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\"\"The Americans will have no Center of Union among them, and no Common Interest to pursue, when the Power and Government of England are finally removed. Moreover, when the Intersections and Divisions of their Country by great Bays of the Sea, and by vast Rivers, Lakes, and Ridges of Mountains;-and above all, when those immense inland Regions, beyond the Back Settlements, which are still unexplored, are taken into the Account, they form the highest Probability that the Americans never can be united ... under any Species of Government whatever. Their Fate seems to be- A DISUNITED PEOPLE, till the End of Time.\" -Josiah Tucker (1781) \"What then is the American, this new man? ... He is an American, who, leaving behind him all his ancient prejudices and manners, receives new ones from the new mode of life he has embraced, the new government he obeys, and the new rank he holds.\"\"-- Provided by publisher.

Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8–6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500–340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600–282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600–193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400–234 300), with 135 900 (75%; [95% CI 93 900–163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10–19). Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. None.

\"Based on the novel by acclaimed writer Gabriel Garcia Marquez, Love in the Time of Cholera is the evocative story of Florentino Ariza and Fermina Daza who, in youth, fall passionately in love. Fermina's father, however, has bigger plans for his daughter and forbids her to marry a lowly telegraph operator. He separates the two, sending Fermina to live with relatives in a remote jungle town. Years pass and when Fermina finally returns, she dismisses Florentino's love and chooses to marry Juvenal Urbino, a wealthy, well-born doctor. Florentino is devastated, but he is a romantic. As he rises in his business career, he whiles away the years in 622 affairs - yet he reserves his heart for Fermina. Juvenal dies at last, and Florentino purposefully attends his funeral. Fifty-one years, nine months and four days after he first declared his love for Fermina, he will do so again. Lauded as one of the greatest love stories of all time and set amid the lush, romantic backdrop of early 20th century Colombia, Love in the Time of Cholera is about the heartache of unrequited love and a man who is willing to wait forever for the woman he loves\"--Copyright description.

Recent reports have demonstrated a decline in bacterial bloodstream infections (BSIs) following adherence to central line insertion practices; however, declines have been less evident for BSIs due to Candida species. We conducted active, population-based laboratory surveillance for candidemia in metropolitan Atlanta, GA and Baltimore, MD over a 5-year period. We calculated annual candidemia incidence and antifungal drug resistance rates. We identified 3,848 candidemia cases from 2008-2013. Compared with 2008, candidemia incidence per 100,000 person-years decreased significantly by 2013 in both locations (GA: 14.1 to 9.5, p<0.001; MD: 30.9 to 14.4, p<0.001). A total of 3,255 cases (85%) had a central venous catheter (CVC) in place within 2 days before the BSI culture date. In both locations, the number of CVC-associated cases declined (GA: 473 to 294; MD: 384 to 151). Candida albicans (CA, 36%) and Candida glabrata (CG, 27%) were the most common species recovered. In both locations, the proportion of cases with fluconazole resistance decreased (GA: 8.0% to 7.1%, -10%; MD: 6.6% to 4.9%, -25%), while the proportion of cases with an isolate resistant to an echinocandin increased (GA: 1.2% to 2.9%, +147%; MD: 2.0% to 3.5%, +77%). Most (74%) echinocandin-resistant isolates were CG; 17 (<1%) isolates were resistant to both drug categories (multidrug resistant [MDR], 16/17 were CG). The proportion of CG cases with MDR Candida increased from 1.8% to 2.6%. We observed a significant decline in the incidence of candidemia over a five-year period, and increases in echinocandin-resistant and MDR Candida. Efforts to strengthen infection control practices may be preventing candidemia among high-risk patients. Further surveillance for resistant Candida is warranted.

Background. Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. Methods. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. Results. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. Conclusions. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.

