Internal Migration and Leprosy in Shanghai from 2000 to 2019: an Epidemiological Study of New Cases.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Massive internal migration from rural to urban areas poses new challenges for leprosy control in Shanghai, China. This retrospective epidemiological study examined new cases of leprosy diagnosed in Shanghai from 2000 to 2019, with emphasis on internal migration cases. There were 145 cases of leprosy in the study period; the majority of cases (89.0%) were internal migrants. Migrant cases had a mean of 25.4 months lag time from onset of symptoms to diagnosis, which was significantly longer than that of resident cases (mean 10.8 months, p < 0.001). Greater lag time from the first visit to diagnosis was observed in migrant cases (mean 23.2 months) compared with resident cases (mean 9.4 months, p < 0.001). A large majority of cases (91.0%) had been misdiagnosed. Internal migrant cases were responsible for most incidences of leprosy in Shanghai. They often did not receive timely diagnosis and treatment, which may have an adverse impact on the prevention of epidemic leprosy.

Case Report: Upper Thoracic Esophageal Paralysis Accompanying a Type 1 Leprosy Reaction.

Type 1 leprosy reactions (T1LRs) occur mainly in patients with borderline leprosy and an unstable immune status. The main symptoms of T1LRs include aggravated skin lesions and nerve damage. Nerve damage involving the glossopharyngeal and vagus nerves causes dysfunction of the nose, pharynx, larynx, and even the esophagus, which are innervated by these nerves. Here, we report a case of upper thoracic esophageal paralysis caused by vagus nerve involvement in a patient with T1LRs. Although infrequent, this serious emergency merits attention.

Case Report: Rifampicin-Induced Thrombocytopenia in a Patient with Borderline Lepromatous Leprosy.

Rifampicin is a highly effective antibacterial drug and an important component of multidrug therapy used to treat leprosy. Side effects of rifampicin are rare with the once-a-month dosage regimen of anti-leprosy multidrug therapy. Here, we report a case of rifampicin-induced thrombocytopenia during anti-leprosy treatment. Although rare, this potential side effect merits attention.

Twenty five years follow up of MB leprosy patients retreated with a modified MDT regimen after a full course of dapsone mono-therapy.

BACKGROUND: The relentless emergence of dapsone resistance amongst M. leprae threatened leprosy control programmes, and increased the relapse rate of patients cured with dapsone monotherapy. OBJECTIVE: The study aimed to analyse the effect on the relapse rate of dapsone-cured multibacillary (MB) leprosy patients, of re-treatment, using a multidrug therapy (MDT) regimen which differed from the WHO recommended regimen. DESIGN: 794 MB leprosy patients who had been released from treatment after dapsone monotherapy were selected, amongst them 657 were re-treated for 1 year using the modified multidrug therapy regimen (mMDT) including rifampicin, clofazimine and dapsone, and 137 patients were observed as control cases. RESULTS: The regimen was well tolerated with good compliance: 620 patients completed re-treatment with mild side effects and a low incidence of leprosy reactions. There was a statistically significant difference between the relapse rates of re-treated and control groups (chi squaredf = 57.44, P < 0.001). Furthermore, the relapses in the re-treated group were significantly more likely to be later than those in the control group (t = 25.62, P < 0.001). CONCLUSIONS: Re-treatment with this modified regimen is acceptable and can reduce the risk of early relapse in dapsone-cured patients. The problem of persisters causing late relapse is likely to remain.

A rare case of type 1 leprosy reactions following tetanus infection in a borderline tuberculoid leprosy patient and a literature review.

BACKGROUND: Type 1 leprosy reaction, also known as "reversal reaction", is related to cellular immune responses to Mycobacterium leprae antigens. The risk factors that trigger type 1 leprosy reactions are poorly understood. Leprosy with concurrent tetanus is rare, and there are no publicly available reports of a leprosy patient infected with tetanus that induced type 1 leprosy reactions. CASE PRESENTATION: A 56-year-old Chinese Han female presented to our hospital with symptoms of erythematous plaques and pain over her left upper limb for 2 days and foreign object sensation in her throat for 3 days. The patient had a 6-year history of leprosy. Type 1 leprosy reactions were initially considered, followed by treatment with methylprednisolone. Two days later, the patient's symptoms were aggravated, with neck muscle tension and difficulty in opening her mouth, and the erythematous plaques had spread over most of her left upper limb. After further careful examinations, we confirmed the diagnosis of tetanus with concurrent type 1 leprosy reactions. The patient was given anti-tetanus treatment for 12 days and anti-leprosy reaction treatment for 4 months; the diseases were eventually controlled. CONCLUSIONS: This report suggests that tetanus infection may be a trigger for type 1 leprosy reactions.

