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5. Age as a risk factor for severe manifestations and fatal outcome of Falciparum Malaria in European patients: observations from TropNetEurop and SIMPID surveillance data. (Major Article)

Author

Muhlberger, N., Jelinek, T., Behrens, R.H., Gjorup, I., Coulaud, J.P., Clerinx, J., Puente, S., Burchard, G., Gascon, J., Grobusch, M.P., Weitzel, T., Zoller, T., Kollaritsch, H., Doolittle, Hilda, Iversen, J., Hatz, C., Schmid, M.L., Bjorkman, A., Fleischer, K., Bisoffi, Z., Guggemos, W., Knobloch, J., Matteelli, A., Schulze, M.H., Laferl, H., Kapaun, A., McWhinney, P., Lopez-Velez, R., Fatkenheuer, G., Kern, P., Zieger, B.W., Kotlowski, A., Fry, G., Cuadros, J., and Myrvang, B.

Subjects
Communicable diseases -- Research, Aging -- Health aspects, Malaria -- Risk factors, Malaria -- Demographic aspects, Malaria -- Complications, Aged -- Patient outcomes, Aged -- Diseases, Plasmodium -- Research, Health, Health care industry
Published
2003

6. Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop. (Major Article)

Author

Jelinek, T., Muhlberger, N., Harms, G., Corachan, M., Grobusch, M.P., Knobloch, J., Bronner, U., Laferl, H., Kapaun, A., Bisoffi, Z., Clerinx, J., Puente, S., Fry, G., Schulze, M., Hellgren, U., Gjorup, I., Chalupa, P., Hatz, C., Matteelli, A., Schmid, M., Nielsen, L.N., Cunha, S. da, Atouguia, J., Myrvang, B., and Fleischer, K.

Subjects
Dengue -- Care and treatment, Dengue -- Diagnosis, Dengue -- Demographic aspects, Travelers -- Health aspects, Health, Health care industry
Published
2002

17. HIV dementia and apolipoprotein E

Author

Dunlop, O., Goplen, A. K., Liestøl, K., Myrvang, B., Rootwelt, H., Christophersen, B., Kvittingen, E-A., and Maehlen, J.

Published
1997

19. Epidemiology and clinical features of vivax malaria imported to Europe: Sentinel surveillance data from TropNetEurop

Author

Malvy DJM, Kotlowski A, Iversen J, Knobloch J, Kapaun A, Kollaritsch H, Hatz C, Holthoff-Stich ML, Laferl H, Myrvang B, Schmid ML, Puente S, Hellgren U, Bisoffi Z, Lopez-Velez R, Matteelli A, McWhinney P, Björkman A, Clerinx J, Behrens RH, Gjørup I, Beran J, Schunk M, Zoller T, Probst M, Gascon J, Jelinek T, Mühlberger N, Kern P, Fry G, Siikamaki H, Schulze MH, Soula G, Paul M, Prat J Gómez i, Lehmann V, Bouchaud O, Cunha S da, Atouguia J, and Boecken G

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. Objectives To present epidemiological and clinical data on imported P. vivax malaria collected at European level. Material and methods Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. Results Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41–158) versus 31 days (inter-quartile range 4–133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. Conclusions TropNetEurop data can contribute to the harmonization of European treatment policies.

Published
2004
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20. Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data

Author

Lingscheid T, Kurth F, Clerinx J, Marocco S, Trevino B, Schunk M, Muñoz J, Gjørup IE, Jelinek T, Develoux M, Fry G, Jänisch T, Schmid ML, Bouchaud O, Puente S, Zammarchi L, Mørch K, Björkman A, Siikamäki H, Neumayr A, Nielsen H, Hellgren U, Paul M, Calleri G, Kosina P, Myrvang B, Ramos JM, Just-Nübling G, Beltrame A, Saraiva da Cunha J, Kern P, Rochat L, Stich A, Pongratz P, Grobusch MP, Suttorp N, Witzenrath M, Hatz C, Zoller T, and TropNet Schistosomiasis Investigator Group

Abstract

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

Published
2017

21. Age as a Risk Factor for Severe Manifestations and Fatal Outcome of Falciparum Malaria in European Patients: Observations from TropNetEurop and SIMPID Surveillance Data

