-------------------- ~Things may happen in my life time to change who I am but I refuse to let them reduce me...~ Posts: 968 | From private | Registered: Jan 2005
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Anyone hear of this? It is called HTLV 1 and HTLV11..
-------------------- ~Things may happen in my life time to change who I am but I refuse to let them reduce me...~ Posts: 968 | From private | Registered: Jan 2005
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treepatrol
Honored Contributor (10K+ posts)
Member # 4117
posted
Why do you have it?
-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
posted
yeah, but nothing was done about it. I looked it up finally and it looks serious. Can't figure out where on earth I got it from. My family did immigrate here from Europe..
It looks to affect certain ethnicities more...
donno..
you find anything on it?
-------------------- ~Things may happen in my life time to change who I am but I refuse to let them reduce me...~ Posts: 968 | From private | Registered: Jan 2005
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treepatrol
Honored Contributor (10K+ posts)
Member # 4117
posted
dang double post
-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
Human T-cell Leukemia Virus Type 1 Molecular Variants, Vanuatu, Melanesia Olivier Cassar, Corinne Capuano,Laurent Meertens, Eliane Chungue, and Antoine Gessain Institut Pasteur de Nouvelle-Cal�donie, Noum�a, France; Institut Pasteur, Paris, France; and World Health Organization, Port-Vila, Vanuatu
Four of 391 Ni-Vanuatu women were infected with variants of human T-cell leukemia virus type 1 HTLV-1 Melanesian subtype C. These strains had env nucleotide sequences 99% similar to each other and diverging from the main molecular subtypes of HTLV-1 by 6% to 9%. These strains were likely introduced during ancient human population movements in Melanesia.
Human T-cell leukemia virus type 1 HTLV-1, a human oncoretrovirus, is the etiologic agent of adult T-cell leukemia and of tropical spastic paraparesis HTLV-1-associated myelopathy. Molecular epidemiologic studies have shown HTLV-1 proviruses to be remarkably stable genetically. The low levels of genetic drift in this virus have been used as a means for monitoring viral transmission and the movement of ancient human populations 1,2. The few nucleotide substitutions observed in HTLV-1 strains are specific to the geographic origin of the patient and are unrelated to viral pathology 1,2. Four major geographic HTLV-1 subtypes have been described: subtype A, cosmopolitan 1,2;subtype B, central African; subtype C, Melanesian 3-6; and subtype D, present in central Africa, mainly in pygmies.
Previous reports have indicated that HTLV-1 is endemic in some remote or ancient populations in Melanesia 3-14. These populations include a small number of tribes from Papua New Guinea especially the Hagahai people 5 and some inhabitants of the Solomon Islands 7. Evidence of HTLV-1 infection has also been found in some aboriginal groups from Australia 8. Rare cases of adult T-cell leukemia and tropical spastic paraparesis HTLV-1-associated myelopathy have also been described in these populations 9.
Genetic characterization of the few available Melanesian HTLV-1 strains has indicated that these HTLV-1 strains are the most divergent, constituting molecular subtype C (also called Melanesian subtype 3,4,6,10 in phylogenetic analyses. The discovery of such divergent variants has increased our understanding of the migration of HTLV-1-infected populations throughout the Pacific region. Furthermore, 1 of the calibration methods frequently used, in phylogenetic analyses, to estimate a time scale for the evolution of HTLV and simian T-cell leukemia virus STLV appears to coincide with the first human migrations to Melanesia and Australia 40,000-60,000 years ago 2.
We carried out a large serologic and molecular study to determine the prevalence of HTLV-1 and associated diseases in the Vanuatu Archipelago. Vanuatu, formerly known as the New Hebrides, is a Y-shaped archipelago made up of 80 islands. It is located in Melanesia, in the South Pacific region, northeast of Australia and south of the Solomon Islands. Vanuatu has a population of 200,000 inhabitants, most of whom 95% are of Melanesian origin and are known as the Ni-Vanuatu.
ecade ago and were not based on stringent serologic criteria 11-14. No molecular characterization data are available for HTLV-1 from this area. The main goals of this study were to evaluate the situation concerning HTLV-1 infection in a remote Ni-Vanuatu population by using stringent serologic criteria for Western blotting and molecular characterization of the viruses.
The Study In February 2002, we recruited 391 women during a clinical survey for sexually transmitted diseases in various remote rural communities of western Ambae Island in the Penama Province of the Vanuatu Archipelago. Ambae Island, also known as Aoba, has a population of 9,500. The women participating in this survey were offered a complete clinical examination, with Papanicolaou test analysis for all women 25 years of age. For each participant, we obtained plasma and buffy coats from 5 mL of blood obtained by venipuncture. The blood samples were rapidly transferred to Institut Pasteur de Nouvelle-Cal�donie, where plasma and buffy coats were isolated, frozen, and stored at -80�C until HTLV screening. Informed consent was obtained from each woman participating in the field survey. This study was approved by the Ministry of Health of the Republic of Vanuatu and was supported by the Vanuatu Family Health Association, a local nongovernmental organization. Samples were taken from 391 women (mean age 36 years, range 16-82 years with the following stratification by age: 11.2% from women 15-24 years of age, 28.4% from women 25-34 years of age, 31.2% from women 35-44 years of age, 17.4% from women 45-54 years of age, and 11.8% from women 55 years of age.
Plasma HTLV-1 antibodies were detected by enzyme-linked immunosorbent assay ELISA HTLV-I+II, Abbott-Murex, Kent, United Kingdom with Western blot HTLV-I/II Blot 2.4, Diagnostic Biotechnology, Singapore used for confirmation. On Western blot, plasma samples were considered HTLV-1-positive if they reacted to the 2 Gag proteins p19 and p24 and both env-encoded glycoproteins: the HTLV-1-specific recombinant gp46-I peptide MTA-1 and the specific HTLV-1 HTLV-2 recombinant GD 21 protein. Plasma samples were considered negative when no band were shown and indeterminate when partially reactive 15,16.
Figure 1. Representative seroreactivity pattern on Western blot that contains a recombinant GD 21...
Figure 2. Unrooted phylogenetic tree generated by the neighbor-joining method by using the 522-bp fragment of the env gene...
Appendix Figure
Appendix Figure. Unrooted phylogenetic tree generated by the neighbor-joining method by using the complete fragment... Forty-nine of the 391 plasma samples studied tested positive or borderline by ELISA, and 4 of these samples displayed full reactivity on Western blot Figure 1. One sample also displayed a typical HTLV gag-indeterminate profile 16, and 6 displayed weak reactivity 19 or GD 21 bands. The 4 plasma samples testing positive by Western blot had higher immunofluorescence assay titers on MT2 HTLV-1 cells than on C19 HTLV-2 cells and high particle agglutination titers Table 1. We carried out a second serologic survey on 64 members of the families of the 4 women seropositive for HTLV-1. This survey identified 2 more infected women; 1 was the mother of an index patient, and the other was the sister-in-law of another index patient Table 1. These results confirm the circulation of HTLV-1 in this population.
High molecular-weight DNA was extracted from buffy coats from the 4 HTLV-1-seropositive women, 5 HTLV-1-seronegative persons, and 6 others with indeterminate Western blot results, by using the QIAamp DNA Blood Mini Kit Qiagen GmbH, Hilden, Germany. The 15 DNA samples studied were subjected to polymerase chain reaction with primers specific for the human b-globin gene to check that cellular DNA was amplifiable for all samples 17. We then subjected DNA samples to 2 series of polymerase chain reaction to obtain the complete long terminal repeat LTR 755 bp and a 522-bp region of the env gene as previously described 18. Fragments of the appropriate size were amplified for the 4 HTLV-1-seropositive women, whereas the other 11 samples yielded negative results. The amplified products were cloned and sequenced, and phylogenetic studies were performed as previously described 18. Both the complete LTR and the 522-bp env fragment were obtained for the 4 HTLV-1-seropositive women.
