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Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, and anatomical site of administration in rabies postexposure prophylaxis.

ABSTRACT: Rabies is a fatal disease that mandates proper prophylaxis after a rabies virus exposure to prevent death. This study evaluated adherence to Centers of Disease Control and Prevention (CDC) recommendations for rabies immune globulin (IG) patient selection, dosing, timing of administration, and anatomical site of administration for rabies postexposure prophylaxis. This retrospective, cross-sectional study included patients who received at least one dose of rabies IG or rabies vaccine at a multi-hospital health system from January 2015 through June 2018. This study included 246 patients, and all of them received at least one dose of rabies vaccine. Two patients had a history of rabies vaccination, did not have an indication for rabies IG, and appropriately did not receive additional rabies IG. Rabies IG was administered to 91% (223 of 244) of patients with an indication. Of 223 patients who received rabies IG, 219 (98%) received doses within 10% of 20 IU/kg of body weight, and all 223 (100%) received rabies IG within 7 days of the first rabies vaccine administration. Only 56% (96 of 170) of patients with a wound that could be infiltrated with rabies IG actually received rabies IG via infiltration into and around the wound. This multi-hospital health system study demonstrated high adherence to guideline recommendations for rabies IG patient selection (91%), dosing (98%), and timing (100%). However, only 56% of eligible patients received rabies IG infiltration at wound sites as recommended by guidelines.

SUBMITTER: Hwang GS

PROVIDER: S-EPMC7012082 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Vaccine-induced B cells differentiate along two pathways. The follicular pathway gives rise to germinal centers (GCs) that can take weeks to fully develop. The extrafollicular pathway gives rise to short-lived plasma cells (PCs) that can rapidly secrete protective antibodies within days of vaccination. Rabies virus (RABV) postexposure prophylaxis (PEP) requires rapid vaccine-induced humoral immunity for protection. Therefore, we hypothesized that targeting extrafollicular B cell responses for activation would improve the speed and magnitude of RABV PEP. To test this hypothesis, we constructed, recovered, and characterized a recombinant RABV-based vaccine expressing murine B cell activating factor (BAFF) (rRABV-mBAFF). BAFF is an ideal molecule to improve early pathways of B cell activation, as it links innate and adaptive immunity, promoting potent B cell responses. Indeed, rRABV-mBAFF induced a faster, higher antibody response in mice and enhanced survivorship in PEP settings compared to rRABV. Interestingly, rRABV-mBAFF and rRABV induced equivalent numbers of GC B cells, suggesting that rRABV-mBAFF augmented the extrafollicular B cell pathway. To confirm that rRABV-mBAFF modulated the extrafollicular pathway, we used a signaling lymphocytic activation molecule (SLAM)-associated protein (SAP)-deficient mouse model. In response to antigen, SAP-deficient mice form extrafollicular B cell responses but do not generate GCs. rRABV-mBAFF induced similar anti-RABV antibody responses in SAP-deficient and wild-type mice, demonstrating that BAFF modulated immunity through the extrafollicular and not the GC B cell pathway. Collectively, strategies that manipulate pathways of B cell activation may facilitate the development of a single-dose RABV vaccine that replaces current complicated and costly RABV PEP.IMPORTANCE Effective RABV PEP is currently resource- and cost-prohibitive in regions of the world where RABV is most prevalent. In order to diminish the requirements for rabies immunoglobulin (RIG) and multiple vaccinations for effective prevention of clinical rabies, a more rapidly protective vaccine is needed. This work presents a successful approach to rapidly generate antibody-secreting PCs in response to vaccination by targeting the extrafollicular B cell pathway. We demonstrate that the improved early antibody responses induced by rRABV-mBAFF confer improved protection against RABV in a PEP model. Significantly, activation of the early extrafollicular B cell pathway, such as that demonstrated here, could improve the efficacy of vaccines targeting other pathogens against which rapid protection would decrease morbidity and mortality.

