumors (39.6 vs 33.2, p =.06) and a significant increase in patients treated with B cell depletion (58.0) vs chemo/targeted therapy (35.7, p =.01) or immunotherapy (29.0, p =.004). No significant difference was found by vaccination status or between the Delta and Omicron waves. If defined as one negative test, mean clearance time was 25.9 days (95% CI 23.6-28.1), and there was a significant difference in patients with hematologic vs solid tumors and in those treated with B cell depletion vs other therapies. However, 16.0% (27/169) of patients had a subsequent positive test after a first negative result, with increased incidence in patients with hematologic malignancy (26.2%, 16/61) and stem cell/adoptive cell transplant (46.2%, 6/13). Conclusions: COVID-19 is a significant barrier to oncologic care, and clearance times remain longer than reported for the general population. In this single center study, clearance time was &gt; 1 month and further increased in patients with hematologic malignancy or on B cell depleting therapy. While adjusting clearance criteria to a single negative test or specific timeframe may be an attractive option to reduce delays, a large proportion of patients may have further positive PCR testing.[Table: see text]

A multicenter, double-blind, randomized, parallel-group, placebo-controlled study to evaluate the efficacy and safety of camostat mesilate in patients with COVID-19 (CANDLE study).

BackgroundIn vitro drug screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19).MethodsThis was a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were enrolled, randomized, and allocated to each group using an interactive web response system. Randomization was performed using a minimization method with the factors medical institution, age, and underlying diseases (chronic respiratory disease, chronic kidney disease, diabetes mellitus, hypertension, cardiovascular diseases, and obesity). The patients, investigators/subinvestigators, study coordinators, and other study personnel were blinded throughout the study. Patients were administered camostat mesilate (600 mg qid; four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2.ResultsOne-hundred fifty-five patients were randomized to receive camostat mesilate (n = 78) or placebo (n = 77). The median time to the first test was 11.0 days (95% confidence interval [CI]: 9.0–12.0) in the camostat mesilate group and 11.0 days (95% CI: 10.0–13.0) in the placebo group. Conversion to negative viral status by day 14 was observed in 45 of 74 patients (60.8%) in the camostat mesilate group and 47 of 74 patients (63.5%) in the placebo group. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified.ConclusionsCamostat mesilate did not substantially reduce the time to viral clearance, based on upper airway viral loads, compared with placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms.Trial registrationClinicalTrials.gov, NCT04657497. Japan Registry for Clinical Trials, jRCT2031200198.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12916-022-02518-7.

Secondary Prevention of Cervical Cancer: ASCO Resource-Stratified Guideline Update.

To update resource-stratified, evidence-based recommendations on secondary prevention of cervical cancer globally. American Society of Clinical Oncology convened a multidisciplinary, multinational Expert Panel to produce recommendations reflecting four resource-tiered settings. A review of existing guidelines, formal consensus-based process, and modified ADAPTE process to adapt existing guidelines was conducted. Other experts participated in formal consensus. This guideline update reflects changes in evidence since the previous update. Five existing guidelines were identified and reviewed, and adapted recommendations form the evidence base. Cost-effectiveness analyses provided indirect evidence to inform consensus, which resulted in ≥ 75% agreement. Human papillomavirus (HPV) DNA testing is recommended in all resource settings; visual inspection with acetic acid may be used in basic settings. Recommended age ranges and frequencies vary by the following setting: maximal: age 25-65 years, every 5 years; enhanced: age 30-65 years, if two consecutive negative tests at 5-year intervals, then every 10 years; limited: age 30-49 years, every 10 years; basic: age 30-49 years, one to three times per lifetime. For basic settings, visual assessment is used to determine treatment eligibility; in other settings, genotyping with cytology or cytology alone is used to determine treatment. For basic settings, treatment is recommended if abnormal triage results are obtained; in other settings, abnormal triage results followed by colposcopy is recommended. For basic settings, treatment options are thermal ablation or loop electrosurgical excision procedure; for other settings, loop electrosurgical excision procedure or ablation is recommended; with a 12-month follow-up in all settings. Women who are HIV-positive should be screened with HPV testing after diagnosis, twice as many times per lifetime as the general population. Screening is recommended at 6 weeks postpartum in basic settings; in other settings, screening is recommended at 6 months. In basic settings without mass screening, infrastructure for HPV testing, diagnosis, and treatment should be developed.Additional information is available at www.asco.org/resource-stratified-guidelines.

