High Anti–Phenolic Glycolipid-I IgM Titers and Hidden Leprosy Cases, Amazon Region

To the Editor: Leprosy remains a serious public health issue. Although the World Health Organization elimination target was achieved in 2000, with a prevalence of <1 case/10,000 persons, despite progress since introduction of multidrug therapy (1), large pockets of poverty remain in which the disease is hyperendemic and underdiagnosed. In fact, in highly disease-endemic areas, the prevalence of previously undiagnosed leprosy cases in the general population has been reported to be 6× higher than the registered prevalence (2). 
 
Most leprosy patients are in India and Brazil. In Brazil, new cases are concentrated in the Northeast, Midwest, and Amazon regions (from state capitals to the inner counties). Access to the health system is poor in these regions because of severe inequalities in the public health system of Brazil (3), 
 
A total of 34,894 new cases were registered in Brazil during 2010 (4), corresponding to an incidence rate of 18.22 cases per 100,000 population. Para State accounted for 10.2% of cases (3,562 cases), an incidence rate of 46.93 per 100,000 population. When only children <15 years of age were considered, Para registered 389 new cases of leprosy in 2010, representing 10.9% of all cases, an incidence rate of 16.52 per 100,000 population. In Oriximina, a county with 62,794 inhabitants in northwestern Para, ≈800 km from Belem, Para’s capital, a mean of 13.8 cases per year were registered for the past 5 years. 
 
In 2010, in Oriximina, we collected plasma samples from 138 students 8–18 years of age, from 35 leprosy patients who received a diagnosis during 2004–2009, and from 126 contacts of these patients (Federal University of Para Research Ethics Committee protocol no. 197/07). We tested all of these samples for anti–phenolic glycolipid-I (PGL-I) IgM; 42% of students, 54.3% of case-patients, and 45% of case-patient contacts were seropositive. In addition to collecting samples, we clinically examined the leprosy patients and their contacts, among whom we identified 3 new leprosy cases. We did not examine students at that time. Contacts were persons from the same household or neighborhood whom the index case-patient described as a person with whom he or she had a close relationship. Leprosy cases were diagnosed in the field on the basis of clinical signs, loss of sensation on the skin lesions, and presence of enlarged nerves. For operational reasons, skin smears were not performed. All cases were diagnosed by 2 leprologists. We used the Ridley-Jopling classification, associated with the indeterminate clinical type, as defined by the Madrid classification. The ELISA cutoff for positive results was arbitrarily established as an optical density of 0.295 based on the average plus 3× the SD of the test results from 14 healthy persons from the Amazon region (5). 
 
Because studies of the seroprevalence among contacts have reported a proportion of seropositive persons ranging from ≈1.9% to 18.4% (6), we returned to Oriximina 16 months after the first visit. We examined 2 groups of students and their contacts; 1 group was positive for anti–PGL-I, and the other group was negative for anti–PGL-I. We visited 44 households in 1 week. From the 35 leprosy patients encountered during the first visit, we selected 25 households to survey (14 with an anti–PGL-I–positive contact in the household and 11 without), and among students with results of anti–PGL-I serology, we selected 19 households (11 positive with an anti–PGL-I–positive contact in the household and 8 without). During our visits to all of these households, we examined 222 persons (Table). 
 
 
 
Table 
 
New leprosy cases detected among selected households, Oriximina, Para State, Brazilian Amazon, 2010 
 
 
 
When we arrived in Oriximina, only 2 cases had been registered in the national notifiable diseases information system. By using our approach, 23 new cases were found after we investigated households that had a person positive for anti–PGL-I (15 multibacillary, 8 paucibacillary); we found only 7 new cases in households where residents were negative for anti–PGL-I (4 multibacillary, 3 paucibacillary) (Table). For comparison, during the last traditional leprosy campaign in Oriximina in 2008, eight new cases were detected. Furthermore, by using our strategy, the local public health service detected 9 additional new cases during the 4 months after our departure from Oriximina. 
 
These data emphasize that contact examination is crucial for identifying new cases (7) and that such investigation must be conducted periodically. Our data also indicate that subclinical infections are highly prevalent among public school students in the Amazon region and that identifying students with positive anti–PGL-I test results can lead to discovery of new leprosy cases among students’ household contacts.


