COVID-19 Contact Tracing Outcomes in Washington State, August and October 2020.

Introduction: Case investigation and contact tracing are important tools to limit the spread of SARS-CoV-2, particularly when implemented efficiently. Our objective was to evaluate participation in and timeliness of COVID-19 contact tracing and whether these measures changed over time. Methods: We retrospectively assessed COVID-19 case investigation and contact tracing surveillance data from the Washington State centralized program for August 1-31, 2020 and October 1-31, 2020. We combined SARS-CoV-2 testing reports with contact tracing data to compare completeness, reporting of contacts, and program timeliness. Results: For August and October respectively, 4,600 (of 12,521) and 2,166 (of 16,269) individuals with COVID-19 were referred to the state program for case investigation. Investigators called 100% of referred individuals; 65% (August) and 76% (October) were interviewed. Of individuals interviewed, 33% reported contacts in August and 45% in October, with only mild variation by age, sex, race/ethnicity, and urbanicity. In August, 992 individuals with COVID-19 reported a total of 2,584 contacts (mean, 2.6), and in October, 739 individuals reported 2,218 contacts (mean, 3.0). Among contacts, 86% and 78% participated in interviews for August and October. The median time elapsed from specimen collection to contact interview was 4 days in August and 3 days in October, and from symptom onset to contact interview was 7 days in August and 6 days in October. Conclusions: While contact tracing improved with time, the proportion of individuals disclosing contacts remained below 50% and differed minimally by demographic characteristics. The longest time interval occurred between symptom onset and test result notification. Improving elicitation of contacts and timeliness of contact tracing may further decrease SARS-CoV-2 transmission.

Poly-helminth Infection in East Guatemalan School Children.

BACKGROUND: Soil transmitted helminths (STH) remain a global public health concern in spite of occasional dosing campaigns. AIMS: To determine baseline prevalence and intensity of STH infection in east Guatemalan school children, and describe the associated epidemiology of anemia, stunting, and wasting in this population. SETTING AND DESIGN: Ten schools in Izabal province (eastern Guatemala) were identified, and 1,001 school children were selected for this study. Half of the schools were used as clinical testing sites (blood and stool). MATERIALS AND METHODS: Anthropometric measures were collected from all children. Over 300 children were tested for anemia and 229 for helminth infection. Ova and parasite specimens were examined via Direct, Kato Katz, and McMaster techniques. Hemoglobin was measured from venipuncture following the hemacue system. STATISTICAL ANALYSIS: Correlation between infection intensities and growth indicators were examined. Chi Square or t tests were used for bivariate analysis. Multiple logistic regression was performed on significant variables from bivariate techniques. RESULTS: Over two-thirds of school children were positive for infection by any STH. Prevalence of Hookworm was 30%; Ascaris, 52%; and Trichuris, 39%, most as low-intensity infection. Over half of the children were co-infected. In bivariate analysis, anemia was significantly associated with polyparasitism. CONCLUSIONS: For a Guatemalan child who experiences a unit decrease in hemoglobin, one expects to see a 24% increase in the odds of being infected with STH, controlling for age, sex, lake proximity, and growth characteristics. Infection with more than one STH, despite low intensity, led to a significant decrease in hemoglobin.

Alterations in growth hormone receptor abundance regulate growth hormone signaling in murine obstructive cholestasis.

Children with cholestatic liver diseases, in particular biliary atresia, may develop an acquired growth hormone (GH) resistance. This is characterized by normal GH secretion, reduced liver GH receptor (GHR) abundance, and reduced circulating insulin-like growth factor I (IGF-I). Consequences include linear growth failure, reduced muscle mass, and increased perioperative morbidity and mortality. However, the molecular basis for altered GH signaling in liver and skeletal muscle in cholestatic liver disease is not known. We hypothesized that reduced IGF-I expression in obstructive cholestasis would be associated with downregulation of the GHR and impaired phosphorylation of signal transducers and activators of transcription (STAT5). Body composition was determined in C57BL/6J male mice after bile duct ligation (BDL) relative to pair-fed (PF) and ad libitum-fed controls. GHR, STAT5, Sp3, and IGF-I expression and/or DNA binding were assessed using immunoblots, electrophoretic mobility shift assays, and/or real time RT-PCR. Fat-free mass was reduced in PF mice relative to ad libitum-fed controls. BDL led to a further reduction in fat mass and fat-free mass relative to PF controls. TNF-alpha was increased in liver and skeletal muscle of BDL mice. This was associated with reduced GH-dependent STAT5 activation and IGF-I RNA expression. GHR expression was reduced in BDL mice; in liver, this was associated with reduced Sp3 binding to a GHR gene promoter cis element. Wasting in murine obstructive cholestasis is due to combined effects of reduced caloric intake and biliary obstruction. GH resistance due to downregulation of GHR expression may be attributed primarily to the obstructive cholestasis; therapies that specifically increase GHR expression may restore GH signaling in this setting.

Tumor necrosis factor alpha blockade restores growth hormone signaling in murine colitis.

BACKGROUND & AIMS: Cytokines including tumor necrosis factor alpha (TNFalpha) may create a state of growth hormone (GH) resistance in Crohn's disease. Anabolic effects of GH are mediated via phosphorylation of the signal transducer and activator of transcription (STAT)5b transcription factor. Although GH resistance in other settings has been linked to a defect in janus kinase-STAT signaling, the molecular basis for GH resistance in colitis was not known. We hypothesized that the GH-induced phosphorylation of STAT5b would be impaired in colitis, and that TNFalpha blockade would restore GH signaling. METHODS: Growth, body composition, and molecular regulators of GH signaling were determined in interleukin-10 null mice with chronic colitis and wild-type controls, +/- treatment with an anti-TNFalpha antibody. RESULTS: Interleukin-10 null mice exhibited significant alterations in growth, body composition, and feed efficiency. Liver insulin-like growth factor 1 expression was reduced in colitic mice. This was associated with down-regulation of GH receptor (GHR) expression and impaired GH-dependent STAT5b activation. Down-regulation of GHR expression was associated with reduced nuclear abundance and DNA binding of the GHR gene-promoter transactivator, Sp3. TNFalpha down-regulated GHR abundance and prevented GH-induced tyrosine phosphorylation of STAT5 in rat hepatocytes in culture. TNFalpha neutralization up-regulated liver GHR abundance and restored GH activation of STAT5 and serum insulin-like growth factor 1 levels in colitic mice; this preceded improvements in weight gain and disease activity. CONCLUSIONS: GH resistance in experimental colitis is caused by down-regulation of GHR expression, thereby reducing GH-dependent STAT5 activation. TNFalpha blockade restores liver GH signaling and improves anabolic metabolism in this setting.