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Treatment Patterns and Effectivness of Anti-Leishmaniasis Agents
Journal of Clinical & Experimental Dermatology Research

Journal of Clinical & Experimental Dermatology Research
Open Access

ISSN: 2155-9554

+44 1478 350008

Research Article - (2018) Volume 9, Issue 3

Treatment Patterns and Effectivness of Anti-Leishmaniasis Agents for Patients with Cutaneous Leishmaniasis at Boru Meda Hospital, South Wollo, North East Ethiopia, 2017/18

Tsehai Seife1, Ayikel Kassa Benecha2, Feleke Tilahun Zewdu2*, Alie Ayal3 and Mastewal Misganaw4
1Department of Dermatology, St Paul Millennium Teaching Hospital, Addis Ababa, Ethiopia
2Department of Dermatology, Boru Meda Hospital, Dessie, Ethiopia
3Public Health, Amhara Regional Health Bureau PHEM officer, Bahir Dar, Ethiopia
4Department of Dermatology, Bahir Dar University, Amhara, Ethiopia
*Corresponding Author: Feleke Tilahun Zewdu, Boru Meda Hospital, Dessie, Ethiopia, Tel: +251-945 107 616 Email:

Abstract

Background: Cutaneous leishmaniasis (CL) is one of the endemic and neglected diseases known to exist in Ethiopian highlands. However, a neglected tropical disease overshadowed by lack of effective anti-leishmaniasis agent in Ethiopia. Thus, high number of population is faced for various degree of socio-economical and psychosocial morbidity. Hence, this study was initiated and conducted from July-February, 2017/18 to assess the patterns and effectiveness of different types of anti-leishmaniasis agents in Boru Meda Hospital, Dessie District.

Methods: A cohort study design was employed in six treatment categories via randomly allocated cutaneouse patients from three clinical types at Boru Meda hospital Dermatology department. Detailed clinical assessment, biopsy/FNAC, and skin slit smear leishmania parasite detection were done to confirm clinical suspension. Then, the intended treatment types were administered for three cycle. Finally the data were analyzed using Epi-info, SPSS and the results presented using graphs and tables.

Results: Among patients with mucocutaneouse leishmaniasis who have took systemic SSG with IL SSG 85.7%, systemic SSG with Allopurinol was as effective as 78.6%. Patients with DCL who took both systemic SSG with Allopurinol 80% and systemic SSG and local therapy both cryotherapy and IL SSG had a clinical cure rate of 85.7%. In addition, patients who diagnosed as localized cutaneouse leishmaniasis and took only cryotherapy 92.3% where as those patients who had a combined local therapy of both cryotherapy and IL SSG therapy showed clinical cure rate of 96.1%.

Conclusion: As our study showed for any clinical type of cutaneouse leishmaniasis, administering combined forms (Pentavalent antimonial with local therapies i.e cryotherapy or/and IL SSG ) of anti-leishmaniasis agents had a better cure rate than single therapies.

Keywords: Cutaneouse leishmaniasis; Pattern of treatments; Effectiveness

Abbreviations

LCL: Localized Cutaneous Leishmaniasis, MCL: Mucocutaneouse Leishmaniasis; DCL: Diffuse Cutaneous Leishmaniasis

Introduction

Cutaneous leishmaniasis (CL) is a chronic, neglected tropical infectious skin disease caused by a group of protozoan parasites of the Leishmania genus. The parasites are transmitted to humans via the bite of phlebotomine sand flies and predominantly target reticulo-endothelial cells [1-3].

Cutaneous leishmaniasis was first described in Ethiopia by an Italian epidemiologist Martogilo in 1913. CL is known by different vernacular name in different localities of Ethiopia such as: “Volbo” in Ocholo, “Finchoftu” in central Shoa, “Kunchir” in Gojam, Gonder and parts of Wollo, “Giziwa” in Tigray, “Chewie” in Sodo, “Simbirahalkani” in Wollega and “Shahegne”in north Shewa [3].

Cutaneouse leishmaniasis can present with a spectrum of clinical manifestations. Ulcerative skin lesions occurring at the site of the bite of the sand fly is the most common cutaneous manifestation (localized CL—LCL). While usually healing spontaneously after several months, it remains disfiguring and stigmatizing and often heals with scarring. There are several more rare forms like diffuse CL (DCL), and muco-cutaneouse leishmaniasis which is often difficult to treat [1,4,5].

