SEARCH · PubMed Health

Results for “LEPROMIN”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources

PubMed1985

Histology of the Mitsuda reaction of healthy adults with no known contacts with leprosy patients.

Mitsuda tests were performed on 100 healthy adult Brazilian males unrelated consanguineously to leprosy patients and with no known contacts with this disease. Three lepromatous patients served as negative Mitsuda controls. The lepromin employed was from Mycobacterium leprae-infected armadillo tissue prepared according to WHO standards. Clinical response to the lepromin inoculation was graded according to the recommendations of the VI International Leprosy Congress held in Madrid (1953). The histological reaction was graded according to the authors' criteria based on the intensity of the granulomatous response. The clinically positive (77), the doubtful (19), and 1 out of 4 clinically negative Mitsuda reactors disclosed histologically positive reactions of different degrees of intensity. A significant association between the clinical and histological readings of the Mitsuda reaction was demonstrated when the results of both readings were grouped in two classes: negative and non-negative. However, the different degrees of the histologically positive lepromin reactions were distributed at random among the clinically positive Mitsuda reactors. The frequency of histologically negative Mitsuda reactors observed among the healthy subjects who had no known contacts with leprosy patients (3%) was significantly low when compared to the frequencies reported in the pertinent literature concerning healthy contacts of patients with Hansen's disease.

Adult↗

PubMed1983

Does isopathic phenomenon occur in leprosy?

Twenty-five patients of leprosy classified according to the criteria of Ridley and Jopling (1966) were studied to verify the existence of isopathic phenomenon, using lepromin and autoclaved BCG as antigens. BCG as well as lepromin injection sites showed tuberculoid granulomas in all the cases of tuberculoid, borderline tuberculoid, mid-borderline and indeterminate leprosy. In lepromatous and borderline lepromatous cases BCG injection sites showed infiltration of foam cells containing AFB and foci of epithelioid cells, while lepromin injection sites showed infiltration of foam cells containing AFB only. These findings in the present study do not support the occurrence of isopathic phenomenon in leprosy with BCG.

BCG Vaccine↗

PubMed1983

[Histopathology of the Mitsuda reaction in healthy adults not in contact with Hansen's disease patients].

A detailed study on the histopathology of Mitsuda's reaction was made in 100 adult non-contact hanseniasis patients inoculated with lepromin A (armadillo). It was found that the histological structure of Mitsuda's reaction with lepromin A does not differ from the one observed with lepromin H. There is also no difference between the histological picture observed in healthy non-contacts and the one found in tuberculoid patients and in contact healthy persons. Mitsuda's reaction in non-contact hanseniasis patients presented variations of histological degree--Classes O (-) I (+/-) II (+) III (++) IV ( )--from no inflammatory reaction and positive bacilli, until formation of a complete tuberculoid granuloma and absence of bacilli. In 97% of the cases reaction was positive. Class III, i.e., represented by incomplete tuberculoid granuloma formed by epithelioid cells with follicular arrangement and lymphocytic halo, predominated in the series (42%). The findings of this research state, once again, that an efficient result of the Mitsuda's reaction depends fundamentally of the histological examination, since in only 16 cases the clinical reading coincided with histopathology. Disaccordance found on the remaining 84 cases was attributed to the secondary alterations (necrosis and suppuration) associated to the histological structure of the Mitsuda reaction follows the Jadassohn-Lewandowsky law and are in accordance with the morphological concept and classification of polar granulomas proposed by Michalany & Michalany.

Adult↗

PubMed1982

[Cellular immunity in leprosy patients].

Forty eight clinically arrested lepromatous patients were submitted to several tests to evaluate cellular immunological competence (PPD, Trichophytin, DNCB, determination of the percentage of T lymphocytes in the peripheral blood, and early and late reactions to the lepromin). The results of the Trychophytin test and of the lymphocyte percentage test did not differ from those of the control group, whereas the results to the PPD test were more often positive for the arrested Virchovian cases. All the patients presented positivity to the DNCB test, and none of them showed positivity to the Fernandez reaction. As for the late reaction to the lepromin, all the patients were negative, although in histopathological testing four degrees of reactivity was observed ranging from focal, non specific inflammatory reaction to granulomatous histiocytic with an epithelioid outline. By means of these results the authors were able to confirm that: 1. There is no cross reactivity between the PPD and lepromin tests. 2. Sulfone therapy does not interfere in immunocellular results for the tests employed. 3. Lepromatous patients respond like the general population to the unspecific sensitivity tests utilized. 4. The finding of histiocytic reaction with epithelioid outline in some biopsies of Mitsuda reaction in lepromatous patients, suggests the presence of a sub-population within this group, probably Borderline patients that suffered during the infection's evolution downgrading of theirs clinic and histological characteristics.

