OBJECTIVE

Given that rabies remains endemic in the Philippines despite government interventions and the pandemicrelated restrictions have hampered its surveillance, this study aimed to estimate the effect of human population, anti-rabies vaccination efforts, and COVID-19 situation on the spread of rabies cases in the districts of Davao City, Philippines.

A retrospective study of the canine records at Davao City Veterinarians’ Office was done from January 2018 to June 2021. Monthly rabies cases were ascertained, and the effect of the human population, COVID-19 season, and vaccination ratio on rabies cases was estimated using panel regression models adjusting for confounding factors.

The reporting of rabies cases was lower during COVID-19 than during the non-COVID-19 season, with an IRR of 0.52 [95% confidence interval (CI): 0.33–0.82]. Furthermore, rabies cases increased by 2.23% (95% CI: 0.60–3.89) per 1% increase in vaccination ratio. Additionally, high-population districts recorded more rabies cases than low-population districts.

Consistency in monitoring rabies cases during the pandemic is suggested as a roadmap for future program initiatives. Vaccination efforts should be reinforced to increase rabies awareness and ensure early response to emerging diseases. Moreover, highpopulated districts should be prioritized in implementing rabies control interventions to gain optimal development.

BACKGROUND AND OBJECTIVE

Rabies continues to be a challenge in Davao City despite the efforts of the city’s local government to vaccinate primarily the non-stray dog population. Meanwhile, studies have shown that time-dependent vaccination strategy is considered a prime factor for a cost-effective rabies control strategy. Hence, this study aims to provide information that will determine the optimal vaccination strategy targeted to the stray dog population that minimizes the rabies-infected dog population and vaccination costs using optimal control theory (OCT).

OCT is used to identify the optimal level of key rabies control, i.e., vaccination. Here, OCT was applied to a modified Susceptible-Exposed-Infectious-Vaccinated (SEIV) compartmental model. The study's key parameters were derived from published articles on rabies in Davao City and similar regions, along with the city's rabies reports.

The findings revealed that while rabies remains endemic in the city, it is possible to reduce the number of cases through consistent implementation of vaccination programs to the exposed and susceptible dog populations. Nevertheless, the feasibility of these findings relies to the effective targeting of vaccine coverage for the dog population. From the simulations performed, the exposed dog population (i.e., pre-rabid dogs) was able to reach zero observation when the transmission rate (?) is 0.001 for all values of anti-rabies vaccine coverages for exposed (?) and susceptible (b) dog populations and ? = 0.01 only when ? = 0.7 and b = 0.7, ? = 0.7 and b = 0.5, and ? = 0.5 and b = 0.7. Consequently, the number of infectious dogs will thereby decrease. Moreover, a nonlinear correspondence was also observed in all scenarios between the vaccination rate and the number of rabies-exposed dogs such that the reduction in the incidence of rabies cases becomes apparent only when the vaccination rate is at least 0.9995.

In high rabies transmissibility scenarios, a time-dependent vaccination strategy demonstrated a reduction in the number of rabies-infected dogs. However, this approach involves a trade-off, limiting the period during which monthly vaccinations can be relaxed. Consequently, a robust and timely vaccination program for dogs is crucial to manage high rabies transmission rates. Lastly, the model simulation underscores the importance of initiating monthly vaccinations.

BACKGROUND

Rabies remains to be a neglected tropical disease in the Philippines, with the country reporting a higher number of cases compared to its counterparts in Asia.

To describe the demographics, animal bite characteristics, and post-exposure prophylaxis of animal bite patients coming in for care at the Research Institute for Tropical Medicine (RITM), a large government referral center for infectious diseases, and animal bites.

Electronic patient records from January 1, 2018 to December 31, 2019 were obtained from the National Rabies Information System (NaRIS) database of the Department of Health, and summarized using applicable descriptive statistics.

A total of 14,614 patients were included over the two-year study period, and more than third of the patients were children below 15 years old, while more than half were adult males. Lower extremities were the most frequently affected area, while with children, more than a third of exposures were in the head and neck areas. Intradermal route was mostly used for the post-exposure prophylaxis, while WHO prequalified vaccines were utilized in more than 90% of the patients. Only 55.7% of patients completed the prophylaxis regimen at RITM.

These findings reflect the significant exposure of children from animal bites, and the non-compliance of patients to the prescribed post-exposure prophylaxis.

