LEPROSY

The term ẓaraʿat is traditionally rendered "leprosy" because of its translation by Greek lepra (lxx, New Testament, and Josephus). The Greek covers a wide range of diseases that produced scales. Greek lepra may have included true leprosy, i.e., Hansen's disease, but is definitely not limited to it. In fact, biblical descriptions of ẓaraʿat do not include the necrosis associated with Hansen's disease. Thus far no skeletons of the biblical period show any signs of Hansen's disease. The term ẓaraʿat is a generic name, embracing a variety of skin ailments, including many non-contagious types. Thus, the illness of Miriam was transient (Num. 12:10–15) and that of Naaman did not prevent him from mixing freely in society (ii Kings 5). Probably only those actually banished from their fellowmen were lifelong sufferers, e.g., the four "lepers" forced to live outside Samaria (ii Kings 7:3–10) and King Uzziah, who was permanently quarantined in separate quarters (ii Chron. 26:19–21). Medical texts of the ancient Near East attribute disease either to black magic or the sufferer's sin (R.C. Thompson, Assyrian Medical Texts (1923); A.L. Oppenheim, Ancient Mesopotamia (1977, 288–305). In the Bible, whenever a reason is given for an attack of ẓaraʿat, it is in connection with a challenge to a duly constituted authority (Zakovitch). Miriam challenged the prophetic supremacy of Moses; Gehazi disobeyed the will of his master Elisha (ii Kings 5:20–27); and Uzziah challenged the exclusive prerogative of the priests to offer incense. In the case of sin and black magic, rituals are prescribed that bear a striking resemblance to those in the Bible (see below), with one critical difference. In contrast to the Mesopotamian situation, in which priests may be healers, the Bible always attributes the healing of individuals to the intervention of prophets (e.g., Gen. 20:7; ii Kings 5). The priest himself only rules on the purity or impurity of the sufferer (Kaufmann).

The Laws of Leviticus 13–14

Leviticus 13–14 is composed of the following sections: the diagnosis of the afflictions of the skin (13:2–28, 38–39, summarized below), of the hair (13:29–37), and of the scalp (13:40–44); the ostracism of the incurable (13:45–46; cf. Lam. 4:15); the diagnosis of the deterioration of garments, due probably to mildew or fungus (13:47–59); the ritual for the rehabilitation of the healed "leper" (14:1–32); the diagnosis of the "leprosy" of houses, probably caused by the spread of dry rot, mineral precipitates, or the growth of lichens and fungi (14:33–53); and the summary (14:54–57). The structure is logical, with houses being put at the end (cf. 14:34), a reflection of the reality of the period in which the texts were written. Though not all the technical terms are understood (see the commentaries), the symptoms given are capable of precise medical definition. The affliction can occur spontaneously (13:2–17), follow a furuncle (13:18–23) or a burn on the skin (13:24–28), or develop on the head or beard (13:29–45). The first symptoms are those of a swelling, or subcutaneous nodule, a cuticular crust (sappaḥat), and whitish-red spot (baheret). "The crux of the matter lay in the degree of cutaneous penetration which the disease had achieved. If it affected the epidermis or outermost layer of skin and did not produce pathological changes in the hairs, the affliction was not regarded as especially serious. As such it might consist of eczema, leukoderma, psoriasis, or some allied cutaneous disease. But if the affliction had infiltrated the dermis (corium) and had caused hairs to split or break off and lose their color, then "leprosy" was to be suspected" (R.K. Harrison). This diagnostic principle also applied to disease affecting the scalp (13:29–37) where the affliction was spoken of as netek (neteq) (jps "scall").

The Role of the Priest

The Israelite priest, while usually not involved in individual healing according to the Bible, is involved in epidemics where he intercedes through sacrifices, Num. 17:11ff.; ii Sam. 24:25 – David officiating as priest. Deut. 24:8–9, which deals with contagious skin diseases enumerated here is a possible exception; and contrast the laws pertaining to gonorrhea, Lev. 15.

The priest was called in to inspect the affliction. If "leprosy" was only suspected but not certain, the priest imposed a seven-day quarantine. At the end of this period the afflicted was examined again, and if no further degeneration was apparent he was isolated for another week, after which he could be pronounced healed. The priest, however, did nothing to promote the cure. His rituals were performed only after the disease had passed. It was the responsibility of the afflicted himself to pray (i Kings 8:37–38; ii Kings 20:2–3) and fast (ii Sam. 12:16) in order to win God's healing. Deuteronomy 24:8–9 charges the people to follow the authority of the priests in all matters dealing with "leprosy," citing as precedent the case of Miriam (see Num. 12:11–16), who challenged the authority of Moses (alternatively, the late writer of Numbers 12 (see Sperling) was inspired by the juxtaposition of priestly authority in matters of "leprosy" with the mention of the unnamed punishment laid on Miriam by God in Deuteronomy 24:9). It is noteworthy that in Miriam's case healing did not come through Aaron the priest, who was a party to the offense, but through the prophet Moses and his prayer. In the Bible, healing comes from God directly (Ex. 15:26) or through the prophet (e.g., Moses, Ex. 15:25; Elisha, ii Kings 2:21; Isaiah, ii Kings 20:7–8).

The Ritual

The prescribed ritual for the healed "leper" is of interest. Three separate ceremonies are required: for the first day (Lev. 14:2–8; also invoked for houses, 14:48–53), the seventh (14:9), and the eighth (14:10–32). The first-day ritual is performed by the priest outside the camp or city from which the "leper" has been banished. Cedar wood, crimson cloth, and a live bird are dipped into an earthen vessel containing a mixture of fresh water and the blood of a second bird. The "leper" (or "leprous" house) is sprinkled with this mixture seven times, after which the live bird is set free. The "leper" is admitted into the camp or city after he washes his clothes, shaves all his hair, and bathes, but he is not allowed to enter his residence. That is permitted him on the seventh day after shaving, laundering, and bathing again. On the eighth day he brings to the sanctuary oil and sheep for various offerings – whole, meal, purification, and reparation. The whole and purification animals may be commuted to birds if the "leper" is poor. However, the reparation lamb and log of oil may not be changed, because the blood of the lamb and the oil are needed to daub the "leper's" right ear lobe, right thumb, and right big toe.