Dinitrochlorobenzene↗

PubMed1994

Diagnostic value of gene probes and its correlation with clinical profile of leprosy in children.

Clinico-bacteriological profile of 73 leprosy patients below 16 years of age was studied. Majority of the patients were males and fell in 11-16 years age group (p < 0.05). Skin lesions were present in all cases on both exposed as well as unexposed areas and their number increased with advancing age. Cutaneous sensations were affected in most of the patients while nerve thickening was observed in 41. As age increased, the disease moved from the tuberculoid end of spectrum towards the lepromatous end (p < 0.05) and the positivity of the skin smears increased (p < 0.05). Majority of the paucibacillary cases were lepromin positive while most multibacillary cases were lepromin negative (p < 0.01). Two M. leprae specific gene probes were applied in 42 cases to assess their diagnostic value. Eighty one per cent cases were picked up by the probes indicating presence of active bacilli. These included all lepromin positive cases, all smear positive cases, and most of smear negative cases (p < 0.05). Seven children with inconclusive histology were also positive. Drug treatment and inadequate size of biopsy sample could explain the negative probe results in 19% cases. This study highlights the immense potential of gene probes in diagnosing leprosy in children.

Adolescent↗

PubMed1993

Sensitization potential and reactogenicity of varying doses of BCG plus killed Mycobacterium leprae: an extended study.

This study is an extension of a previous study on an antileprosy combination vaccine of BCG plus killed Mycobacterium leprae (KML) regarding its sensitization potential and reactogenicity. The study was extended to see if by reducing the dose of BCG in the combination vaccine the incidence of suppurative adenitis could be reduced without a significant reduction in the level of postvaccination skin-test responses. The study included 860 individuals, and three preparations of the combination vaccine [BCG 0.05 mg + 6 x 10(8) KML (I), BCG 0.05 mg + 5 x 10(7) KML (II), BCG 0.01 mg + 5 x 10(7) KML (III)] along with normal saline (i.v.) were used. Each individual received one of these four preparations by random allocation. They were also tested with Rees' M. leprae soluble antigen (MLSA) and lepromin A 12 weeks after vaccination. Reactions to the MLSA were measured after 48 hr; reactions to lepromin A after 48 hr and 3 weeks. The character and size of the local response at the vaccination site were recorded at the third, eighth, and 15th week postvaccination. The results of the study showed that by halving the dose of BCG in the combination vaccine BCG plus 6 x 10(8) KML a) the incidence of suppurative regional adenitis was reduced significantly, b) there was no significant change in the post-vaccination response at 12 weeks as measured by Rees' MLSA and lepromin A, and c) the evolution of the vaccination lesion was somewhat prolonged. This dose was found satisfactory for use in a comparative antileprosy vaccine trial in South India.

Adolescent↗

PubMed1996

Immunological profiles of leprosy patients and healthy family contacts toward M. leprae antigens.

In this study, we measured simultaneously the in vitro and in vivo T lymphocyte reactivities and the antibody responses of leprosy patients and healthy family contacts (HFC) toward Mycobacterium leprae antigens. The in vitro lymphoproliferative response of the HFC to leprosin A was comparable to that of tuberculoid leprosy patients. However, their skin-test reactivity to Dharmendra lepromin was considerably higher compared to the in vitro response to leprosin A. A significant number of HFC failed to respond to M. leprae antigens, both in vitro and in vivo, and the unresponsiveness to either test was not related to the type of leprosy patients in the household. A marginal correlation was observed between the skin-test reactivity of HFC and the age of the individuals. Even though a significant proportion of HFC showed positive anti-PGL-I IgM levels, none showed a positive titer in the serum antibody competition test toward the M. leprae-specific epitope My2. A positive anti-PGL-I IgM response together with a negative lepromin skin-test reactivity showed a clear downward trend from the lepromatous pole toward the tuberculoid pole. A small number of HFC, all contacts of lepromatous patients, were lepromin skin-test negative with positive anti-PGL-I IgM levels, but the majority among them showed T-cell reactivity to mycobacterial antigens in vitro. These results are discussed in relation to immunological correlates of the susceptibility to M. leprae infection.

