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New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries (1986)

Chapter: Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae

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Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

Appendix D-7
The Prospects for Immunizing Against Mycobacterium leprae

DISEASE DESCRIPTION

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which grow predominantly in the skin and nerves. It is a spectral disease, in that patients present a wide variety of forms and symptoms. At one pole of the spectrum is tuberculoid leprosy: a strong cell-mediated immune response is mounted and the infection is localized and restricted, although often with concomitant damage to nerves. At the opposite pole is lepromatous leprosy: cell-mediated immune responses to antigens of M. leprae fail, and the organisms spread throughout the skin and nerves, often reaching 10 billion acid-fast bacilli per cm2 skin.

Responses in the majority of patients are between these extremes. Because the organism grows in Schwann cells around the nerves, the classical symptoms of anesthesia, nerve damage, mutilation, and deformity are still found in about one-third of all cases. A comprehensive review of leprosy and strategies for its control has been presented by Bloom and Godal (1983).

The historical stigma associated with leprosy, which remains very strong in most countries of the world, often results in socioeconomic disruption of the lives of patients and their families, irrespective of treatment. Fear of this prejudice may inhibit patients who have early lesions from seeking treatment.

PATHOGEN DESCRIPTION

Mycobacterium leprae remains the only major human bacterial pathogen that cannot be cultivated in the laboratory. Until recently, scientific research depended on the ability to grow large quantities of

The committee gratefully acknowledges the efforts of B.R.Bloom, who prepared major portions of this appendix, and the advice and assistance of S.K.Noordeen. The committee assumes full responsibility for all judgments and assumptions.

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

the organism in the nine-banded armadillo and on studies of localized infection in mice. A new report on laboratory-induced leprosy in monkeys suggests that mangabey monkeys may provide an important nonhuman primate model in which to study the transmission and pathogenesis of the disease (Wolf et al., 1985).

The waxy coat and cell wall structure of M. leprae are similar to those of other acid-fast bacilli, including M. tuberculosis, but DNA hybridization studies indicate that M. leprae has a rather distant taxonomic relationship to other known mycobacteria. M. leprae is thought to grow very slowly in vivo, with a doubling time of between 7 and 14 days (Shepard and McRae, 1965).

HOST IMMUNE RESPONSE

Antibodies against M. leprae are found in patients with all stages of the disease and may be most prevalent in those with lepromatous leprosy. There is a remarkable inverse correlation between the histopathological classification of disease severity in leprosy and the level of cell-mediated immune responses. Patients at the tuberculoid end of the spectrum have cell-mediated immunity and few bacilli; patients at the lepromatous end exhibit no cell-mediated immunity to M. leprae and high bacillary loads (Bloom and Godal, 1983).

DISTRIBUTION OF DISEASE

Geographic Distribution

Leprosy is found in virtually all tropical and subtropical countries. A third of all cases occur in Southeast Asia, and the remainder occurs primarily in Africa and South America. At one time, the disease existed in epidemic form in Norway and in other parts of Europe and the Mediterranean, but for reasons not entirely clear it has been largely eliminated from Europe (Irgens, 1980; Sansarricq, 1981, 1982).

Disease Burden Estimates

Considerable disagreement and uncertainty exist regarding the epidemiology of leprosy infection, transmission, and pathogenesis (Fine, 1982). The estimates given below relate to clinically symptomatic cases of disease, that is, where permanently impaired neurological function or tissue damage is apparent.

The Special Programme for Research and Training in Tropical Diseases (SPRTTD, 1985) conservatively estimates the global prevalence of leprosy to be 10.6 million cases, the vast majority of which are in developing countries. Information on incidence is scant, but several studies suggest that the annual incidence roughly approximates one-tenth of existing prevalence (Noordeen, personal communication, 1984). On

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

this basis, the annual global incidence would be about 1.06 million cases. For the purposes of this assessment, all new cases are assumed to have some clinical symptoms that result in some permanent (but possibly mild) disability (category D)—such as minor neurological deficit. The proportion of cases in children (14 years of age and younger) is approximately 20 percent of detected cases (17.4 to 29 percent; Noordeen, personal communication, 1984) and is probably higher for new cases. Hence, it is assumed that 25 percent of new cases occur in the 5 to 14 years age group and 75 percent in the 15 to 59 years age group.

