Of 633 consecutively enrolled febrile patients, 321 (50.7%) had antileptospiral IgM antibodies or high titers of antileptospiral antibodies. Seven patients with histories of only urban exposure to leptospires had severe pulmonary manifestations; of these, 5 patients died; 4 of the deaths were caused by pulmonary hemorrhage, and 1 was caused by acute respiratory distress syndrome and multiorgan failure. Real-time, quantitative PCR assay showed high levels of leptospiremia (>or=10(4) leptospires/mL) in most fatal cases; 1 patient, from whom tissue specimens were obtained at autopsy, had >or=10(5) leptospires/g of lung, kidney, and muscle tissue. DISCUSSION. This study demonstrates the underdiagnosis of leptospirosis in a region of high endemicity and the underrecognition of grave pulmonary complications. Pulmonary involvement in leptospirosis was present in urban but not rural areas. Presumptive treatment for leptospirosis should be initiated immediately in the appropriate epidemiological and clinical context.

The roles of innate immune responses in protection from or pathogenesis of severe leptospirosis remain unclear. We examined the role of Toll-like receptors (TLRs) in mouse infection and macrophage responses to Leptospira. C3H/HeJ mice (TLR4 deficient) and C3H/HeJ-SCID mice, but not C3H/OuJ mice (TLR4 intact), died after intraperitoneal infection with Leptospira interrogans serovar Icterohaemorrhagiae. Death in both C3H/HeJ mouse strains was associated with jaundice and pulmonary hemorrhage, similar to the patient from whom the isolate was obtained. In chronic sublethal infection, TLR4-deficient mice harbored more leptospires in liver, lung, and kidney than control mice. Heat-killed Leptospira stimulated macrophages to secrete proinflammatory cytokines, tumor necrosis factor alpha, interleukin-6, and macrophage inflammatory protein 2 not inhibited by polymyxin B, suggesting that leptospiral lipopolysaccharide (LPS) did not drive these responses. Anti-TLR4 and anti-MD-2 but not anti-CD14 monoclonal antibodies inhibited cytokine production. Peritoneal macrophages from CD14؊/؊ and TLR2 ؊/؊ mice exhibited no defect in cytokine responses to Leptospira compared to controls. Macrophages from C3H/HeJ, TLR4 ؊/؊ , and MyD88 ؊/؊ mice secreted far-lower levels of cytokines than wild-type macrophages in response to Leptospira. TLR4 plays a crucial role in protection from acute lethal infection and control of leptospiral burden during sublethal chronic infection. Cytokine responses in macrophages correlated with leptospiral clearance. These TLR4-dependent but CD14/TLR2-independent responses are likely mediated by a leptospiral ligand(s) other than LPS.

s_cid=mm7045e1_w † † COVID-19 was confirmed with laboratory detection of SARS-CoV-2 by reverse transcription-polymerase chain reaction or antigen test. § § Patients with MIS-C as the reason for hospitalization included patients who met the clinical case definition for MIS-C (clinically severe illness requiring hospitalization in a person aged <21 years with fever, laboratory evidence of inflammation, multisystem [≥2] organ involvement and no alternative plausible diagnosis, and evidence of current or recent SARS-CoV-2 infection by reverse transcription polymerase chain reaction, serology or antigen test, or COVID-19 exposure within the 4 weeks preceding symptom onset [https:// emergency.cdc.gov/han/2020/han00432.asp]) and were hospitalized for diagnosis and management of MIS-C, based on chart review.

Background In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies Methods PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7–May 6, 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire Results Overall, 2,875 individuals at 24 shelters and nine unsheltered outreach events underwent SARS-CoV-2 testing and 2,860 (99.5%) had conclusive test results. SARS-CoV-2 prevalence was 2.1% (36/1,684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases compared with RT-PCR. Prevalence by shelter ranged 0%–27.6%. Repeat testing 3–4 weeks later at four shelters documented decreased SARS-CoV-2 prevalence (0%–3.9%). Nine of 24 shelters completed shelter assessments and implemented IPC measures as part of the COVID-19 response Conclusions PEH living in shelters experienced higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission

The majority of Americans are overweight, and the incidence of obesity continues to increase. This trend predisposes people to a number of deleterious consequences, including the metabolic syndrome and other conditions that lead to a greater number of hospital admissions. Invasive candidiasis is an important nosocomial infection that results from these admissions. Echinocandins such as micafungin are indicated for treatment. We have previously demonstrated that overweight patients exhibit higher micafungin systemic clearance (SCL) than leaner patients. We hypothesized that obese and extremely obese people would show even higher SCL than merely overweight patients. To test this, we performed a prospective study of 36 adult volunteers randomized to receive a single dose of either 100 mg or 300 mg of micafungin whose body mass index fell within one of the following categories: <25, 25 to 40, and >40 kg/m 2 . The male-to-female ratio was 1:1. The minimum weight was 43 kg, the median 97 kg, and the maximum weight 155 kg. A two-compartment model was examined using the maximum likelihood solution via the expectation-maximization algorithm. Men had a higher median SCL of 1.53 liters/h versus 1.29 liters/h (P ‫؍‬ 0.01) in the Mann-Whitney U-test. The typical SCL was 1.04 liters/h but increased by a factor of (weight/66) 0.75 as weight increased above 66 kg. Thus, the relationship between micafungin SCL and weight in adults is best described by fractal-geometry-based laws. Furthermore, micafungin SCL continues to increase as weight increases, with no obvious plateau. This leads to a requirement for strategies to determine individualized dosing levels for obese and extremely obese patients.The mass of an object is determined according to the amount of substance the object contains and for humans is measured in kilograms in accordance with the International System (SI) of units. In SI units, the term "weight" refers to force and is measured in Newtons. In colloquial English usage, however, the term "weight" is often used as equivalent to mass. In this report, we retain that colloquial use of the term "weight." In 1960s America, the average weight of men 20 to 74 years old was 76 kg and that of women was 64 kg (22), close to the oft-quoted average for men of 73 kg and average for women of 63 kg. Over the intervening decades, it has become increasingly difficult to find these people of "average" weight. By 2002, the average weight for men was 86 kg and that for women 74 was kg (22). By 2008, 68% of Americans were overweight (body mass index [BMI] Ն 25 kg/m 2 ), 34% were obese (BMI Ն 30 kg/m 2 ), and 6% were morbidly obese (BMI Ն 40 kg/m 2 ) (6). Unfortunately, the increasing rates of obesity are not confined to Americans or even the American continent; obesity is now a worldwide problem. Beyond the obvious and unfortunate large increase in patients with the metabolic syndrome, the problem of weight also has a direct impact on dosing practices. Kleiber's law states that the whole organism metabolic rate is proportional to an i...