This complex ceremonial is elucidated by comparison with similar prescriptions in the ancient world. There is much evidence of the banishment of evil by carriers (J. Frazer, The Golden Bough, 6 (1935), 249ff.), especially animals (e.g., Hittite: F. Sommer and H. Ehelolf, Das hethitische Ritual des Papanikri von Komana (1924), iii 45, Rev. iv, 5ff.; Mesopotamia and Israel: see *Azazel). Aspersions of materials such as cedar, scarlet wool, and hyssop are also known (e.g., J. Laesse, Studies in the Assyrian Ritual… (1955); R.C. Thompson, The Devils and Evil Spirits of Babylon, vol. 2, 1904). Moreover, a letter of Nergal-sharrani to King Esarhaddon refers to an apotropaic prayer and a ritual for kamūnu fungus, which appeared in the inner court of the temple of Nab – and for the kattarru fungus on the walls of storehouses (R.F. Harper, Assyrian and BabylonianLetters, 4 (1896), no. 367 = saa xiii:71). Clearly, then, the purpose of the "leper's" ritual of the first day was to exorcise the demonic disease and banish it to a place of no return, e.g., the desert (see *Azazel) or the open country in the case of the leper (ha-sadeh; Lev. 14:7, 53). In keeping with p's exclusion of the priest from participation in the healing of individuals, the ritual is prescribed only after "the priest sees that the 'leper' is healed" (14:3). If ritual purification is the purpose of the ritual of the first day, why its week-long extension? Here, in keeping with the priestly system of scaled impurities, a severe defilement endures for eight days after healing and calls for a three-stage purification, which reduces and finally eliminates this vestigial impurity (see *Purity and Impurity, Ritual). The rite of the first day enables the leper to mingle with, but not touch, the members of his community, nor can he enter a confined space lest he defile what it holds (see 14:8b; rabbinic מאהיל, cf. Kelim 1:4; Neg. 13:3, 7, 8, 11; Jos., Ant., 3:261ff.; Jos., Apion, 1:279ff.; cf. Num. 19:14). These restrictions are removed only at the end of the seventh day, after he has again shaved, laundered, and bathed.

Having been restored to his community and household, he is still impure vis-à-vis the realm of the sacred: he has to be rehabilitated in the eyes of his God (ten times the text insists that the ritual is "before the Lord," Lev. 14:11–31). In the eighth-day ritual – the third and final stage – he therefore brings to the sanctuary a complex of sacrifices. The purification offering purges the sacred area of the defilement brought on by his "leprosy" (see *Atonement); the whole and meal offerings expiate the sin that might have caused his affliction (e.g., Miriam, see above); the reparation offering is his expiation in case he has trespassed on sancta (maʿal, a sin punishable by leprosy, e.g., Uzziah, ii Chron. 26:16–21; cf. Lev. 5:14–19; and see *Sacrifices). The blood of the animal of reparation and the oil are successively daubed on the extremities of his body so that he may have access to the sanctuary and its sancta (as far as allowed to a layman). That sanctification is the purpose of this ritual is demonstrated by the consecration service of the priest (Ex. 29; Lev. 8), where the daubing of the same parts of the body is prescribed and where a mixture of oil and sacrificial blood is used (in sprinkling, not in daubing: note verb qadesh "sanctify." Ex. 29:21; Lev. 8:30). Israel's sanctification motif is illuminated by comparison with similarly structured rituals in the ancient Near East, where there is abundant attestation of daubing (see *Anointing). The incantations recited during the ritual smearing of persons, the statues of gods, and buildings testify that its object is purificatory and apotropaic: to wipe off and ward off the incursions of menacing demonic forces. Hence it is always the vulnerable parts of bodies (extremities) and of structures (corners, entrances) that are smeared with substances with alleged special properties (e.g., Pritchard, Texts, 338). The Bible's "leprosy" laws are directed toward the larger community and do not constitute a priest's manual. As such, whatever additional incantations and exorcisms that may have been performed are lost to us. The purificatory and apotropaic are steps in the healed "leper's" rehabilitation, which enabled him to return to his community and qualified him to have access to the Sanctuary and God. Ezekiel's ritual of consecration for the altar is strikingly analogous: blood is to be daubed on its horns and the corners of its two gutters, located at its middle and bottom (Ezek. 43:20). These points correspond to a person's ear lobe, thumb, and big toe. There can be no question that the purpose of this altar ritual (as in the consecration of the priests) is sanctificatory; the same must be said of the eighth-day ritual for the "leper."

[Jozeph Michman (Melkman) /

S. David Sperling (2^nd ed.)]

In the Second Temple and Talmud

The laws of leprosy are given in great detail in the Talmud, and a whole tractate of the Mishnah and Tosefta, *Nega'im, is devoted to them. It is reported that in the courtyard of the Temple itself, on the northwest, there was the Chamber of the Lepers where the lepers remained after they had been cured, and where they bathed on the eighth day of their purification, awaiting their admittance for the anointing of their toes (Neg. 14:8; Mid. 2:5). In the New Testament there are numerous references to lepers. In the two instances in which Jesus is said to have cured lepers (one an individual – Luke 5:12–14; cf. Matt. 8:3; and the other a group of ten – Luke 17:12), he told them, "Go show yourself to the priest," after their cure, and one passage (Luke 5:14) adds, "and make an offering for thy cleansing, as Moses commanded…" This is evidence that the biblical laws were in operation, both as regards the functions of the priest and the obligatory offering. The Apostles are told in general to cleanse the lepers (Matt. 10:8; Luke 7:22).

On the other hand there are hardly any references in the tannaitic period to actual cases of leprosy. Tosefta Negaim (6:1) includes the "house affected by leprosy" (Lev. 14:34–53) among those laws which "never were and never will be," their purpose being merely "to expound and receive reward therefore" (cf. *Rebellious Son). Eleazar b. Simeon, however, adds that there was a site in the vicinity of Gaza which used to be called "the enclosed ruin" (which was presumably a house affected by leprosy which had been destroyed in accordance with the law (Lev. 14:45)), and Simeon b. Judah of Kefar Akko (according to the amendment of Elijah Gaon of Vilna) said that there was a site in Galilee which used to be pointed out as having within its bounds leprous stones. It is also stated that according to the halakhah, the law of quarantine for lepers fell into abeyance when the Jubilee year (see *Sabbatical Year and Jubilee) was not in operation (cf. Tosef., Ber. 5b top), i.e., presumably during the Second Temple period.

Josephus, who was both a priest and lived during the time of the Temple, in his description of the Mosaic laws, states that it was forbidden to the leper to "come into the city at all [or] to live with any others, as if they were in effect dead persons." He makes a sharp contrast between this law and the fact that "there are lepers in many nations who are yet in honor, and not only free from reproach and avoidance, but who have been great captains of armies, and been entrusted with high office in the commonwealth and have had the privilege of entering into holy places and temples" (Ant., 3:261–9). It is possible, however, that this passage is merely a reference to Naaman, the commander of the army of Syria (ii Kings 5, especially vs. 5 and 18).

