Recurrent acquired ocular toxoplasmosis associated with Kyrieleis plaques and documented allergy to sulfonamide-A treatment proposal for two rare conditions.

The aim of this study was to describe a case of a patient with ocular toxoplasmosis, which has resulted in Kyrieleis plaques formation (segmental periarteritis associated with severe inflammation) and later follow-up and alternative treatment due to documented allergy to sulfonamide. A 33-year-old Brazilian woman diagnosed with acute toxoplasmosis, initially treated with sulfonamide, developed a critical cutaneous rash. Cotrimoxazole was changed to clindamycin and pyrimethamine, and prednisone was started. The medication was maintained for 45 days. Four months later, she developed retinal lesions suggestive of toxoplasmosis with Kyrieleis plaques in the upper temporal vessels. Pyrimethamine, clindamycin, and prednisone were initiated until healing. She presented reactivation months later, and a suppressive treatment with pyrimethamine was instituted for one year. This is the first report to use the combination of clindamycin with pyrimethamine in the treatment and recurrence prophylaxis for OT in a documented allergy to sulfonamide.

Case Report: In Situ and Systemic Immune Response to Mucosal Leishmaniasis in an HIV-Infected Patient.

In situ and systemic evaluations of the immune responses of HIV-infected patients to mucosal leishmaniasis have been poorly described. We describe a recently diagnosed HIV-infected patient with mucosal leishmaniasis who was characterized by a CD4 count of 85 cells/mm3 and nasal septum destruction resulting from pruritic and ulcerated nasal mucosa with crust formation and progression over 2 years. In situ and systemic immune evaluations of T cell activation, memory, and exhaustion were conducted using cytofluorometric assays, and sequencing of the Leishmania species was performed. The immune profile of HIV-infected patient with mucosal leishmaniasis shows a mixed Th1/Th2 pattern and an activated and exhausted status.

Liposomal drug delivery systems for the treatment of leishmaniasis.

Human le ishmaniasis is a vector-borne, neglected infectious disease that is widely distributed in America, Africa, Europe, and Asia. Current therapy is based on old and toxic drugs, including antimonials, aminoglycosides, and amphotericin. As a neglected disease, investment in the development of new therapeutic molecules is scarce. Considering these aspects, the optimization of treatment through novel delivery systems for current therapeutic agents is an attractive alternative. The encapsulation into liposomes of drugs used in treating leishmaniasis increases the concentration of these molecules in macrophages, which may not only increase the chance of cure but also expand their therapeutic spectrum to include resistant Leishmania, as well as reducing toxicity since the drug is less exposed to healthy cells. The classical example is the liposomal formulation of amphotericin B, a well-established therapeutic option that uses liposomes to decrease the progression of renal failure in patients. However, loading other leishmanicidal drugs into liposomes, such as pentavalent antimonials, presents an opportunity for innovative and cheaper therapeutic options for the treatment of human leishmaniasis. This review aims to discuss liposomes as a drug delivery system for leishmanicidal drugs.

Case Report: Cutaneous Leishmaniasis in a Rheumatoid Arthritis Patient Receiving Methotrexate.

The immunosuppressive effect of methotrexate has rarely been associated with reactivation of cutaneous leishmaniasis. Here we present a case of a cutaneous leishmaniasis patient with atypical clinical symptoms without splenomegaly but with cutaneous manifestations after treatment of rheumatoid arthritis with methotrexate and blood recovery of the parasite. Next-generation sequencing was used to identify Leishmania infantum chagasi in the patient's blood sample.

Identification of Leishmania species by next generation sequencing of hsp70 gene.

Leishmaniasis is a major public health problem worldwide. Although next generation sequencing technology has been widely used in the diagnosis of infectious diseases, it has been scarcely applied in identification of Leishmania species. The aim of this study was to compare the efficiency of MinION™ nanopore sequencing and polymerase chain reaction restriction fragment length polymorphism in identifying Leishmania species. Our results showed that the MinION™ sequencer was able to discriminate reference strains and clinical samples with high sensitivity in a cost and time effective manner without the prior need for culture.

