Influence of Intestinal Helminth Burden on Clinical Manifestations, Therapeutic Response, and Leishmania braziliensis Load in Patients with New World Cutaneous Leishmaniasis

Leishmania braziliensis is the most important cause of cutaneous leishmaniasis (CL) in the Americas. A Th1-type immune response is required to control Leishmania infection, but an exaggerated inflammatory response leads to the development of ulcers seen in CL. Infection with intestinal helminths has the potential to inhibit the Th1 response in a manner that depends both on the species of helminth present as well as the burden of helminthiasis. We conducted a prospective cohort study of CL patients from an endemic area between January and December 2017 with either negative or high intestinal helminth burden to characterize relationships between helminth burden, L. braziliensis quantification within CL lesions, clinical aspects of CL, and therapeutic response. Of 234 participants with leishmaniasis who underwent stool examination at the time of diagnosis, 45% had detectable helminth infection. The overall cure rate after 90 days was 66%, with a median time to resolution of disease of 40 days (interquartile range: 30–65 days). There was no significant association between the type of helminth infection or the magnitude of intestinal helminth burden at the time of diagnosis and L. braziliensis genomic DNA (gDNA) detected in biopsies from CL lesions. Likewise, there was no association between helminth burden and response to treatment after 90 days. Considering quantification of parasite DNA in CL lesions, participants who were cured at 90 days had a median of 0.017 ng/mg gDNA, and participants who failed therapy had a median of 0.091 ng/mg gDNA (P = 0.03). The results indicate that cutaneous Leishmania load may influence therapeutic response in CL.

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Influence of Obesity on Clinical Manifestations and Response to Therapy in Cutaneous Leishmaniasis caused by Leishmania braziliensis

Clinical Infectious Diseases ◽

10.1093/cid/ciab236 ◽

2021 ◽

Author(s):

Tainã Lago ◽

Lucas Carvalho ◽

Mauricio Nascimento ◽

Luiz H Guimarães ◽

Jamile Lago ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Clinical Presentation ◽

Clinical Manifestations ◽

Healing Time ◽

Response To Therapy ◽

Leishmania Braziliensis ◽

Cutaneous Lesions ◽

Cytokine Levels ◽

Cure Rates ◽

The Impact

Abstract Background Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by a single ulcer or multiple cutaneous lesions with raised borders. Cure rates below 60% are observed in response to meglumine antimoniate therapy. We investigated the impact of obesity on CL clinical presentation and therapeutic response. Methods A total of 90 age-matched CL patients were included (30 obese, 30 overweight and 30 with normal BMI). CL was diagnosed through documentation of L. braziliensis DNA by PCR or identification of amastigotes in biopsied skin lesion samples. Serum cytokine levels were determined by chemiluminescence. Antimony therapy with Glucantime (20mg/kg/day) was administered for 20 days. Results Obese CL patients may present hypertrophic ulcers rather than typical oval, ulcerated lesions. A direct correlation between BMI and healing time was noted. After one course of Antimony, cure was achieved in 73% of patients with normal BMI, 37% of overweight subjects, yet just 18% of obese CL patients (p<0.01). Obese CL cases additionally presented higher leptin levels than overweight patients or those with normal BMI (p<0.05). Conclusions Obesity modifies the clinical presentation of CL and host immune response, and is associated with greater failure to therapy.

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Integrated Analysis Reveals That miR-193b, miR-671, and TREM-1 Correlate With a Good Response to Treatment of Human Localized Cutaneous Leishmaniasis Caused by Leishmania braziliensis

Frontiers in Immunology ◽

10.3389/fimmu.2018.00640 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 7

Author(s):

Sara Nunes ◽

Icaro Bonyek Silva ◽

Mariana Rosa Ampuero ◽

Almério Libório Lopes de Noronha ◽

Lígia Correia Lima de Souza ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Response To Treatment ◽

Integrated Analysis ◽

Leishmania Braziliensis

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Efficacy and Tolerability of Miltefosine in the Treatment of Cutaneous Leishmaniasis

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1238 ◽

2020 ◽

Author(s):

JeanAnne M Ware ◽

Elise M O’Connell ◽

Thomas Brown ◽

Lauren Wetzler ◽

Kawsar R Talaat ◽

...

