Monitoring the effects of preventive therapy in the federated states of Micronesia

International Journal of Leprosy and Other Mycobacterial Diseases, Dec 1999 by Cho, Sang-Nae, Walsh, Gerald P, Brennan, Patrick J

The objective of this study was to assess the effects of the chemoprophylaxis of leprosy on Mycobacterium leprae transmission among residents of the FSM, by measuring the prevalence of antibodies to antigens of M. leprae among residents in FSM after the administration of chemoprophylaxis, and to attempt, by polymerase chain reaction (PCR), to detect M. leprae-specific DNA in nasal-swab samples obtained from among residents after chemoprophylaxis.

MATERIALS AND METHODS

A total of 3304 serum samples were obtained during the study period, including 1725 samples before chemoprophylaxis and 1125 one year after the first dose of chemoprophylaxis. Serum samples were obtained from two sources: from residents who presented to the leprosy team for screening and chemoprophylaxis; and from individuals who visited the health centers in Pohnpei, Chuuk and Kosrae States for reasons other than leprosy. Serum samples were stored frozen until examination for the presence of antibodies to M. leprae antigens.

To determine the proportions of individuals on whose nasal mucosa M. leprae-specific DNA could be detected by PCR, nasalswab samples were obtained from those who presented to the leprosy team at the time of screening. A total of 1240 nasalswab samples were obtained, including 629 samples obtained before chemoprophylaxis and 611 samples one year after the first dose of chemoprophylaxis. The surface of the nasal mucous membrane was wiped with a cotton-tipped swab which was then placed in L4 buffer and stored at room temperature until it could be transported to the laboratory.

RESULTS

First, sera from 1065 individuals who presented to the hospitals for reasons other than leprosy were examined. IgM antibodies to PGL-I, an M. leprae-specific antigen, were detected by ELISA using a neoglycoconjugate antigen, ND-0-BSA, which had been prepared in Fort Collins, Colorado, U.S.A. Using absorbance of 0.20 as the lower limit of seropositivity, the rate of seropositivity was 12.3 percent among residents of Pohnpei State, 13.9 percent in Chuuk State, and 5.9 percent in Kosrae State. The lower seropositivity rate in Kosrae State is consistent with the lower prevalence of leprosy in that state. The difference of seropositivity between Chuuk and Pohnpei States is not significant. The rate of seropositivity was highest among those aged 21-30 years (19.1 percent), followed by those aged 11-20 (15.1 percent) and the group aged 31-40 years (13.3 percent). That more than 13 percent of young children in Chuuk State were seropositive suggests that, before chemoprophylaxis, active transmission of M. leprae was still occur-ring.

Next, sera from 245 people, who presented to the health centers for reasons other than leprosy, and from 610 people one year after chemoprophylaxis were examined. The rate of seropositivity among those who had been administered chemoprophylaxis was 20.6 percent, virtually the same as the rate (20.0 percent) among a second group of 660 residents prior to chemoprophylaxis. The prevalence of anti-PGL-I antibodies among those visiting the health centers was 17.5 percent, a bit higher than that during the first year in Pohnpei State. The rate of seropositivity was again highest among those aged 11-20 years, followed by that of the age group 21-30. These results suggest that young adults in Pohnpei State have the greatest chance of exposure to M. leprae, even one year after chemoprophylaxis. Another explanation is that anti-PGL-I antibodies decay only slowly

In an effort to investigate more directly the effect of chemoprophylaxis on the levels of anti-PGL-I antibodies, the sera of those who had taken the first dose of chemoprophylaxis and whose sera were obtained one year later were examined for changes of seroreactivity. A total of 81 paired serum samples were tested side by side. Of the 81 pairs, 21 (25.9 percent) were seropositive before chemoprophylaxis and 21 (25.9 percent)-not all the same pairswere also seropositive one year after chemoprophylaxis, suggesting that there had been no significant impact on the rate of seropositivity by the first dose. However, some of the 81 demonstrated a substantial decrease of antibody level after chemoprophylaxis. Five individuals became seronegative after chemoprophylaxis, and the mean absorbance of the seropositive sera decreased from 0.41 to 0.37. Thus, chemoprophylaxis may result in a decline of the antiPGL-I antibody level, although the difference of the means is not statistically significant. In addition, there were also some persons whose antibody levels increased after chemoprophylaxis, and five people became seropositive, suggesting that there may have been exposure to M. leprae after the chemoprophylaxis had been administered. Such a phenomenon is also consistent with continuing active transmission of M. leprae in the community.

In another effort to measure the effects of chemoprophylaxis, paired serum samples from high-school students in Pohnpei State and age-matched samples obtained from hospitals in Kosrae were examined in a randomized fashion for the presence of antibodies to MLSA and lipoarabinomannan (LAM), soluble antigens of M. leprae. There was no difference in the prevalence of antibodies to MLSA and LAM before and one year after chemoprophylaxis among high-school students in Pohnpei State: 24 percent were seropositive to LAM and 16 percent to MLSA. These results suggest that one dose of chemoprophylaxis had no significant effect on the prevalence of antibodies to M. leprae antigens.