19.3 Nervous System Infections: Meningitis & CSF Patterns, Encephalitis, Rabies and DOH PEP, Spinal Cord Infections, Tetanus & Botulism, Paralytic Shellfish Poisoning

Why this area matters

The TOS nervous system area lists:

• meningitis and encephalitis;
• PSP (red tide);
• the spinal cord;
• rabies and other viral diseases of the nervous system.

Rabies is endemic in the Philippines. Animal bite treatment centers see very large numbers of exposures every year, and human rabies is almost always fatal. Red tide warnings regularly close shellfish harvesting in Philippine bays. Questions ask you to read a CSF profile, pick the organism by age, categorize an animal bite correctly, or recognize a toxin syndrome.

Meningitis

• Clinical signs: fever, headache, neck stiffness and altered mental status. Kernig and Brudzinski signs indicate meningeal irritation. A petechial or purpuric rash suggests meningococcemia.
• Order of steps:
  • take blood cultures and give antibiotics without delay;
  • do a CT scan before lumbar puncture only if there are focal signs, papilledema, coma or immunosuppression;
  • give dexamethasone with or before the first antibiotic dose in suspected pneumococcal meningitis in adults.
• Close contacts of meningococcal disease receive rifampicin, ciprofloxacin or ceftriaxone prophylaxis.
• Eosinophilic meningitis in the Philippines suggests Angiostrongylus cantonensis (rat lungworm), acquired by eating raw snails or contaminated vegetables. Patients have headache and paresthesias with more than 10% eosinophils in the CSF.

Encephalitis

• Herpes simplex virus type 1 is the most common cause of sporadic fatal encephalitis:
  • fever, behavior change, aphasia and seizures;
  • hemorrhagic necrosis of the temporal lobes on MRI;
  • red cells in the CSF;
  • diagnosis by CSF PCR;
  • treatment with IV acyclovir at once.
• Japanese encephalitis virus, a flavivirus:
  • spread by Culex mosquitoes breeding in rice fields, with pigs and wading birds as amplifying hosts;
  • endemic in the Philippines;
  • most infections are silent, but encephalitis can cause parkinsonian features and seizures, with high mortality and lasting deficits;
  • prevented by JE vaccine.
• Other viral causes: dengue (encephalopathy), measles (acute encephalitis and later subacute sclerosing panencephalitis), varicella, enteroviruses and Nipah virus. Nipah caused an outbreak in the Philippines linked to horse slaughter and eating horse meat.

Rhabdoviridae: Rabies Virus Pathogenesis & DOH PEP Categories

Rabies virus is an enveloped, bullet-shaped, single-stranded negative-sense RNA virus belonging to the genus Lyssavirus, family Rhabdoviridae. It is transmitted through the saliva of infected mammals; dogs cause most human rabies cases in the Philippines.

Neuropathogenesis & Histopathology

Following subcutaneous or intramuscular inoculation via a bite or scratch, the rabies virus glycoprotein binds to nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction or neural cell adhesion molecules (NCAM). The virus replicates locally in striated myocytes before entering unmyelinated peripheral nerve terminals. It travels centripetally to the spinal cord and central nervous system via retrograde fast axonal transport driven by dynein motors at a rate of 50 to 100 mm/day.

Within the brain, it infects neurons of the limbic system, brainstem, and hippocampus, subsequently spreading centrifugally along autonomic nerves to the salivary glands, cornea, and facial skin. Histopathologically, rabies is diagnosed post-mortem by the presence of Negri bodies: sharply demarcated, round or oval eosinophilic intracytoplasmic inclusion bodies located inside the Purkinje cells of the cerebellum and pyramidal neurons of the hippocampus.

Clinical Course

The incubation period ranges from 1 to 3 months (shorter with head and neck bites). The clinical course begins with a prodrome of fever and paresthesia or intense pruritus at the healed bite site. It then advances to either encephalitic (furious) rabies (80% of cases: fluctuating agitation, autonomic instability, and pathognomonic hydrophobia and aerophobia, where the sight, sound, or mention of water triggers violent, painful pharyngeal muscle spasms) or paralytic (dumb) rabies (20% of cases: ascending symmetrical flaccid paralysis resembling Guillain-Barré syndrome). Both forms advance inexorably to coma, cardiorespiratory arrest, and death; rabies carries a case-fatality rate approaching 100% once clinical signs appear.

Philippine DOH Post-Exposure Prophylaxis (PEP) Protocol

The Anti-Rabies Act of 2007 (RA 9482) created the National Rabies Prevention and Control Program, and DOH Administrative Order 2018-0013 sets the current management of rabies exposures:

Wound care: wash and flush immediately and vigorously with soap or detergent and water, preferably for 10 minutes, then apply alcohol, povidone-iodine or another antiseptic. Avoid suturing, which may push virus deeper.