Author

Mühlberger, N., Jelinek, T., Behrens, R. H., Gjørup, I., Coulaud, J. P., Clerinx, J., Puente, S., Burchard, G., Gascon, J., Grobusch, M. P., Weitzel, T., Zoller, T., Kollaritsch, H., Beran, J., Iversen, J., Hatz, C., Schmid, M. L., Björkman, A., Fleischer, K., Bisoffi, Z., Guggemos, W., Knobloch, J., Matteelli, A., Schulze, M. H., Laferl, H., Kapaun, A., McWhinney, P., Lopez-Velez, R., Fôtkenheuer, G., Kern, P., Zieger, B. W., Kotlowski, A., Fry, G., Cuadros, J., Myrvang, B., Mühlberger, N., Jelinek, T., Behrens, R. H., Gjørup, I., Coulaud, J. P., Clerinx, J., Puente, S., Burchard, G., Gascon, J., Grobusch, M. P., Weitzel, T., Zoller, T., Kollaritsch, H., Beran, J., Iversen, J., Hatz, C., Schmid, M. L., Björkman, A., Fleischer, K., Bisoffi, Z., Guggemos, W., Knobloch, J., Matteelli, A., Schulze, M. H., Laferl, H., Kapaun, A., McWhinney, P., Lopez-Velez, R., Fôtkenheuer, G., Kern, P., Zieger, B. W., Kotlowski, A., Fry, G., Cuadros, J., and Myrvang, B.

Abstract

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases

Published
2017

22. Epidemiology and Clinical Features of Imported Dengue Fever in Europe: Sentinel Surveillance Data from TropNetEurop

Author

Jelinek, T., Mühlberger, N., Harms, G., Corachán, M., Grobusch, M. P., Knobloch, J., Bronner, U., Laferl, H., Kapaun, A., Bisoffi, Z., Clerinx, J., Puente, S., Fry, G., Schulze, M., Hellgren, U., Gjørup, I., Chalupa, P., Hatz, C., Matteelli, A., Schmid, M., Nielsen, L. N., da Cunha, S., Atouguia, J., Myrvang, B., Fleischer, K., Jelinek, T., Mühlberger, N., Harms, G., Corachán, M., Grobusch, M. P., Knobloch, J., Bronner, U., Laferl, H., Kapaun, A., Bisoffi, Z., Clerinx, J., Puente, S., Fry, G., Schulze, M., Hellgren, U., Gjørup, I., Chalupa, P., Hatz, C., Matteelli, A., Schmid, M., Nielsen, L. N., da Cunha, S., Atouguia, J., Myrvang, B., and Fleischer, K.

Abstract

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF

Published
2017

23. Epidemiology and clinical features of vivax malaria imported to Europe: Sentinel surveillance data from TropNetEurop

Author

Mühlberger, N, Jelinek, T, Gascon, J, Probst, M, Zoller, T, Schunk, M, Beran, J, Gjørup, I, Behrens, Rh, Clerinx, J, Björkman, A, Mcwhinney, P, Matteelli, A, Lopez-Velez, R, Bisoffi, Z, Hellgren, U, Puente, S, Schmid, Ml, Myrvang, B, Holthoff-Stich, Ml, Laferl, H, Hatz, C, Kollaritsch, H, Kapaun, A, Knobloch, J, Iversen, J, Kotlowski, A, Malvy, Dj, Kern, P, Fry, G, Siikamaki, H, Schulze, Mh, Soula, G, Paul, M, i Prat J, Gómez, Lehmann, V, Bouchaud, O, da Cunha, S, Atouguia, J, and Boecken, G

Subjects
Adult, Male, Travel, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Research, imported, Animals, Europe, Female, Humans, Malaria, Vivax, Plasmodium vivax, Sentinel Surveillance, Vivax, Malaria, lcsh:Infectious and parasitic diseases, parasitic diseases, lcsh:RC109-216
Abstract

Background Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. Objectives To present epidemiological and clinical data on imported P. vivax malaria collected at European level. Material and methods Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. Results Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41–158) versus 31 days (inter-quartile range 4–133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. Conclusions TropNetEurop data can contribute to the harmonization of European treatment policies.

