Guidelines for the diagnosis and treatment of neuroangiostrongyliasis: updated recommendations.

A subcommittee of the Hawaii Governor's Joint Task Force on Rat Lungworm Disease developed preliminary guidelines for the diagnosis and treatment of neuroangiostrongyliasis (NAS) in 2018 (Guidelines, 2018). This paper reviews the main points of those guidelines and provides updates in areas where our understanding of the disease has increased. The diagnosis of NAS is described, including confirmation of infection by real-time polymerase chain reaction (RTi-PCR) to detect parasite DNA in the central nervous system (CNS). The treatment literature is reviewed with recommendations for the use of corticosteroids and the anthelminthic drug albendazole. Long-term sequelae of NAS are discussed and recommendations for future research are proposed.

Workshop on research priorities for management and treatment of angiostrongyliasis(1).

In a concluding session of the workshop, the participants developed a list of 115 research and outreach needs, outlining the top 5-7 needs in each of 8 areas (Table). For complete information, including presenter details and abstracts, visit the workshop website at www.hawaii.edu/cowielab/Angio%20website%20home.htm.

Special Feature: Diagnosis and Treatment of Neuroangiostrongyliasis in Hawai'i.

Angiostrongylus cantonensis is a metastrongylid lungworm of rats with a global distribution and the cause of neuroangiostrongyliasis in humans. In Hawai'i, neuroangiostrongyliasis cases have occurred sporadically since 1960; however, in 2001, the number of cases on Maui and Hawai'i Island began to increase significantly. Since most human treatment trials have been conducted in Thailand, where the disease is usually mild, there is a need to develop treatment protocols for Hawai'i, where there is a broader disease spectrum. In 2018, preliminary guidelines for the diagnosis and treatment of neuroangiostrongyliasis were developed for Hawai'i's physicians. This article summarizes those guidelines and provides additional recommendations for individuals who recently ingested an infected intermediate host.

History of U.S. military contributions to the study of diarrheal diseases.

Diarrhea, a scourge upon humanity since preliterate times, has been the particular nemesis of military forces. The Armed Forces of the United States have been in the forefront in the diagnosis, treatment, and prevention of diarrheal illness. U.S. military scientists and physicians implemented the first mandatory typhoid inoculation program, contributed to advances in water chlorination, and pioneered the use of antibiotics for typhoid fever. U.S. Navy physicians refined the intravenous treatment of cholera, reducing the death rate from 20% to less than 1%. Their studies of electrolyte and fluid balance in cholera, and the subsequent development of oral rehydration therapy for cholera and other diarrheal illness, have saved millions of lives worldwide. U.S. Army researchers refuted the desquamation theory of cholera pathogenesis, isolated the cholera exotoxin, and developed improved cholera vaccines. U.S. Army and Navy researchers pioneered the use of antibiotics for the treatment of typhoid fever, made major contributions to the treatment of dysentery, developed algorithms for the treatment of traveler's diarrhea, and continue active development of traveler's diarrhea and dysentery vaccines. U.S. military diarrheal research has directly contributed to the welfare of hundreds of millions of people.

Clinical aspects of eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis, the rat lungworm.

Angiostrongylus Eosinophilic Meningitis is caused by human infection with larvae of the rat lungworm, Angiostrongylus cantonensis. The clinical presentation includes a spectrum of disease, from meningitis through radiculitis, cranial nerve abnormalities, ataxia, encephalitis, coma, and rarely death. The condition is diagnosed by recognizing the triad of: the clinical syndrome, eosinophils in the cerebrospinal fluid or blood, and exposure history. A history of eating raw or poorly cooked snails is classic, but ingestion of other intermediate hosts or unwashed produce (such as lettuce) harboring hosts is not uncommon. Several serologic tests exist but none has yet been fully validated. There is good evidence that a 2 week course of high dose corticosteroids shortens the duration and severity of symptoms. There is somewhat weaker evidence that albendazole reduces symptoms. The combination of prednisolone and albendazole is being used more commonly for treatment. Some suggestions for future research are given.