Coccidioidomycosis consists of a spectrum of disease, ranging from a mild, self-limited, febrile illness to severe, life-threatening infection. It is caused by the soil-dwelling fungi, Coccidioides immitis and C. posadasii, which are present in diverse endemic areas. Climate changes and environmental factors affect the Coccidioides lifecycle and influence infection rates. The incidence of coccidioidomycosis has risen substantially over the past two decades. The vast majority of Coccidioides infections occur in the endemic zones, such as California, Arizona, Mexico, and Central America. Infections occurring outside those zones appear to be increasingly common, and pose unique clinical and public health challenges. It has long been known that elderly persons, pregnant women, and members of certain ethnic groups are at risk for severe or disseminated coccidioidomycosis. In recent years, it has become evident that persons with immunodeficiency diseases, diabetics, transplant recipients, and prisoners are also particularly vulnerable.

Abstract Immune checkpoint inhibitor (ICI)-induced hypophysitis is an immune-mediated pituitary inflammation that tends to cause long-term pituitary deficiency. Management of ICI-induced hypophysitis includes corticosteroids for acute inflammation and long-term hormone replacement due to irreversible pituitary cell damage. We report a case of recurrent hypophysitis following ICI rechallenge for metastatic melanoma. A 33-year-old woman with recurrent metastatic melanoma with adrenal, pelvic, and inguinal metastases developed recurrent hypophysitis during treatment with ipilimumab and nivolumab which recurred with rechallenge >5 years later. In both cases, headache was the most notable symptom and brain MRI showed pituitary enlargement and edema without evidence of metastases. Central adrenal insufficiency and symptoms caused by mass effect were treated with acute high-dose corticosteroids and long-term replacement corticosteroids. Based on recurrence and failure of symptomatic treatment with continued steroid treatment, ICI was discontinued. This case illustrates that hypophysitis may recur with ICI rechallenge, challenging traditional assumptions that chronic, irreversible irAEs are unlikely to recur or flare. The regenerative potential of pituitary cells after ICI-induced damage or additional damage to previously unaffected cells may be more conceivable than previously realized. Additional research on the potential for recurrent ICI-induced endocrinopathies are needed. This article reports a case of recurrent hypophysitis following immune checkpoint inhibitor rechallenge for metastatic melanoma.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent one of the most critical emerging antimicrobial-resistance threats globally. Data from low-and middle-income countries (LMICs) are increasingly reported as a part of global efforts to improve surveillance, and they demonstrate a high and increasing burden of CRE. However, containment of CRE using all recommended infection prevention and control (IPC) strategies requires substantial resources, which may be limited in LMICs. We conducted a review of the literature to better understand how approaches to CRE containment in LMICs have varied. Methods: We conducted a literature search using electronic databases (Medline, Embace, Cochrane Library, and Global Health) with no limit to study design or publication year. Search terms consisted of 3 categories: CRE, IPC, and LMIC. Additional publications were also identified from the references of identified articles. Publications were screened for eligibility; non-English articles and studies on other gram-negative organisms were excluded from the analysis. Control measures in included studies were categorized as active surveillance, hand hygiene, contact precautions, isolation, education, environmental control, monitoring and feedback, and other. Results: In total, 2,667 publications were identified using the databases and an additional 24 were manually identified. After deduplicating and screening for eligibility, 27 publications were included in the analysis. Overall, 21 publications (78%) were outbreak reports and 3 (11%) were quasi-experimental studies in settings of high rates of CRE. Also, 23 (85%) described a successful reduction in CRE. Among those 23 publications, 22 publications described adequate descriptions of IPC measures implemented, and the median number of IPC measures was 4.5 (range, 1–8). Environmental control was the most commonly utilized intervention (n = 19, 86%), followed by hand hygiene (n = 14, 64%) and contact precautions (n = 14, 64%). Three publications did not show a reduction in CRE despite the combination of IPC measures (median, 4.5). Overall, 13 publications utilized some method of active surveillance, but complete details on methodology were often lacking. In addition, 4 studies (15%) used only horizontal measures (defined as hand hygiene, environmental control, and/or education) and successfully controlled the CRE outbreaks. Conclusions: Among published reports, successful approaches to CRE control have been reported from LMICs. Use of only horizontal approaches, which are often lower cost and simpler to implement than some vertical strategies, have demonstrated some success; however, additional experience with identifying and implementing cost-effective strategies is needed. Funding: None Disclosures: None