Keyword(s):

Adverse Events ◽

Cutaneous Leishmaniasis ◽

Leishmania Major ◽

Standard Of Care ◽

Leishmania Species ◽

Response To Treatment ◽

Prior History ◽

Leishmania Braziliensis ◽

Alternative Treatment Option ◽

Leishmania Panamensis

Abstract Background Cutaneous leishmaniasis (CL) is a neglected tropical disease causing an estimated 1 million new cases annually. While antimonial compounds are the standard of care worldwide, they are associated with significant adverse effects. Miltefosine, an oral medication, is United States (US) Food and Drug Administration approved to treat CL caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis. Evidence of efficacy in other species and side-effect profiles in CL has been limited. Methods Twenty-six patients with CL were treated with miltefosine at the US National Institutes of Health. Species included L. braziliensis (n = 7), L. panamensis (n = 5), Leishmania mexicana (n = 1), Leishmania infantum (n = 3), Leishmania aethiopica (n = 4), Leishmania tropica (n = 2), Leishmania major (n = 1), and unspeciated (n = 3). Demographic and clinic characteristics of the participants, response to treatment, and associated adverse events were analyzed. Results Treatment with miltefosine resulted in cure in 77 % (20/26) of cases, with cures among all species. Common adverse events included nausea/vomiting (97%) and lack of appetite (54%). Clinical management or dose reduction was required in a third of cases. Gout occurred in 3 individuals with a prior history of gout. Most laboratory abnormalities, including elevated creatinine and aminotransferases, were mild and normalized after treatment. Conclusions Our data suggest that miltefosine has good but imperfect efficacy to a wide variety of Leishmania species. While side effects were common and mostly mild to moderate, some resulted in discontinuation of therapy. Due to oral administration, broad efficacy, and manageable toxicities, miltefosine is a viable alternative treatment option for CL, though cost and lack of local availability may limit its widespread use.

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Diabetes Modifies the Clinic Presentation of Cutaneous Leishmaniasis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa491 ◽

2020 ◽

Vol 7 (12) ◽

Author(s):

Alexsandro S Lago ◽

Filipe R Lima ◽

Augusto M Carvalho ◽

Camilla Sampaio ◽

Neuza Lago ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Mononuclear Cells ◽

Clinical Manifestations ◽

Interferon Γ ◽

Cure Rate ◽

Cutaneous Lesions ◽

Inflammatory Cytokine Production ◽

Polymerase Chain ◽

And Gender ◽

Histopathologic Findings

Abstract Background Cutaneous leishmaniasis (CL) caused by L. braziliensis is characterized by 1 or multiple well-limited ulcerated lesions. Diabetes mellitus (DM) impairs neutrophil and monocyte function, and there is a report of vegetative lesions in a patient with both diseases in Morocco. Here we evaluate the influence of DM on clinical manifestations, immune response, and in the treatment of CL. Methods The participants were 36 DM patients with CL and 36 patients with CL without DM, matched by age and gender. The diagnosis of CL was performed by documentation of DNA of L. braziliensis by polymerase chain reaction in the lesion biopsy and histopathologic findings. All patients were treated with Glucantime (Sanofi-Aventis) 20 mg/kg of weight per day for 20 days. Results There was no difference in the majority of the clinical variables between the groups, and the cure rate in patients with CL and DM (67%) was similar to that observed in CL patients (56%; P ˃ .05). The most important finding was the documentation that 36% of the patients with DM and CL had atypical cutaneous lesions characterized by large superficial ulcers without defined borders. High levels of interferon-γ, tumor necrosis facor, and interleukin-1β were detected in the supernatants of mononuclear cells stimulated with Leishmania antigen in patients with DM and atypical CL. Moreover, while cure was observed in only 33% of the patients with DM and atypical CL lesions, it was observed in 85% of patients with typical lesions (P < .05). Conclusions DM modifies the clinical presentation of CL, enhances pro-inflammatory cytokine production, and impairs response to antimony therapy.

