Rat bite as a cause of diabetic foot ulcer in sub-Saharan Africa.

There have been relatively few reports of foot ulcers in diabetes resulting from rat bite. The findings were derived from people attending a single specialist service in Dar es Salaam for diabetic foot ulcers (DFUs) between 1 January 1999 and 31 December 2016. Details from people presenting for the first time with an ulcer judged to be caused by rat bite were compared with those with from other causes of foot ulcer. There were 426 first recorded foot ulcer episodes (in 179 people) judged to be caused by rat bite. The affected population was significantly younger (mean 55.9 vs 57.5 years, P = .037) and had a lower body mass index (26.5 vs 27.9, P = .008) than controls with other types of foot ulcer. They also presented significantly sooner (7.8 vs 18.2 days, P < .001) and were more likely to heal (85.8 vs 5.5%, P < .001), even though there was also a trend towards an increased risk of death (9.1% vs 5.3%, P = .032). Rat bite is an uncommon cause of DFU, but is not rare. Although the incidence of ulcer healing is higher than in a general foot ulcer population, the incidence of death is also higher.

When is pneumonia not pneumonia: a clinicopathologic study of the utility of lung tissue biopsies in determining the suitability of cadaveric tissue for donation.

Healthcare-associated pneumonia (HCAP) represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic culture results. It is often difficult to distinguish between pneumonia, underlying pulmonary disease, or conditions with pulmonary complications; this is compounded by the often-subjective clinical diagnosis of pneumonia. We conducted this study to determine the utility of post-mortem lung biopsies for diagnosing pneumonia in tissue donors diagnosed with pneumonia prior to death. Subjects were deceased patients who had been hospitalized at death and diagnosed with pneumonia. Post-mortem lung biopsies were obtained from the anatomic portion of the cadaveric lung corresponding to chest radiograph abnormalities. Specimens were fixed, stained with hematoxylin and eosin, and read by a single board-certified pathologist. Histological criteria for acute pneumonia included intense neutrophilic infiltration, fibrinous exudates, cellular debris, necrosis, or bacteria in the interstitium and intra-alveolar spaces. Of 143 subjects with a diagnosis of pneumonia at time of death, 14 (9.8 %) had histological evidence consistent with acute pneumonia. The most common histological diagnoses were emphysema (53 %), interstitial fibrosis (40 %), chronic atelectasis (36 %), acute and chronic passive congestion consistent with underlying cardiomyopathy (25 %), fibro-bullous disease (12 %), and acute bronchitis (11 %). HCAP represents a major diagnostic challenge because of the relatively low sensitivity and specificity of clinical criteria, radiological findings, and microbiologic testing. We found that attending physician-diagnosed pneumonia did not correlate with post-mortem pathological diagnosis. We conclude that histological examination of cadaveric lung tissue biopsies enables ascertainment or rule out of underlying pneumonia and prevents erroneous donor deferrals.

Locating, quantifying and characterising radiation hazards in contaminated nuclear facilities using a novel passive non-electrical polymer based radiation imaging device.

This paper provides a summary of recent trials which took place at the US Department of Energy Oak Ridge National Laboratory (ORNL) during December 2010. The overall objective for the trials was to demonstrate that a newly developed technology could be used to locate, quantify and characterise the radiological hazards within two separate ORNL hot cells (B and C). The technology used, known as RadBall(®), is a novel, passive, non-electrical polymer based radiation detection device which provides a 3D visualisation of radiation from areas where effective measurements have not been previously possible due to lack of access. This is particularly useful in the nuclear industry prior to the decommissioning of facilities where the quantity, location and type of contamination are often unknown. For hot cell B, the primary objective of demonstrating that the technology could be used to locate, quantify and characterise three radiological sources was met with 100% success. Despite more challenging conditions in hot cell C, two sources were detected and accurately located. To summarise, the technology performed extremely well with regards to detecting and locating radiation sources and, despite the challenging conditions, moderately well when assessing the relative energy and intensity of those sources. Due to the technology's unique deployability, non-electrical nature and its directional awareness the technology shows significant promise for the future characterisation of radiation hazards prior to and during the decommissioning of contaminated nuclear facilities.