Estimation of Leishmania spp. infection in asymptomatic people from Muzaffarpur, Bihar, India by antigen-antibody and skin testing.

Asymptomatic VL is a concern, considering the risk of transmission in highly endemic areas due to human-to-human transmission. The aim of this study was to report the sero-epidemiological prevalence in Bihar, India, a highly endemic area of VL, using the leishmanin skin test (LST) and the direct agglutination test (DAT). This was a cross-sectional study performed in Muzaffarpur, Bihar, India. Relatives of patients with VL were tested by LST and DAT. Other epidemiological data were evaluated and correlated with tests results. Forty individuals (either previous or current patients), and 109 household contacts were studied. There were 36% of male visceral leishmaniasis family members versus 17.57% of females visceral leishmaniasis family members, thus showing more males with symptomatic disease than females (p< 0.01). All visceral leishmaniasis cases had positive DAT tests, but only 37% of past cases were positive on the skin testing. Amongst healthy household contacts, 34% were DAT-positive, whilst 21% were LST-positive. The overall positivity for both assays combined was 44.8% and 23.8% were DAT-positive alone. The finding of high infection prevalence amongst asymptomatic individuals, and the estimation of those at greater risk for overt disease (DAT-positive alone) are important in the development of future disease control policies.

Lipid nanoparticles for amphotericin delivery in the treatment of American tegumentary leishmaniasis.

Leishmaniasis occurs in the five continents and represents a serious public health challenge, but is still a neglected disease, and the current pharmacological weaponry is far from satisfactory. Triglyceride-rich nanoparticles mimicking chylomicrons (TGNP) behave metabolically like native chylomicrons when injected into the bloodstream. Previously we have shown that TGNP as vehicle to amphothericin B (AB) for treatment of fungi infection showed reduced renal toxicity and lower animal death rates compared to conventional AB. The aim of the current study was to test the tolerability and effectiveness of the TGNP-AB preparation in a murine model of Leishmania amazonensis infection. The in vitro assays determined the cytotoxicity of TGNP-AB, AB, and TGNP in macrophages and promastigote forms and the leishmanicidal activity in infected macrophages. The in vivo toxicity tests were performed in healthy mice with increasing doses of TGPN-AB and AB. Then, animals were treated with 2.5 mg/kg/day of AB, 17.5 mg/kg/day of TGNP-AB, or TGNP three times a week for 4 weeks. TGNP-AB formulation was less cytotoxic for macrophages than AB. TGNP-AB was more effective than AB against the promastigotes forms of the parasite and more effective in reducing the number of infected macrophages and the number of amastigotes forms per cell. TGNP-AB-treated animals showed lower hepatotoxicity. In addition, TGNP-AB group showed a marked reduction in lesion size on the paws and parasitic load. The TGNP-AB preparation attained excellent leishmanicidal activity with remarkable lower drug toxicity at very high doses that, due to the toxicity-buffering properties of the nanocarrier, become fully tolerable.

Comparative study on liposomal amphotericin B and other therapies in the treatment of mucosal leishmaniasis: A 15-year retrospective cohort study.

BACKGROUND: Liposomal amphotericin B (L-AMB) has been used for mucosal leishmaniasis (ML), but comparative studies on L-AMB and other drugs used for the treatment of ML have not been conducted. The present study aimed to evaluate the outcome of patients with ML who were treated with L-AMB. METHODS: This is a 15-year retrospective study of Brazilian patients with a confirmed diagnosis of ML. The therapeutic options for the treatment of ML consisted of L-AMB, amphotericin B lipid complex (ABLC), deoxycholate amphotericin B (d-AMB), itraconazole, antimonial pentavalent, or pentamidine. Healing, cure rate and adverse effects (AEs) associated with the drugs used to treat this condition were analyzed. RESULTS: In 71 patients, a total of 105 treatments were evaluated. The outcome of the treatment with each drug was compared, and results showed that L-AMB was superior to other therapeutic regimens (P = 0.001; odds ratio [OR] = 4.84; 95% confidence interval [CI] = 1.78-13.17). d-AMB had worse AEs than other treatment regimens (P = 0.001, OR = 0.09; 95% CI = 0.09-0.43). Approximately 66% of the patients presented with AEs during ML treatment. Although L-AMB was less nephrotoxic than d-AMB, it was associated with acute kidney injury compared with other drugs (P <0.05). CONCLUSION: L-AMB was more effective than other therapies for the treatment of ML. However, a high incidence of toxicity was associated with its use. Therapeutic choices should be reassessed, and the development of new drugs is necessary for the treatment of ML.

