Viral co-infections in leprosy: a scoping review.

CONTEXT: The most reported viral co-infections in leprosy are human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), and SARS-CoV-2. In co-infections, the burden of an agent can be increased or decreased by the presence of others. To address this issue, we need to fully understand their prevalence, risk factors, immunology, clinical manifestations, and treatment. The purpose of this scoping review is to describe the clinical and epidemiological characteristics of the most reported viral co-infections in leprosy to inform clinicians and guide future research. METHODS: The authors conducted a literature search of five databases for articles on each of the aforementioned co-infections published prior to October 2022. Two independent reviewers conducted the selection process and identified 53 papers meeting the study inclusion criteria. The data extraction process and evidence synthesis were conducted by one reviewer and double-checked by a second one, consistent with best practice recommendations for scoping reviews. RESULTS: For all assessed viruses, most studies reported prevalence rates in leprosy patients higher than the general population. Studies found that HTLV, HBV, and HCV chronic infections were highest in multibacillary leprosy, whereas HIV was mostly found in paucibacillary leprosy, and SARS-Cov-2 affected leprosy subtypes equally. Overall, co-infections were also associated with higher rates of leprosy reactions, except for COVID-19. Forty-six percent of the studies discussed issues related to treatment, which led to favorable outcomes for the most part. CONCLUSIONS: This review summarizes the existing literature on viral co-infections in leprosy patients, generating valuable insights and recommending areas for future research.

Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load.

Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). METHODS: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases "Emilio Ribas", São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). RESULTS: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. CONCLUSIONS: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome.

Co-presentation of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis and adult-onset infective dermatitis associated with HTLV-1 infection.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), infective dermatitis associated with HTLV-1 (IDH), and various other clinical conditions. Several of these diseases can occur in association. OBJECTIVE: Report an association of diseases related to HTLV-1 infection, occurring in an unusual age group. METHODS: Dermatological and laboratory exams were consecutively performed in HTLV-1-infected individuals from January 2008 to July 2010 in the HTLV Outpatient Clinic at the Institute of Infectious Diseases "Emilio Ribas" in São Paulo, Brazil. RESULTS: A total of 193 individuals (73 HAM/TSP and 120 asymptomatic carriers) were evaluated, three of which were associated with adult-onset IDH and HAM/TSP. In all three cases, the patients were affected by IDH after the development and progression of HAM/TSP-associated symptoms. LIMITATIONS: Small number of cases because of the rarity of these diseases. CONCLUSION: We draw attention to the possibility of co-presentation of adult-onset IDH in patients with a previous diagnosis of HAM/TSP, although IDH is a disease classically described in children. Thus, dermatologists should be aware of these diagnoses in areas endemic for HTLV-1 infection.

Human T-lymphotropic virus 1 (HTLV-1) infection--dermatological implications.

Human T-lymphotropic virus type 1 (HTLV-1) is a type C retrovirus primarily endemic to Japan, Central and South America, the Middle East, regions of Africa, and the Caribbean. Currently, an estimated 10-20 million people worldwide are infected with this virus. Although the majority of infected individuals remain asymptomatic, HTLV-1 is the causative agent of a number of disorders, notably adult T-cell leukemia/lymphoma (ATLL) and a progressive demyelinating neurological disorder, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition to ATLL and HAM/TSP, HTLV-1 has been associated with a spectrum of skin disorders, such as infective dermatitis associated with HTLV-1, crusted scabies, and leprosy. The understanding of the interaction between virus and host response has improved markedly, but there are still few treatment options.

Increased prevalence of human T cell lymphotropic virus type 1 in patients attending a Brazilian dermatology clinic.

Brazil may have the highest absolute number of individuals infected by human T cell lymphotropic virus type 1 (HTLV-1). It has been suggested that the prevalence of HTLV-1 is increased in patients with skin diseases. This study shows a higher prevalence of this infection in 1,229 patients attending a Brazilian dermatology clinic (0.7%) when compared to blood donors (0.22%). Of note, one additional patient tested positive for HTLV-2. The main skin diseases described in HTLV-1 seropositives were vitiligo (2 cases), dermatophytosis (2 cases), and leprosy (2 cases). A 23-year-old woman received a diagnosis of infectious dermatitis.

