Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus

Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.     

Failure of multiple-site intradermal postexposure rabies vaccination in patients with human immunodeficiency virus with low CD4+ T lymphocyte counts.

Human immunodeficiency virus (HIV)-infected patients with low CD4(+) T lymphocyte counts had a poor neutralizing antibody response to pre- and postexposure rabies vaccination. This study of HIV-infected patients with CD4(+) T lymphocyte counts < 200/microL indicated that patients had a poor response after 4-site intradermal vaccinations (4-4-4-0-2-2, doubling the intradermal doses of cell-culture rabies vaccine).     

Development of a cocktail of recombinant-expressed human rabies virus-neutralizing monoclonal antibodies for postexposure prophylaxis of rabies

To provide a cost-effective and safe replacement for human rabies immunoglobulin (HRIG), we used DNA recombinant technology to express 3 human rabies virus-neutralizing human monoclonal antibodies (huMAbs) in a rhabdovirus vector (RhV). Infection of either baby hamster kidney cells or CHO cells, with the resulting RhV-huMAb recombinant viruses, yielded high-level production (< or =40 micro g/mL/48 h) of RhV recombinant-expressed huMAbs (rhuMAbs) that differ in both isotype and epitope-recognition specificity. A cocktail of these rhuMAbs neutralizes several fixed and street wild-type rabies viruses (RVs). Mice and hamsters treated only once with this rhuMAb cocktail after infection with a lethal dose of RV were protected. In the mouse models, the postexposure prophylaxis (PEP) efficacy obtained with the rhuMAb cocktail was comparable to that obtained with HRIG, a finding strongly suggesting that rhuMAbs should be given serious consideration for use in future PEP of humans.     

Prescribing practices in a population-based HIV postexposure prophylaxis program

OBJECTIVES: To characterize factors associated with being prescribed triple or double postexposure prophylaxis (PEP) against HIV in a population-based program. METHODS: Individuals potentially exposed to HIV received a 5 day starter kit of either double or triple antiretroviral PEP between April 1999 and November 2000 and did/did not receive the remaining 23 days PEP. Data were collected through dispensation of kits. Logistic regression identified characteristics independently associated with being prescribed triple therapy starter kits and with any 23 day follow-up. RESULTS: Of 2064 people receiving 5 day PEP [403 (20%) triple and 1661 (80%) double], 590 (29%) received 23 day follow-up. Independently associated with being prescribed triple therapy starter kits were being male [adjusted odds ratio (AOR) 1.38; 95% confidence interval (CI) 1.10-1.74; P = 0.006), occupational mucocutaneous injuries (AOR 1.70; 95% CI, 1.14-2.55; P = 0.010), and community needlesticks (AOR 2.04; 95% CI, 1.54-2.69; P < 0.001). Independently associated with being prescribed the 23 day follow-up were being male (AOR 1.24; 95% CI, 1.00-1.53; P = 0.04), community mucocutaneous incidents (AOR 2.83; 95% CI, 1.41-5.70; P = 0.004), community needlesticks (AOR 1.75; 95% CI, 1.33-2.29; P < 0.001), and having received triple therapy as the starter kit (AOR 2.61; 95% CI, 2.07-3.29; P < 0.001). CONCLUSIONS: Being prescribed triple therapy starter PEP was associated with being male and with experiencing an occupational mucocutaneous or community needlestick injury. Receiving the remaining 23 days PEP was associated with being male, experiencing a community mucocutaneous or needlestick injury, and triple therapy as the initial 5 day starter PEP.     

The primary hamster kidney cell rabies vaccine: adaptation of viral strain, production of vaccine, and pre- and postexposure treatment

The hamster kidney cell rabies vaccine was investigated as a substitute for classical nervous tissue rabies vaccine. The Beijing strain of fixed rabies virus was adapted to primary hamster kidney cells (PHKCs), and four types of rabies vaccine (plain, adjuvant, concentrated, and concentrated adjuvant vaccines) were developed for human use. The potencies of the vaccines met the requirements of the World Health Organization, and these vaccines elicited rather satisfactory antibody responses in volunteers. The postexposure use of vaccine was evaluated in 301 individuals, 97 of whom had been bitten by proven rabid animals. None of the individuals contracted rabies during the observation period. After several years of field trials with both pre- and postexposure vaccines, the evidence indicates that the PHKC rabies vaccines are effective and safe for human use.     

Zoster in patients infected with HIV: a review.

Varicella-zoster virus (VZV), a member of the human herpesvirus family, causes childhood chickenpox (varicella), becomes latent in sensory ganglia, and reactivates years later in immunocompromised and elderly persons to produce shingles (herpes zoster). Early in the AIDS epidemic, zoster was noted in adults and children infected with HIV. Severe and debilitating zoster-associated dermatological, ophthalmic, and neurological complications may occur in patients infected with HIV. Antiviral therapy can modify the duration of zoster and alleviate its attendant complications. Varicella vaccine may boost the immunity and prevent virus reactivation. VZV immune globulin (VZIG) prevents or modifies clinical illness in persons who have been exposed to varicella or zoster.     

