Decoding Immuno-Competence: A Novel Analysis of Complete Blood Cell Count Data in COVID-19 Outcomes.

BACKGROUND: While 'immuno-competence' is a well-known term, it lacks an operational definition. To address this omission, this study explored whether the temporal and structured data of the complete blood cell count (CBC) can rapidly estimate immuno-competence. To this end, one or more ratios that included data on all monocytes, lymphocytes and neutrophils were investigated. MATERIALS AND METHODS: Longitudinal CBC data collected from 101 COVID-19 patients (291 observations) were analyzed. Dynamics were estimated with several approaches, which included non-structured (the classic CBC format) and structured data. Structured data were assessed as complex ratios that capture multicellular interactions among leukocytes. In comparing survivors with non-survivors, the hypothesis that immuno-competence may exhibit feedback-like (oscillatory or cyclic) responses was tested. RESULTS: While non-structured data did not distinguish survivors from non-survivors, structured data revealed immunological and statistical differences between outcomes: while survivors exhibited oscillatory data patterns, non-survivors did not. In survivors, many variables (including IL-6, hemoglobin and several complex indicators) showed values above or below the levels observed on day 1 of the hospitalization period, displaying L-shaped data distributions (positive kurtosis). In contrast, non-survivors did not exhibit kurtosis. Three immunologically defined data subsets included only survivors. Because information was based on visual patterns generated in real time, this method can, potentially, provide information rapidly. DISCUSSION: The hypothesis that immuno-competence expresses feedback-like loops when immunological data are structured was not rejected. This function seemed to be impaired in immuno-suppressed individuals. While this method rapidly informs, it is only a guide that, to be confirmed, requires additional tests. Despite this limitation, the fact that three protective (survival-associated) immunological data subsets were observed since day 1 supports many clinical decisions, including the early and personalized prognosis and identification of targets that immunomodulatory therapies could pursue. Because it extracts more information from the same data, structured data may replace the century-old format of the CBC.

A rare case of scedosporium apiospermum osteomyelitis in an immunocompetent patient.

Scedosporium, a widespread filamentous fungus found in diverse environments, has experienced a rise in cases due to escalating malignancies and chronic immunosuppression. Clinical manifestations span mycetoma, airway involvement, and various infections, with osteomyelitis being a notable complication. We present a case of a 77-year-old female initially displaying cutaneous Scedosporium signs, which progressed to osteomyelitis. The patient, with a history of trauma, chronic low dose steroid use, and underlying conditions, presented with a foot injury caused by her dog. Despite initial management, worsening symptoms led to the identification of Scedosporium. A comprehensive approach involving debridement, antimicrobial therapy, and reduction of immunosuppression resulted in clinical improvement. The rarity of zoonotic transmission, diagnostic challenges, and antifungal efficacy are also discussed. The patient's positive trajectory emphasizes early diagnosis, targeted treatment, and vigilance in managing immunosuppression. An adaptable treatment protocol is proposed based on risk factors. Considering the rising opportunistic fungal infections and delayed culture results, initiating empirical antifungals based on clinical judgment and regional prevalence is vital for favorable outcomes.

Half a Century in Hiding: A Unique Case of Tuberculoid Leprosy with an Unprecedented Incubation Period.

BACKGROUND Leprosy, also known as Hansen's disease, is a neglected tropical disease with low prevalence in the United States. The disease's long incubation period can cause delayed presentation, and most affected individuals have a history of travel or work in leprosy-endemic regions. The immune response to Mycobacterium leprae determines the clinical characteristics of leprosy, with tuberculoid leprosy being characterized by well-defined granulomas and involvement of peripheral nerves. The recommended treatment is a combination of dapsone and rifampin for 12 months. CASE REPORT A 78-year-old man with a history of extensive travel to Africa and Asia 50 years ago, presented with a non-tender, non-pruritic, and hypopigmented skin lesion on his left knee. Biopsy results confirmed granulomatous inflammation and the presence of Mycobacterium leprae, leading to a diagnosis of tuberculoid/paucibacillary leprosy. The patient received dapsone and rifampin treatment, which resulted in symptom improvement. CONCLUSIONS The patient's long incubation period of 50 years between exposure and symptom onset is remarkable and possibly one of the longest reported for tuberculoid leprosy. It emphasizes the importance of considering leprosy in cases with an extensive travel history and long incubation periods. Our patient's case presented contradictory staining results, suggesting potential sampling variation or a rare mixed leprosy form. Based on his clinical findings, he was diagnosed with tuberculoid leprosy. Early diagnosis and treatment are crucial to prevent irreversible nerve damage and improve patient outcomes. Healthcare providers should be vigilant in acquiring a detailed travel history to facilitate early diagnosis and appropriate management of leprosy cases.

