Treatment of mucocutaneous leishmaniasis - A systematic review.

Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases "PubMed" and "Lilacs" from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.

Rickettsioses: Cutaneous findings frequently lead to diagnosis - a review.

While epidemic typhus caused by Rickettsia prowazekii posed a significant threat in Europe before and throughout World War II due to its high mortality, the condition fortunately no longer plays a significant role. Nevertheless, rickettsioses, such as African tick bite fever, have been increasingly diagnosed in travelers returning from sub-Saharan Africa. Caused by Rickettsia africae, African tick bite fever presents with characteristic cutaneous findings such as eschar (tache noir) and a rash. Similar findings are also observed in Mediterranean spotted fever caused by Rickettsia conorii. On the other hand, Rocky Mountain spotted fever - caused by Rickettsia rickettsii - is characterized by a rash without an eschar, in combination with distinctly more severe general symptoms. The objective of the present CME article is to familiarize dermatologists with the spectrum of the most common types of rickettsiosis in humans, including their epidemiology, clinical presentation, diagnostic workup, and treatment. Recognition of characteristic cutaneous manifestations and their correct interpretation facilitate early diagnosis. Prompt initiation of treatment usually results in recovery without sequelae.

Leprosy - an overview of clinical features, diagnosis, and treatment.

Leprosy is a chronic infectious disease caused by Mycobacterium (M.) leprae. Worldwide, 210,758 new cases were diagnosed in 2015. The highest incidence is found in India, Brazil, and Indonesia. While the exact route of transmission remains unknown, nasal droplet infection is thought to be most likely. The pathogen primarily affects the skin and peripheral nervous system. The disease course is determined by individual host immunity. Clinically, multibacillary lepromatous variants are distinguished from paucibacillary tuberculoid forms. Apart from the various characteristic skin lesions, the condition is marked by damage to the peripheral nervous system. Advanced disease is characterized by disfiguring mutilations. Current treatment options are based on WHO recommendations. Early treatment frequently results in complete remission without sequelae. While paucibacillary forms are treated with rifampicin and dapsone for at least six months, multibacillary leprosy is treated for at least twelve months, additionally requiring clofazimine. Leprosy reactions during therapy may considerably aggravate the disease course. Besides individual treatment, WHO-supported preventive measures and strategies play a key role in endemic areas.

Microbiological laboratory diagnostics of neglected zoonotic diseases (NZDs).

This review reports on laboratory diagnostic approaches for selected, highly pathogenic neglected zoonotic diseases, i.e. anthrax, bovine tuberculosis, brucellosis, echinococcosis, leishmaniasis, rabies, Taenia solium-associated diseases (neuro-/cysticercosis & taeniasis) and trypanosomiasis. Diagnostic options, including microscopy, culture, matrix-assisted laser-desorption-ionisation time-of-flight mass spectrometry, molecular approaches and serology are introduced. These procedures are critically discussed regarding their diagnostic reliability and state of evaluation. For rare diseases reliable evaluation data are scarce due to the rarity of samples. If bio-safety level 3 is required for cultural growth, but such high standards of laboratory infrastructure are not available, serological and molecular approaches from inactivated sample material might be alternatives. Multiple subsequent testing using various test platforms in a stepwise approach may improve sensitivity and specificity. Cheap and easy to use tests, usually called "rapid diagnostic tests" (RDTs) may impact disease control measures, but should not preclude developing countries from state of the art diagnostics.

Food and drinking water hygiene and intestinal protozoa in deployed German soldiers.

