Joseph Torresi

Illness in Travelers Visiting Friends and Relatives: A Review of the GeoSentinel Surveillance Network

Travelers returning to their country of origin to visit friends and relatives (VFRs) have increased risk of travel-related health problems. We examined GeoSentinel data to compare travel characteristics and illnesses acquired by 3 groups of travelers to low-income countries: VFRs who had originally been immigrants (immigrant VFRs), VFRs who had not originally been immigrants (traveler VFRs), and tourist travelers. Immigrant VFRs were predominantly male, had a higher mean age, and disproportionately required treatment as inpatients. Only 16% of immigrant VFRs sought pretravel medical advice. Proportionately more immigrant VFRs visited sub-Saharan Africa and traveled for >30 days, whereas tourist travelers more often traveled to Asia. Systemic febrile illnesses (including malaria), nondiarrheal intestinal parasitic infections, respiratory syndromes, tuberculosis, and sexually transmitted diseases were more commonly diagnosed among immigrant VFRs, whereas acute diarrhea was comparatively less frequent. Immigrant VFRs and traveler VFRs had different demographic characteristics and types of travel-related illnesses. A greater proportion of immigrant VFRs presented with serious, potentially preventable travel-related illnesses than did tourist travelers.

GeoSentinel surveillance of illness in returned travelers, 2007-2011.

BACKGROUND International travel continues to increase, particularly to Asia and Africa. Clinicians are increasingly likely to be consulted for advice before travel or by ill returned travelers. OBJECTIVE To describe typical diseases in returned travelers according to region, travel reason, and patient demographic characteristics; describe the pattern of low-frequency travel-associated diseases; and refine key messages for care before and after travel. DESIGN Descriptive, using GeoSentinel records. SETTING 53 tropical or travel disease units in 24 countries. PATIENTS 42 173 ill returned travelers seen between 2007 and 2011. MEASUREMENTS Frequencies of demographic characteristics, regions visited, and illnesses reported. RESULTS Asia (32.6%) and sub-Saharan Africa (26.7%) were the most common regions where illnesses were acquired. Three quarters of travel-related illness was due to gastrointestinal (34.0%), febrile (23.3%), and dermatologic (19.5%) diseases. Only 40.5% of all ill travelers reported pretravel medical visits. The relative frequency of many diseases varied with both travel destination and reason for travel, with travelers visiting friends and relatives in their country of origin having both a disproportionately high burden of serious febrile illness and very low rates of advice before travel (18.3%). Life-threatening diseases, such as Plasmodium falciparum malaria, melioidosis, and African trypanosomiasis, were reported. LIMITATIONS Sentinel surveillance data collected by specialist clinics do not reflect healthy returning travelers or those with mild or self-limited illness. Data cannot be used to infer quantitative risk for illness. CONCLUSION Many illnesses may have been preventable with appropriate advice, chemoprophylaxis, or vaccination. Clinicians can use these 5-year GeoSentinel data to help tailor more efficient pretravel preparation strategies and evaluate possible differential diagnoses of ill returned travelers according to destination and reason for travel. PRIMARY FUNDING SOURCE Centers for Disease Control and Prevention.

Fever in returned travelers: review of hospital admissions for a 3-year period.

We reviewed 232 consecutive patients admitted to a tertiary-care hospital under the care of an infectious diseases unit for management of febrile illness acquired overseas. A total of 53% presented to hospital within 1 week of return and 96% within 6 months. Malaria was the most common diagnosis (27% of patients), followed by respiratory tract infection (24%), gastroenteritis (14%), dengue fever (8%), and bacterial pneumonia (6%). Pretravel vaccination may have prevented a number of admissions, including influenza (n=11), typhoid fever (n=8) and hepatitis A (n=6). Compared to those who had not traveled to Africa, those who had were 6 times more likely to present with falciparum than nonfalciparum malaria. An itinerary that included Asia was associated with a 13-fold increased risk of dengue, but a lower risk of malaria. Palpable splenomegaly was associated with an 8-fold risk of malaria and hepatomegaly with a 4-fold risk of malaria. As a cause of fever, bacterial pneumonia was > or =5 times more likely in those who were aged >40 years.

Malaria in travelers: a review of the GeoSentinel surveillance network.

