Correction: Lacy et al. Human Rabies Treatment-From Palliation to Promise. Viruses 2024, 16, 160.

In the original publication [...].

Human Rabies Treatment-From Palliation to Promise.

Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies.

Maternal and Neonatal Outcomes of Pregnant Women with Abnormal 50 g Glucose Challenge Tests in Nakhon Si Thammarat, Thailand: A Retrospective Study.

(1) Background: An abnormal 50 g glucose challenge test (50 g GCT) during pregnancy, even without a diagnosis of gestational diabetes mellitus (GDM), may result in undesirable obstetric and neonatal outcomes. This study sought to evaluate the outcomes in pregnant women with abnormal 50 g GCT in secondary care hospitals in Thailand. (2) Methods: A total of 1129 cases of pregnant women with abnormal 50 g GCT results who delivered between January 2018 and December 2020 at Thasala, Sichon, and Thungsong hospitals were retrospectively reviewed and divided into three groups: abnormal 50 g GCT and normal 100 g oral OGTT (Group 1; n = 397 cases), abnormal 50 g GCT and one abnormal 100 g OGTT value (Group 2; n = 452 cases), and GDM (Group 3; n = 307 cases). (3) Results: Cesarean section rates in group 3 (61.9%) were statistically higher than those in groups 1 (43.6%) and 2 (49.4%) (p < 0.001). In addition, the highest rate of birth asphyxia was found in group 2 (5.9%), which was significantly higher than that in Groups 1 (1.8%) and 3 (3.3%) (p = 0.007). (4) Conclusions: Pregnant women with abnormal 50 g GCTs without a diagnosis of GDM had undesirable maternal and neonatal outcomes, as well as those who had GDM, suggesting that healthcare providers should closely monitor them throughout pregnancy and the postpartum period.

Time to Revise the WHO Categories for Severe Rabies Virus Exposures-Category IV?

Rabies is a devastating disease and affects millions of people globally, yet it is preventable with appropriate and timely postexposure prophylaxis (PEP). The current WHO exposure categories (Categories I, II, and III) need revision, with a special Category IV for severe exposures. Rare cases of PEP failure have occurred in severe bites to the head and neck. Multiple factors, including route, wound severity, depth, contamination, viral dose, proximity to highly innervated areas and the CNS, and the number of lesions, remain unconsidered. Injuries in areas of high neural density are the most significant considering lyssavirus pathophysiology. Current recommendations do not account for these factors. A Category IV designation would acknowledge the severity and the increased risk of progression. Subsequently, patient management would be optimized with wound care and the appropriate administration of rabies-immune globulin/monoclonal antibodies (RIG/MAbs). All Category IV exposures would be infiltrated with the full dose of intact RIG (i.e., human RIG or MAbs) if the patient was previously unvaccinated. More concentrated RIG/MAb formulations would be preferred. As a world rabies community, we cannot tolerate PEP failures. A fourth WHO categorization will improve the care of these high-risk patients and highlight the global health urgency of this neglected disease.

"Effects of Tobacco Smoke on Aeroallergen Sensitization and Clinical Severity among University Students and Staff with Allergic Rhinitis".

Allergic diseases, affecting a variety of organs, have continuously increased both in developed and developing countries. Tobacco smoke exposure increases prevalence of allergic rhinitis (AR) and may affect allergic sensitization. This study was designed to compare indoor-aeroallergen sensitization between those not exposed and exposed to tobacco smoke in university students and staff with allergic rhinitis. A cross-sectional descriptive study among university students and staff with allergic rhinitis was performed from February 1, 2018, to March 31, 2019. Questionnaires regarding demography, clinical symptoms, and tobacco smoke exposure were implemented. A current smoker was defined as using, at least, 1 cigarette per day for, at least, 1 month. A secondhand smoker was defined as the one who never smoked, but lived with a current smoker, at least, for 1 month. A skin prick test for eight common indoor aeroallergens, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Periplaneta americana, cat dander, dog dander, para grass, careless weed, and Cladosporium spp., was performed. Sensitization was defined as positivity to, at least, 1 aeroallergen. One hundred and twenty-eight adult patients were eligible participants for the study, and 68 cases (53.10%) were classified as having tobacco smoke exposure. Among these, most of them were secondhand smokers (50 cases, 73.50%). There was no statistically significant difference between exposure and nonexposure to tobacco smoke and indoor aeroallergen sensitization, except for the Periplaneta americana antigen (p=0.013). Most of those in the nonexposure group (34 cases, 56.70%) were classified as having intermittent allergic rhinitis, whereas the tobacco exposure group had significantly more prevalence of severe clinical symptoms. In conclusion, tobacco smoke exposure did not appear to have much influence on aeroallergen sensitization for 7 of the 8 antigens examined. However, for the Periplaneta americana antigen, there was a highly significant correlation with patients experiencing worsened allergic rhinitis symptoms. Overall, it was observed that allergic rhinitis patients exposed to tobacco smoke had more severe clinical symptoms. Future studies should look for other potential antigens of interest, such as mould. Implementation of public health practices reducing exposure to tobacco smoke could have benefits in allergic rhinitis patients.

