Topic Update

The sick returned traveller

The sick returned traveller

Volume 11, Issue 1 January 2016  (download full article in pdf)

 

Editorial note:

With increasing international travel, awareness and knowledge on the microbiology aspects of the returning traveller is essential, in order for timely diagnosis of infectious diseases acquired abroad and for administration of effective clinical management and public health control measures. In this issue of the Topical Update, Dr. Samson Wong presents a synopsis of the conditions associated with the returned traveller, which will be of practical application to any medical professional. We welcome any feedback or suggestion. Please direct them to Dr. Janice Lo (e-mail: janicelo@dh.gov.hk), Education Committee, The Hong Kong College of Pathologists. Opinions expressed are those of the authors or named individuals, and are not necessarily those of the Hong Kong College of Pathologists.

 

Dr. Samson SY WONG
Assistant Professor, Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
 

Introduction

The number of international travellers has been increasing over the past 20 years. In 1995, there were 530 million international arrivals; this figure increased to 1,138 million in 2014 [1]. This rising trend has only been punctuated in 2003 and 2009, coinciding with two infectious disease epidemics, SARS and pandemic influenza, respectively. With the unprecedented volume, speed, and reach of international travel comes an increasing number of patients who developed travel-related health issues. About 15–64% international travellers may develop health problems during their travel [2–5]. The risk depends on the duration of travel, destination, behaviour of the travellers, and the use of prophylactic measures. In most studies, gastrointestinal (usually in the form of travellers’ diarrhoea) and respiratory illnesses are the commonest complaints, followed by skin problems, fever, and other conditions such as altitude sickness, envenoming, accidents and injuries. In this article, we shall focus on the concerns and precautions in the laboratory diagnosis of some important infections in the returned travellers.

 

Spectrum of infections and approach to the sick returned traveller

The spectrum of travel-related infections is diverse. A large body of information is available from individual centres and from GeoSentinel which consists of 63 travel clinics in 29 countries on 6 continents (http://wwwnc.cdc.gov/travel/ page/geosentinel. Accessed on 2 December 2015). However, similar data are lacking in Hong Kong, and one should note that the prevalence of different infections in the literature may not be applicable locally because of differences in the adoption of prophylactic measures and habits of travel. Data from the more recent GeoSentinel surveillance are consistent with earlier studies in that the commonest illnesses in returned travellers affected the gastrointestinal tract, respiratory system, skin, or presented as fever or systemic illnesses (Table 1) [6–9]. Fever is a common manifestation in such patients, which may occur as an undifferentiated febrile illness or be associated with specific symptoms such as rash, arthritis/arthralgia, or other localizing symptoms. The presence of localizing signs and symptoms helps to narrow the differential diagnoses. Most studies in the literature described malaria as one of the commonest causes of fever, followed by dengue in the more recent series (Table 2). Although malaria is certainly a diagnosis not to be missed, it is not the commonest aetiology of fever in returned travellers in Hong Kong. For example, in 2014, 23 cases of malaria and 112 cases of dengue were notified to the Department of Health [10]. Given that both diseases are primarily imported from endemic countries, dengue would be commoner as a cause of fever in the travellers in Hong Kong.

The clinical approach should always begin with a thorough history including a detailed itinerary (with stopovers), potential exposure history, and prophylactic measures. Despite the long list of differential diagnoses to each clinical syndrome, the most likely causes can often be suggested by the geographical areas visited, the likely incubation period of the disease, and the relevant exposure history. Some important infections associated with specific exposures are listed in Table 3. Subsequent choice of organ imaging and laboratory investigations is guided by the most likely diagnosis. It is important that after the initial assessment, one must not miss conditions that are clinically severe and potentially treatable, as well as those that have a high risk of hospital or community transmission. Severe infections must be investigated and treated urgently, such as sepsis, severe malaria, haemorrhagic fevers, and central nervous system infections. Examples of diseases that require prompt infection control precautions include viral haemorrhagic fevers, Middle East respiratory syndrome (MERS), avian influenza and infections caused by other novel influenza viruses.

 

Important clinical syndromes and laboratory investigations

Malaria

Malaria must always be considered as a potential cause of fever occurring in anyone who develops fever seven days after travelling to an endemic area [11]. Missing a case of malaria, especially falciparum malaria, can lead to serious and often fatal outcomes which in turn, may lead to medicolegal litigations. There are no pathognomonic clinical signs and symptoms of malaria. Patients are sometimes erroneously diagnosed to have influenza or gastroenteritis initially because of the non-specific clinical symptoms [12–15]. The textbook description of periodic fever is only present in 8–23% of malaria patients [12, 13]. Appropriate laboratory testing must be performed in any patient with a compatible travel history.

The diagnosis of malaria is conventionally made by examination of the thin and thick blood films. The four species of human Plasmodium, P. vivax, P. ovale, P. malariae, and P. falciparum are distinguished morphologically. In the past decade, the simian malaria P. knowlesi has emerged as an important cause of human malaria in some Southeast Asian foci, especially in Malaysian Borneo. P. knowlesi infection of travellers has been well reported. The difficulty with P. knowlesi is that its morphology closely resembles other human plasmodia, especially P. malariae. Definitive speciation can generally be made using molecular techniques [16]. Quantification of the level of parasitaemia is essential for falciparum malaria both upon initial diagnosis and serial examination of the blood smear because the level of parasitaemia carries prognostic significance and failure to reduce the level of parasitaemia after antimalarial treatment could signify drug resistance.

Any positive blood smear results must be conveyed to the attending clinician immediately. This is especially critical for P. falciparum which is a medical emergency in the non-immune travellers. It is important to remember that one single negative blood smear cannot exclude malaria. It is generally recommended that in patients with a negative blood smear but with a high clinical suspicion for malaria, at least three blood smears must be repeated over 48 hours to exclude the diagnosis [17–19]. Alternatives to microscopic diagnosis of malaria include antigen detection and nucleic acid amplification tests (NAAT) from peripheral blood. Immunochromatographic antigen detection kits are widely accepted as a form of rapid diagnostic test [20]. These are particularly useful as a form of point-of-care testing and in situations where experienced microscopists are not available. The major drawbacks include the limited sensitivity in patients with low level parasitaemia and their inability to differentiate all four species of human plasmodia. Speciation is clinically essential because P. vivax and P. ovale infections require radical cure with primaquine. NAAT is currently the most sensitive method for detection of bloodborne parasites and mixed infections, and also allows definitive speciation in problematic cases, including P. knowlesi infection [21]. Availability is, however, currently limited to a few centres and the turnaround time is often too long for routine diagnostic purposes.

