Evaluation of Thermotherapy for the Treatment of Cutaneous Leishmaniasis in

Kabul, Afghanistan

Najibullah Safi, MD, MSc. HPM

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Presentation outline

• Introduction

• Methodology

• Result

• Conclusion and recommendations

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Introduction

• Leishmaniasis is the third most important vector-bornedisease

• One of the largest foci of cutaneous Leishmaniasis in world is in Kabul

• In Afghanistan, the majority of cases are caused by Leishmaniasis Tropica

• Due to mass migration of infected individuals, irregular treatment, and absence of vector control measures, the infection has now spread to areas that previously were non-endemic

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Introduction cont.

• Treatment can be challenging:• Factors influencing the treatment include:

• The size, number, appearance of the lesions, duration of the lesion prior to treatment, severity of mucosal involvement, immunosuppression, co-infections, prior anti-leishmanial treatment, location of the lesion, age of the patient

• Factors such as immunity, variable clinical response to treatments, drug toxicity, drug resistance, HIV co-infection, and compliance all influence treatment outcome

• Antimonials have been used for more than half a century in the treatment of Leishmaniasis

• Antimonials can have serious adverse effects when given intra-muscularly, and are also quite expensive

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Methodology

• Objectives:• To determine the effectiveness of local thermotherapy by radiofrequency

compared to intra-lesional injection of Glucantime in the management of CL

• To generate reliable evidence that could guide the development of aprotocol for the treatment of cutaneous Leishmaniasis in Afghanistan

• Hypothesis: Thermotherapy is as effective as intra-lesionalGlucantime for the treatment of cutaneous Leishmaniasis

• Research design: Randomized Controlled Trial

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Methodology cont.

• Study setting: Leishmaniasis treatment center, kabul

• Study population: Patient visiting the treatment center

• Inclusion criteria: Aged of 5 years or older, with a single cutaneous Leishmaniasis lesion confirmed by parasitology

• Sample size: 195 individuals in each arm

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Methodology cont.

• Intervention: • A single thermotherapy treatment, which consisted of an application of

localized heat of 50 degrees Celsius for 30 seconds

• Current standard therapy:• Five intra-lesional administrations of Glucantime (2-7 ml depending on size of

the lesion) in seven-days intervals

• Ethical consideration:• IRB approval

• Informed consent

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Methodology cont.

• Definition of treatment outcome: • Cure: defined as complete re-epithelialization with no inflammation

• Failure: defined as no improvement, with the lesion unchanged orworse compared with its status at the start of treatment

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Methodology cont.

• Statistical analysis: • Statistical Analysis System (SAS)• Descriptive analysis was carried out on all baseline characteristics• For continuous variables, mean/median and standard deviation (SD)

were calculated• For categorical variables, proportions were reported and tested• The descriptive statistics were computed for intervention and standard

therapy groups separately and compared using appropriate statistical tests

• To adjust for the effects of other variables on the outcome, logistic regression analyses were applied

• For each associated factor, the odds ratio at 95% confidence intervals were estimated to evaluate the association of each variable with the outcome

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Results

Characteristic Thermotherapy group (n=189)

Glucantime group (n=193) P-Value

Age (Year)

Median 14 13 0.246

Age interval 5-70 5-75

Sex of subject (n,%)

Male 85 (48.0) 92 (52.0) 0.59

Female 104 (50.7) 101 (49.3)

Body weight (Kg)

Mean (SD) 42.5 (23.3) 39.01 (18.3) 0.1

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Results cont. Age Distribution

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Results cont.

Baseline characteristics

(49.2)

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Results cont.

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Results cont.

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Discussion

• Several studies have reported the successful administration of intra-lesional antimony to cure Old World cutaneous leishmaniasis, but few studies have compared thermotherapy with antimonials

• Earlier studies showed that Leishmania parasites do not multiply at temperature greater than 39ºC in vitro

• These findings led to studies investigating the efficacy of thermotherapy treatment with hot-water baths

• The overall cure rate was 78.2% (299/382) for both treatments; in the Glucantime group, the cure rate was 74% (143/193) and in the Thermotherapy group it was 82.5% (156/189), tested by Pearson Chi-square (P-value=0.045)

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Discussion cont.

• An earlier study in Afghanistan compared intra-lesional and intra-muscular antimony versus Thermotherapy; cure rates were 69.4% for thermotherapy, 75.3% for intra-lesional SSG

• Surgical excision of lesions is generally not recommended because of the high risk of local relapse and disfiguring

• Thermotherapy devices deliver localized heat directly to a lesion and can be convenient for use in primary healthcare facilities

• We found that a single treatment with localized heat is more effective than the administration of intra-lesional Glucantime in univariate analysis

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Conclusion and recommendations

• Thermotherapy might be considered as an alternative to antimony for the treatment of cutaneous Leishmaniasis

• Thermotherapy is a cost-effective alternative to traditional treatment in those areas of endemicity where the number of cases is high and focal

• There are two main advantages to thermotherapy compared with antimony treatment:• First, patient compliance rate improved

• Second, treatment is administered locally, and the treatment schedule is shorter

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Conclusion and recommendations

• The shorter administration schedule also increases the patient turnover rate

• The tested thermotherapy method uses a handheld device and limited additional medical equipment, making it suitable for field conditions

• In our study, size of the lesion has significantly association with treatment outcome: the larger the lesion, the less likelihood of cure

• In Afghanistan, thermotherapy proved to be effective, safe, and relatively noninvasive for treating patients with cutaneous Leishmaniasis

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Acknowledgement

• The contribution of co-authors: • COL Gary D. Davis, MC, USA

• Mohammed Nadir, MD, MSc

• Hamida Hamid, MD

• COL Leon L. Robert, Jr., MS, USA

• MAJ Alan J. Case, MS, ARNG

• Ms Firestone for financial support

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Thanks

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