Postexposure Prophylactic Treatment Research Articles

Update on Managing the Risks of Exposure to Lentiviral and Retroviral Vectors.

This paper aims to review the risks associated with using lentiviral and retroviral vectors in research and clinical settings and to propose an update to an effective treatment plan. Risks of exposure were evaluated based on vector design, safety features, viral tropism, transgene, and means and modes of transmission. These risks were weighed against the potential risks and benefits of current HIV medications. We recommend the following post-exposure prophylactic treatment for significant lentiviral vector exposures: 1) dolutegravir 50 mg. taken once a day for 7 days; and 2) tenofovir disoproxil fumarate 300 mg. taken once a day for 7 days (28 days of both medications for replication-competent vectors). Due to the highly efficient delivery of transgenes by modern lentiviral and retroviral vectors, post-exposure prophylaxis is indicated to prevent vector integration and oncogenic risks.

Case Report and Literature Review of Occupational Transmission of Monkeypox Virus to Healthcare Workers, South Korea.

We report a case of occupational monkeypox virus infection from a needlestick injury in a healthcare worker in South Korea and review similar reports in the literature during 2022. Postexposure prophylactic treatment with a third-generation smallpox vaccine and antiviral agent tecovirimat inhibited local virus spread and alleviated lesion pain.

Application of a caprylate/chromatography purification process for production of a high potency rabies immune globulin from pooled human plasma

BackgroundHuman rabies immunoglobulin (RIG) is an integral part of post-exposure prophylactic treatment of rabies (along with rabies vaccination). Infiltration of most, if not all, of the RIG dose at the wound site is recommended. RIG produced by a caprylate/chromatography manufacturing process (RIG-C; HyperRAB) increased the potency and purity of this product over the existing licensed RIG from a solvent/detergent process (RIG-S/D; HyperRAB-S/D). MethodsA series of studies were conducted to characterize the content and purity of RIG-C. A single-dose pharmacokinetic study in rabbits was performed to compare intramuscular (IM) immunoglobulin products manufactured by two different purification processes, solvent/detergent (IGIM-S/D) and caprylate/chromatography (IGIM-C). ResultsRIG-C was found to be a highly purified IgG formulation with high monomer content and formulated with twice the anti-rabies potency of RIG-S/D while maintaining the same overall protein concentration. RIG-C facilitates IM administration at the wound site by halving the injection volume. The new caprylate/chromatography process eliminated detectible levels of pro-coagulant impurities and IgA that were carried through in the prior S/D process. These impurities have been associated with thrombotic complications and allergic reactions in susceptible patients. After single dose administration, IGIM-C was pharmacokinetically equivalent to IGIM-S/D in rabbits. ConclusionRIG-C is a more potent RIG formulation with less impurities yielding a safer and more convenient product with similar pharmacokinetic profile.

An unusual case of fatal rabies encephalitis despite completing postexposure prophylaxis

Rabies continues to be a major health scourge in many developing countries including India. It can be effectively prevented by providing postexposure prophylactic treatment. Failure of Rabies postexposure prophylaxis (PEP) is a rare occurrence. Our patient, a 39-year-old Male, was bitten by stray dog on the left hand. It was Category III dog bite for which proper wound care and PEP 5 doses of antirabies cell culture vaccine and Human Rabies Immunoglobulin was given. Two days after completing the 5th dose of PEP, he presented with fever, neck rigidity, drooling of saliva, pain, and numbness in the left hand along with auditory and visual hallucinations without hydrophobia and aerophobia. On 2nd say of hospitalization, he developed progressive respiratory difficulty and decreased oxygen saturation for which he was intubated and put on invasive ventilator support. However, he suffered fatal cardiac arrest and succumbed to his illness. Based on his symptoms, a clinical diagnosis of febrile encephalopathy with differential diagnosis of acute rabies encephalitis was made. On autopsy, his brain was markedly congested and histopathological examination was suggestive of acute rabies encephalitis. However, no Negri bodies were seen. Further examination of brain tissue by immunohistochemical labeling revealed numerous Negri bodies and confirmed the diagnosis of rabies encephalitis.

