South African Rabies Guidelines — Questions

Routine rabies post-exposure prophylaxis is not indicated here, for two reasons:

1. The animal. Rodents and small terrestrial mammals (moles, rats, mice, squirrels, hamsters, rabbits) are not known rabies reservoirs anywhere. South African rabies cycles are maintained in domestic dogs, black-backed jackals, yellow mongoose, bat-eared fox and bats, not moles.

2. The region. Cape Town and the Western Cape are not high-risk for rabies. The canid cycle is concentrated in KwaZulu-Natal, Eastern Cape, Mpumalanga, Free State and Limpopo. A bat-eared fox cycle is recognised in parts of the Western and Northern Cape, but not in urban gardens.

Practical advice:

• Wound care: wash thoroughly with soap and running water for several minutes; disinfect with chlorhexidine or povidone-iodine.
• Tetanus prophylaxis should be reviewed and updated if needed; this is a puncture wound.
• Antibiotics: consider amoxicillin-clavulanate prophylactically for a clearly contaminated bite.
• No rabies vaccine, no RIG.
• Counsel the patient about the very low risk and document the discussion.
• Atypical caveat: if the mole was behaving abnormally (aggressive, paralysed, diurnal in a normally nocturnal species), submit the carcass for laboratory testing; otherwise observation is not feasible for wild rodents.

This is a WHO Category III exposure in a high-endemicity region: the Eastern Cape is one of South Africa’s primary rabies-endemic provinces. The stray dog cannot be observed and must be assumed rabid. Full post-exposure prophylaxis is indicated without delay.

1. Wound care (immediate). Wash all wounds with soap and running water for 15 minutes; flush with copious water; disinfect with chlorhexidine 0.05% or povidone-iodine 10%. Avoid suturing unless required for haemostasis. Avoid local anaesthetic infiltration at the wound (risk of forcing virus into deeper tissues). Tetanus booster and consider antibiotic prophylaxis (amoxicillin-clavulanate) for a contaminated bite wound.

2. Rabies vaccine. 4-dose IM schedule on days 0, 3, 7, and one day between 14 and 28. In a child under 2 years, give in the anterolateral thigh (not deltoid, not gluteal). Identical adult dose (one full vial per administration).

3. Rabies immunoglobulin (RIG). 20 IU/kg HRIG (or 40 IU/kg ERIG if HRIG unavailable). Infiltrate the entire calculated dose into and around the wounds. Do not give the remainder at a distant intramuscular site (this is the current SA practice, a change from older guidance). Dilute with saline if wounds are multiple or small. Never mix RIG into the same syringe as the vaccine.

4. Source-animal action. Notify Veterinary Services. The stray dog should be captured if safe; if euthanised, the whole brain is submitted to the NICD in 50% glycerol-saline for fluorescent-antibody testing. PEP continues regardless while awaiting the result.

5. Follow-up. Document the visit and the schedule. Review on each vaccine day. Ensure the child completes all 4 doses. Confirm tetanus cover and monitor the wound for infection. Notify the local public-health authority.

6. Counsel the family on the rationale (without scaring them): rabies is invariably fatal once symptoms begin; full and timely PEP is essentially 100% effective.

No single specimen is sensitive at every stage, so a panel is submitted.

Ante-mortem:

• Saliva: at least 500 μL, one specimen daily on 3 consecutive days, collected by syringe or suction (not sputum); RT-PCR.
• CSF: at least 500 μL in an untreated sterile tube; RT-PCR, plus anti-rabies neutralising antibody in an unvaccinated patient.
• Nuchal skin biopsy: 5 to 6 mm wide and 5 to 7 mm deep, including hair follicles and the nerves at their base; on saline-moistened gauze with no fixative; DFA or RT-PCR.

Post-mortem:

• Brain tissue: 2 cm cubes from the cerebellum and cerebrum, in 50% glycerol-saline and never formalin; DFA is the gold standard.

All samples go to the NICD, leak-proof and marked “suspected rabies”. A single negative does not exclude rabies; repeat sampling is essential.