Most cutaneouse leishmaniasis lesions are self-limiting and may heal in 1-5 years. In spite of this, treatment is justified in a variety of cases, namely early lesions, multiple lesions, lesions involving cosmetically sensitive sites, mucosal lesions, disseminated lesions and patients with significant immunosuppression [2,6]. The disease still presents a therapeutic problem in several parts of the world. To-date, there is no safe, simple, cheap and effective ambulatory treatment for cutaneouse leishmaniasis. Pentavalent antimony compounds, “the best drug of a bad bunch” still remain the mainstay of treatment in the majority of cases. Antimony compounds have the disadvantage of both toxicity and clinical resistance in at least 40% of cases in certain regions where they have been in use for a long time [6-8].

Cutaneouse leishmaniasis in the Old world is predominantly caused by L. tropica and L. major , it is still estimated that several ten thousands of cases are due to L. aethiopica. These predominantly occur in Ethiopia, and more exceptionally in Kenya. Within Ethiopia, the annual cutaneouse leishmaniasis burden is estimated at around 20.000 to 40.000 cases per year [9], of which 99% is thought to be due to L aethiopica [10]. A recent study estimated almost 30 million of Ethiopians to be at risk for CL. CL in Ethiopia is a zoonotic disease, mainly occurring in the highland regions, involving rock [11].

The classic therapy for all forms of leishmaniasis uses pentavalent antimonials as sodium stibogluconate (SSG) and meglumine antimoniate (MA) administered intravenously or intramuscularly. Other systemic treatments used are amphotericin B deoxycholate (AB) and liposomal amphotericin (LAB), both intravenously, and intramuscular paromomycin. Local treatments based on intralesional pentavalent antimonials, topical paromomycin, thermotherapy, or cryotherapy are used for certain cases of cutaneous leishmaniasis. But as few studies in the New world cutaneouse leishmaniasis revealed that the combined therapies between systemic sodium stibogluconate (SSG) with Allopurinol, ketoconazol, cryotherapy and intra-lesional SSG showed promising effects for patients with cutaneouse leishmaniasis [12-14]. Thus, this study was aims to assess the patterns of treatment and its effectiveness among patients with six categories of cutaneouse leishmaniasis for treatment type under study.

Methods

This research was conducted from July-February, 2017/18 in Boru Meda hospital, 10 km away from Dessie district where located in eastern Zone of Amhara National Regional State at the north eastern edge of the Ethiopian highlands 411 km from the region capital city and 470 km north of Addis Ababa (capital of the country) situated between 11007'21.33''N, 39038’05.87’’ E with an elevation of 2, 706 meters (8878 ft) above sea level.

Boru Meda hospital was established by Sudan interior Mission (SIM) in 1955 G.C. The hospital is landed in a field bounded by mountain especially in the west and north direction in addition to the mountain. The primary objective at time of establishment of the hospital was focusing to give care on ophthalmology and dermatology services. Thus, it serves on both service area for more than 40 years but now the hospital gives a comprehensive service i.e. Emergency, outpatient service and Gynecology and obstetrics and inpatient service with 140 beds among these 45 beds was assigned for dermatology ward. Regarding human resource there are 9 specialists among these 2 of them are dermatologists and fairly adequate numbers of all the other health professionals constituted in the health care team.

The hospital provides serves for a total of 2.5 million catchment population of south Wollo, North wollo, Oromia especial zone, South Tigray and Afar region. In addition to the dermatology case diagnosis and treatment the hospital is used as a training center for health professionals in the surrounding health facilities, and used as internship and attachment site for wollo university medical department student.

The hospital had longtime experience in dermatology and ophthalmology services and the only hospital in east Amhara that gives diagnosis and management for cutaneouse leishmaniasis. Thus, most patients with cutaneouse leishmaniasis come to Boru Meda hospital since the treatment and field of specialty are available there.

This research was conducted on the treatment patterns, outcomes and effectiveness for intervention of various forms of cutaneouse leishmaniasis. A total of 97 cutaneouse leishmaniasis (MCL 28, LCL 52 and DCL 17) patients in Boru Meda hospital, dermatology department in three outpatients departments between July-February, 2017/18 one who come for the seek of curative, preventive and rehabilitation services to the hospital.

During this eight months study period, 97 patients were included in the study. 82 patients enrolled in the study whose skin slit smear positive, 9 patients have negative skin slit smear and suggestive FNAC result and the rest 6 patients were included after clinically diagnosed. But one patient was excluded from the study at the beginning of the study due to deviated RFT and LFT.

