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. 2020 Dec 23;148(5):591–597. doi: 10.1017/S0031182020002413

Epidemiological and pathological characteristics of Cutaneous Leishmaniasis from Baluchistan Province of Pakistan

Aisha Khan 1, Rawan Sajid 1, Shaista Gul 2, Ashiq Hussain 3, Mohammad Tahir Zehri 3, Shumaila Naz 4, Sami Simsek 5, Shahid Waseem 6, Muhammad Sohail Afzal 7, Syed Kamran Ul Hassan Naqvi 1, Muhammad Qasim 8, Haroon Ahmed 1,✉
PMCID: PMC10950375  PMID: 33353570

Abstract

Cutaneous Leishmaniasis (CL) is considered a neglected tropical disease which in Pakistan can now be considered as a growing public health problem. The exact figures on the magnitude of the disease are lacking both at the national and regional level and only a few health centres are available for diagnosis of CL. The present study was designed to identify the epidemiology of CL infection from August 2018 to December 2019 and to assess clinical aspects of CL in Baluchistan Province of Pakistan. A total of 4072 clinically suspected CL cases were analysed statistically. The highest number of CL cases were reported in May, followed by April, January and then July, February and June and the lowest number of cases were observed in March and November. The highest prevalence rate was found in males where 38% of reported cases were aged 0–9 years. The majority (24.4%) of lesions were found on the hands followed by the face in which cheeks, ears and nose were the effected organs. About 50% of the participants have single lesion while 14% of the participants had two and nearly 3% of the participants have six lesions. The atypical clinical presentations were observed in Baluchistan and common unusual presentations were lupus erythematosus. The study findings suggest that more epidemiological studies and health education campaigns are needed for the population awareness regarding CL in Baluchistan. It is recommended that risk factors should be evaluated to establish control and management strategies to prevent disease at the individual and community level.

Key words: Clinical features, Cutaneous Leishmaniasis, Leishmania tropica, Pakistan

Introduction

Leishmaniasis is a group of parasitic infections caused by flagellate protozoans of genus Leishmania that are transmitted through the bite of infected female phlebotomine sand fly (Elmahallawy et al., 2014). More than 20 species of Leishmania are capable of causing the disease (Georgiadou et al., 2015; WHO, 2020) with clinical manifestations including Cutaneous Leishmaniasis (CL), Mucocutaneous Leishmaniasis, Diffuse Cutaneous Leishmaniasis and Visceral Leishmaniasis (also known as kala-azar) (Desjeux, 2004; WHO, 2010; Ghatee et al., 2020). Leishmaniasis has been reported in 98 countries affecting about 350 million people worldwide, making it one of the seven most common as well important neglected tropical diseases (Torres-Guerrero et al., 2017; de Souza et al., 2018). CL being the most common and widely distributed variety claims between 0.7 and 1.2 million cases reported worldwide annually (Alvar et al., 2012). About 95% of the incidents are reported from three epidemiological regions i.e. South America, the Mediterranean Basin and spread throughout the Middle East to Central Asia (Torres-Guerrero et al., 2017). More than 85% of new CL cases appeared in Afghanistan, Algeria, Bolivia, Brazil, Colombia, Iran, Iraq, Pakistan, the Syrian Arab Republic and Tunisia during 2018 (Zijlstra, 2016; WHO, 2020).