Vaccine: government animal bite treatment centers use the intradermal regimen: 0.1 mL of PVRV or PCECV at two sites (both deltoids) on Days 0, 3 and 7. The Day 28 dose may be omitted for WHO-prequalified vaccines (the 2-2-2-0-0 regimen). A delayed dose continues the schedule rather than restarting it.

Vaccinated animals: for a Category II bite by a dog or cat, vaccine may be withheld only if the animal is healthy and can be observed for 14 days and has an updated vaccination record for the past 2 years. If it shows signs of rabies, vaccine and RIG are given at once. Category III exposures always receive vaccine and RIG. PEP is not required for bites of rats, mice, guinea pigs, hamsters, rabbits, reptiles, birds, insects or fish.

Administration of Rabies Immune Globulin (RIG)

RIG gives immediate passive immunity until vaccine-induced antibodies appear:

• Human RIG (HRIG): 20 IU/kg.
• Equine RIG (ERIG) or F(ab')2: 40 IU/kg. ERIG is clinically equivalent to HRIG, and skin testing before ERIG is highly recommended.
• Technique: infiltrate the computed dose into and around all wounds, even healed ones. If it is not enough, dilute it two- or three-fold with sterile saline. Any volume left after infiltration does not need to be injected IM and may be reserved, aseptically, for the next patient. Never exceed the computed dose, because excess RIG blunts the vaccine response.
• Timing: give RIG with the first vaccine dose on Day 0. If it is unavailable, it may still be given up to 7 days after the first vaccine dose, but not later, because active immunity has begun.

Infections of the spinal cord

• Poliomyelitis:
  • Poliovirus, an enterovirus spread by the fecal-oral route, destroys anterior horn cells. The result is asymmetric flaccid paralysis with no sensory loss.
  • The Philippines was certified polio-free with the Western Pacific Region in 2000 but had an outbreak of circulating vaccine-derived poliovirus in 2019.
  • Acute flaccid paralysis (AFP) surveillance of children under 15 detects new cases.
  • Immunization uses oral polio vaccine and inactivated polio vaccine (IPV).
• Spinal epidural abscess, usually S. aureus, causes back pain, fever and rapidly progressive cord compression. It needs urgent MRI and drainage.
• Pott disease (spinal TB) and HTLV-1 tropical spastic paraparesis cause slower myelopathies.

Tetanus and botulism

• Tetanus:
  • spores of C. tetani enter wounds or the umbilical stump;
  • tetanospasmin blocks GABA and glycine release, causing trismus, risus sardonicus, opisthotonos and generalized spasms with intact consciousness;
  • neonatal tetanus follows unclean cord care and is prevented by tetanus-diphtheria vaccination of mothers and clean delivery;
  • management is wound debridement, human tetanus immune globulin, metronidazole, benzodiazepines for spasms, airway support and active immunization (disease does not give immunity).
• Botulism:
  • preformed toxin in home-canned or fermented food blocks acetylcholine release;
  • patients develop descending flaccid paralysis beginning with the cranial nerves (diplopia, ptosis, dysphagia), with a clear sensorium and no fever;
  • infant botulism follows ingestion of spores, classically in honey;
  • treatment is antitoxin and ventilatory support.

Paralytic shellfish poisoning (PSP, red tide)

• Source:
  • blooms of toxic dinoflagellates, in Philippine waters mainly Pyrodinium bahamense, produce saxitoxin;
  • filter-feeding shellfish (mussels, oysters, clams) concentrate it;
  • the toxin is heat-stable, so cooking does not make shellfish safe.
• Mechanism: saxitoxin blocks voltage-gated sodium channels in nerve and muscle, similar to tetrodotoxin from puffer fish.
• Clinical course:
  • within 30 minutes to a few hours: tingling and numbness of the lips, tongue and face that spread to the limbs, with a floating sensation, ataxia, dysarthria and dysphagia;
  • in severe cases, respiratory muscle paralysis within 2 to 12 hours;
  • consciousness is usually preserved.
• Management: there is no antidote. Care is supportive: early gastric decontamination with activated charcoal if the patient is seen early and the airway is protected, close observation, and mechanical ventilation. Patients who survive the first 12 to 24 hours usually recover fully.
• Prevention: the Bureau of Fisheries and Aquatic Resources (BFAR) monitors coastal waters and issues shellfish bulletins. Shellfish from areas under a red tide warning must not be harvested, sold or eaten. Fish, squid, shrimp and crabs are safe to eat if fresh and cleaned well, with the internal organs removed.