Natasha S. Hochberg

Anisakidosis: Perils of the Deep

Anisakidosis, human infection with nematodes of the family Anisakidae, is caused most commonly by Anisakis simplex and Pseudoterranova decipiens. Acquired by the consumption of raw or undercooked marine fish or squid, anisakidosis occurs where such dietary customs are practiced, including Japan, coastal regions of Europe, and the United States. Severe epigastric pain, resulting from larval invasion of the gastric mucosa, characterizes gastric anisakidosis; other syndromes are intestinal and ectopic. Allergic anisakidosis is a frequent cause of foodborne allergies in areas with heavy fish consumption or occupational exposure. Diagnosis and treatment of gastric disease is usually made by a compatible dietary history and visualization and removal of the larva(e) on endoscopy; serologic testing for anti-A. simplex immunoglobulin E can aid in the diagnosis of intestinal, ectopic and allergic disease. Intestinal and/or ectopic cases may require surgical removal; albendazole has been used occasionally. Preventive measures include adequately freezing or cooking fish.

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.

Prevention of Tuberculosis in Older Adults in the United States: Obstacles and Opportunities

BACKGROUND Persons ≥65 are a growing proportion of the US population and are at increased risk for tuberculosis disease. The objective of the study was to examine rates and identify risk factors for tuberculosis among older adults in the United States. METHODS Average rates and rate ratios for tuberculosis by age group, race/ethnicity, country of birth, calendar year, and long-term care facility residence were calculated using Centers for Disease Control and Prevention tuberculosis case reports and Census Bureau data. RESULTS Older adults accounted for 21.9% of tuberculosis cases in the United States between 1993 and 2008. Average yearly tuberculosis rates over sixteen years were 10.9 per 100 000 (95% confidence interval [CI], 10.8-11.0) in older adults compared with 7.3 per 100 000 (95% CI, 7.3-7.4) in persons aged 21-64 (rate ratio [RR], 1.5; 95% CI, 1.5-1.5). Among older adults, tuberculosis rates increased with age from 9.6 per 100 000 in persons aged 65-74 to 14.2 per 100 000 in persons aged ≥85 years. Older persons at higher risk for tuberculosis include men (RR, 2.1; 95% CI, 2.1-2.2), American Indians/Alaska Natives (RR 3.6; 95% CI, 3.4-3.9), those in long-term care facilities (RR 2.3; 95% CI, 2.2-2.3), and the foreign-born (RR 5.1; 95% CI, 5.0-5.2). CONCLUSIONS Elimination of tuberculosis in the United States will require addressing the substantial burden of disease among older persons, especially men, non-whites, long-term care facility residents, and foreign-born persons. Use of interferon-γ release assay testing may help prioritize persons with greatest need for treatment of latent tuberculosis infection, as new shorter and less toxic regimens make latent tuberculosis treatment in older adults more attractive.

The complexity of diagnosing latent tuberculosis infection in older adults in long-term care facilities

OBJECTIVES In the USA, tuberculosis disease rates are highest in older adults. Diagnostic testing for latent tuberculosis infection (LTBI) has not been evaluated carefully in this group. The aim of this study was to define the relationship between tuberculin skin test (TST) results, T-SPOT.TB results, and T-cell responses to Mycobacterium tuberculosis antigens. METHODS Long-term care facility residents with known prior TST results (positive or negative) were retested with TSTs and T-SPOT.TB. Prior exposure to M. tuberculosis was assessed by quantifying T-cell activation to mycobacterial antigens in vitro. RESULTS The median age of the 37 participants was 77 years (range 57-98 years). Among 18 participants with a prior positive TST, three (16.7%) had a negative TST when retested (TST reversion); two had a negative T-SPOT.TB. Of the 15 who were historically and currently TST-positive, four (26.7%) had a negative T-SPOT.TB and one (6.7%) had a borderline result. Percentages of CD4+ T-cells responding to mycobacterial antigens were higher in participants with positive TST and T-SPOT.TB (18.2%) compared to those with a positive TST but negative T-SPOT.TB (6.4%, p=0.16) and negative TST and T-SPOT.TB (5.9%, p<0.001). CONCLUSIONS LTBI testing in older adults is complicated by TST reversion and TST-positive/T-SPOT.TB-negative discordance, which may reflect clearance of infection or waning immunity.

Bordetella pertussis infections in travelers: data from the GeoSentinel global network

Background: Pertussis is a highly contagious, vaccine-preventable respiratory infection that is endemic worldwide. There are limited data regarding the occurrence of pertussis in travelers. The objective of this study is to identify travel-related pertussis cases reported to the GeoSentinel Surveillance Network. Methods: This is a descriptive, retrospective analysis of GeoSentinel records from 25 travel/tropical medicine clinics in 16 countries. Frequencies of demographic and travel-related characteristics and symptoms of 74 cases of pertussis in travelers and new immigrants from 1999 to 2015 were analysed. Results: There were 74 probable and confirmed cases of pertussis in the GeoSentinel database; median age was 44 years, and 38 (51%) patients were female. Tourism was the most common reason for travel (41; 55%). Country of exposure was determined in 66 cases with travelers returning from India and China constituting the highest number of cases (10 cases each; 15% each). Seventy of 74 (95%) patients had respiratory symptoms, while fatigue and fever were reported by 21 (28%) and 20 (27%), respectively. Immunization status against pertussis was unknown. Most cases were reported after 2005 (69; 93%). Conclusions: Our study describes 74 cases of pertussis acquired during travel and reported to the GeoSentinel Network. Pertussis should be considered in returned travelers who present with respiratory symptoms. Surveillance and detection of imported cases are important to prevent onward transmission in the community. The pre-travel consultation provides an opportunity to verify immunization status and provide routine vaccinations such as pertussis.