Outbreak of Middle East Respiratory Syndrome Coronavirus in Camels and Probable Spillover Infection to Humans in Kenya.

The majority of Kenya’s > 3 million camels have antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV), although human infection in Africa is rare. We enrolled 243 camels aged 0–24 months from 33 homesteads in Northern Kenya and followed them between April 2018 to March 2020. We collected and tested camel nasal swabs for MERS-CoV RNA by RT-PCR followed by virus isolation and whole genome sequencing of positive samples. We also documented illnesses (respiratory or other) among the camels. Human camel handlers were also swabbed, screened for respiratory signs, and samples were tested for MERS-CoV by RT-PCR. We recorded 68 illnesses among 58 camels, of which 76.5% (52/68) were respiratory signs and the majority of illnesses (73.5% or 50/68) were recorded in 2019. Overall, 124/4692 (2.6%) camel swabs collected from 83 (34.2%) calves in 15 (45.5%) homesteads between April–September 2019 screened positive, while 22 calves (26.5%) recorded reinfections (second positive swab following ≥ 2 consecutive negative tests). Sequencing revealed a distinct Clade C2 virus that lacked the signature ORF4b deletions of other Clade C viruses. Three previously reported human PCR positive cases clustered with the camel infections in time and place, strongly suggesting sporadic transmission to humans during intense camel outbreaks in Northern Kenya.

Three elderly asymptomatic SARS-CoV-2 infected patients in ICU.

Previous studies on asymptomatic COVID-19 carriers indicated that asymptomatic infections always occurred in people in community or patients in general wards, prone to be young and middle aged people. Limited data are available for asymptomatic infections in critically ill patients in intensive care unit or elderly people. Here we reported three elderly asymptomatic SARS-CoV-2 infected patients in intensive care unit. These three elderly patients had negative CT images and 14 consecutive negative RT-PCR test results, with dynamic changes in IgG-IgM antibody levels without any clinical symptoms, which might be related to their weakened immune responses due to elder age (over 85 years old) and the history of hypertension. Therefore, combining nucleic acid RT-PCR and the IgM-IgG antibody test can provide more accurate SARS-CoV-2 infection diagnosis, especially for elderly asymptomatic patients.

Factors associated with prolonged viral detection in asymptomatic and mildly symptomatic patients with SARS-CoV-2 infection.

Data on the clinical course and duration of viral RNA detection in patients with mild or asymptomatic coronavirus disease 2019 are limited. In this retrospective analysis, clinical characteristics and serial real-time reverse transcriptase-polymerase chain reaction (RT-PCR) results were reviewed in a cohort of 1186 asymptomatic and mildly symptomatic coronavirus disease 2019 patients in South Korea. Factors associated with prolonged duration of RT-PCR positivity for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) were also evaluated. Patients with two consecutive negative RT-PCR tests ≥ 24 hours apart were considered to be in virologic remission and discharged. The average virologic remission period, defined as the number of days from diagnosis to virologic remission, was 22.0 ± 9.7 days; patients with longer than 30 days accounted for 21.2% (251/1186) of the population. Patients who took longer than 30 days to achieve virologic remission had a higher frequency of overall symptoms (p < 0.001) and respiratory symptoms (p < 0.001). In multivariate analysis using Cox-proportional hazard regression, it was confirmed that respiratory symptoms (hazard ratio [HR], 0.7372; 95% confidence interval [CI], 0.6540-0.8311) and gastrointestinal symptoms (HR, 0.8213; 95% CI, 0.6970-0.9679) were independent factors associated with prolonged virologic remission. Age and co-morbidity such as diabetes and hypertension were not associated with the prolonged RT-PCR positivity. A considerable percentage of asymptomatic and mildly symptomatic patients with coronavirus disease 2019 showed prolonged RT-PCR positivity for SARS-CoV-2; which was independently associated with the presence of symptoms, but not with age and co-morbidity.

Added Value of an Anti-Ebola Serology for the Management of Clinically Suspected Ebola Virus Disease Patients Discharged as Negative in an Epidemic Context.

