Winnie W. Ooi

Leprosy and the peripheral nervous system: Basic and clinical aspects

Leprosy is one of the most common causes of nontraumatic peripheral neuropathy in the developing world. The causative agent, Mycobacterium leprae, has a predilection for Schwann cells, where the organism multiplies unimpeded by organism‐specific host immunity, resulting in destruction of myelin, secondary inflammatory changes, and destruction of the nerve architecture. The cardinal diagnostic features of leprosy are anesthetic skin lesions, neuropathy, and positive skin smears for the bacilli. However, patients may rarely present without skin lesions in pure neuritic leprosy. Electrodiagnostic findings early in the disease reveal demyelinating features, such as slowing of conduction velocity and prolongation of latencies, but as the disease progresses secondary axonal damage commonly ensues. Electrodiagnostic studies are also useful to monitor for toxicity secondary to therapy, particularly thalidomide‐associated neuropathy. Nerve biopsy of a sensory cutaneous nerve is sometimes essential to confirm a diagnosis of leprosy. Significant advances in understanding of the pathogenesis, mapping of the genome, and other advances in molecular biology may result in better preventive and therapeutic modalities, and the goal of eradicating leprosy as a global problem may yet be realized. Muscle Nerve 30: 393–409, 2004

International travel by persons with medical comorbidities: understanding risks and providing advice.

OBJECTIVE To describe the medical conditions, travel plans, counseling, and medications prescribed for high-risk international travelers. PATIENTS AND METHODS This cross-sectional study was conducted from March 1, 2008, through July 31, 2010, in 5 clinics in the greater Boston area. We assessed all travelers seen for pretravel care and compared demographic characteristics, travel plans, pretravel counseling, and interventions for healthy and high-risk travelers (as defined by medical history or pregnancy). RESULTS Of 15,440 travelers, 2769 (17.9%) were high-risk; 644 of 2769 (23.3%) were immunocompromised travelers, 2056 (74.3%) had medical comorbidities, and 69 (2.5%) were pregnant women. The median age of high-risk travelers was 47 years compared with 32 years for healthy travelers (P=.0001). High-risk travelers visited the clinic a median of 25 days (range, 10-44 days) before departure. Overall, 2562 (93.9%) of high-risk travelers visited countries with medium or high risk of typhoid fever, 2340 (85.7%) visited malaria-risk countries, and 624 (22.8%) visited yellow fever-endemic countries. Of travelers to yellow fever-endemic countries, 8 of 23 (34.8%) pregnant women and 64 of 144 (44.4%) immunocompromised travelers received yellow fever vaccine. Of eligible high-risk travelers, 11 of 76 (14.5%) received a pneumococcal vaccine, 213 of 640 (33.3%) influenza vaccine, and 956 of 2681 (35.7%) either tetanus-diphtheria or tetanus-diphtheria-pertussis vaccine. CONCLUSION High-risk travelers made up nearly 20% of patients in these travel clinics, and they mostly traveled to destinations with malaria and typhoid risk. For health care professionals caring for travelers with underlying medical problems, providing appropriate travel counseling and making vaccine decisions, such as for yellow fever, are complex. Travelers with complicated medical histories may warrant evaluation by an experienced travel medicine specialist.

A Calcified Taenia solium Granuloma Associated with Recurrent Perilesional Edema Causing Refractory Seizures: Histopathological Features

We describe the first detailed histological description of an excised calcified Taenia solium granuloma from a patient who developed recurrent seizures associated with perilesional edema surrounding a calcified cysticercus (PEC). The capsule, around a degenerated cysticercus, contained marked mononuclear infiltrates that extended to adjacent brain, which showed marked astrocytosis, microgliosis, and inflammatory perivascular infiltrates. The presence of large numbers of mononuclear cells supports an inflammatory cause of PEC. Immunosuppression or anti-inflammatory measures may be able to treat and prevent PEC and recurrent seizures.

Knowledge, attitudes, and practices of US practitioners who provide pre-travel advice.