Scenario	WHO category	Wound care	Vaccine	RIG
(a) Previously vaccinated, skin-penetrating bite from rabid dog	III	Soap + water; disinfect	2-dose IM vaccine: days 0 and 3	None; endogenous immunity is reactivated by the boost
(b) Child licked over the nose by rabid dog	III (mucosal contact)	Soap + water; disinfect	Full 4-dose IM schedule: days 0, 3, 7, and 14–28	20 IU/kg HRIG, infiltrated entirely into / around the wound area (face/nose)
(c) 18-month-old, skin-piercing bites on thigh from suspected rabid dog	III	Soap + water for 15 min; disinfect	Full 4-dose IM schedule: days 0, 3, 7, and 14–28; anterolateral thigh (deltoid not recommended under 2 years)	20 IU/kg HRIG, infiltrated entirely into the wounds

RIG window. RIG must be given on day 0 with the first vaccine dose, or as soon as possible thereafter. After day 7 from the first vaccine dose, RIG is no longer indicated: endogenous neutralising antibody has begun to develop, and adding passive antibody at that point will reduce the patient’s own vaccine response.

If RIG is unavailable on day 0, source it urgently and give it as soon as possible within the 7-day window. Never inject RIG into the same anatomical site or the same syringe as the vaccine, because they neutralise each other.

The 10-day observation rule applies only to domestic dogs, cats and ferrets, which shed rabies virus in saliva only within the 10 days preceding clinical signs. A bite from one of these animals carries no risk if the animal remains healthy at 10 days.

The practical algorithm:

• Start PEP immediately if there is any reasonable risk.
• Quarantine and observe the dog/cat/ferret for 10 days under veterinary supervision.
• If the animal remains clinically healthy at day 10, PEP may be stopped.
• If the animal develops signs of rabies or dies during observation, complete PEP and submit brain tissue for testing.

The rule does not extend to wild animals, stray dogs that cannot be reliably observed, or any other species.

The WHO categories stratify exposure by skin breach:

• Category I: no skin breach (touching, feeding a healthy-appearing animal, licks on intact skin). No PEP; wash the area.
• Category II: nibbling of uncovered skin, minor scratches or abrasions without bleeding. Vaccine alone (full schedule), no RIG.
• Category III: single or multiple transdermal bites or scratches, mucosal contact (eyes, nose, mouth), licks on broken skin, any contact with a bat. Vaccine + RIG at full schedule.

The “any contact with a bat = Category III” rule reflects the bat-bite paradox: bat teeth are tiny and bites may leave no visible wound.

Bat teeth are tiny and bat bites can leave no visible wound. Documented rabies fatalities have followed unrecognised bat exposures: the patient denies any bite and no wound is found, yet the virus is transmitted nonetheless. Any direct bat contact is treated as Category III when there is plausible exposure (bat in a room with a sleeping or otherwise incapacitated person, with a child, or any contact with bare skin or hair).

Management:

• Wash any potentially exposed areas with soap and water.
• Capture the bat if safe to do so, for laboratory testing.
• Offer full PEP: vaccine + RIG.
• PEP may be stopped if the bat tests negative.

A previously-vaccinated patient (prior PrEP or prior PEP) is given an abridged 2-dose schedule on days 0 and 3 with no RIG. Endogenous immunity is rapidly boosted by the vaccine, and providing RIG would unnecessarily suppress the patient’s own response.

The full 4-dose-plus-RIG schedule is reserved for unvaccinated patients. If the exposure occurs within 3 months of completing a previous PEP course, no further PEP is needed at all.

A patient with HIV who is on effective ART, clinically well and virologically suppressed is not considered immunocompromised for the purposes of rabies vaccination. The standard 2-dose IM PrEP schedule on days 0 and 7 applies, with normal expected seroconversion.

The extended 3-dose schedule (days 0, 7, 21–28) is reserved for genuinely immunocompromised patients: symptomatic HIV with low CD4 counts, active cancer chemotherapy, high-dose corticosteroids (≥20 mg/day prednisone for ≥2 weeks), or transplant immunosuppression. Inactivated rabies vaccine is safe at any CD4 count.

The NICD-recommended nuchal biopsy is 5–6 mm in diameter and 5–7 mm deep, taken from the nape of the neck at the hairline. It must include hair follicles and the cutaneous nerves at the base of the follicles, the structures in which rabies virus is detected by direct fluorescent antibody (DFA) or RT-PCR.

