Hepatitis B antigen in a leprosy hospital

A survey of hospital patients with lepromatous and with tuberculoid leprosy showed 5% of the former and 6.3% of the latter to be carriers of hepatitis B antigen. These findings contradict the hypothesis of a genetically determined predisposition; opportunity for infection appears rather to be the determining factor. It was also found that (1) the number of carriers was higher among patients staying longer in hospital; (2) titres of antigen in patients with lepromatous leprosy were higher than in those with tuberculoid leprosy or in controls; and (3) antigen titres measured twice at an interval of 4 months indicated that the carrying of hepatitis B antigen in patients with leprosy is stable and persistent.     

HIV-M. Leprae Interaction: Can HAART Modify the Course of Leprosy?

It has been speculated that, as seen in tuberculosis, human immunodeficiency virus (HIV) and Mycobacterium leprae (M. leprae) co-infection may exacerbate the pathogenesis of leprosy lesions and/or lead to increased susceptibility to leprosy. However, to date, HIV infection has not appeared to increase susceptibility to leprosy. In contrast, initiation of antiretroviral treatment (ART) has been reported to be associated with anecdotal activation of M. leprae infection and exacerbation of existing leprosy lesions. To determine whether ART is associated with worsening of the manifestations of leprosy, a cohort of leprosy patients recruited between 1996 and 2006 at the Oswaldo Cruz Foundation (FIOCRUZ) Leprosy Outpatient Clinic in Rio de Janeiro, Brazil, was studied longitudinally. ART treatment of HIV/leprosy co-infection was associated with the tuberculoid type, paucibacillary disease, and lower bacillary loads. CD4 lymphocyte counts were higher among HIV/leprosy patients at the time of leprosy diagnosis, while viral loads were lower compared with the time of HIV diagnosis. The conclusion was that ART and immune reconstitution were critical factors driving the development and/or clinical appearance of leprosy lesions.     

The susceptibility of chickens to Trypanosoma brucei subspecies

Chickens were susceptible to infection with three different stocks of the subgenus Trypanozoon: two of presumptive Trypanosoma b. brucei and one of T. b. rhodesiense. Two groups of chickens were used: the first hatched following inoculation with either T. b. brucei or T. b. rhodesiense during embryonic development, and the second were infected as adult birds. In both experimental groups, parasitaemia persisted for prolonged periods, but was mostly subpatent and detectable only by subinoculation of blood into mice. In chickens infected as embryos, parasitaemias were patent for five weeks after hatching, but subpatent thereafter (to weeks 13 to 17). Quantitative estimations of the parasitaemias of seven of the birds hatched from embryos inoculated with T. b. brucei revealed fluctuations in the number of circulating trypanosomes, with an initial peak between days 2 to 9 after hatching. Between weeks 13 to 17 after hatching the chickens appeared to have recovered spontaneously from the trypanosome infections. Homologous challenge at week 20 failed to produce a recrudescence of parasitaemia, indicative of a possible acquired immunity.The infections of ten chickens inoculated with either T. b. brucei or T. b. rhodesiense as adult birds were microscopically subpatent throughout the observation period of six weeks, but subinoculation of blood into mice showed the chickens were parasitaemic from week one and thereafter. Different aspects of infection of avian hosts by the Trypanozoon subspecies are discussed.     

Seropositivity to anti-phenolic glycolipid-I in leprosy cases, contacts and no known contacts of leprosy in an endemic and a non-endemic area in northeast Brazil

The seroprevalence rates of IgM anti-phenolic glycolipid-I (PGL-I) antibodies in four study groups with differing exposure to Mycobacterium leprae in Ceará, Brazil were investigated between March 2005 and August 2006. The first three groups in a high prevalence area included 144 cases of leprosy, their 380 contacts and 317 participants with no known leprosy contact. The fourth group in a low prevalence area consisted of 87 participants with no known leprosy contact living in an area in which no cases of leprosy had been reported in the previous 6 months. Seropositivity and levels of IgM antibodies to PGL-I were investigated using ELISA. The seropositivity levels of anti-PGL-I among the different clinical forms of leprosy cases were 61% for lepromatous, 25% for tuberculoid and 27% indeterminate. The levels of anti-PGL-I antibodies in the endemic area differentiated leprosy cases from non-cases. However, the seropositivity was similar among contact cases (15.8%) and no known leprosy contact cases from high (15.1%) and low (13.8%) prevalence areas. The seropositivity of both contacts and no known contacts was much higher than previously reported among no known contacts in other endemic areas. The study indicates that anti-PGL-I antibodies are not useful as immunological markers of household leprosy contacts and no known leprosy contacts in endemic areas.     