This report analyzes the occurrence of Cryptosporidium spp., E. histolytica, and G. intestinalis in stool of returnees from military deployments and the impact of hygiene precautions. Between 2007 and 2010, stool samples of 830 returnees that were obtained 8-12 weeks after military deployments in Afghanistan, Uzbekistan, the Balkans, Democratic Republic of the Congo/Gabonese Republic, and Sudan and 292 control samples from non-deployed soldiers were analyzed by PCR for Cryptosporidium spp., E. histolytica, G. intestinalis, and the commensal indicator of fecal contamination E. dispar. Data on hygiene precautions were available. The soldiers were questioned regarding gastrointestinal and general symptoms. Among 1122 stool samples, 18 were positive for G. intestinalis, 10 for E. dispar, and no-one for Cryptosporidium spp. and E. histolytica. An increased risk of acquiring chronic parasitic infections in comparison with non-deployed controls was demonstrated only for G. intestinalis in Sudan, where standardized food and drinking water hygiene precautions could not be implemented. Standard food and drinking water hygiene precautions in the context of screened military field camps proved to be highly reliable in preventing food-borne and water-borne chronic infections and colonization by intestinal protozoa, leading to detection proportions similar to those in non-deployed controls.

Rapid identification of Leishmania spp. in formalin-fixed, paraffin-embedded tissue samples by fluorescence in situ hybridization.

OBJECTIVE: To describe and validate fluorescence in situ hybridization (FISH), a new method of Leishmania spp. identification. FISH allows for a rapid detection of target organisms by specific binding of fluorescently labelled oligonucleotide probes to ribosomal RNA. METHODS: Two genus-specific, fluorescently labelled Leishmania spp. FISH probes were designed and evaluated with a panel of 18 Leishmania spp. and six Trypanosoma spp. including well-defined strains and clinical isolates. In addition, the FISH probes were tested in comparison with Giemsa staining in formalin-fixed, paraffin-embedded tissues of five mice that had been artificially infected with Leishmania major strains, leading to concordant results. Finally, 11 tissue samples of patients with cutaneous leishmaniasis, four tissue samples of patients with visceral leishmaniasis, and one native bone marrow sample of a patient with visceral leishmaniasis were analysed with FISH and Giemsa staining. RESULTS: Concordant results were achieved by FISH and Giemsa staining in 15/16 specimens. CONCLUSION: This analysis provides proof of principle that FISH is a suitable method for the rapid and easy detection of Leishmania spp. in formalin-fixed, paraffin-embedded tissue samples. Because of the good contrast of Leishmania spp. in tissue, FISH facilitates the identification of these organisms in tissue samples even by less experienced investigators.

[Diagnosis and therapy of cutaneous and mucocutaneous Leishmaniasis in Germany]. / S1-Leitlinie--Revision November 2010 Diagnostik und Therapie der kutanen und mukokutanen Leishmaniasis in Deutschland.

The incidence of cutaneous and mucocutaneous Leishmaniasis (CL/MCL) is increasing globally, also in Germany, although the cases are imported and still low in number. The current evidence for the different therapies has many limitations due to lack of sufficient studies on the different Leishmania species with differing virulence. So far there is no international gold standard for the optimal management. The aim of the German joint working group on Leishmaniasis, formed by the societies of Tropical Medicine (DTG), Chemotherapy (PEG) and Dermatology (DDG), was to establish a guideline for the diagnosis and treatment of CL and MCL in Germany, based on evidence (Medline search yielded 400 articles) and, where lacking, on consensus of the experts. As the clinical features do not necessarily reflect the involved Leishmania species and, as different parasite species and even geographically distinct strains of the same species may require different treatments or varying dosages or durations of therapy, the guidelines suggest for Germany to identify the underlying parasite prior to treatment. Because of relevant differences in prognosis and ensuing therapy species should be identified in i) New World CL/MCL (NWCL/ MCL) to distinguish between L. mexicana-complex and subgenus Viannia, ii) in suspected infections with L. mexicana-complex to distinguish from L. amazonensis, and iii) in Old World CL (OWCL) to distinguish between L. infantum and L. major, L. tropica, or L. aethiopica. A state-of-the-art diagnostic algorithm is presented. For recommendations on localized and systemic drug treatment and physical procedures, data from the accessible literature were adjusted according to the involved parasite species and a clinical differentiation into uncomplicated or complex lesions. Systemic therapy was strictly recommended for i) complex lesions (e. g. > 3 infected lesions, infections in functionally or cosmetically critical areas such as face or hands, presence of lymphangitis), ii) lesions refractory to therapy, iii) NWCL by the subgenus Viannia or by L. amazonensis, iv) in MCL and v) in recalcitrant, or disseminating or diffuse cutaneous courses. In e. g. infection with L. major it encompasses miltefosine, fluconazole and ketoconazole, while antimony or allopurinol were here considered second choice. Local therapy was considered appropriate for i) uncomplicated lesions of OWCL, ii) L. mexicana-complex and iii) pregnant women. In e. g. infection with L. major it encompasses perilesional antimony, combined with cryotherapy, paromomycin 15 %/in methylbenzethoniumchlorid 12 % and thermotherapy. The group also stated that there is an urgent need for improving the design and the way of publishing of clinical trials in leishmaniasis.

