Waleed S. Al-Salem

Bio: Waleed S. Al-Salem is an academic researcher from Liverpool School of Tropical Medicine. The author has contributed to research in topics: Leishmaniasis & Cutaneous leishmaniasis. The author has an hindex of 9, co-authored 14 publications receiving 488 citations.

A new perspective on cutaneous leishmaniasis-Implications for global prevalence and burden of disease estimates.

Abstract: This article considers the current public health perspective on cutaneous leishmaniasis (CL) and its implications for incidence, prevalence, and global burden of disease calculations. CL is the most common form of leishmaniasis and one of a small number of infectious diseases increasing in incidence worldwide [1] due to conflict and environmental factors in the Middle East (“Old World”) and the Americas (“New World”)—regions where it is most prevalent. Recently, the disease has reached hyperendemic levels in the conflict zones of the Syrian Arab Republic, Iraq, and Afghanistan while simultaneously affecting refugees from those regions [2]. Nevertheless, CL is not seen as a priority for policymakers because it is not life limiting. This is evidenced by a lack of commitment in recent years to preventive campaigns and patient provision (limited diagnostic capacity, knowledge of treatment, drug availability) in a number of endemic countries.

Old World Cutaneous Leishmaniasis and Refugee Crises in the Middle East and North Africa.

Abstract: The Syrian refugee crisis has precipitated a catastrophic outbreak of Old World cutaneous leishmaniasis now affecting hundreds of thousands of people living in refugee camps or trapped in conflict zones. A similar situation may also be unfolding in eastern Libya and Yemen. Leishmaniasis has been endemic in Syria for over two centuries, with the first case ever reported being as early as 1745, when it was known as the “Aleppo boil” [1,2]. Old World cutaneous leishmaniasis (CL) is characterized most notably by disfiguring skin lesions, nodules, or papules, and in the Middle East and North Africa (MENA) region it is primarily caused either by Leishmania tropica (anthroponotic) or L. major (zoonotic), with some sporadic cases also caused by L. infantum (Box 1) [3–5]. In North Africa, a chronic form of CL also can be caused by L. killicki [6–7]. Box 1. Old World Cutaneous Leishmaniasis (CL) in the MENA Region Anthroponotic CL Major etiologic agent: Leishmania tropica [4,5,7] Major vector: Phlebotomus sergenti [4,5] Zoonotic CL Major etiologic agent: L. major [4,5,7] Minor etiologic agent: L. infantum [4,5] Vectors: Ph. papatasi for L. major; Ph. perfiliewi, Ph. perniciosus, Ph. longicuspis, and Ph. ariasi for L. infantum [5] Major animal reservoirs: Rodents (L. major) and dogs (L. infantum) [4,7] Although Old World CL is generally not fatal, clinical symptoms can lead to disfiguring scars that result in social stigmatization and psychological consequences. The World Health Organization (WHO) has estimated that around 2.4 million disability-adjusted life years (DALYs) are lost due to CL and visceral leishmaniasis (VL) globally [8]; however, the number of DALYs attributed to CL is still under evaluation. The 2013 Global Burden of Disease Study determined that CL causes only 41,700 DALYs [9], while other studies have found that these figures may represent profound underestimates [10,11]. Studies observing the impact of marring CL facial scars have found that the social stigmatization involved leads to anxiety, depression, and decreased quality of life for patients [12]. The scars can lead to a changed perception of self and can limit individuals’ abilities to participate in society, further decreasing their social, psychological, and economic well-being, as employment opportunities become scarce. Women, adolescents, and children are particularly susceptible to the social stigmatization of disfiguring scars [13]. The hardships caused by CL extend beyond physical symptoms and manifest most prominently in patients’ social, psychological, and economic well-being. Like many neglected tropical diseases (NTDs), CL not only occurs in settings of poverty but the disease also has the ability to perpetuate and reinforce poverty, catalyzing a positive feedback loop between disease and poverty [14]. For many of these reasons, the WHO classifies leishmaniasis as one of 17 NTDs [15], although the cutaneous form is often not prioritized in major global health initiatives, unlike the NTDs now targeted by integrated preventive chemotherapy [11].

A review of visceral leishmaniasis during the conflict in South Sudan and the consequences for East African countries.