By the time of the compilation of the Mishnah and Tosefta, at the beginning of the third century, the laws of leprosy were regarded as the most abstruse and complicated of laws. Eleazar b. Simeon on one occasion said to R. Akiva, "What have you to do with aggadah? Turn to the subject of leprosy" (Ḥag. 14a). Although, according to the Talmud, leprosy did not exist in Babylon "because they eat turnips and drink beer and bathe in the Euphrates" (Ket. 77b), it seems to have existed in Ereẓ Israel in mishnaic and amoraic times. R. Johanan and Resh Lakish stated that it is forbidden to walk four cubits, or 100 cubits (dependent upon whether there was a wind blowing at the time) to the east of a leper; R. Meir refrained from eating eggs which came from a district where lepers lived; R. Ammi and R. Assi never entered such a district; when Resh Lakish saw one he would cast stones at him, exclaiming, "get back to your location and do not contaminate other people"; and R. Eleazar b. Simeon would hide from them (Lev. R. 16:3). As Katzenelson points out, since the segregation enjoined in the Bible no longer applied in talmudic times, this segregation and its consequences were the result of popular feeling, and not a legal requirement. There is a geonic responsum which states explicitly, "among the people of the east, that is, in Babylonia, at the present time, if, God forbid, a scholar should be affected by leprosy, he is not excluded from the synagogue or the schools, since today the injunction, 'thy camp shall be holy' (Deut. 23:15; i.e., the laws of ritual cleanness) no longer applies" (Sha'arei Teshuvah, no. 176).

Reference should be made to the allegation first mentioned by the Egyptian historian *Manetho, and repeated by *Chaereman, *Lysimachus, and other Egyptian writers hostile to the Jews, and quoted by *Apion, to the effect that not only was Moses a leper, but the children of Israel were expelled from Egypt because they suffered from leprosy. Indeed, according to Lysimachus the seventh day was called Sabbaton because of the leprous disease of the groin which they suffered which is called Sabbo in Egyptian (Jos., Apion, 1:227ff., 2:20–21).

In the Aggadah

Aside from the practical issue of the observance of the regulations of ritual cleanness in general, and of the laws of leprosy in particular after the destruction of the Temple, it should be noted that the rabbis derived from the laws of leprosy a moral lesson. Homiletically interpreting the word meẓora as connected with moẓi shem ra, "the person guilty of slander or libel," they regarded leprosy primarily as a divine punishment for this evil, an interpretation which receives historical support by the punishment of Miriam for her slander of Moses (Num. 12:1–15), and the rabbis add that Aaron suffered the same punishment for the same reason (Shab. 97a). Among other sins which bring leprosy as retribution are "the shedding of blood, taking oaths in vain, incest, arrogance, robbery, and envy" (Ar. 16a), as well as benefiting from sacred objects (Lev. R. 17:3). From the combination of the cedar, which represents haughtiness, and the hyssop, the symbol of lowliness, in the purification rites for the leper (Lev. 14:4) the rabbis derived the lesson that man should ever humble himself (see Rashi to Lev. 14:4). The leper was one of the four unfortunates considered to suffer a living death (Ned. 64b; Sanh. 47a; cf. Num. 12:12). That leprosy was assumed to result from a lack of hygiene is indicated not only by the reason given for its absence in Babylon (see above), but also from such statements as that it comes from flies (Ḥag. 14a), whereas the notion that children born from intercourse with a menstruant woman will be afflicted by it (Lev. R. 15:5) is more likely to be related to issues of sin and impurity than to hygiene. The aggadah makes a considerable addition to the number of characters mentioned in the Bible as having been struck with leprosy. They include Cain (Gen. R. 22:12), the daughter of Pharaoh (Ex. R. 1:23), Aaron (see above), Doeg (Sanh. 106b), David (Sanh. 107a), Goliath (Lev. R. 17:3), and Vashti (Meg. 12b). According to the Midrash, the reference to the pharaoh who died (Ex. 2:23) actually refers to the fact that he was afflicted with leprosy. His advisers told him that the only cure was to bathe morning and evening in the blood of 150 Hebrew children, but the decree was averted by God, who in his compassion cured Pharaoh (Ex. R. 1:34).

[Louis Isaac Rabinowitz]

bibliography:

Kaufmann, Y., Toledot, 1 (1937), 539–58; Kaufmann, Y., Religion, 103–10; R.K. Harrison, in: idb, 3 (1962), 111–3, 331–4. in the second temple and talmud: I.M. Rabbinowicz, La Médicine du Talmud (1880), 107ff.; G.N. Minkh, Prokaza i pes (1890); J. Preuss, Biblisch-talmudische Medizin (1923³), 369–90; J.L. Katzenelson, Ha-Talmud ve-Ḥokhmat ha-Refu'ah (1928), 304–53; H.L. Strack and P. Billerbeck, Kommentar zum Neuen Testament aus Talmud und Midrash, 14 (1928), 745–63; Ginzberg, Legends, index; A.R. Short, The Bible and Modern Medicine (1953), 74–83. add. bibliography: Y. Zakovitch, Every High Official (1986); B. Levine, jps Torah Commentary Leviticus (1989), 75–92; J. Milgrom, Leviticus 1–16 (ab; 1991); D. Wright and R. Jones, in: abd, 4:277–82; R. Biggs, in: cane iii, 1916; H. Avalos, Illness and Health Care in the Ancient Near East (1996), 233–420; S.D. Sperling, in: huca, 70–71 (1999–2000), 39–55.

Leprosy

Definition

Leprosy is a slowly progressing bacterial infection that affects the skin, peripheral nerves in the hands and feet, and mucous membranes of the nose, throat, and eyes. Destruction of the nerve endings causes the the affected areas to lose sensation. Occasionally, because of the loss of feeling, the fingers and toes become mutilated and fall off, causing the deformities that are typically associated with the disease.

Description

Leprosy is also known as Hansen's disease after G. A. Hansen, who in 1878 identified the bacillus Mycobacterium leprae that causes the disease.

The infection is characterized by abnormal changes of the skin. These changes, called lesions, are at first flat and red. Upon enlarging, they have irregular shapes and a characteristic appearance. The lesions are typically darker in color around the edges with discolored pale centers. Because the organism grows best at lower temperatures the leprosy bacillus has a preference for the skin, the mucous membranes and the nerves. Infection in and destruction of the nerves leads to sensory loss. The loss of sensation in the fingers and toes increases the risk of injury. Inadequate care causes infection of open wounds. Gangrene may also follow, causing body tissue to die and become deformed.

Because of the disabling deformities associated with it, leprosy has been considered one of the most dreaded diseases since biblical times, though much of what was called leprosy in the Old Testament most likely was not the same disease. Its victims were often shunned by the community, kept at arm's length, or sent to a leper colony. Many people still have misconceptions about the disease. Contrary to popular belief, it is not highly communicable and is extremely slow to develop. Household contacts of most cases and the medical personnel caring for Hansen's disease patients are not at particular risk. It is very curable, although the treatment is long-term, requiring multiple medications.

The World Health Organization (WHO) puts the number of identified leprosy cases in the world at about 600,000 as of the early 2000s. Seventy percent of all cases are found in just three countries: India, Indonesia, and Myanamar (Burma). The infection can be acquired, however, in the Western Hemisphere as well. There are about 5000 reported cases in the United States as of 2004, almost all of which involve immigrants from developing countries. Cases also occur in some areas of the Caribbean. Although it was thought for many years that only humans are affected by the disease, 15% of wild armadillos in southern Texas and Louisiana have been found to be infected with M. leprae.

