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Visceral (VL) and cutaneous leishmaniasis (CL) are public health problems in the southwest of Saudi Arabia. The causative parasites, the vectors and the possible animal reservoirs In that area were all unknown before this study began. Because of the size of the area and to achieve the different aims of the study, a laboratory was established in Abha City which is in the centre of the study area, altitude approximately 2000 m. More than 50 isolates from CL lesions, 17 from VL patients and 700 human filter paper blood samples were collected. Eighty nine feral dogs were captured In Kala-azar endemic areas and examined for Leishmania. More than 8,000 sandflies collected from fixed stations were examined and more than 1600 Phlebotomus females were dissected. Forty four human isolates from human CL lesions were typed by the isoenzyme technique which showed that L. tropica is responsible for CL in both lowlands (altitude about 450 - 700 m) and the highlands (altitude about 2000 m). Only one zymodeme (LON-63) was found in the isolates from the lowlands but, in the highlands, four zymodemes (LON-10, 71, 72 and 73) were found. Zymodemes LON-10 and LON-71 were also Isolated from Phlebotomus sergenti, which has been shown clearly to be a major vector of L. tropica In the highlands. Animal susceptibility experiments showed. that neither BALB/c mice nor the golden hamster were susceptible to L. tropica. L. donovani sensu lato zymodeme LON-42 causes zoonotic Infantile Kala-azar in areas at altitudes of up to 700m. Neither the vector nor the reservoir host were identified in spite of an active search for them. The limited sero-epidemiological survey using the ELISA procedure revealed a high frequency of antibodies in children in Al Baha province, much greater than was previously believed to exist. Feral dogs In this area were found to be carriers of typical L. infantum, NOT the parasite found in man. The prevalence rate in dogs was high (19.3%). The dog's possible role in the epidemiology of Kala-azar in the study area is discussed. The entomological studies revealed that six species of Phlebotomus exist in the study area, with Ph. sergenti as the dominant species In the highlands and Ph. bergeroti in the lowlands. Some species such as Ph. arabicus are limited to high altitudes (about 2000 m), and others such as Ph. alexandri to low altitudes (up to 700 m). Ph. orientalis was found mainly in the highlands but a few samples were collected from the lowlands. Sergentomyi species were abundant in all areas. The seasonal distribution based on a longitudinal study indicated that the population peak in both ecological areas (high and lowlands) occurs in July. The factors Including the collection method and trap sites controlling the apparent seasonal distributions are discussed. Statistical data on the total cases of CL and VL reported In The Kingdom are presented and data from the study area are compared with those from other areas such as the Eastern Province (where L. major is dominant) to give an overall picture of the leishmaniases throughout the country.

A dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,in fulfillment of the requirements for the degree of Master of Science in Medicine. Johannesburg, South Africa, 2015 / Plasmodium falciparum remains the most virulent cause of malaria. With increasing drug resistance to artemisinin and other antimalarial drugs, combined with an absence of an effective vaccine, there’s a critical need for new agents to complement existing treatment and prophylaxis. Therefore, the aim of the study was to evaluate the in vitro antimalarial activity and potential toxicity to mammalian cells of select synthetic and natural colourants, nucleoside and imidazo[1,2a]pyridine (IP) analogues on the erythrocytic stages of the 3D7 chloroquine-sensitive strain of P. falciparum. The P. falciparum 3D7 strain was maintained in vitro according to standard methods. Quinine and chloroquine were used as positive controls. The tritiated hypoxanthine incorporation assay was used for evaluating the ability of test compounds to inhibit the growth of P. falciparum. Active test compounds were tested in combination studies with quinine. Uninfected human red blood cell (RBC) toxicity was analysed spectrophotometrically. The ability of test compounds to inhibit -haematin formation, a metabolic pathway that sequesters toxic haem within the parasites, was determined. Cytotoxic activity of active compounds was evaluated on two human cell lines (HEK293 and K562) using the [3H]-thymidine incorporation assay. Data was analysed using the one-way ANOVA test and reported as the mean ± standard deviation of at least triplicate experiments and significant difference when p < 0.05. Of the 56 compounds tested, the synthetic colourants showed the most potent antimalarial activity. Methylene blue and safranin O were most potent with IC50 values of 4.19 ± 0.16 nM and 86.50 ± 2.61 nM, respectively, compared to quinine (IC50: 103.90 ± 8.30 nM), and displayed negligible toxicity to uninfected human RBCs. Combination studies with methylene blue and quinine demonstrated a synergistic interaction. Methylene blue also demonstrated the highest selectivity indices (480 and 968) compared to quine (180). Curcumin (diferuloylmethane), a natural extract was active (IC50: 2.29 ± 0.18 μg/ml) against P. falciparum, but significantly (p < 0.05) less potent than quinine. Curcumin was 78-fold more active in inhibiting -haematin formation than quinine, indicating of a possible mechanism of action. The most active nucleoside analogue, JLP118.1 (IC50: 1.79 ± 0.12 μM), demonstrated inhibitory activity against the trophozoite stage of P. falciparum. The imidazopyridine analogue, IP-4, displayed the least potent antimalarial activity (IC50: 15.3 ± 0.41 μM) of the synthetic compounds tested, with low selectivity indices < 1. The study has confirmed the potent antimalarial activity and relative safety of methylene blue as well as its potential as an antimalarial drug. The nucleoside and imidazopyridine analogues showed promising activity and with structural modification their potency and selectivity indices may be enhanced.