Conclusions The gp21 gene sequences of the 4 HTLV-1 strains involved were almost identical 99.6%-99.8 % nucleotide similarity and were very similar to those of Melanesian strains. These strains were closely related 99.4% to certain strains from Solomon Islanders Mel 4, 8 but were only 97.1%-98.3% similar to strains from Papua New Guinea residents Mel 2, 7 and from Australian aborigines MSHR-1, respectively. Finally, the sequences of these new strains diverged from those of HTLV-1 strains from the 3 other main molecular subtypes A, B, D by 6% to 9%.
The 4 new HTLV-1 LTR sequences were also very closely related 98%-100% nucleotide similarity. They displayed 2% nucleotide divergence from Mel 5 from a Solomon Islander, the only available LTR from all the HTLV-1 subtype C strains. However, they also displayed up to 11% nucleotide divergence from HTLV-1 strains from other molecular subtypes.
Phylogenetic analyses were performed on all the available env and LTR HTLV-1 sequences from Melanesia, and on several representatives of HTLV-1 and STLV-1 strains from the various subtypes/subgroups as described 18, by the neighbor-joining N method. Similar tree topologies were obtained for both genomic regions Figure 2 and Appendix Figure. Analyses of these trees confirmed that the 4 novel Vanuatu HTLV-1 strains were closely related to all available HTLV-1 subtype C strains Table 2. Indeed, in the env analysis, which included 71 HTLV-1 strains including 12 Melanesian strains and 1 from an Australian aborigine, Table 2 and 55 STLV-1 strains, the 4 new HTLV-1 strains clustered with subtype C Figure 2. This subtype only includes strains from Australia, Papua New Guinea, the Solomon Islands, and Vanuatu. Within this clade are at least 2 subgroups, strongly supported phylogenetically: 1 comprises the Vanuatu strains and most of the strains from the Solomon Islands bootstrap values of 88%, and the other comprises the 3 isolates from Papua New Guinea the Hagahai population, with a bootstrap value of 100%. Two other unique and divergent strains, the only strain available from an Australian aborigine MSHR-1 and the other from a Solomon Islander Mel-12, may represent prototypes of 2 other clades within the Melanesian subtype C.
In conclusion, we report, for the first time, the presence of HTLV-1 infection in a Ni-Vanuatu population living in remote villages. We also demonstrate that the viruses infecting these Ni-Vanuatu persons are novel HTLV-1 molecular variants belonging to the Melanesian divergent C subtype. This finding suggests that these viruses were introduced into Vanuatu by ancient migrations of Melanesian populations. The first people to reach Santa Cruz, Banks, Vanuatu, and the Loyalties Islands 3,600 years ago seem to have been Austronesian speakers 19. Epidemiologic and clinical surveys are under way in this area to determine the extent of such retroviral infection and associated neurologic and hematologic diseases. In addition, studies of viral and mitochondrial/nuclear DNA are being conducted and should provide insight into the migrations of the first settlers and the origin, evolution, and modes of dissemination of such retroviruses.
Acknowledgments We thank Myriam Abel, Maturine Tary, Rose Bahor, Yvanna Taga, and Rachel Wells for their continual support and interest in this work; Blandine Boulekone, H�l�ne Walter, and Woreka Mera for field work; Sylviane Bassot, Fran�oise Charavay, and Fr�deric Touzain for excellent assistance during serologic testing of the samples; and Renaud Mahieux for critically reviewing this manuscript.
This study received financial support from the Institut Pasteur, the Institut Pasteur de Nouvelle-Caledonie, and the Regional Office for the Western Pacific of the World Health Organization WHO-WPRO. Laurent Meertens was supported by a fellowship from the Caisse Nationale d'Assurance Maladie CANAM and the Pasteur-Weizmann Foundation.
Mr. Cassar is a PhD student whose primary research interests are the clinical and molecular epidemiology and physiopathology of dengue viruses. He is currently working on the epidemiology of HTLV-1 in Melanesian populations.
References Gessain A, Gallo RC, Franchini G. Low degree of human T-cell leukemia/lymphoma virus type I genetic drift in vivo as a means of monitoring viral transmission and movement of ancient human populations. J Virol. 1992;66:2288-95. Slattery JP, Franchini G, Gessain A. Genomic evolution, patterns of global dissemination, and interspecies transmission of human and simian T-cell leukemia/lymphotropic viruses. Genome Res. 1999;9:525-40. Gessain A, Boeri E, Yanagihara R, Gallo RC, Franchini G. Complete nucleotide sequence of a highly divergent human T-cell leukemia lymphotropic virus type I HTLV-I variant from Melanesia: genetic and phylogenetic relationship to HTLV-I strains from other geographical regions. J Virol. 1993;67:1015-23. Gessain A, Yanagihara R, Franchini G, Garruto RM, Jenkins CL, Ajdukiewicz AB, et al. Highly divergent molecular variants of human T-lymphotropic virus type I from isolated populations in Papua New Guinea and the Solomon Islands. Proc Natl Acad Sci U S A. 1991;88:7694-8. Saksena NK, Sherman MP, Yanagihara R, Dube DK, Poiesz BJ. LTR sequence and phylogenetic analyses of a newly discovered variant of HTLV-I isolated from the Hagahai of Papua New Guinea. Virology. 1992;189:1-9. Yanagihara R. Geographic-specific genotypes or topotypes of human T-cell lymphotropic virus type I as markers for early and recent migrations of human populations. Adv Virus Res. 1994;43:147-86. Yanagihara R, Ajdukiewicz AB, Garruto RM, Sharlow ER, Wu XY, Alemaena O, et al. Human T-lymphotropic virus type I infection in the Solomon Islands. Am J Trop Med Hyg. 1991;44:122-30. Bastian I, Gardner J, Webb D, Gardner I. Isolation of a human T-lymphotropic virus type I strain from Australian aboriginals. J Virol. 1993;67:843-51. Seaton RA, Wembri JP, Nwokolo NC. Clinical associations with human T-cell lymphotropic virus type-I in Papua New Guinea. Med J Aust. 1996;165:403-6. Nerurkar VR, Song KJ, Bastian IB, Garin B, Franchini G, Yanagihara R. Genotyping of human T cell lymphotropic virus type I using Australo-Melanesian topotype-specific oligonucleotide primer-based polymerase chain reaction: insights into viral evolution and dissemination. J Infect Dis. 1994;170:1353-60. Asher DM, Goudsmit J, Pomeroy KL, Garruto RM, Bakker M, Ono SG, et al. Antibodies to HTLV-I in populations of the southwestern Pacific. J Med Virol. 1988;26:339-51. Brindle RJ, Eglin RP, Parsons AJ, Hill AV, Selkon JB. HTLV-1, HIV-1, hepatitis B and hepatitis delta in the Pacific and South-East Asia: a serological survey. Epidemiol Infect. 1988;100:153-6. Nicholson SR, Efandis T, Dimitrakakis M, Karopoulos A, Lee H, Gust ID. HTLV-I infection in selected populations in Australia and the western Pacific region. Med J Aust. 1992;156:878-80. Zhao LG, Yanagihara R, Mora C, Garruto RM, Wong TW, Gajdusek DC. Prevalence of human T-cell lymphotropic virus type I infection in Singapore: a preliminary report. Asia Pac J Public Health. 1991;5:236-8. Gessain A, Mahieux R, De The G. HTLV-I "indeterminate" Western blot patterns observed in sera from tropical regions: the situation revisited. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;9:316-9. Mauclere P, Le Hesran JY, Mahieux R, Salla R, Mfoupouendoun J, Abada ET, et al. Demographic, ethnic, and geographic differences between human T cell lymphotropic virus HTLV type I-seropositive carriers and persons with HTLV-I Gag-indeterminate Western blots in Central Africa. J Infect Dis. 1997;176:505-9. Mahieux R, Horal P, Mauclere P, Mercereau-Puijalon O, Guillotte M, Meertens L, et al. Human T-cell lymphotropic virus type 1 gag indeterminate Western blot patterns in Central Africa: relationship to Plasmodium falciparum infection. J Clin Microbiol. 2000;38:4049-57. Meertens L, Rigoulet J, Mauclere P, Van Beveren M, Chen GM, Diop O, et al. Molecular and phylogenetic analyses of 16 novel simian T cell leukemia virus type 1 from Africa: close relationship of STLV-1 from Allenopithecus nigroviridis to HTLV-1 subtype B strains. Virology. 2001;287:275-85. Cavalli-Sforza LL, Menozzi P, Piazza A. Australia, New Guinea, and the Pacific Islands. In: The history and geography of human genes. Princeton NJ: Princeton University Press; 1994. p. 343-71.