The utility of Gram stains and culture in the management of limb ulcers in persons with diabetes.

In Tanzania, limited laboratory services often preclude routine identification of microorganisms that cause infections in persons with diabetes. Thus, we carried out this study to determine the utility of a Gram stain alone versus culture in guiding appropriate antimicrobial therapy. During February 2006 to December 2007 (study period), deep tissue biopsies were obtained from persons with diabetes presenting to the Muhimbili National Hospital (MNH) with infected limb ulcers. Specimens were Gram-stained then cultured for bacteria and fungi. Biopsies were obtained from 128 patients. Of 128 cultures, 118 (92%) yielded bacterial or fungal growth; 59 (50%) of these 118 cultures yielded mixed growth (80% included Gram-negative organisms); 38 (32%) and 20 (17%) yielded Gram-negative and Gram-positive organisms alone, respectively. The predictive value positive of a Gram stain for bacterial growth was 93% (110/118); a Gram-positive stain was 75% (15/20) predictive of growth of Gram-positive organisms whereas a Gram-negative stain was 82% (31/38) predictive of growth of Gram-negative organisms. In regions with limited resources, a Gram stain of an ulcer biopsy that is carefully procured is largely predictive of the type of microorganism causing infection. Gram staining of deep tissue biopsies might have a potential role to play in the management of infected diabetic limb ulcers.

Polymicrobial Prosthetic Valve Endocarditis Due to Neisseria gonorrhoeae and Pseudomonas fluorescens in a Patient With Tetralogy of Fallot: A Case Report.

Disseminated gonococcal infections are rare clinical entities and a few progress to endocarditis. Endocarditis caused by Pseudomonasis even more infrequent, with the few reported cases associated with either intravenous drug use, prosthetic heart valves, or pacemakers. We report a case of a 25-year-old male patient with Tetralogy of Fallot presenting with anasarca and diagnosed with endocarditis due to Neisseria gonorrhoeae and Pseudomonas fluorescens. To our knowledge, this is the first case of tissue-proven infective endocarditis due to P. fluorescens with concomitant N. gonorrhoeae bacteremia. Clinical management of polymicrobial endocarditis in young adults includes obtaining a detailed sexual history, using multiple diagnostic methods to confirm endocarditis, and promptly initiating broad-spectrum antibiotic therapy.

Chemical modification and design of anti-miRNA oligonucleotides.

Antisense techniques have been employed for over 30 years to suppress expression of target RNAs. Recently, microRNAs (miRNAs) have emerged as a new class of small, non-coding, regulatory RNA molecules that widely impact gene regulation, differentiation and disease states in both plants and animals. Antisense techniques that employ synthetic oligonucleotides have been used to study miRNA function and some of these compounds may have potential as novel drug candidates to intervene in diseases where miRNAs contribute to the underlying pathophysiology. Anti-miRNA oligonucleotides (AMOs) appear to work primarily through a steric blocking mechanism of action; these compounds are synthetic reverse complements that tightly bind and inactivate the miRNA. A variety of chemical modifications can be used to improve the performance and potency of AMOs. In general, modifications that confer nuclease stability and increase binding affinity improve AMO performance. Chemical modifications and/or certain structural features of the AMO may also facilitate invasion into the miRNA-induced silencing complex. In particular, it is essential that the AMO binds with high affinity to the miRNA 'seed region', which spans bases 2-8 from the 5'-end of the miRNA.

Health care-associated infection outbreak investigations by the Centers for Disease Control and Prevention, 1946-2005.