One-third of leprosy patients face the threat of progressive disease, which can result in severe physical disability and social stigmatization (SPRTTD, 1985). Patients who contract the disease early in life or who progress rapidly will spend part of their remaining lifetime with mild, moderate, and then severe chronic disability (categories D, E, and F). Patients who contract the disease later in life or who progress slowly may not experience the most severe consequences (some patients will not progress but will have already incurred mild chronic disability, category D). Most of the progression is thought to occur before the age of 60 (Bloom, personal communication, 1985). Hence, for ease of calculation, all transitions to moderate or severe categories are assumed to occur in the 15 to 59 years age group.

Leprosy is unique in exhibiting such progression and variability; it does not easily lend itself to description by the use of the morbidity category/age group matrix used in this exercise to display the incidence of disease consequences. To permit comparison of leprosy with other diseases by this method, some simplification of the epidemiological presentation of the disease is necessary.

One-third of all cases in any cohort are assumed to progress. This represents, on the average, 353,333 patients moving each year to the moderate or severe status. Half of these transitions are assumed to be to the moderate category and half to the severe category (176,667 to each). The annual number of new cases in category D in the 15 to 59 years age group (795,000) is reduced accordingly (by 353,333).

The life expectancy of leprosy patients is probably shortened by a few years, more so in the lepromatous forms (Sansarricq, 1981). Deaths are probably a consequence of other infections or intoxications (e.g., tetanus) resulting from physical injury or mutilation and/or depressed immune function. However, few data exist on which to base death estimates. It has therefore been assumed (arbitrarily) that leprosy patients have a 1 percent higher death rate than the general population. For a normal crude death rate of 10 per 1,000 for developing countries, this would result in about 1,060 premature deaths within a population of 10.6 million leprosy patients.

These deaths are assumed to occur predominantly before the age of 60 years (i.e., 90 percent in the 15 to 59 years age group and 10 percent in the 60 years and over age group).

The annual disease burden estimated to result from leprosy is shown in Table D-7.1.

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

TABLE D-7.1 Disease Burden: Mycobacterium leprae

 

Under 5 Years

5–14 Years

15–59 Years

60 Years and Over

Morbidity Category

Description

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

Number of Cases

Duration

A

Moderate localized pain and/or mild systemic reaction, or impairment requiring minor change in normal activities, and associated with some restriction of work activity

 

B

Moderate pain and/or moderate impairment requiring moderate change in normal activities, e.g., housebound or in bed, and associated with temporary loss of ability to work

 

C

Severe pain, severe short-term impairment, or hospitization

 

D

Mild chronic disability (not requiring hospitalization, institutionalization, or other major limitation of normal activity, and resulting in minor limitation of ability to work)

 

n.a.

265,000

n.a.

441,667a

n.a.

 

n.a.

E

Moderate to severe chronic disability (requiring hospitalization, special care, or other major limitation of normal activity, and seriously restricting ability to work)

 

n.a.

 

n.a.

176,667

n.a.

 

n.a.

F

Total impairment

 

n.a.

 

n.a.

176,667

n.a.

 

n.a.

G

Reproductive impairment resuliting in infertility

 

n.a.

 

n.a.

 

n.a.

 

n.a.

H

Death

 

n.a.

 

n.a.

954

n.a.

106

n.a.

aNumber represents new cases (795,000) minus progressing cases (353,333).