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Disseminated Cutaneous Leishmaniasis in Colombia: Report of 27 Cases

Case Reports in Dermatology ◽

10.1159/000441120 ◽

2015 ◽

Vol 7 (3) ◽

pp. 275-286 ◽

Cited By ~ 10

Author(s):

Iván D. Vélez ◽

Alejandra Jiménez ◽

Daniel Vásquez ◽

Sara M. Robledo

Keyword(s):

Cutaneous Leishmaniasis ◽

Causative Agent ◽

Clinical Manifestations ◽

Mixed Race ◽

Upper Extremities ◽

Response To Treatment ◽

Kala Azar ◽

Clinical Presentations

Disseminated leishmaniasis (DL) is a poorly described disease that is frequently misdiagnosed as other clinical manifestations of cutaneous leishmaniasis (CL) such as diffuse CL or post-kala-azar dermal leishmaniasis. Twenty-seven cases of DL diagnosed between 1997 and 2015 are described. A higher prevalence was observed in men (mean age 32 years). The number of lesions per patient ranged from 12 to 294, distributed mainly in the upper extremities, face and trunk. The lesions were mostly plaques or nodules. Seven patients had nasal mucous damage, 74% of the patients were of mixed race, 92% lived in northwestern Colombia, and Leishmania (Viannia) panamensis was identified as the causative agent in 58% of cases. Eighteen patients recovered with pentavalent antimonial. The importance of distinguishing DL from those other clinical presentations is based on the fact that disseminated, diffuse and post-kala-azar CL are very different in etiology, clinical manifestations and response to treatment and prognosis.

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Clinical and haematological characteristics of human trichostrongyliasis

Journal of Helminthology ◽

10.1017/s0022149x17001225 ◽

2018 ◽

Vol 93 (2) ◽

pp. 149-153 ◽

Cited By ~ 3

Author(s):

L. Ghanbarzadeh ◽

M. Saraei ◽

E.B. Kia ◽

F. Amini ◽

M. Sharifdini

Keyword(s):

Statistical Significance ◽

Demographic Data ◽

Age Groups ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Stool Examination ◽

Clinical Aspects ◽

Northern Iran ◽

Examination Methods ◽

Group Sex

AbstractTrichostrongylusspp. are primarily parasites of ruminants, but humans can become infected as accidental hosts. Information about the clinical aspects of human trichostrongyliasis is limited. This study investigated the clinical and haematological characteristics of a large number of trichostrongyliasis patients. In the Fouman district of Guilan Province in northern Iran, during 2015–2016, 60 patients were identified as positive forTrichostrongylusspp., using stool examination methods. The clinical manifestations and demographic data of all patients were recorded and further analysed. Twenty-three patients (38.3%) were male and 37 (61.7%) were female. Among the individuals infected only withTrichostrongylus, only nine patients (16.4%) were asymptomatic. Forty-six patients (83.6%) presented with gastrointestinal (76.3%), pulmonary (30.9%) and cutaneous (12.7%) symptoms. No statistically significant relationship was found between clinical manifestations and sex or age groups. Ten patients (18.1%) revealed eosinophilia and five (9.1%) presented with hypochromic microcytic anaemia. The relationship between eosinophilia and age group, sex and clinical manifestations showed no statistical significance. Our study indicated that trichostrongyliasis may be a major parasitic aetiology for gastrointestinal symptoms and eosinophilia in rural residents of endemic areas.