Objectives: To determine the knowledge, attitude, and practices (KAP) on rabies prevention and control among primary care providers of children 0-18 years old. Methodology: This is an analytical cross-sectional study conducted among primary care providers of children 0- 18-years old in Barangay Sambag I, Cebu City, Philippines. A questionnaire to determine the KAP on rabies prevention and control, originally developed by Lañada et al., was modified and contextualized to the local setting. Respondents with at least 75% correct answers per domain were considered to have good overall knowledge, attitude, and practices. Furthermore, each question under the above domains was analyzed separately to determine any gaps in KAP. Results were recorded as frequencies and percentages. The association of KAP to one another and the respondents’ profiles were analyzed using Chi-square test with a level of significance of 0.05. Results: Among 285 respondents, 59.3% had poor knowledge, 35.8% had wrong practices, and 21.8% had negative attitude on rabies prevention and control. We found that 92.6% did not know that rabies is incurable. As to practices, performing “tandok” (42.5%), or the act of removal of rabies from a wound by using an animal horn, and applying herbal medicines (34%) were still done. Use of dog restraint (44.6%) and euthanasia (40%) weren’t favorable to study participants. Surprisingly, non-dog owners had good knowledge and positive attitude than dog owners. Conclusion Our study showed that majority of the study population had poor knowledge on rabies prevention and control, on disease transmission, and on the incurability of rabies. While majority had a positive attitude and correct practices, the unacceptability on the use of a dog restraint and euthanasia, especially among dog owners, were still evident.
Rabies ; Knowledge

Vasculitis refers to the inflammation and damage of blood vessel walls. This presents as erythematous macules or palpable purpura with a predilection for dependent parts, particularly the legs. Vesicles and bullae are less common manifestations. Vasculitis can be idiopathic or associated with infections, systemic diseases, drugs, or vaccines. Vaccine-associated vasculitis has been reported in BCG, influenza, hepatitis, and more recently, COVID-19 vaccines. However, there is limited data on the adverse events associated with rabies vaccine administration.

A 53-year-old Filipino male presented with petechiae evolving into purpura and urticarial targetoid plaques with bullae on the extremities and trunk, after administration of inactivated purified Vero cell rabies vaccine (Verorab, Sanofi Pasteur) due to a Category 3 bite. There were no mucosal lesions. Nikolsky and Asboe-Hansen signs were negative. The patient had no previous reactions to drugs or vaccines.

Histopathology results confirmed the diagnosis of vasculitis. Resolution of skin lesions was achieved with administration of intravenous steroids and oral antihistamines.

Community surveys conducted in three Philippine provinces report the incidence of animal bites at 50 injuries per 1,000 population (5 percent) per year with 45 percent of patients seeking medical treatment at animal bite treatment centers.

There is limited data on adverse events associated with rabies vaccine administration. In general, allergic reactions to vaccines are rare, occurring in approximately 1 in 50,000 to 1 in 1,000,000 doses. These reactions may be due to antigens, residual media, stabilizers, preservatives, or other excipients in the vaccine.

Rash, urticaria, and pruritus have been reported, along with injection site reactions such as erythema, edema, and pain. Fever, malaise, headaches, low mood, purpura, urticaria, Stevens-Johnson Syndrome and erythema multiforme may also occur.

Adequate documentation and reporting of adverse reactions due to vaccines contributes to long-term safety studies and establishing treatment guidelines.

Objective: To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. Methods: A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. Results: The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (P<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (P>0.05). Conclusion: The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.
Humans ; Rabies Vaccines ; Antibodies, Viral ; Antibodies, Neutralizing ; Rabies virus ; Vaccination ; Rabies/prevention & control*