Risk of diabetes in HIV infected veterans pre- and post-HAART and the role of HCV coinfection

We examined the association of hepatitis C virus (HCV) infection with diabetes in veterans infected with human immunodeficiency virus (HIV) before and after the institution of highly active antiretroviral therapy (HAART). The role of age, race, liver disease, alcohol, and drug diagnoses upon the risk of diabetes was also determined. Male veterans with HIV who entered care between 1992 and 2001 were identified from the Veterans Affairs (VA) administrative database. Demographic and disease data were extracted. Kaplan-Meier curves were plotted to determine the incidence of diabetes. Unadjusted and adjusted hazards ratios for diabetes were determined using Cox regression method. A total of 26,988 veterans were studied. In multivariate Cox regression analysis, factors associated with a diagnosis of diabetes included increasing age (HR, 1.44 per 10-year increase in age; 95% CI, 1.39-1.49), minority race (African American: HR, 1.35; 95% CI, 1.24-1.48; Hispanic: HR, 1.63; 95% CI, 1.43-1.86), and care in the HAART era (HR, 2.35; 95% CI, 2.01-2.75). There was a significant interaction between care in the HAART era and HCV infection, with HCV infection being associated with a significant risk of diabetes in the HAART era (HR, 1.39; 95% CI, 1.27-1.53) but not in the pre-HAART era (HR, 1.01; 95% CI, 0.75-1.36). In conclusion, HIV-infected veterans in the HAART era are at a higher risk for diabetes compared with those in the pre-HAART era. HCV coinfection is associated with a significantly higher risk of diabetes in the HAART era, but not in the pre-HAART era. HCV-HIV coinfected patients should be aggressively screened for diabetes.     

Risk of rabies transmission and adverse effects of postexposure prophylaxis in health care workers exposed to a fatal case of human rabies

On May 27, 2008, a patient died from rabies at the Cayenne Hospital in French Guiana. Postexposure prophylaxis vaccination was implemented for all health care workers exposed to this patient. Examining the management of such a rare risk reveals important factors in the education of personnel who may have contact with a patient with rabies, to permit appropriate risk assessment and reduce unnecessary postexposure prophylaxis, taking into account the risks and costs of adverse events.     

Management of occupational and nonoccupational postexposure HIV prophylaxis

The principles of managing patients with recent HIV exposure are similar whether the exposure occurs in an occupational or nonoccupational setting. For both settings, clinicians should assess the likelihood that HIV and other bloodborne viruses will be transmitted as a consequence of the exposure; advise the patient about the risks and benefits of treatment; choose an appropriate antiretroviral treatment regimen (if the decision is made to treat); screen for other illnesses that may complicate treatment or follow-up; counsel patients about the importance of adhering to treatment; promote safe-sex practices and methods to avoid future exposures; follow the patient for potential side effects of treatment; and provide follow-up care including repeat HIV testing for seroconversion, surveillance for primary HIV infection, and reinforcement of counseling messages.     

Myocardial ischaemia in a child infected with influenza B

Cardiac involvement is a rare complication of infection by the influenza B virus. It usually presents with ventricular dysfunction, arrhythmias, or both. We report a 13-year-old boy with clinical, electrocardiographic, and laboratory findings of myocardial ischaemia during an otherwise silent acute infection with influenza B. Coronary endothelial injury constituted a potential underlying mechanism, and microthrombosis was promoted by high levels of lipoprotein(a) in the serum.     

Cryptococcal fungemia and probable histoplasmosis in a patient infected with HIV. Case report

Background

Those infected by human immunodeficiency virus (HIV) have a higher risk of opportunistic infections. The risk is related to the level of immunosuppression. We report a case of a young male with the unusual scenario of three opportunistic infections occurring simultaneously: Cryptococcosis, Histoplasmosis and Cryptosporidiosis. Histoplasmosis and cryptococcosis are major causes of morbimortality in immunocompromised patients due to HIV infection.

Case presentation

We report the case of a patient with HIV infection with a CD4 T lymphocyte cell (CD4) count of 2 cells/mm3, who presented with 6?months of diarrhea, non-productive dry cough, nocturnal diaphoresis, fever, weight loss, and a maculopapular rash. He had a concurrent infection with three opportunistic microorganisms: fungemia by cryptococcosis, disseminated histoplasmosis confirmed by detection of the antigen in urine and chronic diarrhea by cryptosporidiosis confirmed by direct observation in feces by modified Ziehl–Neelsen stain. The patient received antifungal treatment with a satisfactory outcome.

Conclusions

There are still regions where HIV detection programs are deficient thus facilitating occurrence of HIV infection cases in advanced stages of immunosuppression. A high level of suspicion of systemic mycoses and concurrent infection by several opportunistic pathogens is required in severely immunocompromised patients.

     

A review of HIV postexposure prophylaxis provision at a genitourinary medicine department

We undertook a retrospective case-note audit of all patients who presented to the Edinburgh genitourinary (GU) medicine department following a potential exposure to HIV infection during the period 1 January 2006 to 31 December 2008. Over the audit period, 81 individuals attended the department, in relation to 85 exposure events. Twenty-three (27%) exposures had occurred in a health-care occupational setting and 50 (59%) in a sexual context. Baseline HIV testing was only performed in 38 (45%) of the 85 exposures. Postexposure prophylaxis (PEP) was initiated in 65 (76%) cases: 61 (94%) received the first dose within the recommended 72 hours. In 68 (80%) of the 85 exposures, the PEP initiation decision tallied with guideline recommendations. Fifty-six of the 65 individuals started on PEP continued beyond 72 hours; 53 of them were reviewed at least once during the course of PEP and had routine blood monitoring performed. Documentation regarding adherence was poor, with only 31 having this recorded in notes. Thirty-seven (66%) individuals who continued on PEP attended for follow-up HIV testing at three months. In summary, the department performed well in some aspects of PEP provision. However, baseline HIV testing and documentation regarding adherence are unsatisfactory and we suggest recommendations to improve this.