Real-time multiplex PCR for simultaneous detection of Campylobacter jejuni, Salmonella, Shigella and Yersinia species in fecal samples.

Diarrheal diseases due to notifiable bacterial infections require rapid diagnosis of the causative pathogens. To facilitate detection, a real-time multiplex PCR was developed that identifies common diarrhea-causing bacteria in fecal samples. On the basis of published sequence data, sets of primers and probes were designed that were specific for Campylobacter jejuni, Salmonella, Shigella/enteroinvasive Escherichia coli EIEC, and Yersinia species, suitable for use in a one-tube PCR assay. The assay was assessed using a list of 137 well-defined intestinal bacterial strains or isolates. Furthermore, 393 routine clinical stool samples were analyzed, and the results of real-time multiplex PCR were compared with those obtained by established microbiological methods. The PCR yielded results within 3h including DNA purification. No false-positive signals or cross-reactions were observed. The analytical sensitivity was 10(3)cfumL(-1) for Campylobacter jejuni, 10(4)cfumL(-1) for Salmonella, and 10(5)cfumL(-1) for Shigella/EIEC and Yersinia, respectively. Compared with culture, PCR detected 79 out of 81 Campylobacter jejuni (97.5%), 71 out of 74 Salmonella (96%), 8 out of 8 Shigella (100%), and 10 out of 10 Yersinia-positive (100%) clinical samples. In culture-negative samples (n=192), PCR additionally detected 2 Shigella, 1 Salmonella, and 5 Campylobacter jejuni infections. Thus, the new real-time multiplex PCR provides reliable results within a short time and might be useful as an additional diagnostic tool whenever time is important in the diagnosis of enteropathogenic bacteria.

[Cutaneous leishmaniasis--an import from Belize]. / Kutane Leishmaniose--Import aus Belize.

Cutaneous leishmaniasis of the New World, in particular when caused by Leishmania (L.) braziliensis, harbours the risk of lymphogenic as well as hematogenic dissemination. This may result in mucocutaneous leishmaniasis causing severe destruction of orofacial structures. Dissemination may occur years after the disappearance of the skin lesions. In contrast, cutaneous leishmaniasis of the old world, is typically restricted to the site of inoculation. Therefore, a conservative diagnostic and therapeutic approach is usually sufficient. Infections acquired in the new world should be treated systemically, if infection with Leishmania (Viannia) braziliensis complex cannot be excluded. Here we report on three Austrian soldiers, who, weeks after having participated in an international jungle patrol course in Belize, presented themselves with multiple ulcers on the upper limbs. Diagnosis of cutaneous leishmaniasis was made based upon histological evaluation of biopsies taken from several ulcers revealing the presence of leishmanial bodies, and detection of amastigote leishmania in smears of material obtained from the ulcers. As species phenotyping could not be performed, infection with L. brasiliensis as well as progression into a mucocutaneous form were possible, demanding systemic therapy. Several treatment options including local cryotherapy with liquid nitrogen, paromomycin (Humatis Pulvis, Parke-Davis) 15% topically or oral fluconazole (Diflucan, Pfizer) 200 mg/d were applied, but showed no effect. Hence, a systemic therapy with intravenous pentamidine (Pentacarinat, Gerot), three times in total, 3-4 mg/kg body weight each, led to a complete regression of the lesions within four weeks.