Objective To create a recombinant rabies virus overexpressing IL-33 and to clarify the effect of IL-33 overexpression on the phenotypic characteristics of recombinant virus in vitro. Methods The IL-33 gene was obtained and amplified from the brain of a highly virulent strain of rabies infected mouse. It was then inserted between the G and L genes of the parental virus LBNSE genome by reversing genetic manipulation and rescuing a recombinant virus overexpressing IL-33. BSR cells or mouse NA cells were infected with recombinant rabies virus (rLBNSE-IL33) and the parental strain LBNSE. Sequencing and fluorescent antibody virus neutralization assay was employed to detect the stability of recombinant virus at multiplicity of infection=0.01. Viral titres focal forming units (FFU) were detected to plot multi-step growth curves (multiplicity of infection=0.01). Cytotoxicity assay kit was used to detect cellular activity. ELISA was adopted to identify the IL-33 in the supernatant of infected cells of different multiplicity of infection. Results Rescued rLBNSE-IL33 overexpressing IL-33 remained stable for at least 10 consecutive generations and had virus titers of approximately 10⁸ FFU/mL. rLBNSE-IL33 was able to express IL-33 at high levels in a dose-dependent manner, but no high expression of IL-33 was detected in the supernatant of cells infected by LBNSE. Examination of the titers of rLBNSE-IL33 and the parental strain LBNSE in BSR and NA cells over 5 days showed no significant differences and similar kinetic properties in growth. Overexpression of IL-33 had no significant effect on the proliferation and activity of infected cells. Conclusion Overexpression of IL-33 does not significantly affect the phenotypic characteristics of recombinant rabies virus in vitro.
Animals ; Cricetinae ; Mice ; Cell Line ; Interleukin-33/genetics* ; Rabies virus/genetics* ; Phenotype

Objective: To understand the knowledge, attitude and behavior of adult residents on influenza, pneumococcus, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, hepatitis B and rabies vaccination in Shandong Province. Methods: From August to September 2022, a multi-stage stratified random sampling method was used to investigate community-dwelling residents aged 18 years old and above in 12 counties (cities and districts) of Shandong Province. A questionnaire survey was used to collect the basic information of the respondents, such as knowledge, attitude and vaccination behavior of influenza, pneumococcus, HPV, HZ, COVID-19, hepatitis B and rabies vaccine. Analysis of variance was used to compare the differences in the respondents' knowledge and attitude scores of different vaccines. The Chi-square test was conducted to compare the differences in vaccination reasons among different characteristics, and a logistic regression model was used to analyze the influencing factors of vaccination behavior. Results: The median age (Q₁, Q₃) of the 2 754 respondents was 39 (29, 57) years ranging from 18 to 94 years, with a number of 1 234 (44.81%) males. The average score of the respondents' understanding of various knowledge about adult vaccines was less than 4 points, with the highest score for understanding which diseases can be prevented by adult vaccines. The average score of consent and necessity for adult vaccines to prevent diseases was greater than 3.6 points. In terms of knowledge demand and trust in information channels, there was a high level of trust in the recommendations of vaccination outpatient staff and clinical doctors [with scores of (4.15±0.79) and (4.02±0.80), respectively]. The highest demand for information on vaccination safety knowledge was (4.18±0.84) points. In recent two years, 52.11% of the population had been vaccinated with other vaccines in addition to the COVID-19 vaccine and rabies vaccine, and 45.44% of the population felt it was necessary to be vaccinated through media publicity. Women, age growth, high education level, and high-income level were the promoting factors for adopting vaccination behavior. Conclusion: Adult residents in Shandong Province have a basic understanding and supportive attitude towards vaccination, but the vaccination behavior rate is still relatively low, with significant differences in sex, age, education level, and income level. It is necessary to further increase efforts in the breadth and depth of adult vaccination promotion and education, as well as promotion strategies targeting different populations.
Adult ; Male ; Female ; Humans ; Adolescent ; COVID-19 Vaccines ; Health Knowledge, Attitudes, Practice ; Influenza, Human ; Papillomavirus Infections ; Rabies Vaccines ; Influenza Vaccines ; COVID-19/prevention & control* ; Hepatitis B ; Herpes Zoster

