Severe multiple rabid dog bite injuries in a child in central China: Continuous 10-year observation and analysis on this case

ABSTRACT

Dog bites are common in rural areas of underdeveloped countries or regions, affecting persons of different ages. Suspected rabid dog bites will lead to more severe outcomes, especially in children because injuries often occur on their heads and faces that are highly innervated parts of the body. In such circumstances, immediate and complete post-exposure prophylaxis (PEP) will be essential, though vaccine hesitancy is a problem. Herein, we report a 4-y-old girl who was seriously bitten by a confirmed rabid dog in rural China. Multiple lacerations and punctures distributed on her head, neck, face, extremities, and back after being bitten. It was in question that surgery or PEP should be performed in priority when the dog was not confirmed rabid at first, but considering the risks of rabies, immediate PEP was provided to her, along with immunogenicity tests to ensure an adequate protective immune response. Because of the severity of her injuries, medical practitioners suggested her parents to bring her to take immunogenicity tests in 1-, 5-, and 10-y intervals to ensure adequate rabies virus-neutralizing antibodies (RVNA) titers. Her parents had a good preference for medical advices, and in the 10-y interval, it was found that her RVNA titer was below protection level, so a booster vaccination was given to her, and 14 d after that, according to immunogenicity test, RVNA titer arose quickly above the protection level.

KEYWORDS:

• Severe dog bites
• PEP
• child
• long-term observation
• vaccine hesitancy

Introduction

Rabies is a worldwide health problem¹ and deadly zoonotic disease, accounted for estimated 59,000 human deaths annually, among which mostly occurred in Africa and Asia.² Approximately 99% of the human rabies cases could be attributed to dog bites.³ Without timely treatments, the onset of rabies is very likely to occur, and it will be 100% fatal.⁴ Prompt post-exposure prophylaxis (PEP) is effective in preventing rabies occurrence, even in seriously bitten and uncommon case.

Patient presentation

On March 31, 2007, a 4-y, 8-month-old girl was severely bitten by her own dog in rural Wuhan, China. Lacerations distributed all around her face, head, neck, limbs, and body. A deep laceration (12 cm in length and 3 cm in width) at occipital reached periosteum and 3 cm below the occipital, and there were two wounds about 2 cm long, 2 cm wide, and 4 cm deep. About 4 cm below and behind her left ear, there was a wound that was 5 cm in length, 3 cm in width, and 5 cm in depth. Multiple perforating wounds were distributed over her head, face, neck, shoulders, left side of the chest, back, and waist. Besides, there were a dozen of scratches and lacerations that cut through dermis on her chest, back, and both upper limbs (Figure 1a). More seriously, there were deep and large wounds on her head, which was a highly innervated part (Figure 1b). She was heavily bleeding when hospitalized, accompanied by listlessness and pale. The dog was a medium-sized local dog and had not received any kind of immunization. Before its bites on the patient, it had lost for 1 week, and when it went back, it developed highly suspected rabid symptoms – salivating, tail clamping, and paroxysmal mania. The girl was not aware of those risk symptoms, missed it so much and wanted to play with it. However, it was out of control and bit her heavily. The Public Security Bureau killed the dog on the spot concerning its dangerous behaviors and the public’s security. And the Public Health Department cut its head and sent it to Wuhan Institute of Biological Products for laboratory tests, buried its body deeply with lime, and sterilized the spot. The dog’s cerebral tissue was taken to perform simple sandwich enzyme-linked immunosorbent assay (ELISA) and fluorescent antibody test in Wuhan Institute of Biological Products. The diagnostic kit for the antigen to rabies virus (ELISA) and mouse monoclonal antibody against rabies virus nucleoprotein marked with FITC were provided by the Institute. The tests were performed in biosafety level-3 (BSL-3) laboratory. After 3 d, both tests proved rabid virus in the dog’s head. Unnoticed tiny wounds without thorough washing and infiltration of RIG contribute to PEP failure,⁵ so we searched carefully and found out over 20 tiny wounds on the patient

Figure 1. (a) Multiple wounds on the patient’s head and back (photographed before suturing).(b) Deep and large wounds on the patient’s head (photographed before suturing).

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Treatments, vaccinations, and immunogenicity results