Arboviruses

The arthropod-borne viruses are fast becoming some of the most important causes of emerging and re-emerging infectious disease outbreaks in tropical and subtropical countries. This is contributed by the global climate and environmental changes, as well as the geographic spread of the vectors, especially mosquitoes. There is a long list of arboviruses, many of which belong to the families of Togaviridae (mosquito-borne; e.g. Chikungunya, Ross River, Eastern, Western, and Venezuelan equine encephalitis viruses), Flaviviridae (e.g. mosquito-borne dengue, yellow fever, Japanese encephalitis, Zika, Murray Valley encephalitis viruses; tick-borne encephalitis virus), and Bunyaviridae (e.g. mosquito-borne Rift Valley fever virus; tick-borne Crimean-Congo haemorrhagic fever virus; sandfly-borne Toscana and sandfly fever viruses) [22].

The global incidence and geographical extent of dengue have been growing over the past five decades with regular outbreaks in different parts of the world [23]. The most recent outbreak is the ongoing epidemic (at the time of writing) in Taiwan, with 39,350 indigenous cases in 2015 (as of 1 December 2015) [24]. This is also the commonest notifiable arbovirus infection in Hong Kong with occasional local transmissions. Dengue is a relatively common cause of fever in returned travellers, causing 2–16.5% of the cases [25]. The disease is traditionally classified into uncomplicated dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. The last two entities are usually associated with secondary infections due to serotypes of the virus that are different from the one causing the first episode of infection. Since 2009, the World Health Organization re-classified the disease into dengue fever and severe dengue, the latter being characterized by severe plasma leakage, bleeding, and organ impairment [23].

Chikungunya is another arbovirus infection that has gained much attention in the past decade since an outbreak started in Kenya in 2004, with subsequent spread to the Indian Ocean islands till 2006, and infected over one third of the population in La Réunion [26]. Outbreaks of this togavirus have been repeatedly reported in recent years, affecting countries in Asia, Africa, the Pacific islands, Central and South Americas. Likewise, infections due to Zika virus received little attention until it caused large outbreaks in the Yap State of Federated States of Micronesia in 2007 and the French Polynesia in 2013 [27]. Zika virus is endemic in various countries in Africa, Asia, Oceania, the Pacific islands, and since 2014, in Latin and South America (especially Brazil, but also Chile, Colombia, Suriname, Jamaica, and Dominican Republic) [27, 28].

Given the large number of arboviruses, the choice of diagnostic tests should be guided by the geographical area(s) of travel and clinical syndrome. Arbovirus infections commonly manifest as systemic febrile illnesses with or without rash, arthralgia or arthritis, encephalitis or meningoencephalitis, or viral haemorrhagic fever (Table 4) [22, 29]. Many of the viruses are geographically restricted. Requests for investigations against specific viruses should be guided by the travel history and clinical manifestations. Viral culture can be performed for some viruses, but this is generally not the test of choice in most circumstances. Viral serology, preferably with paired sera for antibody testing, is one of the options of investigation, though the availability of serological tests for rarer infections is limited. Antibody testing is readily available for arboviruses such as dengue, Japanese encephalitis, and chikungunya. It should be remembered that antibody testing may be negative in the very early stage of disease, and a second serum should always be obtained. The paired antibody profile in dengue patients can also help to differentiate primary from secondary infections. Another drawback in viral antibody testing is the potential cross reactivity between different viruses, which is common among flaviviruses for example. In terms of dengue diagnostics, detection of the viral NS1 antigen in serum is superior to IgM antibody detection in the first two to three days after disease onset, a window period where IgM is often negative [30]. A combined NS1 antigenaemia and IgM antibody testing is currently a common approach to initial diagnosis of dengue. The use of NS1 lateral flow assay kits may even allow point-of-care testing for dengue, and if the roles of urine and saliva NS1 are substantiated by further studies, this will facilitate the diagnosis of dengue in resource-limited settings [31, 32]. NAAT is another option for early diagnosis of dengue which also permits detection of co-infection by different serotypes (and with other arboviruses) and genotyping of the infecting viral strains [33–35]. Antibody detection (IgM and IgG) and NAAT can also be used for the diagnosis of chikungunya and Japanese encephalitis. Consultation with clinical virologists should be made in order to choose the most appropriate tests, especially when unusual viral agents are suspected.

Enteric syndromes

Important enteric infections encountered in returned travellers include travellers’ diarrhoea, enteric fever, and amoebiasis. Travellers’ diarrhoea is the commonest travel-related infection, affecting 10–40% of individuals travelling from developed to developing countries [36]. It is most often a bacterial infection caused by various diarrhoeagenic Escherichia coli (especially enterotoxigenic strains) and other enteorpathogens such as Campylobacter, Salmonella, and Shigella. Other pathogens include viruses (especially Norovirus, classically associated with passenger ships) and parasites (such as Cryptosporidium, Giardia, Cyclospora) as well as mixed infections. Most cases of travellers’ diarrhoea are self-limiting. Specific microbiological investigations may not be necessary in milder cases, but should be considered in those with more severe manifestations (such as fever, dysentery, bloody diarrhoea, cholera-like symptoms), persistent symptoms, or in immunocompromised individuals [36]. Specific requests for viral agents (antigen detection or NAAT for Rotavirus, NAAT for Norovirus) or special concentration and staining for protozoa (e.g. modified acid-fast staining for Cryptosporidium, Cyclospora, and Cystoisospora) are necessary if routine bacterial cultures are unremarkable.

Enteric fever in Hong Kong can be indigenous or imported. This is most commonly due to typhoid and paratyphoid fevers, caused by Salmonella enterica Typhi and Paratyphi (A, B, C) respectively. Laboratory diagnosis of typhoid and paratyphoid fevers remains problematic. A positive culture from blood or other specimens (stool, urine, bone marrow) provides the definitive diagnosis, though this is not always possible due to the kinetics of bacterial shedding and circulation at different sites or prior antibiotic usage, and that bone marrow culture (the most sensitive type of specimen) is not routinely performed in this setting. Serological testing has been an important adjunct to diagnosis. Unfortunately, the widely available Widal’s test is neither sensitive nor specific for this purpose, especially when only a single serum is tested. Newer serological assays such TUBEX TFTM (IDL Biotech, Sweden) and TyphidotTM (Reszon Diagnostics, Malaysia) have improvements over the Widal’s test, but their performance in the field has not been encouraging [37, 38]. Perhaps more promising in the future is the detection of Salmonella Typhi and Paratyphi in peripheral blood by NAAT [39]. This approach has the additional benefit of detecting other circulating pathogens as a panel (e.g. using multiplex PCR) for systemic febrile illnesses in travellers, such as Plasmodium, Babesia, Rickettsia, Orientia, and other pathogenic bacteria and viruses [40].