Antibodies, Bacterial↗

PubMedDate not supplied

Sensitization and reactogenicity of two doses of candidate antileprosy vaccine Mycobacterium w.

M.w vaccine is one of the antileprosy vaccines under test in an ongoing comparative vaccine trial in South India. The objective of the present study was to examine the sensitizing ability, as measured by skin test reactions to Rees' MLSA and lepromin, and reactogenicity of M.w vaccine in the local population. Two doses of M.w, 1 x 10(9) bacilli and 5 x 10(9) bacilli, were used, in two separate studies of 395 and 400 "healthy" individuals aged 1-65 years. In each study, the study subjects received either M.w vaccine or normal saline (control), by random allocation. The results showed that healing of vaccination lesions was uneventful although the healing process was somewhat prolonged with the higher dose. The mean size of lesions was 7.0 mm and 9.5 mm with the low and high doses of the vaccine, respectively. The results also showed that M.w vaccine in a dose of 1 x 10(9) bacilli, failed to induce post-vaccination sensitization as measured by reactions to Rees' MLSA and by Fernandez and Mitsuda reactions to lepromin-A. However, when the dose of the vaccine was increased to 5 x 10(9) bacilli the mean sizes of post-vaccination reactions to Rees' MLSA and lepromin-A (both early and late) were significantly larger in the vaccine group compared to that in the control group. The sensitizing effect attributable to the vaccine was of the order of 1.5 mm to 1.8 mm.

Adolescent↗

PubMedDate not supplied

Study of gene probes in childhood leprosy.

The objective was to detect nucleic acids of M. leprae in skin lesions of leprosy patients and study the effect of treatment on these nucleic acids, using r-RNA gene probes, using a cross sectional study. The study was carried out at Department of Paediatrics, S.N. Medical College, Agra and Department of Microbiology, Central JALMA Institute for leprosy, Agra. The study included 32 cases of leprosy less than 16 years of age, divided into 3 groups viz. without treatment (12 cases), in middle of treatment (11 cases) and at the end of treatment (9 cases). All cases were subjected to a detailed history and thorough clinical examination. All of them had smear examination and lepromin test done and their skin biopsies were subjected to gene detection. Nucleic acids were isolated from skin biopsies of all cases by standard procedure. After dot blotting of these nucleic acids, they were hybridised with radioactive (p32) r-RNA probes. The results were interpreted after getting the X-ray films processed with background signals from controls. Majority of cases were between 13-16 years of age. As age advanced, the disease moved from tuberculoid end of spectrum towards lepromatous end (p < 0.05). Majority of paucibacillary (PB) cases were lepromin positive while majority of multibacillary (MB) cases were lepromin negative (p < 0.05). In specimens of untreated cases, 50% of PB specimens and 87.5% of MB specimens were positive for r-RNA probes. In multibacillary type 100% smear positive specimens and 67% smear negative specimens were positive for r-RNA probes. In patients during the middle of treatment positivity for r-RNA decreased and 20% of PB specimens and 16.6% MB specimens were positive. At the end of treatment (1 year for PB cases and 2 years for MB cases), the results of r-RNA were negative, which indicated that the treatment regimens used in the study were effective. This study supports the usefulness of r-RNA probes as a diagnostic and therapeutic tool in childhood leprosy.

Adolescent↗

PubMed1991

Risk factors for type-1 reactions in borderline leprosy patients.