Published
2004

24. The incidence of malaria in travellers to South-East Asia: is local malaria transmission a useful risk indicator?

Author

Behrens, R H, Carroll, B, Hellgren, U, Visser, L G, Siikamäki, H, Vestergaard, L S, Calleri, G, Jänisch, T, Myrvang, B, Gascon, J, Hatz, C, Behrens, R H, Carroll, B, Hellgren, U, Visser, L G, Siikamäki, H, Vestergaard, L S, Calleri, G, Jänisch, T, Myrvang, B, Gascon, J, and Hatz, C

Abstract

BACKGROUND: The presence of ongoing local malaria transmission, identified though local surveillance and reported to regional WHO offices, by S-E Asian countries, forms the basis of national and international chemoprophylaxis recommendations in western countries. The study was designed to examine whether the strategy of using malaria transmission in a local population was an accurate estimate of the malaria threat faced by travellers and a correlate of malaria in returning travellers. METHODS: Malaria endemicity was described from distribution and intensity in the local populations of ten S-E Asian destination countries over the period 2003-2008 from regionally reported cases to WHO offices. Travel acquired malaria was collated from malaria surveillance reports from the USA and 12 European countries over the same period. The numbers of travellers visiting the destination countries was based on immigration and tourism statistics collected on entry of tourists to the destination countries. RESULTS: In the destination countries, mean malaria rates in endemic countries ranged between 0.01 in Korea to 4:1000 population per year in Lao PDR, with higher regional rates in a number of countries. Malaria cases imported into the 13 countries declined by 47% from 140 cases in 2003 to 66 in 2008. A total of 608 cases (27.3% Plasmodium falciparum (Pf)) were reported over the six years, the largest number acquired in Indonesia, Thailand and Korea. Four countries had an incidence > 1 case per 100,000 traveller visits; Burma (Myanmar), Indonesia, Cambodia and Laos (range 1 to 11.8-case per 100,000 visits). The remaining six countries rates were < 1 case per 100,000 visits. The number of visitors arriving from source countries increased by 60% from 8.5 Million to 13.6 million over the 6 years. CONCLUSION: The intensity of malaria transmission particularly sub-national activity did not correlate with the risk of travellers acquiring malaria in the large numbers of arriving visitors. I

Published
2010

27. Sequential changes in hematologic and biochemical parameters in African tick bite fever.

Author

Jensenius, M, Fournier, P-E, Hellum, K B, Wesslén, L, Caruso, G, Priǿ, T, Lǿhne, K, Vene, S, Raoult, D, Myrvang, B, Jensenius, M, Fournier, P-E, Hellum, K B, Wesslén, L, Caruso, G, Priǿ, T, Lǿhne, K, Vene, S, Raoult, D, and Myrvang, B

Abstract

OBJECTIVE: To evaluate the sequential changes and to estimate the frequencies of abnormalities in some commonly measured biological variables in patients with African tick bite fever (ATBF), an emerging spotted fever group (SFG) rickettsiosis in international travelers to rural sub-Saharan Africa. METHODS: A study was done of hemoglobin, total leukocyte count, absolute lymphocyte count, blood platelet count and serum levels of C-reactive protein (S-CRP), alanine aminotransferase (S-ALAT), aspartate aminotransferase, lactic dehydrogenase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, sodium and creatinine during the first two weeks of illness and prior to the institution of antirickettsial therapy in 108 patients with travel-associated ATBF. RESULTS: There were significant falls in mean total leukocyte count, mean absolute lymphocyte count, and mean platelet count, and significant increases in mean S-CRP and S-ALAT. During the first ten days of illness, elevated S-CRP, lymphopenia and elevated S-ALAT were detected in 91.7%, 73.3% and 40.7% of patients, respectively. Most abnormalities were mild. For 55 patients who underwent both S-CRP and absolute lymphocyte count determination, at least one parameter was abnormal in 52 (94.5%) patients. CONCLUSIONS: The sequential changes in many biological parameters during the acute phase of ATBF mimic those reported in other SFG rickettsioses. Mild abnormalities are frequent, with increased S-CRP and lymphopenia being the two most consistent findings