Tick-borne trauma: an unusual presentation of anaplasmosis.

INTRODUCTION: Tick-borne diseases present a special problem in Connecticut and the Northeastern United States. The tick species Ixodes scapularis known for Lyme disease may also infect humans with anaplasmosis, while other tick species [Amblyomma spp.] may transmit ehrlichiosis. These illnesses may present in various ways depending on the virulence of the organism and variable host factors. CASE PRESENTATION: Our patient presented as a motor vehicle trauma presumably from encephalopathy secondary to anaplasmosis. Unusual features of the patient's case led to the causative diagnosis on peripheral blood smear examination. CONCLUSION: Tick-borne diseases are endemic in Connecticut. The astute clinician should maintain a healthy vigilance for these illnesses. Although our patient presented as a trauma, the presumed precipitating disease could have been treated. Physician awareness and patient education may lessen the impact of these diseases.

A surview of recent patents on anti-infective therapy for Clostridium difficile.

Clostridium difficile has become the most common infectious cause of healthcare-associated diarrhea, with serious morbidity, prolonged hospitalization and even death. Treatment of the disease utilizing today's therapies does not guarantee a successful outcome. In the past decade, many new ideas and inventions have surfaced exploring different treatment strategies of Clostridium difficile associated diarrhea (CDAD). These treatments include antitoxins, novel antimicrobials, immunoglobulins and large inert synthetic compounds. In this paper, we survey of a number of representative patents issued from 2000 to the present targeting treatment of this difficult and dreaded disease.

Use of daptomycin in the treatment of vancomycin-resistant enterococcal urinary tract infections: a short case series.

BACKGROUND: Vancomycin-resistant enterococci are a leading cause of hospital-acquired urinary tract infection and a growing concern for the clinician. The aim of this study was to evaluate the effectiveness of daptomycin in the treatment of patients with vancomycin-resistant enterococcal urinary tract infection treated in our 200-bed community-based institution. METHODS: Patients with confirmed symptomatic vancomycin-resistant enterococcal urinary tract infection identified by infectious disease consultation between January 1, 2007, and December 8, 2009, vancomycin-resistant enterococci-positive urine culture, and urinary symptoms and/or pyuria on urinalysis, and treated with daptomycin, were included in this case series. Daptomycin was generally administered at a planned dosage regimen of ≥ 5 mg/kg every 24 hours in patients with normal to moderately impaired kidney function or every 48 hours in patients with severe kidney disease. Microbiologic cure was defined as eradication of vancomycin-resistant enterococci in urine cultures taken after the completion of daptomycin treatment. Clinical cure was defined by symptom resolution, as assessed by the infectious disease clinician caring for the patient. RESULTS: Included in this case series are 10 patients who received daptomycin for confirmed vancomycin-resistant enterococcal urinary tract infection. Patients had a history of extensive hospital stays. Chart review revealed that all levels of kidney function (3, 2, 3, and 2 patients with kidney disease classified as normal, mild, moderate, and severe/kidney failure, respectively) were represented in the sample and that patients with (n = 5) or without (n = 5) previous urinary tract infection and with (n = 3) or without (n = 7) Foley catheters were included. Treatment with daptomycin achieved clinical cure and vancomycin-resistant enterococcal eradication in all cases in this series. CONCLUSION: Treatment with daptomycin was well tolerated and effective in all patients in this series, regardless of renal function, history of urinary tract infection, or Foley catheter use. This study adds to emerging clinical evidence that daptomycin is a valuable treatment for vancomycin-resistant enterococcal urinary tract infection.