Leprosy and confinement due to leprosy show high association with hepatitis C in Southern Brazil.

Leprosy is a disease, which is accompanied by cellular immunity defects, which may increase the susceptibility of patients in developing co-infections. The association of leprosy with hepatitis C virus (HCV) infection, human immunodeficiency virus types 1 and 2 (HIV 1+2) infection and human T-lymphotropic virus types I and II (HTLV I+II) infection have previously been described in different populations. In this study, the prevalence of these infections was determined in 199 Southern Brazilian leprosy patients and in 681 matched controls. Antibodies to HCV were positive in 3.52% of the patients (7/199) and in 0.15% of the controls (1/681; odds ratio (OR)=24.79; 95% CI=3.03-202.74; p=0.0002). An increased risk of HCV infection was observed in institutionalized patients (OR=14.95; 95% CI=1.76-127.03; p=0.004) and in the lepromatous form of the disease (OR=7.67; 95% CI=0.43-136.62; p=ns). Anti-HIV 1+2 antibodies were positive in only one out-patient (1/199; 0.50%) and in none of the controls (0/681; OR=3.43; 95% CI=0.21-55.16; p>0.05). No leprosy patient was positive for anti-HTLV I+II antibodies. These results demonstrate an increased prevalence of HCV infection in leprosy patients from South Brazil and that both institutionalization and lepromatous form of the disease confer higher risk to HCV infection. These data emphasizes the importance of monitoring hepatitis C and leprosy interactions and the need of special care to institutionalized and lepromatous patients in preventing HCV co-infection.

Decreased survival of HTLV-I carriers in leprosy patients from the Democratic Republic of the Congo: a historical prospective study.

In this historical prospective study using sera stored for 22 years, we investigated the effect of HTLV-I infection on survival in a population of leprosy patients in the Democratic Republic of the Congo (formerly Zaire). We also determined the distribution of HTLV-I by subpopulation, age, and gender. Stored sera taken from a population of leprosy patients and controls in 1969 were tested for HTLV-I. Follow-up survival data on these patients were obtained in 1991. The sera collected in 1969 from 520 individuals was used to determine the prevalence of HTLV-I. Included in this number were 328 patients resident in the sanatorium. Survival and other data were available for 327 of these. A multivariate survival analysis using a logistic regression model was performed to evaluate the influence of HTLV-I status, age, type of leprosy, gender, duration of hospitalization, and ethnic group on survival. The overall prevalence of HTLV-I among the 520 individuals in the prevalence study was 34%, with 37.4% in the leprosy group and 25.2% in the control group (p < 0.01). Multivariate analysis using logistic regression showed that females of the Mongo and Ngombe ethnic group taken together were significantly more likely to be infected than the other groups (OR = 3.67, 95% CI: 2.14 to 6.30). A comparison of the death rates directly standardized for age and sex showed that the rate was significantly higher for HTLV-I positive (5.5/100 person-years of observation) compared with HTLV-I negative (3.6/100 person-years of observation). A survival analysis using the Cox model showed a risk ratio of 1.4 (CI: 1.04 to 1.89) for those infected with HTLV-I. An increase in the death rate was associated with HTLV-I infection in leprosy inpatients. The decreased survival associated with HTLV-I infection may result from an increased susceptibility to a variety of diseases.

PIP: Preservation of stored sera collected in 1969 from leprosy patients at a sanatorium in the Democratic Republic of the Congo's Equator Province enabled an analysis of the survival of carriers of human T-cell lymphotropic virus type 1 (HTLV-1). The HTLV-1 prevalence in the sera collected from 377 leprosy patients and 143 controls in 1969 was 34% (37.4% and 25.2%, respectively). Multivariate survival analysis was performed to evaluate the impact of HTLV-1 status, age, type of leprosy, gender, duration of hospitalization, and ethnic group on the survival of leprosy patients. Members of the Mongo ethnic group were more likely than those of the Ngombe ethnic group to be infected. After adjustment for age and sex, mortality was significantly higher among HTLV-1-positive cases (5.5 per 100 person-years of observation) than HTLV-1-negative persons (3.6 per 100 person-years of observation). A survival analysis using the Cox model revealed a mortality risk ratio of 1.4 (95% confidence interval, 1.04-1.89) for HTLV-1-positive individuals. The reduced survival observed in HTLV-1-infected leprosy patients presumably resulted from concomitant increased susceptibility to other diseases.