Causes and symptoms

The organism that causes leprosy is a rod-shaped bacterium called Mycobacterium leprae. This bacterium is related to Mycobacterium tuberculosis, the causative agent of tuberculosis. Because special staining techniques involving acids are required to view these bacteria under the microscope, they are referred to as acid-fast bacilli (AFB).

When Mycobacterium leprae invades the body, one of two reactions can take place. In tuberculoid leprosy (TT), the milder form of the disease, the body's immune cells attempt to seal off the infection from the rest of the body by surrounding the offending pathogen. Because this response by the immune system occurs in the deeper layers of the skin, the hair follicles, sweat glands, and nerves can be destroyed. As a result, the skin becomes dry and discolored and loses its sensitivity. Involvement of nerves on the face, arms, or legs can cause them to enlarge and become easily felt by the doctor. This finding is highly suggestive of TT. The scarcity of bacteria in this type of leprosy leads to it being referred to as paucibacillary (PB) leprosy. Seventy to eighty percent of all leprosy cases are of the tuberculoid type.

In lepromatous (LL) leprosy, which is the second and more contagious form of the disease, the body's immune system is unable to mount a strong response to the invading organism. Hence, the organism multiplies freely in the skin. This type of leprosy is also called the multibacillary (MB) leprosy, because of the presence of large numbers of bacteria. The characteristic feature of this disease is the appearance of large nodules or lesions all over the body and face. Occasionally, the mucous membranes of the eyes, nose, and throat may be involved. Facial involvement can produce a lion-like appearance (leonine facies). This type of leprosy can lead to blindness, drastic change in voice, or mutilation of the nose. Leprosy can strike anyone; however, children seem to be more susceptible than adults.

Well-defined skin lesions that are numb are the first symptoms of tuberculoid leprosy. Lepromatous leprosy is characterized by a chronic stuffy nose due to invasion of the mucous membranes, and the presence of nodules and lesions all over the body and face.

Although patients with leprosy are commonly thought not to suffer pain, neuroapthic pain caused by inflammation of peripheral nerve endings is increasingly recognized as a major complication of the disease in many patients. Corticosteroids may be given to reduce the inflammation.

The incubation period of the leprosy bacillus varies anywhere from six months to ten years. On an average, it takes four years for the symptoms of tuberculoid leprosy to develop. Probably because of the slow growth of the bacillus, lepromatous leprosy develops even more slowly, taking an average of eight years for the initial lesions to appear.

It is still not very clear how the leprosy bacillus is transmitted from person to person; about 50% of patients diagnosed with the disease have a history of close contact with an infected family member. Since untreated patients have a large number of M. leprae bacilli in their nasal secretions, it is thought that transmission may take place via nasal droplets. The milder tubercular form of leprosy may be transmitted by insect carriers or by contact with infected soil.

The incidence of leprosy is highest in the poverty belt of the globe. Therefore, environmental factors such as unhygienic living conditions, overpopulation, and malnutrition may also be contributing factors favoring the infection.

It is also possible that genetic factors are involved in susceptibility to leprosy. In 2003, scientists conducting a genome scan of a large Vietnamese family with many cases of leprosy found that susceptibility to the disease was linked to region q25 on the long arm of chromosome 6. Further study indicated that the leprosy susceptibility gene lies within a region shared by two genes for Parkinson's disease. Further research may confirm that the emergence of leprosy in certain individuals is related to inheritance of genes for Parkinson's disease.

Diagnosis

One of the hallmarks of leprosy is the presence of AFB in smears taken from the skin lesions, nasal scrapings, or tissue secretions. In patients with LL leprosy, the bacilli are easily detected; however, in TT leprosy the bacteria are very few and almost impossible to find. In such cases, a diagnosis is made based on the clinical signs and symptoms, the type and distribution of skin lesions, and history of having lived in an endemic area.

The signs and symptoms characteristic of leprosy can be easily identified by a health worker after a short training period. There is no need for a laboratory investigation to confirm a leprosy diagnosis, except in very rare circumstances.

In an endemic area, if smears from an individual show the presence of AFB, or if he has typical skin lesions, he should definitely be regarded as having leprosy. Usually, there is slight discoloration of the skin and loss of skin sensitivity. Thickened nerves accompanied by weakness of muscles supplied by the affected nerve are very typical of the disease. One characteristic occurrence is a foot drop where the foot cannot be flexed upwards, affecting the ability to walk.

Treatment

The most widely used drug for leprosy is dapsone (DDS). However, the emergence of dapsone-resistant strains prompted the introduction of multidrug therapy, or MDT. MDT combines dapsone, rifampin (Rifadin; also known as rifampicin), and clofazimine (Lamprene), all of which are powerful antibacterial drugs. Patients with MB leprosy are usually treated with all three drugs, while patients with PB leprosy are only given rifampin and dapsone. Usually three months after starting treatment, a patient ceases being infectious, though not everyone with this disease is necessarily infectious before treatment. Depending on the type of leprosy, the time required for treatment may vary from six months to two years or more.

Each of the drugs has minor side effects. Dapsone can cause nausea, dizziness, palpitations, jaundice and rash. A doctor should be contacted immediately if a rash develops. Dapsone also interacts with the second drug, rifampin. Rifampin increases the metabolizing of dapsone in the body, requiring an adjustment of the dapsone dosage. rifampin may also cause muscle cramps, or nausea. If jaundice, flu-like symptoms or a rash appear, a doctor should be contacted immediately. The third drug, clofazimine may cause severe abdominal pain and diarrhea, as well as discoloration of the skin. Red to brownish black discoloration of the skin and bodily fluids, including sweat, may persist for months to years after use.

Thalidomide, the most famous agent of birth defects in the twentieth century, is now being used to treat complications of leprosy and similar diseases. Thalidomide regulates the immune response by suppressing a protein, tumor necrosis factor alpha.

Leprosy patients should be aware that treatment itself can cause a potentially serious immune system response called a lepra reaction. When antibiotics kill M. leprae, antigens (the proteins on the surface of the organism that initiate the body's immune system response) are released from the dying bacteria. In some people, when the antigens combine with the antibodies to M. Leprae in the bloodstream, a reaction called erythema nodosum leprosum may occur, resulting in new lesions and peripheral nerve damage. Cortisonetype medications and, increasingly, thalidomide are used to minimize the effects of lepra reactions.

In some cases, severe ulcers caused by leprosy may be treated surgically with small skin grafts.

Prognosis

Leprosy is curable; however, the deformities and nerve damage associated with leprosy are often irreversible. Preventions or rehabilition of these defects is an integral part of management of the disease. Reconstructive surgery, aimed at preventing and correcting deformities, offers the greatest hope for disabled patients. Sometimes, the deformities are such that the patients will not benefit from this type of surgery.

