Treatment of recurrent erythema nodosum leprosum with infliximab.
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Antibodies, Monoclonal↗
Biomedical subjects
William R Faber
Publications and source records attributed to William R Faber.
Etiology and incidence of chronic ulcers in Blantyre, Malawi.
BACKGROUND: Little information is available on the incidence and etiology of chronic ulcers in the tropics. Therefore, the incidence and etiology of chronic skin ulcers were assessed in out-patients at the Department of Dermatology and in in-patients at the Departments of Dermatology, Surgery, Medicine, and Pediatrics, Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. METHOD: In a 10-week study period, 44 patients (31 males, 70%) with chronic skin ulcers were diagnosed from 6292 patients seen by the departments involved. RESULTS: The mean age of patients with ulcers was 38 years (range, 9 months to 82 years). The most frequent cause of ulcers was bacterial infection (n=22), followed by malignancy (n=11) and trauma (n=7). CONCLUSION: In contrast with developed countries, venous and diabetic ulcers were uncommon. In addition to bacterial infections, a surprisingly large number of malignancies were found in this study. We speculate that human immunodeficiency virus (HIV) infection, which is seen with a high prevalence at QECH, is a contributing factor. Because of the large number of malignancies, we recommend early histopathologic investigation of chronic ulcers in this part of Africa.
Adolescent↗
Risk factors for developing leprosy--a population-based cohort study in Indonesia.
We identified risk factors associated with increased yearly incidence rates of leprosy in five island populations. Age, sex, household size and Mycobacterium leprae-specific antibodies as well as contact factors were studied. Of 94 index patients (patients diagnosed in 2000), 43 (46%) were classified as multibacillary (MB), 17 (19%) were seropositive for PGL-1 [corrected] antibodies and 6 (7%) had M. leprae DNA in nasal swabs as determined by polymerase chain reaction (PCR) testing. All PCR positive patients were also seropositive. Forty-four of 4903 initially symptom free persons developed leprosy within 4 years, giving an incidence rate of 298 per 1000 person-years. Men had a 22 times higher risk [95% confidence interval (CI): 1.2-4.1] of developing leprosy than women. People living in households with more than 7 members had a 3.1 times higher risk (95% CI: 1.3-7.3) than households of 1-4 members. Persons who were seropositive in 2000 had a 3.8 times higher risk (95% CI: 1.1-12.6) than seronegative persons. Household contacts of MB patients had an adjusted hazard ratio (aHR) of 4.6 (95% CI: 1.6-12.9) and household contacts of PCR positive patients an aHR of 9.36 (95% CI: 2.5-34.9) compared with non-contacts. Patients with PCR positive nasal swabs, suggesting nasal excretion of M. leprae, are probably the patients with the highest transmission potential. Since all index patients who were PCR positive were also seropositive, serology seems an adequate tool to identify these patients. Preventing seropositive persons from becoming seropositive and infectious patients might break the chain of transmission.
Adolescent↗
Quantitative nucleic acid sequence-based assay as a new molecular tool for detection and quantification of Leishmania parasites in skin biopsy samples.
Currently available methods for the diagnosis of cutaneous leishmaniasis (CL) have low sensitivities or are unable to quantify the number of viable parasites. This constitutes a major obstacle for the diagnosis of the disease and for the study of the effectiveness of treatment schedules and urges the development of improved detection methods. In this study, quantitative nucleic acid sequence-based amplification (QT-NASBA) technology was used to detect and quantify Leishmania parasites in skin biopsy samples from CL patients. The assay is based on the detection of a small subunit rRNA (18S rRNA), which may allow for the detection of viable parasites. The QT-NASBA assay was evaluated using in vitro-cultured promastigotes and amastigotes and 2-mm skin biopsy samples from Old and New World CL patients. The study demonstrated that the lower detection limit of the QT-NASBA was two parasites per biopsy sample. Parasites could be quantified in a range of 2 to 11,300,000 parasites per biopsy sample. The QT-NASBA could detect levels of parasites 100-fold lower than those detected by conventional PCR. Test evaluation revealed that the QT-NASBA had a sensitivity of 97.5% and a specificity of 100% in the present study. The QT-NASBA is a highly sensitive and specific method that allows quantification of both Old and New World Leishmania parasites in skin biopsy samples and may provide an important tool for diagnosis as well as for monitoring the therapy of CL patients.