Published
2003

30. Imported Schistosomiasis in Europe: Sentinel Surveillance Data from TropNetEurop

Author

Grobusch, M. P., primary, Mühlberger, N., additional, Jelinek, T., additional, Bisoffi, Z., additional, Corachán, M., additional, Harms, G., additional, Matteelli, A., additional, Fry, G., additional, Hatz, C., additional, Gjørup, I., additional, Schmid, M. L., additional, Knobloch, J., additional, Puente, S., additional, Bronner, U., additional, Kapaun, A., additional, Clerinx, J., additional, Nielsen, L. N., additional, Fleischer, K., additional, Beran, J., additional, Cunha, S., additional, Schulze, M., additional, Myrvang, B., additional, and Hellgren, U., additional

Published
2006
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40. Treatment with Interferon-Alpha2a Alone or Interferon-Alpha2a plus Ribavirin in Patients with Chronic Hepatitis C Previously Treated with Interferon-Alpha2a.

Author

Bell, H., Hellum, K., Harthug, S., Myrvang, B., Ritland, S., Mæland, A., von der Lippe, B., Bjøro, K., Skaug, K., Gutigard, B. G., Raknerud, N., and Simmonds, P.

Subjects
INTERFERONS, HEPATITIS C
Abstract

Background: Preliminary results from combination therapy with interferon-alpha and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising, with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-reponders or relapsers after IFN treatment. Methods: In a multicenter study we randomized 53 HCV RNA-positive patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis C, and all were recruited from a previous IFN study: 26 were previous non-responders and 27 responders with relapse. Group A received interferon-alpha2a, 4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200 mg/day, in combination with the same dose of interferon-alpha2a for 6 months. Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%), type 2 in 3 (6%), and type 3 in 26 (49%). Results: Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of 26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In previous relapse patients sustained loss of viremia was more frequent in genotype 3 (50%) than in genotype 1 (11%) patients (P = 0.022). Conclusions: In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often (50%) than type-1 patients (11%). Previous IFN responders with relapse responded better than previous non-responders. [ABSTRACT FROM AUTHOR]

Published
1999
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41. Immunoglobulin class specific antibodies to M. leprae in leprosy patients, including the indeterminate group and healthy contacts as a step in the development of methods for sero-diagnosis of leprosy.

Author

Melsom, R., Harboe, M., Myrvang, B., Godal, T., and Belehu, A.

Subjects
HANSEN'S disease patients, IMMUNOGLOBULIN G, IMMUNOGLOBULIN M, HANSEN'S disease, COMMUNICABLE diseases, BLOOD proteins
Abstract

IgA, IgM and IgG anti-AM leprae antibody activity was quantitated by solid phase radioimmunoassay in groups of untreated leprosy patients throughout the spectrum, in lepromatous leprosy patients treated for more than 10 years, in an indeterminate leprosy group, and in a non-leprosy control group. IgA, IgM and IgG anti-M. leprae antibody activity increased from the group of healthy individuals exposed to M. leprae but without clinical signs of leprosy to tuberculoid (BT and BT/TT) and further to lepromatous (BL to LL) leprosy. There was a considerable overlap in IgA antibody activity, while the overlap between controls and tuberculoid and lepromatous leprosy was less than 20% in the IgM and IgG assays. After more than 10 years of treatment, the IgG anti-M. leprae activity had decreased markedly, whereas there was less effect in the IgA assay and no significant change in the IgM assay. In contrast to earlier findings; the group of'strictly indeterminate leprosy' showed signs of an active humoral immune response against M. leprae. The IgM anti-AM. leprae activity was higher in indeterminate leprosy than in the control group with virtually no overlap. IgA anti-M. leprae was higher in indeterminate leprosy, but with considerable overlap with the controls. No difference between these two groups was found in the IgG assay. The results are discussed in relation to the value of the various immunoglobulin specific anti-M. leprae assays for different purposes, including development of techniques for sero-diagnosis of leprosy. [ABSTRACT FROM AUTHOR]

Published
1982

42. The Effect of Treatment with α-Interferon on Hepatitis G/GBV-C Viraemia.

Author

JARVIS, L. M., BELL, H., SIMMONDS, P., HAWKINS, A., HELLUM, K., HARTHUG, S., MÆLAND, A., RITLAND, S., MYRVANG, B., VON DER LIPPE, B., RAKNERUD, N., and SKAUG, K.