The level of nurses' knowledge on occupational post exposure to hepatitis B infection in the Tamale metropolis, Ghana

BackgroundHealth care workers especially nurses in developing countries are at serious risk for infection from blood-borne pathogens particularly hepatitis B virus (HBV) — because of the high prevalence of such pathogens in many poorer regions of the world. Employers are required to establish exposure-control plans that include post exposure follow-up for their employees and to comply with incident reporting requirements.This study assessed the level of knowledge and awareness of nurses in the Tamale Metropolis of Ghana on occupational post exposure measures to hepatitis B, and their risk of being infected. Hepatitis B vaccination status of nurses was also assessed.MethodsA cross-sectional study was conducted involving 108 nurses of varied categories who were selected by simple random sampling from west and central hospitals in the Tamale Metropolis of Ghana. Data was collected using a semi-structured questionnaire. SPSS version 16 was used for the analysis of data.ResultsNinety-four percent (94.4%) of the nurses considered themselves susceptible to occupational infection of HBV. About 23.4% were able to mention all the key elements of the post exposure management with 12.1% having adequate knowledge on post exposure prophylactic treatment against HBV. However, only 48 (44.4%) nurses have received hepatitis B vaccination. Thirty-six (75%) of those immunized had received three doses as required while the remaining had less than 3 doses. Some (38.9%) recap used needles before disposal and 30.2% do not decontaminate blood and body fluids before disposal.ConclusionNurses are aware of their risk of occupational exposure to hepatitis B but lack the requisite knowledge on post exposure management as well as measures that reduce the exposure. Nurses should familiarize with the principles of post exposure management as part of job orientation and on-going job training. Also, there is a need for a national policy on occupational safety and health which should include HB vaccination of health care workers as a requirement for appointment into the health service.

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.

Psychotic Disorder after Contact with a Potentially Rabid Animal and Post-Exposure Prophylactic Anti-Rabies Treatment

We present the case of a 19-year-old who developed psychotic symptoms after exposure to a potentially rabid animal and post-exposure prophylactic treatment. This case serves to remind physicians to fully explore the possibility of a nonpsychiatric origin of de novo psychotic symptoms and provides indirect evidence in favor of the possible involvement of the immune system in the development of psychotic disorders.

A retrospective study on imported Malaria in Jordan. 1. Malaria among Jordanian UN peacekeeping forces

Malaria is considered as one of the most threatening diseases affecting peacekeeping forces serving in malaria endemic countries. The Jordanian Armed Forces participated in many of the United Nations peacekeeping missions in over 20 countries across the world. Thin and thick blood smears were collected from military personnel returning to Jordan, and relevant data including occupation, age, sex, residence address and the country they served in were recorded. Mefloquine 250 mg/week was prescribed for prophylaxis during the period of stay for three contingents of Jordanian military forces deployed to East Timor. Members of two contingents were given post exposure prophylactic treatment of Doxycycline 100 mg coupled with Primaquine 15 mg daily for 14 days soon after returning to Jordan. Blood smears were taken from all soldiers suspected to be affected by malaria, and were monitored over a period of 15 weeks. A total of 811 malaria cases were reported during 1992-2011 among Jordanian military personnel whom served in over 20 countries. Most cases were reported among troops returning from Eretria (54.74%), East Timor (18.86%), Ivory Coast (9.12%) and Sierra Leone (5.1%). Troops aged between 20-40 years constituted 96.3% of the total reported cases. The majority of infections were due to Plasmodium vivax (83.5%), followed by Plasmodium falciparum (13.6%). The attack rates (AR) of malaria/100 soldiers among the three contingents were 10.8% for Timor 1, with no post-exposure prophylaxis, and 2.8% for Timor 2 and 3 with post-exposure prophylaxis. There was an evident reduction of malaria attack rate and relapse rate between the two groups Timor 1 (without post-exposure prophylaxis) and Timor 2 and 3 (given post exposure prophylaxis).