Type-1 or reversal reactions are the major cause of nerve damage and disability in leprosy. We wished to determine whether there were any clinical or laboratory markers that identified patients with an increased risk of type-1 reaction. 42 (31%) of 136 Nepalese borderline leprosy patients (97 male, 39 female; age range 7-73 years) had a type-1 reaction during the first 2 years of multi-drug therapy. Before therapy, 41 (98%) of the 42 patients were seropositive for antibodies to one of three mycobacterial antigens. Seropositivity for IgM antiphenolic-glycolipid-1 (PGL-1) antibodies, but not IgG anti-lipoarabinomannan or anti-Mycobacterium leprae 35 kDa protein antibodies, was significantly associated with subsequent manifestation of a type-1 reaction (p less than 0.001). The concentration of IgM anti-PGL-1 antibodies in serum was significantly higher in patients in whom a type-1 reaction developed. The risk attributable to anti-PGL-1 seropositivity was independent of leprosy class, skin smear positivity, and the presence of other anti-M leprae antibodies (adjusted odds ratio = 8.7, p less than 0.001). In the 87 patients who had a lepromin test, anti-PGL-1 seropositivity and lepromin reactivity were significant independent risk factors for subsequent reaction. 78% of patients with positive lepromin reactivity and IgM anti-PGL-1 antibodies had type-1 reactions. Patients with these risk factors should be carefully monitored during antimicrobial therapy to permit early initiation of anti-inflammatory treatment thus minimising permanent nerve damage and resultant disability.

Adolescent↗

PubMed1994

T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in tuberculosis and leprosy.

Lymphoproliferation and gamma interferon (IFN-gamma) secretion in response to 28 overlapping 20-mer synthetic peptides covering the complete sequence of the mature (295-amino-acid) 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis and Mycobacterium bovis BCG (MTAg85A) was examined by using peripheral blood mononuclear cell (PBMC) cultures from healthy tuberculin- and lepromin-positive volunteers and from patients with tuberculosis and leprosy. Peptide recognition was largely promiscuous, with a variety of human leukocyte antigen haplotypes reacting to the same peptides. PBMC from all tuberculin-positive subjects reacted to Ag85, and the majority proliferated in response to peptide 6 (amino acids 51 to 70), peptides 13, 14, and 15 (amino acids 121 to 160), or peptides 20 and 21 (amino acids 191 to 220). PBMC from tuberculosis patients demonstrated a variable reactivity to Ag85 and its peptides, and the strongest proliferation was observed against peptide 7 (amino acids 61 to 80). MTAg85A peptides were also recognized by PBMC from healthy lepromin-positive volunteers and paucibacillary leprosy patients (again in a promiscuous manner), but despite a 90% homology between the 85A proteins of M. leprae and M. tuberculosis, the peptides recognized were different. PBMC from lepromin-positive healthy contacts reacted against peptide 2 (amino acids 11 to 30), peptide 5 (amino acids 41 to 60), and peptides 25 and 26 (amino acids 241 to 270). PBMC from paucibacillary patients reacted preferentially against peptide 1 (amino acids 1 to 20) and peptide 5. Multibacillary patients were not reactive to Ag85 or the MT85A peptides. IFN-gamma production was generally detected simultaneously with positive lymphoproliferative responses, although peptide 1 mostly stimulated proliferation and peptides 27 and 28 mostly elicited an IFN-gamma response. In conclusion, regions 41 to 80 and 241 to 295 demonstrated powerful and promiscuous T-cell-stimulatory properties, resulting in proliferative responses and IFN-gamma secretion, respectively, in the majority of reactive subjects tested in this study. These results could be of value in the development of a subunit vaccine for tuberculosis and leprosy.

Amino Acid Sequence↗

PubMed1994

Indeterminate leprosy: a seroimmunological and histochemical evaluation.

An effort was made to differentiate indeterminate (IND) leprosy from other types of the paucibacillary (PB) group of leprosy and to identify among indeterminate leprosy cases those which may evolve to multibacillary (MB) leprosy, using serological, immunological and histochemical parameters. A total of 92 untreated, histologically classified (TT-19, BT-30, IND-32) patients, including 11 cases diagnosed as nonspecific dermatitis (NSD), which were clinically strongly suspected to be leprotic, were screened for antibodies against PGL-I, 35-kDa and LAM antigens. Lepromin tests and antigen demonstration in tissue by indirect immunoperoxidase staining were also carried out. Though a qualitative analysis did not differentiate, a quantitative analysis in terms of a cumulative index (CI) showed a higher antibody level amongst the indeterminate group of patients than the other groups included in PB leprosy. Also, the lepromin negative indeterminate group patients showed a higher CI than the lepromin positive cases, indicating that perhaps these may be the cases which may develop into MB leprosy. Thus, the semiquantification of antibody levels in the form of a CI may be a useful parameter to predict the possible evolution of a given case of indeterminate leprosy. Interestingly 64% of NSD cases had either antigen or antibody which indicated that they were probably cases of leprosy.