These patients were categorized in six different treatment patterns. Then, these patients were categorized randomly based on their clinical category and drugs took as; LCL (26 only cryotherapy, 26 combined intra-lesional SSG with cryotherapy), MCL; (14 Allopurinol with SSG intramuscular (IM) or intravenous (IV), 14 combined SSG IV/IM with intralesional SSG) and DCL; (10 Allopurinol with SSG IM or IV, 7 combined SSG IV/IM, cryotherapy, and Intralesional SSG). Then, the patients were assessed for the clinical improvement or cure after providing respective treatment options for three cycle or 90 days while admitting them in Boru Meda Hospital.

Meantime, those patients who took systemic SSG were had regular base line (CBC, SGOT, SGOPT, ALP, BUN, Creatinine, electrolyte and ECG for children who are less than ten years) at the beginning and every a couple of weeks with daily vital sign and conducting a grand round every week with ward Nurses, seniors and daily by assigned Nurses who follow those case on treatments which were available in the hospital.

Besides, all findings laboratory findings, deviated vital signs, clinical improvements, patients complain and drug took were recorded in the data sheets for respective clinical groups every week after grand round.

Finally, the clinical variables, drug took, socio-demographic data and outcomes were entered in to Epi-info and then for the seek of analysis it was export in to SPSS. Then, the outcome variables were presented through tables and charts.

Definition

“Clinical cure” was defined as complete epithelialization or visually healed at 2 ± 1 month after completion of therapy.

“Clinical response”-The response of the leishmanial skin lesions was determined at the end of therapy and at the following 1, 2 and 3 month time points.

“Complete clinical response” was defined as 100% reepithelialization of an ulcer or/and a return of that area of skin to a clinically healed appearance.

“Clinical improvement” was defined as 75%–99% reepithelialization (for non ulcerative lesions or/and 75%–99% decrease in the size of the initial lesion).

“Clinical failure” was less than complete epithelialization or visually not healed at 2 ± 1 month after treatment completion.

LCL: Nodular or indurated lesion which may have ulcerated at the center, with a raised and erythematous edge around it. There may be several of these lesions close to each other, and they may spread into each other to form one large lesion. It may heal with a scar.

MCL: Lesions marked by involvement of naso-oral and pharyngeal mucosa. These can often be destructive and mutilating causing difficulties in eating and drinking.

DCL: This is a chronic, progressive condition that starts with few papular or nodular lesions followed by a gradual dissemination of the infection leading to multiple papular, nodular and plaque lesions involving larger areas of the skin that often do not ulcerate. Lesions are polyparasitic and resemble lepromatous leprosy.

Ethical approval

Ethical approval was obtained from Boru Meda Hospital with a permission from the Amhara public health institute. Verbal informed consent was obtained from all admitted patients under study who comes for the seek of diagnosis and treatment of cutaneouse leishmaniasis in Boru Meda hospital dermatology department for collecting observational data via checklist, taking sample when necessary and performing physical examination during weekly follow up and grand round.

Result

Socio-demographic data

Most of the study subjects who exposed for various forms of therapy were male, 62 (63.9%), age ranges from 16-45 years, 43 (44.3%) and 71 (73.2%) patients were from rural area with high numbers of patients with cutaneouse leishmaniasis come from Dessie town, Zonal city of South Wollo zone (Table 1).

Ser. No Variables Characteristic Frequency
      N %
1 Age 42005 33 35
16-45 45 45.4
Above 45 19 19.6
2 Sex Female 35 36.1
Male 62 63.9
3 Educational Status Illiterate 23 23.7
Grade1-8 41 42.3
Grade9-12 26 26.7
Diploma and above 7 7.3
4 Address Rural 71 73.2
Urban 26 26.8
5 Family Income Farming 51 52.3
Merchants 23 23.7
Civil servants 14 14.4
Others 9 9.6

Table 1: Characteristics of cutaneouse leishmaniasis cases who received treatment in Boru Meda Hospital, Dessie, Northeast Ethiopia, 2017.

Moreover, 23 (23.7%) of patients under study was illiterate unable to read and write, and 51 (52.3%) were farmer with income source of farming and pastoralist.

Clinical characteristics

The patients were admitted to the hospital for a standardized period of time for up to three cycles with a couple of weeks rest in between to the cycle. Thus, all patients were complete their respective treatment patterns except one patient whose RFT and LFT elevated more than three times to the normal range was excluded to the study at the beginning of the study.