Since 1946, Centers for Disease Control and Prevention (CDC) personnel have investigated outbreaks of infections and adverse events associated with delivery of health care. CDC Epidemic Intelligence Service officers have led onsite investigations of these outbreaks by systematically applying epidemiology, statistics, and laboratory science. During 1946-2005, CDC Epidemic Intelligence Service officers conducted 531 outbreak investigations in facilities across the United States and abroad. Initially, the majority of outbreaks involved gastrointestinal tract infections; however, in later years, bloodstream, respiratory tract, and surgical wound infections predominated. Among pathogens implicated in CDC outbreak investigations, Staphylococcus aureus, Enterococcus species, Enterobacteriaceae, nonfermentative Gram-negative bacteria, or yeasts predominated, but unusual organisms (e.g., the atypical mycobacteria) were often included. Outbreak types varied and often were linked to transfer of colonized patients or health care personnel between facilities (multihospital outbreaks), national distribution of contaminated products, use of invasive medical devices, or variances in practices and procedures in health care environments (e.g., intensive care units, water reservoirs, or hemodialysis units). Through partnerships with health care facilities and local and state health departments, outbreaks were terminated and lives saved. Data from investigations invariably contributed to CDC-generated guidelines for prevention and control of health care-associated infections.

The 'Step by Step' Diabetic Foot Project in Tanzania: a model for improving patient outcomes in less-developed countries.

Foot complications cause substantial morbidity in Tanzania, where 70% of leg amputations occur in diabetic patients. The Step by Step Foot Project was initiated to train healthcare personnel in diabetic foot management, facilitate transfer of knowledge and expertise, and improve patient education. The project comprised a 3-day basic course with an interim period 1-year of for screening, followed by an advanced course and evaluation of activities. Fifteen centres from across Tanzania participated during 2004-2006 and 12 during 2004-2007. Of 11,714 patients screened in 2005, 4335 (37%) had high-risk feet. Of 461 (11%) with ulcers, 45 (9·8%) underwent major amputation. Of 3860 patients screened during 2006-2007, there was a significant increase in the proportion with ulcers and amputations compared with 2005 (P < 0·001), likely a result of enhanced case finding. During 2005-2008, there was a fall in the incidence of foot ulcers in patient referrals to the main tertiary care centre in Dar es Salaam and a parallel fall in amputation among these referrals. In conclusion, the Step by Step Foot Project in Tanzania improved foot ulcer management for persons with diabetes and resulted in permanent, operational foot clinics across the country. This programme is an effective model for improving outcomes in other less-developed countries.

Mycobacterium abscessus exit-site infection in peritoneal dialysis patients: should we ever aim to salvage the catheter?

Improvements in the exit-site care for peritoneal dialysis (PD) patients have uncovered a trend for increasing incidence of rapidly growing nontuberculous mycobacterium exit-site infections (ESI). Among these, Mycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates. The international society of PD guidelines encourage PD catheter removal in patients with M. abscessus peritonitis but, do not have evidence-based recommendations for the management of ESIs related to this organism. We report an unusual case in which an asymptomatic end-stage renal disease patient with multiple favorable clinical characteristics, i.e., no apparent immunodeficiency, sensitivity pattern showing possibility of treatment with multiple antibiotics, no evidence of peritonitis, and early clinical response, was treated with a 9-month combination antimicrobial regimen administered orally and intraperitoneally. Despite excellent clinical response with a resolution of the ESI, our patient relapsed quickly, within 30 days of stopping antimicrobial therapy and required PD catheter removal. Our case, taken together with available published case reports, highlights the futility of the conservative approach towards the M. abscessus ESI and makes the cases for early PD catheter removal in these patients.

Chloroquine and hydroxychloroquine in the context of COVID-19.

Chloroquine and closely related structural analogs, employed initially for the treatment of malaria, are now gaining worldwide attention due to the rapidly spreading pandemic caused by severe acute respiratory syndrome-coronavirus-2, named coronavirus disease (COVID) of 2019 (COVID-19). Although much of this attention has a mechanistic basis, the hard efficacy data for chloroquine/hydroxychloroquine in the management of the clinical syndrome of COVID-19 have been limited thus far. This review aims to present the available in vitro and clinical data for the role of chloroquine/hydroxychloroquine in COVID-19 and attempts to put them into perspective, especially in relation to the different risks/benefits particular to each patient who may require treatment.