CL is highly endemic in Pakistan and spread extensively due to massive out-migration from endemic to non-endemic areas and vice versa (Kassi et al., 2008). CL affects people of low social-economic status and is associated with undernutrition, population displacement, lack of shelter and a weak immune system (WHO, 2010). The burden of disease in Pakistan has been reported to be surpassed by 400 000 cases reported in 2016 that makes about 10% of CL cases globally (Blum et al., 2004) with both anthroponotic (ACL) and zoonotic (ZCL) forms of CL (Alvar et al., 2012). ACL occasionally occurring due to Leishmania tropica, is widespread and most grave public health problem in Pakistan (Hussain et al., 2018). The urban areas of Punjab and Sindh provinces are of high CL endemicity (Iftikhar et al., 2003; Kakarsulemankhel, 2004; Katakura, 2009), the Afghan refugee camps in Northwest Frontier Province, now called Khyber Pakhtunkhwa (Simon Brooker et al., 2004) and the surrounding tribal belt of Federally Administrated Tribal Areas (FATA) (Khan et al., 2016; Qureshi et al., 2016; Irum et al., 2021). CL is also widely distributed in sub-urban localities of Baluchistan province (Bhutto et al., 2009; Ejaz et al., 2008; Hussain et al., 2018), Gilgit Baltistan (Ayub et al., 2003), Azad Jammu and Kashmir (Mughal, 2014; Shaheen et al., 2020). The ZCL type, caused by Leishmania major, has its reservoir populations in feral animals predominantly gerbils such as Rhombomys opimus in rural and sub-urban localities of Punjab, Baluchistan and Sindh provinces (Bhutto et al., 2003; Afghan et al., 2011).

Leishmaniasis has diverse clinical manifestations and may appear similar to a large variety of other conditions (Afghan et al., 2011; Antinori et al., 2012). CL is identified by the appearance of one or more well-defined ulcerous lesions (Bacellar et al., 2002; Carvalho et al., 2008), usually found on uncovered areas of the body i.e. forearms, legs and face where sand-fly bites occur most often (Salman et al., 1999; Chaudhary et al., 2008). After 4–12 weeks of a bite, a small erythematous papule appears at the bite site which gives off a seropurulent discharge, which later on dries up and then a ‘volcanic’ nodulo-ulcer appear which is classical for CL (Iddawela et al., 2018). These lesions can develop into other morphological forms such as lupoid, keloidal, psoriasiform, erysipeloid, verrucous, zosteriform, tumorous, eczematoid and acneform (Bari and Raza, 2010; Shamsuddin et al., 2017; Iddawela et al., 2018). Routinely used diagnostic methods are direct clinical observations and micro-scopical examination of lesion aspiration samples. Alternative diagnostic options include histopathology and polymerase chain reaction (PCR) but due to the low frequency of parasites, PCR may give false-negative results. The practice of using PCR as a diagnostic tool is also uncommon worldwide and not easily applied to clinical health settings (Weirather et al., 2011; Tsukayama et al., 2013; de Paiva-Cavalcanti et al., 2015). The sensitivity of enzyme-linked immunosorbent assay is 50% in the case of co-infection due to less circulating antibodies in blood (Sinha et al., 2005; de Souza et al., 2011; Abeijon et al., 2012). The treatment relies on chemotherapy and the first line of treatment for all types of leishmaniasis are the medications containing pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate. But unfortunately, the treatment failure has been reported for this class of drug because the parasite has shown resistance to this class of drug and its authenticity and clinical value has been challenged (Croft et al., 2006; Llanos-Cuentas et al., 2008).

CL is one of the neglected diseases in Pakistan and exact figures on the magnitude of the disease are lacking both at national and regional levels and only a few health centres are available for diagnosis of CL. The limitation/absence in the diagnosis and treatment increase the need for an epidemiological survey of the disease in the country (Afghan et al., 2011). Despite the disease endemicity, the information regarding the epidemiology of CL in Pakistan is incomplete (Khan et al., 2016). Baluchistan is one of the provinces located in the southwest of Pakistan and its geographical distribution has made it a camping ground for sand-fly due to disturbances of the habitats and deforestation (Firdous et al., 2009). Because of the major teaching and tertiary care hospitals located in Quetta, most of CL patients have been reported in Quetta (Kassi and Kasi, 2005). This may be due to mass migration from adjoining areas of Afghanistan and the absence of field epidemiological surveys (Shakila et al., 2006).

The present study was designed with an aim to identify epidemiology and to assess clinical aspects of CL in Baluchistan Province of Pakistan.

