Cutaneous Leishmaniasis In Ethiopia Research Articles

First report of cutaneous leishmaniasis caused by Leishmania donovani in Ethiopia

BackgroundLeishmaniasis is a common neglected tropical disease in Ethiopia. Visceral leishmaniasis (VL) caused by Leishmania donovani presents in the lowlands, while cutaneous leishmaniasis (CL) affects people living in the highlands. Although CL is described as being caused by Leishmania aethiopica, there is also evidence of L. tropica and L. major isolated from a patient, sand flies and potential reservoirs. Information on species causing CL in Ethiopia is patchy, and no nation-wide study has ever been done. Understanding which species are causing CL in Ethiopia can have important implications for patient management and disease prevention.MethodsWe analyzed stored routine samples and biobanked DNA isolates from previously conducted studies of CL patients from different centers in the north, center and south of Ethiopia. Species typing was performed using ITS-1 PCR with high-resolution melt (HRM) analysis, followed by HSP70 amplicon sequencing on a selection of the samples. Additionally, sociodemographic, clinical and laboratory data of patients were analyzed.ResultsOf the 226 CL samples collected, the Leishmania species could be determined for 105 (45.5%). Leishmania aethiopica was identified in 101 (96.2%) samples from across the country. In four samples originating from Amhara region, northwestern Ethiopia, L. donovani was identified by ITS-1 HRM PCR, of which two were confirmed with HSP70 sequences. While none of these four patients had symptoms of VL, two originated from known VL endemic areas.ConclusionsThe majority of CL was caused by L. aethiopica, but CL due to L. tropica and L. major cannot be ruled out. Our study is the first to our knowledge to demonstrate CL patients caused by L. donovani in Ethiopia. This should spark future research to investigate where, how and to which extent such transmission takes place, how it differs genetically from L. donovani causing VL and whether such patients can be diagnosed and treated successfully with the currently available tools and drugs.Graphical

Protocol for a prospective observational cohort study of cutaneous leishmaniasis in Ethiopia

Background: Cutaneous leishmaniasis (CL) is a skin neglected tropical disease, with an estimated 40,000 new cases each year in Ethiopia. CL causes ulcers, nodules, and plaques on the skin, and in some instances the destruction of the nasopharyngeal mucosa and cartilage. Some CL lesions may heal spontaneously, whilst other lesions may require therapies which are associated with discomfort, adverse effects, prolonged treatment, and a frequent lack of a complete response. Scarring, a sequela of CL, causes permanent disfigurement and is associated with stigma linked with a reduction in health-related quality of life. The choice of treatment for CL is based upon factors including the causative species; the number, extent, size, and location of lesions; and the availability of treatments. The development of robust evidence for CL treatment is hindered by a lack of validated and appropriate outcome measures and few data to support hypothesis-generation and trial design. There is a paucity of prospective data with well-defined treatment outcomes for CL caused by L. aethiopica. Aim: The overall aim of this study is to improve the understanding of the health and economic burden of CL. Methods: We have designed an observational, multi-centre cohort study to examine treatment outcomes for CL in Ethiopia which includes clinical outcomes, laboratory outcomes, patient reported outcome measures, scar assessments and cost effectiveness. We aim to recruit up to 750 participants across two hospital sites. We present here the protocol for this cohort study with a 12-month follow up period for each participant. Conclusions: These data will inform the design of randomized controlled trials to evaluate new treatment strategies, with appropriate economic evaluations. This will help improve evidence-based guidelines and support evidence-led policy decisions, not only in Ethiopia but also globally.

Genome diversity of Leishmania aethiopica.