Comprehensive care involves teaching patients to care for themselves. If the patients have significant nerve damage or are at high risk of developing deformities, they must be taught to take care of their insensitive limbs, similar to diabetics with lower leg nerve damage. Lacking the sensation of pain in many cases, the patients should constantly check themselves to identify cuts and bruises. If adequate care is not taken, these wounds become festering sores and a source of dangerous infection. Physiotherapy exercises are taught to the patients to maintain a range of movement in finger joints and prevent the deformities from worsening. Prefabricated standardized splints are available and are extremely effective in correcting and preventing certain common deformities in leprosy. Special kinds of footwear have been designed for patients with insensitive feet in order to prevent or minimize the progression of foot ulcers.

Prevention

By early diagnosis and appropriate treatment of infected individuals, even a disease as ancient as leprosy can be controlled. People who are in immediate contact with the leprosy patient should be tested for leprosy. Annual examinations should also be conducted on these people for a period of five years following their last contact with an infectious patient. Some physicians have advocated dapsone treatment for people in close household contact with leprosy patients.

The WHO Action Program for the Elimination of Leprosy adopted a resolution calling for the elimination of leprosy around the world by the year 2005. This goal is not likely to be reached, however; a computer simulation performed for WHO by a team of Dutch researchers in 2004 indicates that leprosy is likely to persist in some parts of the world until 2020, although its incidence will continue to decline.

KEY TERMS

Endemic area— A geographical area where a particular disease is prevalent.

Gangrene— Death of tissue due to loss of blood supply followed by bacterial invasion and putrefaction.

Incubation period— The time it takes for symptoms to develop after initial exposure to a disease-causing organism.

Lesion— Any visible, local abnormality of the tissues of the skin, such as a wound, sore, rash, or boil.

Mucous membranes— The inner tissue that covers or lines body cavities or canals open to the outside, such as nose and mouth. These membranes secrete mucus and absorb water and salts.

Nasal scraping— Pathological material obtained for clinical study by scratching the inner surface of the nose with a clinical instrument.

Nodules— A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch.

Pathogen— Any disease-producing agent or microorganism.

Smear— A specimen prepared for microscopic study by spreading the material across a slide and treating it with a specific stain.

Resources

BOOKS

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Infectious Diseases Caused by Mycobacteria." In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

PERIODICALS

Buschman, E., and E. Skamene. "Linkage of Leprosy Susceptibility to Parkinson's Disease Genes." International Journal of Leprosy and Other Mycobacterial Diseases 72 (June 2004): 169-170.

Jayaseelan, A., and W. Aithal. "Pinch Skin Grafting in Non-Healing Leprous Ulcers." International Journal of Leprosy and Other Mycobacterial Diseases 72 (June 2004): 139-142.

Meima, A., W. C. Smith, G. J. van Oortmarssen, et al. "The Future Incidence of Leprosy: A Scenario Analysis." Bulletin of the World Health Organization 82 (May 2004): 373-380.

Stump, P. R., R. Baccarelli, L. H. Marciano, et al. "Neuropathic Pain in Leprosy Patients." International Journal of Leprosy and Other Mycobacterial Diseases 72 (June 2004): 134-148.

ORGANIZATIONS

American Leprosy Missions. 1 ALM Way, Greenville, SC 29601. (1-800-LEPROSY).

British Leprosy Relief Association, LEPRA. Fairfax House, Causton Road, Colchester, Essex CO1 1PU, UK.

INFOLEP, Leprosy Information Services. Postbus 95005,1090 HA, Amsterdam, Netherlands. 〈[email protected]〉.

WHO/LEP, Action Programme for the Elimination of Leprosy. 20 Avenue Appia CH-1211, Geneva 27, Suisse. 〈http://www.who.ch/programmes/lep/lep_home.htm〉.

OTHER

Cherath, Lata. "Leprosy." A Healthy Me Page. 〈http://www.ahealthyme.com/topic/topic100587076〉.

Leprosy

The cause of leprosy

The leprosy continuum

Treatment of leprosy

A leprosy vaccine?

Resources

Leprosy, also called Hansen’s disease, is responsible for active disease or disability in about four million people worldwide. Caused by an unusual bacterium called Mycobacterium leprae, leprosy primarily affects humans. Leprosy is found in tropical areas, such as Africa, South and Southeast Asia, and Central and South America. In the United States, cases of leprosy have been reported in areas of Texas, California, Louisiana, Florida, and Hawaii. Leprosy can take many forms, but the most familiar form is characterized by skin lesions and nerve damage. Although active leprosy is curable with various antibiotic drug therapies, it remains a devastating illness because of its potential to cause deformity, especially in the facial features.

The cause of leprosy

M. leprae is an unusual bacterium for several reasons. The bacterium divides very slowly; in some

tests, researchers have noted a dividing time of once every twelve days. This differs from the dividing time of most bacteria, which is once every few hours. M. leprae cannot be grown on culture media, and is notoriously difficult to culture within living animals. Because of these culturing difficulties, researchers have not been able to investigate these bacteria as closely as they have other, more easily cultured, bacteria. Questions remain unanswered about M. leprae; for instance, researchers are still unclear about how the bacteria are transmitted from one person to another, and are studying the role an individual’s genetic makeup plays in contracting and the progression of the disease.

Because M. leprae almost exclusively infects humans, animal models for studying leprosy are few. Surprisingly, a few species of armadillo can also be infected with M. leprae. Wild armadillos have been appearing with a naturally occurring form of leprosy. If the disease spreads in the armadillo population, researchers will not be able to use these animals for leprosy studies, since study animals must be completely free of the disease as well as the bacteria that cause it. Mice have also been used to study leprosy, but laboratory conditions, such as temperature, must be carefully controlled in order to sustain the infection in mice.

Scientists have been able to determine some facts about M. leprae from their experiments. M. leprae is temperature-sensitive; it favors temperatures slightly below normal human body temperature. Because of this predilection, M. leprae infects superficial body tissues such as the skin, bones, and cartilage, and does not usually penetrate to deeper organs and tissues. M. leprae is an intracellular pathogen; it crosses host cell membranes and lives within these cells. Once inside the host cell, the bacterium reproduces. The time required by these slow-growing bacteria to reproduce themselves inside host cells can be anywhere from a few weeks to as much as 40 years. Eventually, the bacteria lyse (burst open) the host cell, and new bacteria are released that can infect other host cells.

Researchers assume that the bacteria are transmitted via the respiratory tract. M. leprae exists in the nasal secretions and in the material secreted by skin lesions of infected individuals. M. leprae may be transmitted by breathing in the bacteria, through breaks in the skin, or perhaps through breast-feeding.

The leprosy continuum

Leprosy exists in several different forms, although the infectious agent for all of these forms is M. leprae. Host factors such as genetic make up, individual immunity, geography, ethnicity, and socioeconomic circumstances determine which form of leprosy is contracted by a person exposed to M. leprae. Interestingly, most people who come in contact with the bacterium— about three-fourths—never develop leprosy, or develop only a small lesion on the trunk or extremity that heals spontaneously. Most people, then, are not susceptible to M. leprae, and their immune systems function effectively to neutralize the bacteria. But one-fourth of those exposed to M. leprae contract the disease, which may manifest itself in various ways.

