Neuroangiostrongyliasis: Global Spread of an Emerging Tropical Disease.

Neuroangiostrongyliasis (NAS) is an emerging parasitic disease caused by the neurotropic nematode Angiostrongylus cantonensis. Since it was first discovered, in rats in southern China in the 1930s, this tropical to subtropical parasite has spread to much of Southeast Asia, the Pacific Islands (including Hawaii), Australia, Japan, South America, the southeastern United States, the Caribbean, Africa, the Canary Islands, and the Balearic Islands. The parasite completes its natural life cycle in snails and slugs (intermediate hosts), and rats (definitive hosts). Humans become accidental hosts after ingesting infective third-stage larvae contained within uncooked or undercooked intermediate or paratenic hosts, an event that sometimes results in NAS, also known as rat lungworm disease. Although A. cantonensis larvae cannot complete their life cycle in humans, their migration into the brain and spinal cord combined with a powerful inflammatory reaction often leads to eosinophilic meningitis and can, in rare instances, lead to coma, paralysis, and death or, in other cases, chronic, disabling neurologic sequelae. Symptoms of NAS are diverse, which often makes it difficult to diagnose. Treatment may include administration of analgesics, corticosteroids, anthelminthics, and repeat lumbar punctures to reduce intracranial pressure. Unfortunately, few medical providers, even in endemic areas, are familiar with A. cantonensis or its epidemiology, diagnosis, and treatment. As the parasite continues to spread and NAS affects more people, medical practitioners, as well as the general public, must become more aware of this emerging zoonosis and the potentially devastating harm it can cause.

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.

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.

Angiostrongylus cantonensis in travelers: clinical manifestations, diagnosis, and treatment.

PURPOSE OF REVIEW: Angiostrongylus cantonensis eosinophilic meningitis is a neglected, yet important emerging disease, which has been increasingly recognized in travelers. In this review, we describe the occurrence of the disease in travelers, sources of infection, clinical manifestations, diagnosis, and currently recommended treatment. RECENT FINDINGS: Various intermediate hosts and/or paratenic hosts can be the source of infection in humans. Serological tests for antibody may be negative early in the course of the disease but PCR for antigen detection in the CSF has recently been developed and may help to make the diagnosis at an earlier stage. High-dose corticosteroids (e.g. prednisolone 60 mg per day for at least 1-2 weeks) are currently the recommended treatment. Efficacy and safety of antihelminthic drugs for treatment remains controversial because of theoretical concerns that they may worsen the inflammatory response to dead and dying worms. Previous clinical trials were conducted with small numbers of participants and were underpowered. Further well designed clinical trials are urgently needed. SUMMARY: Awareness about increasing numbers of A. cantonensis eosinophilic meningitis in travelers is very important. Travelers should be advised about possible sources of infection. Diagnosis should be confirmed by antigen or antibody detection in blood or CSF. High-dose corticosteroids are the recommended treatment. The efficacy of various antihelminthic drugs is unproven. A large-scale, double-blind, randomized, controlled trial of antihelminthic drug involving antihelminthic drugs such as albendazole is necessary to prove the efficacy before formally advocating their use on a regular basis.

Differential diagnosis of illness in travelers arriving from Sierra Leone, Liberia, or Guinea: a cross-sectional study from the GeoSentinel Surveillance Network.

BACKGROUND: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in West Africa since late 2013, has led to export of cases to Europe and North America. Clinicians encountering ill travelers arriving from countries with widespread Ebola virus transmission must be aware of alternate diagnoses associated with fever and other nonspecific symptoms. OBJECTIVE: To define the spectrum of illness observed in persons returning from areas of West Africa where EVD transmission has been widespread. DESIGN: Descriptive, using GeoSentinel records. SETTING: 57 travel or tropical medicine clinics in 25 countries. PATIENTS: 805 ill returned travelers and new immigrants from Sierra Leone, Liberia, or Guinea seen between September 2009 and August 2014. MEASUREMENTS: Frequencies of demographic and travel-related characteristics and illnesses reported. RESULTS: The most common specific diagnosis among 770 nonimmigrant travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe malaria in 267 (86%) and non-P. falciparum malaria in 43 (14%). Acute diarrhea was the second most common diagnosis among nonimmigrant travelers (n = 95 [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary tract infection, and influenza-like illness occurred in only 26, 9, and 7 returning travelers, respectively. Few instances of typhoid fever (n = 8), acute HIV infection (n = 5), and dengue (n = 2) were encountered. LIMITATION: Surveillance data collected by specialist clinics may not be representative of all ill returned travelers. CONCLUSION: Although EVD may currently drive clinical evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea, clinicians must be aware of other more common, potentially fatal diseases. Malaria remains a common diagnosis among travelers seen at GeoSentinel sites. Prompt exclusion of malaria and other life-threatening conditions is critical to limiting morbidity and mortality. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Pre-exposure rabies vaccination among US international travelers: findings from the global TravEpiNet consortium.