The maximum density of anopheline mosquitoes that can be permitted in the absence of continuing transmission of filariasis

Using two years of mosquito collections from two fixed stations on Guadalcanal it was possible to compare the average man-biting rate with the prevalence of microfilaraemia. One area was found to be free of infection while the other still had one positive case. The DDT residual spraying had caused a change in biting habits of A. farauti No. 1 allowing a greater density of mosquitoes to bite man at times when they had lower microfilaria densities. This difference was compared with the pre-spray density so that the maximum permissible number of mosquitoes biting man without transmission of filariasis taking place, could be calculated.A theoretical value for m of 19.84 had been worked out previously, this study gave a corrected observed value of m of approximately 20, very close to the calculated theoretical value. The situation studied here probably showed incomplete interruption of transmission, so it was considered preferable to recommend a figure of 0.66 average vector man-biting rate per hour indoors for the critical value.     

Immunological problems in leprosy research

This paper discusses the evidence for and against the view that the spectrum of pathological changes in leprosy, extending from the lepromatous form to the tuberculoid form, may be caused by differences in the immune responses of patients. Patients with the tuberculoid form of leprosy generally have well-developed specific cell-mediated immunity, but in a large proportion of patients with lepromatous leprosy the specific cell-mediated immunity to Mycobacterium leprae and sometimes to other antigens seems to be deficient, whereas the circulating antibody response is well-developed. Techniques for assessing the immune response in patients are described in detail with the objective of improving the comparability of such investigations. The paper also discusses the importance of several investigatory approaches to clinical leprosy and the value of animal models for leprosy research.     

BCG vaccination in leprosy: final results of the trial in Karimui, Papua New Guinea, 1963-79

The efficacy of BCG vaccine in preventing the clinical manifestations of leprosy in a tuberculosis-free area of Papua New Guinea is reported. Between 1963 and 1966 a total of 5356 subjects, randomized to receive BCG or saline inoculations, were examined for leprosy before the vaccination and surveillance was continued until 1979. BCG afforded 48% protection against clinical leprosy, being most effective against borderline tuberculoid leprosy and in children vaccinated when under 15 years old. Protection was evident within 12 months in those vaccinated between the ages of 10 and 15 years but was delayed in other age groups. There was evidence for accelerated manifestations of tuberculoid leprosy in children vaccinated when under 5 years of age. Tuberculin sensitivity was more likely to be sustained following multiple BCG inoculations; vaccinees with sustained tuberculin sensitivity had the lowest incidence of leprosy, but protection was also evident in tuberculin-negative vaccinees. These results may have implications for ongoing trials of leprosy vaccine incorporating BCG.     

A comparison of electrophoretic methods for isoenzyme characterization of trypanosomatids. I: Standard stocks of Trypanosoma cruzi zymodemes from northeast Brazil

An investigation of the relative merits of cellulose acetate electophoresis (CAE) and starch-gel electrophoresis (SGE) was made for 18 enzymes of T. cruzi using standard stocks of zymodemes Z1, Z2 and Z3. The 18 enzymes were those shown previously to be the most suited to routine screening of T. cruzi on starch-gel, namely, aspartate aminotransferase (E.C.2.6.1.1. ASAT); alanine aminotransferase (E.C.2.6.1.2. ALAT); phosphoglucomutase (E.C.-2.7.5.1. PGM); glucosephosphate isomerase (E.C.-5.3.1.9. GPI); malate dehydrogenase (oxaloacetate decarboxylating) (NADP⁺) (E.C. 1.1.1.40. ME); glucose-6-phosphate dehydrogenase (E.C.1.1.1.49 G6PD); malate dehydrogenase (E.C. 1.1.1.37. MDH); aconitate hydratase (E.C.4.2.1.3. ACON); isocitrate dehydrogenase (NADP⁺) (E.C.1.1.1.42. ICD); alcohol dehydrogenase (NADP⁺) (E.C.-1.1.1.2. ADH); lactate dehydrogenase (E.C.1.1.1.27. LDH); aminopeptidase (cytosol) (E.G.3.4.11.1. PEP); pyruvate kinase (E.C.2.7.1.40. PK); phosphoglycerate kinase (E.C.2.7.2.3. PGK); enolase (E.C.4.2.1.11. ENO); hexokinase (E.C.2.7.1.1. HK); mannose phosphate isomerase (E.C.5.3.1.8. MPI); and glutamate dehydrogenase (E.C.1.4.1.2. GD). Of these MDH and PEP failed to give satisfactory patterns on CAE. The cellulose acetate zymograms of the other 16 enzymes were as good as, and in some cases better than, those of starch. Increased CAE resolution for ME and G6PD enabled all three zymodemes to be distinguished. Single CAE bands replaced double SGE bands in some cases, and vice versa, without affecting the zymodeme classification. It was concluded that CAE and SGE were both suitable for isoenzyme characterization and were complementary to each other. CAE characterization of T. cruzi was recommended for use in field work and simple laboratories because of its simplicity, transportability, low maintenance requirements and low capital expenditure. Isoelectric focusing (IEF) of ASAT, ALAT, GPI and PGM on Ampholine PAG plates gave poor results, in our hands, and was considered impracticable for routine characterization of T. cruzi.     