Project description:Introduction Each year, an estimated 25000 rabies death occurs in Africa. Post-exposure prophylaxis (PEP) remains the only proven approach in preventing rabies deaths. Most of rabies deaths occur among those who delayed, did not receive, or complete rabies PEP. The aim of this study was to determine the pattern of animal bite, factors associated with delays in initiating, and nonadherence to rabies PEP regimen. Method Data on clients reporting for rabies PEP in a tertiary hospital setting in Ghana were collected from 2013 to 2016. Demographics, place, and source of exposure were collected. Other information obtained included adherence to the PEP protocol and GPS coordinates of the town of animal bites. The shortest distance between the GPS coordinates of town of animal bite and the site of administration of the rabies PEP was calculated. A total of 1030 individuals received rabies PEP over the period. Results Overall, 52.9% (545) were males while 47.1% (485) were females. Majority of the cases were between the age group 1–10 years accounting for 29.2%. Dog bites accounted for 96.5% (n?=?994). Cats, nonhuman primates, human bites, respectively, accounted for 1.8% (n?=?18), 1.2% (n?=?12), and 0.6% (n?=?6) of all bites. Majority of bites occurred at home (66.2% (n?=?646)). Also, 31.6% (n??=?308) and 2.3% (n?=?22) of bites occurred on the streets and neighbors/friends' homes, respectively. Only, 18.7% initiated PEP within 24 hours of bite. Rabies PEP regimen completion rate was 95.2% (n?=?976). The median distance travelled to access rabies PEP was 7.87?km (IQR, 3.58–16.27) km. Overall, 34.7% (n?=?344) had the animal bite within 4.99?km radius of the treatment room of KBTH. Clients who delayed in initiating rabies PEP were 2.6 (95% CI, 1.3–5.1) times more likely to be males and 2.0 (1.1–3.9) times more likely to receive bites in a location more than 5?km radius from the KBTH treatment room. Gender, age, and distance of bite from the treatment room were not associated with the likelihood of not completing rabies PEP schedule. Discussion. Bites from suspected rabies infected animals remain a problem in southern Ghana. There are significant delays in initiating PEP for rabies prevention. Most animal bite victims are children ten years and below. Male gender and bites more than 5?km radius from the site of rabies PEP administration were most significant factors associated with delays in initiating rabies PEP. There is the need for adopting strategies to encourage prompt initiation and adherence to PEP.

Project description:BACKGROUND:Human rabies is a notifiable condition in Thailand, and 46 confirmed and probable cases were reported from 2010-2015; eleven were reported from Eastern Thailand. Although rabies is vaccine preventable, more than 90% of persons who died of rabies in Thailand either did not receive or inappropriately discontinued post-exposure prophylaxis (PEP). In 2012 Thailand launched a national animal rabies elimination program with the goal of elimination by 2020. One of the policies of this national program is to improve detection of animal rabies exposures, access to PEP, and adherence to vaccine schedules. To achieve this goal, several hospital-based electronic PEP surveillance systems have been instituted throughout Thailand. METHOD:Data from a voluntary, electronic hospital-based, rabies exposure and PEP surveillance system was analyzed from eight provinces in Eastern Thailand for the time period January 1 -December 31, 2015. The surveillance system collects data from all persons who present to an R36-integrated healthcare facility with a suspected rabies exposure, including characteristics of the biting animals, categorization of the rabies exposure, and adherence to PEP recommendations. The crude rate of healthcare seeking for a suspected rabies exposure was assessed by province, and a multivariable linear regression model was developed to determine the potential extent of undetected rabies exposures due to bite treatment at healthcare facilities that do not utilize the R36 system. Suspected rabies exposures were described by patient demographics, location of wound, and disposition of the offending animal. A comparison of adherence to intramuscular and intradermal vaccination regimens was performed and odds ratios were calculated for factors related to unadvised PEP discontinuation. RESULT:6,204 suspected rabies exposures were reported from eight Eastern Thailand provinces, yielding a crude exposure rate of 106 reported rabies exposures per 100,000 population. When adjusted for under-detection due to non-participating hospitals and province-level demographic differences, the estimated suspected rabies exposure rate was 204/100,000. Dogs were the main source of exposure (77.8%) and children age <15 years and elderly age >60 years had the highest overall reported exposure rate (189.7 and 189.2/100,000). Adherence to either the intramuscular 5-dose or the intradermal 4-dose PEP regimen was low (15.8% and 46.5%, respectively); rabies immunoglobulin was received by only 15% of persons for whom it was indicated. Persons with rabies exposures were more likely to discontinue the vaccination series against medical advice if they were male, aged 16-45, if they received immunoglobulin, or if received the intramuscular regimen. CONCLUSION:When adjusting for number of reporting hospitals, province population density, number of hospitals per population and average family income, the expected report rate increased 1.9-fold, indicating that there is likely a high level of under-detection of persons seeking medical care for suspected rabies exposures. Expanded implementation of electronic surveillance systems will likely improve reporting and the epidemiologic knowledge of rabies exposures. Analysis of data collected from this system revealed very low rates of adherence to rabies vaccination recommendations. PEP adherence was better by the intradermal route, which provides more support for its use in situations where it is economically feasible.

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Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, and anatomical site of administration in rabies postexposure prophylaxis.

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