A systemic review of Mycobacterium nebraskense case reports up to october 2023, featuring our unique case study.

Background: Mycobacterium nebraskense is a rare, slow growing nontuberculous mycobacterium species with limited documented cases. This systematic review aims to comprehensively analyze the clinical characteristics, presentation, and management of M. nebraskense infections by analyzing the available literature, including a newly reported case that we present in this article. Methods: A comprehensive search was conducted using PubMed and Google Scholar to identify relevant cases up to October 2023. Only seven reported cases were found, highlighting the scarcity of information on this pathogen. Results: Our analysis revealed several key findings. First, gender disparities were observed, with females being more susceptible to M. nebraskense infections. Additionally, a significant portion of patients presented with asymptomatic infections. Most affected individuals were over the age of 60, emphasizing potential age-related susceptibility. Comorbidity profiles varied widely among cases, and patients with preexisting lung comorbidities were at an increased risk of infection. The decision to treat or observe depended on clinical presentation, with even immunosuppressed individuals not always requiring treatment. Regarding treatment, we proposed an empirical approach with amikacin, clarithromycin, or rifabutin, considering the reported resistance to doxycycline and minocycline. Combination therapy was commonly employed to minimize resistance development, consistent with mycobacterial infection management. Conclusion: This study underscores the need for further research to validate these findings and enhance our understanding of M. nebraskense infections. As limited data are available, this review aims to provide valuable insights into a rare and emerging pathogen to guide clinical practice and future research endeavors.

Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.

With more than 5 million fatalities and close to 300 million reported cases, COVID-19 is the first documented pandemic due to a coronavirus that continues to be a major health challenge. Despite being rapid, uncontrollable, and highly infectious in its spread, it also created incentives for technology development and redefined public health needs and research agendas to fast-track innovations to be translated. Breakthroughs in computational biology peaked during the pandemic with renewed attention to making all cutting-edge technology deliver agents to combat the disease. The demand to develop effective treatments yielded surprising collaborations from previously segregated fields of science and technology. The long-standing pharmaceutical industry's aversion to repurposing existing drugs due to a lack of exponential financial gain was overrun by the health crisis and pressures created by front-line researchers and providers. Effective vaccine development even at an unprecedented pace took more than a year to develop and commence trials. Now the emergence of variants and waning protections during the booster shots is resulting in breakthrough infections that continue to strain health care systems. As of now, every protein of SARS-CoV-2 has been structurally characterized and related host pathways have been extensively mapped out. The research community has addressed the druggability of a multitude of possible targets. This has been made possible due to existing technology for virtual computer-assisted drug development as well as new tools and technologies such as artificial intelligence to deliver new leads. Here in this article, we are discussing advances in the drug discovery field related to target-based drug discovery and exploring the implications of known target-specific agents on COVID-19 therapeutic management. The current scenario calls for more personalized medicine efforts and stratifying patient populations early on for their need for different combinations of prognosis-specific therapeutics. We intend to highlight target hotspots and their potential agents, with the ultimate goal of using rational design of new therapeutics to not only end this pandemic but also uncover a generalizable platform for use in future pandemics.

Recommendation on Orbiting Sample Cleanliness.

