Epidemiological features of cutaneous leishmaniasis in diagnosed patients from an endemic area (central Morocco)

Abstract

Cutaneous leishmaniasis represents the most neglected tropical disease across the world. In Morocco, this disease is endemic and constitutes a major public health problem, with a national control program been implemented. The current study aimed to determine the pattern and epidemiological features of cutaneous leishmaniasis in affected patients in an area covered by the CL control and prevention program (Central Morocco). A total of 161 patients suspected for cutaneous leishmaniasis were diagnosed according to WHO laboratory methods, and 82 cases were confirmed positive for CL. The reports were analysed by patients’ socio-geographic status, gender and age. The number and distribution of CL lesions by location, gender and age were investigated. Overall the confirmed cases, 89 % were infected by Leishmania tropica versus 21 % for Leishmania major. Females were significantly more affected than males (p < 0.01). Children (0–15 years), especially those ≤ 7 years of age, were the most affected. For the distribution of lesions, single lesion cases were largely preponderant (70.7 %) compared to multiple lesions. Face location was significantly more frequent (62.2 %) compared to limbs (26.8 %). Face lesions were found more prevalent in children than in adults while limb lesions were highly observed in adults. The pattern of the disease is affected by many factors (e.g. environment, gender, age, etc.) and has specifics to be considered in prevention and control programs in endemic areas.

Introduction

Cutaneous leishmaniasis (CL) is a major tropical vector-borne zoonotic disease of public health importance caused by species of the Leishmania parasite. It is known as disfiguring disease causing skin lesions in different members of body in human. CL is a worldwide affection and endemic in many countries, and a significant expansion of Leishmania-endemic regions due to climate change, man-made projects with environmental impact and massive rural-urban migration was reported (WHO 2007; McMichael and Lindgren 2011). The number of new CL cases has reached to 1.5 million people in the world; however, the actual rate is grossly underestimated and may be several times more than the reported because of the higher number of unrecorded cases and notification was not compulsory in most countries where millions of people are at risk (Desjeux 2004; Alvar et al. 2012). In Morocco, as CL is endemic in several regions of the country, the notification is compulsory and a prevention and control program of the disease was implemented. Control activities include sandfly vector and animal reservoir control, active and passive detection, early treatment and case management, health education and sensitization in schools and in endemic localities, with community implication. Moreover, inter-sectoral collaboration between public health, agricultural, and local authorities has been developed to achieve significant decrease in CL occurrence (MoH 2010; WHO 2010). The undergone control program resulted in an overall non-uniform decreasing trend in CL occurrence declining from 8707 cases in 2010 to 4946 cases in 2016 (MoH 2016).

In order to plan appropriate approaches to the prevention and control of CL and improve the efficiency of existing programs, it is recommended to carry out epidemiological studies and collect information from endemic areas about aspects of factors affecting the spread of the disease (World Health Assembly 2007). In Central Morocco area very few recent comprehensive epidemiological studies have yet been performed on CL (Zougaghi et al. 2011; Zouirech et al. 2018). The present study aimed to investigate epidemiology profile and clinical features of CL among the patients referred to the Regional Laboratory of Epidemiological Diagnostic and Environmental Hygiene during three-year period.

Materials and methods

The current study involved 161 patients with suspected CL lesions. The sample from each suspected lesion was smeared on a glass slide, stained using Giemsa stain, and then the slide was checked under microscopic magnification (1000x) in search for Leishmania amastigotes according to WHO laboratory methods (WHO 1991). The parasitologic smear was considered positive when it showed leishmanial parasites as amastigotes, generally intracellular inside monocytes. Demographic data and clinical details were recorded and included age, gender, socio-geographic status (rural vs. urban origin), date of lesion appearance, consultation date, the number and site of lesions, history of travel to an endemic locality.

The therapeutic indications differ depending on the clinical form including size of lesion, number and location of lesions, species of Leishmania involved and patient immunologic status. Treatment options for CL lesions may include topical treatments, peri-lesional injection and systemic therapy, according to recommended protocols for CL Treatment (MoH 2010).

Statistical analysis

Descriptive statistical analysis was performed to assess variables and trends (e.g. mean numbers, medians, standard deviation and proportions). The Chi-square test was used to determine the associations between the various potential risk factors such as age, sex, year variation and comparison of the occurrence frequencies and distribution of lesions. All data were analysed using Excel and SPSS software (version 17), with a p value < 0.05 was considered as statistically significant.

Results

In the three-year period follow up 82 cases (50.9 %) were confirmed positive. Of the 82 patients, CL cases due to Leishmania tropica were largely predominant compared to those caused by Leishmania major with respective proportions of 89 % (73 cases) and 11 % (9 cases) and the observed difference was significant (p < 0.001).

