A clinical and immunological study of four babies of mothers with lepromatous leprosy, two of whom developed leprosy in infancy.

One hundred thirteen women and 27 healthy controls were studied throughout pregnancy, at delivery, and followed up with their babies during lactation. Thirty-eight of the mothers with lepromatous leprosy were found to have solid-staining bacilli in skin smears or biopsies, and hence were considered potentially highly infectious to their unborn children by hematogenous spread via the placenta. Two babies of mothers within this group were diagnosed as having leprosy on clinical and histological grounds. A third baby could well have had leprosy, but the case was not proven. The fourth baby did not have leprosy and, although it did have ringworm, was thus deemed to be a reasonable control. The leprosy skin lesions were first observed at a special followup clinic when the children were between the aged of 9 and 17 months. The demonstration of IgA and IgM anti-M. leprae antibodies in cord sera was taken as an indication of intrauterine immunologic stimulation, and hence transplacental transmission of M. leprae. The two babies with proven leprosy showed an early and significant increase in serum IgA and in particular serum IgM anti-M. leprae antibody activity. A third baby, suspected of having leprosy but in whom the diagnosis was not proven, showed a similar but less marked increase in serum IgA and IgM activity. The fourth baby showed no such rise in anti-M. leprae activity. A decrease in serum IgG anti-M. leprae antibody activity could be demonstrated in one of the babies with leprosy after healing of the leprosy lesions, but not in the second baby.

Pregnancy and leprosy: the consequences of alterations of cell-mediated and humoral immunity during pregnancy and lactation.

One hundred fourteen Ethiopian women with leprosy and 33 healthy women without leprosy were studied prospectively throughout 119 and 37 pregnancies, respectively, and followed up during lactation. Fifty-five women showed worsening of their leprosy status; in 31 (56%) this was observed during the third trimester of pregnancy. Forty women were diagnosed as having Type 1 lepra reaction; in 20 (50%) the first occurrence was during the first six months of lactation. Twenty-eight women had Type 2 lepra reaction, which in 19 (68%) first occurred during the third trimester of pregnancy or the first six months of lactation. These adverse effects of pregnancy on leprosy are thought to be associated with suppression of maternal cell-mediated immunity during gestation and recovery postpartum. Implications for the obstetrician, physician and leprosy health worker are discussed.

IgA, IgM and IgG anti-M. leprae antibodies in babies of leprosy mothers during the first 2 years of life.

IgA, IgM and IgG anti-M. leprae antibody activity was estimated by solid phase radioimmunoassay in repeated serum samples from cord sera to sera taken 2 years after birth from 29 babies of mothers with lepromatous leprosy (Group 1) and 16 babies of mothers with tuberculoid leprosy and non-leprosy control mothers (Group 2). IgA anti-M. leprae antibody activity could be detected in 30% and IgM anti-M. leprae antibody activity in 50% of cord sera from Group 1, but not in any of the cord sera from Group 2. After birth, there was a significantly higher increase of IgA and IgM anti-M. leprae antibody activity in sera taken 3-6 months after birth from babies of Group 1 compared to Group 2, but the IgA and IgM activity in sera taken after 6 months of age showed the same increase in the two groups. IgG anti-M. leprae antibody activity showed a marked decrease in sera from both Groups 1 and 2 taken 3-6 and 6-9 months after birth compared to the activity in the cord sera. No increase of the IgG activity could be demonstrated even in sera taken 15-24 months after birth in any of the two groups. These findings are discussed in relation to possible transfer of M. leprae bacilli across the placenta, the influence of M. leprae and other mycobacteria exposure on the antibody activity, the poor IgG anti-M. leprae antibody response and subclinical leprosy infection in babies exposed to leprosy below 2 years of age.

Class specific anti-Mycobacterium leprae antibody assay in lepromatous leprosy (BL-LL) patients during the first two to four years of DDS treatment.

