Intravenous Drug Misuse Research Articles

The Road Ahead: Advancing Antifungal Vaccines and Addressing Fungal Infections in the Post-COVID World.

In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.

Evaluation of heparin infusion rates in patients with intravenous drug misuse.

To evaluate the hypothesis that patients with a history of intravenous drug misuse (IVDM) initiated on weight-based heparin infusions require higher than expected infusion rates to achieve therapeutic activated partial thromboplastin time (aPTT). This study is a multicenter, retrospective chart review of patients with a history of IVDM who were admitted to an acute care site between 10/1/2015 and 9/30/2020 and treated with continuous heparin infusions. Patients were identified using ICD9 and ICD10 codes and included if they had a documented history of IVDM within the past six months. Variables of particular interest included: median heparin infusion rates to maintain therapeutic aPTT, average time to reach therapeutic aPTT, and International Society of Thrombosis and Haemostasis Criteria for moderate to severe bleeding. Of the 41 patients who met the inclusion and exclusion criteria, 39 achieved therapeutic aPTT while on a weight-based heparin infusion. All heparin infusions were initiated at a rate of 18 units/kg/hr then titrated per institutional heparin infusion protocols. The mean time to therapeutic aPTT was 38.48 h ± 26.4 h with a mean infusion rate of 27.64 ± 7.14 units/kg/hr. To maintain therapeutic anticoagulation, infusion rates 150% higher than the initial rate were required. Of the 39 patients who achieved therapeutic aPTT, 85% (33) met criteria for heparin resistance, defined as greater than 35,000 units of heparin daily. No statistical significance could be derived from this retrospective chart review as therapeutic heparin rates were evaluated in comparison to initial infusion rate, rather than a control group. The findings in this study demonstrate a possible clinical association of the reduced antithrombin activity previously described in opiate misusers. To efficiently achieve therapeutic anticoagulation, it may be appropriate to consider use of heparin antiXa monitoring in place of aPTT or utilization of increased initial heparin infusion rates.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11239-021-02615-z.

Both-sided native valve infective endocarditis in a drug addict with incidental pneumoconiosis

Involvement of both right and left heart chambers with infective endocarditis is extremely rare. In this case report, we aimed to present a rare case of Infective endocarditis (IE) in an intravenous & inhalational drug misuse involving both cardiac chambers with incidental pneumoconiosis.

Ocular candidiasis in intravenous drug misusers

PurposeTo study the characteristics, the management and evolution of Candida endophthalmitis among intravenous drug misusers in the era of new systemic antifungal agents.MethodsRetrospective, descriptive study of patients with ocular candidiasis performed at Pitié‐Salpêtrière hospital, Paris, France, from 2002 to 2015.Results12 patients (14 eyes) had fungal endophtalmitis associated with drug misuse. Mean age at diagnosis was 41.1 years old and 83% of patients were male. Misuse of buprenorphine and morphin sulfate were noted in 83 and 17% respectively. 50% had polymedications. The way of infection was 50% hand transmission and 50% salivary transmission. Many of them had systemic co‐infections: hepatitis B, C, D or Human Immunodeficiency Virus. Patients presented with chorioretinitis (50%), endophthalmitis (57%) or both (36%). The microbiological diagnosis was obtained from anterior chamber tap (50%), vitrectomy (57%), skin, hair or mouth sample (7% each). 36% of the samples were positive and gave a fungal identification (75% positive for Candida albicans; 25% positive for Candida tropicalis and dubliniensis). At diagnosis of endophtalmitis, mean visual acuity was 0.9 log MAR and 0.3 logMAR after resolution of endophthalmitis. Patients received fluconazole (50%), voriconazole (42%) or amphotericin B (8%), associated with intravitreal injections of amphotericin B (50%) or vitrectomy (50%). Mean time of treatment was 2 months.ConclusionsFungal endophthalmitis is a sight‐threatening disease most commonly caused by Candida species. It is important to maintain a high index of suspicion of Candida ocular infection, particularly among intravenous drug users, even if they have drug substitution. Infection is mostly due to the preparation process. An early treatment based on antifungal agents highly improve the visual prognosis.