Five forms of leprosy are recognized, and a person may progress from one form to another. The least serious form is tuberculoid leprosy. In this form, the skin lesions and nerve damage are minor. Tuberculoid leprosy is evidence that the body’s cellular immune response—the part of the immune system that seeks out and destroys infected cells—is working at a high level of efficiency. Tuberculoid leprosy is easily cured with antibiotics.

If tuberculoid leprosy is not treated promptly, or if a person has a less vigorous cellular immune response to the M. leprae bacteria, the disease may progress to a borderline leprosy, which is characterized by more numerous skins lesions and more serious nerve damage. The most severe form of leprosy is lepromatous leprosy. In this form of leprosy, the skin lesions are numerous and cause the skin to fold, especially the skin on the face. This folding of facial skin leads to the leonine (lionlike) features typical of lepromatous leprosy. Nerve damage is extensive, and people with lepromatous leprosy may lose the feeling in their extremities, such as the fingers and toes. Contrary to popular belief, the fingers and toes of people with this form of leprosy do not spontaneously drop off. Rather, because patients cannot feel pain because of nerve damage, the extremities can become easily injured. Sometimes these injuries are severe, and fingers and toes are cut off by sharp objects which the patient cannot even detect.

Lepromatous leprosy occurs in people who exhibit an efficient antibody response to M. leprae but an inefficient cellular immune response. The antibody arm of the immune system is not useful in neutralizing intracellular pathogens such as M. leprae; therefore, people who initially react to invasion by M. leprae by making antibodies may be at risk for developing more severe forms of leprosy. Researchers are not sure what determines whether a person will react with a cellular response or an antibody response; current evidence suggests that the cellular immune response may be controlled by a special gene. If a person has this gene, he or she will probably develop the less severe tuberculoid leprosy if exposed to M. leprae.

Treatment of leprosy

Treatments for leprosy have improved considerably over the past 40 years and contributed to the rapid decline of the disease. Beginning in the 1950s, an antibiotic called dapsone was used to treat leprosy, offering the first hope of a cure for persons with the disease. Dapsone’s main disadvantage was that the patient had to take the medication daily throughout his or her lifetime. In addition, the M. leprae in some patients underwent genetic mutations that rendered it resistant to the antibiotic. In the 1980s, the problem of resistance was tackled with the advent of multidrug therapy. Bacteria are less likely to become resistant to drugs given in combination. The new multidrug treatment time was also considerably shorter. Currently, mutidrug therapy (MDT) with rifampin, clofazimine, and dapsone for six months to one year is the standard.

One risk of treatment, however, is that antigens-the proteins on the surface of M. leprae that initiate the host immune response—are released from the dying bacteria. In some people, when the antigens combine with antibodies to M. leprae in the bloodstream, a reaction called erythema nodosum leprosum may occur, resulting in new lesions and peripheral nerve damage. Some leprosy experts are experimenting with the drug thalidomide to treat this reaction, with good results. But because thalidomide causes severe birth defects, women of childbearing age must be carefully monitored while taking the drug.

KEY TERMS

Antibody response— The part of the immune system that marks foreign cells, such as bacteria, for destruction by other immune cells.

Cellular immune response— The part of the immune system that destroys infected cells.

Lepromatous leprosy— The most severe form of leprosy, characterized by numerous lesions and extensive nerve damage.

Resistance— In bacteria, the acquisition of genetic mutations that render the bacteria invulnerable to the action of antibiotics.

Tuberculoid leprosy— The least severe from of leprosy, characterized by a few skin lesions and little nerve damage.

A leprosy vaccine?

An effective, readily available, and reliable vaccine to protect against leprosy does not yet exist. One vaccine tested in Venezuela combined a vaccine originally developed against tuberculosis, called Bacille Calmette-Guerin (BCG), and heat-killed M. leprae cultured from infected armadillos. Another vaccine tested in India used a relative of M. leprae called M. avium. The advantage of this vaccine is that M. avium is easy to culture on media and is thus, cheaper than the Venezuelan vaccine. Both vaccines have shown mixed results in human trials. The latest strategy involves testing plasmid DNA vaccines in mice with the goal of creating immunity against both leprosy and tuberculosis simultaneously.

See also Antibody and antigen.

Resources

BOOKS

Guld, Tony. A Disease Apart: Leprosy in the Modern World. New York: St. Martin’s Press, 2005.

Tayman, John. The Colony: The Harrowing True Story of the Exiles of Molokai. New York, Scribner’s, 2006.

OTHER

World Health Organization. “Leprosy Today.” <http://www.who.int/lep/en/> (accessed November 26, 2006).

Kathleen Scogna

Leprosy

What Is Leprosy?

How Common Is Leprosy?

Is the Disease Contagious?

What Are the Signs and Symptoms?

How Is Leprosy Diagnosed?

Can Leprosy Be Treated?

What Are the Complications and Course of Leprosy?

How Can Leprosy Be Prevented?

Resources

Leprosy (LEH-pro-see) is a chronic*, infectious disease that damages the skin, peripheral nerves*, and mucous membranes* of the mouth, throat, and eyes. Leprosy also is known as Hansen disease.

*chronic

(KRAH-nik) means continuing for a long period of time.

*peripheral

(puh-RIH-fer-ul) nerves are a network of nerve fibers throughout the body that send and receive messages to and from the central nervous system (the brain and spinal cord).

*mucous membranes

are the moist linings of the mouth, nose, eyes, and throat.

KEYWORDS

for searching the Internet

and other reference sources

Hansen disease

Lepromatous leprosy

Multibacillary Hansen disease

Mycobacterium leprae

Paucibacillary Hansen disease

Tuberculoid leprosy

What Is Leprosy?

His equipment was inadequate and his colleagues thought his theories were laughable. Still, Gerhard Henrik Armauer Hansen (1841–1912) spent day after day bent over his microscope, determined to prove that leprosy was caused by bacteria. And he did. In 1873 the Norwegian physician identified the rod-shaped bacterium Mycobacterium leprae (my-ko-bak-TEER-e-um LEH-pray) as the cause of the illness. Hansen’s discovery was immensely valuable in the treatment of leprosy, and it was a scientific milestone—the first proof that bacteria could cause human disease. Today, the use of the word “leper” is considered insulting, because it defines a person by the disease he or she has. Many advocates for people with leprosy prefer to call it Hansen disease.

The name paucibacillary (paw-sih-BAH-sih-lair-e) Hansen disease comes from the Latin word pauci, meaning few, and is used to describe a mild form of leprosy. Paucibacillary Hansen disease begins in the peripheral nerves and spreads to the skin, causing patches of skin to become numb and hypopigmented, which means that the skin has lost its coloring and appears white. Multibacillary (mul-tie-BAH-sih-lair-e) Hansen disease is a more severe form of the disease. Multibacillary Hansen disease also causes skin lesions (LEE-zhuns), or patches of damaged tissue; nodules, or lumps; and thickening of the skin. Without treatment, this type of leprosy can worsen over time, resulting in severe skin and tissue damage and disfigurement.

