A Severe Case of Rat Lungworm Disease in Hawai‘i

Abstract

A 23-year-old man living on the island of Hawai‘i developed a life threatening case of eosinophilic meningitis caused by infection with Angiostrongylus cantonensis (rat lungworm disease: RLWD). He was comatose for 3 months, incurring brain and nerve damage sufficiently extensive that he was not expected to recover. The case was complicated by secondary infections of methicillin-resistant Staphylococcus aureus, Clostridium difficile, and pneumonia, which resulted in an empyema requiring a thoracoscopy and decortication. He was treated with prednisone, mebendozal, and pain medication for RLWD, and antibiotics and antifungal medications for the secondary infections. The administration of herbal supplements was requested by the family and approved, and these were administered through a gastric tube. Less than a month after being declared in a persistent vegetative state the man was able to talk, eat, and had regained some muscle functions. After release from the hospital he continued the use of supplements and received treatments of intravenous vitamin therapy. Four years after onset of the illness he is able to ride a bicycle, is a part time student, plays guitar, and is fluent in two foreign languages. RLWD is an emerging tropical disease of growing importance in Hawai‘i.

Introduction

Rat lungworm disease (RLWD) is a global, emerging tropical disease of growing importance in the Hawaiian Islands, particularly on Hawai‘i Island itself, where the majority of the cases have occurred. The disease is caused by a nematode, Angiostrongylus cantonensis, first discovered in China in 1935¹ but now reported from other parts of Asia, Australia, the Caribbean, Pacific islands, Brazil, and Ecuador.² Since the first case of eosinophilic meningitis putatively caused by A. cantonensis was reported in 1945, more than 2,800 cases of RLWD have been reported in approximately 30 countries.² Snails and slugs are the intermediate hosts and the semi-slug Parmarion martensi, a recent invasive arrival in the Hawaiian Islands,3 is thought to be primarily responsible for recent outbreaks of RLWD on the Island of Hawai‘i.⁴ In the area where the disease outbreak occurred, the Puna district of Hawai‘i island, P. martensi are very numerous and in surveys 77.5% of specimens were infected with the infective third larval stage of A. cantonensis.⁴ Recent qPCR techniques⁵ have shown infection levels to be as high as almost 7000 parasites in a single semi-slug.⁶

RLWD cases in Hawai‘i since 2004 have resulted in permanent disability, coma, and death. In a 50 month study period (January 2001–February 2005) 24 of 84 cases of eosinophilic meningitis were attributed to infection by Angiostrongylus cantonensis.⁷ Cases occurred primarily in two clusters: November 2004 – January 2005 and December 2008 – February 2009. An informal report sent to the College of Pharmacy, University of Hawai‘i at Hilo, from the State of Hawai‘i Department of Health (November 2011) reported 35 documented cases of RLWD in Hawai‘i since January 2001. Because diagnosis is difficult, especially in mild cases, case numbers may well be higher. The case described in this paper was one of two, non-connected cases of RLWD that resulted in coma around the same time (December 2008/January 2009). Both victims were initially diagnosed with flu and not admitted to the Hilo Medical Center even after multiple visits to the emergency room. When finally admitted, doctors at the center were unfamiliar with the disease and appropriate treatment. In the particular case documented in this paper, the family and a community member presented physicians with peer reviewed publications from Southeast Asia that outlined the use of steroids and anthelmintics in cases of RLWD and requested these treatments be administered.

Early treatment could be a significant factor in improved recovery, making the awareness of this disease and its treatment important in Hawai‘i. The need for studies on long-term recovery is equally important, for, while most victims have not succumbed to the disease, neither have those most seriously affected recovered fully. Pain medication is usually prescribed for the ongoing symptoms many victims suffer, and many of these have permanent disabilities. No studies have been done in Hawai‘i on long-term recovery from RLWD.

Case Report

A 23-year-old man from the Kapoho area of the Puna District on Hawai‘i island was hospitalized at the Hilo Medical Center on December 26, 2008. Before becoming ill he was healthy and active. Prior to hospitalization he suffered from severe headache, stomach pain, and muscle and joint pain. He was taken to the emergency room twice, treated with morphine for pain, and released. He was admitted on his third visit when he was unable to urinate. Shortly after his admission he developed skin sensitivity such that even a light touch caused great distress. He was eventually diagnosed with eosinophilic meningitis resulting from parasitic infection by Angiostrongylus cantonensis, probably caused by accidental ingestion of an infected slug host. He was prescribed prednisone to suppress the immune system, as well as morphine and oxycodene for pain. On January 2, treatment with the anthelmintic mebendozal was begun (10 mg/kg for 14 days).