The National Aeronautics and Space Administration-European Space Agency (NASA-ESA) Mars Sample Return (MSR) campaign involves the collection of samples on Mars by the Perseverance (Mars 2020) rover and their return to Earth. To accomplish this, the Orbiting Sample container (OS) will be sent to Mars to accommodate the collected samples then launched from Mars and returned to Earth, where the samples will be removed for examination in the Sample Return Facility (SRF). Crucial to this entire sequence will be establishment of the required level of cleanliness inside the OS. In February 2021, the NASA Headquarters' Mars Sample Return Program and Office of Planetary Protection assembled an MSR OS Tiger Team (OSTT) to discuss the appropriate cleanliness level options of the interior of the OS. The team's remit was primarily focused on evaluating the trade-offs between Planetary Protection cleanliness levels 4a and 4b. These cleanliness levels are determined by the Committee on Space Research (COSPAR) planetary protection regulations, where 4a requires <300 bacterial spores/m2 and <3 x 105 bacterial spores on the spacecraft (in this case, the interior of the OS) and 4b mandates the more stringent requirement of <30 bacterial spores on the spacecraft. This report documents the consensus opinion submitted by the OSTT that recommended the interior of the OS be cleaned to a 4a requirement with any feasible added effort toward 4b. This report provides, as well, the rationale for that decision.

Vaccine-Derived Poliovirus Outbreaks and Events - Three Provinces, Democratic Republic of the Congo, 2017.

The last confirmed wild poliovirus (WPV) case in Democratic Republic of the Congo (DRC) had paralysis onset in December 2011 (1). DRC has had cases of vaccine-derived polioviruses (VDPVs) documented since 2004 (Table 1) (1-6). After an outbreak of 30 circulating VDPV type 2 (cVDPV2) cases during 2011-2012, only five VDPV2 cases were reported during 2013-2016 (Table 1) (1-6). VDPVs can emerge from oral poliovirus vaccine (OPV types 1, 2, or 3; Sabin) polioviruses that have genetically mutated resulting in reversion to neurovirulence. This process occurs during extensive person-to-person transmission in populations with low immunity or after extended replication in the intestines of immune-deficient persons following vaccination (1-6). During 2017 (as of March 8, 2018), 25 VDPV cases were reported in three provinces in DRC: in Tanganyika province, an emergence with one VDPV2 case (pending final classification) in Kabalo health zone and an emergence with one ambiguous VDPV type 1 (aVDPV1) case in Ankoro health zone; in Maniema province, an emergence with two cVDPV2 cases; and in Haut Lomami province, an emergence with 20 cVDPV2 cases that originated in Haut Lomami province and later spread to Tanganyika province (hereafter referred to as the Haut Lomami outbreak area) and an emergence with one aVDPV type 2 (aVDPV2) case in Lwamba health zone (Table 1) (Figure) (6). Outbreak response supplementary immunization activities (SIAs) were conducted during June-December 2017 (Table 2) (6). Because of limitations in surveillance and suboptimal SIA quality and geographic scope, cVDPV2 circulation is likely continuing in 2018, requiring additional SIAs. DRC health officials and Global Polio Eradication Initiative (GPEI) partners are increasing human and financial resources to improve all aspects of outbreak response.

A review of evaluations of electronic event-based biosurveillance systems.

Electronic event-based biosurveillance systems (EEBS's) that use near real-time information from the internet are an increasingly important source of epidemiologic intelligence. However, there has not been a systematic assessment of EEBS evaluations, which could identify key uncertainties about current systems and guide EEBS development to most effectively exploit web-based information for biosurveillance. To conduct this assessment, we searched PubMed and Google Scholar to identify peer-reviewed evaluations of EEBS's. We included EEBS's that use publicly available internet information sources, cover events that are relevant to human health, and have global scope. To assess the publications using a common framework, we constructed a list of 17 EEBS attributes from published guidelines for evaluating health surveillance systems. We identified 11 EEBS's and 20 evaluations of these EEBS's. The number of published evaluations per EEBS ranged from 1 (Gen-Db, GODsN, MiTAP) to 8 (GPHIN, HealthMap). The median number of evaluation variables assessed per EEBS was 8 (range, 3-15). Ten published evaluations contained quantitative assessments of at least one key variable. No evaluations examined usefulness by identifying specific public health decisions, actions, or outcomes resulting from EEBS outputs. Future EEBS assessments should identify and discuss critical indicators of public health utility, especially the impact of EEBS's on public health response.