Materials and methods

Study area

The study was carried out in different districts of Baluchistan covering the surface area of 347 190 km2 and constituting 44% of Pakistan's total landmass located between 30.12N and 67.01E. It has borders to Afghanistan from the north and north-west and to Iran from the south-west and has a population of around 10 million inhabitants predominantly (76%) rural. Physically, the topography is diverse and divided into four distinct zones: upper highlands, lower highlands, plains and deserts altitude ranging from 600 m from the valley floor to 3700 m above the mean sea levels. The climate varied from semi-arid summers to semi-arid winter with temperature as high as 50°C and as low as 1°C where the annual average temperature is about 19°C and average annual rainfall for Quetta is 44 millimetres (Kakarsulemankhel, 2004) (Table 1).

Table 1.

Description of the study sites

Study site Coordinates Altitude (m) Total HUs Climate
Annual average rainfall (mm) Annual Average humidity (%) Temperature (°C)
T min T max T Average
Chagai 28.98° N, 62.45° E 850 29 746 47 34 6 37 22
Quetta 30.17° N, 66.97° E 1679 87 091 44 34 1 35 19
Sibi 29.55° N, 67.88° E 130 25 700 21 25 12 45 31
Ziarat 30.39° N, 67.71° E 2543 4503 71 34 1 35 19
Kharan 28.58° N, 65.41° E 692 35 630 27 25 10 43 26
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masl, meters above sea level; Total HUs, Total housing units; T min, minimum temperature; T max, maximum temperature.

Epidemiological investigation

Due to the lack of ground-level research and treatment limitations, the epidemiological status of CL in the study area was not known. Based on university hospital records between August 2018 and December 2019, 4072 cases of CL were reported from the Baluchistan.

Ethics statement

The study was approved by the IRB & Ethics Committee of National University of Medical Sciences (NUMS), Rawalpindi, Pakistan under reference number 06/R&D/NUMS.

Sample collection and microscopy

A total of 4072 clinically suspected cases of CL visited the Department of Microbiology, Bolan Medical College, Quetta from different areas of Baluchistan. The selected patients were photographed and specific medical explanations for these lesions were obtained from the dermatologist. The samples were collected from the patients after both written and verbal informed consent was obtained. The lesion sample from CL patients was obtained using needle aspiration method. The overlying dry scab was rubbed off with an alcohol gauze pad and approximately 0.1–0.2 mL sterile saline solution injected into the lesion and aspiration fluid was obtained. The slides of smears from each patient were fixed with absolute methyl alcohol and stained with Giemsa stain for parasitological investigation. The slides were examined under the light microscope at 100× magnification for the presence of Leishmania spp. amastigotes (Kassi et al., 2004).

Statistical analysis

The CL data were documented into Microsoft Excel and analysed using SPSS (SPSS Inc., Chicago, Illinois, USA) version 26.0. Prevalence of CL in different age groups and gender was calculated. The Chi-square test (χ2) and frequencies of demographic characteristic were used for categorical data. Monthly distribution of CL cases for the years of 2018 and 2019 was calculated in form of percentage. Moreover, the prevalence of CL by age groups with 95% confidence limits were analysed. The statistical significance was set for all statistical tests at P value <0.05 (two-sided).

Results

In the present study, a total of 4072 individuals comprising both males and females were studied from the period of August 2018 to December 2019 and analysed with respect to age, gender and body parts affected by CL.

Clinical features of CL patients

Of the 4072 CL cases, 50.6% (2062/4072) were positive by direct microscopy. The effect of CL in a different age group is depicted in Fig. 1a–f. The lesions were more prevalent among young individuals as compared to older adults. Exposed parts of the body (hand, cheeks and nose) were the main affected areas. Different clinical forms were observed based on clinical morphology of the CL patients' lesion. These lesions diverge from mild to moderate papulonodular form which is <1 cm in diameter to more severe and complex forms. One of the forms was dry type papulonodular lesions with erythematous smooth and superficial papule on the face and size varied from 0.5 to 1 cm (Fig. 1a). Other form presented the clinically infiltrated ulceration which was ulcerated lesion and present the dry type (Fig. 1b). Among CL patients, lupus erythematosus was most common with unusual presentations ranging from scaly and crusted plaque to enlarged erythematous and infiltrated plaque on the elbow wrapped with white and dry scales mimicking psoriasis (Fig. 1c, d and e). A psoriasiform lesion was also observed on the nose of a CL patient which was characterized by an infiltrated plaque (Fig. 1f).