Entamoeba histolytica infection most often manifests as amoebic colitis; extraintestinal amoebiasis is less frequently seen and the usual presentation is amoebic liver abscess. Intestinal infection is mainly diagnosed by faecal microscopy. As in the case of other enteric parasites, multiple stool samples (usually at least three) should be examined. E. histolytica is morphologically identical to at least three other species of Entamoeba, viz. E. dispar, E. moshkovskii, and E. bangladeshi. Definitive identification is best achieved by molecular methods. Antigen detection assays are viable alternatives for the detection E. histolytica in stool [41]. Some of these kits can concurrently detect other enteric protozoa such as Giardia intestinalis and Cryptosporidium. Not all of the antigen detection assays, however, are able to differentiate E. histolytica and E. dispar. Microscopy is less useful in amoebic liver abscesses; amoebae are seen in only 20% or less of liver aspirates [42]. Stool samples of patients with amoebic liver abscesses have positive microscopy for E. histolytica in only 8–44% of the cases [42]. Antibody testing is helpful in the diagnosis of amoebic liver abscess; a positive serology is present in over 95% of the patients [41–43]. The major drawback of serology is that it cannot differentiate active from past infections with E. histolytica, and hence it is less useful for populations in endemic areas.

Other issues

Space does not permit further discussion on other travel-related infections. Two more recent issues may require attention from clinical and laboratory colleagues. Firstly, the transmission of epidemic-prone infectious diseases through travel, and in particular, air travel, has caused much concern in the past few years. Examples include avian influenza and other novel influenza viruses, MERS-CoV (and the SARS-CoV in 2003), Ebola virus and other agents of viral haemorrhagic fevers. Although these are relatively uncommon causes of infection in returned travellers (with the exception of pandemic influenza in 2009), transnational spread of these infections remains a constant threat to non-endemic countries and contingency plans for surveillance, screening, clinical management, infection control, and laboratory diagnostics must be formulated in anticipation [44].

Secondly, the importation of antibiotic-resistant bacteria from travellers has emerged as another menace [45–47]. The main microbes of concern include extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae, multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci. These may be causing active infections or merely colonizing the travellers. Areas with the highest risks are the Indian subcontinent, Southeast Asia, and Africa [48–51]. Encounters with hospitals or medical facilities abroad could be due to medical problems that appeared during travel or being part of an increasingly popular medical tourism. Admission screening for multidrug-resistant organisms should be considered for patients with recent hospitalization in overseas facilities.

And not just for the microbiologists

Although the majority of tests for infective complications among the returned travellers are performed by the clinical microbiology laboratory, other specialties of clinical pathology may sometimes be involved in the investigation. The commonest scenario is the examination of peripheral blood films by haematology colleagues for malaria parasites. In addition to Plasmodium species, other pathogens that may be seen in the blood films include Babesia spp., Trypanosoma spp. (the African T. brucei gambiense and T. brucei rhodesiense, as well as the American T. cruzi), microfilariae, and the spirochaete bacterium Borrelia spp. The identification of Babesia spp. is sometimes mistaken for Plasmodium spp. because of the presence of intra-erythrocytic ring forms [52]. The travel history, especially when the destination is not a malaria-endemic region, should alert the microscopist to the possibility of babesiosis. Other morphological features that are suggestive of Babesia include the absence of stipplings and malarial pigments, presence of multiple pleomorphic rings within a single erythrocyte, and arrangement of the parasites in a Maltese cross appearance. Borrelia burgdorferi, the cause of Lyme disease, is possibly the best-known Borrelia species. However, B. burgdorferi is not normally seen in the peripheral blood smear. When spirochaetes are observed, the possibility of tick-borne or louse-borne relapsing fever should be considered. Tick-borne borrelioses are zoonoses caused by over 30 species of Borrelia and they have a global occurrence. Louse-borne relapsing fever, on the other hand, is restricted to countries in the Horn of Africa (Ethiopia, Eritrea, Somalia, and Sudan) nowadays. It is caused by Borrelia recurrentis which causes infection in humans only. The significance of louse-borne relapsing fever as a potential re-emerging infection is highlighted by the recent cases reported amongst asylum seekers who travelled to Europe from East Africa [53–56]. Definitive identification of Borrelia species requires molecular testing of the blood sample by sequencing of the 16S rRNA gene and other targets.

In addition to blood smear examination, the anatomical pathologist may encounter unexpected or unusual infections. Some of these infections may present as subacute or chronic lesions and may be seen in immigrants from foreign countries rather than recent travellers. Examples include colonic or liver biopsies with E. histolytica or Schistosoma; soft tissue or visceral lesions due to larval stages of nematodes (such as dirofilariasis or onchocerciasis) or cestodes (such as sparganosis, cysticercosis); skin biopsy in patients with cutaneous or mucocutaneous leishmaniasis; bone marrow, liver, spleen, or lymph node biopsies in patients with visceral leishmaniasis. Most of these are relatively rare in Hong Kong, but they may spice up our otherwise mundane everyday routines.

References

1   World Tourism Organization (UNWTO). Press release No.: 15006, 27 January 2015. Available at: http://media.unwto.org/press-release/2015-01-27/over-11-billion-tourists-travelled-abroad-2014. Accessed on 29 November 2015.

2   Steffen R, Rickenbach M, Wilhelm U, Helminger A, Schär M. Health problems after travel to developing countries. J Infect Dis 1987;156:84–91.

3   Ahlm C, Lundberg S, Fessé K, Wiström J. Health problems and self-medication among Swedish travellers. Scand J Infect Dis 1994;26:711–717.

4   Hill DR. Health problems in a large cohort of Americans traveling to developing countries. J Travel Med 2000;7:259–266.

5   Rack J, Wichmann O, Kamara B, Günther M, Cramer J, Schönfeld C, Henning T, Schwarz U, Mühlen M, Weitzel T, Friedrich-Jänicke B, Foroutan B, Jelinek T. Risk and spectrum of diseases in travelers to popular tourist destinations. J Travel Med 2005;12:248–53.

6   Harvey K, Esposito DH, Han P, Kozarsky P, Freedman DO, Plier DA, Sotir MJ; Centers for Disease Control and Prevention (CDC). Surveillance for travel-related disease—GeoSentinel Surveillance System, United States, 1997–2011. MMWR Surveill Summ 2013;62:1–23.