Influenza forecasting in human populations: a scoping review.

Forecasts of influenza activity in human populations could help guide key preparedness tasks. We conducted a scoping review to characterize these methodological approaches and identify research gaps. Adapting the PRISMA methodology for systematic reviews, we searched PubMed, CINAHL, Project Euclid, and Cochrane Database of Systematic Reviews for publications in English since January 1, 2000 using the terms "influenza AND (forecast* OR predict*)", excluding studies that did not validate forecasts against independent data or incorporate influenza-related surveillance data from the season or pandemic for which the forecasts were applied. We included 35 publications describing population-based (N = 27), medical facility-based (N = 4), and regional or global pandemic spread (N = 4) forecasts. They included areas of North America (N = 15), Europe (N = 14), and/or Asia-Pacific region (N = 4), or had global scope (N = 3). Forecasting models were statistical (N = 18) or epidemiological (N = 17). Five studies used data assimilation methods to update forecasts with new surveillance data. Models used virological (N = 14), syndromic (N = 13), meteorological (N = 6), internet search query (N = 4), and/or other surveillance data as inputs. Forecasting outcomes and validation metrics varied widely. Two studies compared distinct modeling approaches using common data, 2 assessed model calibration, and 1 systematically incorporated expert input. Of the 17 studies using epidemiological models, 8 included sensitivity analysis. This review suggests need for use of good practices in influenza forecasting (e.g., sensitivity analysis); direct comparisons of diverse approaches; assessment of model calibration; integration of subjective expert input; operational research in pilot, real-world applications; and improved mutual understanding among modelers and public health officials.

Effect of aggressively driven intravenous iron therapy on infectious complications in end-stage renal disease patients on maintenance hemodialysis.

For treating end-stage renal disease-associated anemia, various strategies to achieve optimal hemoglobin levels with lower erythropoiesis stimulating agent doses are being tried. One of these involves the use of a high dose [transferrin saturation (TSAT) >30%] of intravenous (IV) iron supplementation. However, due to in vitro effects of iron on stimulating bacterial growth, there are concerns of increased risk of infection. The safety of higher iron targets with respect to infectious complications (bacteremias, pneumonias, soft tissue infections, and osteomyelitis) is unknown. This was a retrospective study of patients on maintenance hemodialysis from a single, urban dialysis center to assess the long-term impact of the higher cumulative use of IV iron, on the incidence of clinically important infections. Our iron protocol was modified in June 2010 to aim for TSAT >30% unless serum ferritin levels were >1200 ng/mL. Data from only those patients who had been on dialysis for the whole duration between June 2009 and May 2011 were included. A total of 140 patients with end-stage renal disease on hemodialysis patients were found to be eligible for the study. There was a statistically significant increase in the mean TSAT and mean serum ferritin with the new anemia management protocol with a significant decrease in the mean erythropoiesis stimulating agent dose requirement. There was no statistically significant increase in the incidence of infectious complications. Although in vitro effects of iron are known to stimulate bacterial growth, a higher IV dose of iron may not increase the risk of infection in such patients.

What we are watching--five top global infectious disease threats, 2012: a perspective from CDC's Global Disease Detection Operations Center.