Leishmania aethiopica is a zoonotic Old World parasite transmitted by Phlebotomine sand flies and causing cutaneous leishmaniasis in Ethiopia and Kenya. Despite a range of clinical manifestations and a high prevalence of treatment failure, L. aethiopica is one of the most neglected species of the Leishmania genus in terms of scientific attention. Here, we explored the genome diversity of L. aethiopica by analyzing the genomes of twenty isolates from Ethiopia. Phylogenomic analyses identified two strains as interspecific hybrids involving L. aethiopica as one parent and L. donovani and L. tropica respectively as the other parent. High levels of genome-wide heterozygosity suggest that these two hybrids are equivalent to F1 progeny that propagated mitotically since the initial hybridization event. Analyses of allelic read depths further revealed that the L. aethiopica - L. tropica hybrid was diploid and the L. aethiopica - L. donovani hybrid was triploid, as has been described for other interspecific Leishmania hybrids. When focusing on L. aethiopica, we show that this species is genetically highly diverse and consists of both asexually evolving strains and groups of recombining parasites. A remarkable observation is that some L. aethiopica strains showed an extensive loss of heterozygosity across large regions of the nuclear genome, which likely arose from gene conversion/mitotic recombination. Hence, our prospection of L. aethiopica genomics revealed new insights into the genomic consequences of both meiotic and mitotic recombination in Leishmania.

Clinical pattern and treatment outcome of Cutaneous Leishmaniasis in two hospitals in Bahir Dar, Ethiopia (2017-2021)

Cutaneous Leishmaniasis (CL) in Ethiopia is caused by a unique species, L. aethiopica. In Ethiopia, there are limited studies that provide detailed clinical descriptions of CL, treatment options, and treatment outcomes. We conducted a descriptive study based on routinely collected data in medical files from two hospitals in Bahir Dar, Ethiopia, from 2017 to 2021. Three months following the end of therapy, we retrieved sociodemographic and clinical data, as well as data on the treatment outcome. Between March 2017 and June 2021, 94 patients were diagnosed with CL at the two hospitals. Of those, 46 (48.9%) of individuals had localized CL, 36 (38.3%) mucocutaneous leishmaniasis (MCL), and 12 (12.8%) diffuse CL. Sixty-five (69.1%) of the participants were men. The most prevalent morphologic appearances were plaque (n = 42, 46.2%), nodule (n = 38, 41.8%), infiltrative (n = 34, 36.2%), crusted (n = 32, 34%), and ulcerated (n = 24, 25.5%). Scarred, volcanic, and patchy lesions were also documented. Systemic pentavalent antimonials were the most common treatment (n = 55, 58.5%), curing 21/38 (55%) of the patients. Pentavalent antimonials were also given intralesionally to seventeen patients (18.1%), with 15/16 (94%) of them being cured. Overall, 61% (40/66) of patients with documented treatment outcomes were cured. As CL in Ethiopia has a wide array of clinical presentations, clinicians should be suspicious of patients from endemic areas who present with dermatologic manifestations. Physicians can employ local treatment as a first line before resorting to systemic therapy.

Burden and risk factors of cutaneous leishmaniasis in Ethiopia: a systematic review and meta-analysis.

Cutaneous leishmaniasis (CL) is a major public health problem in Ethiopia. About 30 million people are at risk, and there are 20,000 to 50,000 new cases annually. It is maintained by rock hyraxes and Phlebotomus sand flies. Different studies showed the presence and risk factors of CL. However, there is no study on the pooled prevalence and risk factors. This study aimed to determine the pooled prevalence and risk factors of CL in Ethiopia. We retrieved published articles from different databases. The review was conducted based on PRISMA guidelines. The meta-analysis was done with Stata software version 14. The forest plot with random-effect model and inverse variance index was used to estimate the pooled prevalence with 95% confidence interval and heterogeneity of articles, respectively. A total of 99,226 people from 19 studies were screened. The overall pooled prevalence of CL was 20.4% with 95% CI (15.67-25.13%). The pooled prevalence is a weighted average of results of the included 19 studies. Highest pooled prevalence, 65.39% (95% CI: 61.14-69.47%), was in Southern Nations, Nationalities and Peoples' Region (SNNPR), and the lowest was 1.53% (95% CI: 1.43-1.63%) in Amhara Region. Children were the most affected age group. Living in a home close to farmlands, outdoor sleeping behavior, the presence of gorge, hyrax, cracked walls, animal dung, and other cases in the neighborhood were identified as risk factors for CL. There is high burden of CL in Ethiopia. Larger surveys are required. Health education on the prevention and control strategies shall be implemented.