7   Hagmann SH, Han PV, Stauffer WM, Miller AO, Connor BA, Hale DC, Coyle CM, Cahill JD, Marano C, Esposito DH, Kozarsky PE; GeoSentinel Surveillance Network. Travel-associated disease among US residents visiting US GeoSentinel clinics after return from international travel. Fam Pract 2014;31:678–687.

8   Boggild AK, Geduld J, Libman M, Ward BJ, McCarthy AE, Doyle PW, Ghesquiere W, Vincelette J, Kuhn S, Freedman DO,Kain KC. Travel-acquired infections and illnesses in Canadians: surveillance report from CanTravNet surveillance data, 2009–2011. Open Med 2014;8:e20–32.

9   Leder K, Torresi J, Libman MD, Cramer JP, Castelli F, Schlagenhauf P, Wilder-Smith A, Wilson ME, Keystone JS, Schwartz E, Barnett ED, von Sonnenburg F,Brownstein JS, Cheng AC, Sotir MJ, Esposito DH, Freedman DO; GeoSentinel Surveillance Network. GeoSentinel surveillance of illness in returned travelers, 2007–2011. Ann Intern Med 2013;158:456–468.

10 Centre for Health Protection. Number of notifications for notifiable infectious diseases in 2014. Available at http://www.chp.gov.hk/en/data/ 1/10/26/43/2280.html. Accessed on 2 December 2015.

11 Warrell DA. Clinical features of malaria. In: Gilles HM, Warrell DA (eds). Bruce-Chwatt’s Essential Malariology, 3rd ed. London: Arnold; 1993. p 35–49.

12 Brook MG, Bannister BA. The clinical features of imported malaria. Commun Dis Rep CDR Rev 1993;3:R28–31.

13 Dorsey G, Gandhi M, Oyugi JH, Rosenthal PJ. Difficulties in the prevention, diagnosis, and treatment of imported malaria. Arch Intern Med 2000;160:2505–2010.

14 Yombi JC, Jonckheere S, Colin G, Van Gompel F, Bigare E, Belkhir L, Vandercam B. Imported malaria in a tertiary hospital in Belgium: epidemiological and clinical analysis. Acta Clin Belg 2013;68:101–106.

15 Cheong HS, Kwon KT, Rhee JY, Ryu SY, Jung DS, Heo ST, Shin SY, Chung DR, Peck KR, Song JH. Imported malaria in Korea: a 13-year experience in a single center. Korean J Parasitol 2009;47:299–302.

16 Antinori S, Galimberti L, Milazzo L, Corbellino M. Plasmodium knowlesi: the emerging zoonotic malaria parasite. Acta Trop 2013;125:191–201.

17 Pasricha JM, Juneja S, Manitta J, Whitehead S, Maxwell E, Goh WK, Pasricha SR, Eisen DP. Is serial testing required to diagnose imported malaria in the era of rapid diagnostic tests? Am J Trop Med Hyg 2013;88:20–23.

18 Centers for Disease Control and Prevention (CDC). Treatment of malaria (guidelines for clinicians). Available at http://www.cdc.gov/malaria/resources/ pdf/clinicalguidance.pdf. Accessed on 2 December 2015.

19 White NJ. The treatment of malaria. N Engl J Med 1996;335:800–806.

20 Mouatcho JC, Goldring JP. Malaria rapid diagnostic tests: challenges and prospects. J Med Microbiol 2013;62:1491–1505.

21 Wong SS, Fung KS, Chau S, Poon RW, Wong SC, Yuen KY. Molecular diagnosis in clinical parasitology: when and why? Exp Biol Med (Maywood) 2014;239:1443–1460.

22 Cleton N, Koopmans M, Reimerink J, Godeke GJ, Reusken C. Come fly with me: review of clinically important arboviruses for global travelers. J Clin Virol 2012;55:191–203.

23 World Health Organization. Dengue: Guidelines for diagnosis, treatment, prevention and control. Available at: http://apps.who.int/iris/bitstream/ 10665/44188/1/9789241547871_eng.pdf. Accessed on 2 December 2015.

24 Centers for Disease Control, R.O.C. (Taiwan). Press release. 1 December 2015. http://www.cdc. gov.tw/english/info.aspx?treeid=bc2d4e89b154059b&nowtreeid=ee0a2987cfba3222&tid=03F130A967838822. Accessed on 2 December 2015.

25 Ratnam I, Leder K, Black J, Torresi J. Dengue fever and international travel. J Travel Med 2013;20:384–393.

26 Burt FJ, Rolph MS, Rulli NE, Mahalingam S, Heise MT. Chikungunya: a re-emerging virus. Lancet 2012;379:662–671.

27 Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Current Zika virus epidemiology and recent epidemics. Ioos S, Mallet HP, Leparc Goffart I, Gauthier V, Cardoso T, Herida M. Med Mal Infect 2014;44:302–307.

28 World Health Organization. Zika virus outbreaks in the Americas. Wkly Epidemiol Rec 2015;90:609–610.

29 Gubler DJ. Human arbovirus infections worldwide. Ann N Y Acad Sci 2001;951:13-24.

30 Matheus S, Pham TB, Labeau B, Huong VT, Lacoste V, Deparis X, Marechal V. Kinetics of dengue non-structural protein 1 antigen and IgM and IgA antibodies in capillary blood samples from confirmed dengue patients. Am J Trop Med Hyg 2014;90:438–443.

31 Gan VC, Tan LK, Lye DC, Pok KY, Mok SQ, Chua RC, Leo YS, Ng LC. Diagnosing dengue at the point-of-care: utility of a rapid combined diagnostic kit in Singapore. PLoS One 2014;9:e90037.

32 Korhonen EM, Huhtamo E, Virtala AM, Kantele A, Vapalahti O. Approach to non-invasive sampling in dengue diagnostics: exploring virus and NS1 antigen detection in saliva and urine of travelers with dengue. J Clin Virol 2014;61:353–358.

33 Sudiro TM, Zivny J, Ishiko H, Green S, Vaughn DW, Kalayanarooj S, Nisalak A, Norman JE, Ennis FA, Rothman AL. Analysis of plasma viral RNA levels during acute dengue virus infection using quantitative competitor reverse transcription-polymerase chain reaction. J Med Virol 2001;63:29–34.

34 Cnops L, Domingo C, Van den Bossche D, Vekens E, Brigou E, Van Esbroeck M. First dengue co-infection in a Belgian traveler returning from Thailand, July 2013. J Clin Virol 2014;61:597–599.

35 Parreira R, Centeno-Lima S, Lopes A, Portugal-Calisto D, Constantino A, Nina J. Dengue virus serotype 4 and chikungunya virus coinfection in a traveller returning from Luanda, Angola, January 2014. Euro Surveill 2014;19. pii: 20730.