The patient began to show improvement. However 16 days after hospital admission (January 11) he began to experience double vision, increasing exhaustion, and stabbing head pain. The following day his manual dexterity decreased significantly and within 24 h he was comatose. An MRI showed inflammation involving white fiber tracts and bilateral basal ganglia, as well as questionable hemorrhagic products scattered throughout white matter tracts of both hemispheres and within the cerebellum. He was intubated, ventilated, and flown to the Queen's Medical Center, Honolulu, for additional diagnosis.

Magnetic Resonance Imaging (MRI) of the brain showed what looked to be worm tracks in his brain. Medical records show his condition reported as “grave with a dismal prognosis and no hope of much recovery.” Evaluation at the Queen's Medical Center showed a left side empyema, hydrocephalus, post encephalitis brain atrophy, and history of eosinophilic meningitis complicated with severe demyelinating encephalitis, and cachexia. Two days later he opened his eyes and was occasionally able to respond to a request to squeeze the hand of a family member or nurse. Eleven days after the patient became comatose a tracheotomy was performed and a gastric tube was inserted. The family then requested the administration of supplements and Chinese herbs. A physician suggested using a Chinese medication (Xing Nao Wan) that had been used in a similar case of A. cantontensis infection of a 23-year-old man in China, which had resulted in coma; however, after four months of treatment that patient recovered and was discharged from the hospital with mild memory loss.⁸ Other supplements requested by the family were used as well; these were the blue-green algae spirulina (Arthrospira platensis) and chlorella (Chlorella vulgaris), as well as noni (Morinda citrifolia).

On January 27, after the tracheal and gastrointestinal tubes were in place, the patient was flown back to the Hilo Medical Center. He was taken off the ventilator, as his breathing was not grossly impaired. However, the tracheal tube remained in place to ensure a clear airway. He remained in ICU for 4 days and was then moved to a nursing unit. On January 31, the supplements used in Honolulu were approved for use at the Hilo Medical Center. These supplements were administered three times a day through the gastrointestinal tube. Curcumin (Curcuma longa) was added to the regime as well as acupuncture treatments. Over a 3-month period, family members assisted with administration of supplements and Chinese medicine, and with medical necessities such as suction of the lungs, tracheal care, and gastrointestinal tube feeding. The patient also underwent daily massage and range of motion exercises.

Shortly after the patient became comatose (January 12) he developed complications including pneumonia, methicillin-resistant Staphylococcus aureus (MRSA), and Clostridium difficile infections. Antibiotics and anti-fungal medications were prescribed for these. The patient was inert as of the time he entered a coma and therefore was manually turned every 2 hr. In early February, his left eye began to drift inward, a result of nerve damage caused by the parasite. In mid February his blood pressure and heart rate began to rise and he was put on blood pressure medication. Soon after it was determined he had an enlarged heart. A brain MRI taken on February 19 reconfirmed the Queen's Medical Center evaluation. A lumbar puncture performed on February 23 had an opening pressure of 25 cm H₂0, WBC 203, 21% neutrophils, 40% lymphocytes, 33% monocytes, protein 102, and leukocytes 32. A shunt to relieve fluid in the brain was discussed, but ongoing infections precluded the operation. The patient ran a persistent fever and was put on antibiotics. His fever did not respond to treatment, and a CAT scan revealed a pleural effusion. A percutaneous thoracentesis was performed on March 3 but was unsuccessful. He was flown to the Queen's Medical Center, Honolulu, for a video assisted thoracoscopy including decortication for persistent empyema, and chest tubes were inserted on March 9. An MRI taken at Queen's determined he had communicating hydrocephalus and he was declared to be in a persistent vegetative state. He was returned to Hilo Medical Center 5 days later.

From the end of January and into February, although clinically comatose, the patient showed some signs of cognizance, responding appropriately to some conversation by what was interpreted by nurses, nurse aides, and family members as laughter or sadness (crying). In mid February the hospital speech therapist began working with the patient on swallowing reflexes, with the desired goal of removing the tracheal tube. By the end of February the patient was able to chew and swallow ice chips, nod yes and no, laugh, and grip hands.

Progress continued into March. On March 3 the tracheal cuff was deflated for a short period of time, allowing the patient to breathe through normal airways. At this time the patient was beginning to move his hands. Progress was impeded by the need for a lung operation and insertion of chest tubes. Chest tubes were removed on March 22, and on March 23 the tracheal cuff was deflated for the entire day and the patient was able to eat yogurt. Physical therapy was also begun on the same day. On March 27 the tracheal tube was changed to a fenestrated tracheal tube, and on March 29 the patient's status was upgraded and he was discharged to the long-term care ward at the Hilo Medical Center.