Adolescent↗
Role of PGL-I antibody detection in the diagnosis of pure neural leprosy.
Pure neural leprosy (PNL) is difficult to diagnose because skin lesions and acid-fast bacilli (AFB) in slit smears are absent. At present, the gold standard for PNL diagnosis is the histopathological examination of a peripheral nerve biopsy. Even so, detection of bacteria is difficult and histological findings may be non-specific. Furthermore, nerve biopsy is an invasive procedure that is only possible in specialized centres. Therefore, there is a need for additional diagnostic methods that may help to confirm the clinical diagnosis of PNL. In the present study, an additional laboratory test, the ELISA for anti-phenolic glycolipid I (PGL-I) IgM antibodies, was performed on 103 individuals with clinical and neurophysiological signs of peripheral neuropathy, of which 67 were diagnosed as PNL patients and 36 remained as 'not diagnosed as PNL', as well as on a control group of 34 patients with other neurological diseases. An antibody response was present in 14/67 (21%) of the patients diagnosed as PNL as compared with 3/34 (9%) of controls. Anti-PGL-I positivity was observed in 5/8 (63%) of the AFB positive cases. Patients whose diagnosis was confirmed solely by Mycobacterium leprae PCR on the nerve sample had 4/25 (16%) seropositivity. In addition, anti-PGL-I antibodies were detected in 9/40 (23%) of the PNL patients who were PCR negative for M. leprae DNA. Moreover, two patients who showed clinical and eletrophysiological manifestations suggestive of PNL were diagnosed with the help of their positive test results in the anti-PGL-I ELISA. In conclusion, detection of antibodies against PGL-I in patients with peripheral neuropathy is useful as an additional laboratory test to help PNL diagnosis.
Antibodies, Bacterial↗
Population survey to determine risk factors for Mycobacterium leprae transmission and infection.
BACKGROUND: Not every leprosy patient is equally effective in transmitting Mycobacterium leprae. We studied the spatial distribution of infection (using seropositivity as a marker) in the population to identify which disease characteristics of leprosy patients are important in transmission. METHODS: Clinical data and blood samples for anti-M. leprae ELISA were collected during a cross-sectional survey on five Indonesian islands highly endemic for leprosy. A geographic information system (GIS) was used to define contacts of patients. We investigated spatial clustering of patients and seropositive people and used logistic regression to determine risk factors for seropositivity. RESULTS: Of the 3986 people examined for leprosy, 3271 gave blood. Seroprevalence varied between islands (1.7-8.7%) and correlated significantly with leprosy prevalence. Five clusters of patients and two clusters of seropositives were detected. In multivariate analysis, seropositivity significantly differed by leprosy status, age, sex, and island. Serological status of patients appeared to be the best discriminator of contact groups with higher seroprevalence: contacts of seropositive patients had an adjusted odds ratio (aOR) of 1.75 (95% CI 0.922-3.31). This increased seroprevalence was strongest for contact groups living < or =75 m of two seropositive patients (aOR = 3.07; 95% CI 1.74-5.42). CONCLUSIONS: In this highly endemic area for leprosy, not only household contacts of seropositive patients, but also people living in the vicinity of a seropositive patient were more likely to harbour antibodies against M. leprae. Through measuring the serological status of patients and using a broader definition of contacts, higher risk groups can be more specifically identified.
Adolescent↗
Elimination of leprosy and its consequences for research.
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Biomedical Research↗
Value of diagnostic techniques for cutaneous leishmaniasis.
BACKGROUND: Traditional diagnostic tests, ie, smear, culture, and histopathology of a skin biopsy specimen, are not always conclusive in patients with a clinical diagnosis of cutaneous leishmaniasis (CL). OBJECTIVE: Our purpose was to find out if a polymerase chain reaction (PCR) specific for Leishmania organisms might be more sensitive than the traditional diagnostic techniques, thereby decreasing the number of false-negative diagnoses. METHODS: In a prospective study, smear, culture, and histopathology of skin biopsy specimens from 46 patients with a possible diagnosis of CL were compared with PCR specific for Leishmania. In addition, the Montenegro test as a measure of cellular immunity against the Leishmania parasite was performed. Proven CL was defined as a case in which at least 1 of the 3 traditional tests showed the presence of Leishmania parasites. RESULTS: Of our 46 patients, 22 had leishmaniasis. Of the traditional tests, culture was the most sensitive but there were no statistically significant differences between the sensitivities of the various tests. PCR results were positive in all cases of proven leishmaniasis. Moreover, 3 patients with the clinical diagnosis of CL and negative findings on traditional tests had positive PCR results. Only 1 patient with a strong clinical suggestion of CL and positive Montenegro test results had negative PCR findings; this patient also had negative smear, culture, and histopathology results. CONCLUSION: PCR appears to be the most sensitive single diagnostic test for CL.