Table 1. Human T-cell leukemia virus type 1 HTLV-1 antibody titers and molecular screening results for HTLV-1-seropositive women from Ambae Island, Vanuatu Archipelago
LTR, long terminal repeat; F, female; M, male; AC, Asymptomatic carrier; TSP/HAM, tropical spastic paraparesis/HTLV-1-associated myelopathy; NA, not available.
Suggested citation for this article: Cassar O, Capuano C, Meertens L, Chungue E, Gessain A. Human T-cell leukemia virus type 1 molecular variants, Vanuatu, Melanesia. Emerg Infect Dis serial on the Internet. 2005 May date cited. Available from http://www.cdc.gov/ncidod/EID/vol11no05/04-1015.htm
THE INTERNATIONAL JOURNAL OF DRUG POLICY, VOL 7, NO 1, 1996
BACKLOADING AND HIV INFECTION AMONG INJECTION DRUG USERS
David Vlahov, Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA
This is a version of a paper presented at the V1th International Conference on the Reduction of Drug Related Harm in Florence, March 1995.
Injection drug users are at increased risk for HIV and other blood-borne infections, primarily through the behaviour of sharing contaminated needles and syringes. Sharingoin be director indirect. Indirect needle sharingincludes the practices of frontloading, backloading, sharing of cookers, cotton and rinse water. Transmission of HIV and other bloodborne infections can occur through sexual activities also. Although interventions directed at injection drug users have focused primarily on the risks associated with needle sharing, such as bleach disinfection and needle exchange, other interventions are needed to reduce transmission related to indirect sharing and sexual activity. A promising strategy involves interventions directed at social networks of injection drug users.
INTRODUCTION
'Backtoading' is a drug injection practice that was initially described by Grundand co-workers 1991, but had been noted by others Smith et al., 1992. Briefly, backtoading is the practice of drawing up drug into the syringe of an injection drug user IDU and then transferring a portion of the solution into a second syringe belonging to another IDU by removing the plunger of the second syringe. Earlier literature referred to a practice called'frontloading'which involves removing the needle rather than the plunger from the second syringe and then drawing back the plunger to allow the first person to squirt in solution. However, most IDUs in the USA use diabetic syringes which have needles that cannot be detached. Therefore the plunger of the syringe must be removed to receive drug, and 'backtoading' is more frequently practised. Although these two different terms add descriptive precision, functionally frontloadingand backloadingare similar. It isfurther noted that the terms 'frontloading' and 'backloading' were coined by social scientists, and that the terms to describe this practice are varied e.g. divid, ing, splitting Smith et at., 1992.
As backloading involves transferring of solution from one syringe to another, there is the possibility that blood-borne pathogens, such as human immunodeficiency virus HIV, can be transmitted. The practice of backloading becomes important to consider in the situation where IDUs are observed to seroconvert yet deny borrowing used i.e. contaminated needles from others. In his original work, Grund reported that 85% of his sample of Dutch IDUs reported this practice, yet Samuels and co, workers reported less than 20% of IDUs in Baltimore reporting this practice 1991. Although the fre, quency of this activity appears to vary geographically, the more important question is the extent to which HIV and other blood-borne infections are transmitted through backloading.
In his original report Grund did not test for HIV antibody 1991. Soon after, Samuels and co-workers tested a sample of IDUs in Baltimorc, specifically those who denied receiving used needles or use of shooting galleries, and the prevalence of HIV infection was no different from those who did not backload. These initial preliminary data suggested that the risk of HIV transmission through backloading was probably trivial, although inferences were limited by the cross-sectional nature of the design Samuels et at., 199 1. Subsequently, a separate cross-sectional study of IDUs in NJw York City found this practice to be positively associated with HIV infection; in particular, this New York study specified rates by whether the IDU was'receptive' i.e. the second person in the backloading practice. This specification represented an advancement in the understanding of risk; still, the study was crosssectional in design and subject to potential residual confounding Jose et al., 1992.
To assess risk of HIV or other blood-borne pathogen infection related to this practice, stronger inferences can be generated from prospective studies. The basic design is to follow, at regular e.g. half, yearly intervals, a seronegative IDU. At each visit information about risk practices is obtained and specimens are obtained to identify seroconversion. The objective is to determine if those who engage in backloading are more likely to seroconvert. We report here two such analyses.
METHODS
Study population
The rationale, organisation and data collection methods for the study have been described in detail elsewhere Anthony et al., 1991; Vlahov et al., 1991.In brief, between February 1988 and March 1989, the Infectious Disease Epidemiology Program of the Johns Hopkins University School of Hygiene and Public Health enrolled injecting drug users in a study of the natural history of HIV infection in a freestanding clinic the ALIVE study. Injecting drug users were recruited by word of mouth from various community agencies in Baltimore, including drug abuse treatment centres, city health department sexually transmitted disease STD clinics, local emergency rooms, state probation and parole offices, university hospital HIV/AIDS clinics, homeless shelters and the street outreach AIDS pre, vention SOAP programme of a local community education group. Clinic staff also distributed brochures at selected housing projects and locations where injecting drug use was evident. Finally, study participants were encouraged to refer eligible friends to the study clinic. Eligibility for enrolment in the study included an age of 18 years or older and a history of injecting illicit drugs at any time within the previous 11 years.
Data collection procedures
At the initial visit, eligible and consenting injecting drug users were enrolled and were assigned a unique and confidential study number subsequently used as the coded identifier on data collection instruments. After venepuncture to collect serum for HIV and other blood-borne pathogens and for antibody assays, each participant was questioned face to face by a trained interviewer in a private room. This standardised baseline interview schedule elicited demo, graphic data, a medical history, and information on drug use and sex practices in the previous 10 years. Questions about drug use included year of initiation, frequency of injection, types of drugs used, needle sharing and use of 'shooting galleries' clandestine locations where needles and syringes are rented. The interviewers also asked about the number of people with whom the participant shared i.e. lent or borrowed needles, and whether the participant engaged in 'following' to receive a shared needle, sharing 'cookers' small containers used to prepare drugs for injection and'backloading'. The section of the baseline questionnaire on history of sex practices asked about the number of different sex partners, by gender, for the previous 10 years, and the proportion of partners with whom the participant engaged in anal-genital sex, sex in exchange for drugsormoney, and in anonymous sex.
After the baseline visit, participants returned in 2-3 weeks to receive HIV antibody test results. All HIV-seropositive and anunsetected sample of HIVseronegative injecting drug users were invited to enrol in a clinical immunological follow-up study. This follow-up study involved half-yearly visits with serology, T-cell subset studies, physical exami, nations, and interviews about medical history, drug use and sex practices in the previous 6 months. Follow-up rates of the HIV-seropositive people have exceeded 85% at each half, yearly visit. The remaining HIV-seronegative people not in the clinical immunological follow-up were invited to return at 6-month intervals for HIV serology and interviews only. Thus, we were able to establish and maintain a cohort of injecting drug users from whom serum specimens and risk behaviour data were collected half-yearly from 1988 to the present or this analysis, we used data as of July 1992.