Abstract: Visceral leishmaniasis (VL), caused predominantly by Leishmania donovani and transmitted by both Phlebotomus orientalis and Phlebotomus martini, is highly endemic in East Africa where approximately 30 thousands VL cases are reported annually. The largest numbers of cases are found in Sudan - where Phlebotomus orientalis proliferate in Acacia forests especially on Sudan’s eastern border with Ethiopia, followed by South Sudan, Ethiopia, Somalia, Kenya and Uganda. Long-standing civil war and unrest is a dominant determinant of VL in East African countries. Here we attempt to identify the correlation between VL epidemics and civil unrest. In this review, literature published between 1955 and 2016 have been gathered from MSF, UNICEF, OCHA, UNHCR, PubMed and Google Scholar to analyse the correlation between conflict and human suffering from VL, which is especially apparent in South Sudan. Waves of forced migration as a consequence of civil wars between 1983 and 2005 have resulted in massive and lethal epidemics in southern Sudan. Following a comprehensive peace agreement, but especially with increased allocation of resources for disease treatment and prevention in 2011, cases of VL declined reaching the lowest levels after South Sudan declared independence. However, in the latest epidemic that began in 2014 after the onset of a civil war in South Sudan, more than 1.5 million displaced refugees have migrated internally to states highly endemic for VL, while 800,000 have fled to neighboring countries. We find a strong relationship between civil unrest and VL epidemics which tend to occur among immunologically naive migrants entering VL-endemic areas and when Leishmania-infected individuals migrate to new areas and establish additional foci of disease. Further complicating factors in East Africa’s VL epidemics include severe lack of access to diagnosis and treatment, HIV/AIDS co-infection, food insecurity and malnutrition. Moreover, cases of post-kala-azar dermal leishmaniasis (PKDL) can serve as important reservoirs of anthroponotic Leishmania parasites.

Cutaneous Leishmaniasis and Conflict in Syria.

Abstract: To the Editor: War, infection, and disease have always made intimate bedfellows, with disease recrudescence characterizing most conflict zones (1). Recently, increasing violence from civil war and terrorist activity in the Middle East has caused the largest human displacement in decades. A neglected consequence of this tragedy has been the reemergence of a cutaneous leishmaniasis epidemic. Old World cutaneous leishmaniasis is one of the most prevalent insectborne diseases within the World Health Organization’s Eastern Mediterranean Region (2). Zoonotic cutaneous leishmaniasis is caused by the protozoan parasite Leishmania major, which is transmitted through the infectious bite of the female Phlebotomus papatasi sand fly; the animal reservoirs are the rodent genera Rhombomys, Psammomys, and Meriones. Anthroponotic cutaneous leishmaniasis is caused by L. tropica and transmitted between humans by the Ph. sergenti sand fly. Until 1960, cutaneous leishmaniasis prevalence in Syria was restricted to 2 areas to which it is endemic (Aleppo and Damascus); preconflict (c. 2010) incidence was 23,000 cases/year (3). However, in early 2013, an alarming increase to 41,000 cutaneous leishmaniasis cases was reported (3,4). The regions most affected are under Islamic State control; 6,500 cases occurred in Ar-Raqqah, Diyar Al-Zour, and Hasakah. Because these places are not historical hotspots of cutaneous leishmaniasis, this change might be attributed to the massive human displacement within Syria and the ecologic disruption of sand fly (Ph. papatasi) habitats. According to the United Nations High Commissioner for Refugees, >4.2 million Syrians have been displaced into neighboring countries; Turkey, Lebanon, and Jordan have accepted most of these refugees. As a result, cutaneous leishmaniasis has begun to emerge in areas where displaced Syrians and disease reservoirs coexist (5). According to the Lebanese Ministry of Health, during 2000–2012, only 6 cutaneous leishmaniasis cases were reported in Lebanon. However in 2013 alone, 1,033 new cases were reported, of which 96.6% occurred among the displaced Syrian refugee populations (5). Similarly in Turkey, nonendemic parasite strains L. major and L. donovani were introduced by incoming refugees (6). Many of the temporary refugee settlements are predisposed to increased risk because of malnutrition, poor housing, absence of clean water, and inadequate sanitation. The combination of favorable climate, abundant sand fly populations, displaced refugees, and deficient medical facilities and services has created an environment conducive to cutaneous leishmaniasis reemergence. For example, refugee settlements in Nizip in southern Turkey have reported several hundred cases (7). Using current datasets published in English and Arabic, we mapped cutaneous leishmaniasis prevalence within Syria and its neighboring countries (Figure). Our results demonstrate that cutaneous leishmaniasis prevalence coincides with the presence of refugee camps (Figure, panel A), which is plausible given the strong association between disease outbreaks and refugee settlements (8). The deterioration of Syrian health systems, including the cessation of countrywide vector control programs, has created an ideal environment for disease outbreaks (9). Likewise, the sand fly vectors are widely distributed throughout the Middle East; expansive Ph. papatasi and Ph. sergenti sand fly populations exist in Syria and Iraq (4). The presence of these vectors in regions of instability can create new cutaneous leishmaniasis foci, which might have debilitating, and often stigmatizing, consequences for residents and deployed military personnel (10). In addition, the distribution of Leishmania spp. overlaps with sand fly habitats (Figure, panel B) and disease reservoirs (W. Al-Salem, unpub. data). Consequently, the movement of large refugee populations into regions that are ill-equipped to manage imported cutaneous leishmaniasis has resulted in outbreaks in Turkey and Lebanon (5,6). Figure Cutaneous leishmaniasis prevalence within Syria and neighboring countries of the World Health Organization’s Eastern Mediterranean Region, 2013. A) Prevalence among refugee camps. Case data were taken from http://datadryad.org/resource/doi:10.5061/dryad.05f5h ... Our findings emphasize the importance of contemporaneous disease tracking to identify human populations at highest disease risk. To ameliorate the current cutaneous leishmaniasis crisis, particularly during the winter when cases start to appear, accurate disease monitoring and strategic training of persons based within refugee camps (medical staff, aid workers, volunteers, and military personnel) needs to be prioritized. Moreover, clinicians and other medical personnel residing in refugee-hosting countries must be suitably trained to diagnose cutaneous leishmaniasis because other local diseases (e.g., sarcoidosis and cutaneous tuberculosis) can have similar manifestations. Along with vector and rodent control, new cutaneous leishmaniasis outbreaks should be managed by prompt diagnosis and treatment, which are even more pertinent given that L. tropica–associated cutaneous leishmaniasis typically is resistant to several treatment regimens. In summary, the coexistence of sand fly populations and Leishmania spp. within refugee camps, together with the considerable influx of persons who already have cutaneous leishmaniasis, create a dangerous cocktail that can lead to an outbreak unprecedented in modern times.