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Polymyalgia Rheumatica - a Disease of the Elderly

Revista de Chimie ◽

10.37358/rc.18.1.6063 ◽

2018 ◽

Vol 69 (1) ◽

pp. 152-154

Author(s):

Vasilica Cristescu ◽

Aurelia Romila ◽

Luana Andreea Macovei

Keyword(s):

Giant Cell Arteritis ◽

Giant Cell ◽

Polymyalgia Rheumatica ◽

Temporal Arteritis ◽

Viral Infections ◽

Clinical Manifestations ◽

The Elderly ◽

Clinical Aspects ◽

Immune Disorder ◽

Markers Of Inflammation

Polymyalgia rheumatica is a disease that occurs mostly in the elderly and is rarely seen in patients less than 50 years of age. Polymyalgia rheumatica is a vasculitis, which manifests itself as an inflammatory disease of the vascular wall that can affect any type of blood vessel, regardless of its size. It has been considered a form of giant cell arteritis, involving primarily large and medium arteries and to a lesser extent the arterioles. Clinical manifestations are caused by the generic pathogenic process and depend on the characteristics of the damaged organ. PMR is a senescence-related immune disorder. It has been defined as a stand-alone condition and a syndrome referred to as rheumatic polyarteritis with manifestations of giant cell arteritis (especially in cases of Horton�s disease and temporal arteritis) which are commonly associated with polymyalgia. The clinical presentation is clearly dominated by the painful girdle syndrome, with a feeling of general discomfort. Polymyalgia and temporal arteritis may coexist or be consecutive to each other in the same patient, as in most of our patients. The present study describes 3 cases of polymyalgia rheumatica, admitted to the Clinic of Rheumatology of Sf. Apostol Andrei Hospital, Galati. The cases were compared with the literature. Two clinical aspects (polymyalgia rheumatica and/or Horton�s disease) and the relationship between them were also considered. Polymyalgia rheumatica is currently thought to have a multifactorial etiology, in which the following factors play a role: genetic factors or hereditary predisposition (some individuals are more prone to this disease), immune factors and viral infections (triggers of the disease). Other risk factors of polymyalgia rheumatica include age over 50 years and the association with giant cell arteritis. The characteristic feature of the disease is girdle pain, with intense stiffness of at least one hour�s duration. Markers of inflammation, erythrocyte sedimentation rate and C-reactive protein are almost always increased at the onset of the disease. Diseases that can mimic the clinical picture of polymyalgia rheumatica are neoplasia, infections, metabolic disorders of the bone and endocrine diseases.

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766. Everything Old is New Again-A Case Series of New World Leishmaniasis in African Children in Portland, Maine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.956 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S428-S428

Author(s):

Jennifer Jubulis ◽

Amanda Goddard ◽

Elizabeth Seiverling ◽

Marc Kimball ◽

Carol A McCarthy

Keyword(s):