Secondary Prophylaxis with Liposomal Amphotericin B in a Patient with Mucosal Leishmaniasis Undergoing Immunobiological Therapy for Active Ankylosing Spondylitis.

Immunosuppressive treatments for rheumatic diseases present special problems in areas endemic for chronic infectious diseases because of the possibility of reactivation. Leishmaniasis is a significant neglected tropical disease caused by different species of protozoan parasites within the genus Leishmania. Amastigotes live as intracellular parasites in a variety of mammalian cells, most notably within phagocytes such as macrophages, and residual parasites can persist even after treatment and healing of the lesions. We herein report a case of relapsing mucosal leishmaniasis after aggressive immunotherapy for ankylosing spondylitis, with requirement for secondary prophylaxis with amphotericin B to prevent reactivation. This approach can be necessary for patients from endemic areas of tegumentary leishmaniasis, who will undergo aggressive immunotherapy.

Reactivation of cutaneous and mucocutaneous tegumentary leishmaniasis in rheumatoid arthritis patients: an emerging problem?

Rheumatoid arthritis (RA) is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX), monoclonal antibodies (mAbs) and prednisone. We report an unusual presentation of cutaneous (CL) or mucocutaneous leishmaniasis (ML) in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.

Reactivation of cutaneous and mucocutaneous tegumentary leishmaniasis in rheumatoid arthritis patients: an emerging problem?

ABSTRACT Rheumatoid arthritis (RA) is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX), monoclonal antibodies (mAbs) and prednisone. We report an unusual presentation of cutaneous (CL) or mucocutaneous leishmaniasis (ML) in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.

Could kDNA-PCR in Peripheral Blood Replace the Examination of Bone Marrow for the Diagnosis of Visceral Leishmaniasis?

The aim of this study was to evaluate whether the molecular (kDNA-PCR) and parasitological diagnosis in peripheral blood (PB) could replace the invasive and painful bone marrow collection (BM) in the diagnosis of visceral leishmaniasis (VL). PB from suspected VL patients was evaluated by parasitological and molecular techniques using as the gold standard (GS) a combination of clinical, epidemiological, and immunochromatographic test (PB-rK39) results and parasitological examination of BM. Based on the GS, 38 samples from 32 patients were grouped: Group 1, 20 samples of VL cases, and Group 2, 18 samples of non-VL cases. In order to evaluate the parasitological and molecular techniques in PB, the samples were examined. From Group 1, PB kDNA-PCR was positive in 20 samples and in 19 of 20 in BM kDNA-PCR examination. However, the parasitological examination of buffy coat was insensitive, being able to detect only 4 cases from Group 1. All samples from Group 2 were negative. We concluded that, for the diagnosis of visceral leishmaniasis, the parasitological examination of peripheral blood was not useful; however, molecular diagnosis by kDNA-PCR, performed in peripheral blood, could be useful to replace the parasitological examination of bone marrow.

Could kDNA-PCR in peripheral blood replace the examination of bone marrow for the diagnosis of visceral leishmaniasis?

The aim of this study was to evaluate whether the molecular (kDNA-PCR) and parasitological diagnosis in peripheral blood (PB) could replace the invasive and painful bone marrow collection (BM) in the diagnosis of visceral leishmaniasis (VL). PB from suspected VL patients was evaluated by parasitological and molecular techniques using as the gold standard (GS) a combination of clinical, epidemiological, and immunochromatographic test (PB-rK39) results and parasitological examination of BM. Based on the GS, 38 samples from 32 patients were grouped: Group 1, 20 samples of VL cases, and Group 2, 18 samples of non-VL cases. In order to evaluate the parasitological and molecular techniques in PB, the samples were examined. From Group 1, PB kDNA-PCR was positive in 20 samples and in 19 of 20 in BM kDNA-PCR examination. However, the parasitological examination of buffy coat was insensitive, being able to detect only 4 cases from Group 1. All samples from Group 2 were negative. We concluded that, for the diagnosis of visceral leishmaniasis, the parasitological examination of peripheral blood was not useful; however, molecular diagnosis by kDNA-PCR, performed in peripheral blood, could be useful to replace the parasitological examination of bone marrow