Disseminated Nocardia beijingensis Masquerading as Pulmonary Tuberculosis in a Patient With Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome.

Case of disseminated Nocardia beijingensis, initially diagnosed and treated by health department as tuberculosis, presented with worsening symptoms and new lesions. Adjustment to antinocardial treatment resulted in significant clinical and radiographic improvement. Maintain a high index of suspicion for Nocardia in patients diagnosed with tuberculosis with worsening lesions despite therapy.

Diabetic foot ulcers and ethnicity in Tanzania: a contrast between African and Asian populations.

To characterise the role of ethnicity in the occurrence of foot ulcer disease in persons with diabetes, we analysed prospectively collected data for persons attending the diabetes clinic at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. A case was defined as any adult presenting to MNH with an ulcer at or below the ankle joint during July 1998-June 2005. We documented clinical and epidemiologic characteristics, progress, interventions and outcome. Seven hundred and eight persons met the case definition - 570 (80%) ethnic Africans and 138 (20%) Asian Indians. Ethnic Africans were more likely to present with gangrene (P < 0.01); Indians were more likely to be obese (P < 0.001) or have large vessel disease (P < 0.001). For Africans, intrinsic complications (neuro-ischaemia or macrovascular disease) delayed ulcer healing; for Asian Indians, mode of intervention (e.g. sloughectomy or glycaemic control with insulin or oral agents) determined the same outcome. Indigenous ethnic African and Asian Indian populations with diabetes display contrasting foot ulcer epidemiology. Peripheral vascular disease and gangrene are playing a larger role in ulcer pathogenesis and outcomes for both ethnic groups than was previously thought. Preventive efforts and interventions should be tailored to the two ethnic groups to achieve complete ulcer healing.

Outbreak of Acinetobacter baumannii associated with extrinsic contamination of ultrasound gel in a tertiary centre burn unit.

BACKGROUND: During 2011 and 2012, an increase in occurrence of multidrug-resistant Acinetobacter baumannii infections was recorded in the Shands Hospital Burn Intensive Care Unit (BICU). An epidemic curve together with strain typing was consistent with an intermittent common source outbreak. An investigation was therefore initiated. AIM: To identify risk factors for A. baumannii infection, characterize the source of the pathogen, implement control measures to terminate the outbreak, and institute preventive measures. METHODS: We conducted a retrospective case-control study; reviewed BICU infection control policies, practices and procedures, and patient exposure to healthcare workers (HCWs), and obtained epidemiologically-directed environmental cultures. FINDINGS: Eleven patients met the case definition. On multivariate analysis, case-patients were more likely to have undergone an ultrasound procedure in the BICU (adjusted odds ratio [AOR]: 19.5; confidence interval [CI]: 2.4-435) or have a FlexiSeal™ device (AOR: 11.9, CI:1.3-276). Epidemiologically-directed cultures of the environment, ultrasound equipment, and ultrasound gel from opened containers on the ultrasound trolley and in the Ultrasound Department were negative for the outbreak pathogen. Culture of an open ultrasound gel dispenser stored in the Ultrasound Department yielded an A. baumannii strain with DNA banding patterns identical to the outbreak strain. CONCLUSIONS: Based on data from our epidemiologic, microbiologic, and observational studies, we believe that inadvertent extrinsic contamination of the gel dispenser occurred in the Ultrasound Department. Contaminated gel was then dispensed into multiuse vials of gel stored on the mobile carts. The outbreak was stemmed by instituting changes in practices in the Ultrasound Department, including introduction of single-use ultrasound vials and storage of ultrasound gel.

Methicillin-resistant Staphylococcus aureus infection in a college football team: risk factors outside the locker room and playing field.

We investigated a cluster of methicillin-resistant Staphylococcus aureus infections in college football players. Risk factors included a history of recurrent skin infections and contact with the skin lesions of persons outside college. The infections were controlled through treatment of carriers with topical mupirocin, chlorhexidine body washes, and enhancement of personal hygiene practices. Varsity and professional teams need to consider similar preventive measures.