Fig. 1.

Fig. 1.

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(a–f) Atypical forms of Cutaneous Leishmaniasis (CL) lesions. (a) Papulonodular lesions, dry type; (b) Ulcerated lesion, dry type; (c) Discoid lupus erythematosus, dry type; (d) Psoriasiform lesion, dry type; (e) Mycetomatous, dry type; (f) Erysipeloid, dry type.

Age and gender-wise distribution of CL

In the present study, the total number of people infected with CL from August to December 2018 was 969. Of the total, 55.3% (536/969) of them were males while 44.7% (433/969) were females. The highest percentage (38%, 368/969) of CL patients was observed aged between 0 and9 years followed by age group 10–19 years which included 29.6% (287/969) of the cases. However, the lowest proportion (6.9%, 67/969) was observed at 30–39 years old (Table 2).

Table 2.

Distribution and prevalence of CL in different age groups and gender for the years 2018 and 2019

Year Age n (%) Male Female
n Positive (%) P value n Positive (%) P value
2018 0–9 368 38 214 97 (45.3) 0.258 154 72 (46.8) 0.481
10–19 287 29.6 164 61 (37.2) 123 57 (46.3)
20–29 122 12.6 72 25 (34.7) 50 20 (40.0)
30–39 67 6.9 24 8 (33.3) 43 17 (39.5)
40+ 125 12.9 62 21 (33.9) 63 22 (34.9)
Total 969 536 212 (39.6) 433 188 (43.4)
2019 0–9 1245 40.1 695 399 (57.4) 0.035 550 313 (56.9) 0.081
10–19 895 28.8 510 270 (52.9) 385 205 (53.2)
20–29 406 13.1 255 130 (51.0) 151 85 (56.3)
30–39 202 6.5 102 48 (47.1) 100 45 (45.0)
40+ 355 11.4 173 80 (46.2) 182 87 (47.8)
Total 3103 1735 927 (53.4) 1368 735 (53.7)
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The total number of people infected with CL during the year 2019 was 3103 with the overall CL infection rate during the year 2019 was higher in males (55.9%, 1735/3103) than females (44.1%, 1368/3103). The highest percentage (40.1%, 1245/3103) was observed at 0–9 years old. Only 28.8% (895/3103) of CL patients were observed in 10–19 years old participants followed by 13.1% (406/3103) in 20–29 years old, 6.5% (202/3103) in 30–39 and 11.4% (355/3103) in 40+ years old (Table 2). Based on different age groups, the frequency of males to females CL patients was different. Males (22.4%), (16.44%) and (8.22%) were affected more than females (17.72%), (12.41%) and (4.87%) at the age of 0–9, 10–19 and 20–29 years, respectively. On the other hand, the disease was higher in females (3.22%) and (5.87%) than males (0.29%) and (0.58%) at the age of 30–39 and 40+ years as represented in Fig. 2.

Fig. 2.

Fig. 2.

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Prevalence of CL according to gender and age Left: Prevalence of CL by age groups with 95% confidence limits for the year 2019. Right: Prevalence of CL by age groups with 95% confidence limits for the year 2018.

Year wise prevalence of CL in different age groups and gender

The findings of the present study revealed that of the total population tested from the period of August–December 2018, 55.3% (536/969) were males and 44.7% (433/969) were females. In total, 41.3% (400/969) of participants were tested positive for lesion aspiration test. Out of which 39.6% (212/536) of males and 43.4% (188/433) of females were positive for lesion aspiration test. The highest percentage (45.3% and 46.8%) in positive lesion aspiration test was found among the participants aged between 0 and 9 years in both males and females, respectively (Table 2). It was observed that the lesion aspiration test was not significantly different by age or gender of participants studied.