Antigens, Bacterial↗

PubMed2000

Mycobacterium w vaccine, a useful adjuvant to multidrug therapy in multibacillary leprosy: a report on hospital based immunotherapeutic clinical trials with a follow-up of 1-7 years after treatment.

A vaccine based on autoclaved Mycobacterium w was administered, in addition to standard multidrug therapy (MDT), to 156 bacteriologically positive, lepromin negative multibacillary leprosy patients compared to a well matched control group of 145 patients with a similar type of disease who received a placebo injection in addition to MDT. The MDT was given for a minimum period of 2 years and continued until skin smear negativity, while the vaccine was given at 3-month intervals up to a maximum of eight doses. The fall in clinical scores and bacteriological indices was significantly more rapid in vaccinated patients, from 6 months onward until years 2 or 3 of therapy. However, no difference was observed in the fall in bacteriological index in the two groups from year 4 onwards. The number of LL and BL patients released from therapy (RFT) following attainment of skin smear negativity, after 24-29 months of treatment was 84/133 (63.1%) in vaccinated and 30/120 (25.0%) in the placebo group; the difference was highly statistically significant (P < 0.0001). In all, 90.2% patients (146/162) converted from lepromin negativity to positivity in the vaccine group, as against 37.9% (56/148) in the placebo group. The average duration of lepromin positivity maintained following eight doses of vaccine administered over 2 years was 3.016 years in the vaccine and 0.920 years in the placebo group. Histological upgrading after 2 years of treatment in the LL type was observed in 34/84 (40.5%) cases in the vaccine and 5/85 (5.9%) cases in the placebo group, the difference being statistically significant (P < 0.001). The incidence of type 1 reactions was significantly higher (30.5%) in the vaccine group than (19.7%) in the placebo group (P = 0.0413); the difference was mainly observed in LL type (P = 0.009). The incidence of type 2 reactions was similar (31.8 and 34.6%) in vaccine and placebo groups. The vaccine did not precipitate neuritis or impairments over and above that encountered with MDT alone. After 5 years of follow-up following RFT, no incidence of bacteriological or clinical relapses was observed in both groups.

Bacterial Vaccines↗

PubMed1988

Evidence that the Mitsuda reaction to Mycobacterium leprae can be mediated by lymphocytes responsive to Mycobacterium tuberculosis.

A positive Mitsuda skin test for delayed type hypersensitivity to Mycobacterium leprae is associated with a high level of protection against lepromatous leprosy, while the value of tuberculin sensitivity in leprosy is less pronounced. Cutaneous lymphocytes, isolated from the Mitsuda reaction of a PPD-positive individual not previously exposed to M. leprae, were cloned with Dharmendra lepromin and analysed for antigen specificity. Thirteen lepromin-responsive cell lines were derived, with greater than 95% certainty that the number of true clones was at least five and the number of functionally monoclonal lines at least seven. All lepromin-responsive clones proliferated in response to PPD as well, implying that PPD-responsive cells can fulfill the helper T cell function required for the in vivo Mitsuda reaction.

Antigens, Bacterial↗

PubMed1979

A placebo controlled clinical trial of transfer factor in lepromatous leprosy.