Clostridium infections associated with musculoskeletal-tissue allografts.

BACKGROUND: Allografts are commonly used in orthopedic reconstructive surgery. In 2001, approximately 875,000 musculoskeletal allografts were distributed by U.S. tissue banks. After the death from Clostridium sordellii sepsis of a 23-year-old man who had received a contaminated allograft from a tissue bank (Tissue Bank A), the Centers for Disease Control and Prevention initiated an investigation, including enhanced case finding, of the methods used for the recovery, processing, and testing of tissue. METHODS: A case of allograft-associated clostridium infection was defined as a culture-proven infection of a surgical site within one year after allograft implantation, from January 1998 to March 2002. We traced tissues to tissue banks that recovered and processed these tissues. We also estimated the rates of and risk ratios for clostridium infections for tissues processed by the implicated tissue bank and reviewed processing and testing methods used by various tissue banks. RESULTS: Fourteen patients were identified, all of whom had received allografts processed by Tissue Bank A. The rates of clostridium infection were 0.12 percent among patients who received sports-medicine tissues (i.e., tendons, femoral condyles, menisci) from Tissue Bank A and 0.36 percent among those who received femoral condyles in particular. The risk-ratio estimates for clostridium infections from tissues processed by Tissue Bank A, as compared with those from other tissue banks, were infinite (P<0.001) for musculoskeletal allografts, sports-medicine tissues, or tendons. Because Tissue Bank A cultured tissues only after treating them with a nonsporicidal antimicrobial solution, some test results were probably false negatives. Tissues from implicated donors were released despite the isolation of clostridium or bowel flora from other anatomical sites or reports of infections in other recipients. CONCLUSIONS: Clostridium infections were traced to allograft implantation. We provide interim recommendations to enhance tissue-transplantation safety. Tissue banks should validate processes and culture methods. Sterilization methods that do not adversely affect the functioning of transplanted tissue are needed to prevent allograft-related infections.

Challenges for management of the diabetic foot in Africa: doing more with less.

Diabetes mellitus reached epidemic proportions in much of the less-developed world over a decade ago. In Africa, incidence and prevalence rates of diabetes are increasing and foot complications are rising in parallel. The predominant risk factor for foot complications is underlying peripheral neuropathy, although there is a body of evidence that confirm the increasing role of peripheral vascular disease. Gangrene and infections are two of the more serious sequelae of diabetic foot ulcer disease that cause long-standing disability, loss of income, amputation or death. Unfortunately, diabetes imposes a heavy burden on the health services in many African countries, where resources are already scarce or cut back. Reasons for poor outcomes of foot complications in various less-developed countries include the following: lack of awareness of foot care issues among patients and health care providers alike; very few professionals with an interest in the diabetic foot or trained to provide specialist treatment; non existent podiatry services; long distances for patients to travel to the clinic; delays among patients in seeking timely medical care, or among untrained health care providers in referring patients with serious complications for specialist opinion; lack of the concept of a team approach; absence of training programs for health care professionals; and finally lack of surveillance activities. There are ways of improving diabetic foot disease outcomes that do not require an exorbitant outlay of financial resources. These include implementation of sustainable training programmes for health care professionals, focusing on the management of the complicated diabetic foot and educational programmes that include dissemination of information to other health care professionals and patients; sustenance of working environments that inculcate commitment by individual physicians and nurses through self growth; rational optimal use of existing microbiology facilities and prescribing through epidemiologically directed empiricism, where appropriate; and using sentinel hospitals for surveillance activities. Allied with the golden rules of prevention (i.e. maintenance of glycaemic control to prevent peripheral neuropathy, regular feet inspection, making an effort not to walk barefooted or cut foot callosities with razors or knives at home and avoidance of delays in presenting to hospital at the earliest onset of a foot lesion), reductions in the occurrence of adverse events associated with the diabetic foot is feasible in less-developed settings.