Puffy hand syndrome

A 45-year-old man presented to the rheumatology outpatient unit with bilateral swelling of the hands from the proximal segments of the fi ngers to the wrist that developed gradually over the past 3 years (fi gure). The oedema was non-pitting and was not aff ected by raising the hands. Function of the hands and fi ngers was not impaired. He had no generalised or pretibial oedema. The patient reported drinking 1–1·5 L of wine per day; medical history was otherwise unremarkable. Blood tests and an ultrasound scan confi rmed hepatitis (alanine aminotransferase [ALT] 175 IU/L, aspartate amino transferase [AST] 170 IU/L, albumin 4·68 mg/dL) with a positive antibody test for hepatitis C virus; hepatitis B virus and HIV tests were negative. Rheumatoid factor was 29 IU/mL (normal <14 IU/mL); anti-nuclear antibodies, anticitrullinated peptide antibodies, complement, protein electrophoresis, and total bilirubin were normal. On further questioning he admitted that he had been injecting high-dose sublingual buprenorphine for more than 5 years, preferentially in the wrist either into or around the veins, three to four times a day. Puff y hand syndrome is a complication of intravenous drug misuse. Users themselves are often aware of the risk, particularly from hand injections, but most physicians, including addiction specialists and general practitioners, rarely encounter this presentation and might not be familiar with it. The frequency of puff y hand syndrome is unknown. The pathogenesis of the oedema probably includes venous and lymphatic insuffi ciency, and the direct toxicity of injected drugs. Biopsy samples of skin and subcutaneous tissue and lymphangiograms can show destruction of the lymphatics that leads to fi brosis of the subcutaneous tissue, probably due to soluble compounds of the drugs that damage lymphatic vessels. Treatment with lowstretch bandaging and the wearing of elastic garments help to decrease the volume in puff y hand syndrome.

Enhanced surveillance of Staphylococcus aureus bacteraemia to identify targets for infection prevention

Surveillance of Staphylococcus aureus bacteraemia (SAB) in Scotland is limited to the number of infections per 100,000 acute occupied bed-days and susceptibility to meticillin. To demonstrate the value of enhanced SAB surveillance to identify targets for infection prevention. Prospective cohort study of all patients identified with SAB over a five-year period in a single health board in Scotland. All patients were reviewed at the bedside by a clinical microbiologist. In all, 556 SAB episodes were identified: 261 (46.6%) were hospital-acquired; 209 (37.9%) were healthcare-associated; 80 (14.4%) were community-acquired; and in six (1.1%) the origin of infection was not hospital-acquired, but could not be separated into healthcare-associated or community-acquired. These were classified as non-hospital-acquired. Meticillin-resistant S.aureus (MRSA) bacteraemia was associated with hospital-acquired and healthcare-associated infections. In addition, there was a significantly higher 30-day mortality associated with hospital-acquired (31.4%) and healthcare-associated (16.3%) infections compared to community-acquired SAB (8.7%). Vascular access devices were associated with hospital-acquired SAB and peripheral venous cannulas were the source for most of these (43.9%). Community-acquired infections were associated with intravenous drug misuse, respiratory tract infections and skeletal and joint infections. Skin and soft tissue infections were more widely seen in healthcare-associated infections. The data indicate that enhanced surveillance of SAB by origin of infection and source of bacteraemia has implications for infection prevention, empirical antibiotic therapy, and health improvement interventions.

Dynamics of HCV in the Presence of Optimal Bleaching

In an effort to slow transmission of blood-borne pathogens among intravenous drug misusers, clinicians through harm reduction programs have tried to educate intravenous drug misusers about the dangers of sharing needles and other injecting equipment. These programs encourage the use of new needles for every injection or, when new equipment is not available, too clean needles by bleaching them before they are reused. In this paper, a mathematical model for the transmission dynamics of hepatitis C virus (HCV) has been proposed and investigated. The impacts of bleaching and individual withdrawal on the transmission dynamics of HCV are discussed through the basic reproductive number and numerical simulations. For the time dependent control, we formulate the appropriate optimal control problem and investigate the necessary conditions for HCV control in order to determine the impact of bleaching on HCV prevalence. Although, bleaching is not 100 % effective, results in this paper suggests that if bleaching is 70 % effective in the absence of time dependent control then cumulative cases of new HCV infections may have a significant decline. However, in the presence of time dependent control we have established that if bleaching is 55 % effective HCV may die out.