3,000 Years of Leprosy

Leprosy has left a trail of pain, suffering, and death that dates back thousands of years. Archeologists have uncovered skeletal remains with erosion in the bones of the nose that is characteristic of leprosy. Researchers translating from ancient Indian and Chinese texts have found descriptions of the disease. As men and armies roamed the globe in search of conquest, the germ that causes leprosy traveled with them. Researchers believe that in the first century B.C., Roman soldiers fighting in Egypt carried the disease home to Italy. In the Middle Ages, the disease spread from Italy throughout Europe. During the Crusades, a series of “holy wars” spanning the eleventh to the thirteenth centuries, European soldiers and pilgrims carried the disease as far as Jerusalem in the Middle East. The disease continued to follow the paths of conquering armies. The Spanish conquistadors and the slave trade brought the disease to the American continents, and European colonists probably spread the disease to islands in the Pacific Ocean.

How Common Is Leprosy?

Throughout human history leprosy has caused untold suffering. Even after Hansen’s groundbreaking discovery, the disease remained unchecked in many parts of the world. In 1991, the World Health Organization (WHO) began a global campaign to reduce the number of cases of leprosy. A decade later the organization announced that it had reached its goal and estimated that there were at that time 600,000 to 750,000 cases of leprosy worldwide. The disease is most common in tropical and subtropical regions, and in 2001, it remained a particular problem in Brazil, India, Madagascar, Mozambique, Nepal, and Myanmar. Leprosy is most common in densely populated areas with poor sanitation and health care, and children are at greater risk than adults of getting the disease. In the United States about 100 cases are reported each year, many of them in people who have recently immigrated.

Is the Disease Contagious?

Leprosy is contagious but does not spread easily. Researchers believe that Mycobacterium leprae is transmitted from person to person via respiratory droplets, bits of moisture that leave the mouth or nose when a person laughs, talks, sneezes, or coughs. Most people seem to have a natural immunity* that enables them to resist the disease. Of those in whom leprosy is diagnosed, most have had prolonged and close contact with someone who has an active infection. Once a person with leprosy has been taking medication for 3 or 4 days, the disease is no longer active or contagious.

*immunity

(ih-MYOON-uh-tee) is the condition of being protected against an infectious disease. Immunity often develops after a germ is introduced to the body. One type of immunity occurs when the body makes special protein molecules called antibodies to fight the disease-causing germ. The next time that germ enters the body, the antibodies quickly attack it, usually preventing the germ from causing disease.

What Are the Signs and Symptoms?

Leprosy begins as an infection in the nerve endings and spreads gradually; the skin near the infected nerves may become numb and hypopigmented. In severe cases, these skin lesions become wider and thicker. The muscles in the hands and feet can become weak or paralyzed (unable to move) because of damage to the peripheral nerves. That loss of sensation can lead to accidental injury, because a person loses the withdrawal reflex that helps protect against injury from hot or sharp objects. Left unchecked, the most severe form of the disease can progress, producing large, disfiguring nodules and enlarged facial features that give a person the lionlike appearance associated with severe leprosy.

How Is Leprosy Diagnosed?

Leprosy is not difficult to diagnose once it is suspected. A procedure in which a tiny piece of skin is scraped or cut away and then examined usually reveals the presence of Mycobacterium leprae in the multibacillary form of leprosy. (The bacteria may not be found using this method in milder, paucibacillary disease.) The procedure can be done quickly and relatively painlessly in a doctor’s office or clinic. It is an important part

of the diagnosis, because in the early stages of the disease leprosy lesions look very much like skin damage caused by other neurocutaneous* diseases. The presence of the characteristic lesions, accompanied by a history of living in areas where the disease is common, is what usually causes doctors to suspect the diagnosis.

*neurocutaneous

(nur-o-kyoo-TAY-nee-us) means affecting the skin and nerves.

As long ago as biblical times, people with the disfiguring signs of leprosy were cast out of their homes and villages and made to live together in isolated colonies. Even in modern times such colonies were established in the Western world, for example, on Penikese Island off Massachusetts and on the Hawaiian island of Molokai. Corbis Corporation (Bellevue)

Can Leprosy Be Treated?

Early diagnosis and treatment are key to stopping the spread of leprosy to other people and preventing long-term damage to the patient. Doctors most often prescribe multidrug therapy (MDT), combining two or three drugs that kill the bacteria: dapsone (DAP-sone), rifampicin (rye-FAM-pih-sin), and clofazimine (klo-FAY-zuh-meen). The MDT approach has been preferred since the early 1980s, when researchers noticed that the bacterium was becoming resistant to some treatments. Patients may take the drugs for as little as 6 months or as long as 2 years. Patients who have become disfigured or who experience disabilities may need surgery to correct these problems.

What Are the Complications and Course of Leprosy?

With MDT, paucibacillary Hansen disease can be cured within 6 to 12 months and multibacillary Hansen disease within 2 years. Untreated, leprosy can cause blindness, permanent nerve damage, and deformity. People may lose the use of their hands or feet, because, over time, the decreased sensation may result in repeated injuries to the limbs.

How Can Leprosy Be Prevented?

Despite centuries in which people with leprosy were vilified, shunned, and even isolated in far-off “leper colonies,” there is no need to separate people with leprosy from the rest of society to avoid the spread of infection. MDT treatment is more effective and far more humane, and it has been determined that leprosy is much less contagious than once was believed. Hand washing, disinfection, and monitoring of close contacts are recommended to help prevent the spread of the disease.

See also

Public Health

Resources

Book

Eynikel, Hilde. Molokai: The Story of Father Damien. Translated by Lesley Gilbert. New York: Alba House, 1999. This is the story of the Belgian priest who cared for thousands of people with leprosy who were banished to the remote island of Molokai in the Hawaiian Islands. The book was made into a movie by the same name that is available on DVD.

Organization

World Health Organization (WHO), Avenue Appia 20, 1211 Geneva 27, Switzerland. The WHO tracks efforts to eradicate leprosy and has links to fact sheets and information on the prevention and control of the disease on its website.

Telephone 011-41-22-791-2111 http://www.who.int

Leprosy

Leprosy, also called Hansen's disease, affects 10 –12 million people worldwide. Caused by an unusual bacterium called Mycobacterium leprae, leprosy primarily affects humans. Leprosy is found in tropical areas, such as Africa, South and Southeast Asia, and Central and South America. In the United States, cases of leprosy have been reported in areas of Texas, California, Louisiana, Florida, and Hawaii. Leprosy can take many forms, but the most familiar form is characterized by skin lesions and nerve damage. Although leprosy is curable with various antibiotics , it remains a devastating illness because of its potential to cause deformity, especially in the facial features. Fortunately, antibiotic regimens are available to treat and eventually cure leprosy.