Acceptability of Hypothetical Dengue Vaccines Among Travelers

BACKGROUND Dengue viruses have spread widely in recent decades and cause tens of millions of infections mostly in tropical and subtropical areas. Vaccine candidates are being studied aggressively and may be ready for licensure soon. METHODS We surveyed patients with past or upcoming travel to dengue-endemic countries to assess rates and determinants of acceptance for four hypothetical dengue vaccines with variable efficacy and adverse event (AE) profiles. Acceptance ratios were calculated for vaccines with varied efficacy and AE risk. RESULTS Acceptance of the four hypothetical vaccines ranged from 54% for the vaccine with lower efficacy and serious AE risk to 95% for the vaccine with higher efficacy and minor AE risk. Given equal efficacy, vaccines with lower AE risk were better accepted than those with higher AE risk; given equivalent AE risk, vaccines with higher efficacy were better accepted than those with lower efficacy. History of Japanese encephalitis vaccination was associated with lower vaccine acceptance for one of the hypothetical vaccines. US-born travelers were more likely than non-US born travelers to accept a vaccine with 75% efficacy and a risk of minor AEs (p = 0.003). Compared with North American-born travelers, Asian- and African-born travelers were less likely to accept both vaccines with 75% efficacy. CONCLUSIONS Most travelers would accept a safe and efficacious dengue vaccine if one were available. Travelers valued fewer potential AEs over increased vaccine efficacy.

Latent Tuberculosis Infection Testing Practices in Long-Term Care Facilities, Boston, Massachusetts

To describe latent tuberculosis infection (LTBI) testing practices in long‐term care facilities (LTCFs).

Existing blood transcriptional classifiers accurately discriminate active tuberculosis from latent infection in individuals from south India

Several studies have identified blood transcriptomic signatures that can distinguish active from latent Tuberculosis (TB). The purpose of this study was to assess how well these existing gene profiles classify TB disease in a South Indian population. RNA sequencing was performed on whole blood PAXgene samples collected from 28 TB patients and 16 latently TB infected (LTBI) subjects enrolled as part of an ongoing household contact study. Differential gene expression and clustering analyses were performed and compared with explicit predictive testing of TB and LTBI individuals based on established gene signatures. We observed strong predictive performance of TB disease states based on expression of known gene sets (ROC AUC 0.9007-0.9879). Together, our findings indicate that previously reported classifiers generated from different ethnic populations can accurately discriminate active TB from LTBI in South Indian patients. Future work should focus on converting existing gene signatures into a universal TB gene signature for diagnosis, monitoring TB treatment, and evaluating new drug regimens.

Low body mass index and latent tuberculous infection: a systematic review and meta-analysis

BACKGROUND The well-documented association between underweight and increased incidence of active tuberculosis (TB) has not been extended to incidence or prevalence of latent tuberculous infection (LTBI). DESIGN After identifying studies that reported a categorical measure of body mass index (BMI) and used the tuberculin skin test (TST) or QuantiFERON®-TB Gold In-Tube (QFT) to measure LTBI, a maximum likelihood random-effects model was used to examine the pooled association between LTBI and low BMI (<18.5 kg/m2), compared with 1) normal BMI (18.5-25 kg/m2) and 2) a complementary group of all others, i.e., non-underweight subjects (BMI 18.5 kg/m2). RESULTS Among studies using TST, the odds ratios (ORs) showed a slight, non-statistically significant decrease in the odds of TST positivity in underweight persons compared with both groups (non-underweight, OR 0.88, 95%CI 0.73-1.05; normal weight, OR 0.96, 95%CI 0.77-1.20). Among studies using QFT, the OR suggested slightly decreased, yet non-significant, odds of QFT positivity in underweight compared with non-underweight subjects (OR 0.92, 95%CI 0.68-1.26), and significantly decreased odds of QFT positivity in underweight compared with normal weight subjects (OR 0.84, 95%CI 0.73-0.98). CONCLUSION These results suggest that underweight persons are not at an increased risk of LTBI. Screening this population for LTBI would not increase the yield of identified LTBI.

Comorbidities in pulmonary tuberculosis cases in Puducherry and Tamil Nadu, India: Opportunities for intervention

Background We aimed to define characteristics of TB patients in Puducherry and two districts of Tamil Nadu, India and calculate the population attributable fractions (PAF) of TB from malnutrition and alcohol. Methods New smear-positive TB cases were enrolled into the Regional Prospective Observational Research for Tuberculosis (RePORT India) cohort. Census and National Family Health Survey data were used for comparisons. Results Data were analyzed for 409 participants enrolled between May 2014-June 2016; 307 (75.1%) were male, 60.2% were malnourished (body mass index [BMI] <18.5 kg/m2), and 29.1% severely malnourished (BMI <16). “Hazardous” alcohol use (based on AUDIT-C score) was reported by 155/305 (50.8%) of males. Tuberculosis cases were more likely than the Puducherry population to be malnourished (62.6% v 10.2% males and 71.7% v 11.3% of females; both p<0.001), and male cases were more likely to use alcohol than male non-cases (84.4% v 41%; p < .001). The PAF of malnutrition was 57.4% in males and 61.5% in females; the PAF for alcohol use was 73.8% in males and 1.7% in females. Conclusions Alcohol use in men and malnutrition are helping drive the TB epidemic in Southern India. Reducing the TB burden in this population will require efforts to mitigate these risk factors.