Enhanced activation of blood neutrophils and monocytes in patients with Ethiopian localized cutaneous leishmaniasis in response to Leishmania aethiopica Neutrophil activation in Ethiopian cutaneous leishmaniasis

Recent studies suggest an essential role of the innate immune effector cells neutrophils and monocytes in protection or disease progression in the early course of Leishmania infection. In areas endemic for cutaneous leishmaniasis in Ethiopia most individuals are exposed to bites of infected sandflies. Still only a minor ratio of the inhabitants develops symptomatic disease. Neutrophils, followed by monocytes, are the first cells to be recruited to the site of Leishmania infection, the initial response of neutrophils to parasites appears to be crucial for the protective response and disease outcome. Our working hypothesis is that neutrophils and/or monocytes in localized cutaneous leishmaniasis (LCL) patients may have defects in function of innate immune cell that contribute to failure to parasite clearance that lead to establishment of infection.The response of cells in Ethiopian LCL patients and healthy controls to Leishmania aethiopica and to the Toll like receptor (TLR) agonists lipopolysaccharide (LPS) and macrophage activating lipopeptide-2 (MALP-2) was investigated by assessing the cell surface expression of CD62L (on neutrophil and monocyte) and CD66b (only on neutrophil), as well as reactive oxygen species (ROS) production by using whole blood-based assays in vitro. No impaired response of neutrophils and monocytes to the microbial constituents LPS and MALP-2 was observed. Neutrophils and monocytes from LCL patients responded stronger to Leishmania aethiopica in the applied whole blood assays than cells from healthy individuals. These experimental findings do not support the hypothesis regarding a possible dysfunction of neutrophils and monocytes in cutaneous leishmaniasis. On the contrary, these cells react stronger in LCL patients as compared to healthy controls. The differential response to L. aethiopica observed between LCL patients and healthy controls have the potential to serve as biomarker to develop FACS based diagnostic/ prognostic techniques for LCL.

Enhanced production of pro-inflammatory cytokines and chemokines in Ethiopian cutaneous leishmaniasis upon exposure to Leishmania aethiopica

The clinical course and outcome of cutaneous leishmaniasis (CL) vary due to the infecting Leishmania species and host genetic makeup that result in different immune responses against the parasites. The host immune response to Leishmania aethiopica (L.aethiopica), the causative agent of CL in Ethiopia, is poorly understood. To contribute to the understanding of the protective immune response in CL due to L.aethiopica, we characterized the cytokine response to L. aethiopica in patients with the localized form of CL (LCL) and age-and sex-matched apparently healthy controls. By applying a whole blood based in vitro culture we found enhanced release of TNF, IL–6, MCP-1 or CCL2, IP-10 or CXCL10, MIP-1β or CCL4 and IL-8 or CXCL8- but not of IL–10CL patients in response to L. aethiopica compared to the controls. No difference was observed between LCL cases and controls in the secretion of these cytokines and chemokines in whole blood cultures treated with the TLR-ligands LPS, MALP-2 or polyI: C. The observed increased secretion of the pro-inflammatory cytokines/chemokines reflects an enhanced response against the parasites by LCL patients as compared to healthy controls rather than a generally enhanced ability of blood leukocytes from LCL patients to respond to microbial constituents. Our findings suggest that the enhanced production of pro-inflammatory cytokines/chemokines is associated with localized cutaneous leishmaniasis caused by L.aethiopica.

Risk map for cutaneous leishmaniasis in Ethiopia based on environmental factors as revealed by geographical information systems and statistics.