The study procedures were reviewed and approved by the Institutional Review Board of the Johns Hopkins University School of Hygiene and Public Health. Consent procedures included a description of the antibody tests, interpretation of what results could mean and an explanation of study requirements; signed consent was obtained. Counseling about HIV risk reduction was provided after completion of the baseline and each half-yearly interview. Participants received modest remuneration for each completed visit.
Serological tests
Screening serum specimens for antibody to HIV- I was done by commercial enzyme-linked immunosor, bent assay ELISA. Specimens that were repeatedly reactive in the ELISA were tested by commercial western blot. A positive western blot was defined as a band at p24 or p3l and either gp41 or gp 120/160; otherwise, the blot was considered negative.
HTLV serological tests were performed in batch on residual sera that had been stored at -70'C. For the first 1000 consecutive study numbers, baseline serum specimens were tested for antibody to HTW For the remaining subjects, the most recently collected specimen until the end of 1990 was tested and baseline specimens of seropositive individuals were then tested. Serum specimens were screened by ELISA HTLVl rgp2 le.Repeatedly reactive specimens were confirmed by immunoblot that incorporated rgp2 le. Band intensity on visual inspection of the immunoblot was classified as very weak'coded as , 'low' 0 , 'medium' 2+ and' high' 3+. Specimens with antibodies to rgp2le and p24 proteins of at least I+ intensity were considered positive. Based on the scheme by Wiktor et al. 1990, discrimination between HTLV-I and HTLV-11 for the baseline positive specimens was estimated on the relative intensity of the p 19 and p24 bands, given the presence of the rgp2 1 band. Immunoblot bands with p24band intensity greater than p 19 were classified as HTLV-11; when p19 intensity was greater than or equal to p24, the bands were classified as HTLV-1. Specimens with bands but not satisfying the criteria for positivity were considered indeterminate and were excluded from analysis.
In August 1992, we tested the most recently collected specimen of all injecting drug users who previously tested HTLV seronegative. Serum samples were tested by ELISA HTLVl rgp2 le and repeatedly reactive specimens were sent to the Centers for Disease Control and Prevention, where they were confirmed and typed as HTLV-1 or HTLV-11 by western blot. Seropositivity was defined by reactivity to rgp2 le, p24 and MTA- I HTLV-1; rgp2 le, p24 and K,55 HTLV-11; or rgp2 le and p24, but no reactivity to MTA- I or K,55 HTLV-1/11. Seroconversion was defined as the presence of an ELISA, negative specimen followed by at least one confirmed HTLV, positive serum sample. All seroconverters had all of their serum specimens collected every 6 months on average tested in parallel by ELISA to confirm the seroconversion and to determine the HTLV seroconversion date. The date of seroconversion was defined as the midpoint between the last seronegative and the first HTW-reactive ELISA result.
Data analysis
To identify risk factors for seroconvers ion, amatched case-control study of seroconverters and seronegative individuals was nested within the prospective study. For each case of seroconversion, up to seven seronegative injecting drug users were matched on date of study entry + 3 months and on duration of follow-up beingat least as long as that for HTLV., positive individuals. Controls were also required to have a visit within 90 days of the first visit at which the IDU had a positive test result. This matching was performed to control for period and maturation effects as participants received counselling ateach visit in the study and education from community sources, including the media, throughout the study. Information for the cases was abstracted from. the interviewcorrespondingto the first seropositive visit and from baseline. Information on the controls was obtained for the visit closest in calendar time to the seroconversion and baseline interviews of the respective cases. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression techniques Rosner, 1982. Correlates of the practice of backloading at baseline were examined by using logistic regression techniques.
RESULTS
Table I shows the univariate analysis of HIV seroconversion by backloading. As the association was not significant no further analyses were performed relating to HIV seroconversion.
Table 2 shows the univariate associations of HTLV-11 seroconversion by drug use practices including backloading. Backloading was significantly associated with HTLV-11 seroconversion with an odds ratio of 4.58 among those who were actively injecting drugs. In a muttivariate model with simultaneous adjustment for other drug use and sex practices, backloading remained significantly associated with HTLV-11 seroconversion data not shown.
TABLE 1: Univariate association of HIV seroconversion and backloading among injection drug users
HIV seroconverter HIV seronegative Odds ratio 95%Cl Backloading Yes 8 41 0.88 No 26 113 0.35, 2.24
Adapted from Samuels et al. 1992.
To examine correlates of the practice of backloading, we cross-tabulated drug use and sex practices by the dichotomous variable of backloading reported by HTLVI1 seronegative individuals at their baseline visit. Variables significantly p < 0.05 associated with backloading in univariate analyses were entered into a multiple logistic regression model. Faztors significantly associat.d with the practice of backtoading included sharing cookers adjusted odds ratio = 7.46; 95% Cl: 3.06, 18.20, a recent abscess at an injection site adjusted odds ratio = 1.90; 95% Cl: 1. 10, 3.27, use of shootinggalleries adjusted odds ratio= 1.49;95%Cl: 1.04,2.13 and injecting cocaine adjusted odds ratio = 3.39; 95%Cl: 1. 2 8,8.94. The practice of backloading was not statistically associated with needle sharing, the practice of following or any of the sex practice variables.
DISCUSSION
The major findings of these analyses were that backloading was associated with HTLV-11 but not HIV seroconversion among injection drug users in Baltimore. In the analysis of HTLV-11 seroconversion, other drug injection practices, including needle sharingand use of shooting galleries, weremore common but not significantly associated with HTLWl seroconversion. As participants underwent risk reduction counselling which included recommendations to avoid needle sharing and use of shooting galleries, but no specific recommendations on the practice of backloading at each half yearly visit, the lack of association for the other behaviours might be the result of socially desirable responding whereas the positive association for backloading could be simply a marker of these other risky behaviours. Given the potential limitations of self-reported behavioral traits, it is intriguing to note that backloading was significantly associated with reports of other high risk drug injection practices, suggesting that backloading indeed could be a marker for these other behaviours.
TABLE 2: Univariate associations of HTLV-11 seroconversion of drug use practices in the previous 6 months for 37 HTLV-11 seroconverters and 192 matched* seronegative controls the ALIVE study, Baltimore, Maryland Variable categories no. of cases no. of controls odds ratio 95% Cl Among recent IDU odds ratio 95% Cl
Frequency of injection None >I/day 7 12 18 54 67 71 1.00 1.43 2.03 0.50-4.08 0.76-5-43 1.00 1.33 0.60-2-97
Cl= confidence interval; IDU= injecting drug use; BL= backload. Matching criteria, + 3 months date of study entry, and duration of follow ,up at least as long in controls as in cases. Information from controls abstracted from interviews 3 months from the first positive interview cases. 'Recent: past 6 months.
Another possible explanation for the observed findings is that HTLV-11 infection is circulating only within a restricted subset or social network of injecting drug users, and it is primarily within this subgroup that the practice of backloading is well established. This possibility, if correct, suggests that the practice of backloading might be a marker of a social network of drug injectors among whom HTLV-11 infection is circulating. Although these two explanations for the observed findings are plausible, future studies should collect additional information to determine if backloading is associated with different cooking procedures, different diluents, and larger amounts of diluents that might allow better viability of infec, tious HTLV-11 in the backloaded syringe. Although additional studies are warranted to examine the observed association, education and counselling to injecting drug users about the risk of transmission of HTLV-11 and other blood,borne pathogens as a result of backloading seems prudent.