Worms on the brain: fatal meningoencephalitis from disseminated strongyloides infection.

Severe, complicated Strongyloides infection can lead to bacterial sepsis and meningitis. We report a case of Strongyloides meningoencephalitis complicating steroid treatment for presumptive asthma. Following a patient's seizure, analysis of cerebrospinal fluid (CSF) revealed numerous Strongyloides worms (filariaform larvae). The finding of threadworms within the central nervous system (CNS) is exceptionally rare. Seven days of ivermectin therapy with subsequent lumbar puncture revealed the organisms were eradicated from the CNS. Unfortunately, the patient never recovered neurologic function and expired after supportive care was withdrawn.

Preventing downstream Clostridium difficile infections with upstream antibiotic management.

Clostridium difficile infection (CDI) remains a devastating cause of hospital-acquired diarrhea. Treatment modalities have centered traditionally on two antibiotics, metronidazole and oral vancomycin. Both drugs, however, have been associated with variable relapse rates up to 20%. Fidaxomicin, a new oral agent with targeted C. difficile activity, may reduce the chance of relapse, but has not yet entered mainstream clinical practice. CDI is associated with significant morbidity and mortality. In the past decade, the emergence of hypervirulent strains has led to medical management failures and the increased need for surgical intervention. Control of the disease requires excellent infection prevention practices, yet can remain a difficult operational challenge. Selective pressure of antibiotic therapy can increase or lessen the risk depending on the agent used. We believe that antibiotic selection for the treatment of patients with any infectious disease must account for the possibility of subsequent severe CDI. We posit 'upstream' antibiotic selection will prevent 'downstream' CDI and potentially ameliorate deficiencies in infection prevention practices. Formal studies evaluating such an endpoint would be useful in this era of dangerous CDI.

Clinical and epidemiological features of human rabies cases in the Philippines: a review from 1987 to 2006.

BACKGROUND: Rabies viral infection causes a fatal encephalomyelitis. In humans, classic features include hydrophobia, aerophobia, hypersalivation, agitation, and neurological symptoms. In the Philippines, canine rabies contributes to a significant burden of human disease. METHODS: We retrospectively reviewed the medical records of 1839 patients admitted to San Lazaro Hospital, Manila, Philippines between 1987 and 2006, with a clinical diagnosis of rabies. We used the World Health Organization case definition for clinical rabies, which is defined by the presence of hydrophobia. RESULTS: Male patients outnumbered females by 2.2 to 1 and twice the number of adults were affected compared with children. Most patients were indigent. Dog bites occurred more than cat bites (97.1% vs. 2.9%) and most cases were caused by a single bite (86.2%), compared to multiple bites (8.7%). Bites to the face, head, and neck led to shorter incubation times, yet the incubation period varied, with most cases (42.7%) occurring in the bracket of 91-365 days post-exposure. Clinical symptoms included hydrophobia in all cases, as per our case definition, and aerophobia in 95.5%; only 9.4% had fever, 9.2% exhibited restlessness, and 6.7% exhibited hypersalivation. Localized neurological symptoms included pain (4.1%), numbness (2.6%), and itching (2.3%). None of the patients received appropriate post-exposure prophylaxis (PEP). CONCLUSIONS: This study examines the largest cohort of rabies patients reported to-date. Better understanding of clinical disease manifestations may help in salvage efforts to save patients with rabies. Knowledge of epidemiological factors will improve preventative efforts to reduce suffering from rabies.

Successful conservative treatment of spontaneous splenic rupture secondary to Babesiosis: a case report and literature review.

Babesiosis is caused by a protozoan parasite of the genus Babesia. In the United States, the usual infective organism Babesia microti, is most commonly transmitted through the bite of an infected Ixodestick. While the majority of patients exhibit sub-clinical signs and symptoms, significant illness can result. Spontaneous splenic rupture is a life-threatening complication of some viral and protozoan infections. We present a case of Babesiosis with spontaneous splenic rupture in which conservative management with blood transfusions and hospital-based care were successful, and the patient was spared splenectomy. To our knowledge, this is the first reported case treated without splenectomy. Our successful experience suggests conservative management may be appropriate for some patients.