Cutaneous leishmaniasis (CL) is a neglected tropical disease strongly associated with poverty. Treatment is problematic and no vaccine is available. Ethiopia has seen new outbreaks in areas previously not known to be endemic, often with co-infection by the human immunodeficiency virus (HIV) with rates reaching 5.6% of the cases. The present study concerns the development of a risk model based on environmental factors using geographical information systems (GIS), statistical analysis and modelling. Odds ratio (OR) of bivariate and multivariate logistic regression was used to evaluate the relative importance of environmental factors, accepting P ≤ 0.056 as the inclusion level for the model's environmental variables. When estimating risk from the viewpoint of geographical surface, slope, elevation and annual rainfall were found to be good predictors of CL presence based on both probabilistic and weighted overlay approaches. However, when considering Ethiopia as whole, a minor difference was observed between the two methods with the probabilistic technique giving a 22.5% estimate, while that of weighted overlay approach was 19.5%. Calculating the population according to the land surface estimated by the latter method, the total Ethiopian population at risk for CL was estimated at 28,955,035, mainly including people in the highlands of the regional states of Amhara, Oromia, Tigray and the Southern Nations, Nationalities and Peoples' Region, one of the nine ethnic divisions in Ethiopia. Our environmental risk model provided an overall prediction accuracy of 90.4%. The approach proposed here can be replicated for other diseases to facilitate implementation of evidence-based, integrated disease control activities.

Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia

BackgroundCutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood.Methodology/Principal FindingsWe have recently shown in an experimental model of cutaneous leishmaniasis that arginase-induced L-arginine metabolism suppresses antigen-specific T cell responses at the site of pathology, but not in the periphery. To test whether these results translate to human disease, we recruited patients presenting with localized lesions of cutaneous leishmaniasis and assessed the levels of arginase activity in cells isolated from peripheral blood and from skin biopsies. Arginase activity was similar in peripheral blood mononuclear cells (PBMCs) from patients and healthy controls. In sharp contrast, arginase activity was significantly increased in lesion biopsies of patients with localized cutaneous leishmaniasis as compared with controls. Furthermore, we found that the expression levels of CD3ζ, CD4 and CD8 molecules were considerably lower at the site of pathology as compared to those observed in paired PBMCs.ConclusionOur results suggest that increased arginase in lesions of patients with cutaneous leishmaniasis might play a role in the pathogenesis of the disease by impairing T cell effector functions.

Treatment response of cutaneous leishmaniasis due to Leishmania aethiopica to cryotherapy and generic sodium stibogluconate from patients in Silti, Ethiopia

Cutaneous leishmaniasis in Ethiopia is caused mainly by Leishmania aethiopica. In this study, the response of L. aethiopica to sodium stibogluconate (SSG) and liquid nitrogen in Silti has been investigated. Patients were divided into two groups by the treating physician and were treated with either liquid nitrogen or SSG. Punch biopsy samples were collected from 54 patients with mean age of 20.61 (± 9.87 SD) years for histological characterization. The histological spectrum found to be type-1, type-2, type-3 and type-4 were 37.0%, 3.7%, 37.0% and 22.2% respectively. One hundred and three patients with a mean age of 18.4 (± 11.7 SD) years were treated with liquid nitrogen. The mean duration of the lesions before the onset of treatment was 8.5 months (± 6.7 SD). Of the 103 patients 80.6% (83/103) were cured, 13.6% (14/103) were dropouts and 5.8% (6/103) did not respond. Twenty patients with a mean age of 19.55 (+1.64 SD) years were treated with Pentostam on conventional dose. Of the 20 patients 85.0% (17/20) were cured, 10.0% (2/20) were unresponsive and 5.0% (1/20) were dropouts. The per protocol cure rate for cryotherapy and Pentostam was 93.3% and 89.5% respectively. Hence, liquid nitrogen can be used as one of the treatment options especially in resource poor settings.

Isolation of Leishmania tropica from an Ethiopian cutaneous leishmaniasis patient

Cutaneous leishmaniasis (CL) in the Old World is caused mainly by three species of Leishmania: L. major, L. tropica and L. aethiopica, and sporadically by L. infantum and L. donovani. In Ethiopia, zoonotic cutaneous leishmaniasis, caused by L. aethiopica, is a major public health problem affecting thousands of people in the highlands. By contrast, little is known about the existence and epidemiology of CL due to L. tropica. In this report, we provide the first well-documented case of CL in Ethiopia caused by L. tropica. The patient acquired the infection in Awash valley of the Ethiopian Rift Valley (northeastern Ethiopia), where Phlebotomus sergenti and P. saevus have previously been found infected by L. tropica. Using the isoenzyme electrophoresis technique, the isolate was found to belong to a variant of L. tropica zymodeme MON-71, one of the new zymodemes found in Ethiopia from P. sergenti in the same region so far. The epidemiological implications of the finding are discussed.