重庆市高校新生正常高值血压的现状及影响因素分析

目的:了解重庆市高校新生正常高值血压的现状及其影响因素,为早期干预提供依据。方法:采用分层抽样法,对4576名入学新生体检结果进行统计分析,根据其血压值分为血压正常组(A组)和正常高值血压组(B组),对比两组学生体检结果。资料采用SPSS19.O软件包进行数据统计分析。结果:B组中有15.2%的人超重、6.3%的人肥胖、12.2%的人肝功异常。三项指标与A组的比较均有统计学意义。B组学生的体检结果均高于A组学生,差异有统计学意义。二元Logistic回归分析显示:B组学生血压升高的最重要的影响因素是肥胖(P<0.001)和腹型肥胖(P<0.001);其次是超重(P<0.001)、肝功异常(P<0.001)、脉搏>100次/分(P<0.005)。结论:重庆市高校新生正常高值血压检出率较高,体重指数、腹型肥胖、脉搏>100次/分、肝功异常是其主要影响因素,应针对相关因素实施干预并定期追踪评价干预效果以维护学生的健康。     

Effectiveness of BCG vaccination among leprosy contacts: a cohort study

The study assessed the effectiveness of BCG vaccination against leprosy among the contacts of 1161 leprosy patients at the FIOCRUZ Leprosy Outpatient Clinic, RJ, Brazil, from June 1987 to December 2006. Following National Leprosy Program guidelines, the clinic has administered one-to-two doses to all healthy contacts since 1991. Among the 5680 contacts, 304 (5.4%) already had leprosy. Of the 5376 eligible healthy contacts, 3536 were vaccinated, 30 of whom were excluded due to previous or current tuberculosis, or HIV. In 18 years of follow up, 122 (2.15%) incident cases were diagnosed (58 vaccinated and 64 not), 28 occurring in the first year of follow up (21 vaccinated, 16 with no scar). The protection conferred by BCG was 56% and was not substantially affected by previous BCG vaccination (50% with a scar and 59% without). The risk of tuberculoid leprosy during the initial months was high among those vaccinated with no scar. However, it had substantially declined by the first year and in the following years, when the protection rate in this group reached 80%. Since Brazil is endemic for leprosy and the detection rate is not declining satisfactorily, vaccinating all contacts could be an effective means of substantially reducing the incidence of leprosy.     

Nutritional status of domestic populations of Triatoma infestans

This paper establishes that the weight: length ratio of Triatoma infestans is superior to weight alone as a measure of nutritional status. The weight: length ratios of adults, V and IV stage nymphs correlated with their time since feeding. The weight: length ratio of V stage nymphs correlated with their life expectancy expressed as days until moulting to the adult stage. The weight: length ratio of wild females measured on capture did not correlate with the number of eggs laid during the next 30 days, but after feeding on chicken in the laboratory this correlation was shown.The mean weight: length ratio of different classes of bugs was used to compare the nutritional status of T. infestans populations in three rural houses in central Brazil. One house was recently constructed, containing a newly-established population of bugs. One house was over 15 years old, containing a long-established bug population. The third house had been abandoned for six months and the bug population was in decline. The three houses were carefully demolished to allow a large sample of bugs to be collected from each. The mean weight: length ratios of adults, unfed V stage, fed and unfed IV stage, and fed and unfed III stage nymphs from the newly-colonized house were significantly higher than those of corresponding classes of bugs from the long-established bug population, and from the declining bug population.This evidence fulfils a prediction previously made by the author and supports the hypothesis that the density of domestic population of T. infestans depends on the nutritional status of the bugs which is, in turn, limited by the number of hosts available.     