Mycobacterium leprae is an unusual bacterium for several reasons. The bacterium divides slowly; in some tests, researchers have noted a dividing time of once every twelve days. This differs from the dividing time of most bacteria , which is about once every few hours. M. leprae cannot be grown on culture media, and is notoriously difficult to culture within living animals. Because of these culturing difficulties, researchers have not been able to investigate these bacteria as closely as they have other, more easily cultured, bacteria. Questions remain unanswered about M. leprae; for instance, researchers are still unclear about how the bacteria are transmitted from one person to another, and are not sure about the role an individual's genetic make up plays in the progression of the disease.

Because M. leprae almost exclusively infects humans, animal models for studying leprosy are few. Surprisingly, a few species of armadillo can also be infected with M. leprae. Recently, however, wild armadillos have been appearing with a naturally occurring form of leprosy. If the disease spreads in the armadillo population, researchers will not be able to use these animals for leprosy studies, since study animals must be completely free of the disease as well as the bacteria that cause it. Mice have also been used to study leprosy, but laboratory conditions, such as temperature, must be carefully controlled in order to sustain the infection in mice.

M. leprae is temperature-sensitive; it favors temperatures slightly below normal human body temperature. Because of this predilection, M. leprae infects superficial body tissues such as the skin, bones, and cartilage, and does not usually penetrate to deeper organs and tissues. M. leprae is an intracellular pathogen; it crosses host cell membranes and lives within these cells. Once inside the host cell, the bacterium reproduces. The time required by these slow-growing bacteria to reproduce themselves inside host cells can be anywhere from a few weeks to as much as 40 years. Eventually, the bacteria lyse (burst open) the host cell, and new bacteria are released that can infect other host cells.

Researchers assume that the bacteria are transmitted via the respiratory tract. M. leprae exists in the nasal secretions and in the material secreted by skin lesions of infected individuals. M. leprae has also been found in the breast milk of infected nursing mothers. M. leprae may be transmitted by breathing in the bacteria, through breaks in the skin, or perhaps through breast-feeding.

Leprosy exists in several different forms, although the infectious agent for all of these forms is M. leprae. Host factors such as genetic make up, individual immunity , geography, ethnicity, and socioeconomic circumstances determine which form of leprosy is contracted by a person exposed to M. leprae. Interestingly, most people who come in contact with the bacterium, about three-fourths, never develop leprosy, or develop only a small lesion on the trunk or extremity that heals spontaneously. Most people, then, are not susceptible to M. leprae, and their immune systems function effectively to neutralize the bacteria. But one-fourth of those exposed to M. leprae contract the disease, which may manifest itself in various ways.

Five forms of leprosy are recognized, and a person may progress from one form to another. The least serious form is tuberculoid leprosy. In this form, the skin lesions and nerve damage are minor. Tuberculoid leprosy is evidence that the body's cellular immune response—the part of the immune system that seeks out and destroys infected cells—is working at a high level of efficiency. Tuberculoid leprosy is easily cured with antibiotics.

If tuberculoid leprosy is not treated promptly, or if a person has a less vigorous cellular immune response to the M. leprae bacteria, the disease may progress to a borderline leprosy, which is characterized by more numerous skins lesions and more serious nerve damage. The most severe form of leprosy is lepromatous leprosy. In this form of leprosy, the skin lesions are numerous and cause the skin to fold, especially the skin on the face. This folding of facial skin leads to the leonine (lion-like) features typical of lepromatous leprosy. Nerve damage is extensive, and people with lepromatous leprosy may lose the feeling in their extremities, such as the fingers and toes. Contrary to popular belief, the fingers and toes of people with this form of leprosy do not spontaneously drop off. Rather, because patients cannot feel pain because of nerve damage, the extremities can become easily injured.

Lepromatous leprosy occurs in people who exhibit an efficient antibody response to M. leprae but an inefficient cellular immune response. The antibody arm of the immune system is not useful in neutralizing intracellular pathogens such asM. leprae; therefore, people who initially react to invasion by M. leprae by making antibodies may be at risk for developing more severe forms of leprosy. Researchers are not sure what determines whether a person will react with a cellular response or an antibody response; current evidence suggests that the cellular immune response may be controlled by a special gene . If a person has this gene, he or she will probably develop the less severe tuberculoid leprosy if exposed to M. leprae.

Treatments for leprosy have improved considerably over the past 40 years. In fact, some experts are encouraged that the drug regimens being tested in various trials throughout the world (including the United States) may eradicate leprosy completely by the year 2010. Beginning in the 1950s, an antibiotic called dapsone was used to treat leprosy, offering the first hope of a cure for persons with the disease. Dapsone's main disadvantage was that the patient had to take the medication daily throughout his or her lifetime. In addition, the M. leprae in some patients underwent genetic mutations that rendered it resistant to the antibiotic. In the 1960s, the problem of resistance was tackled with the advent of multidrug therapy. Bacteria are less likely to become resistant to several drugs given in combination. The new multidrug treatment time was also considerably shorter-typically about four years. Currently, researchers offer a new drug combination that includes an antibiotic called oflaxicin. Oflaxicin is a powerful inhibitor of certain bacterial enzymes that are involved in DNA coiling. Without these enzymes, the M. leprae cannot copy the DNA properly and the bacteria die. The treatment time for this current regimen is about four weeks or less, the shortest treatment duration so far.

One risk of treatment, however, is that antigens—the proteins on the surface of M. leprae that initiate the host immune response—are released from the dying bacteria. In some people, when the antigens combine with antibodies to M. leprae in the bloodstream, a reaction called erythema nodosum leprosum may occur, resulting in new lesions and peripheral nerve damage. In the late 1990s, the drug thalidomide was approved to treat this reaction, with good results. Because thalidomide may cause severe birth defects, women of childbearing age must be carefully monitored while taking the drug.

A promising development in the treatment and management of leprosy is the preliminary success shown by two different vaccines. One vaccine tested in Venezuela combined a vaccine originally developed against tuberculosis , called Bacille Calmette-Guerin (BCG), and heat-killed M. leprae cultured from infected armadillos. The other vaccine uses a relative of M. leprae called M. avium. The advantage of this vaccine, currently being tested in India, is that M. avium is easy to culture on media and is thus cheaper than the Venezuelan vaccine. Both vaccines have performed well in their clinical trials, leading many to hope that a vaccine against leprosy might soon be available.

The World Health Organization announced in January, 2002, that during the previous decade, the number of active cases of leprosy worldwide had been reduced by 90%. Control of leprosy still eludes six countries, Brazil, India, Madagascar, Mozambique, Myanmar and Nepal, with approximately 700,000 ongoing cases identified worldwide in 2002. In conjunction with the World Health Organization, these countries have committed to accelerating control efforts, including early access to current drug therapy. The worldwide reduction and control of leprosy stands as one of the major world health initiatives of modern times.

See also Bacteria and bacterial infection; Mycobacterial infections, atypical