BACKGROUND As international travel increases, many health care professionals are being asked to provide pre-travel advice. We designed an anonymous web-based survey to assess the extent to which primary care providers (PCPs) provide travel medicine advice and how their understanding and delivery of itinerary-specific advice and management compare with that of travel medicine specialists. METHODS We surveyed randomly selected US PCPs registered in the Pri-Med Institute (now pmiCME) database and US travel medicine specialists from the International Society of Travel Medicine (ISTM), American Society of Tropical Medicine and Hygiene (ASTMH), and Centers for Disease Control and Prevention (CDC) yellow fever (YF) vaccine provider mailing lists. SAS software (SAS Institute, Cary, NC, USA) was used for all analyses. RESULTS Of 14,932 e-mails sent to valid e-mail addresses, 902 yielded complete or partially completed surveys (6.0% response rate). Eighty percent of respondents personally provided pre-travel advice (95% of travel medicine specialists versus 73% of PCPs). About two thirds of PCPs (68%) providing pre-travel consultations saw <50 travelers per year whereas 30% of travel medicine specialists saw <50 travelers per year. More travel medicine specialists (59%) than PCPs (18%) saw >500 travelers per year. Familiarity with travel-specific vaccines (YF, Japanese encephalitis) and provision of written educational materials increased as volume of travelers increased. Familiarity with antimalarial side effects and malaria resistance patterns, and knowledge scores based on brief pre-travel scenarios were higher in travel medicine specialists, ASTMH or ISTM certificate holders, and respondents who saw more pre-travel patients. CONCLUSIONS Many PCP survey participants provided pre-travel advice, but most saw few travelers. Volume of travelers and holding an ASTMH or ISTM certificate had the greatest influence on knowledge of travel medicine and provision of appropriate advice and recommendations. Creating easily accessible travel medicine education programs for US providers from a wide range of disciplines is needed to improve the management of travelers.

Health challenges of young travelers visiting friends and relatives compared with those traveling for other purposes.

Background: The study objective was to assess differences in demographics and travel health challenges between youths ⩽18 years old traveling internationally to visit friends and relatives (VFRs) compared with those traveling for other purposes (non-VFR). Methods: The Boston Area Travel Medicine Network consists of 5 clinics collecting anonymous data from international pretravel consultations. Data on all travelers ⩽18 years of age seen between January 2008 and July 2010 were used. VFRs were compared with non-VFRs on demographics, primary language, trip characteristics, travel vaccinations administered, malaria prophylaxis and antidiarrheal medications prescribed. Results: Thirty-five percent (610/1731) listed VFR as their purpose of travel. Almost half of VFRs were <5 (46%) years old compared with <5% of non-VFRs. Thirty percent of US-born VFRs with foreign-born parents were ⩽2 years compared with 4% of foreign-born VFR children and 3% of US-born VFRs with US-born parents. More VFRs than non-VFRs planned travel to countries that were yellow fever holoendemic, had malaria risk and were high-risk for typhoid (44% versus 20%, 39% versus 12%, 25% versus 15%, P < 0.01). VFRs were less likely than non-VFRs to be prescribed atovaquone-proguanil (adjusted prevalence ratio = 0.57, confidence interval = 0.44–0.72) and to have had an antidiarrheal medication prescribed (adjusted prevalence ratio = 0.68, confidence interval = 0.60–0.75). Conclusions: To reduce travel-related morbidity, healthcare providers should be prepared to give travel advice to parents of VFR infants and children, particularly those US-born VFRs with foreign-born parents, regarding antimalarial and antidiarrheal medications and preventing yellow fever, malaria and typhoid.

International Regulations for Automobile Driving and Epilepsy

BACKGROUND Many patients with epilepsy travel abroad and drive automobiles with the assumption that policies, rules, and regulations on epilepsy and driving are similar to those of their home countries. This paper investigates the driving restrictions and other pertinent information on this issue in foreign countries. METHODS A questionnaire was sent to 231 neurologists (chosen from American neurological and epilepsy societies) from 84 countries and to 230 official (embassies and consulates) representatives of 134 countries asking for the local rules and regulations and their comments on driving and epilepsy. RESULTS One hundred and sixty-six responses were received from 96 of 134 (72%) countries. One hundred and six neurologists (of 231 queried [46%]) responded. In 16 countries, persons with epilepsy are not permitted to drive. In the remaining countries, these patients must have a seizure-free period of 6 to 36 months. This period varies according to the type of seizure. In five countries, physicians must report the names of these patients to their local authorities. In many countries, the rules and regulations are being reevaluated and changed. CONCLUSIONS Patients with epilepsy who plan to drive overseas are advised to contact local embassies and consulates, well before their trips (and keep records of the communications) to obtain the latest information on the rules and regulations governing the driving of automobiles in those countries.