Liver dysfunction in haemophilia

Liver function was studied in 139 of 291 haemophiliacs known to a single Regional Haemophilia Centre including patients with classical haemophilia, Christmas disease and von Willebrand's disease. In 57 patients, six-monthly liver function tests over a five year period were also available. Thirty-nine of the 139 patients had had jaundice or hepatitis and 56 had a positive test for HBsAb in the blood although few of these had had an identifiable clinical illness. Fifty-eight haemophiliacs had elevated serum aminotransferases at the time of study, but the five year review revealed only six patients who had had persistently abnormal results, although none had clinically evident liver disease. Liver dysfunction was unrelated to a history of hepatitis, to a positive HBsAb test, or to age, type of haemophilia, factor level or frequency of factor replacement treatment. Abnormalities of liver function in haemophilia appear to be unrelated to past or present hepatitis B infection in most cases and may not be related to any single transmitted infectious agent.     

Cell-mediated immunological processes in leprosy

A large number of organisms such as viruses, protozoa, helminths, fungi and bacteria, especially mycobacteria, need cell-mediated immunological processes for their elimination. As well as being involved in protection, cell-mediated immunological processes are also involved in a number of allergic reactions to products derived from mycobacteria. Cell-mediated immunological processes can be demonstrated by a number of in vitro reactions. Leprosy can present with a wide range of different clinical patterns. The clinical spectrum of leprosy can be shown to depend on the degree of the cell-mediated immune response of the host against Mycobacterium leprae. Thus in tuberculoid leprosy there is a high degree of cell-mediated immune response whereas in lepromatous leprosy such a response is virtually absent. There appears to be a constitutional predisposition to lepromatous leprosy. In addition to a specific loss of cell-mediated immune response against Myco. leprae, there is also a non-specific drop in the ability of patients with lepromatous leprosy to show other aspects of cell-mediated immune response, e.g., contact sensitivity and skin homograft rejection. There is also a relative impairment of the ability of lymphocytes to react in vitro. Lymph nodes from patients with lepromatous leprosy show a deficiency in those areas associated with the development of cell-mediated immune responses.     

Atypical findings in a rat model for parenteral nutrition–induced cholestasis

The pathophysiology of parenteral nutrition–associated cholestasis (PNAC) in young children is poorly understood. The composition of the total parenteral nutrition (TPN) is reported to be of importance for the occurrence of PNAC. In this study, the effects of parenteral nutrition with different caloric loads and different amounts of lipids were studied in a rat model for PNAC. Four different groups of male Wistar rats were used. In 3 groups, a central catheter was placed in the right jugular vein. The first group (group A) received NaCl 0.9% and had free access to food and water; the other two (groups C and D) received TPN, containing 1142 and 1611 J kg⁻¹ d⁻¹, respectively. In group B, the common bile duct was ligated. Animals were killed after 7 or 14 days; at these points, liver enzymes were measured, and liver histology was assessed. In the bile duct ligation group, all liver enzymes significantly increased compared with baseline. Liver enzymes did not significantly change in the other groups. Histology showed cholestatic changes in the bile duct ligation group. In the parenteral nutrition groups, significant steatotic changes were found, and in the high caloric TPN group, more so than in the TPN group. In this study, TPN was not associated with abnormal liver function tests or with histological evidence of cholestasis. Total parenteral nutrition was associated with steatosis in this rat model, which is a finding commonly reported in the literature. Therefore, it is questionable whether the rat is a good model for TPN-associated cholestasis.     

Immunological problems in leprosy research: 1

This Memorandum reviews the present status of knowledge of the immunology of leprosy, with particular attention to developments since the publication of a similar review in 1970. The different types of lepromin reaction and their significance in healthy contacts and in patients with tuberculoid and lepromatous leprosy are discussed. The immunological responsiveness of patients with leprosy is also considered, with special attention to in vitro methods for evaluating this response. Part 2 of the Memorandum will cover possible mechanisms of altered immune response in leprosy (including a tentative scheme to explain the possible genesis of the lepromatous lesion); genetic, nutritional, and hormonal factors; the possibility of vaccination; attempts at immunotherapy; and areas in which further research is needed. A detailed protocol for evaluating the effect of transfer factor in leprosy will be included as an annex.     