BackgroundSurvivors from Ebola virus disease (EVD) may be at the origin of EVD resurgence.MethodsSimultaneous reactivity to at least 2 Ebola virus or Zaire ebolavirus (EBOV) antigens was detected in 11 of 488 (2.3%; 95% confidence interval [CI], 1.1–4.0) suspected EVD patients who were discharged as negative after 2 consecutive negative tests during the 10th Ebola outbreak in the Democratic Republic of the Congo.ResultsAfter extrapolating the total number of individuals discharged as negative during the entire outbreak, we estimated a total of 1314 additional missed Ebola cases.ConclusionsThese findings emphasize the usefulness of an EBOV serology analysis and the importance of extending epidemic surveillance to clinically suspected cases who were discharged as negative.

ЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ ДЕЛАМАНИД-СОДЕРЖАЩИХ РЕЖИМОВ У ПАЦИЕНТОВ С ЛЕКАРСТВЕННО УСТОЙЧИВЫМ ТУБЕРКУЛЕЗОМ И КОМОРБИДНОЙ СЕРДЕЧНО-СОСУДИСТОЙ ПАТОЛОГИЕЙ

Aim. To study the effectiveness of treatment with delamanid-containing regimens in patients with multidrug-resistant and extensively drug-resistant tuberculosis and comorbid cardiovascular diseases, to assess the frequency, structure, and severity of adverse events in the cardiovascular system in this group of patients. Materials and methods. The study included 125 adult patients with multidrug and extensive drug resistance who started treatment with delamanid-containing regimens from July 2016 to February 2018 at the Republican Research and Practical Center for Pulmonology and Tuberculosis and six regional anti-TB institutions. The main group included patients with multiple and extensive drug resistance and comorbid cardiovascular diseases (N = 46). The control group included patients with multiple and extensive drug resistance without comorbid cardiovascular diseases (N = 79). The formulation and coding of the diagnosis (the underlying disease and comorbid diseases (conditions)) corresponded to the International Classification of Diseases (ICD) of the 10th revision. Adverse events were classified according to the international dictionary MedDRA (Medical Dictionary for Regulatory Activities). The severity of adverse events classification complied with CTCAE (Common Terminology Criteria for Adverse Events). The severity of adverse events was determined in accordance with the definitions of ICH (The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), and the treatment outcomes were identified in accordance with clinical guidelines and WHO recommendations. The study materials were the data from the medical records of the patients in the E-Register "Tuberculosis". Sputum culture conversion was defined as two consecutive negative test results. Treatment outcomes were classified as successful and unsuccessful. For the analysis of adverse events, each event was considered as a unit of analysis both in the aggregate of all adverse events in the cardiovascular system and in groups of patients. Testing of statistical hypotheses was carried out at a critical level of significance p = 0.05, i.e. the difference was considered statistically significant if p &lt; 0.05. Results. The effectiveness of treatment with delamanid-containing regimens in the group of patients with comorbid cardiovascular diseases was 88.0%, sputum conversion after 6 months of treatment (abacillation by culture) was observed in 93.0% of patients in this group, when compared no statistical difference was present in the effectiveness of treatment (p = 3.841) of the patients of the main group and those of the comparison group. In the analysis of long-term results, only one patient with cardiovascular comorbidity (3.0%) had a relapse of tuberculosis more than one year after successful treatment. 78.0% of patients of the main study group (with comorbid cardiovascular diseases) and 70.0% of the comparison group manifested cardiovascular adverse events during treatment. The most common adverse event in both groups was prolongation of the QTcF interval, which was recorded in 37.0% of patients with comorbid cardiovascular diseases and in 42.0% of patients without cardiovascular diseases (p = 0.597). Timely correction and careful monitoring of adverse events made it possible to avoid the development of life-threatening conditions in both groups of patients. In this regard, no withdrawal of anti-tuberculosis drugs was registered due to cardiovascular adverse events, including those due to the prolongation of the QTcF interval. The highest frequency of cardiovascular adverse events was detected during the first month of treatment of patients, then, in the course of treatment, it decreased, which may indirectly indicate the absence of a cumulative cardiotoxic effect of delamanid-containing treatment regimens. Conclusions. Treatment with delamanid-containing regimens in adult patients with multidrug-resistant tuberculosis and comorbid cardiovascular disease was effective and had an overall favorable cardiovascular safety profile comparable to the comparison group. Despite a large number of cardiovascular adverse events, they were manageable at the program level (prevailing at the initial stages of treatment, having light, mild or moderate severity, having been relieved), which made it possible to complete anti-tuberculosis treatment with delamanid-containing regimens.