Before firm conclusions are drawn, several study limitations should be acknowledged. The injecting drug users recruited for this study were volunteers from the community, and the extent to which they can be considered representative of drug users in Baltimore or other cities is unknown. Although the hidden nature of drug use precluded the generation of a population frame from which to draw a random. sample, the large study population recruited and the similarity in demographic characteristics and HIV seroprevalence with prison and treatment-based samples of injecting drug users in Baltimore Lange et at., 1987; Vlahov et al., 1990 serve to min imise concerns that this study population was unusual.
Validity of self reports for risk behaviours is another methodological concern. However, biological validation of selfreported risky behaviours is limited. Multiple methodological studies of injecting drug users indicate reasonable reliability and validity of self-reports Samuels et al., 1992. In this study, in which participants received risk reduction counselling at each half-yearly visit, dampening of reports of high-risk behaviors that were targeted during counseling might be expected. Although all participants received the same counseling after the interviews but before receipt of HIV test results, which should minimize concerns of a differential in reporting by seroconversion status, we cannot exclude the possibilities that an overall effect of socially desirable responding might have influenced the measure of association. However, an earlier report suggests that the effect might be minimal.
With these limitations acknowledged, the epidemiological evidence suggests that there might be a risk of transmitting blood-borne pathogens through backloading. Discouraging this practice seems to be a prudent public health policy.
ACKNOWLEDGEMENTS
This research was supported by grants from the National Institute on Drug Abuse.
David Vlahov, PhD, Associate Professor, Department of Epidemiology, The Johns Hopkins School of Hygiene and Public Health, Room 894, 624 N - Broadway, Baltimore, Maryland 21205, USA.
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GrundJP, Kaplan CD, AdriaansNFPet al. 1991. Drugsharing and HIV transmission risks: the practice of frontloading in the Dutch injecting drug using population. Journal of Psychoactive Drugs 23: 1-10.
Jose B, Friedman SR, Neaigus et al. 1992. 'Frontloading' is associated with HIV infection among drug injectors in New York City. Paper presented at the 8th International Conference on AIDS, Amsterdam, The Netherlands, July 23.
Lange WR, Snyder FR, Lozovsky D et al. 1987, HIV infection in Baltimore: antibody seroprevalence rates among parenteral drug abusers and prostitutes. Maryland Medical Journat36:61-75.
Latkin CA, Vlahov D, Anthony JC 1993. Socially desirable responding and self-reported HIV infection risk behaviors among intravenous drug users. BnitishJournalofAddiction88: 517-26.
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Samuels, Vlahov D, AnthonyJC et al. 1991. The practice of frontloading among . intravenous drug users: associations With HIV antibody. AIDS 5:343.
S1mueIsJ, Vlahov D, AnthonyJC, Chaisson RE 1992. Measurement of risk behaviors among intravenous drug users. BritishJournal ofAddiction 87:417-28.
Smith A, Vlahov D, Menon AS, Anthony JC 1992, Terminology for drug injection practices among intravenous users in Baltimore. International journal of the Addictions 27: 435-53.
Vlahov D, MufiozA, BrewerF etal. 1990 Seasonal andannual trends of antibody to human immunodeficiency virus type 1 HIV-1 among male inmates entering Maryland prisons. AIDS 4:345-50.
Vlahov D, Anthony JC, Mufioz A et al. 1991. ALIVE Study: A longitudinal study of HIV infection among intravenous drug users. Journal of Drug Issues 21: 755-71.
Vlahov D, Astemborski J, Solomon L et al. 0 994. Field effectiveness of needle disinfection among injecting drug users. Journal of Acquired Immune Deficiency Syndrome 7: 760-6.
Wiktor SZ, Alexander SS, Shaw GM et al. 1990. Distinguishing between HTLV- I andHTLV-11 by Western blot. TheLancet335:1533.
Research article . Pulmonary function testing in HTLV-I and HTLV-II infected humans: a cohort study Edward L Murphy1, 2 , Helen E Ownby3 , James W Smith4 , George Garratty 5 , Sheila T Hutching5 , Ying Wu6, 7 and Dannie I Ameti6 1University of California San Francisco, San Francisco, CA, USA 2Blood Centers of the Pacific, San Francisco, CA, USA 3American Red Cross Blood Services, Southeastern Michigan Region, Detroit, MI, USA 4Oklahoma Blood Institute, Oklahoma City, OK, USA 5American Red Cross Blood Services, Southern California Region, Los Angeles, CA, USA 6Westat, Rockville, MD, USA 7Current address: Bristol-Myers Squibb, Wallingford, CT, USA
BMC Pulmonary Medicine 2003, 3:1 doi:10.1186/1471-2466-3-1
Received 14 May 2003 Accepted 28 July 2003 Published 28 July 2003
2003 Murphy et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. Background
HTLV-I infection has been linked to lung pathology and HTLV-II has been associated with an increased incidence of pneumonia and acute bronchitis. However it is unknown whether HTLV-I or -II infection alters pulmonary function.
Methods
We performed pulmonary function testing on HTLV-I, HTLV-II and HTLV seronegative subjects from the HTLV outcomes study HOST, including vital capacity VC, forced expiratory volume in one second FEV1, and diffusing lung capacity for carbon monoxide DLCO corrected for hemoglobin and lung volume. Multivariable analysis adjusted for differences in age, gender, race/ethnicity, height and smoking history.
Results
Meanm standard deviation pulmonary function values among the 257 subjects were as follows: FVC = 3.74 0.89 L, FEV1 = 2.93 0.67 L, DLCOcorr = 23.82 5.89 ml/min/mmHg, alveolar ventilation VA = 5.25 1.20 L and DLCOcorr/VA = 4.54 0.87 ml/min/mmHg/L. There were no differences in FVC, FEV1 and DLCOcorr/VA by HTLV status. For DLCOcorr, HTLV-I and HTLV-II subjects had slightly lower values than seronegatives, but neither difference was statistically significant after adjustment for confounding.
Conclusions
There was no difference in measured pulmonary function and diffusing capacity in generally healthy HTLV-I and HTLV-II subjects compared to seronegatives. These results suggest that previously described HTLV-associated abnormalities in bronchoalveolar cells and fluid may not affect pulmonary function.
Human T-lymphotropic virus type I HTLV-I has been associated with sporadic cases of chronic bronchiolitis and alveolitis, especially in patients with concurrent HTLV associated myelopathy HAM 1,2. HTLV type II HTLV-II has been epidemiologically associated with increased incidences of bronchitis and pneumonia among HTLV-II infected persons 3,4.
Biological studies have demonstrated increased levels of CD3+/CD25+ lymphocytes 5, HTLV-I proviral load and HTLV-I tax/rex mRNA expression 6,7, HTLV-I specific IgA 8, soluble interleukin-2 receptors 9, beta-chemokines 7 and soluble intracellular adhesion molecule-1 ICAM-1 10, in bronchoalveolar lavage fluid from HTLV-I infected humans. In addition, mice transgenic for HTLV-I p40 tax had lymphocytic infiltration of peribronchial and perivascular lung tissues associated with intrapulmonary expression of tax mRNA 11. In general, patients with HTLV myelopathy or uveitis had more pronounced biological changes, but some of these studies also found biological changes in the lungs of asymptomatic HTLV-I carriers.
However, whether HTLV-I or HTLV-II alters pulmonary function is unknown. Such information is important because the pathologic spectrum of these chronic human retroviral infections has not been completely described. In addition, such information would be useful to physicians who must counsel or treat persons found to be HTLV-I or -II seropositive by serologic screening at the time of blood donation, military service, or as part of clinical care associated with injection drug use.
We therefore performed standardized pulmonary function testing PFT on HTLV-I and HTLV-II infected persons participating in the HTLV Outcomes Study HOST, a prospective multicenter cohort study of the health outcomes of HTLV infection that was initiated as part of the National Heart Lung and Blood Institute Retrovirus Epidemiology Donor Study.