On March 30 a Passy-Muir Valve was provided to allow for speech therapy, and on the same day a standing table was used by physical therapists to help the patient stand for the first time. By this time the patient was regaining use of his forearms. On April 1 the patient spoke for the first time and was able to converse in short sentences. The pain in his legs that was present near the beginning of his illness had generally subsided, replaced by a feeling of cold and numbness on his left leg and arm and areas of his face, and he had lost use of two fingers on his left hand. His short-term memory was greatly impaired but his long-term memory was intact. His gaze was disconjugate with some nytagmus present, and he had severe ataxia, some hallucinations, and insomnia. Over the course of the month his swallowing reflexes improved, and he was able to eat and drink. By the end of April, while still extremely weak, he was able to walk a short distance (6–8 m) with a walker and two assistants. He was released from the Hilo Medical Center on April 30, 2009.

Use of Supplements

There are many claims for supplements that have not yet been validated scientifically. However, plant-based medicines have been used by various cultures for hundreds, if not thousands, of years. In this case, doctors had no hope for recovery. Therefore various supplemental treatments (Table 1) were administered through the stomach tube on a daily basis as it was agreed that they may provide some benefits and would probably not cause harm.

Table 1.

Supplements and vitamin treatments administered.

Supplement	Brand	Dosage	Other information
In hospital
Spirulina (Arthrospira platensis)	Hawaiian Pacifica	0.5 tsp 3x/day	Phytonutrient, blue-green alga, superior source of digestible protein, source of omega-3 fatty acids and gamma-linolenic acid
Chlorella (Chlorella vulgaris)	NOW Foods	0.25 tsp 3x/day	Phytonutrient, blue-green alga, source of chlorophyll
Noni (Morninda citrifolia)	Eclectic Institute	2 capsules 3x/day	Freeze dried fruit
Curcumin (Curcuma longa)	Pure Encapsulations	2 capsules 3x/day	Anti inflammatory
Bu Nao Wan	Plum Flower	4–6 tablets 3x/day	Replacement for Xing Nao Wan, contains Schisandra chinensis
Additional after release from hospital
EPA/DHA (eicosapentaenoic acid/docosahexaenoic acid) from fish oil	Pure Encapsulations	2 capsules (1,000 mg per capsule) 3x/day	Omega-3 fatty acids for cognitive function, promotes oxygen and nutrient delivery to the brain, supports cardiovascular health, important for optimal joint function
Acetyl-l-carnitine	Pure Encapsulations	500 mg 2x/day	Enhances cellular energy and neurotransmitter metabolism
Vitamins B1 (benfotiamine), B12 (methylcobalamin)	Nerve Support Formula	4 capsules 3x/day	Decreases symptoms of peripheral neuropathy
5-HTP (100 mg)	Pure Encapsulations	1 capsule 3x/day	Supports serotonin levels that can lead to positive effects on emotional well-being and wake/sleep cycles

Four months after release from hospital, the patient began vitamin therapy. The treatment and doses were prescribed by a licensed doctor and administered by a registered nurse. The therapy consisted of two intravenous nutrient infusions administered at alternating sessions as a drip. One was a phosphatidylcholine/glutathione mixture; the other consisted of high doses of vitamin C plus B vitamins and trace minerals, sometimes referred to as a Myers Cocktail after its creator, Dr. John Myers, of Johns Hopkins University.

The intravenous treatments were administered 3 times per week for 4 months. Within 14 days of beginning treatments the patient's left eye began to straighten and he remarked on improved vision and mental clarity. Additionally, both of his physical therapists commented that the ataxia and his ability to tell left from right had improved. Within 3 weeks of beginning the intravenous injections his sleeping and bowel and bladder symptoms showed signs of improvement, he was able to begin walking without two canes for support, and he was able to walk longer distances (∼100 m) without having to rest.

Discussion

After discharge from hospital the patient still suffered from the severe and debilitating effects of the disease. His recovery, while painful and slow, has been steady. Four years after the onset of the disease he continues to take supplements. Those he consistently takes are fish oil, curcumin, vitamins B-1 and B-12, acetyl l-carnitine and 5HTP. His use of prescription medications ceased within 6 months of being released from the hospital. He still experiences problems with balance and vision, and he still suffers from bouts of insomnia. Lack of energy and vigor were extreme issues for 3 years. However in the fourth year after the onset of the illness he has shown marked improvement. He is currently enrolled as a part-time student at a local community college. His vision is somewhat corrected with glasses, which allow him to read and write. His balance has improved with physical therapy and an exercise regime that focuses on core strength. He is able to ride a bicycle to and from classes and for other purposes. He plays guitar and is fluent in two foreign languages. In light of the dim prognosis given at onset of the disease, the recovery is considerable, indeed, quite remarkable. The protocol at Hilo Medical Center has now improved for victims presenting with symptoms of RLWD. Cases of RLWD on Hawai‘i island have resulted in permanent disability, making this serious disease worthy of further research to develop effective treatment, particularly for the long-term neurological effects.

Conflict of Interest

The author identifies no conflict of interest.