title: Epidemiological characterization and control of Old World cutaneous leishmaniasis in the Kingdom of Saudi Arabia
Creators: name: Al Salem, Waleed
Publisher: name: University of Liverpool Repository
Year: 2016

description: A better understanding of cutaneous leishmaniasis (CL) epidemiology will lead to improved intervention methods to combat CL outbreaks and prevent disease re-emergence. CL is endemic throughout the Kingdom of Saudi Arabia (KSA), and new disease control tools are needed. In this thesis, I studied various aspects essential to the design of a new CL control strategy, including parasite species identification, patient response to anti-leishmanial drug treatment, sandfly species identification, assessment of sandfly biting exposure and risk of disease transmission, implementation of an integrated control strategy, and development of a potential new CL diagnostic tool for use in CL endemic setting. It was found that Leishmania major (responsible for zoonotic CL) and Leishmania tropica (responsible for anthroponotic CL) are the main causative agents of CL in KSA, with over 75% of all human cases caused by the former. The current national CL treatment regimen consists of application of topical clotrimazole/fucidine cream followed by 1-2 courses of intralesional sodium stibogluconate; however, treatment efficacy is highly variable and the reasons for this are not well understood. As part of this PhD study, tests to determine the efficacy of this standard CL treatment regime in several endemic regions of KSA were performed. Most L. major patients responded favourably to drug treatment, although treatment success varied greatly depending on geographical location. In contrast, 60% of L. tropica cases proved completely unresponsive to the same treatment protocol. Furthermore, the development of secondary infections (SI) around or within the CL lesion significantly favoured the treatment response of L. major patients, but had no effect on L. tropica cases. These findings indicate that there is an urgent need to implement alternative CL treatment protocols based on these parameters, and also indicate a possible increase in drug-resistant parasites. In this epidemiological study, the potential correlation between the type of immunity generated after exposure to sandfly bites and disease outcome was monitored by measuring anti-SP32 antibody levels. Constant exposure of the local residents to sandflies may help prevent development of severe CL disease outcomes. Notably, comparison of the levels of anti-saliva antibodies of local individuals with migrant labour indicated that the latter had significantly higher levels of anti-saliva marker and also developed a more severe pathology. This implies that the corresponding governmental sectors need to assess all transmission risk areas, as well as greatly improve housing conditions to minimize the risk of non-local construction workers contracting CL. This is essential as CL drug treatment is costly and currently non-local workers comprise around one third of the KSA population. Additionally, a disease control strategy based on a combination of vector and reservoir control methods was designed to combat zoonotic CL outbreaks. Construction sites at Al-Ahsa, known to be highly endemic for zoonotic CL, were monitored by a vector control team between 2012 and 2014. The control strategy was applied following the outbreak using mechanical, reservoir and vector control methods. No CL cases were reported after the control team’s intervention. This case study suggests that implementation of a health impact assessment should be carried out, as well as a control strategy, in areas that share a similar CL ecology and environment in order to minimize incidence cases. As part of my PhD, I developed a potential new diagnostic tool by using an ELISA assay method to measure the levels of anti-α-galactosyl antibodies in human sera using synthetic neoglycoproteins (NGPs). The assay sensitivity was 96% for L. major (95% CI 94%–98%) and 91% for L. tropica (95% CI 86%–98%). In addition, the assay had higher sensitivity than microscopy analysis, which only detected 68% and 45% of L. major and L. tropica infections, respectively. Furthermore, improvement of the selectivity in recognizing different α-galactosylated NGPs suggests that this assay could potentially be developed into a rapid diagnostic test for use in resource-poor settings. Overall, this thesis should help set a basis for designing a national strategy for CL elimination in KSA.