Study design and patient population
The enrollment and follow-up procedures of the HOST have been described in detail elsewhere 4. In brief, persons found to be seropositive for HTLV-I and HTLV-II at the time of routine or autologous blood donation in 1990-1992 at five United States blood centers were eligible for enrollment. HTLV-I and HTLV-II infection status was confirmed with type-specific serology and/or polymerase chain reaction testing. Subjects have been followed approximately every two years with health history questionnaires, physical examinations, and blood testing. At the third biennial visit in 1995-1997, we performed PFT on a randomly selected subset of HTLV-I and -II positive subjects at four of the five HOST centers American Red Cross Blood Services Southeastern Michigan Detroit, MI, American Red Cross Blood Services Southern California Los Angeles, CA, Blood Centers of the Pacific San Francisco, CA, and the Oklahoma Blood Institute Oklahoma City, OK. We also selected seronegative subjects at the same four centers by strata based upon the age, sex and racial distribution of the HTLV positive subjects, and asked them to undergo PFT.
PFT Procedures
In performing the PFTs, we followed standards published by the American Thoracic Society 12. Spirometers were calibrated according to these standards, and subjects performed three forced expirations. We measured forced vital capacity FVC in liters, forced expiratory volume at one second FEV1, diffusing lung capacity corrected for hemoglobin DLCOcorr and diffusing lung capacity corrected for hemoglobin and alveolar ventilation DLCOcorr/VA. Each subject's best effort, as judged by the highest sum of vital capacity and FEV1 from among three expiratory efforts, was used in the analysis.
Statistical analysis
For each of the pulmonary function measures, means and 95 percent confidence intervals were calculated. The mean of each parameter was compared between the HTLV-I, HTLV-II and seronegative groups using ANOVA tests PROC GLM. Outcome variables, FVC, FEV1, DLCOcorr and DLCOcorr/VA were all treated as continuous variables in the model. Multivariable analysis was performed using linear regression, adjusting for age quartiles: 40, 41-47, 47-53 and 54+, gender male or female, race/ethnicity White, Black, Hispanic, Asian/other, smoking history nonsmokers, ex-smokers, and current smokers and weight study population quartiles, 66 kg, 67-78 kg, 79-88.5 kg and 88.5 kg. The model evaluated differences in pulmonary function parameters and their statistical significance when all important confounders, such as smoking, and characteristics of the study subjects were taken into consideration. Due to the limited number of subjects, we were unable to stratify the analysis by center. Nonetheless, power calculations revealed that the study was able to detect a 10 percent difference compared to seronegatives in the parameters measured with power 1 - beta of 0.65 to 0.85 for HTLV-I, and 0.82 to 0.96 for HTLV-II. All analyses were done using SAS SAS version 6.12, Cary, NC.
For each of the pulmonary function measures, means and 95 percent confidence intervals were calculated. The mean of each parameter was compared between the HTLV-I, HTLV-II and seronegative groups using ANOVA tests. Multivariable analysis, adjusted for age, gender, race/ethnicity, smoking history and weight, was performed using linear regression. Due to the limited number of subjects, we were unable to stratify the analysis by center. Power calculations revealed that, relative to the seronegatives, the study was able to detect a 10 percent decrease in the parameters measured with power 1 - beta of 0.65 to 0.85 for HTLV-I and 0.82 to 0.96 for HTLV-II. All analyses were done using SAS SAS version 6.12, Cary, NC. The Committee on Human Research of the University of California San Francisco, San Francisco, CA, USA, has approved the study.
Results Among the 258 subjects enrolled in the study, one subject had only one instead of three expiratory efforts recorded. This subject was eliminated from further analysis, leaving a study population of 257; none had adult T-cell leukemia or HTLV associated myelopathy. The HTLV-I and HTLV-II subjects were comparable to seronegative subjects with regard to age, gender and race/ethnicity, except that HTLV-I subjects were somewhat older, and more likely to be of black race/ethnicity and to be former smokers Table 1. Although the three groups were of similar height, HTLV-I infected subjects had a non-significant trend toward lower body weight. Thirty-one percent of the HTLV-II subjects were current smokers, compared to only 11 percent of the HTLV-I and seronegative groups. Dating from study enrollment in 1990-92, incident cases of medically-diagnosed pneumonia or acute bronchitis were reported by 22 percent of HTLV-I, 33 percent of HTLV-II, and 21 percent of seronegative subjects in the current analysis. Data on log10 proviral load were available from 38 of 46 HTLV-I subjects mean = -2.97, standard error 0.24 copies per PBMC and from 67 of 84 HTLV-II subjects mean = -3.46, standard error 0.21 copies per PBMC.
Mean standard deviation pulmonary function values among all 257 subjects were as follows: FVC = 3.74 0.89 L, FEV1 = 2.93 0.67 L, DLCOcorr = 23.82 5.89 ml/min/mmHg, alveolar ventilation VA = 5.25 1.20 L and DLCOcorr/VA = 4.54 0.87 ml/min/mmHg/L. These data were comparable to mean values for men and women combined reported by the First National Health and Nutrition Examination NHANES I of FVC = 3.82, FEV1 = 2.94 and DLCOcorr = 26.605 13. In our study, FVC and FEV1 were also corrected for height squared in meters yielding values of 1.34 0.24 L/m2 and 1.05 0.20 L/m2, respectively. There was also no significant difference in small airway flow FEF25-75 between HTLV infected and seronegatives p = 0.47, data not shown.
Figures 1 through 4 show the raw pulmonary function values, stratified by HTLV status. The HTLV-I group had slightly lower mean FVC, FEV1 and DLCOcorr than did the seronegative group, but no such difference was apparent for the HTLV-II group.
The results of the multivariable linear regression analysis are presented in Table 2. For both FVC and FEV1 adjusted for height squared, mean values were only minimally smaller for the HTLV-I group, and no different at all for the HTLV-II group, both compared to HTLV seronegatives. For DLCOcorr, the HTLV-I group had mean values that were about ten percent lower, and the HTLV-II group about five percent lower, compared to seronegatives. However these differences narrowed after adjustment for potential confounding variables and neither was statistically significant, although there was a trend toward lower adjusted DLCOcorr for the HTLV-I group. DLCO corrected for alveolar ventilation DLCOcorr/VA showed no differences between both HTLV groups and seronegatives in either the unadjusted or the multivariable analysis. Finally, there was no association between DLCO and the level of HTLV-I or HTLV-II proviral load among the HTLV seropositives
Discussion This study did not reveal significant differences between HTLV-I or -II infected and uninfected persons in pulmonary function or diffusing capacity, after adjustment for confounding variables. This normal pulmonary function data are in contrast to previous reports of bronchio-alveolitis and differences in biological measurements in broncho-alveolar lavage fluid among persons with HTLV-I infection 1,7.
Most previous reports of HTLV-I bronchio-alveolitis reported more frequent and severe pathological and biological abnormalities of bronchoalveolar lavage fluid in patients with HTLV myelopathy or uveitis compared to HTLV-I carriers without apparent disease 6,8,14. Since our patients were without overt inflammatory disease, we cannot comment on potential pulmonary function abnormalities in patients with clinical inflammation. Likewise a rare case of bronchio-alveolitis among our study group could have had pulmonary function abnormalities that were masked by our comparison of mean values among the HTLV-I, HTLV-II and seronegative groups. Finally, our subjects could have had clinical or subclinical pulmonary inflammation due to HTLV-I or HTLV-II infection, but this inflammation was not of sufficient severity or duration to manifest measurable decrements in overt pulmonary function.