In the year 2019, 55.3% (1735/3103) of participants were males and 44.7% (1368/3103) were females. A total of 53% of participants were tested positive for lesion aspiration test and among these 53.4% (927/1735) were males and 53.7% (735/1368) were females. The highest frequency (57%) of lesion aspiration test was tested positive between age 0 and 9 years regardless of age and gender and lowest frequency (47% and 45%) was observed of the participants aged between 30 and 39 years for both males and females, respectively (Table 2).

Site-specific distribution of lesion

The majority 24.4% (757/3103) of lesions were found on the hands followed by face in which cheeks, ears and nose were most affected. The number of lesions per person ranged from 1 to 6 (Fig. 3). Approximately 50% of the participants had single lesion while 14% of the participants had two and nearly 3% of the participants have six lesions during the study period of 2018 and 2019. Most of the lesions were erythematosus with unusual presentations ranging from scaly and crusted plaque to enlarged erythematous and infiltrated plaque.

Fig. 3.

Fig. 3.

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Number and percentageof male and female patients with active lesions in 2018 and 2019.

Month-wise distribution of CL

The findings of the study revealed that highest number of CL cases (23.6%, 229/969) was found in December followed by October (22%, 213/969) and August (21.9%, 212/969) during the year 2018. During the year 2019, the highest number of CL cases were observed in May (16.6%, 514/3103) followed by April (13.5%, 418/3103), January (12.5%, 388/3103) and then July (9.6%, 298/3103), February (8.7%, 271/3103) and June (8.5%, 264/3103). The lowest number of CL cases were observed in March (2.7%, 85/3103) and November (3.7%, 116/3103) (Table 3).

Table 3.

Monthly distribution of CL cases for the years of 2018 and 2019

Year Month n %
2018 August 212 21.9
September 128 13.2
October 213 22.0
November 187 19.3
December 229 23.6
Total 969
2019 January 388 12.5
February 271 8.7
March 85 2.7
April 418 13.5
May 514 16.6
June 264 8.5
July 298 9.6
August 156 5
September 163 5.3
October 216 7
November 116 3.7
December 214 6.9
Total 3103
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Discussion

CL is one of the prevalent vector-borne diseases in Pakistan which affects people with lower income and is linked to poor housing conditions, migration, inadequate nutrition, vector control failures and immuno-compromised conditions like HIV/AIDS (Alvar et al., 2006). CL has been reported from all over Pakistan specially from native surrounding areas of FATA and KPK (Khan et al., 2016; Qureshi et al., 2016; Khan et al., 2019), urban-rural areas of Sindh and Punjab (Iftikhar et al., 2003), Azad Jammu and Kashmir (Mughal, 2014; Shaheen et al., 2020) and sub-urban localities of Baluchistan province (Bhutto et al., 2003; Ejaz et al., 2008; Rahman and Rehman, 2017). It is presumed that uninfected regions with the borders adjacent to endemic areas are at risk and colonization of a large number of populations in areas where sand-fly is endemic is one of the reasons of CL outbreaks (Simon Brooker et al., 2004).

The current study has been conducted in Baluchistan province which is a high-altitude region and borders to Afghanistan and Iran where CL is endemic (Ghatee et al., 2020). The studied area has the highest CL prevalence rate where dominant specie is L. tropica and in addition about 1500 cases of CL were reported in Afghan refugee camps in Pakistan in 2002 (Kakarsulemankhel, 2004). In another study Rahman and Rehman (2017) also reported a significantly high level of CL among Afghans compared to the local Pakistani population (32.5% vs 20.3%). However, the prevalence of CL due to L. major has also been reported from the Southern part of Baluchistan (Bhutto et al., 2009). Thus, the present study was designed for the aim of identifying the epidemiology and assessing the clinical aspects of CL in Baluchistan.