36 Steffen R, Hill DR, DuPont HL. Traveler’s diarrhea. A clinical review. JAMA 2015;313(1):71–80.

37 Parry CM, Wijedoru L, Arjyal A, Baker S. The utility of diagnostic tests for enteric fever in endemic locations. Expert Rev Anti Infect Ther 2011;9:711–725.

38 Thriemer K, Ley B, Menten J, Jacobs J, van den Ende J. A systematic review and meta-analysis of the performance of two point of care typhoid fever tests, Tubex TF and Typhidot, in endemic countries. PLoS One 2013;8:e81263.

39 Tennant SM, Toema D, Qamar F, Iqbal N, Boyd MA, Marshall JM, Blackwelder WC, Wu Y, Quadri F, Khan A, Aziz F, Ahmad K, Kalam A, Asif E,Qureshi S, Khan E, Zaidi AK, Levine MM. Detection of typhoidal and paratyphoidal Salmonella in blood by real-time polymerase chain reaction. Clin Infect Dis 2015;61 Suppl 4:S241–250.

40 Watthanaworawit W, Turner P, Turner C, Tanganuchitcharnchai A, Richards AL, Bourzac KM, Blacksell SD, Nosten F. A prospective evaluation of real-time PCR assays for the detection of Orientia tsutsugamushi and Rickettsia spp. for early diagnosis of rickettsial infections during the acute phase of undifferentiated febrile illness. Am J Trop Med Hyg 2013;89:308–310.

41 Ali IK. Intestinal amebae. Clin Lab Med 2015;35:393–422.

42 Singh U, Petri Jr WA. Amebas. In: Gillespie S, Pearson RD (eds). Principles and Practice of Clinical Parasitology. Chichester: John Wiley & Sons; 2001. p 197–218.

43 Fotedar R, Stark D, Beebe N, Marriott D, Ellis J, Harkness J. Laboratory diagnostic techniques for Entamoeba species. Clin Microbiol Rev 2007;20:511–532.

44 Wong SS, Wong SC. Ebola virus disease in nonendemic countries. J Formos Med Assoc 2015;114:384–398.

45 Epelboin L, Robert J, Tsyrina-Kouyoumdjian E, Laouira S, Meyssonnier V, Caumes E; MDR-GNB Travel Working Group. High rate of multidrug-resistant gram-negative bacilli carriage and infection in hospitalized returning travelers: a cross-sectional cohort study. J Travel Med 2015;22:292–299.

46 Von Wintersdorff CJ, Penders J, Stobberingh EE, Oude Lashof AM, Hoebe CJ, Savelkoul PH, Wolffs PF. High rates of antimicrobial drug resistance gene acquisition after international travel, The Netherlands. Emerg Infect Dis 2014;20):649–657.

47 Josseaume J, Verner L, Brady WJ, Duchateau FX. Multidrug-resistant bacteria among patients treated in foreign hospitals: management considerations during medical repatriation. J Travel Med 2013;20:22–28.

48 Vila J. Multidrug-resistant bacteria without borders: role of international trips in the spread of multidrug-resistant bacteria. J Travel Med 2015;22:289–291.

49 Kuenzli E, Jaeger VK, Frei R, Neumayr A, DeCrom S, Haller S, Blum J, Widmer AF, Furrer H, Battegay M, Endimiani A, Hatz C. High colonization rates of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in Swiss travellers to South Asia—a prospective observational multicentre cohort study looking at epidemiology, microbiology and risk factors. BMC Infect Dis 2014;14:528.

50 Peirano G, Laupland KB, Gregson DB, Pitout JD. Colonization of returning travelers with CTX-M-producing Escherichia coli. J Travel Med 2011;18:299–303.

51 Freeman JT, McBride SJ, Heffernan H, Bathgate T, Pope C, Ellis-Pegler RB. Community-onset genitourinary tract infection due to CTX-M-15-producing Escherichia coli among travelers to the Indian subcontinent in New Zealand. Clin Infect Dis 2008;47:689–692.

52 Chau C. First reported case of imported babesiosis in Hong Kong. Communicable Disease Watch 2006;3:1–3.

53 Wilting KR, Stienstra Y, Sinha B, Braks M, Cornish D, Grundmann H. Louse-borne relapsing fever (Borrelia recurrentis) in asylum seekers from Eritrea, the Netherlands, July 2015. Euro Surveill 2015;20. pii: 21196.

54 Goldenberger D, Claas GJ, Bloch-Infanger C, Breidthardt T, Suter B, Martínez M, Neumayr A, Blaich A, Egli A, Osthoff M. Louse-borne relapsing fever (Borrelia recurrentis) in an Eritrean refugee arriving in Switzerland, August 2015. Euro Surveill 2015;20:2–5.

55 Hoch M, Wieser A, Löscher T, Margos G, Pürner F, Zühl J, Seilmaier M, Balzer L, Guggemos W, Rack-Hoch A, von Both U, Hauptvogel K, Schönberger K, Hautmann W, Sing A, Fingerle V. Louse-borne relapsing fever (Borrelia recurrentis) diagnosed in 15 refugees from northeast Africa: epidemiology and preventive control measures, Bavaria, Germany, July to October 2015. Euro Surveill 2015;20(42).

56 Lucchini A, Lipani F, Costa C, Scarvaglieri M, Balbiano R, Carosella S, Calcagno A, Audagnotto S, Barbui AM, Brossa S, Ghisetti V, dal Conte I, Caramello P, di Perri G. Louse-borne relapsing fever among east African refugees, Italy, 2015. Emerg Infect Dis 2016. In press. Available at http://wwwnc.cdc.gov/eid/article/22/2/15-1768_article. Accessed on 28 November 2015.

 

Table 1. Illnesses in returned international travellers from GeoSentinel surveillance.

Country

USA [6]

USA [7]

Canada [8]

Global centres [9]

Years

1997–2011

2000–2012

2009–2011

2007–2011

Number of travellers studied

10,032

9,624

4,365

42,173

Systems involved

 

 

 

 

Gastrointestinal tract

45%

58.4%

43.7%

34.0%

Respiratory system

8%

10.8%

5.4%

10.9%

Skin

12%

16.6%

14.7%

19.5%

Fever or systemic illness

14%

18.2%

10.8%

23.3%

Neurological system

 

 

 

1.7%

Genito-urinary tract and gynaecological system, sexually-transmitted infections

 

 

 

2.9%

 

Table 2. Causes of fever in returned international travellers from GeoSentinel surveillance.