High Anti-Phenolic
Glycolipid-I IgM Titers and Hidden Leprosy Cases, Amazon Region To the Editor: Leprosy remains a serious public health issue. Although the World Health Organization elimination target was achieved in 2000, with a prevalence of <1 case/10,000 persons, despite progress since introduction of multidrug therapy (1), large pockets of poverty remain in which the disease is hyperendemic and underdiagnosed. In fact, in highly disease-endemic areas, the prevalence of previously undiagnosed leprosy cases in the general population has been reported to be 6× higher than the registered prevalence (2).
Most leprosy patients are in India and Brazil. In Brazil, new cases are concentrated in the Northeast, Midwest, and Amazon regions (from state capitals to the inner counties).
Access to the health system is poor in these regions because of severe inequalities in the public health system of Brazil (3) We tested all of these samples for anti-phenolic glycolipid-I (PGL-I) IgM; 42% of students, 54.3% of case-patients, and 45% of case-patient contacts were seropositive. In addition to collecting samples, we clinically examined the leprosy patients and their contacts, among whom we identifi ed 3 new leprosy cases. We did not examine students at that time. Contacts were persons from the same household or neighborhood whom the index case-patient described as a person with whom he or she had a close relationship. Leprosy cases were diagnosed in the fi eld on the basis of clinical signs, loss of sensation on the skin lesions, and presence of enlarged nerves. For operational reasons, skin smears were not performed. All cases were diagnosed by 2 leprologists. We used the Ridley-Jopling classifi cation, associated with the indeterminate clinical type, as defi ned by the Madrid classifi cation. The ELISA cutoff for positive results was arbitrarily established as an optical density of 0.295 based on the average plus 3× the SD of the test results from 14 healthy persons from the Amazon region (5).
Because studies of the seroprevalence among contacts have reported a proportion of seropositive persons ranging from ≈1.9% to 18.4% (6), we returned to Oriximiná 16 months after the fi rst visit. We examined 2 groups of students and their contacts; 1 group was positive for anti-PGL-I, and the other group was negative for anti-PGL-I. We visited 44 households in 1 week. From the 35 leprosy patients encountered during the fi rst visit, we selected 25 households to survey (14 with an anti-PGL-I-positive contact in the household and 11 without), and among students with results of anti-PGL-I serology, we selected 19 households (11 positive with an anti-PGL-Ipositive contact in the household and 8 without). During our visits to all of these households, we examined 222 persons (Table).
When we arrived in Oriximiná, only 2 cases had been registered in the national notifi able diseases information system. By using our approach, 23 new cases were found after we investigated households that had a person positive for anti-PGL-I (15 multibacillary, 8 paucibacillary); we found only 7 new cases in households where residents were negative for anti-PGL-I (4 multibacillary, 3 paucibacillary) (Table). For comparison, during the last traditional leprosy campaign in Oriximiná in 2008, eight new cases were detected. Furthermore, by using our strategy, the local public health service detected 9 additional new cases during the 4 months after our departure from Oriximiná.
These data emphasize that contact examination is crucial for LETTERS identifying new cases (7) and that such investigation must be conducted periodically. Our data also indicate that subclinical infections are highly prevalent among public school students in the Amazon region and that identifying students with positive anti-PGL-I test results can lead to discovery of new leprosy cases among students' household contacts.

Acknowledgments
We thank André Luiz Correa de Sousa, Márcia Leão, and Anna Elizabeth Martins Alves for collecting the samples and data from the patients; Sabrina Sampaio Bandeira for the patient impairment evaluation; Domingos Diniz, Miguel Canto, and the Programa de Ação Interdisciplinar at Oriximiná for logistical support and fruitful discussions; John Spencer for supplying the native PGL-I and technical support with the ELISA; the Oriximiná health secretary and community health agents; and the study participants.   *Households were selected from among 35 leprosy patients encountered during the first visit (25 households, 14 with an anti-PGL-I-positive contact in the household and 11 without) and among students with results of anti-PGL-I serology (19 households, 11 with an anti-PGL-I-positive contact in the household and 8 without). PGL-I, phenolic glycolipid-I. †Fisher exact test comparing case-patients and non-case-patients among those positive or negative for anti-PGL-I IgM revealed a statistically significant difference (p = 0.0280).