In the current study, CL infection is more prevalent in males (55%) as compared to females with similar findings reported by Shaheen et al. (2020) in Azad Jammu and Kashmir, by Galgamuwa et al. (2017) in Sri Lanka, by Aara et al. (2013) in India by Alavinia et al. (2009) and in Iran. It may be due to the reason that activities of the males are mostly out-door and have maximum chances of being bitten by sand fly while females are confined to indoor activities (Gadisa et al., 2015). The current study indicated that 38% of reported CL cases were in children aged 0–9 years followed by adults 10–19 years of age with a prevalence rate of 29% and is in concordance with other studies (Kakarsulemankhel, 2004; Aara et al., 2013; Qureshi et al., 2016; Yohannes et al., 2019; Shaheen et al., 2020). This might be due to a weak immune system and food deprivation of children (Zijlstra, 2016). In contrast to this, Aara et al. (2013) reported a higher prevalence of CL cases in 21–30 years age group whereas in our study lower cases of CL were found in 30–39 years old and 40+ as also reported by Nawaz et al. (2010). As lifelong immunity develops following infection with CL, it is understandable why infection is more common in young individuals.

In the present study, most CL cases appeared to have localized symptoms and most lesions were present on the exposed parts of the body particularly hands, nose, ears and cheeks. Similar results were observed in studies carried out in Ethiopia and Turkey where most of the lesions also appeared on the face (Bari, 2008; Uzun et al., 2018; Yohannes et al., 2019). For the locations of the lesions, it is of the opinion that it is difficult to cover up the face and is exposed for biting of sand flies at night-time which is a crucial time for the parasite spread (Aara et al., 2013). Correspondingly to the findings of Özbilgin et al. (2019), 77% lesion appeared on uncovered parts of the body. In the present findings, the common unusual presentations were lupus erythematosus followed by the papulonodular lesion, ulcerated lesion and less common psoriasiform lesion. In CL, atypical clinical presentations were progressively observed in Pakistan and it has been speculated that limitations of these atypical cases in certain geographical regions could be due to new strain of Leishmania parasite (Bari, 2008). In our study, approximately 50% of the CL cases had a single lesion, 14% had two lesions and remaining had three to six lesions. Our results were similar to the findings of Shaheen et al. (2020) who also reported the presence of the single lesion in 56% of the CL cases. Other studies conducted by Talari et al. (2006) and Qureshi et al. (2016) also showed the highest number of single lesions in CL cases. CL cases with two or more lesions on the body might be due to exposure to the sandflies for a long time.

Although CL cases were reported throughout the entire year, the highest number of cases were detected in May, followed by April, January and then July, February and June. The lowest number of cases was during March and November. Similar findings have been reported by Shaheen et al. (2020) that warm months are the peak season of CL in Pakistan. This could be due to the reason that sand flies are more active during the warm weather and consumes more blood for the development of their eggs. The current study has shown rising drift in the number of CL cases in Baluchistan and is a disease of public health importance. It is suggestive that different atypical clinical forms of CL depend on host immune response, number and site of parasites inoculated and host nutritional status (Bari, 2008). The study highlights the importance of early detection of erythematic skin lesion and proper management and treatment of CL to prevent a future outbreak of the disease especially in areas where leishmaniasis is endemic. The study also suggests that the use of insecticides, bed nets and new therapies for parasite can also help in the control of leishmaniasis.

Concluding remarks

In conclusion, the current findings suggest that more epidemiological studies are needed in Baluchistan and health education campaigns for population awareness regarding the CL. It is recommended to evaluate the risk factors and to establish control and management strategies to prevent disease at an individual and community level in Baluchistan. It is also recommended to conduct further reservoir studies to understand the vertical transmission of disease among various hosts.

Authors' contributions

HA designed and supervised the study. AK and RS collected the data, drafted and wrote the manuscript along with SN. AH, SG and MTZ contributed to data and sample collection. MQ did the statistical analysis. SS revised the manuscript along with MSA. All authors read and approved the final manuscript.

Financial support

This research was partially supported by Pakistan Science Foundation under Project No. PSF-TUBITAK/Med /P-NUMS(09).

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards. The study was approved by the IRB & Ethics Committee under project ‘A new and combined approach for the diagnosis of cutaneous leishmaniasis, a neglected vector-borne disease’ and letter reference number 06/R&D/NUMS.

Data

Raw data cannot be made publicly available due to ethical restrictions imposed by the Institutional Ethical Committee on human rights related to research. However, data can be provided on request.

Conflict of interest

The authors declare that they have no conflict of interest.

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