Unusual manifestations of Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is an increasing nosocomial problem. New, more-virulent strains of C. difficile have spread across North America and Europe. Health care institutions now face a greater incidence of disease, often with greater severity. A need for surgical management for control of infection is on the increase. The clinical appearance of CDI is changed. METHODS: We report four unusual and severe cases of CDI in surgical patients with a review of the relevant literature. RESULTS: One patient developed CDI and required a colectomy for a perforated viscus. He developed C. difficile ileitis 12 days later that responded to medical therapy. Another patient who underwent a colectomy for infrarenal aortic occlusion, later in his hospital course, developed C. difficile ileitis and died. The third patient was hospitalized for several months for hypertension and associated morbidities. Eventually he developed severe abdominal pain and was found to have a small bowel mural abscess that grew C. difficile on culture. A fourth patient, taking long-term antibiotics for a surgical site infection of the knee, developed unexplained leukocytosis without diarrhea. Colonoscopy revealed pseudomembranous colitis that advanced to toxic megacolon. She required a colectomy and ultimately died from the disease. CONCLUSIONS: Patients are at high risk from CDI in this modern era. Disease manifestations may differ from the typical presentation. A heightened awareness for diagnosing this dangerous, evolving disease is paramount.

Implanted-port-catheter-related sepsis caused by Acidovorax avenae and methicillin-sensitive Staphylococcus aureus.

Acidovorax avenae is a gram-negative rod in the family Comamonadaceae and a phytopathogen found in the environment. Human infections caused by members of the Comamonadaceae are extremely rare. We report a case of implanted-port-catheter-related sepsis caused by Acidovorax avenae and methicillin (meticillin)-sensitive Staphylococcus aureus (MSSA).

Bloodstream infections in hospitalized adults with sickle cell disease: a retrospective analysis.

Bloodstream infections (BSI) are a common cause of morbidity and mortality in people with sickle cell disease (SCD). In children with SCD, BSI are most often caused by encapsulated organisms. There is a surprising paucity of medical literature that is focused on evaluating SCD adults with BSI. We reviewed the charts of adults with SCD and BSI who were admitted to our hospital between April 1999 and August 2003. During this period a total of 1,692 hospital admissions for 193 adults with SCD were identified and 28% of these patients had at least 1 episode of positive blood cultures, with 69 episodes (17%) considered true BSI. Nosocomial BSI occurred in 34 episodes (49%). Among community BSI, in contrast to BSI in children with SCD, Streptococcus pneumoniae was rarely encountered. A high incidence of staphylococcal BSI in adults with SCD was noted. Twenty-eight percent of all BSI were caused by Staphylococcus aureus, and 15 of 22 isolates (68%) of these were methicillin-resistant. Gram-negative organisms, anaerobes, and yeast were found in 21 (27%), 3 (4%), and 4 isolates (5%) of BSI, respectively. Since over 80% of BSI were considered catheter-related, the higher incidence of gram-positive bacterial infections was likely due to the presence of indwelling central venous catheters. Empiric therapy for adults with SCD suspected of having BSI, especially in the presence of indwelling central venous catheters, should include antimicrobial therapy targeted at gram-positive bacteria (especially MRSA) and gram-negative bacteria. Also, if patients are critically ill, consideration should be made to include antifungal agents. Additional research into the adult SCD population appears necessary to further define this problem.

Anti-HIV-1 microbicides -- 'chemical condoms' designed to limit the scourge of the HIV-1 pandemic.

The HIV pandemic continues to spread throughout the world, particularly affecting populations in developing countries. Women now comprise half of those infected. Efforts to limit this scourge need to be maximally implemented. A multi-faceted approach, including the research and advance of microbicides - or 'chemical condoms' - offers promise. Microbicides are self-administered, prophylactic products designed to protect against sexually transmitted pathogens, including HIV-1. Important features include safety, efficacy and user acceptability. This review summarizes some of the important products in the development pipeline.