Evaluation of immune responses to combined hepatitis A and B vaccine in HIV-infected children and children on immunosuppressive medication

ObjectiveA phase IV interventional study with a combined hepatitis A and B vaccine was conducted in HIV-infected children and children receiving immunosuppressive medication for treatment of rheumatic diseases to evaluate immune responses. MethodsBoth groups (1–16 years of age) received combined (inactivated) HAV and (rDNA) HBV vaccine Ambirix® at months 0 and 6. Serum samples were taken at four time points and tested for anti-HAV and anti-HBs antibodies. Anti-HAV concentrations ≥20mIU/mL or anti-HBs concentrations ≥10mIU/mL were considered protective. Seropositivity percentages were calculated and geometric mean concentrations (GMCs) were compared by nonparametric Mann–Whitney U-test or Kruskal–Wallis one-way-analysis-of-variance. ResultsOf 80 HIV-infected children who completed the study, 67 were HAV-susceptible and 68 HBV-susceptible at enrolment. Of 80 children with rheumatic diseases who completed the study, 65 were HAV-susceptible and 74 HBV-susceptible at enrolment. Immune responses to HAV after first dose of vaccine in both study groups were low: 71% and 55% respectively, whereas immune responses after the second dose were 99% and 100% respectively. Immune response to HBV after first dose of vaccine in both groups was also low: 27% and 17% respectively. Immune responses after the second dose were 97% and 93%, respectively. A larger proportion of children on combination antiretroviral therapy (cART) and of children with viral load <50copies/mL responded to HBV, and also showed a significantly higher GMC. ConclusionsAlthough immune response after full series of combined HAV and HBV vaccine in both groups was excellent and comparable to healthy children, a substantial proportion of both groups was not protected for HAV after first dose of vaccine. This protection gap is especially important for HAV in travel health and postexposure prophylactic treatment: both groups of children should be serologically tested for anti-HAV prior to travel to ensure protection if there is no time to await second dose of vaccine.

CPC-043 Effectiveness and Change of the Protocol For Antiretroviral Treatment Following Exposure to HIV

BackgroundThe average risk of infection after occupational exposure to HIV is 0.3% (0.2–0.5% percutaneous exposure, 0.01–0.5% contact with mucous or non-intact skin) and after sexual exposure 0.01–3%, depending on sexual...

Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry for Rapid Identification of Tick Vectors

A method for rapid species identification of ticks may help clinicians predict the disease outcomes of patients with tick bites and may inform the decision as to whether to administer postexposure prophylactic antibiotic treatment. We aimed to establish a matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) spectrum database based on the analysis of the legs of six tick vectors: Amblyomma variegatum, Rhipicephalus sanguineus, Hyalomma marginatum rufipes, Ixodes ricinus, Dermacentor marginatus, and Dermacentor reticulatus. A blind test was performed on a trial set of ticks to identify specimens of each species. Subsequently, we used MALDI-TOF MS to identify ticks obtained from the wild or removed from patients. The latter tick samples were also identified by 12S ribosomal DNA (rDNA) sequencing and were tested for bacterial infections. Ticks obtained from the wild or removed from patients (R. sanguineus, I. ricinus, and D. marginatus) were accurately identified using MALDI-TOF MS, with the exception of those ticks for which no spectra were available in the database. Furthermore, one damaged specimen was correctly identified as I. ricinus, a vector of Lyme disease, using MALDI-TOF MS only. Six of the 14 ticks removed from patients were found to be infected by pathogens that included Rickettsia, Anaplasma, and Borrelia spp. MALDI-TOF MS appears to be an effective tool for the rapid identification of tick vectors that requires no previous expertise in tick identification. The benefits for clinicians include the more targeted surveillance of patients for symptoms of potentially transmitted diseases and the ability to make more informed decisions as to whether to administer postexposure prophylactic treatment.