BACKGROUND: People who travel to areas with high rabies endemicity and have animal contact are at increased risk for rabies exposure. We examined characteristics of international travelers queried regarding rabies vaccination during pretravel consultations at Global TravEpiNet (GTEN) practices during 2009-2010. MATERIAL AND METHODS: We performed bivariate and multivariable analyses of data collected from 18 GTEN clinics. Travel destinations were classified by strength level of rabies vaccination recommendation. RESULTS: Of 13,235 travelers, 226 (2%) reported previous rabies vaccination, and 406 (3%) received rabies vaccine at the consultation. Common travel purposes for these 406 travelers were leisure (26%), research/education (17%), and nonmedical service work (14%). Excluding the 226 who were previously vaccinated, 8070 (62%) of 13,009 travelers intended to visit one or more countries with a strong recommendation for rabies vaccination; 1675 (21%) of these 8070 intended to travel for 1 month or more. Among these 1675 travelers, 145 (9%) were vaccinated, 498 (30%) declined vaccination, 832 (50%) had itineraries that clinicians determined did not indicate vaccination, and 200 (12%) remained unvaccinated for other reasons. In both bivariate and multivariate analyses, travelers with trip durations >6 months versus 1-3 months (adjusted odds ratio [OR]=4.9 [95% confidence interval [CI] 2.1, 11.4]) and those traveling for "research/education" or to "provide medical care" (adjusted OR=5.1 [95% CI 1.9, 13.7] and 9.5 [95% CI 2.2, 40.8], respectively), compared with leisure travelers, were more likely to receive rabies vaccination. CONCLUSIONS: Few travelers at GTEN clinics received rabies vaccine, although many planned trips 1 month long or more to a strong-recommendation country. Clinicians often determined that vaccine was not indicated, and travelers often declined vaccine when it was offered. The decision to vaccinate should take into account the strength of the vaccine recommendation at the destination country, duration of stay, availability of postexposure prophylaxis, potential for exposure to animals, and likelihood of recurrent travel to high-risk destinations.

Global TravEpiNet: a national consortium of clinics providing care to international travelers--analysis of demographic characteristics, travel destinations, and pretravel healthcare of high-risk US international travelers, 2009-2011.

BACKGROUND: International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness. METHODS: We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011. RESULTS: The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low- or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelers were visiting malaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported ≥1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers' diarrhea. Hepatitis A and typhoid were the most frequently administered vaccines. CONCLUSIONS: Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel.

Sequelae of World War II: an outbreak of chronic cutaneous nontuberculous mycobacterial infection among Satowanese islanders.

BACKGROUND: After World War II, residents of Satowan (population, 650 persons), an outer island in the state of Chuuk, Federated States of Micronesia, noted a high prevalence of a chronic, progressive skin disease known locally as "spam." METHODS: Island residents who had chronic, progressive verrucous or keloidal plaques for >3 months were considered case patients. Tissue specimens were obtained for culture, histopathological analysis, mycobacterial polymerase chain reaction (PCR), and comparison with the hsp65 gene of Mycobacterium marinum. We performed a case-control study involving all cases and randomly selected control individuals from the community. RESULTS: A total of 39 case patients were identified, with a median age of 26.0 years (range, 8-82 years); 74.4% were male, and the mean duration of disease was 12.5 years. A total of 98 control individuals were enrolled. Results of all 19 mycobacterial tissue cultures were negative, and histopathological analysis of all 9 lesions showed suppurative granulomatous inflammation with negative results of mycobacterial and fungal stains. In 7 of 9 paraffin-embedded samples, nontuberculous mycobacterial DNA was detected by PCR, and 2 sequenced products had 95% and 87% identity to M. marinum. All case patients were taro farmers (odds ratio, undefined; P < .01), and among taro farmers, when the analysis was controlled for sex, contact with water-filled World War II-era bomb craters was associated with infection (odds ratio, 8.2; P < .01). CONCLUSIONS: "Spam disease" is a chronic, progressive skin disease of high prevalence on Satowan and is associated with taro farming and contact with World War II-era bomb craters. Histopathological and PCR data demonstrate a nontuberculous mycobacterial infection as the cause.

Comparison of serology and isolates for the identification of infecting leptospiral serogroups in Hawaii, 1979-1998.

Laboratory confirmation of leptospirosis is usually accomplished serologically, without isolates, using the microscopic agglutination test (MAT). However, optimal performance of the MAT is dependent on the knowledge of enzootic serogroups and serovars so that an appropriate MAT antigen testing battery can be established. Infecting leptospiral serogroups can be identified serologically without isolates, using the MAT, or by serogrouping of isolates, but little information is available regarding the correlation between these methods. The identification of infecting serogroups for 53 culture-confirmed leptospirosis cases, diagnosed in Hawaii between 1979 and 1998, using serology and culture isolates were compared. The overall agreement between the two methods was good (kappa = 0.71, 95% CI: 0.56, 0.86). However, the agreement varied between serogroups from 0 to 100%. In establishing the prevalence of serogroups, results obtained via MAT serology (in the absence of serogrouped isolates) should be considered presumptive rather than definitive.

Leptospirosis in Hawaii, 1974-1998: epidemiologic analysis of 353 laboratory-confirmed cases.

The epidemiologic characterization of leptospirosis in the United States has been limited by difficulties associated with both case detection and confirmation. In addition, leptospirosis was eliminated from the list of National Notifiable Diseases in 1995. From 1974 until the cessation of national surveillance, Hawaii consistently had the highest reported annual incidence rate in the United States. From 1974 through 1998, 752 leptospirosis cases were reported in the State of Hawaii. Of these, 353 had exposures within the state and were laboratory confirmed. The mean annual incidence rate was 1.29 per 100,000. Cases were predominately male. Rates were highest in rural areas. Occupational exposures diminished over time while recreational exposures increased. This series represents the first large U.S. leptospirosis surveillance report since 1979. With leptospirosis recently being identified as a re-emerging zoonosis, continued national surveillance and case reporting should be reconsidered.