Objective: To understand the setting of adult vaccination clinics and the situation of adult vaccination in Shandong province, and provide the date basis for the construction and development of adult vaccination clinics in Shandong province. Methods: Multi-stage stratified cluster random sampling was used to survey the settings, personnel allocation, operation status, and adult vaccination status of child-adult vaccination clinics and adult vaccination clinics. A random sampling survey was conducted for hydrophobia vaccination clinics in 12 counties (cities, districts) of Shandong province. The settings and vaccination status of different types of adult vaccination clinics were compared and analyzed using analysis of variance or χ²-test. Results: Among the investigated counties (cities, districts), the child-adult vaccination clinics, the adult vaccination clinics, and the hydrophobia vaccination clinics accounted for 59.51%, 7.97% and 32.52%, respectively. The construction model could be divided into three models: child-adult vaccination clinic model, child-adult and hydrophobia vaccination clinic model, child-adult, adult and hydrophobia vaccination clinic model. The child-adult vaccination clinics had been set up for a long time (≥3 years accounted for 94.33%) and were set up by public primary medical institutions (public institutions accounted for 93.81% and primary institutions accounted for 92.78%). Each vaccination clinic was equipped with full-time and part-time staff of (3.19±3.01) and (3.72±4.32). The adult vaccination clinics had been set up for a short time (≥3 years accounted for 94.33%) and were set up by public/private primary/secondary medical institutions in urban areas (urban areas accounted for 100%, primary institutions accounted for 69.23%, and private institutions accounted for 57.69%). Each vaccination clinic was equipped with full-time and part-time staff of (2.46±2.87) and (3.08±3.53). The coverage of influenza vaccine (InfV), human papillomavirus vaccine (HPV) and hepatitis B vaccine (Hep B) reached 100%, 98.45% and 97.42% in children-adult vaccination clinics, and 88.46%, 84.62% and 73.08% in adult vaccination clinics, respectively. The hydrophobia vaccination clinics only provided rabies vaccine for human use (RabV) and tetanus vaccine (TV) vaccination simultaneously. A total of 819.8 thousand doses of adult vaccines were administered in 2021. The adult inoculation doses of RabV, lnfV and HPV accounted for 42.60%, 27.47% and 17.54% of the total inoculation doses, respectively. The inoculation doses of InfV, HPV and RabV accounted for 49.33%, 21.97% and 13.80% of child-adult vaccination clinics, respectively. The inoculation doses of HPV, HepB and RabV accounted for 49.36%, 15.40% and 14.71% of adult vaccination clinics, respectively. The proportion of RabV reached 94.44% in the hydrophobia vaccination clinics alone. Conclusion: Adult vaccination is at the initial stage in Shandong province. The children's vaccination clinic is mainly responsible for adult vaccination. The variety of adult vaccines is relatively concentrated, and the adult vaccination rate is lower. The construction and publicity of adult vaccination should be further strengthened.
Adult ; Humans ; Papillomavirus Infections ; Rabies ; Influenza Vaccines ; Vaccination ; Ambulatory Care Facilities ; Papillomavirus Vaccines

Objective: To understand the knowledge, attitude and behavior of adult residents on influenza, pneumococcus, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, hepatitis B and rabies vaccination in Shandong Province. Methods: From August to September 2022, a multi-stage stratified random sampling method was used to investigate community-dwelling residents aged 18 years old and above in 12 counties (cities and districts) of Shandong Province. A questionnaire survey was used to collect the basic information of the respondents, such as knowledge, attitude and vaccination behavior of influenza, pneumococcus, HPV, HZ, COVID-19, hepatitis B and rabies vaccine. Analysis of variance was used to compare the differences in the respondents' knowledge and attitude scores of different vaccines. The Chi-square test was conducted to compare the differences in vaccination reasons among different characteristics, and a logistic regression model was used to analyze the influencing factors of vaccination behavior. Results: The median age (Q₁, Q₃) of the 2 754 respondents was 39 (29, 57) years ranging from 18 to 94 years, with a number of 1 234 (44.81%) males. The average score of the respondents' understanding of various knowledge about adult vaccines was less than 4 points, with the highest score for understanding which diseases can be prevented by adult vaccines. The average score of consent and necessity for adult vaccines to prevent diseases was greater than 3.6 points. In terms of knowledge demand and trust in information channels, there was a high level of trust in the recommendations of vaccination outpatient staff and clinical doctors [with scores of (4.15±0.79) and (4.02±0.80), respectively]. The highest demand for information on vaccination safety knowledge was (4.18±0.84) points. In recent two years, 52.11% of the population had been vaccinated with other vaccines in addition to the COVID-19 vaccine and rabies vaccine, and 45.44% of the population felt it was necessary to be vaccinated through media publicity. Women, age growth, high education level, and high-income level were the promoting factors for adopting vaccination behavior. Conclusion: Adult residents in Shandong Province have a basic understanding and supportive attitude towards vaccination, but the vaccination behavior rate is still relatively low, with significant differences in sex, age, education level, and income level. It is necessary to further increase efforts in the breadth and depth of adult vaccination promotion and education, as well as promotion strategies targeting different populations.
Adult ; Male ; Female ; Humans ; Adolescent ; COVID-19 Vaccines ; Health Knowledge, Attitudes, Practice ; Influenza, Human ; Papillomavirus Infections ; Rabies Vaccines ; Influenza Vaccines ; COVID-19/prevention & control* ; Hepatitis B ; Herpes Zoster