Canine Rabies: A Looming Threat to Public Health.

Simple SummaryThis review is guided by three questions: What is canine rabies? Why is it a looming threat to public health? Why should we care about canine rabies being a public health threat? It seeks to answer these questions and notes that canine rabies is viral zoonosis with dogs being the major vectors. The disease is a looming threat to public health because rabid dogs bite humans, resulting in thousands of deaths every year. We should care about this evolving situation because, in general, rabies is a neglected disease for which there are vaccines, preventive measures, post-exposure prophylaxis, and control protocols.Rabies is an acute, fatal viral disease that infects domestic and wild animals and is transmissible to humans. Worldwide, rabies kills over 55,000 people every year. The domestic dog plays a pivotal role in rabies transmission. Domestic dogs are not only part of our daily lives but also of our immediate surroundings, and this is reflected in the rise in pet dog ownership in developed and developing countries. This is important given that more frequent exposures and interactions at the animal-human interface increases the likelihood of contracting zoonotic diseases of companion animals. Despite existing vaccines and post-exposure prophylactic treatment, rabies remains a neglected disease that is poorly controlled throughout much of the developing world, particularly Africa and Asia, where most human rabies deaths occur. It is believed that with sustained international commitments, global elimination of rabies from domestic dog populations, the most dangerous vector to humans, is a realistic goal.

Age-prioritized use of antivirals during an influenza pandemic

BackgroundThe WHO suggested that governments stockpile, as part of preparations for the next influenza pandemic, sufficient influenza antiviral drugs to treat approximately 25% of their populations. Our aim is two-fold: first, since in many countries the antiviral stockpile is well below this level, we search for suboptimal strategies based on treatment provided only to an age-dependent fraction of cases. Second, since in some countries the stockpile exceeds the suggested minimum level, we search for optimal strategies for post-exposure prophylactic treatment of close contacts of cases.MethodsWe used a stochastic, spatially structured individual-based model, considering explicit transmission in households, schools and workplaces, to simulate the spatiotemporal spread of an influenza pandemic in Italy and to evaluate the efficacy of interventions based on age-prioritized use of antivirals.ResultsOur results show that the antiviral stockpile required for treatment of cases ranges from 10% to 35% of the population for R0 in 1.4 – 3. No suboptimal strategies, based on treatment provided to an age-dependent fraction of cases, were found able to remarkably reduce both clinical attack rate and antiviral drugs needs, though they can contribute to largely reduce the excess mortality. Treatment of all cases coupled with prophylaxis provided to younger individuals is the only intervention resulting in a significant reduction of the clinical attack rate and requiring a relatively small stockpile of antivirals.ConclusionOur results strongly suggest that governments stockpile sufficient influenza antiviral drugs to treat approximately 25% of their populations, under the assumption that R0 is not much larger than 2. In countries where the number of antiviral stockpiled exceeds the suggested minimum level, providing prophylaxis to younger individuals is an option that could be taken into account in preparedness plans. In countries where the number of antivirals stockpiled is well below 25% of the population, priority should be decided based on age-specific case fatality rates. However, late detection of cases (administration of antivirals 48 hours after the clinical onset of symptoms) dramatically affects the efficacy of both treatment and prophylaxis.

Cost-benefit of stockpiling drugs for influenza pandemic.

We analyzed strategies for the use of stockpiled antiviral drugs in the context of a future influenza pandemic and estimated cost-benefit ratios. Current stockpiling of oseltamivir appears to be cost-saving to the economy under several treatment strategies, including therapeutic treatment of patients and postexposure prophylactic treatment of patients' close contacts.