The distribution of the investigated patients by environment of residence (rural versus urban), gender and age is presented in Table 1. Among the 82 patients who had CL 63.4 % (52 cases) hailed from urban environment while 36.6 % (30 cases) were residents of rural areas. The observed difference was statistically significant (p < 0.05).

Table 1.

Frequency of cutaneous leishmaniasis in confirmed patients by gender, age and area of residence

	Gender
	Male		Female		Total
	Number	%	Number	%	Number	%
Age group (years)
0–7	16	19.5	18	21.9	34	41.4
8–15	6	7.3	10	12.2	16	19.5
18–49	6	7.3	13	15.8	19	23.2
50–80	3	3.65	10	12.2	13	15.8
Residence
Rural	11	13.4	19	23.2	30	36.6
Urban	20	24.4	32	39.0	52	63.4
Total	31	37.8	51	62.2	82	100.0

With respect to gender factor, the proportion of affected females was statistically significant as compared to males with respective levels of 62.2 % (51 cases) and 37.8 % (31 cases), and a male to female infection ratio of 0.61:1 (p < 0.5). For both genders, children (≤ 15 years) were significantly more likely to be infected than adults (≥ 18 years) (p < 0.05) (Table 1). For patients’ age, the youngest patient was 8 months of age and the oldest was 80 years, with a mean age of 20.1 years. The distribution of affected patients by age groups revealed that children were significantly more infected than adults with respective proportions of 61 % (50 cases) and 39 % (32 cases) (p < 0.001). The highest proportion of CL cases (41.5 %) were between 8 months and 7 years of age. For adults, the age group 18–49 years was the most affected accounting for 23.2 % (19 cases). For both children and adults, significantly, more females had CL than males (p < 0.05).

The number, location sites and distribution of lesions were investigated. A total of 165 lesions were accounted in the CL affected 82 patients. The number of lesions per patient ranged from 1 to 16 lesions with an average of 2.01. Most patients had a single lesion (58 patients; 70.7 %), whereas 17 cases (20.7 %) had 2–4 lesions, 6.1 % (5 patients) had 5–7 lesions (Fig. 1), while only 2 cases (2.4 %) with more than 7 lesions were recorded. The single to multiple lesions ratio was 2.4:1. The observed differences were statistically significant (p < 0.001).

Fig. 1.

Distribution of CL affected patients by lesions’ number

Most of the diagnosed patients had lesions located in face than limbs with respective proportions of 62.2 % (51 cases) and 26.8 % (22 cases) corresponding to a face to limbs ratio of 2.3:1, and the recorded difference was statistically significant (p < 0.001). Limb lesions were seen either in upper and lower extremities or in both with respective levels of 15.9 %, 8.5 % and 2.4 %; whereas five patients (6.1 %) had combined locations with lesions in face, upper and/or lower limbs simultaneously. Only a single case of trunk and back site was reported (1.2 %), and none of the patients had mucosal lesions (Table 2). The distribution of the 165 detected lesions by site of occurrence revealed that most of them were located in face (47.3 %) and limbs (47.9 %) (p > 0.05); and only 4.8 % (8 lesions) were found in locations other than face and limbs. By age group, 75 lesions (45.5 %) were found in children with a mean number of 1.5 per case versus 90 lesions (54.5 %) detected in adults with a mean of 2.8 per case. The average number of lesions was found to be significantly higher in adults as compared to children (p < 0.01).

Table 2.

The anatomic locations of cutaneous leishmaniasis lesions in the affected patients by gender and age group

Site	Gender				Age group				Total
	Females		Males		Children		Adults
	Cases	%	Cases	%	Cases	%	Cases	%	Cases	%
Face	31	37.8	20	24.4	41	50.0	10	12.2	51	62.2
Limbs	15	18.3	7	8.5	5	6.1	17	20.7	22	26.8
Back	0	0.0	1	1.2	0	0.0	1	1.2	1	1.2
Face and limbs	3	3.7	2	2.4	2	2.4	3	3.7	5	6.1
Face-limbs-trunk	1	1.2	0	0.0	1	1.2	0	0.0	1	1.2
Other	1	1.2	1	1.2	1	1.2	1	1.2	2	2.4
Total	51	62.2	31	37.8	50	61.0	32	39.0	82	100

Of the 82 patients with CL, 41 children (50 %) had lesions in face alone versus 10 adults (12.2 %), whereas limb lesions were detected in 17 adults (20.7 %) against 5 children (6.1 %). Combined lesions in face and limbs were observed with respective proportions of 2.4 % (2 cases) and 3.7 % (3 cases) in children and adults (Table 2). This finding reveals that face lesions were significantly more frequent in children than adults, while limb lesions were more frequently observed in adults. In fact, of a total of 78 face lesions, 54 (69.23 %) were in children while only 24 lesions (30.8 %) were in adults. Conversely, of 103 limb lesions, only 16 (15.5 %) lesions were detected in children versus 87(84.5 %) for adults, and the respective face to limb lesions ratios in children and adults were 3.4:1 and 0.4:1 (p < 0.01) (Fig. 2).