Country

USA [6]

USA [7]

Canada [8]

Global centres [9]

Years

1997–2011

2000–2012

2009–2011

2007–2011

Number of patients presenting with fever or systemic illness

1802

1748

675

9817

Diagnoses

 

 

 

 

Malaria

19.4%

27.4%

11.9%

28.7%

Dengue

11.1%

12%

7.1%

15.0%

Chikungunya

 

 

0.9%

1.7%

Enteric fever

 

6.1%

4.1%

4.8%

Respiratory tract infections

 

 

6.7%

 

Active tuberculosis

 

 

7%

 

Urinary tract infection

 

 

1.5%

 

Rickettsioses

 

4.7%

0.7%

3.0%

Leptospirosis

 

 

 

0.8%

Brucellosis

 

 

0.9%

0.3%

Hepatitis A and E

 

 

 

1.7%

Acute HIV infection

 

 

 

0.9%

Viral syndrome

17.1%

18.5%

 

 

Unspecified febrile illness

8.2%

 

 

 

Epstein-Barr virus infection and infectious mononucleosis-like syndrome

4.4%

8.7%

 

 

 

Table 3. Exposure history that should raise suspicion to specific infections.

Exposure

Potential infective complications

Sex, blood, body fluids, surgical operations, intravenous drug use

Hepatitis B and C, HIV infection, syphilis

Tattoos, body piercing, other body modification procedures

Hepatitis B and C, HIV infection, syphilis, non-tuberculous mycobacterial infections

Hospitalization

Antibiotic-resistant bacteria (colonization or infection)

Ingestion of raw or undercooked food

Various foodborne infections including bacterial and viral gastroenteritis, protozoal and helminth infections, brucellosis, listeriosis, toxoplasmosis, hepatitis A and E

Soil

Histoplasmosis, coccidioidomycoses, other endemic mycoses,
cutaneous larva migrans, strongyloidiasis

Freshwater

Schistosomiasis (Katayama fever), leptospirosis

Arthropod bites

Various arthropod-borne infections, such as dengue, chikungunya, Zika virus infection, rickettsioses, relapsing fevers, malaria, babesiosis, leishmaniasis, trypanosomiasis, dirofilariasis

Dog, bat and other animal bites

Rabies, bat rabies, herpes B virus infection, bite wound infections

Animals and animal products

Hantaviruses, Lassa fever, Crimean-Congo haemorrhagic fevers, avian influenza, MERS, plague, rat-bite fevers, leptospirosis, Q fever, brucellosis, tularaemia, anthrax, psittacosis.

Note that the exact risk of specific infections depends not only on the exposure history, but the geographical location of exposures.

 

Table 4. Some common arboviruses and their typical clinical syndromes.

Common clinical syndromes

Common causative agents

Systemic febrile illness ± rash

Dengue virus, West Nile virus, Yellow fever virus, Zika virus, chikungunya virus

Arthralgia, arthritis ± rash

Chikungunya virus, Ross River virus, Barmah Forest virus, dengue virus, West Nile virus, O’nyong’nyong virus

Encephalitis or meningoencephalitis

Japanese encephalitis virus, Murray Valley encephalitis virus, St. Louis encephalitis virus, West Nile virus, tick-borne encephalitis virus, California encephalitis virus, La Crosse virus, Rift Valley fever virus, Toscana virus, Eastern equine encephalitis virus, Venezuelan equine encephalitis virus, Western equine encephalitis virus

Viral haemorrhagic fevers

Crimean-Congo haemorrhagic fever, Rift Valley fever virus, yellow fever virus, dengue virus, Kyasanur Forest disease virus, Omsk haemorrhagic fever, severe fever with thrombocytopenia syndrome virus

Note that the clinical syndromes and severity of disease caused by any single arbovirus can vary substantially. For example, many infections can either be subclinical or manifest as undifferentiated fever or produce a fulminant disease, such as viral haemorrhagic fever or meningoencephalitis. The likelihood of various potential pathogens depends on the exact geographical areas involved.

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Pathology of Non-Alcoholic Fatty Liver Disease

"Non-alcoholic fatty liver disease1" by Nephron - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Non-alcoholic_fatty_liver_disease1.jpg#/media/File:Non-alcoholic_fatty_liver_disease1.jpg

Volume 10, Issue 1, January 2015

Dr. Anthony W.H. Chan

Associate Professor Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a serious global health problem and associated with over-nutrition and its related metabolic risk factors including central obesity, glucose intolerance, dyslipidaemia and hypertension. It is the most common metabolic liver disease worldwide and its prevalence in most Asian countries is similar to that in the States, Europe and Australia. About 10-45% of Asian population have NAFLD. With “westernized” sedentary lifestyle, the prevalence of NAFLD in general urban population in the mainland China is about 15%. NAFLD is even more prevalent in Hong Kong. Our recent study demonstrated that NAFLD is found in 27.3% of Hong Kong Chinese adults by using proton-magnetic resonance spectroscopy. We further realized that 13.5% of Hong Kong Chinese adults newly develop NAFLD in 3-5 years. Both prevalence and incidence of NAFLD in Hong Kong are alarmingly high. Accurate diagnosis of NAFLD is crucial to allow prompt management of patients to reduce morbidity and mortality. NAFLD is composed of a full spectrum of conditions from steatosis to steatohepatitis (NASH) and cirrhosis. Various non-invasive tests, based on clinical, laboratory and radiological tests, have been developed to assess the degree of steatosis and fibrosis in NAFLD. However, liver biopsy remains the gold standard for characterizing liver histology in patients with NAFLD, and is recommended in patients with NAFLD at high-risk of steatohepati tis and advanced fibrosis (bridging fibrosis and cirrhosis), and concurrent chronic liver disease of other aetiology. This article reviews pathological features of NAFLD and highlights some practical points for our daily diagnostic work.

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Molecular Classification and Genetic Alterations of Diffuse Large B-cell Lymphoma

"Glass ochem" by Purpy Pupple - Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Glass_ochem.png#/media/File:Glass_ochem.png

Volume 9, Issue 2, July 2014

Dr CHOI Wai Lap

Department of Clinical Pathology Tuen Mun Hospital

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the commonest subtype of non-Hodgkin lymphoma, accounting for about 30% to 40% of newly diagnosed non-Hodgkin lymphoma worldwide and in Hong Kong. DLBCL is heterogeneous in clinical presentation, morphology, immunophenotype, cytogenetics and prognos is. In the WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues published in 2008, several specific clinicopathological entities of DLBCL have been recognized, while leaving the rest to DLBCL, not otherwise specified, which is by far the most prevalent entity among the large B-cell lymphomas. In the following discussion, the term DLBCL will be used interchangeably with DLBCL, not otherwise specified.