Segregation analysis of leprosy in families of northern Thailand

Sixty-three families with multiple instances of leprosy were identified through a major leprosy treatment center in northern Thailand. Complex segregation analyses for single major genes or polygenic inheritance were performed using the maximum-likelihood routine POINTER to determine the most likely etiologic model of genetic susceptibility. Liability differences between men and women were considered in these models. When individuals were considered to be affected because they had any form of leprosy, a generalized major gene model with nearly dominant parameters on the liability scale, but additive penetrances, was found to be the most likely. When only those individuals who had tuberculoid forms of leprosy were considered to be affected, a recessive model was found to be the most likely; however, the discrimination between various models was poor. Further analyses are necessary to delineate genetic mechanisms to explain these apparently divergent results. In particular, methods of testing two locus models should be considered.     

ABO blood groups in relation to hepatitis-B surface antigen (Australia antigen)

The ABO blood groups and their relationship with Australia antigen (HBsAg) were studied in 500 blood donors and 76 patients. Most of the blood donors belonged to group ‘B’ while the Australia antigen (HBsAg) was prevalent in the blood group ‘A’ (9·30%). 76 patients clinically diagnosed as viral hepatitis showed a similar trend, having the highest percentage of HBsAg positivity in ‘A’ group (35·71%). In both, this was found statistically significant (P > 0·005). None of those with AB blood group showed HBsAg.     

Density regulation of domestic populations of Triatoma infestans in Brazil

Twenty old houses in a rural area of central Brazil were sampled monthly for Triatoma infestans during 16 months. The samples indicated peak adult emergence between January and May, preceded by peak emergence of stage V, IV and III nymphs respectively. Stage I and II nymphs were rarely taken in the samples. A much smaller peak of adult emergence occurred in September; thus the two peaks of adult emergence during the year were consistent with the approximately six months duration of egg-to-adult development usually recorded in laboratory studies.During January, 1977, when the study began, all houses were searched for dead bugs, exuviae, eggs and eggshells. These samples were used to calculate stage mortalities, from which a simple life-table was constructed. These data were combined with laboratory data concerning stage development times and female longevity and fecundity. Sensitivity analysis of the life-table showed it to be most sensitive to small changes in daily mortality rate and total egg-to-adult development time.The data were used to advance an hypothesis that the size of domestic populations of T. infestans is mainly controlled by changes in the egg-to-adult development time and, to a lesser extent, by changes in female reproductivity. Both these factors are in turn controlled by the nutritional status of the bug population, which, if the supply of food, i.e. number of hosts, is constant, is dependent upon the density of the bug population. It is argued that this mechanism of density regulation functions within limits set by the prevailing ambient temperature.     

Serology in leprosy

A critical survey of the literature on serology in leprosy has shown that sera taken from lepromatous patients display some striking differences in comparison with sera from tuberculoid patients. The tests most frequently employed were complement-fixation, haemagglutination, electrophoresis, precipitation and immunofluorescence, together with a variety of antigens not only from lepromas but also from Mycobacterium tuberculosis and other actinomycetales.     

Association between smoking, acetaldehyde dehydrogenase-2 1-1 status, and alcohol drinking among Taiwanese polyvinyl chloride workers

To study the factors affecting alcohol consumption among Taiwanese workers, we conducted an investigation of the association between alcohol drinking and smoking, aldehyde dehydrogenase-2 (ALDH2) status, alcohol dehydrogenase-2 (ADH2) status, any history of abnormal liver function, and hepatitis B and C viral infection. The subjects included 207 male workers who had been followed-up with respect to liver function periodically since 1992. Information relating to current alcohol consumption and smoking habits was obtained by an interviewer-administered questionnaire in 1996, and any history of liver function and hepatitis B and C virus infection was obtained from previous medical surveillance. Genotypes of ALDH2 and ADH2 were determined by polymerase chain reaction/restriction fragment polymorphism assay. Results have revealed that smoking and ALDH2 1-1 status were associated with current alcohol consumption (respectively: odds ratio, 23.3; P < 0.01 and odds ratio, 14.5; P < 0.05). Neither a history of abnormal liver function nor a history of hepatitis B and/or C infection was associated with current alcohol consumption. It seems that only those with ALDH2 1-1 who are smokers consume alcohol. We conclude that smoking and inherited ALDH2 1-1 are the most important determinants of alcohol consumption. In addition to the medical advice of physicians in their yearly health check-ups, worksite health-promotion programs based on both alcohol consumption habits and smoking cessation should be instituted forthwith, particularly for those who demonstrate the potential for developing liver damage.