Fig. 2.

Distribution of the number of cutaneous leishmaniasis lesions by gender and age group

For the distribution of lesions by gender, females with lesions in face accounted for 37.8 % of the investigated group, versus 18.3 % for those with limb lesions, while respective rates of 24.4 % and 8.5 % were recorded for males. For both groups, combined lesions in face and limbs and/or other site were scarcely observed (Table 2). For the number of lesions by gender, in total 116 lesions (70.3 %) were accounted in females with an average of 2.3 lesions per case, versus 49 lesions (29.7 %) and an average of 1.6 lesions for males. The observed difference by gender was statistically significant (p < 0.01). Moreover, females had a total of 54 lesions (32.7 %) in face and 57 lesions (34.5 %) in limbs, while significantly lower numbers were detected in males with respective levels of 24 lesions (14.5 %) and 22 lesions (13.3 %) (p < 0.01).

Concerning the temporal variation in patients’ admission, most of the patients were referred to the diagnosis unit of the Laboratory during January-March with a level of 41.5 % (34 cases). Similar proportions were recorded in July-September and October-December with respective levels of 25.6 % and 23.2 %, while the lowest consultation rate occurred during April-June reaching 9.8 %. On the basis of the patients’ records, the delay between the lesion appearance and seeking for diagnostic date ranged from 1 to 23 months with a mean of 5.4 ± 4.4 months. Fore for 35.4 % and 39.6 % of affected patients the lesions appearance occurred in July-September and October-December, respectively.

Discussion

Cutaneous leishmaniasis is an important public health problem in developing countries including Morocco where a prevention and control program was implemented. In most cities no active local transmission of CL has been notified. However, CL foci may exist in the surrounding areas and peri-urban zones. In the present study, all of the recorded CL cases consist in individuals who hailed from endemic zones, or habitants of the urban localities with the history of travel showing that they had at least one travel to other provinces with CL foci. CL causal agent in Morocco, is represented by three species of Leishmania: L. major, L. tropica, and L. infantum (Zougaghi et al. 2011; MoH 2010; WHO 2010). In the current study Leishmania tropica cases were largely predominant (89 %) compared to Leishmania major (11 %). This finding is consistent with previous studies reports indicating that Leishmania tropica is the main etiologic agent of CL in the area, being responsible of up to 90 % of CL cases (Zougaghi et al. 2011; MoH 2016; Zouirech et al. 2018).

The highest proportion of CL cases originated from urban zones (63.4 %) as compared to those residing in rural areas with an urban to rural infection ratio of 1.73:1. This may be due to the fact that people have travelled from urban areas to the endemic localities, and/or people in rural areas were infected during childhood and would have acquired immunity (Nilforoushzadeh et al. 2014). The reports indicated that all the affected patients among town-dwellers were imported cases who had a history of travel to endemic zones, in line with findings of several studies (Aara et al. 2013; Nilforoushzadeh et al. 2014; Soltani et al. 2019).

Most of patients were admitted in the diagnosis unit of the laboratory during January-March with a level of 41.5 % (34 cases) and the delay between the lesion appearance and the diagnostic date ranged from 1 to 23 months with a mean of 5.4 months. Harms et al. (2003) reported a median delay of 4 months, with a range of 3 weeks to 2 years, while other reports found a median delay of 5 months with a range of 5 weeks to 6 months (Arce et al. 2013). Similarly, in Syria, Abazid et al. (2012) found that delay between first noticing CL lesion and treatment seeking ranged from immediately to 1 year (mean: 2.4 months; median: 2 months). CL lesions are usually painless resulting in a delay to seek treatment. Delay may also be related to inadequate information about the disease, or lack of awareness, with negative perceptions and attitude, towards treatment access and options (Nassiri et al. 2016; Fikre et al. 2017).

In most of cases lesions appeared in July-September and October-December. The time of infection occurrence is related to incubation period of parasite in patients. Previous reports revealed a seasonal pattern in the occurrence of CL infection with higher incidence in summer and autumn, suggesting the existence of correlations between climatic variables, vector’s activity and human contaminations (Gandacu et al. 2014; Nikouee et al. 2017; Simon et al., 2017). Zouirech et al. (2018) found that the monthly evolution of CL cases in Azilal (Morocco) correlated perfectly with that of sandfly populations, taking into account a gap of 5–6 month latency period between infection and the onset of symptoms.