Treatment of cutaneous leishmaniasis by photodynamic therapy: Reply*1

We read with interest the comments contained in the letter by Drs El-On, Katz, and Weinrauch regarding our report on treatment of cutaneous leishmaniasis (CL) with photodynamic therapy (PDT). Although the diagnosis of CL resting on clinical presentation and typical histology is not in doubt, we are in complete agreement that posttreatment tissue cultures could have substantiated our claim of efficacy of PDT. Comparing various parasitological methods, Mengistu et al1Mengistu G Akuffo H Fehniger T.E Negese Y Nilsen R Comparison of parasitological and immunological methods in the diagnosis of leishmaniasis in Ethiopia.Tran R Soc Trop Med Hyg. 1992; 86: 154-157Abstract Full Text PDF PubMed Scopus (28) Google Scholar found tissue cultures to be more sensitive than direct smears and histology (56%, 40%, and 37% sensitivity, respectively) in the diagnosis of CL in Ethiopia. However, Leishmania culture techniques require substantial experience to produce reliable results, they are sensitive to contamination, and the yield decreases with the age of the lesions. Our experience with PDT for CL also includes verification of clearing by direct smears: In a recent open study, we have treated a series of 11 Israeli CL patients with a total of 32 lesions.2Enk C.D Fritsch C Jonas F Nasereddin A Ingber A Jaffe C.L et al.Treatment of cutaneous leishmaniasis with photodynamic therapy.Arch Dermatol. 2003; 139: 432-434Crossref PubMed Scopus (95) Google Scholar Therapeutic endpoints were disappearance of amastigotes by direct smear, reduction of lesion size, and cosmetic outcome. All but one lesion became amastigote negative after only two treatments, at which time the mean reduction in lesion size constituted 67 %. The cosmetic results were excellent, and no relapses were noted within the 6-month follow-up period. The combined experiences from these two PDT studies are highly suggestive of the efficacy of PDT in the treatment of CL. We also agree with El-On et al that spontaneous healing or delayed effect of sodium stibogluconate given 5 months earlier, in theory, might have caused the clinical improvement; in fact, we specifically state so in the discussion. However, the cross-over design makes this possibility highly unlikely. Then again, in the hierarchy of clinical evidence, case reports rank rather low, and introduction of post-treatment tissue cultures or even the most sophisticated cross-over design will not change the fact that the true value of PDT in the treatment of CL can only be determined in future randomized controlled trials. PDT constitutes a novel and promising therapeutic modality; however, the procedure is time consuming, expensive, and requires special equipment. For these reasons PDT is probably not an option for the majority patients with CL living in endemic areas as correctly observed by El-On et al. However, for travelers returning with CL to their countries of origin in the developed world, or for immigrants to these countries like our patient, PDT might constitute a rapid and attractive therapeutic alternative that should be taken into consideration.

The use of direct agglutination test (DAT) in serological diagnosis of Ethiopian cutaneous leishmaniasis

Leishmania aethiopica (L.a.) is the main species of Leishmania that causes Ethiopian cutaneous leishmaniasis (ECL). The routine diagnosis of ECL depends on parasitological examination of smear, culture or biopsy. In this study, DAT was set-up and evaluated for its diagnostic performance using defined sera of 45 ECL patients, 18 visceral leishmaniasis (VL) patients, 12 patients with other diseases, and 37 normal controls. The test was also evaluated in 64 patients clinically diagnosed as ECL, leprosy, or other skin diseases. Using L.a. derived antigen, the sensitivity and specificity of the test was determined to be 90.5% and 91.8% respectively. However, using antigen derived from a non-homologous strain, only 4 sera of 21 active ECL patients were positive. Eighteen sera of VL patients were positive irrespective of the different antigen sources. The data show that DAT can be a useful addition to the diagnosis of ECL.