Gene expression profiling and molecular classification of DLBCL

Gene expression profiling (GEP) is the simultaneous measurement of the transcription levels of thousands of genes to their corresponding messenger RNAs (mRNAs). GEP can be achieved by various technologies including DNA microarray, serial analysis of gene expression (SAGE) and most recently next generation sequencing (RNA-Seq). Using DNA microarray technology on DLBCL, two distinct molecular subgroups were discovered based on the similarity of their gene expression pattern with a possible cell of origin (COO): the germinal centre B-cell-like (GCB-cell-like, or abbreviated as GCB) and the activated B-cell-like(ABC-like, or abbreviated as ABC). These molecular subgroups showed significantly different survival rates when treated with conventional cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapeutic regimen.

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Thyroid Dyshormonogenesis

Volume 9, Issue 1, January 2014

Dr YUEN Yuet Ping

Department of Chemical Pathology Prince of Wales Hospital

Introduction

Congenital hypothyroidism (CH) is an important preventable cause of mental retardation. To prevent irreversible brain damages caused by hypothyroidism, sufficient doses of thyroxine should be started within a few weeks after birth.(1) Since neonates with CH have no obvious or minimal clinical manifestations, biochemical screening in the newborn period has become the best public health strategy for early detection of affected neonates. In Hong Kong, a territory-wide screening programme for CH was started in 1984.(2) Cord blood samples are collected immediately after birth for measurement of thyroid stimulating hormone (TSH) by a single laboratory dedicated for newborn screening. The incidence of CH in Hong Kong was reported to be 1 in 2,404, which is comparable to that in other populations.

Causes of congenital hypothyroidism

The aetiologies of CH are summarized in Table 1.(7) Approximately 80-85% of CH are caused by thyroid dysgenesis, which is a group of congenital disorders of thyroid gland development or migration. Affected patients may have complete thyroid gland aplasia, hypoplasia or ectopic glands. The large majority of thyroid dysgenesis cases are sporadic and only about 5% has a genetic basis.(8,9) Thyroid dyshormonogenesis describes a group of inherited disorders which affect the biochemical pathway of thyroid hormone synthesis. These disorders collectively account for 10-15% of CH cases. Approximately 1/4 of patients with CH in Hong Kong have some forms of thyroid dyshormonogenesis.(10) Some neonates detected by newborn screening program have transient instead of permanent CH. Although this subgroup of patients does not require life- long thyroid hormone replacement, early identification and treatment in early years of life is equally important.(11) The time course of recovery of the hypothalamic-pituitary-thyroid axis in patients with transient CH depends on the underlying cause. Although most of the transient CH are due to acquired conditions such as iodine deficiency or maternal transfer of autoantibodies, a few genetic causes have been described.

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Epidemiology of Cervical Human Papillomavirus Infection in Hong Kong: Implications on Preventative Strategy

Volume 8, Issue 2, July 2013

Prof. Paul KS Chan

Professor, Department of Microbiology, Prince of Wales Hospital The Chinese University of Hong Kong

Introduction

The family Papillomaviridae is comprised of a large group of viruses found in many mammalian species. Infection with papillomaviruses can be asymptomatic or results in the development of benign or malignant neoplasia. Cervical cancer is the most important consequence, in terms of disease burden, of human papillomavirus (HPV) infection. To date, the genomic sequences of more than 150 HPV types have been characterized. Of these, more than 40 types can infect the female genital tract, and at least 15 types are epidemiologically linked to cervical cancer. Over the last few years, there has been a vast increase in using HPV DNA detection as an adjunctive or primary tool in cervica l cancer screening programmes. Primary prevention of cervical cancers associated with the two most common types (HPV16 and HPV18) can now be achieved by vaccination. A thorough understanding on the epidemiology of cervical HPV infection is essential to maximize the clinical benefits and cost-effectiveness of HPV-based diagnostic tests and vaccines. In this review, some key epidemiological features of HPV infection in Hong Kong are presented to assist the formulation of strategies applicable to Hong Kong.

Prevalence of infection

“How common is cervical HPV infection?” This is always the first question to ask before any advice on vaccination can be made. Local studies on “well-women” self-referred for cervical screening showed that the prevalence of cervical HPV infection (defined as having an HPV DNA-positive cervical scrape sample) was around 8% among adult women aged 26-45 years. 1,2 The figure “1 in 12” is recommended for public education. While the studies reported a significant association between number of life-time sexual partners and smoking exposure, the prevalence among those without any recognizable risk factors is high enough to recommend vaccination in general for everyone.

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Laboratory Testing For Anti-NMDAR In Autoimmune Encephalitis: The HSSA- Pathology Queensland Experience

Volume 8, Issue 1, January 2013

Bob Wilson MSc, FFS(RCPA), Kerri Prain, BSc, David Gillis, FRCPA FRACP FFS(RCPA) and Richard Wong GDM FRCPA FRACP FRCP.

Division of Immunology, Central Laboratory, HSSA-Pathology Queensland, Royal Brisbane and Women’s Hospitals, Herston, Brisbane, 4061, Australia.

Introduction

The spectrum of antibodies against intracellular, cell surface and synaptic neuronal antigens has expanded rapidly in recent years. The antigenic targets include ion channels, receptors involved in neurotransmission across synapses and proteins associated with them. There are now more than twenty anti-neuronal antibodies detected in association with neurological diseases. These antibodies may be associated with underlying malignancies and are commonly referred to as paraneoplastic antibodies (PNAs). Many PNAs have been correlated with neurological manifestations and fall into two groups: those that are cytotoxic for example anti-purkinje cell antibody-1 (PCA-1/Yo) and anti-neuronal nuclear antibody-1 (ANNA-1/Hu); and others that have functional activity, such as anti-N-Methyl-D-Aspartate receptor (NMDAR) and anti-Voltage-gated potassium channel (VGKC). Recently there has been a marked interest in both anti-NMDAR and anti-VGKC antibodies as the presence of these antibodies identify patients with treatable neurological disease.

Anti-NMDAR was initially described as a paraneoplastic antibody associated with ovarian teratoma, with a characteristic clinical picture of encephalitis with psychiatric features, cognitive dysfunction and seizures. 1 2 Although subsequent case series have confirmed that ovarian teratoma is a frequent association, it has become apparent that many patients who are positive for anti-NMDAR do not have evidence of an associated malignancy.

There is also some evidence supporting the need for rapid identification of anti-NMDAR. Patients who are diagnosed and treated with immuno-suppressive/immunomodulatory therapy within 40 days of disease onset, have been reported to have a better clinical outcome than those treated after 40 days.