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

PROBABLE VACCINE TARGET POPULATION

Epidemiologists disagree about the probable vaccine target population for a leprosy vaccine. Some have argued that it would be most cost-effective to restrict vaccination to high-risk individuals identified by traditional case detection methods. Another alternative would be to target the vaccine for newly infected individuals. Recent serologic studies indicate that there is at least one unique antigen on M. leprae, a phenolic glycolipid (SPRTTD, 1985). It may be possible to develop serologic techniques using the glycolipid and monoclonal antibodies to screen high-risk populations. The practicality and cost of screening, if it becomes feasible, would have to be weighed against the simplicity of general communication to populations at risk.

The committee chose to focus on a vaccine candidate for leprosy that could be delivered to the general population. If the candidate were sufficiently immunogenic in young children, it could be delivered as part of the World Health Organization Expanded Program on Immunization (WHO-EPI).

Vaccine Preventable Illness*

An exceptionally small proportion of all leprosy cases (probably less than 0.1 percent) occurs in children under 5 years of age. Thus, a vaccine that is 100 percent effective, that could be delivered in infancy, and that could provide long-lasting immunity theoretically could prevent 100 percent of leprosy cases.

SUITABILITY FOR VACCINE CONTROL

The belief that leprosy is suitable for vaccine control is based, in part, on reports of successful immunotherapy in patients with lepromatous leprosy (Convit et al., 1979, 1983; Samuel et al., 1984; SPRTTD, 1985). These patients received a mixture of killed armadillo-derived M. leprae and live BCG (Bacillus Calmette-Guérin) vaccine. Skin test conversions and histopathological upgrading of lesions occurred in about 65 to 85 percent of the lepromatous patients, and some appeared to be cured. It should be noted that all patients in this study received concurrent antimicrobial chemotherapy (ethical considerations require that such therapy be provided).

Results from four major controlled trials provide other evidence for the suitability of leprosy for vaccine control. In those trials, BCG had some protective efficacy against leprosy, ranging from 80 percent in Uganda to 20 percent in Burma (Fine, 1985).

*  

Vaccine preventable illness is defined as that portion of the disease burden that could be prevented by immunization of the entire target population (at the anticipated age of administration) with a hypothetical vaccine that is 100 percent effective (see Chapter 7).

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

It is expected that immunization of uninfected or unexposed individuals also could produce a cell-mediated immune response. Ideally, this could thwart development of overt clinical disease. However, if the vaccine were somewhat less effective, it might only reduce the severity of the disease (i.e, convert multibacilliferous lepromatous forms of the disease to borderline or tuberculoid forms).

Alternative Control Measures and Treatments

Problems in leprosy control have been extensively reviewed (Bloom and Godal, 1983; Sansarricq, 1981; SPRTTD, 1985).

Despite the efforts of governmental and private agencies and the availability of an inexpensive and nontoxic therapeutic drug, control of leprosy transmission has not been achieved. A significant amount of transmission probably occurs prior to the diagnosis of leprosy. Also, it appears that some organisms that are not genetically drug resistant, persist in sequestered places and are protected from the effects of chemotherapy; these may reappear and disseminate when chemotherapy is stopped. Finally, drug resistance has become a problem.

The recent emergence of both secondary and primary resistance to dapsone, the principal drug used to treat leprosy patients for the past 20 years, is a compelling reason for vaccine development. The prevalence of drug resistance has risen in some areas from 1 to 2 cases per 1,000 in 1966 to as high as 100 per 1,000 in 1981 (SPRTTD, 1983). Resistance to dapsone, compounded by the considerable expense of rifampin and the generally unacceptable side effects (skin coloration) of clofazimine, necessitates the pursuit of preventive, immunization strategies.

PROSPECTS FOR VACCINE DEVELOPMENT

Approaches to immunotherapy and immunoprophylaxis for leprosy have recently been reviewed in the report of the SPRTTD (1985), which provides an extensive bibliography of research on leprosy treatment and prevention.

Efforts to develop potential leprosy vaccines are based on the following premises and observations:

  • Cell-mediated immunity rather than antibody production against M. leprae antigens is required for protection.