BACKGROUND Malaria is a common and important infection in travelers. METHODS We have examined data reported to the GeoSentinel surveillance network to highlight characteristics of malaria in travelers. RESULTS A total of 1140 malaria cases were reported (60% of cases were due to Plasmodium falciparum, 24% were due to Plasmodium vivax). Male subjects constituted 69% of the study population. The median duration of travel was 34 days; however, 37% of subjects had a travel duration of < or =4 weeks. The majority of travellers did not have a pretravel encounter with a health care provider. Most cases occurred in travelers (39%) or immigrants/refugees (38%). The most common reasons for travel were to visit friends/relatives (35%) or for tourism (26%). Three-quarters of infections were acquired in sub-Saharan Africa. Severe and/or complicated malaria occurred in 33 cases, with 3 deaths. Compared with others in the GeoSentinel database, patients with malaria had traveled to sub-Saharan Africa more often, were more commonly visiting friends/relatives, had traveled for longer periods, presented sooner after return, were more likely to have a fever at presentation, and were less likely to have had a pretravel encounter. In contrast to immigrants and visitors of friends or relatives, a higher proportion (73%) of the missionary/volunteer group who developed malaria had a pretravel encounter with a health care provider. Travel to sub-Saharan Africa and Oceania was associated with the greatest relative risk of acquiring malaria. CONCLUSIONS We have used a global database to identify patient and travel characteristics associated with malaria acquisition and characterized differences in patient type, destinations visited, travel duration, and malaria species acquired.

Vitamin D Deficiency Is Associated with Tuberculosis and Latent Tuberculosis Infection in Immigrants from Sub-Saharan Africa

Among African immigrants in Melbourne, Victoria, Australia, we demonstrated lower geometric mean vitamin D levels in immigrants with latent tuberculosis infection than in those with no Mycobacterium tuberculosis infection (P=.007); such levels were also lower in immigrants with tuberculosis or past tuberculosis than in those with latent tuberculosis infection (P=.001). Higher vitamin D levels were associated with lower probability of any M. tuberculosis infection (P=.001) and lower probability of tuberculosis or past tuberculosis (compared with latent tuberculosis infection; P=.001).

The virological and clinical significance of mutations in the overlapping envelope and polymerase genes of hepatitis B virus.

The potential for hepatitis B virus (HBV) to alter its genome is considerable. This occurs because the virus utilizes a reverse transcription step in replicating the viral genome. Like human immunodeficiency virus, the reverse transcriptase of HBV is error prone and as a consequence of specific selection pressures within a host a population of viral quasispecies emerges. HBV mutants with survival advantages over the wild type virus appear within the selective in vivo environment. Some of these viruses include HBV vaccine escape and anti-viral resistant mutants that have changes in the envelope (S) and polymerase genes, respectively. In addition, the genome of HBV is organised in to overlapping reading frames. The S gene is completely overlapped by the polymerase gene. As a consequence, mutations in the S gene may produce changes in the overlapping polymerase gene. Similarly, mutations in the polymerase gene may produce changes in the S gene. The virological and clinical significance of such overlapping mutations is unclear. However, we have shown that certain mutations in either the S or polymerase gene produce functionally significant changes in the respective overlapping gene. Treatment of chronic hepatitis B carriers with long-term lamivudine (LMV) results in the selection of HBV mutants that are resistant to this nucleoside analogue. The polymerase mutations associated with LMV resistance produce changes in the overlapping S gene and in its envelope protein (hepatitis B small antigen, HBsAg) that results in a reduced antigenicity of the HBsAg protein. The selection of vaccine escape mutants by HBV vaccination or hepatitis B immune globulin is associated with changes in the S gene that are accompanied by mutations in the fingers sub-domain of the polymerase protein. When combined with polymerase mutations that are associated with resistance to LMV the changes within the fingers sub-domain of the viral enzyme behave as compensatory mutations that are able to restore the replication of LMV resistant HBV. The ability to change a viral protein by mutations in an overlapping but unrelated viral gene may produce HBV mutants with altered antigenicity and/or replication and a natural history that may be distinctly different to wild type HBV.