Infectious complications of human T cell leukemia/lymphoma virus type I infection.

Infection with human T cell leukemia/lymphoma virus type I (HTLV-I) has been etiologically associated with two diseases: adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Increasing evidence suggests that HTLV-I infection may be associated with immunosuppression and, as a consequence, affect the risk and expression of several other infectious diseases, of which the best studied are strongyloidiasis, tuberculosis, and leprosy. In strongyloidiasis, coinfection with HTLV-I appears to result in a higher rate of chronic carriage, an increased parasite load, and a risk of more severe infection. In tuberculosis, a decrease in delayed-type hypersensitivity to Mycobacterium tuberculosis has been established, but whether this decrease is clinically significant has yet to be determined. In leprosy, an increased risk of disease is suggested, but the published studies are all too poorly controlled to draw definite conclusions.

Prevalence of human T cell lymphotropic virus (HTLV) types I and II and human immunodeficiency virus type 1 infections among persons with Hansen's disease in New York City.

One-hundred seven consecutive patients attending a New York Hansen's disease clinic from November 1990 through June 1991 were tested for retroviruses. This cohort included 58 patients diagnosed with Hansen's disease after the onset of the AIDS epidemic, 54 of whom immigrated to the United States before diagnosis of Hansen's disease (median, 7 years). The overall rate (1.9%) of human T cell lymphotropic virus (HTLV) type I infection was low. Two (3.6%) of 55 Caribbean-born patients had polymerase chain reaction (PCR)-documented HTLV-I infection, but this incidence was not higher than expected in persons without Hansen's disease. No patient had PCR-documented evidence of either HTLV-II or human immunodeficiency virus (HIV) type 1 infection. The low rate of HIV-1 among those studied was likely related to an absence of classic HIV risk behavior because about half of the cohort could have incubated Mycobacterium leprae for a prolonged period while infected with HIV-1.

The prevalence of human T-cell leukemia virus type I infection in patients with hematologic and nonhematologic diseases in an adult T-cell leukemia-endemic area of Japan.

In order to clarify the prevalence of human T-cell leukemia virus type I (HTLV-I) infection in the Kagoshima district, Japan, a highly endemic area for HTLV-I, antibodies for HTLV-I (anti-HTLV-I) were examined in the sera of 6167 from healthy residents and patients with various hematologic and nonhematologic diseases. In healthy residents, including blood donors, the prevalence of anti-HTLV-I was 11.9% (562/4741 persons). The prevalence increased with age, and was significantly higher in in females than in males (P less than 0.01). The prevalence of anti-HTLV-I in blood donors was 8.5%. In In hematologic diseases, the prevalence of anti-HTLV-I was 98.3% in ATL, 28.9% in lymphoproliferative disorders except ATL, and 10.6% in myeloproliferative disorders. In nonhematologic diseases, the prevalence of anti-HTLV-I was shown to be 29.5% in pulmonary tuberculosis, 25.8% in leprosy, 33.8% in chronic renal failure (CRF), 21.9% in autoimmune diseases, and 47.8% in strongyloidiasis. The various diseases except myeloproliferative disorders had significantly higher prevalence of anti-HTLV-I than healthy residents (P less than 0.01 or 0.05). For autoimmune diseases, the prevalence of anti-HTLV-I in patients with blood transfusion (55.6%) was higher than in those without blood transfusion (8.7%), and healthy residents. In hemodialysis patients with CRF who had received blood transfusions the prevalence of anti-HTLV-I increased with the number of blood transfusions. Therefore, HTLV-I transmission via blood transfusion would partially explain these high prevalence of anti-HTLV-I. However, the prevalence of anti-HTLV-I in hemodialysis patients with CRF was statistically higher than that in healthy residents, regardless of blood transfusion (P less than 0.01). Furthermore, hemodialysis patients showed significantly higher prevalence of anti-HTLV-I than healthy residents, even at a younger age. Patients with pulmonary tuberculosis and leprosy showed the same results as hemodialysis patients. These results suggest that possibility that HTLV-I infection has some relation not only to ATL but also to other diseases. Therefore, it seems very important to halt the spread of HTLV-I transmission as soon as possible.