Pregnancy and leprosy neuropathy.

Women with leprosy (even apparently cured) run a serious risk of deterioration in nerve function when they become pregnant. During pregnancy and lactation the woman with leprosy may suffer: relapse, reactivation and transient exacerbation maximally in late pregnancy; ENL in the first and third trimesters, continuing with nerve damage postpartum; RR maximally postpartum, even after MDT and RFT; neuritis affecting almost 50% of women in any pregnancy/lactation, in most cases as "silent" neuritis with new motor and sensory loss, even after MDT-RFT, and stocking-and-glove anaesthesia even in PB women and post MDT-RFT. Those incubating the infection develop overt disease frequently in reaction. This tragic cycle can only be stopped by a combination of: (i) leprologists and leprosy control personnel understanding the problems of leprosy in pregnant and lactating mothers; (ii) well-planned health education for leprosy patients, and both leprosy and maternal health care workers and (iii) the highest standard of clinical supervision during pregnancy, prolonged lactation and at regular intervals during the woman's reproductive life, even after she would normally be released from surveillance after completion of multiple drug treatment (MDT).

An historical and clinical review of the interaction of leprosy and pregnancy: a cycle to be broken.

Since earliest history the person with leprosy has been shut out from society. Laws have prohibited marriage and allowed divorce of those with leprosy. Segregation of the sufferer from the rest of society has been followed by separation of the sexes, and of leprous parents from their children. With the advent of antileprotic drugs, first dapsone then multidrug therapy (MDT), infection can be treated, individuals made non-infectious, and the pool of infection in the community reduced. The clinical signs of leprosy are due not to the degree of infection but to the immunological status of the host. Hormonal changes at puberty and in pregnancy can cause variation of the host's immune status. Pregnancy in women with leprosy is a hazardous undertaking. First appearance of leprosy, reactivation of the disease and relapse in 'cured' patients is likely to occur particularly in the third trimester of pregnancy. Leprosy reactions caused by variation in cell mediated and humoral immunity are triggered off by pregnancy: type 1 reaction (reversal reaction, RR) occurs post partum, while type 2 reaction (erythema nodosum leprosum, ENL) peaks in late pregnancy. Both types of reaction continue long into lactation. Neuritis with loss of both sensory and motor function is associated with relapse and reaction. Relapse, reaction and nerve damage, especially 'silent neuritis', with subsequent deformity and disability, occur not only in women on apparently effective treatment but also in those who have received MDT and have been released from treatment (RFT). To prevent disability, research is urgently needed into the mechanisms of early and late reaction and neuritis. Pregnancy is not only a trigger factor for reaction but an ideal in vivo model for research. Up to 20% of children born to mothers with leprosy may develop leprosy by puberty. While early leprosy in young children is self-healing, when marriage and childbearing take place at an early age the daughters of mothers with leprosy are likely to run the risk of experiencing the adverse effects of pregnancy on leprosy. Increased awareness and health education, as well as long term surveillance of 'cured' leprosy patients, are essential to break a potentially vicious cycle of leprosy and pregnancy. Women with cured leprosy could play an important role in screening for and detection of both early leprosy in children and late, post-MDT RFT, nerve damage in their mothers.

The placenta in leprosy.

Eighty-one placentae from women with leprosy and 17 placentae from healthy controls were subjected to a detailed macroscopic, light microscopic, ultrastructural, immunopathological, microbiological and biochemical study. The placental morphology and immunohistology were normal, and there was no morphological evidence of infection of the placenta due to M. leprae. No acid-fast bacilli or acid-fast bacillary granules were seen on light microscopy of any of the placentae from leprous women, although homogenates from two out of seven placentae from women with very active lepromatous leprosy contained acid-fast bacilli in very small numbers. The small placental size of women with leprosy, most marked in those with lepromatous leprosy, appears to be due to a decrease in placental cell size, rather than to a reduced number of cells in the placenta. It is postulated that the small placenta and reduced fetal birth weight observed in lepromatous leprosy are a consequence of depressed maternal immune reactivity.

Humoral defence factors in the breast milk of Ethiopian women with leprosy and healthy controls.

Secretory IgA, lactoferrin, albumin, and total protein were quantitated in colostrum and milk samples obtained from 215 Ethiopian nursing mothers over a period ranging from 1 day to 2 yr postparturition. IgG, IgM, C3, and C4 complement components were quantitated in 11 day 1 samples. The subjects were classified into three groups: lepromatous leprosy, borderline lepromatous leprosy, and a nonlepromatous group consisting of women with tuberculoid leprosy and healthy controls. Results obtained from the above groups were also compared with a group from Edinburgh. No major variation in levels of secretory IgA, lactoferrin, albumin, and total protein was found between the three groups of Ethiopian women. Results from the Edinburgh group were significantly higher, mainly in the level of total protein. When the individual proteins were expressed as a percentage of the total protein, there was no difference between the milk samples from the Ethiopian and Edinburgh mothers.

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.

Estrogen excretion in pregnant women with leprosy: evidence of diminished fetoplacental function.

Estrogen excretion was assayed in 64 women with leprosy and 15 healthy control women. The mean estrogen excretion was lower in women with leprosy than in controls and the incidence of subnormal estrogen values was higher in the leprosy patients than in the controls. There was an association between infant birth weight and frequency of subnormal estrogen excretion. These features were most marked in women with lepromatous leprosy and are further evidence of diminished fetoplacental function in women with leprosy.

Neuritis in pregnancy and lactation.

One hundred and forty-six women were studied during and after 153 pregnancies (31 healthy contacts: 34 pregnancies; 115 leprosy patients: 119 pregnancies). One healthy contact and 51 leprosy patients developed neuritis during the study period. All leprosy patients, including those who were considered to be cured and had stopped treatment, were at risk. Neuritis was accompanied by Type 1 and Type 2 lepra skin reactions and/or deterioration of the patients' leprosy status; this was particularly the case when neuritis was associated with nerve pain or tenderness (overt neuritis). Neuritis without nerve pain or tenderness (silent neuritis), preceded by the complaint of "rheumatism" and the clinical finding of enlarged peripheral nerves, was seen more frequently than overt neuritis (48:37 episodes). Insidious silent neuritis with loss of sensory and motor function during lactation was a particularly dangerous and hitherto undescribed risk of pregnancy.

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.