Travel Health Knowledge, Attitudes and Practices among Australasian Travelers

BACKGROUND Although the Asia Pacific region is the focus of the fastest-growing tourist and travel industry, few data are available on the knowledge, attitudes and practices (KAP) of travelers from this region with regard to travel-related infectious diseases. METHODS We conducted a cross-sectional survey among travelers at the departure lounges of five airports in Australasia (Singapore, Kuala Lumpur, Taipeh, Melbourne, Seoul) whose travel destinations were Asia, Africa or South America. Two standardized questionnaires directed towards KAP in travel health, travel immunizations and malaria were administered. RESULTS Of 2,101 respondents (82% Asian, 17% Western), 31% had sought pretravel health advice and only 4% sought travel health advice from the travel medicine specialist. The risk of vaccine-preventable infectious diseases and malaria at the destination country was perceived to be low. Overall, fewer than 5% of travelers had been vaccinated in preparation for their trip. The most frequent travel vaccinations were for hepatitis A and B. Only 40% of travelers to malaria-endemic areas carried malaria prophylaxis. Compared to Western travelers, those of Asian nationality were significantly less likely to obtain pretravel advice and malaria prophylaxis and to receive travel vaccinations. CONCLUSION There is an urgent need for increased awareness about travel-related infectious diseases among Asian travelers, and greater uptake of pretravel health advice, vaccinations and malaria prophylactic measures.

Seasonality, Annual Trends, and Characteristics of Dengue among Ill Returned Travelers, 1997–2006

Atypical patterns may indicate onset of epidemic activity.

In Vitro Susceptibilities of Wild-Type or Drug-Resistant Hepatitis B Virus to (−)-β-d-2,6-Diaminopurine Dioxolane and 2′-Fluoro-5-Methyl-β-l-Arabinofuranosyluracil

ABSTRACT Prolonged treatment of chronic hepatitis B virus (HBV) infection with lamivudine ([−]-β-l-2′,3′-dideoxy-3′ thiacytidine) or famciclovir may select for viral mutants that are drug resistant due to point mutations in the polymerase gene. Determining whether such HBV mutants are sensitive to new antiviral agents is therefore important. We used a transient transfection system to compare the sensitivities of wild-type HBV and four lamivudine- and/or famciclovir-resistant HBV mutants to adefovir [9-(2-phosphonyl-methoxyethyl)-adenine; PMEA] and the nucleoside analogues (−)-β-d-2, 6-diaminopurine dioxolane (DAPD) and 2′-fluoro-5-methyl-β-l-arabinofuranosyluracil (l-FMAU). The drug-resistant mutants contained amino acid substitutions in the polymerase protein. We found that the M550I and M550V plus L526M substitutions, which confer lamivudine resistance, did not confer cross-resistance to adefovir or DAPD, but conferred cross-resistance to l-FMAU. The M550V substitution in isolation conferred a similar phenotype to M550I, except that it did not confer significant resistance to l-FMAU. The L526M substitution, which is associated with famciclovir resistance, conferred cross-resistance to l-FMAU but not to adefovir or DAPD. Inhibition of HBV secretion by DAPD, l-FMAU, and adefovir did not always correlate with inhibition of the generation of intracellular HBV replicative intermediates, suggesting that these analogs may preferentially inhibit specific stages of the viral replication cycle.

Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam

Eight genotypes (A‐H) of hepatitis B virus (HBV) have been identified. However, the impact of different genotypes on the clinical course of hepatitis B infection remains controversial. We investigated the frequency and clinical outcome of HBV genotypes and genotype mixtures in HBV‐infected patients from Vietnam, Europe, and Africa. In addition, we analyzed the effects of genotype mixtures on alterations in in vitro viral replication. In Asian patients, seven genotypes (A‐G) were detected, with A, C, and D predominating. In European and African patients, only genotypes A, C, D, and G were identified. Genotype mixtures were more frequently encountered in African than in Asian (P = .01) and European patients (P = .06). In Asian patients, the predominant genotype mixtures included A/C and C/D, compared to C/D in European and A/D in African patients. Genotype A was more frequent in asymptomatic compared with symptomatic patients (P < .0001). Genotype C was more frequent in patients with hepatocellular carcinoma (HCC; P = .02). Genotype mixtures were more frequently encountered in patients with chronic hepatitis in comparison to patients with acute hepatitis B (P = .015), liver cirrhosis (P = .013), and HCC (P = .002). Viral loads in patients infected with genotype mixtures were significantly higher in comparison to patients with a single genotype (P = .019). Genotype mixtures were also associated with increased in vitro HBV replication. In conclusion, infection with mixtures of HBV genotypes is frequent in Asia, Africa, and Europe. Differences in the replication‐phenotype of single genotypes compared to genotype‐mixtures suggest that co‐infection with different HBV‐genotypes is associated with altered pathogenesis and clinical outcome. (HEPATOLOGY 2006;43:1375–1384.)