Post-kala-azar dermal leishmaniasis and leprosy: case report and literature review.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a dermal complication of visceral leishmaniasis (VL), which may occur after or during treatment. It has been frequently reported from India and the Sudan, but its occurrence in South America has been rarely reported. It may mimic leprosy and its differentiation may be difficult, since both diseases may show hypo-pigmented macular lesions as clinical presentation and neural involvement in histopathological investigations. The co-infection of leprosy and VL has been reported in countries where both diseases are endemic. The authors report a co-infection case of leprosy and VL, which evolved into PKDL and discuss the clinical and the pathological aspects in the patient and review the literature on this disease. CASE PRESENTATION: We report an unusual case of a 53-year-old female patient from Alagoas, Brazil. She presented with leprosy and a necrotizing erythema nodosum, a type II leprosy reaction, about 3 month after finishing the treatment (MDT-MB) for leprosy. She was hospitalized and VL was diagnosed at that time and she was successfully treated with liposomal amphotericin B. After 6 months, she developed a few hypo-pigmented papules on her forehead. A granulomatous inflammatory infiltrate throughout the dermis was observed at histopathological examination of the skin biopsy. It consisted of epithelioid histiocytes, lymphocytes and plasma cells with the presence of amastigotes of Leishmania in macrophages (Leishman's bodies). The diagnosis of post-kala-azar dermal leishmaniasis was established because at this time there was no hepatosplenomegaly and the bone marrow did not show Leishmania parasites thus excluding VL. About 2 years after the treatment of PKDL with liposomal amphotericin B the patient is still without PKDL lesions. CONCLUSION: Post-kala-azar dermal leishmaniasis is a rare dermal complication of VL that mimics leprosy and should be considered particularly in countries where both diseases are endemic. A co-infection must be seriously considered, especially in patients who are non-responsive to treatment or develop persistent leprosy reactions as those encountered in the patient reported here.

Facial structure alterations and abnormalities of the paranasal sinuses on multidetector computed tomography scans of patients with treated mucosal leishmaniasis.

BACKGROUND/OBJECTIVES: Mucosal leishmaniasis (ML) is a progressive disease that affects cartilage and bone structures of the nose and other upper respiratory tract structures. Complications associated with ML have been described, but there is a lack of studies that evaluate the structural changes of the nose and paranasal sinuses in ML using radiological methods. In this study, we aimed to assess the opacification of the paranasal sinuses in patients with treated ML and any anatomical changes in the face associated with ML using multidetector computed tomography scans (MDCT) of the sinuses. We compared the findings with a control group. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated 54 patients with treated ML who underwent CT scans of the sinuses and compared them with a control group of 40 patients who underwent orbital CT scans. The degree of sinus disease was assessed according to the Lund-Mackay criteria. Forty of the 54 patients with a history of ML (74.1%) had a tomographic score compatible with chronic sinusitis (Lund-Mackay ≥4). CT scans in the leishmaniasis and control groups demonstrated significant differences in terms of facial structure alterations. Patients from the ML group showed more severe levels of partial opacification and pansinus mucosal thickening (42.6%) and a greater severity of total opacification. Patients from the ML group with a Lund-Mackay score ≥4 presented longer durations of disease before treatment and more severe presentations of the disease at diagnosis. CONCLUSION/SIGNIFICANCE: CT scans of the sinuses of patients with ML presented several structural alterations, revealing a prominent destructive feature of the disease. The higher prevalence in this study of chronic rhinosinusitis observed in CT scans of patients with treated ML than in those of the control group suggests that ML can be considered a risk factor for chronic rhinosinusitis in this population (p<0.05).