Immunoblot analysis of sera from Ethiopian cutaneous leishmaniasis by antibody class.

We have determined the specificity of the classes of anti-leishmanial antibodies which are detectable in serum from patients with active cutaneous leishmaniasis. On immunoblots, differences exist in the patterns of antigen recognition by IgG, IgM, IgA and IgE antibodies present in localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL) patient serum. Each class of antibody showed differing patterns of banding to the various molecular species of parasite antigens. There was significant variation in the specificities of the IgG antibody reactivities between individual patients. The patterns of IgM binding were generally homogeneous and restricted to antigens with M(r) greater than 40 kDa. The only class of anti-Leishmania antibodies which showed shared patterns of common antigen recognition by all of the patients studied were IgA antibodies. The reactivities of IgE antibodies encompassed two antigens of M(r) 36 and 46-48 kDa which were not recognized by any of the other isotypes. Such antibody class associated reactivity may be useful in the design of serodiagnostic assays for the detection of Leishmania infection or other infectious agents.

Generation of species-specific DNA probes for Leishmania aethiopica

We report here the cloning of kinetoplast DNA (kDNA) sequences from Leishmania aethiopica in order to develop a specific and sensitive method for the identification of the parasite. Analysis of the cloned kDNA sequences showed different taxonomic specificities demonstrating sequence diversity within the kinetoplast DNA. Cloned whole minicircle hybridized with all Old World Leishmania species tested. Some cloned fragments of minicircle kDNA hybridized with Leishmania species causing cutaneous leishmaniasis in the Old World, but not with the viscerotropic species. Two L. aethiopica-specific clones were found. These clones hybridized with all L. aethiopica isolates tested, but did not react with other Leishmania species. The nucleotide sequence of the L. aethiopica-specific R3 clone is presented. Clones hybridizing with only some of the L. aethiopica isolates were also identified, although none of them showed specificity only for isolates causing localized (LCL) or diffuse (DCL) form of cutaneous leishmaniasis in Ethiopia.

In situ characterization of the cutaneous immune response in Ethiopian cutaneous leishmaniasis.

Cryostat sections from 10 patients with localized cutaneous leishmaniasis (LCL) and eight patients with diffuse cutaneous leishmaniasis (DCL) from Ethiopia were studied with immunofluorescence methods for the phenotypic characterization of cells in the lesions. Higher numbers of Leu 2+ and Leu 3+ cells (P less than 0.005) were found in LCL than in DCL, while the Leu 3a + b/Leu 2a ratios were the same. No differences were found in the numbers of transferrin receptor, HLA-DR, and HLA-DQ expressing cells in the granulomas. Significantly (P less than 0.0001) lower numbers of IL-2 receptors expressing (Tac+) cells were found in DCL than LCL lesions, suggesting interference in the activation of the T cells. IL-2-containing cells were absent in DCL and were found in LCL lesions. Epidermal keratinocytes above the LCL but not the DCL lesions expressed HLA-DR (but not HLA-DQ) antigen, suggesting a lower gamma-interferon production in the DCL granulomas. The number of Langerhans' cells (Leu 6+) was higher in the epidermis of DCL (P less than 0.005) than in LCL, while a lower number of Leu 6+ cells were seen in the dermal lesions (P less than 0.001). These observations could account for some of the mechanisms responsible for the disturbed immunostimulation and immunoregulation observed in the lesions of DCL.

The biology of a laboratory colony of Phlebotomus longipes Parrot & Martin (Diptera: Phlebotomidae).