Subjects
INTERFERONS, HEPATITIS, AMINOTRANSFERASES
Abstract

Background: Hepatitis G virus (HGV) or GBV-C is frequently detected in patients co-infected with hepatitis C virus (HCV). This study investigated host and virologic factors influencing the response to HGV/GBV-C to α-interferon treatment. Methods: HGV/GBV-C was detected and quantified by nested polymerase chain reaction. The influence of variables such as liver biopsy appearance, liver function abnormalities, and response of HCV to interferon treatment was monitored. Results: Fourteen of the 25 HGV/GBV-C-infected patients treated with interferon (3-6 MIU three times a week for 6 months) became non-viraemic during treatment, although all relapsed after treatment withdrawal at 6 months, with no net change in virus load between 0 and 12 months. Conclusions: Predictive factors for clearance of HGV/GBV-C viraemia by interferon were pre-treatment severity of liver disease (median Knodell score of 4, compared with 7 for non-responders; P = 0.030) and alanine aminotransferase levels (median, 114, 182 for non-responders; P = 0.039). Clearance was associated with the treatment response of HCV. Nine of 13 who cleared HGV/GBV-C also cleared HCV, compared with 3 of 11 HGV/GBV-C non-responders; P = 0.05). The shared susceptibility of HGV/GBV-C and HCV to interferon treatment suggests a link between the mechanism of clearance of the two viruses. [ABSTRACT FROM AUTHOR]

Published
1998
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43. IMMUNE RESPONSIVENESS TO <em>MYCOBACTERIUM LEPRAE</em> AND OTHER MYCOBACTERIAL ANTIGENS THROUGHOUT THE CLINICAL AND HISTOPATHOLOGICAL SPECTRUM OF LEPROSY.

Author

Myrvang, B., Godal, T., Ridley, D. S., Fröland, S. S., and Song, Y. K.

Subjects
*MYCOBACTERIAL diseases, *HANSEN'S disease, *MYCOBACTERIUM, *IMMUNOLOGY, *IMMUNE response, *IMMUNOLOGIC diseases
Abstract

Immunological responsiveness was studied throughout the clinical and histopathological spectrum of leprosy (Ridley-.Jopling scale) by the methods of lymphocyte transformation, leucocyte migration inhibition and delayed skin hypersensitivity, The response to Mycobactertuim leprae showed by all methods a continuous decrease from strong responses in the polar tuberculoid (TT) group to virtually negative responses in the polar lepromatous (LL) group. There was a good agreement between the iii vitro methods and the lepromin skin test, giving support to the latter as a useful tool in the evaluation of immune responsiveness to Al. leprae in leprosy patients. The immune response to BCG and PPD on the other hand, decreased only slightly towards the lepromatous pole of the spectrum, confirming the high degree of specificity of the immune defect in lepromatous leprosy. Patients grouped histologically as subpolar tuberculoid (TT/BT) reacted particularly strongly to BCG and PHD. As it is likely that the methods used mainly measured T-lymphocyte function. the clinicopathological manifestations of leprosy appear to reflect the strength of the cellular immune response against M. leprae. Thus the findings give strong support to the concept of a host-determined, immunological diseases pectrum as expressed in the Ridley-Jopling classification. [ABSTRACT FROM AUTHOR]

Published
1973

45. CHARACTERIZATION OF THE CELLULAR IMMUNE DEFECT IN LEPROMATOUS LEPROSY: A SPECIFIC LACK OF CIRCULATING MY CO BACTERIUM LEPRAE- REACTIVE LYMPHOCYTES.

Author

Godal, T., Myklestad, Berit, Samuel, Dorothy R., and Myrvang, B.

Subjects
HANSEN'S disease, SERUM, THYMIDINE, TUBERCULOSIS, LYMPHOCYTES, BCG vaccines
Abstract