Antiretroviral Drug Resistance in Non-Subtype B HIV-1, HIV-2 and Siv

Patients infected with HIV-1 of subtype other than B ('non-subtype B') or with HIV-2 are being treated with antiretroviral drugs in increasing numbers. In addition, healthcare providers and laboratory workers working with clinical specimens or animals infected with HIV, SIV or SHIV are at risk of being exposed to the virus and might require post-exposure prophylactic treatment. Thus, it is important to understand the inherent antiviral susceptibility of non-subtype B HIV-1, HIV-2 and SIV to currently available antiretroviral drugs, which have been developed with subtype B HIV-1-infected patients as the primary target population. In addition, knowledge about the consequences of treatment failure in non-subtype B HIV-1- and HIV-2-infected patients, with respect to the development of drug resistance, is crucial for designing optimal treatment strategies. This review summarizes the current state of knowledge in these areas. Non-subtype B group M HIV-1 appears to be susceptible to available agents, but follows several unique pathways to resistance to some drugs that have important clinical implications. Group O HIV-1 is naturally resistant to the non-nucleoside reverse transcriptase inhibitors (NNRTIs). HIV-2 and SIVsm are also naturally resistant to the NNRTIs as well as the protease inhibitor amprenavir. More research into the clinical responses to existing drugs and interpretation of genotypic information is needed, as well as development of diagnostic assays specific for non-subtype B HIV-1 and HIV-2.

Prevalence of Rabies in the Striped Skunk (Mephitis mephitis) in Kansas from 1966 to 1986

Prevalence of Rabies in the Striped Skunk (Mephitis mephitis) in Kansas from 1966 to 1986

Rhesus Diploid Rabies Vaccine (Adsorbed), A New Rabies Vaccine

Rhesus diploid-cell-strain rabies vaccine (RDRV) (adsorbed) is a new rabies vaccine intended for use in man. Sixty volunteers were given five doses of RDRV at 0, 3, 7, 14, and 28 days to simulate prophylactic treatment of persons exposed to a rabid animal. Thirty-five volunteers were given commercial high-titer rabies immune globulin, 20 IU/kg, before the first dose of RDRV, and 25 were given RDRV without prior rabies immune globulin. Antibody responses at 14, 28, and 42 days were comparable with those reported with human diploid rabies vaccine. Simulated postexposure prophylactic treatment with RDRV was associated with acceptable levels of local and constitutional symptoms. ( JAMA 1983;249:2663-2665)

'Epidemiological' treatment in venereal diseases other than syphilis.

The use of prophylactic and epidemiologic treatment in trichomoniasis nongonococcal urethritis and gonorrhea is reviewed in relation to the epidemiologic profile of these diseases. Epidemiologic treatment is widely used with male partners of females with vaginal trichomoniasis although the risk of infection may be less than 50%. It is also used with female partners of males with nongonococcal urethritis but there is no evidence that such treatment prevents recurrences in infected males. Treatment of gonorrhea is administered in the presence of positive smears but in advance of culture results. This approach justified on the basis of the seriousness of the disease and the time-consuming and complex nature of accurate diagnosis is practiced in 92% of female and 98% of male venereal disease clinics in Great Britain. The use of postexposure prophylactic treatment when the venereal status of the source of exposure is unknown is not approved in the UK but is used in selective cases in 15% of clinics. Epidemiologic treatment is used routinely in 5.8% of male clinics and 22% of female clinics. When clinical evidence of gonorrhea exists these percentages increase to 12.2 and 28.4 respectively. 22.2% of male clinics and 76.1% of female clinics use epidemiologic treatment at least in selected cases when there is epidemiologic and clinical evidence of infection. Selection is most likely to be used for wives regular partners pregnant women those about to travel treatment defaulters promiscuous persons and passive male homosexuals. Clinicians who advocate epidemiologic treatment stress the importance of examination and follow-up. Patients should be examined by smear and culture at the 1st visit and treated patients should be followed as if the disease had been identified. A discussion which follows this article illustrates the controversy surrounding epidemiologic treatment. Concern is expressed that it will be used indiscriminately that a deterioration of clinical standards will result and that lowered rates of disease prevalence will not be noted. (summary in FRE)