  • Human M. leprae can be grown in sufficient amounts in armadillos to provide a first-level vaccine for human use.

  • Purified, killed, armadillo-derived M. leprae have been shown to produce cell-mediated immunity in mice and guinea pigs (Mehra and Bloom, 1979; Shepard et al., 1978).

  • Killed, purified M. leprae have been shown to induce protection in mice against challenge with viable M. leprae (Shepard, 1983).

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
  • Armadillo-derived M. leprae vaccine has been purified to exclude virtually all contaminating armadillo proteins and is currently being produced by the Wellcome Research Laboratories in the United Kingdom. It is being used in Phase 1 sensitization studies in 31 normal human volunteers in Norway, where it has been found to engender delayed hypersensitivity without untoward side effects (SPRTTD, 1985). It also is being tested in 64,000 contacts in Venezuela as part of a controlled prophylactic trial.

  • BCG trials provided some degree of protection against leprosy in Burma (22 percent), New Guinea (44 percent), S. India (33 percent), and Uganda (80 percent) (Fine, 1985). These results suggest that more specific vaccines are needed and that different levels of protection may be obtained in different populations. Consequently, multiple field trials will be needed to evaluate any candidate vaccine(s).

Researchers are now examining the characteristics of three potential leprosy vaccines: a killed M. leprae vaccine; a combined M. leprae and BCG vaccine; and a vaccine containing cultivable, cross-reactive mycobacteria.

Initial studies with volunteers have focused on the capacity of the purified, killed M. leprae vaccine to induce cell-mediated immunity in naive individuals in a nonendemic area (Gill et al., In press). All recipients became sensitized to skin test reactivity, and there were no untoward side effects. If it were to be tested in the field, an M. leprae vaccine could lead to resistance or could limit any future disease to a subclinical infection. At a minimum, it might decrease transmission by shifting potential cases of the disease from the multibacilliferous lepromatous form to the tuberculoid form. The disadvantage of this strategy is that patients already harboring lepromatous leprosy in a subclinical or unrecognized form would not be protected and would continue to spread infection.

The combined vaccine, consisting of killed M. leprae and live BCG, has been shown by Convit to induce cell-mediated immunity in previously unresponsive lepromatous patients and to markedly improve their disease status (see above). A large percentage of patients showed a dramatic reduction in the number of bacilli in the tissues. Field trials of this combined vaccine in prophylactic studies involving 64,000 patient contacts in Venezuela and a total population in Malawi (108,000 people) are based on the premise that the combined vaccine will both immunize naive individuals and have some immunotherapeutic effects in patients harboring subclinical infections (SPRTTD, 1985).

Recently, two strains of cultivable mycobacteria isolated in India, ICRC bacillus and Mycobacterium W, have been reported to be immunologically cross-reactive with M. leprae and capable of inducing sensitization to M. leprae antigens in lepromatous patients. The results appear to be similar to those produced by the combined vaccine described above (Deo et al., 1983; Talwar and Fotedar, 1983). However, in a mouse model neither vaccine was effective in preventing M. leprae infections (SPRTTD, 1985). While both sets of findings are only preliminary, the possibility exists that a cultivable organism that can be mass-produced at much lower cost than armadillo-derived bacilli

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

might possess both specific components cross-reactive with antigenic determinants required for protection against M. leprae and foreign determinants comparable to those in BCG (capable of exerting an adjuvant effect or altering unresponsiveness).

Following Phase 1 trials with vaccines produced from these organisms and some small-scale sensitization studies, several large vaccination trials should be carried out to compare them with the combined vaccine and the killed M. leprae vaccine. The relative effectiveness of these vaccines should be examined in several different populations. Plans for the testing of these various vaccine candidates are described in the report of the SPRTTD (1985).