Latin America ◽

Cutaneous Leishmaniasis ◽

New World ◽

Pediatric Patients ◽

Data Extraction ◽

Clinical Manifestations ◽

Case Series ◽

Surgical Excision ◽

Skin Lesions ◽

Travel History

Abstract Background Leishmaniasis has many clinical manifestations and treatment regimens, dependent on species and host. Old world leishmaniasis is found primarily in Africa and Asia, and is associated with visceral disease, while new world disease, seen primarily in Latin America, is more commonly mucocutaneous. We present a case series of pediatric African patients with New World cutaneous leishmaniasis (NWCL). Methods Data extraction was performed via chart review, analyzing travel history, clinical presentation, diagnosis, and management in children with cutaneous leishmaniasis presenting to the pediatric infectious diseases clinic in Portland, ME. Biopsy specimens were sent to the federal CDC for identification by PCR and culture. Results Five cases of NWCL were diagnosed in pediatric patients in Maine from November 2018 through February 2020. Median age of patients was 10 years (range 1.5-15 years). Four cases (80%) occurred in children from Angola or Democratic Republic of Congo, arriving in Maine via Central/South America, with one case in a child from Rwanda who arrived in Maine via Texas. Three patients had multiple skin lesions and two had isolated facial lesions. Leishmaniasis was not initially suspected resulting in median time to diagnosis of 5 months (range 1-7 months). Four patients were initially treated with antibacterials for cellulitis and one was treated with griseofulvin. After no improvement, patients underwent biopsy with 2 patients diagnosed with L panamensis, 1 with L braziliensis, 1 with mixed infection (L panamensis and L mexicana), and 1 with Leishmania species only. One patient was managed with surgical excision, 3 with ketoconazole, and 1 was observed off therapy. Four patients were referred to otolaryngology. All continue to be followed in infectious disease clinic. Conclusion We present five cases of new world cutaneous leishmaniasis in African pediatric patients arriving to Maine through Latin America or Texas. Patients were diagnosed with cellulitis, tinea corporis or atopic dermatitis initially, underscoring importance of high index of suspicion in migrant patients. Detailed travel history and epidemiologic knowledge is essential to diagnosis, as patients may present with illness not congruent with country of origin. Optimal therapy remains unclear. Disclosures All Authors: No reported disclosures

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Clinical outcomes of syphilis in HIV-negative and HIV-positive MSM: occurrence of repeat syphilis episodes and non-treponemal serology responses

Sexually Transmitted Infections ◽

10.1136/sextrans-2020-054887 ◽

2021 ◽

pp. sextrans-2020-054887

Author(s):

Silvia Achia Nieuwenburg ◽

Ricardo Jamie Sprenger ◽

Maarten Franciscus Schim van der Loeff ◽

Henry John Christiaan de Vries

Keyword(s):

Hiv Infection ◽

Controlled Trial ◽

Clinical Manifestations ◽

Response To Treatment ◽

Disease Stage ◽

Hiv Positive ◽

Sexual Risk Behaviour ◽

Serological Response ◽

History Of ◽

Hiv Negative

ObjectivesHIV-positive men who have sex with men (MSM) may be at a higher risk of repeat syphilis, have different clinical manifestations and have a different serological response to treatment compared with HIV-negative MSM. The objective of this study was to assess whether HIV-negative and HIV-positive MSM with infectious syphilis (primary, secondary or early latent) differed in history of previous syphilis episodes, disease stage and non-treponemal titre of initial and repeat episodes, and the titre response 6 and 12 months after treatment. Furthermore, determinants associated with an inadequate titre response after treatment were explored.MethodsThis retrospective analysis used data of five longitudinal studies (four cohorts; one randomised controlled trial) conducted at the STI clinic in Amsterdam, the Netherlands. Participants were tested for syphilis and completed questionnaires on sexual risk behaviour every 3–6 months. We included data of participants with ≥1 syphilis diagnosis in 2014–2019. Pearson’s χ² test was used to compare HIV-negative and HIV-positive MSM in occurrence of previous syphilis episodes, disease stage of initial and repeat syphilis episode and non-treponemal titre treatment responses.ResultsWe included 355 participants with total 459 syphilis episodes. HIV-positive MSM were more likely to have a history of previous syphilis episodes compared with HIV-negative MSM (68/90 (75.6%) vs 96/265 (36.2%); p<0.001). Moreover, HIV-positive MSM with repeat syphilis were less often diagnosed with primary syphilis (7/73 (9.6%) vs 36/126 (28.6%)) and more often diagnosed with secondary syphilis (16/73 (21.9%) vs 17/126 (13.5%)) and early latent syphilis (50/73 (68.5%) vs 73/126 (57.9%)) (p=0.005). While not significantly different at 12 months, HIV-negative MSM were more likely to have an adequate titre response after 6 months compared with HIV-positive MSM (138/143 (96.5%) vs 66/74 (89.2%); p=0.032).ConclusionsIn repeat syphilis, HIV infection is associated with advanced syphilis stages and with higher non-treponemal titres. HIV infection affects the serological outcome after treatment, as an adequate titre response was observed earlier in HIV-negative MSM.

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