Post-exposure prophylaxis (PEP) for rabies with purified chick embryo cell vaccine: a systematic literature review and meta-analysis

<p><b>Introduction</b>: Fifteen million people each year receive post-exposure prophylaxis (PEP) to prevent rabies, yet the disease remains neglected and highly under-reported.</p> <p><b>Areas covered</b>: In this systematic literature review, we assessed the immunogenicity, efficacy, and safety of a purified chick embryo cell-culture rabies vaccine (PCECV) for PEP against rabies by intramuscular (IM) or intradermal (ID) administration. We performed meta-analyses to compare immunogenicity according to the route of vaccine administration, study population, and PEP regimen, such as number of doses, and concomitant rabies immunoglobulin.</p> <p><b>Expert commentary</b>: There were 54 estimates of immune responses to vaccination, which showed that in the overall population, after starting PEP with PCECV by the IM or ID route (≥2.5 IU per dose), almost all individuals had rabies virus neutralizing antibody (RVNA) titers above the World Health Organization (WHO) recommended serological threshold for an adequate immune response to vaccination (RVNA ≥0.5 IU/ml by day 14). In the overall population, PCECV had an acceptable safety profile. However, given that there are 59,000 human rabies deaths reported annually, the challenge is to improve access to PCECV for PEP against human rabies.</p

Occurrence of selected clinical manifestations [n/total] and their predictive value (%) for DHF among dengue infected cases.

<p>Occurrence of selected clinical manifestations [n/total] and their predictive value (%) for DHF among dengue infected cases.</p

The number of dengue infected patients who had prolonged symptom (for 3 or more days) [n (%)].

<p>NA = not applicable.</p>a<p>significantly more common in DHF compared to DF and UF, but no difference between DF and UF.</p>b<p>significantly less common in UF compared to DF and DHF, but no difference between DF and DHF.</p>c<p>significantly more common in UF compared to DF and DHF, but no difference between DF and DHF.</p>d<p>significantly less common in DF compared to UF and DHF, but no difference between UF and DHF.</p

The prevalence of common symptoms in dengue infection by the day of illness.

<p>The prevalence of common symptoms in dengue infection by the day of illness.</p

Symptoms and disease severity from different dengue serotypes [n (%)].

<p>Symptoms and disease severity from different dengue serotypes [n (%)].</p

The prevalence (%) of clinical manifestation of dengue diseases from previous studies.

<p>ND = no data.</p>a<p>include both myalgia and arthralgia.</p

Dengue incidence.

<p>(<b>A</b>) Shown is the incidence by school in each year. (<b>B</b>) Shown is the incidence by school in all years.</p

Dengue Infection in Children in Ratchaburi, Thailand: A Cohort Study. I. Epidemiology of Symptomatic Acute Dengue Infection in Children, 2006–2009

<div><h3>Background</h3><p>There is an urgent need to field test dengue vaccines to determine their role in the control of the disease. Our aims were to study dengue epidemiology and prepare the site for a dengue vaccine efficacy trial.</p> <h3>Methods and Findings</h3><p>We performed a prospective cohort study of children in primary schools in central Thailand from 2006 through 2009. We assessed the epidemiology of dengue by active fever surveillance for acute febrile illness as detected by school absenteeism and telephone contact of parents, and dengue diagnostic testing. Dengue accounted for 394 (6.74%) of the 5,842 febrile cases identified in 2882, 3104, 2717 and 2312 student person-years over the four years, respectively. Dengue incidence was 1.77% in 2006, 3.58% in 2007, 5.74% in 2008 and 3.29% in 2009. Mean dengue incidence over the 4 years was 3.6%. Dengue virus (DENV) types were determined in 333 (84.5%) of positive specimens; DENV serotype 1 (DENV-1) was the most common (43%), followed by DENV-2 (29%), DENV-3 (20%) and DENV-4 (8%). Disease severity ranged from dengue hemorrhagic fever (DHF) in 42 (10.5%) cases, dengue fever (DF) in 142 (35.5%) cases and undifferentiated fever (UF) in 210 (52.5%) cases. All four DENV serotypes were involved in all disease severity. A majority of cases had secondary DENV infection, 95% in DHF, 88.7% in DF and 81.9% in UF. Two DHF (0.5%) cases had primary DENV-3 infection.</p> <h3>Conclusion</h3><p>The results illustrate the high incidence of dengue with all four DENV serotypes in primary school children, with approximately 50% of disease manifesting as mild clinical symptoms of UF, not meeting the 1997 WHO criteria for dengue. Severe disease (DHF) occurred in one tenth of cases. Data of this type are required for clinical trials to evaluate the efficacy of dengue vaccines in large scale clinical trials.</p> </div

Symptoms of dengue infection [n (%)].

a<p>significantly more common in DHF compared to DF and UF, but no difference between UF and DF.</p>b<p>significantly less common in UF compared to DF and DHF, but no difference between DF and DHF.</p>c<p>significantly more common in DHF compared to DF and UF, and more common in DF compared to UF.</p

Physical findings in dengue infection [n/number observed (%)].

a<p>significantly less common in UF compared to DF and DHF, but no difference between DF and DHF.</p>b<p>significantly more common in DHF compared to DF and UF, and more common in DF compared to UF.</p