A laboratory colony of an Ethiopian sand fly, Phlebotomus longipes , was maintained over a period of 3 years in a London laboratory through 9 generations of a 1st colony and 7 generations of a 2nd colony. Breeding was carried out successfully on a plaster-of-Paris base in a newly designed breeding vessel, the “Tower-vial,” modified from the KM-vial, which was also employed in earlier stages of colonization. The larval diet initially consisted of autoclaved rabbit feces for the earlier generations, but in later generations liver, or yeast, formed the main constituent of the larval diet. First-stage larvae were attracted to these diets which resulted also in rapid growth and a high percentage of larvae pupating to yield adults. At 25°C, females oviposited from 11 to 95 eggs (mean 52) 7–9 days after a full blood meal; eggs hatched 7–8 days later. The mean life cycle from egg to adult emergence was shortest (about 45 days) on a larval diet of liver. Feeding of adults on a sugar solution, and of females on blood from man and other animals is described. Females fed most readily on the human arm 2 to 3 days after emergence. Sugar-fed males and females lived as long as 35 days, and blood-fed females lived for 5–6 days and occasionally longer (about 10 days) at 80% rh and 25°C in cages in an insectary. At least 3 partial blood meals could be taken by a female in 5 days. These findings are consistent with P. longipes being competent as a vector of cutaneous leishmaniasis in Ethiopia. Copulation was preceded by courtship (epigamic behavior). A single male mated with more than 1 female and inseminated 3 out of 5 females over a 24-hr period.

The parasite causing cutaneous leishmaniasis in Ethiopia

The parasite causing cutaneous leishmaniasis in Ethiopia

Diffuse cutaneous leishmaniasis in ethiopia: II Treatment

The treatment of 33 cases of diffuse cutaneous leishmaniasis in Ethiopia is presented. Pentamidine isethionate and amphotericin B have proved the two drugs to which the parasite is consistantly sensitive. Both are seriously toxic and better drugs are needed. Weekly or fortnightly pentamidine at the lowest dose that will produce a response is probably the best treatment; the glucose tolerance test should be performed weekly. Antimonals are usually ineffective but N-methylglucamine antimoniate shows some activity in high, approaching toxic, doses. The apparent effect of chloroquine may be due to its anti-inflammatory properties. Cycloguanil pamoate, primaquine and its analogue 349-C59 and macrocyclon may be useful if given in much higher doses than generally recommended. Toxic effects of these drugs have not so far been encountered. Relapse almost inevitably follows treatment and can occur repeatedly and up to 15 months later. Treatment must be repeated or prolonged for several months after the apparent elimination of the parasite in order to achieve cure. Before the patient is “cured,” the disease in relapse usually shows a tuberculoid histology and is accompanied by a positive leishmanin test, after which a further course of any effective drug will “cure” him. Without such an immune conversion it is very difficult to cure the patient.

Diffuse cutaneous leishmaniasis in Ethiopia I. The clinical and histological features of the disease

The clinical and histological features of 33 cases of diffuse cutaneous leishmaniasis (DCL) seen in Ethiopia are described. The disease starts as a nodule, usually on a limb. After a period of months or years, during which the initial lesion may rarely ulcerate, or even disappear, it starts to spread locally and distant metastases appear on the face, arms and legs; in appearance and distribution they bear some resemblance to leprosy. The disease spreads slowly, does not ulcerate, invade the viscera or heal. The patient remains remarkably well and there are no consistently abnormal findings in the blood or urine. Smears from the lesions show numerous amastigotes (L-D bodies). The histology is characterized by a thin epidermis and an intense dermal infiltration with macrophages, many of them vacuolated and stuffed with parasites; lymphocytes are absent or scanty. Under the influence of treatment the histology changes towards the tuberculoid. The leishmanin skin test is negative. Reasons are given why DCL in Ethiopia is not post kala-azar dermal leishmaniasis, and the features that distinguish it from simple oriental sore are presented. An attempt has been made to correlate the clinical and histological findings and to show that, whereas the distribution of the lesions is a feature of the parasite, the appearance of the lesions and their histology is a feature of the host's immune response. A histological classification, which indicates the state of the patient's cellular immune response, is given. In untreated DCL this response is absent. The state of reaction is not useful or protective. The frequency with which lymphatic damage was seen in these cases is considered as a possible cause, as opposed to effect, of the disease. The differential diagnosis is discussed.