The effects of repeated injections of transfer factor over a period of 20 weeks were investigated in fourteen bacteriologically positive patients at the lepromatous side of the leprosy spectrum. All patients showed negative (0 mm induration) skin tests to M. leprae antigens (i.e. leprolin and lepromin). Of these patients, seven were treated with transfer factor with a total of 9 units (1 unit being equivalent to 5 x 10(8) lymphocytes) and seven with a placebo. Maintenance treatment with clofazimine was continued. Transfer factor was prepared from the lymphocytes of donors who showed positive skin tests to M. leprae antigens (i.e. leprolin greater than or equal to 12 mm induration, average 15.5 mm or lepromin greater than or equal to 8 mm induration, average 13.6 mm), as well as a positive lymphocyte transformation in vitro to M. leprae (the average transformation being higher than the average transformation of lymphocytes of tuberculoid leprosy patients). No differences were found between the two groups as regards the clinical course of the disease, the histopathological and bacteriological evaluation of skin biopsies, changes in skin test reactivity to various antigens (i.e. lepromin, leprolin, PPD, Mumps, C. albicans, Tr. rubrum and Varidase), as well as the lymphocyte transformation in vitro to various mitogens (i.e. PHA, PWM, Con A) and antigens (i.e. M. leprae, leprolin, PPD, BCG, Mumps, C. albicans, Trichophyton and Varidase). No evidence was found to suggest that transfer factor is a valuable adjuvant in the treatment of lepromatous leprosy patients or that it increases cell-mediated immune reactivity towards M. leprae.

Antigens, Bacterial↗

PubMed1993

IL-6 production in response to purified mycobacterial heat-shock proteins and to antigen 85 in leprosy.

IL-6 production was examined in PBMC cultures from healthy leprosy contacts and from leprosy patients stimulated with the purified mycobacterial 18-, 65-, and 70-kDa heat-shock proteins (hsp) and the secreted fibronectin-binding antigen 85 (Ag85). In lepromin-negative contacts, the 70-kDa hsp was the only antigen capable of eliciting significant IL-6 production. In lepromin-positive contacts, Ag85, the 65- and the 70-kDa hsp induced substantial IL-6 titers. IL-6 levels induced with the 70-kDa antigen were about fourfold higher than with the 65-kDa hsp or with Ag85. The 18-kDa antigen did not induce any IL-6 in these healthy contacts. PBMC from tuberculoid leprosy patients produced even more elevated levels of IL-6, and PBMC from lepromatous leprosy patients produced extremely high levels of IL-6. All antigens were capable of inducing IL-6 in leprosy patients. Highest levels were found in cultures stimulated with the 65-kDa hsp, and lowest levels were in cultures stimulated with the 18-kDa hsp.

Antigens, Bacterial↗

PubMed1989

ICRC 'anti-leprosy vaccine'.

A vaccine containing ICRC bacilli, which are leprosy-derived cultivable mycobacteria, induces lepromin conversion in LL patients and lepromin-negative persons. 'Up-grading' of lesions and reversal reaction are observed in some vaccinated patients. The bacillus shows antigenic cross-reactivity with Mycobacterium leprae. These observations provided the basis for launching a large-scale field trial of the vaccine in India in February 1987. The objective of the two-arm trial is to assess efficacy of the ICRC vaccine against BCG, which forms the control arm, in lowering the incidence of leprosy in healthy household contacts of leprosy patients. Recently, a very high molecular weight fraction, named PP-I, has been isolated from the sonicate of ICRC bacilli. PP-I, which is a glycolipoprotein, is a strong T-cell immunogen and shows antigenic cross-reactivity with a similar fraction isolated from M. leprae. A 'subunit' vaccine containing the PP-I of ICRC bacilli is currently undergoing phase I and II clinical trials in India.

Adolescent↗

PubMed1990

Immunotherapeutic effects of a vaccine based on a saprophytic cultivable mycobacterium, Mycobacterium w in multibacillary leprosy patients.

Immunotherapy with a vaccine consisting of autoclaved Mycobacterium w was given in addition to chemotherapy in 54 multibacillary, lepromin negative patients belonging to BB, BL and LL types of leprosy. Thirty-seven patients with similar types of diseases received chemotherapy and placebo injections. The 'vaccine' was repeated every 3 months. Bacterial clearance was more rapid in the vaccinated patients. Two lepromatous leprosy patients with initial bacterial index (BI) of 1.8 and 2.8 became bacteriologically negative in 1 year. One LL patient with BI of 6.0 had a BI fall to 0.16 after four doses of the vaccine. None of the LL patients belonging to placebo group during the same time period became bacteriologically negative. Rapid bacterial clearance was accompanied by distinct signs of clinical improvement. One hundred percent of BB, 85.7% of BL patients and 61.5% of LL patients converted to lepromin positivity after four doses of the vaccine. A significant number of vaccinated patients demonstrated an upgrading in skin lesions histopathologically.

Bacterial Vaccines↗