Data from the cohort study from which these subjects were drawn has revealed an increased incidence of pneumonia and acute bronchitis among HTLV-II, and to a lesser degree HTLV-I, infected humans 3,4. Those results were based upon analyses of reported physician diagnoses of these illnesses, and were adjusted statistically to account for differences in socioeconomic status, cigarette smoking and alcohol intake between HTLV infected and uninfected subjects. Although we initially attributed these illnesses to an increased susceptibility to bacterial infection, we now propose the hypothesis that these diagnoses may have been due to immunological mechanisms as in cases of HTLV-I bronchio-alveolitis. The negative results of current study, although reassuring to persons with HTLV-I or HTLV-II infection, cannot exclude either of these hypotheses.
Strengths of the current study include its setting in a well characterized cohort study of humans with laboratory confirmed HTLV-I and HTLV-II infection, and the inclusion of an appropriate control group. Due to information gathered in the cohort study, we were also able to control for other potential confounding variables such as cigarette smoking and alcohol intake. Weaknesses include moderate size of the study, which made us unable to detect PFT differences that were less than about ten percent. PFT's were done at four different sites, which could have resulted in increased variability of the results. The PFTs that we used may be insensitive to minor degrees of pulmonary damage, and with this cross-sectional data we may have missed a progressive loss of pulmonary function over time in the HTLV groups.
Conclusions In conclusion, this moderate size study did not reveal any statistically significant differences in pulmonary function between generally healthy HTLV-I or -II infected persons and comparable HTLV seronegatives. However it could not rule out subtle differences in lung inflammation that might lead to functional impairment over a longer follow-up period. Further studies of the immunologic characteristics of bronchoalveolar lavage cells from HTLV-I or -II infected humans are needed, especially in persons with a history of recurrent pneumonia or acute bronchitis but without myelopathy or uveitis.
1. Sugimoto M, Kitaichi M, Ikeda A, Nagai S, Izumi T: Chronic bronchioloalveolitis associated with human T-cell lymphotrophic virus type I infection. Curr Opin Pulm Med 1998, 4:98-102. PubMed Abstract
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2. Matsuse T, Fukuchi Y, Hsu CY, Nagase T, Higashimoto N, Teramoto S, Matsui H, Sudo E, Kida K, Morinari H, Fukayama M, Ouchi Y, Orimo H: Detection of human T lymphotropic virus type I proviral DNA in patients with diffuse panbronchiolitis. Respirology 1996, 1:139-144. PubMed Abstract
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3. Murphy EL, Glynn SA, Fridey J, Sacher RA, Smith JW, Wright DJ, Newman B, Gibble JW, Ameti DI, Nass CC, Schreiber GB, Nemo GJ: Increased prevalence of infectious diseases and other adverse outcomes in human T lymphotropic virus types I- and II-infected blood donors. Retrovirus Epidemiology Donor Study REDS Study Group. J Infect Dis 1997, 176:1468-1475. PubMed Abstract
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4. Murphy EL, Glynn SA, Fridey J, Smith JW, Sacher RA, Nass CC, Ownby HE, Wright DJ, Nemo GJ: Increased incidence of infectious diseases during prospective follow-up of human T-lymphotropic virus type II- and I-infected blood donors. Retrovirus Epidemiology Donor Study. Arch Intern Med 1999, 159:1485-1491. PubMed Abstract Publisher Full Text
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5. Mukae H, Kohno S, Morikawa N, Kadota J, Matsukura S, Hara K: Increase in T-cells bearing CD25 in bronchoalveolar lavage fluid from HAM/TSP patients and HTLV-I carriers. Microbiol Immunol 1994, 38:55-62. PubMed Abstract
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6. Mita S, Sugimoto M, Nakamura M, Murakami T, Tokunaga M, Uyama E, Araki S: Increased human T lymphotropic virus type-1 HTLV-1 proviral DNA in peripheral blood mononuclear cells and bronchoalveolar lavage cells from Japanese patients with HTLV-1-associated myelopathy. Am J Trop Med Hyg 1993, 48:170-177. PubMed Abstract
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7. Seki M, Higashiyama Y, Mizokami A, Kadota J, Moriuchi R, Kohno S, Suzuki Y, Takahashi K, Gojobori T, Katamine S: Up-regulation of human T lymphotropic virus type 1 HTLV-1 tax/rex mRNA in infected lung tissues. Clin Exp Immunol 2000, 120:488-498. PubMed Abstract Publisher Full Text
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8. Sugimoto M, Imamura F, Matsumoto M, Sonoda E, Cho I, Ando M: Pulmonary involvement in patients with human T lymphotropic virus type 1-associated myelopathy: the presence of specific IgA antibody in bronchoalveolar lavage fluid. Am J Trop Med Hyg 1993, 48:803-811. PubMed Abstract
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9. Sugimoto M, Nakashima H, Matsumoto M, Uyama E, Ando M, Araki S: Pulmonary involvement in patients with HTLV-I-associated myelopathy: increased soluble IL-2 receptors in bronchoalveolar lavage fluid. Am Rev Respir Dis 1989, 139:1329-1335. PubMed Abstract
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10. Seki M, Higashiyama Y, Kadota J, Mukae H, Yanagihara K, Tomono K, Kohno S: Elevated levels of soluble adhesion molecules in sera and BAL fluid of individuals infected with human T-cell lymphotropic virus type 1. Chest 2000, 118:1754-1761. PubMed Abstract Publisher Full Text
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11. Kawakami K, Miyazato A, Iwakura Y, Saito A: Induction of lymphocytic inflammatory changes in lung interstitium by human T lymphotropic virus type I. Am J Respir Crit Care Med 1999, 160:995-1000. PubMed Abstract Publisher Full Text
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12. Lung function testing: selection of reference values and interpretative strategies. American Thoracic Society Am Rev Respir Dis 1991, 144:1202-1218. PubMed Abstract
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13. Neas LM, Schwartz J: Pulmonary function levels as predictors of mortality in a national sample of US adults. Am J Epidemiol 1998, 147:1011-1018. PubMed Abstract
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14. Sugimoto M, Mita S, Tokunaga M, Yamaguchi K, Cho I, Matsumoto M, Mochizuki M, Araki S, Takatsuki K, Ando M: Pulmonary involvement in human T-cell lymphotropic virus type-I uveitis: T-lymphocytosis and high proviral DNA load in bronchoalveolar lavage fluid. Eur Respir J 1993, 6:938-943. PubMed Abstract
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It dosent look good considering it messes with your immune system like lyme does.
Human T cell leukaemia virusesHuman T cell leukaemia viruses HTLV-1 and 2 belong to the large family of retroviruses, which in-cludes the HIV-1 virus indeed HIV-1 was previouslyknown as HTLV-3. In 1985, HTLV-1 was serologically linked to a progressive spastic paraparesis, knownas tropical spastic paraparesis in the West Indies. In Japan, a similar syndrome called HTLV-1 associatedmyelopathy HAM has been described. HTLV-1 isendemic in southern Japan and Taiwan but mostseropositive individuals are asymptomatic, with lessthan 1% developing a neurological complication.Infection can be spread by sexual, parenteral, or verti-cal transmission. The incubation period for HTLV-1can exceed 20 years, with HAM often recognized in the fifth decade as progressive spasticity of the legs, although occasionally acute cases resembling transverse myelitis may occur. Serological testing forHTLV-1 infection is available but definitive treatment for clinical cases remains to be determined.17 -------------------------------------------------------------------------------- INFECTIOUS DISEASES THAT MIMIC MS Lyme disease LD is an infection caused by Borrelia burgdorferi, a bacterium carried by deer ticks. Untreated, the bacterium travels through the bloodstream, causing severe fatigue, a stiff, aching neck, tingling or numbness in the extremities, and facial palsy. The primary symptom is usually a rash that radiates from the tick bite. Diagnosis should be made on the basis of symptoms and evidence of a tick bite, not blood tests, which can often give false results if performed in the first month after infection.