In addition, 33 (34%) of the patients who were included to the study had history of herbal application with significant scar around the lesions (Leishmania recidivans). But the rest 64 (66%) patients did not have history of any herb application nor any medicine from the health institution (Table 2).

    Result (N, %)
Ser. No Investigation type Total tested Positive
1 Skin slit smear 97 (100%) 82 (85%)
2 Biopsy/FNAC 15 (15.5%) 6 (40%)
3 Clinical diagnosed 9  
4 Total 97  

Table 2: Diagnostic methods used for cutaneouse leishmaniasis cases detection who received treatment in Boru Meda Hospital, Dessie, Northeast Ethiopia, 2017/18. FNAC-Fine Needle Aspiration Cytology.

A total of 97 cutaneouse leishmaniasis with three clinical types (MCL 28, LCL 52 and DCL 17), and six category intended to took as LCL (26 only cryotherapy, 27 combined intra-lesional SSG with cryotherapy), MCL; (14 only SSG intramuscular (IM) or IV, 14 combined SSG IV/IM with intralesional SSG) and DCL; (10 only SSG IM or IV, 7 combined SSG IV/IM, cryotherapy, and Intralesional SSG) (Figure 1).

clinical-experimental-dermatology-pie-chart

Figure 1: A pie chart shows the clinical cure rate of anti-leishmaniasis within the three cycles of treatment regimens in Boru Meda Hospital, Dessie, North east Ethiopia, 2017.

Among those cutaneouse leishmaniasis patients who were admitted and took drugs in different clinical types had an overall clinical cure rate or improvement about 94.8% with respective improvement MCL (89.3%), DCL (90.0%) and LCL (98.0%) (Table 3).

    Frequency
Ser. No Clinical variables N %
1 Scar lesions 41 42.3
2 Herbal application 33 34
3 Previous Rx Hx 37 38
4 Co-morbid 6 6.2

Table 3: Clinical characteristics for cutaneouse leishmaniasis cases who received treatment in Boru Meda Hospital, Dessie, Northeast Ethiopia, 2017/18.

Those patients with mucocutaneouse leishmaniasis who have took systemic sodium stibogluconate with intralesional for 14 patients was effective (85.7%) whereas the clinical cure rate for those patients who took systemic SSG with Allopurinol was 78.6%.

For patients who diagnosed as diffused cutaneouse leishmaniasis, 10 patients were admitted and took both systemic SSG and Allopurinol but the curative rate was as high as 80% where as those 7 patients who took systemic SSG and local therapy both cryotherapy and IL SSG had a clinical cure rate of 85.7%.

A total of 52 patients who diagnosed as localized cutaneouse leishmaniasis and took local therapy provide different clinical improvements in a combined and single treatment pattern. 26 patients who had only cryotherapy showed clinical cure of 92.3% at the 3rd dose whereas the rest 26 patients had a combined cryotherapy and IL SSG therapy with a cure rate of 96.1% (Table 4).

      Clinical response/Cure
Ser. No CL Types Treatment Regimen   1st dose 2nd doses 3rd doses Cure rate % Over all %
      N Y N Y N Y N    
1 MCL SSG IM + Allopurinol 14 9 5 2 3 0 3 78.6 82.2
    SSG IM + IL 14 8 6 4 2 0 2 85.7
2 DCL SSG IM + Allopurinol 10 3 7 3 4 2 2 80 82.9
    SSG + Cryotherapy + IL 7 4 3 2 1 0 1 85.7
3 LCL Cryotherapy 26 17 9 6 3 1 2 92.3 94.2
    IL + Cryotherapy 26 12 14 8 6 5 1 96.1

Table 4: Treatment patterns of cutaneouse leishmaniasis cases in Boru Meda Hospital, Dessie, Northeast Ethiopia, 2017.

Discussion

Though the magnitude of cutaneouse is not yet precisely known in Ethiopia, it results a numerous socio-economical and psychosocial effects on the population. Moreover, all the available anti-leishmania agents are considered as ineffective for Leishmania aethiopica [2,3]. But cutaneouse leishmaniasis patients who are admitted and as out patients for various patterns of treatment showed promising cure rate where agents are administered as a single and combined ways.