Previously, a slight decrease in antibodies against M. leprae antigen 7 was demonstrated after one year of dapsone (DDS) treatment in 14 of 15 patients with lepromatous (BL-LL) leprosy. The same patients have now received DDS from 11/2 to 4 years (median 3 years) and sera taken at the start, during, and at the end of the observation period have been retested for antibodies against M. leprae antigen 7 by radioimmunoassay and tested for IgA-, IgM-, and IgG-anti-M. leprae antibody activity by solid phase radioimmunoassay. Both IgA- and IgG-anti-M. leprae antibody activity and the activity of antibodies against M. leprae antigen 7 showed a decrease in activity after three years of DDS treatment to a median value of about one third of the activity in the sera taken at the start of the study. A smaller but significant decrease in IgM-anti-M. leprae antibody activity could be demonstrated. A transient increase in antibody activity (both measured by RIA and sRIA) could be demonstrated and related to reactions (reversal reaction and ENL) in five patients. No significant correlation could be found when IgA-, IgM-, and IgG-anti-M. leprae antibody activity was compared with antibodies against M. Leprae antigen 7 in individual sera.

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

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

IgA and IgM antibodies against Mycobacterium leprae in cord sera and in patients with leprosy: an indicator of intrauterine infection in leprosy.

A solid-phase radioimmunoassay was developed for demonstration and quantification of IgA and IgM anti-M. leprae antibodies. IgA and IgM anti-M. leprae antibodies were demonstrated in a lepromatous serum pool, in various amounts in individual patients with lepromatous leprosy, and in lower concentration in tuberculoid leprosy and non-leprosy controls. IgA and IgM anti-M. leprae antibodies were demonstrated in cord sera from babies of mothers with leprosy. The reliability of fetal IgA and IgM antibody synthesis as an indicator of intrauterine infection in leprosy is discussed.

Antibodies against Mycobacterium leprae antigen 7 from birth to 18 months of age: an indicator of intra-uterine infection in leprosy.

All babies of three non-leprosy mothers and ten tuberculoid leprosy mothers and four of five babies of mothers with inactive lepromatous leprosy showed a decline in serum concentration of antibodies against M. leprae antigen 7 during the first 4 months of life, as expected from catabolism of maternal IgG. By contrast, ten of twenty babies of mothers with active lepromatous leprosy showed a decline in concentration of anti-M. leprae 7 antibodies considerably less than expected. This indicates that these babies have been stimulated by M. leprae antigen 7, either as free antigen or by viable M. leprae before birth, and thus that leprosy may occur as a congenital infection. Studies of anti-M. leprae antibodies in repeated serum samples obtained during the first 18 months of life indicated that children of mothers with bacilliferous leprosy are frequently exposed to M. leprae to a sufficient extent to stimulate the immune system of the baby to production of anti-M. leprae antibodies during this period. The consequences of this exposure to M. leprae should be ascertained by careful clinical studies.

In vitro modulation of lymphocyte responses to phytohaemagglutinin by plasma in mother and baby at the time of birth. Increased lymphocyte responses in babies of mothers with lepromatous leprosy.

Peripheral blood lymphocytes from nineteen healthy mothers, mothers with borderline tuberculoid leprosy and fourteen mothers with borderline or polar lepromatous leprosy, and their newborn babies, were stimulated in vitro with phytohaemagglutinin (PHA). The responses in medium supplemented by serum from a pool of healthy non-pregnant individuals were compared with responses in medium supplemented by plasma from the mothers or from their babies, to assay for the presence of non-specific effects on T-cell responses. It was found that plasma from the mothers at the time of labour profoundly suppressed their own lymphocyte responses to PHA. However, the lymphocyte responses of healthy mothers were not significantly suppressed when cultivated in the presence of plasma from the babies, indicating that the suppressive factor(s) of normal pregnancy did not pass the placental barrier. Plasma from mothers with leprosy had a greater inhibitory effect on their babies' lymphocytes than plasma from healthy mothers. This raises the possibility that plasma from leprosy patients contains suppressive factors other than those associated with pregnancy. Babies of lepromatous leprosy mothers, who might have been exposed to mycobacterial antigens in utero, had higher PHA responses than the other babies, possibly due to a compensatory reaction to early stresses in the immune system.