Disease outbreaks of international public health importance continue to occur regularly; detecting and tracking significant new public health threats in countries that cannot or might not report such events to the global health community is a challenge. The Centers for Disease Control and Prevention's (CDC) Global Disease Detection (GDD) Operations Center, established in early 2007, monitors infectious and non-infectious public health events to identify new or unexplained global public health threats and better position CDC to respond, if public health assistance is requested or required. At any one time, the GDD Operations Center actively monitors approximately 30-40 such public health threats; here we provide our perspective on five of the top global infectious disease threats that we were watching in 2012: 1 avian influenza A (H5N1), 2 cholera, 3 wild poliovirus, 4 enterovirus-71, and 5 extensively drug-resistant tuberculosis11†Current address: Division of Integrated Biosurveillance, Armed Forces Health Surveillance Center, US Department of Defense, Silver Spring, MD, USA.

Sexually transmitted infection testing of adult film performers: is disease being missed?

BACKGROUND: Undiagnosed sexually transmitted infections (STIs) may be common in the adult film industry because performers frequently engage in unprotected oral and anal intercourse, STIs are often asymptomatic, and the industry relies on urine-based testing. METHODS: Between mid-May and mid-September 2010, a consecutive sample of adult film industry performers recruited from a clinic in Los Angeles, California, that provides medical care to performers was offered oropharyngeal, rectal, and urogenital testing for Gonorrhea, and rectal and urogenital testing for Chlamydia. RESULTS: During the 4-month study period, 168 participants were enrolled: 112 (67%) were female and 56 (33%) were male. Of the 47 (28%) who tested positive for Gonorrhea and/or Chlamydia, 11 (23%) cases would not have been detected through urogenital testing alone. Gonorrhea was the most common STI (42/168; 25%) and the oropharynx the most common site of infection (37/47; 79%). Thirty-five (95%) oropharyngeal and 21 (91%) rectal infections were asymptomatic. Few participants reported using condoms consistently while performing or with their personal sex partners. CONCLUSIONS: Adult film industry performers had a high burden of STIs. Undiagnosed asymptomatic rectal and oropharyngeal STIs were common and are likely reservoirs for transmission to sexual partners inside and outside the workplace. Performers should be tested at all anatomical sites irrespective of symptoms, and condom use should be enforced to protect workers in this industry.

Effect of lower calcium dialysate on laboratory abnormalities in chronic kidney disease-associated mineral and bone disorder.

Increased vascular calcification, possibly due to the biochemical problem of calcium (Ca) and phosphate excess, has been associated with cardiovascular disease in patients with end stage renal disease. The use of a lower dialysate Ca concentration (<2.50 mEq/L) has been postulated as one of the methods to prevent long-term Ca accumulation. Concern, however, has been raised over the possibility that using a low Ca dialysate may lead to an increase in the intact parathyroid hormone concentration and therefore the need for higher doses of vitamin D analogs. This may thus mitigate the much desired long-term benefits. With an aim to decrease the total Ca load in our patients, the standard dialysate Ca concentration in our outpatient dialysis center was decreased from 2.5 to 2.25 mEq/L in September 2009. We found that the use of a lower Ca dialysate in our maintenance hemodialysis patients led to a significant reduction in the mean serum Ca concentration without a significant increase in serum parathyroid hormone levels or an increase in vitamin D analogs/Ca-based phosphate binder dose requirements. Further prospective studies are needed to assess the impact of this intervention on long-term cardiovascular morbidity and mortality.

Clinicopathological evaluation of 100 cases of mucinous carcinoma of breast with emphasis on axillary staging and special reference to a micropapillary pattern.