Therapeutic Dilemma of Refractory Erythema Nodosum Leprosum.

AbstractErythema nodosum leprosum (ENL), also known as type II leprosy reaction, is a severe immune-mediated complication of multibacillary leprosy. For ENL, corticosteroids and thalidomide are the mainstays of treatment. Other immunosuppressants, such as clofazimine, cyclosporine, and azathioprine have also been used. Although most patients with ENL respond well to conventional treatments, a small number are refractory to these therapies and have severe morbidity or mortality. We report the case of a 24-year-old man with refractory ENL treated with high-dose corticosteroids for 15 months. The patient developed steroid-dependence and serious adverse effects, and died of an intracranial infection.

Osteoarthritis, labour division, and occupational specialization of the Late Shang China - insights from Yinxu (ca. 1250 - 1046 B.C.).

This research investigates the prevalence of human osteoarthritis at Yinxu, the last capital of the Late Shang dynasty (ca. 1250-1046 B.C.), to gain insights about lifeways of early urban populations in ancient China. A total of 167 skeletal remains from two sites (Xiaomintun and Xin'anzhuang) were analyzed to examine osteoarthritis at eight appendicular joints and through three spinal osseous indicators. High osteoarthritis frequencies were found in the remains with males showing significantly higher osteoarthritis on the upper body (compared to that of the females). This distinctive pattern becomes more obvious for males from Xiaomintun. Furthermore, Xiaomintun people showed significantly higher osteoarthritis in both sexes than those from Xin'anzhuang. Higher upper body osteoarthritis is speculated to be caused by repetitive lifting and carrying heavy-weight objects, disproportionately adding more stress and thus more osseous changes to the upper than the lower body. Such lifting-carrying could be derived from intensified physical activities in general and specialized occupations in particular. Higher osteoarthritis in males may reveal a gendered division of labour, with higher osteoarthritis in Xiaomintun strongly indicating an occupational difference between the two sites. The latter speculation can be supported by the recovery of substantially more bronze-casting artifacts in Xiaomintun. It is also intriguing that relatively higher osteoarthritis was noticed in Xiaomintun females, which seems to suggest that those women might have also participated in bronze-casting activities as a "family business." Such a family-involved occupation, if it existed, may have contributed to establishment of occupation-oriented neighborhoods as proposed by many Shang archaeologists.

Osteoarchaeological Studies of Human Systemic Stress of Early Urbanization in Late Shang at Anyang, China.

Through the analysis of human skeletal remains and mortuary practice in Yinxu, this study investigates the impact of early urbanization on the commoners during the Late Shang dynasty (ca. 1250-1046 B.C.). A total of 347 individuals examined in this study represent non-elites who were recovered from two different burial contexts (formally buried in lineage cemeteries and randomly scattered in refuse pits). Frequencies of enamel hypoplasia (childhood stress), cribra orbitalia (childhood stress and frailty) and osteoperiostitis (adult stress) were examined to assess systemic stress exposure. Our results reveal that there was no significant difference in the frequency of enamel hypoplasia between two burial groups and between sexes, suggesting these urban commoners experienced similar stresses during childhood, but significantly elevated levels of cribra orbitalia and osteoperiostitis were observed in the refuse pit female cohort. Theoretically, urbanization would have resulted in increased population density in the urban centre, declining sanitary conditions, and increased risk of resource shortage. Biologically, children would be more vulnerable to such physiological disturbance; as a result, high percentages of enamel hypoplasia (80.9% overall) and cribra orbitalia (30.3% overall) are observed in Yin commoners. Adults continued to suffer from stress, resulting in high frequencies of osteoperiostitis (40.0% total adults); in particular, in the refuse pit females who may also reflect a compound impact of gender inequality. Our data show that the non-elite urban population in the capital city of Late Shang Dynasty had experienced extensive stress exposure due to early urbanization with further social stratification only worsening the situation, and eventually contributing to collapse of the Shang Dynasty.

Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.

BACKGROUND: The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. METHODOLOGY/PRINCIPAL FINDINGS: Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. CONCLUSIONS/SIGNIFICANCE: Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.

Autophagy gene polymorphism is associated with susceptibility to leprosy by affecting inflammatory cytokines.

Autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. Leprosy is caused by the infection of Mycobacterium leprae (M. leprae). The objective of the study was to investigate the association between polymorphisms in IRGM, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of M. leprae. Two polymorphisms in IRGM, rs4958842 and rs13361189, were tested in 412 leprosy cases and 432 healthy controls. Levels of inflammatory cytokines including interleukin 1 beta, IL-4, IL-6, and interferon gamma (INF-γ) were measured after the infection of M. leprae in the peripheral blood mononuclear cell (PBMC) of subjects with different genotypes of rs13361189. Data showed that prevalence of rs13361189TC and CC genotypes were significantly higher in leprosy patients than in healthy controls (odds ratio (OR) = 1.49, 95 % confidence interval (CI) 1.09-2.04, P = 0.012; OR = 2.58, 95 % CI 1.65-4.05, P < 0.001; respectively). Furthermore, the frequency of rs13361189CC genotype was increased in patients with complications than those without complications (P = 0.011). When analyzing the effect of rs13361189 polymorphism on M. leprae infection, we identified that M. leprae-infected PBMC with rs13361189CC genotype expressed significantly elevated levels of INF-γ and IL-4 than those with TT genotype. Our results suggested autophagy gene polymorphism was associated with the increased risk of leprosy by affecting inflammatory cytokines.

Mycobacterium leprae upregulates IRGM expression in monocytes and monocyte-derived macrophages.

Leprosy is caused by the infection of Mycobacterium leprae, which evokes a strong inflammatory response and leads to nerve damage. Immunity-related GTPase family M protein (IRGM) plays critical roles in controlling inflammation. The objective of the study was to investigate whether IRGM is involved in the infection of M. leprae. Levels of IRGM were assessed in M. leprae-infected CD4(+) T cells, monocytes, and monocyte-derived macrophages. Data revealed that both protein and mRNA levels of IRGM were increased in monocytes after M. leprae infection. Interestingly, monocyte-derived macrophages showed more prominent IRGM expression with M. leprae infection, whereas the bacteria did not affect IRGM in CD4(+) T cells. Furthermore, we assessed levels of IRGM in CD4(+) T cells and monocytes from 78 leprosy patients and 40 healthy controls, and observed upregulated protein level of IRGM in the monocytes from leprosy patients. Also, IRGM expression was inversely correlated with the severity of the disease. These findings suggested a close involvement of IRGM in M. leprae infection and indicated a potential mechanism of defending M. leprae infection.

Interleukin 4-590T/C polymorphism and susceptibility to leprosy.

BACKGROUND: Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Cell-mediated (Th1) immune response and humoral (Th2) immune response play different roles in leprosy infection. Interleukin 4 (IL-4) is a typical Th2 cytokine. It is a critical mediator of the Th1/Th2 balance. OBJECTIVE: The objective of this study is to investigate the association between IL-4 gene -590T/C polymorphism and the susceptibility to leprosy in a Chinese population. METHODS: The IL-4 variant -590T/C was detected by polymerase chain reaction-restriction fragment length polymorphism in 432 leprosy cases and 465 age-matched healthy controls. Data were analyzed using the chi-square test. RESULTS: Frequencies of the IL-4-590TC and CC genotypes and the -590C allele were significantly lower in patients with leprosy than in healthy controls (odds ratio [OR]=0.74, 95% confidence interval [CI] 0.55-0.99, p=0.044; OR=0.46, 95% CI 0.25-0.84, p=0.010; and OR=0.68, 95% CI 0.54-0.86, p=0.001, respectively). CONCLUSIONS: Our data suggest that the -590T/C polymorphism of the IL-4 gene is associated with decreased susceptibility of leprosy.