On the Role of Optimal Counseling and Antiviral Therapy on Controlling HCV among Intravenous Drug Misusers

Hepatitis C virus (HCV) remains a major health challenge despite the availability of highly effective antiviral drugs. Prior studies suggest that many physicians are reluctant to treat intravenous drug misusers due to low levels of treatment adherence associated with intravenous drug misusers. HCV treatment guidelines and recommendations stipulate that HCV patients in treatment should abstain from intravenous drug misuse activities in order to reduce the likelihood of treatment failure, drug resistance, reinfection, superinfection, or mixed infection. In this paper, a mathematical model for exploring the transmission dynamics of HCV among intravenous drug misusers is proposed. The model incorporates essential characteristics of intravenous drug misusers such as relapse and nonadherence to treatment guidelines. With the aid of optimal control theory we assess the effects of time dependent HCV screening and treatment. Results from this study provide a framework for designing the appropriate strategies on controlling the long-term dynamics of HCV among intravenous drug users.

Mathematical analysis of hepatitis C model for intravenous drug misusers: Impact of antiviral therapy, abstinence and relapse

Despite advances in hepatitis C therapy and better knowledge of viral/host factors related to disease progression, hepatitis C virus (HCV) remains the leading cause of chronic liver disease, causing progression to end-stage liver disease (ESLD) as well as the development of hepatocellular carcinoma. In this paper a mathematical model for assessing the impact of antiviral therapy, abstinence and relapse on the transmission dynamics of HCV is formulated and analyzed. A threshold quantity known as the reproductive number has been computed, and the stability of the steady states has been investigated. The dynamical analysis reveals that the model has globally asymptotically stable steady states. The impacts of antiviral therapy, abstinence and relapse on the transmission dynamics of HCV are discussed through the basic reproductive number and numerical simulations.

HEPATITIS C VIRUS AND INTRAVENOUS DRUG MISUSE: A MODELING APPROACH

Hepatitis C virus (HCV) is a blood-borne infection that can lead to progressive liver failure, cirrhosis, hepatocellular carcinoma and death. A deterministic mathematical model for assessing the impact of daily intravenous drug misuse on the transmission dynamics of HCV is presented and analyzed. A threshold quantity known as the reproductive number has been computed. Stability of the steady states has been investigated. The dynamical analysis reveals that the model has globally asymptotically stable steady states. The impact of daily intravenous drug misuse on the transmission dynamics of HCV has been discussed through the basic reproductive number and numerical simulations.

ON THE ROLE OF SCREENING AND EDUCATIONAL CAMPAIGNS ON CONTROLLING HCV IN CORRECTIONAL INSTITUTIONS

The prevalence of infection with hepatitis C virus (HCV) is higher among prison inmates compared with the general population because of the high proportion of intravenous drug misusers. In this paper, a mathematical model for the spread of HCV in correctional institutions is developed and analyzed. The impact of educational campaigns and screening of HCV infected individuals is examined. In the presence of screening, the study suggests that targeted education campaigns of more than 50% will be highly effective in controlling the sharing of injection equipment among intravenous drug users, thereby reducing HCV prevalence within the correctional institutions. Further, we applied optimal control theory to the proposed model. The controls represent educational campaigns and screening. The objective is based on minimizing cumulative latent and infectious cases within the correctional institution, while maximizing the number of susceptible nonintravenous drug misusers. The optimal control is characterized and numerically solved. Overall, the application of optimal control theory in this study suggests that, more effort should be devoted to educational campaigns compared to screening.

A Mathematical Model for Assessing the Impact of Intravenous Drug Misuse on the Dynamics of HIV and HCV within Correctional Institutions

Unsafe injecting practices, blood exchange, the use of nonsterile needles, and other cutting instruments for tattooing are common in correctional institutions, resulting in a number of blood transmitted infections. A mathematical model for assessing the dynamics of HCV and HIV coinfection within correctional institutions is proposed and comprehensively analyzed. The HCV-only and HIV-only submodels are first considered. Analytical expressions for the threshold parameter in each submodel and the cointeraction are derived. Global dynamics of this coinfection shows that whenever the threshold parameter for the respective submodels and the coinfection model is less than unity, then the epidemics die out, the reverse condition implies disease persistence within correctional institutions. Numerical simulations using a set of plausible parameter values are provided to support analytical findings.