Cutaneous leishmaniasis and co-morbid major depressive disorder: A systematic review with burden estimates

Abstract: BACKGROUND Major depressive disorder (MDD) associated with chronic neglected tropical diseases (NTDs) has been identified as a significant and overlooked contributor to overall disease burden. Cutaneous leishmaniasis (CL) is one of the most prevalent and stigmatising NTDs, with an incidence of around 1 million new cases of active CL infection annually. However, the characteristic residual scarring (inactive CL) following almost all cases of active CL has only recently been recognised as part of the CL disease spectrum due to its lasting psychosocial impact. METHODS AND FINDINGS We performed a multi-language systematic review of the psychosocial impact of active and inactive CL. We estimated inactive CL (iCL) prevalence for the first time using reported WHO active CL (aCL) incidence data that were adjusted for life expectancy and underreporting. We then quantified the disability (YLD) burden of co-morbid MDD in CL using MDD disability weights at three severity levels. Overall, we identified 29 studies of CL psychological impact from 5 WHO regions, representing 11 of the 50 highest burden countries for CL. We conservatively calculated the disability burden of co-morbid MDD in CL to be 1.9 million YLDs, which equaled the overall (DALY) disease burden (assuming no excess mortality in depressed CL patients). Thus, upon inclusion of co-morbid MDD alone in both active and inactive CL, the DALY burden was seven times higher than the latest 2016 Global Burden of Disease study estimates, which notably omitted both psychological impact and inactive CL. CONCLUSIONS Failure to include co-morbid MDD and the lasting sequelae of chronic NTDs, as exemplified by CL, leads to large underestimates of overall disease burden.

Cutaneous leishmaniasis: recent developments in diagnosis and management.

Abstract: This review focuses on recent developments in the diagnosis, treatment, management, and strategies for the prevention and control of cutaneous leishmaniasis (CL) caused by both Old and New World Leishmania species CL is caused by the vector-borne protozoan parasite Leishmania and is transmitted via infected female sandflies The disease is endemic in more than 98 countries and an estimated 350 million people are at risk The overall prevalence is 12 million cases and the annual incidence is 2–25 million The World Health Organization considers CL a severely neglected disease and a category 1 emerging and uncontrolled disease The management of CL differs from region to region and is primarily based on local experience-based evidence Most CL patients can be treated with topical treatments, but some Leishmania species can cause mucocutaneous involvement requiring a systemic therapeutic approach Moreover, Leishmania species can vary in their sensitivity to available therapeutic options This makes species determination critical for the choice of treatment and the clinical outcome of CL Identification of the infecting parasite used to be laborious, but now the Leishmania species can be identified relatively easy with new DNA techniques that enable a more rational therapy choice Current treatment guidelines for CL are based on poorly designed and reported trials There is a lack of evidence for potentially beneficial treatments, a desperate need for large well-conducted studies, and standardization of future trials Moreover, intensified research programs to improve vector control, diagnostics, and the therapeutic arsenal to contain further incidence and morbidity are needed

The history of leishmaniasis

Abstract: In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical distribution, initial evidence of the disease in ancient times, first accounts of the infection in the Middle Ages, and the discovery of Leishmania parasites as causative agents of leishmaniasis in modern times. With respect to the origin and dispersal of Leishmania parasites, the three currently debated hypotheses (Palaearctic, Neotropical and supercontinental origin, respectively) are presented. Ancient documents and paleoparasitological data indicate that leishmaniasis was already widespread in antiquity. Identification of Leishmania parasites as etiological agents and sand flies as the transmission vectors of leishmaniasis started at the beginning of the 20th century and the discovery of new Leishmania and sand fly species continued well into the 21st century. Lately, the Syrian civil war and refugee crises have shown that leishmaniasis epidemics can happen any time in conflict areas and neighbouring regions where the disease was previously endemic.