Relationship of Blood Level and Susceptibility in Voriconazole Treatment of Histoplasmosis

Monitoring of voriconazole serum levels has been advocated by Smith et al. as a method of ensuring adequate drug exposure in treating invasive mycoses (9). Voriconazole blood levels may vary considerably between subjects as a consequence of genetic polymorphisms that dictate variable clearance and nonlinear elimination (4, 5, 7, 8, 10). Among patients taking 200 mg twice a day, trough voriconazole concentrations range from below 0.100 μg/ml to nearly 10 μg/ml in several studies (2, 4, 5, 6). Although clinical trial data are lacking, voriconazole is occasionally used to treat Histoplasma capsulatum infections. In this report, we determined blood levels in patients treated with voriconazole as a secondary therapy for histoplasmosis, usually because of intolerance of other antifungal therapies, mostly amphotericin B or itraconazole. Serum specimens from nine patients with disseminated histoplasmosis that had been submitted for antigen testing were later tested for serum levels of voriconazole (3). All nine patients were considered to have improved clinically during secondary oral voriconazole treatment at a dose of 200 mg twice daily. All patients had received voriconazole for at least 2 weeks before blood concentrations were determined, but the exact timing of the blood specimens obtained following the oral administration of voriconazole was not recorded. Specimens had been frozen for up to 4 years prior to the determination of serum drug levels. Our experience with a similar compound, itraconazole, showed no loss of activity after 4 years at −20°C. Furthermore, the levels observed in the patients in this study are consistent with levels obtained in real-time testing of fresh specimens. Isolates of H. capsulatum for this patient cohort were unavailable for voriconazole susceptibility testing; therefore, archived H. capsulatum isolates from AIDS patients who had either primary or relapsed histoplasmosis were employed for this testing by a modified CLSI (formerly NCCLS) method as described previously (1). A comparison of voriconazole susceptibilities (by MIC measurements) of these archived H. capsulatum isolates from patients with both primary and relapsed disease (Fig. ​(Fig.1)1) was made with the random voriconazole blood levels measured from the nine patients who were being treated with the drug for disseminated histoplasmosis (Fig. ​(Fig.11). FIG. 1. Comparison of antifungal susceptibilities of primary and relapse isolates of H. capsulatum to voriconazole and random voriconazole blood levels in patients receiving voriconazole for the treatment of histoplasmosis. The left-hand axis depicts the MIC ... Among 20 samples for the nine patients, voriconazole concentrations ranged from undetectable to 8.00 μg/ml (Fig. ​(Fig.1).1). Voriconazole blood levels were highly variable and possibly inadequate in several of our patients, with two random blood levels clearly falling below the median MIC for primary (0.015 μg/ml) and relapsed (0.030 μg/ml) isolates. Three other levels fell below the lowest calibrator (0.125 μg/ml) for serum voriconazole levels, and therefore we do not know if they were below these MIC medians. There were questions about medication compliance in three patients, two of whom had levels of <0.125 μg/ml. Nonetheless, all nine patients had already improved in response to amphotericin B or itraconazole before voriconazole was started, and no patient relapsed while receiving voriconazole, despite the documented low drug levels. Pascual et al. reported a 90% response for patients with aspergillosis or candidiasis with voriconazole trough levels of >1.0 mg/ml and only a 54% response for patients with lower troughs (6). Smith et al. reported findings for 28 patients with invasive mycoses, mostly aspergillosis, and observed favorable responses for 100% (10/10) of patients with random serum levels, >2.05 μg/ml, compared with unfavorable responses for 44% of patients with lower concentrations (9). Among our nine patients with histoplasmosis, random levels were <2.05 μg/ml in 60%, <1.0 μg/ml in 45%, and <0.125 μg/ml in 30%. Although we cannot establish a “subtherapeutic level” from our cases, since all appear to have responded to the therapies given, we suggest that levels that measure below the calibrator level of 0.125 μg/ml might be considered subtherapeutic. This task is further complicated by the paucity of voriconazole MIC data for histoplasmosis. Given the variability in serum levels in patients receiving voriconazole for histoplasmosis, the relatively high MIC90 of voriconazole for H. capsulatum noted herein, and the lack of prospective trials establishing the effectiveness of voriconazole for the treatment of histoplasmosis, we suggest that it may be prudent to measure trough concentrations of voriconazole in patients receiving it for treatment of histoplasmosis to ensure detectable drug levels.