Patients with mucocutaneouse leishmaniasis (MCL) who have took systemic sodium stibogluconate via intra muscular or/ and intravenous with weekly intralesional pattern was as effective as 85.7%. This result was consistent with a study in Silti (Southern Ethiopia) (85%) [2] and a report from WHO (82%) [12]. This might be due to both researches were conducted on old world cutaneouse leishmaniasis cases with administration of parental SSG and local therapy (IL SSG). But the result was relatively low when compared to a study conducted in United States [13] and report from Medicines and Health care products Regulatory Agency (90%) [14]. This might be due to different etiological agents that cause leishmaniasis in New world and Old world. But to the contrary the result was too high relative to the research done in ALERT-Ethiopia though the causative agent and geographical location and treatment pattern is the same. Such a difference might be due to duration of treatment. Meaning in ALERT a study was conducted for a month or a cycle but this study was done for three cycles. On the other way round, those patients who took systemic SSG with Allopurinol showed a cure rate of 78.6%. This result was relatively higher with the study conducted in Saudi Arabia (71%) [13]. This might be difference in etiologic agents and treatment phases or cycle (3;1).

Patients with diffused cutaneouse leishmaniasis (DCL), who have took systemic sodium stibogluconate via intra muscular or/ and intravenous with Allopurinol showed the curative rate was as high as 80%. This result was relatively higher with the research conducted in Tigray-Ethiopia (75%). This might be due to treatment cycle and application of different herbs. Meaning this study was conducted on patients who took for three cycles but one cycle in Tigray where as nearly half of the study subjects in Tigray and 34% in Boru Meda had herb application. But those who took systemic SSG and combined local therapy both cryotherapy and IL SSG had a clinical cure rate of 85.7%. This result were relatively lower when compared to the study conducted in United Arab Emirate (100%) [13]. This might be due to different strains of causative agents, application technique (using cryo gun vs. cotton tipped) and one third of the cases had history of herb application in our clinic.

A total of 52 patients who diagnosed as localized cutaneouse leishmaniasis and took local therapy provide different clinical improvements in a combined and single treatment pattern. 26 patients who had only cryotherapy showed clinical cure rate of 92.3% at the 3rd dose only two patients had very good improvement but few satellite popular lesion around the mother lesions. This was relatively higher from the study conducted in United Arab Emirates (68%) [13], Turkish study (68%) [15] and Tigray (60-70%) [3]. Such a difference might be due to duration and numbers of applications i.e 12 weeks of application vs. 6 weeks and 6-8 times, application technique (using cotton tipped vs. cryo gun) and size of lesions. But to the contrary our result is relatively low when compared to trials in Egypt (100%) [16], This might be due to application of cryotherapy for undetermined times, till all lesions are cleared. In addition, other groups containing 26 patients had a combined cryotherapy and IL SSG therapy with a cure rate of 96.1%. This result was relatively higher when compared to report from Turkey (81.8%) [17] and Colombia (68%). This might be due to numbers of cryotherapy application (6-8 vs. 2-4 times) and application of IL and cryotherapy (we applied cryotherapy 2-3 days of IL SSG vs. application of both local at the same time).

Conclusions

Cutaneouse leishmaniasis is a neglected tropical disease overshadowed by lack of effective anti-leishmaniasis agent in Ethiopia. Thus, high number of population is faced for various degree of socio-economical and psychosocial morbidity.

As our study showed a combined anti- leishmaniasis agents like SSG IM with IL, SSG IM with local therapies (cryotherapy+IL SSG), cryotherapy only or combined both local therapies (cryotherapy+IL SSG) results 85.7% (MCL), 85.7% (DCL)&%, 92.3% (LCL)and 96.1% (LCL) effectiveness for respective clinical category, respectively.

Thus, for any clinical type of cutaneouse leishmaniasis administering combined forms (Pentavalent antimonial with local therapies i.e cryotherapy or/and IL SSG ) of anti-leishmaniasis agents had a better cure rate than single therapies.

Acknowledgements

This research received financial support from Boru Meda Hospital for laboratory investigation of the patients. The authors gratefully acknowledge Boru Meda Hospital for providing us free access to their laboratory facilities and Mr Asressie (Candidates of PhD in Public health) for his technical support on analysis and refining data of this manuscript. The authors also extend special acknowledgement to the target patients/participants of the study for provision of useful information.

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Citation: Seife T, Benecha AK, Zewdu FT, Ayal A, Misganaw M (2018) Treatment Patterns and Effectivness of Anti-Leishmaniasis Agents for Patients with Cutaneous Leishmaniasis at Boru Meda Hospital, South Wollo, North East Ethiopia, 2017/18. J Clin Exp Dermatol Res 9: 450.

Copyright: © 2018 Seife T, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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