The biopsy is placed on sterile gauze moistened with saline or water and covered to prevent drying. No fixative is used, because formalin destroys the virus and renders the specimen unsuitable for DFA and RT-PCR.

Rabies is a Category 1 Notifiable Medical Condition in South Africa, requiring immediate notification through the NICD NMC system.

This is more urgent than the Category 2 framework that applies to viral hepatitis (which allows seven days for written or electronic notification). Animal rabies is separately notifiable under the Animal Diseases Act, 1984 (Act No. 35 of 1984) through state Veterinary Services, with surveillance coordinated by the NICD and DALRRD under a One-Health framework.

The preferred handling for post-mortem rabies-suspect brain tissue is 2 cm × 2 cm cubes from both the cerebellum and the cerebrum, submerged in 50% glycerol-saline (half glycerol, half PBS) in a screw-top container, never glass, and transported as soon as possible.

Critically, the tissue must not be fixed in formalin: formalin destroys viral antigen and renders DFA testing impossible. If 50% glycerol-saline is unavailable, fresh-frozen tissue sent without delay is the alternative. The Forensic Pathologist usually collects the specimen.

Rabies is notifiable on both axes:

• Human cases through the Notifiable Medical Conditions (NMC) framework, reported to the Department of Health (typically via the NICD NMC App).
• Animal cases under the Animal Diseases Act, 1984 (Act No. 35 of 1984), reported to state Veterinary Services (Department of Agriculture, Land Reform and Rural Development).

Surveillance is coordinated under a One-Health framework, with laboratory confirmation centralised at the NICD reference laboratory. Both suspected and confirmed cases must be reported; notification is not conditional on laboratory confirmation.

Classical RABV in South Africa is maintained in two main terrestrial cycles:

• Canid cycle: domestic dogs (the principal source of human exposure) plus black-backed jackals in the wild. Dominant in KwaZulu-Natal, the Eastern Cape, Mpumalanga, Free State and Limpopo.
• Mongoose (herpestid) cycle: yellow mongoose (Cynictis penicillata) on the central plateau; rarer human exposures.

A separate bat-eared fox cycle is recognised in the Western and Northern Cape, the western Free State, Eastern Cape and North West.

Approximately 10 laboratory-confirmed human cases are recorded annually in SA (with 16 in 2018), concentrated in the eastern provinces.

The direct fluorescent antibody (DFA) test on brain tissue is the gold-standard post-mortem diagnostic. Performed on smears or impressions of brain tissue (typically brainstem and cerebellum), it has greater than 99% sensitivity and specificity and produces results within hours.

RT-PCR on the same tissue is a complementary molecular test. Histology for Negri bodies is supportive but less sensitive than DFA. In South Africa, post-mortem rabies confirmation is centralised at the NICD reference laboratory; whole brain is submitted in 50% glycerol-saline.

The current standard PrEP schedule is 2 doses IM on days 0 and 7. This replaced the older 3-dose schedule (days 0, 7, 21–28). Equivalent intradermal options (2 sites per visit on days 0 and 7) provide a dose-sparing alternative.

Immunocompromised patients require the extended 3-dose schedule on days 0, 7 and 21–28, IM (single site) or ID (2 sites).

Boosters are guided by neutralising antibody titres, typically every 2 years for ongoing high-risk exposure (veterinarians, lab workers).

The NICD Specimen Collection Guide recommends at least 500 μL of saliva per specimen collected by syringe or suction device, with one specimen submitted daily on three consecutive days.

Sputum is not acceptable as a substitute. The serial-day strategy maximises diagnostic yield because saliva shedding is intermittent, and starting as soon as rabies enters the differential is important, because patients often present late in disease and the testing window may be brief.

Current practice is to infiltrate the entire calculated dose into and around the wound(s), a change from older guidance that split the dose between local infiltration and a distant IM site. If the wound is small and the full volume cannot be accommodated, dilute with normal saline rather than diverting the remainder to a distant site.

Doses:

• HRIG (human): 20 IU/kg
• ERIG (equine): 40 IU/kg

Critical rules: never mix RIG with the vaccine in the same syringe; never inject RIG into the same anatomical site as the vaccine, because they neutralise each other. RIG must be given within 7 days of the first vaccine dose; after day 7, endogenous antibody is present and RIG is no longer indicated.