Those who live or work in residential areas surrounded by tick-infested woods, or enjoy hiking, camping, fishing and hunting, or live in endemic areas are at increased risk for this disease.
Human T-cell lymphotrophic virus-1 HTLV-1 is associated with progressive spinal cord dysfunction. Symptoms include spasticity, partial paralysis of the lower limbs, bladder and bowel incontinence, and impotence. HTLV-1 can be ruled out with a titer, which is a type of elevated antibody test. "HTLV-1 affects the spinal cord and does appear similar to primary progressive MS," Burks explains. "But HTLV-1 primarily occurs in the Caribbean, so it is important to ask about travel to endemic areas. Besides the Caribbean, these areas include Southern Japan and less commonly, the Pacific Coast of South America, Equatorial Africa and the Southern United States. HTLV-1 is also common among intravenous drug users."
PI: Manuel Moro, D.V.M., M.P.H., Ph.D., Assistant Professor, Department of Diagnostic Medicine and Pathobiology, Kansas State University.
Abstract: The blood parasite, Babesia microti and the spirochetal agent of Lyme disease, Borrelia burgdorferi, are both transmitted by the deer tick, Ixodes scapularis and are transmitted in arease that are currently endemic for Lyme disease. In humans, infection with these two organisms may occur alone or in combination. Prospective studies indicate that persistence of infection with B. burgdorferi and B. microti are enhanced by concurrent infection and result in an increased severity of symptoms. Our laboratory has demonstrated increase arthritis severity associated with downregulation of IL-10 and IL-13 cytokines in a murine model of coinfection. From these data we hypothesize that, during coinfection, B. microti downregulates the expression of IL-10 and IL-13 which in turn increases inflammation of joints and create and adequate milieu for B. burgdorferi persistence. To test this hypothesis, we propose to 1 determine if downregulation of IL-10 and/or IL-13 cytokines directly results in an increase of arthritis during coinfection; 2 identify the temporal expression of key inflammatory chemokines directly from the arthritic joints in a murine model coinfection; 3 determine in vivo gene expression of selected prototype genes from B. burgdorferi from joints during coinfection. Theses tudies will lead ultimately to a better understanding of the mechanisms by which coinfected individuals may be at higher risk of Lyme arthritis and may identify new therapeutic targets for Lyme borreliosis and bebesiosis coinfection.
Dr. Moro
Roles of P30 in HTLV-1 Latency
PI: Christophe Nicot, Ph.D., Assistant Professor, Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center.
Abstract: The human T-cell lymphotropic virus type 1 HTLV-I is epidemiologically associated with an aggressive and fatal T-cell type leukemia/ lymphoma designated Adult T-cell Leukemia/ Lymphoma ATLL. HTLV-I infection is also associated with a progressive myelopathy designated Tropical Spastic Paraparesis/ HTLV-I-Associated Myelopathy TSP/HAM of probable immune-mediated pathogenesis. It is estimated that 20 to 30 million people worldwide are infected with HTLV-I. HTLV-I possesses unusual features that would not predict its survival in an immune-competent host: The virus is poorly infectious but elicits a vigorous humoral and cellular host immune response. In addition, HTLV-I is mainly replicated in vivo through division of infected cells and therefore presents a very low antigenic variability. However, in spite of these apparent disadvantages the virus has persisted in humans for more than 100,000 years, indicating that HTLV-I has efficiently adapted to its host. We have recently found that HTLV-I has evolved a protein p30 that interacts specifically with the tax/rex viral RNA encoding positive regulators of virus expression. Because p30 is unable to shuttle out of the nucleus, tax/rex RNA is trapped in the nucleus and expression of these proteins is inhibited.
The goals of this study are to investigate the molecular mechanisms involved in p30-viral RNA interactions and p30 effects on transcription leading to inhibition of virus replication. Three specific aims are proposed. Aim 1 Investigate post transcriptional regulation of p30 to design small inhibitors. Aim 2 Investigate expression of p30 in ATL or TSP/HAM patient samples infected with HTLV-I at different stages of the disease. Aim 3 Identify cellular proteins interacting with HTLV p30 and involved in retention pathways.
Viruses are very small organisms - most cannot even be seen with an ordinary microscope. They consist of a small group of genes in the form of DNA or RNA surrounded by a protein coating. Viruses cannot reproduce on their own. They need to enter a living cell and "hijack" the cell's machinery to make more viruses. Some viruses do this by inserting their own DNA or RNA into that of the host cell. When this insertion affects the host cell's genes, it may push the cell toward becoming cancerous.
Several viruses are now known or suspected of being linked with cancer in humans. Our growing knowledge of the role of viruses as a cause of cancer may lead to vaccines that prevent or treat certain human cancers in the future.
Human T-Lymphotrophic Virus-1 HTLV-1
HTLV-1 has been linked with a type of lymphocytic leukemia and non-Hodgkin lymphoma called adult T-cell leukemia/lymphoma ATL. This cancer is found mostly in southern Japan, the Caribbean, Central Africa, parts of South America, and in some immigrant populations in the southeastern United States. In addition to ATL, the virus also causes a form of degenerative nerve disease called tropical spastic paraparesis TSP that is especially common in Japan and in the Caribbean basin.
HTLV-1 belongs to a class of viruses called retroviruses. These viruses use RNA instead of DNA for their genetic code. They cannot reproduce on their own. They make up for this by having an enzyme called reverse transcriptase, which allows them to change their RNA genes into DNA. Some of the new DNA genes can become part of the chromosomes of the human cell infected by the virus. This can change the genes in human cells that normally control how often the cell divides, potentially causing cancer. Retroviruses have long been known as causes of leukemia in various animal species.
HTLV-1 is similar to another human retrovirus, the human immunodeficiency virus HIV that causes AIDS although HTLV-1 does not cause AIDS. In humans, HTLV-1, like HIV, can be spread in several ways:
sexual intercourse most often from a male partner injection with a contaminated needle blood transfusion from mother to child during pregnancy or at birth in breast milk Not everyone exposed to the virus becomes infected. For example, HTLV-1 infected mothers have about a 10% to 30% chance of passing on the virus to their children.
Screening of all donated blood in the United States has greatly reduced the chance of infection through transfusion and has helped control the potential spread of HTLV-1 infection.
A survey of blood donors in locations around the United States indicated an overall prevalence of HTLV-1 infection of about 0.025% 1 out of every 4,000 people. About 2% to 10% of people who have received multiple transfusions or who use intravenous drugs will become infected with HTLV-1.
Once infected, a person's chance of developing ATL can be up to about 5%, usually after a long latent period 20 or more years. Latent means that the virus is still present in the body but is dormant inactive and not causing symptoms.
-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
It sounds bad, but...my kind is 11 or 2 so I'm not sure of the difference with the two. It seems to me the 1 is way worse and 2 not so bad?
I wonder if it mimicks lyme?
daniella
-------------------- ~Things may happen in my life time to change who I am but I refuse to let them reduce me...~ Posts: 968 | From private | Registered: Jan 2005
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treepatrol
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HTLV-2 was isolated from a cell line established from a variant form of hairy cell leukemia (8, 51). HTLV-2 has nucleotide sequence similarity to HTLV-1 and similar biological properties (47, 51). For instance, HTLV-2 transforms primary human T cells with efficiency similar to that of HTLV-1 in vitro. HTLV-2, however, is rarely associated with leukemias similar to ATL and has been associated with only a few cases of lymphoproliferative diseases (51). Thus, HTLV-2 appears not to induce malignant growth of infected cells in vivo and hence is a useful tool to understand the pathogenesis of ATL. From HLV2 rarely associated
-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
treepatrol
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-------------------- Do unto others as you would have them do unto you. Remember Iam not a Doctor Just someone struggling like you with Tick Borne Diseases.
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