The blastogenic response of leucocyte cultures from patients with tuberculoid and lepromatous leprosy has been studied. The leucocytes from the two groups were studied simultaneously and cultivated in the same pool of normal human serum. While the leucocytes from twenty-eight tuberculoid patients responded quite strongly to Mycobacterium leprae after 7 days of culture (average lymphocyte transformation 11.1%), there was a complete lack of response in similar cultures from twenty-seven lepromatous patients (average 0.1% transformed cells). These results were confirmed by studies on cellular incorporation of 3H-thymidine in the cultures from four tuberculoid and four lepromatous patients. This lack of response was quite specific as leucocytes from several lepromatous patients responded to BCG. Furthermore, four patients with both lepromatous leprosy and tuberculosis responded as strongly to BCG and PPD as tuberculous patients without leprosy. In the mixed leucocyte reaction, between two lepromatous or two tuberculoid patients respectively, the lepromatous cells responded well (average 15.0%) and comparably to tuberculoid cells (average 12.1 %). The blastogenic response of purified lymphocytes to M. leprae revealed a similar pattern, i.e. the tuberculoid cells responded well, while again there was a lack of response in the lepromatous group. It is concluded that the lepromatous patients lack circulating lymphocytes responding to M. leprae, indicating that their immunological defect as observed in the present study has features in common with immunological tolerance. [ABSTRACT FROM AUTHOR]

Published
1971

46. Evidence that the Mechanism of Immunological Tolerance ('Central Failure') Is Operative in the Lack of Host Resistance in Lepromatous Leprosy.

Author

Godal, T., Myrvang, B., Frøland, S. S., Shao, J., and Melaku, G.

Subjects
CELLULAR immunity, HANSEN'S disease, LYMPHOCYTE transformation, SERUM, MYCOBACTERIAL diseases
Abstract

The cellular immune defect in lepromatous leprosy has been studied. The following observations have been made: 1) Three lepromatous patients who had been on anti-leprosy treatment for more than 10 years still failed to respond to M. leprae by lymphocyte transformation (mean 0.2%) while they responded strongly to BCG (mean 34.2%) and PPD (mean 56.1%). 2) Lepromatous serum failed to inhibit M. leprae-induced lymphocyte transformation and M. leprae-induced leukocyte migration inhibition. 3) Lepromatous lymphocytes revealed a reduced capacity to attach M. leprae to their surface. The only experimental condition compatible with the observed characteristics would seem to be a state of immunological tolerance to an antigen (or antigens) of M. leprae. The lasting nature of this non-responsive state suggests that it plays a primary role in the pathogenesis of lepromatous leprosy. [ABSTRACT FROM AUTHOR]

Published
1972
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47. Death rates and causes of death in cohorts of serum hepatitis patients followed up for more than 20 years

Author

*, S. GJERULDSEN, §, ABDELNOOR, M., OPJORDSMOEN, S., and MYRVANG, B.

Abstract

A cohort of 214 drug addicts with serum hepatitis and a cohort of 193 hepatitis patients without drug addiction were examined in respect of death rates, causes of death and a number of risk factors for reduced survival. The death rate was significantly higher among the drug addicts than among non-addicts. The annual mortality rate was 1·5% in the drug addict group and 0·7% in the non-addict group. The highest relative risk of death was 860 for female drug addicts in age group 15–24 compared to females of the same age in the general population. The most prevalent cause of death in the drug addict group was drug overdose (53%), whereas in the other group 66% died from various somatic diseases. Hepatitis or complications of viral hepatitis played no role as cause of death among the drug addicts, and infections as a whole were also responsible for very few deaths. For male drug addicts, imprisonment before admission and leaving hospital without the doctors' permission were risk factors for early death.

Published
2001

48. Behavior of Mycobacterium lepraein Human Macrophages In Vitro

Author

Samuel, Dorothy R., Godal, T., Myrvang, B., and Song, Y. K.

Abstract

Attempts have been made to cultivate Mycobacterium lepraein human macrophages in vitro. In 27 out of 55 experiments a two- to ninefold increase (mean 2.31 ± 1.46) in acid-fast organisms were observed over a period of 1.5 to 3 months of cultivation. No such increase was observed with heat-killed bacilli (mean fold increase 0.88 ± 0.19). Macrophages were necessary for obtaining increases. No multiplication was observed on artificial media. A close correlation between increases of acid-fast organisms and changes in viability as determined by the morphology of the bacilli (morphologic index) was found. The increases in acid-fast organisms could be inhibited by anti-leprosy drugs. It is concluded that multiplication of M. lepraemay take place inside human macrophages in vitro. Multiplication appears not to be dependent on whether the macrophages are derived from lepromatous or tuberculoid patients or healthy individuals. Moreover, multiplication took place both at 33 and 37 C. The applicability of this method is at present limited by the restricted survival of human macrophages in vitro.

Published
1973
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