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Virtual Electron Microscopy – update after one year of routine use

Volume 7, Issue 2, July 2012

Dr. King Chung Lee

Consultant Pathologist, St. Paul’s Hospital

Honorary Consultant, Queen Elizabeth Hospital

Background

Virtual microscopy using whole slide scanning has become increasingly popular in quality assurance program, teaching of pathologists and undergraduates and reproducibility studies 1-2. This concept was first extended to electron microscope (EM) about a year ago 3. This is made possible by two discoveries. Firstly, a free software component capable of stitching sequential pictures into a virtual slide that can be read by another free software. Secondly, an EM function capable of capturing up to 500 images covering a specified area automatically. Because of the simplicity acceptable degree of user intervention during the process and unsurpassed advantages over the conventional method, it was quickly adopted in routine renal biopsy diagnostic EM service and become the only routine service virtual microscopy system in Hong Kong. For those who are interested, you can download a sample from http://kvisit.com/SsKKqAQ and view it by Aperio ImageScope software, which was available for free download from the Aperio website, http://www.aperio.com/download-imagescope-viewer.asp

Summary of implementation

In the last year, over 400 renal biopsy cases were handled in our EM laboratory and over 1000 virtual ultrathin sections were generated (average 2.7 sections per case). The average EM time used in capturing is about 50 minutes per section. The average computing time is 40 minutes per section. The virtual ultrathin sections were either directly interpreted by Pathologists or screened and annotated by our EM tec hnologist before passing to Pathologists.

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Chronic lymphocytic leukaemia – the role of conventional and molecular cytogenetics

Volume 7, Issue 1, January 2012

Dr W. S. Wong

Associate Consultant, Department of Pathology, Queen Elizabeth Hospital

Dr. K.F. Wong Chief of Service, Department of Pathology, Queen Elizabeth Hospital

Introduction

Chronic lymphocytic leukaemia (CLL) is the commonest chronic lymphoproliferative disorder of mature B-cells and affects mainly elderly. It is characterized by the presence of≥5x109/L monoclonal and often CD5+CD23+B-lymphocytes in peripheral blood. Haematogists usually have no problem in reaching the diagnosisas the majority of the cases have classical morphological and immunophenotypic features; however, it is an extremely heterogeneous disease clinically with highly variable clinical course.

Some patients are asymptomatic and do not require treatment while others progress early and require aggressive treatment. A number of clinical and biological parameters as well as molecular biomarkers have been demonstrated to predict the clinical outcome of the disease [1]. Molecular diagnostics has greatly improved the understanding of pathogenesis of CLL by pointing to candidate genes, for example 17p13 deletion, a common genetic aberration seen in CLL, corresponds to a tumour suppressor gene TP53. Moreover, different genetic subgroups have been shown to be associated with different prognosis: poor survival in 17p or 11q deletions and better survival in trisomy 12, normal karyotype or 13q deletion with the best survival found in isolated 13q deletion [2]. Cytogenetic studies may also help in the diagnosis of problem cases with atypical morphology or immunophenotypic profiles.

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Laboratory Role in Toxicology: From Diagnostic to Theranostic

Volume 6, Issue 1, July 2011

Dr W. T. Poon

Associate Consultant, Department of Pathology, Princess Margaret Hospital

Introduction

Toxicology analysis involves detection, identification and measurement of foreign compounds and their metabolites in biological and other specimens. It plays a useful role in them a nagement of poisoned patients when the diagnosis is in doubt, the administration of antidotes or protective agents is contemplated, or the use of active elimination therapy is being considered. As the scope and complexity of clinical toxicology continues to increase, continuing effort is required for the laboratory to expand its diagnostic capability and coverage. Apart from patient care, identification of a lethal or emerging toxin also serves to provide useful information for toxico-vigilance of potential public health threats and helps to prevent further poisonings. Some common and important herbal poisonings that have occurred in Hong Kong would be discussed as examples.

Apart from poisoning diagnosis, laboratory test can be used to predict the risk of adverse event to drugs in individual patients. It is now feasible to identify the genetic basis for certain toxic side effects and drugs will then be prescribed only to those who are not genetically at risk. Theranostic is the term used to describe the process of diagnostic therapy for individual patients - to test them for possible reaction to taking a new medication and to tailor a treatment for them based on the test results. In Hong Kong, genotyping for human lymphocyte HLA-B*1502 is recommended prior to administering carbamazepine for patients in order to avoid the development of Stevens-Johnson syndrome. An increasing number of pharmacogenetic tests are now available for clinical application. The criteria required of a pharmacogenetic test to make it useful for local application would be discussed.

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Discovery of novel microbes: more and more coronaviruses after the SARS epidemic

Volume 5, Issue 2, December 2010

WOO, Patrick CY

Professor, Department of Microbiology, The University of Hong Kong

Coronavirus study group, International Committee for Taxonomy of Viruses

Introduction

The Coronaviridae family is classified into two subfamilies, Coronavirinae and Torovirinae. Members of the Coronavirinae subfamily are in general referred to as coronaviruses. Phenotypically, coronaviruses are enveloped viruses of 120-160 nm in diameter. Under electronmicroscopy, coronaviruses have a crown-like appearance and the name “coronavirus” is derived from the Greek word κορώνα, which means crown. Genotypically, coronaviruses are positive-sense, single-stranded RNA viruses with genome sizes of about 30 kb, the largest genome size among all RNA viruses. Traditionally, coronaviruses were classified into three groups based on their antigenic relationships. Groups 1 and 2 are madeup of mammalian coronaviruses and group 3 aviancoronaviruses. Recently, the Coronavirus Study Group of the International Committee for Taxonomy of Viruses (ICTV) has proposed three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, to replace these threetraditional groups of coronaviruses. Before 2003, there were less than 10 coronaviruses with complete genomes available, with only two human coronaviruses, namely human coronavirus 229E (HCoV-229E) and human coronavirus OC43 (HCoV-OC43), which were discovered in the 1960s. The SARS epidemic in 2003 has boosted interest in coronavirus research globally; and most notably, in the discovery of novel coronaviruses and their genomics. In the past six years, our group has discovered 13 novel coronaviruses, including one novel human coronavirus [human coronavirus HKU1 (HCoV-HKU1)], SARS-related Rhinolophus batcoronavirus (SARSr-Rh-BatCoV), eight other bat coronaviruses and three avian coronaviruses, and has sequenced the genomes of nine of them(1-5). Others have also discovered additional coronaviruses, the most notable being human coronavirus NL63 (HCoV-NL63), discovered by a group in the Netherlands (6).

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