Efforts are under way to produce a second stage vaccine using recombinant DNA technology. Little is known about the molecular biology of mycobacteria, but researchers recently have been able to clone and express M. leprae genes in E. coli (Young et al., 1985). Clones producing M. leprae-specific antigenic determinants can be identified using monoclonal antibodies. Recent evidence suggests that some recombinant clones express antigens recognized by immune T-lymphocytes, and it will be important to develop means of introducing these potentially protective genes into a cultivable mycobacterium. The result would be specific protective antigens in an inexpensive and easily cultivable vaccine. If this introduction can be achieved, the possibility of introducing genes for antigens of a variety of infectious agents into BCG that have unique adjuvant activity could lead to the development of a unique multivaccine vehicle (Bloom and Mehra, 1984).

Neither the killed preparation of M. leprae nor the cross-reactive cultivable organism is expected to produce significant untoward side effects, although they will have to be monitored in early Phase 1 trials. BCG has been used in hundreds of millions of people over the past 50 years with remarkably few side effects, can be given at birth, and costs only 5 cents per vaccination. It is anticipated that if there are any side effects, they will occur primarily in members of the general population who harbor subclinical infections. Theoretically, the induction of cell-mediated immunity through vaccination could result in some nerve damage in these individuals. The Venezuelan trials of the combined M. leprae and BCG vaccine have found no evidence of such an effect (Convit et al., 1983).

Because leprosy develops slowly and has a relatively low prevalence, comprehensive vaccine field trials generally will require 5 to 15 years of follow-up. To optimize the chances of early demonstration of protection, the early studies of vaccines were undertaken in contacts of lepromatous patients, who are thought to have an increased risk (four-to sixfold) of contracting leprosy.

The discovery of a potential animal model for lepromatous leprosy (Wolf et al., 1985) may mean that vaccine efficacy trials in humans will require less time and resources than previously expected. However, determination of the duration of protection in humans will still be a lengthy process.

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

Problems to be Overcome

Major economic, political, and social problems may hamper efforts to evaluate potential vaccine candidates for leprosy. Research and field studies to determine which vaccines are most appropriate for specific populations will be expensive. Some areas of the developing world that possess the field and clinical expertise to participate in vaccine trials and evaluations lack the national political commitment to initiate and carry out essential background work. The most significant social question will be whether the identification of an effective vaccine for leprosy and the development of suitable delivery systems can overcome the universal stigma associated with the disease.

REFERENCES

Bloom, B.R. 1985. Personal communication, Albert Einstein College of Medicine, Bronx, N.Y.

Bloom, B.R., and T.Godal. 1983. Selective primary health care: strategies for control of disease in the developing world. V. Leprosy. Rev. Infect. Dis. 5(4):765–780.

Bloom, B.R., and V.Mehra. 1984. Vaccine strategies for the eradication of leprosy. Pp. 368–389 in New Approaches to Vaccine Development, R.Bell and G.Torrigiani, eds. Basel, Switzerland: Schwabe and Co. AG.


Convit, J., M.Aranzazu, M.Pinardi, and M.Ulrich. 1979. Immunological changes observed in indeterminate and lepromatous leprosy patients and Mitsuda-negative contacts after the inoculation of a mixture of Mycobacterium leprae and BCG. Clin. Exp. Immuno. 36:214,

Convit, J., M.Aranzazu, M.Ulrich, M.Zuniga, M.E. De Aragon, J.Alvarado, and O.Reyes. 1983. Investigations related to the development of a leprosy vaccine. Int. J. Lepr. 51:531–539.


Deo, M.G., C.V.Bapt, V.Bhalerao, R.M.Chaturvedi, W.S.Bhatki, and R.G.Chulawala. 1983. Antileprosy potential of ICRC vaccine: A study in patients and healthy volunteers. Int. J.Lepr. 51:540–549.


Fine, P.E.M. 1982. Leprosy: The epidemiology of a slow bacterium. Epidemiol. Rev. 4:161–188.