A severe case of Angiostrongylus eosinophilic meningitis with encephalitis and neurologic sequelae in Hawa'i.

Angiostrongylus eosinophilic meningitis is caused by infection with larvae of the rat lungworm, Angiostrongylus cantonensis. We report the case of an adult who ingested a raw, giant African snail (Achatina fulica) on the island of O'ahu in Hawa'i and developed an eosinophilic meningoencephalitis with severe headache, confusion, sixth cranial nerve palsy, ataxia, limb weakness, and paresthesia. He was treated with lumbar punctures to relieve pressure, high dose corticosteroids, and 14 days of albendazole. He had a prolonged convalescence, requiring 3 months of prednisone, and still had evidence of motor nerve weakness 4 months after exposure. A field investigation at the site of exposure yielded 5 of 9 Achatina fulica snails with evidence of A. cantonensis DNA by PCR. Cerebrospinal fluid samples from the patient were negative acutely but positive on day 15 of symptoms, using an investigational, real-time PCR assay. We discuss clinical management of this case in light of the current medical literature.

Etiology of acute, non-malaria, febrile illnesses in Jayapura, northeastern Papua, Indonesia.

We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997-2000, 226 patients (127 males and 99 females) 1-80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had ≥ 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli-positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics.

Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human immunostimulatory sequences and the GM-CSF gene increases immunogenicity and protection from virus challenge in Aotus monkeys.

A dengue-1 DNA vaccine containing sequences encoding premembrane and envelope proteins (DIME) was previously shown to elicit virus neutralizing antibodies in rhesus and Aotus monkeys, and the primates were partially protected from viremia upon challenge. To increase the neutralizing antibody levels and subsequent protection from virus challenge, four strategies were evaluated: (a) coimmunization with a plasmid expressing Aotus GM-CSF gene; (b) coimmunization with a plasmid containing human immunostimulatory sequences (ISS); (c) coimmunization with both the GM-CSF gene and ISS; and (d) delivery of vaccine using the needle-free Biojector system. Vaccination with the mixed formulation containing DIME, GM-CSF gene, and ISS, by either needle injection or Biojector, led to neutralizing antibody titers that were stable for up to 6 months after vaccination. Furthermore, 6 of 7 monkeys (85%), and 7 of 8 monkeys (87%) receiving this formulation were completely protected from viremia when challenged 1 and 6 months after vaccination, respectively. This is a significant improvement compared to our previous study in which one of three monkeys (33%) receiving just the DIME vaccine was completely protected from viremia at 6 months after immunization.

Tolerability of azithromycin as malaria prophylaxis in adults in northeast papua, indonesia.

Drug tolerability affects compliance. We evaluated the tolerability levels of azithromycin (750-mg loading dose plus 250 mg/day; n = 148 subjects), doxycycline (100 mg/day; n = 75), and placebo (n = 77) as prophylaxis against malaria in Indonesian adults over 20 weeks. Self-reported and elicited symptoms, health perception, hearing, hematology, and biochemistry were assessed. The loading dose was well tolerated. The frequencies (number per person-years [p-yr]) of all daily reported symptoms were similar in the three arms of the study: 40.2/p-yr for azithromycin, 39.7/p-yr for doxycycline, and 38.2/p-yr for placebo. Relative to those who received placebo, azithromycin recipients complained more often of heartburn (rate ratio = 10.5 [95% confidence interval, 2.8 to 88.1]), paresthesia (2.03 [1.08 to 4.24]), and mild (1.55 [1.01 to 2.48]) and severe (11.2 [1.34 to infinity ]) itching but less often of fever (0.21 [0.09 to 0.49]) and tinnitus (0.09 [0.04 to 0.21]). Azithromycin recipients showed no evidence of clinical hearing loss or hematologic, hepatic, or renal toxicity. One azithromycin recipient developed an erythematous rash. Daily azithromycin was well tolerated by these Indonesian adults during 20 weeks of treatment.