BACKGROUND: Pure mucinous breast carcinoma (PMBC) is uncommon and associated with better prognosis than mixed mucinous breast carcinoma (MMBC). A micropapillary pattern in PMBC has been identified although its prognostic significance is questionable. METHODS: A retrospective review of 100 cases of mucinous carcinoma diagnosed between 2000 and 2009 was conducted. Two broad categories were studied: PMBC (more than 90% mucinous component; n=45) and MMBC (less than 90% mucinous component; n=55). PMBC was further subclassified as hypocellular/type A (n=37) and cellular/type B (n=8). Receptor status, clinicomorphological and prognostic features were compared without patient follow-up. RESULTS: Mean age at diagnosis in PMBC and MMBC was 60 and 63 years, while mean tumour size was 1.65 and 2.5 cm, respectively. Mean age in type A and type B PMBC patients was 75 and 55 years, respectively. The majority of PMBCs were well differentiated, with two poorly differentiated cases as well. The majority of MMBCs were moderately differentiated. A micropapillary pattern was seen in 20% of PMBCs. Sentinel lymph nodes were positive in 18.5% of PMBCs and 16% of MMBCs. Non-sentinel lymph nodes were positive in 14% of PMBCs and 39% of MMBCs. A micropapillary pattern was seen in 60% of LN positive PMBCs and 14% of LN negative PMBCs. Furthermore, 95% of PMBCs were ER(+), 84% were PR(+) and 9% were Her-2(+); 91% of MMBCs were ER(+), 87% were PR(+) and 33% were Her-2(+). CONCLUSIONS: PMBCs with a micropapillary pattern were more frequently associated with nodal disease. PMBCs with axillary disease had one or more of the following: micropapillary pattern, high nuclear grade, Her-2 positivity, smaller tumour size or younger age. Hence, axillary staging by sentinel lymph node biopsy is recommended in PMBCs.

Not all injection drug users are created equal: heterogeneity of HIV, hepatitis C virus, and hepatitis B virus infection in Georgia.

Injection drug users (IDU) are widely believed to have accelerated the looming HIV/AIDS epidemic now faced by the Russian Federation and countries of the former Soviet Union. However, IDUs may be heterogeneous with regard to risk behaviors, and a subpopulation may be responsible for the majority of blood-borne pathogen transmission. We studied 926 adult injection drug users (IDU) from the cities of Tbilisi, Batumi, and Poti in Georgia, a small country in the Caucuses region between the Black and Caspian Seas, between 1997 and 1998. Study participants were administered a confidential questionnaire and were tested for antibody to HIV, hepatitis C virus (HCV), hepatitis B virus surface antigen (HBsAg), and hepatitis B core antibody (anti-HBc). Five (0.5%) individuals were positive for HIV; 539 (58.2%), for HCV; 67 (7.2%), for HBsAg; and 475, for (51.3%) anti-HBc. Surveyed individuals, 88.7%, reported sharing needles with others, and needle sharing with more than 10 other individuals versus no sharing was a highly significant predictor (OR: 278.12, 95% CI: 77.57, 997.20) of HCV seropositivity. In adjusted analysis, individuals who usually injected stolen medical/synthetic drugs had significantly lower odds of HCV (OR: 0.38, 95% CI: 0.22, 0.68) and HBV (OR: 0.58, 95% CI: 0.37, 0.90) than individuals most commonly injecting opium. Despite some limitations, these results suggest the presence of substantial heterogeneity between different injection drug-using groups in Georgia. Identification of high-risk IDU subpopulations is vital to efficiently target risk reduction programs and to prevent confounding by risk status in large HIV/AIDS behavioral intervention and vaccine trials.

Variation in clinical presentation of childhood group A streptococcal pharyngitis in four countries.

We conducted a cross-sectional study from September 2001 to August 2003 during which children between 2 and 12 years of age presenting with complaint of sore throat were recruited from urban pediatric clinics in Brazil, Croatia, Egypt and Latvia. The objective of the study was to compare clinical signs and symptoms of children presenting to urban pediatric clinics with sore throat in and between countries and to identify common clinical criteria predicting group A beta hemolytic streptococcal (GAS) pharyngitis. Using a single standard protocol in all four sites, clinical data were recorded and throat swabs obtained for standard GAS culture in 2040 children. Signs and symptoms were tested for statistical association with GAS positive/negative pharyngitis, and were compared using chi(2) tests, ANOVA and Odds Ratios. Clinical signs of GAS pharyngitis in children presenting to clinics varied significantly between countries, and there were few signs or symptom that could statistically be associated with GAS pharyngitis in all four countries, though several were useful in two or three countries. Our results indicate that the clinical manifestations of pharyngitis in clinics may vary by region. It is therefore critical that clinical decision rules for management of pharyngitis should have local validation.