For the gender factor, significantly more females than males were affected with a male to female infection ratio of 0.61:1. These findings corroborate those of studies carried out in other Moroccan areas reporting a male to female infection ratio of 0.7:1 (Bennis et al. 2015; El Alem et al. 2016; El Hamouchi et al. 2019), in line with reports from other countries (Yemisen et al. 2008; Gandacu et al. 2014). The higher occurrence of CL among females might have cultural and social background. In many areas women may be more exposed to the disease as they have to work outdoor where sandflies are more common. Moreover females were reported to seek more for consultation than males (Adawi and Hilmi 2012; Bennis et al. 2015). However, another study in the same region found that CL prevalence was slightly higher in females (sex ratio: 0.9) but the observed difference was not significant (Zouirech et al. 2018), in accordance with the findings of Nawaz et al. (2020).

With respect to age factor, the current study revealed that CL affects all ages and children (≤ 15 years) were significantly more affected than adults (≥ 18 years). Within children and adults, the highest frequencies were recorded for the age groups ≤ 7 years and 18–49 years, respectively. For both children and adults, females were significantly more affected than males. Similar reports from Iran and Morocco found children aged less than 15 years as highest risk group, with rates up to 90 % (Zougaghi et al. 2011; Rostami et al. 2013; Zouirech et al. 2018). However, other studies indicated that most of CL patients were below 5 years of age (Layegh et al. 2013; Nikouee et al. 2017). The reason of high CL infections rate in children may be that they spend most of their time outdoors; moreover, their clothing makes them susceptible to sandflies’ bites. Low CL rates of elderly patients may be a result of being infected during early ages, acquiring long-term immunity. Furthermore, adults may be less likely to seek treatment for CL lesions because disfiguring scars may not be as important for them as for youngsters (Akçali et al. 2007; Aara et al. 2013; Rostami et al. 2013).

Based on the study results, lesions number ranged from 1 to 16 lesions per case with an average of 2.1. Single lesion cases were significantly predominant as compared to multiple lesions cases. Face and limbs were the most commonly affected, with highly significant involvement of face location (cheeks, nose, forehead and chin) and uncommon location such as back and trunk were very scarce. These findings corroborate those of Gitari et al. (2018) showing that 92 % of CL cases had facial lesions while 8 % had lesions on ears and extremities.

Combined locations were rarely observed. Comparative results were reported in previous studies indicating that single lesions and face location were predominant. In general, face and limbs are uncovered regions of the body, therefore mostly exposed parts providing larger surface area for sandfly, and more prone to clinical manifestation of CL infection (Akçali et al. 2007; Aara et al. 2013). Previously reported studies found that the number of lesions was variable with a predominance of single lesion cases and face involvement, with reported ranges varying from 1 to 200 lesions (Simon et al. 2017; Bousslimi et al. 2010). In contrast, the study by El Hamouchi et al. (2019) in South-Cental Morocco found 72.8 % of patients having multiple lesions ( ≥ = 2), with an average of 5.16; and most of lesions were located in the upper limbs. According to Dedet et al. (2003), the number of lesions per patient could probably be a result of the physiological characteristics of the vector with respect to feeding behaviour. Multiple lesions might be seen as sandflies may have a discontinuous blood-sucking habit, and may sting several times at every attack, causing the development of several lesions on the skin (WHO 2010).

The distribution of lesions by gender revealed that significantly, the majority of lesions occurred in females (70.3 %), with a significant difference in mean lesions number between the two genders. In addition, females were more likely to have lesions in face, conversely to males. This finding may be a direct reflection of the cultural habits related to clothing as limbs are covered parts for females; supported by previous reports indicating that distribution of lesions on the body depends on the form of dress (Dedet et al. 2003; Nawaratna et al. 2007). By way of example, it was reported that the occurrence of facial lesions is lower in countries where women use to cover faces (Adawi and Hilmi 2012). By age group, for children, the risk of having a CL lesion in face was significantly higher than in limbs, whereas in adults, limbs lesions were significantly more frequently observed than in children. This finding is in agreement with previous surveys reporting significant differences in the clinical features of CL lesions between children and adults, with face location as the most involved body parts in children while lesions on upper and lower limbs affected older patients (Delgado et al. 2008; Layegh et al. 2013; Nikouee et al. 2017). However, other investigations detected no association between lesion type and patients’ sex or age (El Hamouchi et al. 2019).

Conclusions

Cutaneous leishmaniasis is considered an endemic disease in Morocco and a prevention and control program of the disease is implemented which includes a combination of intervention strategies concerning the parasite, sand-fly vector and an animal reservoir host. The current study revealed that the pattern and clinical epidemiology of disease may be affected by many factors (e.g. socio-geographic status, gender, age, environment etc.) which have to be considered in prevention and control programs in endemic areas. More studies are required to assess the disease epidemiology in the country and more effort should be made for better control of the infection and reduce its prevalence as well as preventing its spread to other regions.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.