Prevalence of Dengue Virus Infection in US Travelers Who Have Lived in or Traveled to Dengue-Endemic Countries

BACKGROUND Dengue virus (DENV) infections may occur in travelers. OBJECTIVES To determine prevalence of anti-DENV IgG antibody in travelers who lived in or visited dengue-endemic countries and to describe risk factors and characteristics associated with infection and subsequent anti-DENV IgG antibody presence. METHODS Participants were enrolled from travel clinics of the Boston Area Travel Medicine Network from August 2008 through June 2009. Demographic information, trip duration, travel history, and a blood sample were collected. Serum samples were tested for anti-DENV IgG antibody by indirect IgG enzyme-linked immunosorbent assay (ELISA), and antibody-mediated virus neutralization by plaque reduction neutralization test (PRNT) for anti-DENV IgG antibody-positive and selected negative samples. Participants were stratified into group 1: born in dengue-endemic countries; group 2: born in nonendemic countries but lived continuously for ≥1 year in a dengue-endemic country; group 3: born in nonendemic countries and traveled to a dengue-endemic country for ≥2 weeks but <1 year. RESULTS Six hundred travelers were enrolled. Anti-DENV IgG antibody was identified in 113 (19%) when tested by ELISA (51% in group 1, 40% in group 2, and 6.9% in group 3) and in 71 (12%) by PRNT (42% primary monotypic and 58% heterotypic reactive responses). Sensitivity and specificity of the ELISA based on PRNT results were 85% to 100% and 79% to 94%, assuming up to 15% misclassification of ELISA negative results. Presence of anti-DENV IgG antibody by ELISA was associated with years lived in dengue-endemic countries and birthplace in the Caribbean for group 1, receipt of Japanese encephalitis vaccine in group 3, and self-reported history of dengue in all three groups. CONCLUSIONS Nineteen percent of participants who were born, lived in, or traveled to dengue-endemic countries had anti-DENV IgG antibody by ELISA; 12% had antibodies by PRNT, 85% of whom had no history of dengue. Presence of DENV antibodies was associated with years lived in dengue-endemic countries and self-reported history of dengue.

Case Report: Zika Virus Meningoencephalitis and Myelitis and Associated Magnetic Resonance Imaging Findings

Zika virus (ZIKV) has a wide clinical spectrum of associated neurologic disease including microcephaly and Guillain-Barre syndrome but, despite its known neurotropism, ZIKV meningoencephalitis and myelitis have been rare complications. We describe a case of ZIKV meningoencephalitis and probable myelitis and its associated magnetic resonance imaging findings that rapidly resolved during recovery in a previously healthy adult.

Hepatitis B screening in US travelers seen at the Boston area travel medicine network.

BACKGROUND Persons born in countries with hepatitis B surface antigen (HBsAg) prevalence ≥2% have increased risk for unrecognized hepatitis B virus (HBV) infection. Testing at pre-travel consultations is a strategy to identify previously undiagnosed HBV infections. Using records of travelers seen at the Boston Area Travel Medicine Network (BATMN) sites, we assessed how these travel clinics currently assess HBV status, describe test results, and describe characteristics of those tested and immunized for HBV. METHODS Demographic data and trip information were collected for all travelers seen at the BATMN sites from June 2008 through July 2010. Proportions of those tested for HBV were determined, and differences between those tested and not tested were analyzed. RESULTS Among 13,732 travelers enrolled during the study period, 2,134 (16%) were born in HBV-risk countries (HBsAg prevalence ≥2%); 532/2134 (25%) had previous HBV test results and 230 (11%) had tests performed at the travel clinic visit. Past results showed that 33/453 (7.3%) were HBV-infected (HBsAg+), 252/481 (52.4%) were immune (anti-HBs+, HBsAg-), 164/303 (54.1%) were susceptible (anti-HBs-, HBsAg-, anti-HBc-), and 38/314 (12.1%) had possible HBV exposure (anti-HBc+, HBsAg-, anti-HBs-). Among 230 travelers tested during the travel clinic visit, 7/213 (3.3%) were HBV-infected, 95/218 (43.6%) were immune, 106/179 (59.2%) were susceptible, and 10/182 (5.5%) had possible HBV exposure. CONCLUSION The travel clinic offers an opportunity to capture, identify, and educate infected persons unaware of their infection, educate those with known results, and initiate preventive action (eg, vaccination) for those still susceptible.