It was decisive to apply PEP to prevent the occurrence of rabies or surgical treatments to avoid infections first because of multiple deep wounds on her head, back, and extremities. The benefits of starting PEP outweighed that of suturing. Therefore, the patient was provided 20-minute thorough washing with 20% soapy water and running clean water. After that, 2% tincture of iodine was applied to wounds for disinfection. RIG was essential, and the maximal quantity that was anatomically feasible should be administered to each wound.⁶ A dose of 20 IU/kg of RIG was necessary, but it was inadequate to infiltrate into all the wounds because the patient was weighed only 12 kg. Thus, two doses of hRIG (200 IU/dose, each dose was 2 mL, manufactured by Wuhan Rui De Biological Products Co. Ltd, Batch No. 200625-1) were prescribed to her, mathematically 33.33 IU/kg for her. One dose was infiltrated into wounds on head, face, and neck, while the other was diluted 15 times with normal saline to infiltrate into the rest of wounds. Vaccines were also administered. Since then, the patient was sent to ICU for hemostasis and anti-infection. Suture operation was performed at 40 hours later. Four hours after suturing, the patient was moved into isolation ward where supportive care and subsequent human rabies vaccinations were provided. However, it was unclear if and how high doses of hRIG would affect active immunization in this specific case. Therefore, excessive doses of vaccines were immunized to avoid the uncertain impact of hRIG, and immunogenicity tests were performed to ensure the expected immune response. Totally eight doses of purified Vero rabies vaccines (PVRV) were administered to her. Each two doses were given on days 0 and 3 and the other four doses were given on days 7,14, 28, and 90, respectively (Supplementary Table 1). For children aged above 2-y old, the recommended IM injection sites are deltoid areas of arms,⁶ yet there were multiple wounds on her upper extremities so at days 0, 3, and 7, vaccines were administered to anterolateral thighs. The following doses were injected in the deltoid region of her right arm (Supplementary Table 1). To ensure adequate antibodies, blood samples were collected to conduct rapid fluorescent focus inhibition test, respectively, on 1, 4, 7, 14, and 90 days after the first vaccination. Considering the severity of her injuries, follow-ups at 1-, 5-, and 10-y intervals with immunogenicity test were done to ensure sustaining adequate protective rabies virus-neutralizing antibodies (RVNA). The last test found that RVNA titer was only 0.2 IU/mL, obviously below the protective level so a booster of purified Vero-cell rabies vaccines (PVRV) at 10-y interval was administered to her on day 3655. Immunogenicity test was performed 14 d after the booster vaccination and RVNA increased to 9.4 IU/mL (Figure 2; Supplementary Table 2).

Figure 2. Circulating RVNA titers in the patient and reference case⁷ after vaccinations. The black dotted line (RVNA = 0.5 IU/mL) indicated minimum limit of protection.

Discussion

Immediate PEP is essential to patients being bitten or scratched by suspected or proven rabid animals. In rural China, the most common pediatric dog bites occurred on upper and lower extremities, and in toddlers, 4% of the dog bites were on heads.⁸ To our knowledge, this is the first documented case in China that was severely bitten and suffered from multiple and deep wounds on head, neck, back, and upper extremities. Both PEP and surgery were critical for the patient. Considering the fatal risks of rabies, PEP was in priority. The WHO position paper issued in April 2018 recommended that the maximal quantity of RIG that is anatomically feasible should be administered to small wounds, and if necessary, it can be diluted with physiological buffered saline to ensure infiltration for large and multiple wounds. However, to fully infiltrate hRIG into all wounds in this patient, the dilution ratio might be so high. It should be noted that several deep wounds were on highly innervated parts of her body. Specific PEP was not precisely in accordance with WHO recommendations because of her rare severity condition, so immunogenicity tests were performed to ensure adequate and sustaining RVNA and ensure effective PEP procedure in preventing rabies. As hRIG was infiltrated more than WHO recommendations, excessive human rabies vaccines were also provided in anterolateral thighs to induce expected immune response. Double doses of vaccine were prescribed on days 0 and 3 because of the consideration that hRIG might affect the immune response. Namely, inadequate vaccine might probably be neutralized by hRIG and could not stimulate active immunity effectively. The half-life of hRIG was 21 d⁹ but an obvious decreasing trend in the previous 7 d was observed (Figure 2). Luckily from day 7, RVNA titer began to increase, possibly the effect of active immune response.

The duration of humoral immunity was long, and the effect was stable. Vaccine-induced memory B cells seemed to persist for life, and effective recall of the immune response to additional doses was documented for decades.¹⁰ Rapid increase of RVNA titer after a booster vaccine indicated that her immunological memory functioned well. If this patient is exposed to rabies again, a booster vaccination will be enough to trigger an adequate immune response, which can be effective and lifesaving. Operation procedure based on WHO-recommended PEP is definitely effective in preventing rabies onset, even in such a rarely severe case.

This successfully treated case was widely reported on local media in Wuhan, China, in 2007, which attracted public attention. Since then, the rabies vaccination rate in Wuhan did not fluctuate greatly in the last decade (Supplementary Table 3; Supplementary Figure 1), though slightly decreased in 2009, 2013, and 2016. It indicated that extensive reports about successful vaccination could help to build up the public’s confidence in vaccines. Vaccine hesitancy is a global problem, and its harmful impact on individuals and communities is dependent on the background epidemiologic picture.¹¹ It is one of ten threats to global health in 2019 (https://www.who.int/emergencies/ten-threats-to-global-health-in-2019). Stated by the WHO, health staff, especially those in communities, remain the most trusted advisor and influencer of vaccination decisions, and they must be supported to provide trusted, credible information on vaccines. For maintaining and improving vaccine uptake among populations, continuous positive reports and health education would be necessary.

This case report provides evidence that PEP based on WHO recommendations are remarkedly effective even in such a severely bitten case. Vaccination is definitely a valid, eligible, and critical approach and one of the most cost-effective ways to avoid diseases in individual and population levels.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Supplementary material

Supplemental data for this article can be accessed at https://doi.org/10.1080/21645515.2019.1676630.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.