Pyrogenic reactions in hemodialysis patients, Hanoi, Vietnam.

Of 33,111 patients admitted to a large hospital in Vietnam from November 2000 through July 2001, a total of 303 were undergoing hemodialysis and had pyrogenic reactions (ie, fever and/or rigors). Ten case patients (3.3%) had documented bacteremia; pathogens were largely waterborne microorganisms. Pyrogenic reactions in case patients might have occurred because of suboptimal water quality or inadequate dialyzer reprocessing procedures.

Investigation of postoperative allograft-associated infections in patients who underwent musculoskeletal allograft implantation.

BACKGROUND: The rate at which allografts are used in surgical procedures has doubled in the United States during the past decade. In 2002, one outpatient surgical center (SC-X) identified a cluster of surgical site infections (SSIs) after anterior cruciate ligament reconstructive surgery (ACLRS). Therefore, we conducted an investigation to determine the extent of the outbreak and to identify risk factors. METHODS: Our investigation included retrospective cohort and observational studies. A case patient was defined as any patient who acquired a SSI after undergoing ACLRS at SC-X between February 2000 and June 2002 (the study period). Data collected included demographic characteristics, clinical information, and graft details, such as processing method (i.e., aseptic or sterile). RESULTS: Of 331 patients who underwent ACLRS during the study period, 11 (3.3%) met the case definition. All infections occurred at the tibial fixation site of the graft and involved 8 different microorganisms; the median time to a positive culture result was 55 days after ACLRS. The infection rate for patients who received aseptically processed allografts was 4.4% (11 of 250 patients), compared with 0% (0 of 81) for patients who received autografts or sterile allografts (P=.07). Use of a supplementary staple for tibial fixation, compared with other fixation methods that did not involve such staples, increased the risk of infection 10-fold in univariate analysis (relative risk [RR], 10.0; 95% confidence interval [CI], 3.0-32.9) and 9-fold when controlling for tissue processing method (RR, 9.0; 95% CI, 2.8-28.8). CONCLUSIONS: The use of sterile allograft tissue appears to be associated with a significant reduction in the risk of postoperative infection, particularly in the presence of adjunctive fixation. Larger clinical studies are necessary to confirm this observation.

Tropical diabetic hand syndrome. Epidemiology, pathogenesis, and management.

The tropical diabetic hand syndrome (TDHS) is a complication affecting patients with diabetes mellitus in the tropics. The syndrome encompasses a localized cellulitis with variable swelling and ulceration of the hands, to progressive, fulminant hand sepsis, and gangrene affecting the entire limb. TDHS is less well recognized than foot infections and not generally classified as a specific diabetes complication. Hand infection was first described in Nigeria in 1984. Since then, the majority of cases have been reported in the African continent and more recently in India. There is often a history of antecedent minor hand trauma (e.g. scratches or insect bites). Presentation to hospital is often delayed due to the patients' unawareness of the potential risks, lack of concern because the initiating trauma might have been trivial, or decision to seek initial help from traditional healers. The first analytic study was done in Dar es Salaam, Tanzania, to characterize the epidemiology, clinical characteristics and risk factors of TDHS. Independent risk factors for TDHS include poorly controlled diabetes, neuropathy, insulin treatment or malnutrition. Clinicians should be aware of these complications and be prepared to immediately admit TDHS patients to hospital for aggressive surgical intervention (i.e. debridement, pus drainage or amputation) and high-dose, intravenous, broad-spectrum antibacterial therapy that includes anti-anaerobic activity. Without prompt, aggressive treatment TDHS can lead to permanent disability, limb amputation (13% of TDHS patients require major upper limb amputation), or death. Prevention strategies include patient and staff education that focuses on proper hand care, nutrition, and the importance of seeking medical attention immediately following hand trauma regardless of the severity of the injury, or at the earliest onset of hand-related symptoms, such as redness or swelling. Prevention of permanent disability and death due to TDHS will require improved management of glycemic levels in resource-limited countries, and surgical intervention during less severe stages of the condition.