Humans↗
Microcirculatory changes in travelers to a tropical country.
BACKGROUND: Travelers to tropical areas seem to be affected by nonhealing leg ulcers more frequently. One of the factors that can affect wound healing in a negative manner is leg edema. This study was performed to determine whether there is increased leg edema in travelers to tropical areas. METHOD: In this study, we measured the capillary filtration rate (CFR) of the lower leg by strain gauge plethysmography, as a measure of leg edema, on location in Surinam. Three groups were included: A, travelers in the first few weeks after arrival; B, travelers who had stayed in the tropics for a minimum of 2 months; C, native inhabitants. RESULTS: The mean CFR (mL/100 mL tissue/min) was significantly higher in group A than in groups B and C; the difference between groups B and C was not significant (group A 0.05 mL/100 mL tissue/min (standard deviation (SD), 0.03) vs. group B 0.02 mL/100 mL tissue/min (SD, 0.02), P = 0.01, and vs. group C 0.02 mL/100 mL tissue/min (SD, 0.02), P = 0.01). CONCLUSIONS: Travelers to tropical areas are affected by increased CFR in the first few weeks after arrival. A prolonged stay leads to the normalization of the CFR. Compression therapy is recommended for travelers to the tropics.
Adult↗
Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T-cell cross-reactivity with Mycobacterium tuberculosis.
In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.
Amino Acid Sequence↗
MR imaging of neuropathic feet in leprosy patients with suspected osteomyelitis.
This study was undertaken to analyze MRI findings in leprosy patients with neuropathic feet, which are suspected of having osteomyelitis. As far as we know, there is no literature concerning osteomyelitis and MRI in neuropathic leprosy feet at present. Therefore, we have included MRI examination of 18 events of suspected osteomyelitis in 12 leprosy patients. All patients with long-standing neuropathic foot problems were clinically suspected of having osteomyelitis. All patients underwent the MRI protocol with the inclusion of Two Point Dixon Chemical Shift Imaging as a fat-suppression sequence. For the MRI evaluation, we used signs that are described in literature for detecting osteomyelitis in diabetic feet. The primary MRI signs were positive in 17 of 18 patients. The secondary MRI signs were positive in 100% of the patients. Our results show that MRI with the use of Two Point Dixon Chemical Shift Imaging is a promising diagnostic modality to detect osteomyelitis in the presence of neurosteoarthropathic changes in patients with leprosy. Whenever available, MRI could play an important role in detecting osteomyelitis in leprosy patients with long-standing neuropathic feet.
Aged↗
Life-threatening mycobacteria infection.
Most mycobacteria cause localized and often harmless infections of the skin. Leprosy, which dates back to approximately 60 bc in India, was supposed to be eliminated as a public health problem by the year 2000. With a new case detection rate between 600,000 and 700,000 yearly however, leprosy, with its sometimes devastating consequences, will be with us for many years to come. Buruli ulcer, named after the area in Uganda where prevalence was high, has spread to new areas, especially in Africa.
Critical Illness↗
Acute hemorrhagic edema of infancy (AHEI).
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Edema↗
Chronic leg ulcer caused by Mycobacterium immunogenum.
Rare tropical skin diseases are seen more frequently in Western countries because of the increased popularity of visiting tropical regions. A 55-year-old white man developed a painless leg ulcer after traveling in Guatemala and Belize. A mycobacterium was cultured from a biopsy specimen and was identified as Mycobacterium immunogenum by 16S recombinant deoxyribonucleic acid sequence analysis. The leg ulcer healed after 6 months of compression therapy and hydrocolloids; a hypopigmented depressed scar remained.
Adult↗