Fine, P.E.M. 1985. The role of BCG in the control of leprosy. The Kellersberger Memorial Lecture. Ethiopian Med. J. 23:179–188.


Gill, H.K., A.S.Mustafa, and T.Godal. In press. Sensitization of normal human volunteers with a candidate vaccine against leprosy. Bull. WHO.


Irgens, L.M. 1980. Leprosy in Norway. An epidemiological study based on a national patient registry. Lepr. Rev. 51(suppl. 1): 1–130.


Mehra, V., and B.R.Bloom. 1979. Induction of cell mediated immunity to Mycobacterium leprae in guinea pigs. Infect. Immun. 23:787–794.


Noordeen, S.K. 1984. Personal communication, World Health Organization, Geneva.


Samuel, N.M., K.Neupani, R.J.W.Rees, J.L.Stanford, and R.B.Adiga. 1984. Vaccination of contacts, normals, and leprosy patients.

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×

Abstracts of the 12th International Leprosy Congress, New Delhi, India. Session II, No. 54.

Sansarricq, H. 1981. Leprosy in the world today. Lepr. Rev. 52(suppl. 1):15–31.

Sansarricq, H. 1982. The Kellersberger Memorial Lecture, 1981: the general situation of leprosy in the world. Ethiop. Med. J. 20:89–106.

Shepard, C.C. 1983. Animal vaccine studies with Mycobacterium leprae. Int. J. Leprosy 51:519–523.

Shepard, C.C., and D.H.McRae. 1965. Mycobacterium leprae in mice: Minimal infectious dose, relationship between staining quality and infectivity and effect of cortisone. J. Bacteriol. 89:365–372.

Shepard, C.C., L.I.Walker, and R.Van Landingham. 1978. Heat stability of Mycobacterium leprae immunogenicity. Infect. Immun. 22:87–93.

SPRTTD (Special Programme for Research and Training in Tropical Diseases). 1983. Primary resistance to dapsone among untreated patients in Bamako and Chingleput. Report of the Subcommittee on Clinical Trials, Scientific Working Group on the Chemotherapy of Leprosy (THELEP). Leprosy Rev. 54:177–183.

SPRTTD (Special Programme for Research and Training in Tropical Diseases). 1985. Leprosy. Pp. 8/1–8/19 in Tropical Disease Research. Seventh Programme Report, 1 January 1983–31 December 1984. Geneva: World Health Organization.


Talwar, G.P., and A.Fotedar. 1983. Two candidate antileprosy vaccines—current status of their development. Int. J. Lepr. 51:550–552.


Wolf, R.H., B.J.Gormus, L.N.Martin, G.B.Baskin, G.P.Walsh, W.M. Meyers, and C.H.Binford. 1985. Experimental leprosy in three species of monkeys. Science 227:529–531.


Young, R.A., V.Mehra, D.Sweetser, T.Buchanan, J.Clark-Curtis, R.W.Davis, and B.R.Bloom. 1985. Genes for the major antigens of the parasite causing leprosy. Nature 316:450–452.

Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 241
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 242
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 243
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 244
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 245
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 246
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 247
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 248
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
Page 249
Suggested Citation:"Appendix D-7: The Prospects for Immunizing Against Mycobacterium leprae." Institute of Medicine. 1986. New Vaccine Development: Establishing Priorities: Volume II, Diseases of Importance in Developing Countries. Washington, DC: The National Academies Press. doi: 10.17226/920.
×
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Common diseases cost the developing world an enormous amount in terms of human life, health, and productivity, as well as lost economic potential. New and effective vaccines could not only improve the quality of life for millions of residents in developing countries, they could also contribute substantially to further economic development. Using data from the World Health Organization and other international agencies, this book analyzes disease burdens, pathogen descriptions, geographic distribution of diseases, probable vaccine target populations, alternative control measures and treatments, and future prospects for vaccine development. New Vaccine Development provides valuable insight into immunological and international health policy priorities.

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