Assessing the impact of educational campaigns on controlling HCV among women in prison settings

Prior studies have shown that imprisonment is a major risk factor for hepatitis C infection, with the risk of infection directly proportional to the length of incarceration. Women are at least twice as likely as men to contract HCV as they have limited access to information, health services and safe intravenous drug injecting equipments. We develop a mathematical model to assess the impact of educational campaigns on controlling HCV among women in prison settings. Equilibria for the model are determined and their stability are examined. Population-level effects of increased educational campaigns to encourage safe injecting practices among women in prison are evaluated through numerical simulations. The results suggest that educating women prisoners about abstaining from intravenous drug misuse may significantly reduce HCV prevalence among women in prison settings. Targeted education campaigns, which are effective at stopping transmission of HCV more than 80% of the time, will be highly effective at controlling the disease among women in prisons.

Neuropsychological alterations in hepatitis C infection: The role of inflammation

About 50% of patients with hepatitis C virus (HCV) infection complain of neuropsychiatric symptoms, "brain fog", weakness, fatigue, and exhibit some degree of quality of life impairment, irrespective of the severity of liver disease. Since the first observation of HCV-related cognitive deficits, 10 studies have been published that have evaluated neuropsychiatric performance in patients with HCV infection and different degrees of hepatic impairment. Unfortunately, these have often included patients with cirrhosis, patients who had acquired the infection through previous intravenous drug misuse, who had a history of relatively recent treatment with interferon, or were on psychoactive medication. In addition, different neuropsychological batteries and tests that explored different cognitive domains were used, which makes the results of the studies difficult to compare. Finally, limited information is available on the pathogenesis of HCV-related cognitive impairment. Cerebral and/or systemic inflammation may be important players but their potential role has not been substantiated by experimental data. The present review outlines the available evidence of the presence of cognitive impairment in patients with HCV infection, with a focus on the potential relationship with cerebral and/or systemic inflammation.

Anthrax in a Scottish intravenous drug user

Anthrax, caused by Bacillus anthracis, is an uncommon disease in the United Kingdom. In December 2009, the first recorded case of injectable anthrax in the UK was diagnosed in Glasgow, Scotland. This case report describes the disease presentation in a detained person in police custody in Dumfries, South West Scotland. The case highlights to forensic physicians the clinical features of anthrax, particularly in relation to intravenous drug misuse and the importance of early recognition. Anthrax and its presence in the UK is discussed.

OC-031 Outreach community testing for hepatitis C in an ethnic population

Introduction Hepatitis C (HCV) is a leading cause of liver disease worldwide The World Health Organisation (WHO) estimates a worldwide prevalence of 170 million or 2.2%, although there is considerable geographical variation, Scotland, due to intravenous drug misuse, has higher prevalence of HCV infection compared with other European countries, estimated at 1% of the population. There is considerable ethnic diversity in Scotland, with a large Pakistani subpopulation. In Pakistan the prevalence of HCV is between 6 and 10%.1 Methods We arranged a series of HCV awareness meetings in Mosques and Pakistani Women9s Associations in Dundee. Thereafter we set up a series of sessions in the same venues offering HCV testing. Venous blood samples were taken for testing of HCV IgG and HBsAg, using the Abbott Architect system. Relevant past medical, family and travel history was also recorded as well as history of risk factors for HCV. Results 170 people were tested, representing 10% of the Dundee Pakistani population of which 145 were male. The mean age±SD was 45.11 (16.7) years. Seven patients (4.1%) of the cohort were Anti HCV positive and five (2.9%) were PCR positive. Only two people had previous testing for HCV, although 86.5% of the cohort had attended their GP within the past 2 years. 76.5% of the cohort had resided in the UK for at least 5 years. Less than 7% of the cohort was born in the UK. Risk factors for HCV transmission were only noted in a minority of patients who were HCV positive. One of seven had a family history and two of seven had a previous injection (IM or IV) in Pakistan. None had a history of drug misuse or transfusion. Of the entire group 33.5% reported previous therapeutic injections and 10% had a previous surgical procedure carried out in Pakistan. 3.5% of the cohort had a blood transfusion. 15.2% reported a family history of HCV infection. Conclusion This pilot project confirms that the Hepatitis C incidence in the healthy Pakistani migrant is higher than the native population. At-risk groups for HCV can be targeted for testing and treatment with outreach clinics. Using Scottish Intercollegiate Guidelines Network (SIGN) recommendations for assessing risk factors we would not have tested majority of those infected.2 Awareness needs to be raised among physicians regarding screening of ethnic populations for HCV.

A Rare Case of Group A Streptococcal Endocarditis with Absence of Valvular Vegetation

Group A streptococcal endocarditis has been described in intravenous drug misusers and as a post-varicella infection in children. We report a 64-year-old man with no prior risk factors who presented with a persistent fever, malaise, polyuria and cola-colored urine. On examination peripheral stigmata of endocarditis without a cardiac murmur and asymptomatic pharyngeal exudates were found. Blood and urine analysis revealed renal failure from suspected glomerulonephritis. Blood cultures revealed fully sensitive Group A streptococci. Transthoracic and transesophageal echocardiographies revealed no vegetation. The Modified Duke's Criteria aided in the diagnosis of definite infective endocarditis, despite the absence of valvular vegetation.

Erysipeloid: a review

Erysipeloid is an occupational infection of the skin caused by traumatic penetration of Erysipelothrix rhusiopathiae. The disease is characterized clinically by an erythematous oedema, with well-defined and raised borders, usually localized to the back of one hand and/or fingers. Vesicular, bullous and erosive lesions may also be present. The lesion may be asymptomatic or accompanied by mild pruritus, pain and fever. In addition to cutaneous infection, E. rhusiopathiae can cause endocarditis, which may be acute or subacute. Endocarditis is rare and has a male predilection. It usually occurs in previously damaged valves, predominantly the aortic valve. Endocarditis does not occur in patients with valvular prostheses and is not associated with intravenous drug misuse. Diagnosis of localized erysipeloid is based on the patient's history (occupation, previous traumatic contact with infected animals or their meat) and clinical picture (typical skin lesions, lack of severe systemic features, slight laboratory abnormalities and rapid remission after treatment with penicillin or cephalosporin).

Puffy hand syndrome due to drug addiction: a case–control study of the pathogenesis

We studied the pathogenesis of puffy hand syndrome of intravenous drug use. We hypothesized that injections of high-dose sublingual buprenorphine, instead of the recommended sublingual administration, could play an important role in lymphatic obstruction and destruction. We set up a case-control study in substitution centres, recruiting intravenous drug addicts with and without puffy hands, respectively. The subjects were asked to answer anonymously a questionnaire of 40 items comprising social and demographic status, history of illicit drugs use, buprenorphine misuse and injection practices. We included 33 cases and 33 controls, mean age of 34 years. They were past heroin users, mainly methadone-substituted. In multivariate analysis, sex (women) (OR = 8.9, P = 0.03), injections in the hands (OR = 5.9, P = 0.03), injections in the feet (OR = 6.5, P = 0.01) and the absence of tourniquet (OR = 7.0, p = 0.02) were significant risk factors for puffy hand syndrome. In 69.7% of the cases and 59.4% of the controls, respectively, there was a high-dose sublingual buprenorphine misuse, although it appeared not to be a significant risk factor for puffy hand syndrome. Injection practices are likely to cause puffy hands syndrome, but buprenorphine misuse should not be considered as a significant risk factor. However, intravenous drug users must still be warned of local and systemic complications of intravenous drug misuse.

Knowledge of deep vein thrombosis among intravenous drug misusers

Aims and MethodAll patients attending the local supervised drug consumption clinics were surveyed over a month. They were asked via a questionnaire to list the risks of injecting drugs, particularly the symptoms and consequences of deep vein thrombosis (DVT). Of 69 patients surveyed, 46 agreed to take part.ResultsOnly 9 patients (20%) had never injected drugs, whereas 16 (43%) of those injecting had injected into the groin; 10 patients (22%) had experienced a venous thrombosis themselves, and 35 (76%) knew of someone who had. Only 30 (65%) knew what a clot or thrombosis was. Pain and swelling were the most commonly reported symptoms, but few drug misusers knew of other symptoms. The best informed were those who had experienced thrombosis themselves recently.Clinical ImplicationsThe results indicate an apparent lack of basic knowledge about the risks of DVT in this sample of drug misusers, and a need for some new initiatives to address health education in this area for all drug misusers.