Mohamed A. Idris

Origin and diversification of the human parasite Schistosoma mansoni

Schistosoma mansoni is the most widespread of the human‐infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult‐stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasites geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within‐species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30–0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country.

Phylogeography of Biomphalaria glabrata and B. pfeifferi, important intermediate hosts of Schistosoma mansoni in the New and Old World tropics

The historical phylogeography of the two most important intermediate host species of the human blood fluke Schistosoma mansoni, B. glabrata in the New World, and B. pfeifferi in the Old World, was investigated using partial 16S and ND1 sequences from the mitochondrial genome. Nuclear sequences of an actin intron and internal transcribed spacer (ITS)‐1 were also obtained, but they were uninformative for the relationships among populations. Phylogenetic analyses based on mtDNA revealed six well‐differentiated clades within B. glabrata: the Greater Antilles, Venezuela and the Lesser Antilles, and four geographically overlapping Brazilian clades. Application of a Biomphalaria‐specific mutation rate gives an estimate of the early Pleistocene for their divergence. The Brazilian clades were inferred to be the result of fragmentation, due possibly to climate oscillations, with subsequent range expansion producing the overlapping ranges. Within the Venezuela and Lesser Antilles clade, lineages from each of these areas were estimated to have separated approximately 740 000 years ago. Compared to B. glabrata, mitochondrial sequences of B. pfeifferi are about 4× lower in diversity, reflecting a much younger age for the species, with the most recent common ancestor of all haplotypes estimated to have existed 880 000 years ago. The oldest B. pfeifferi haplotypes occurred in southern Africa, suggesting it may have been a refugium during dry periods. A recent range expansion was inferred for eastern Africa less than 100 000 years ago. Several putative species and subspecies, B. arabica, B. gaudi, B. rhodesiensis and B. stanleyi, are shown to be undifferentiated from other B. pfeifferi populations.

The phylogeography of Indoplanorbis exustus (Gastropoda: Planorbidae) in Asia

BackgroundThe freshwater snail Indoplanorbis exustus is found across India, Southeast Asia, central Asia (Afghanistan), Arabia and Africa. Indoplanorbis is of economic importance in that it is responsible for the transmission of several species of the genus Schistosoma which infect cattle and cause reduced livestock productivity. The snail is also of medical importance as a source of cercarial dermatitis among rural workers, particularly in India. In spite of its long history and wide geographical range, it is thought that Indoplanorbis includes only a single species. The aims of the present study were to date the radiation of Indoplanorbis across Asia so that the factors involved in its dispersal in the region could be tested, to reveal potential historical biogeographical events shaping the phylogeny of the snail, and to look for signs that I. exustus might be polyphyletic.ResultsThe results indicated a radiation beginning in the late Miocene with a divergence of an ancestral bulinine lineage into Assam and peninsular India clades. A Southeast Asian clade diverged from the peninsular India clade late-Pliocene; this clade then radiated at a much more rapid pace to colonize all of the sampled range of Indoplanorbis in the mid-Pleistocene.ConclusionsThe phylogenetic depth of divergences between the Indian clades and Southeast Asian clades, together with habitat and parasitological differences suggest that I. exustus may comprise more than one species. The timescale estimated for the radiation suggests that the dispersal to Arabia and to Southeast Asia was facilitated by palaeogeographical events and climate change, and did not require human involvement. Further samples from Afghanistan, Africa and western India are required to refine the phylogeographical hypothesis and to include the African Recent dispersal.

Effective control of hookworm infection in school children from Dhofar, Sultanate of Oman: a four-year experience with albendazole mass chemotherapy

After 4 years of mass chemotherapy with a single annual dose of albendazole 400 mg, health education and promotion of environmental health, the prevalence of Necator americanus in Wilayat Tagah, Dhofar, Oman was reduced from 40 to 1.3% and from 6 to 0%, respectively, among rural and urban school children. Stool samples with egg load >1000 egg/gm were reduced from 28 to 0% after the first year of intervention and maintained as such in subsequent years.

Influence of pattern of exposure, parasite genetic diversity and sex on the degree of protection against reinfection with Schistosoma mansoni

This paper analyzed, experimentally, the influences of pattern of exposure, parasite genetic diversity, and parasite sex on the degree of protection against reinfection with Schistosoma mansoni in the mouse. The results show that, (1) in infections with one male parasite genotype, successive infections induced a significant decrease in the infectivity of the parasite and significant increases in the spleen and liver weights compared to mass infections, (2) successive infections with one male genotype induced a significant decrease in the infectivity of the parasite compared to successive infections with five male genotypes, and (3) genotype infectivities were determined by the order at which they were used in the successive infections. These results are discussed in terms of protective effect and concomitant immunity and provide an ecological explanation of the natural sex-biased dispersal toward the male schistosomes.

Source of drug resistant Plasmodium falciparum in a potential malaria elimination site in Saudi Arabia

A major challenge to the success of malaria control program in Saudi Arabia is the high influx of expatriates and holy visitors from malaria endemic countries. In the present study we examined whether drug resistant parasite genotypes reported in Jazan region, southwest of Saudi Arabia are imported or developed locally. We examined 178 Plasmodium falciparum isolates for alleles of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), associated with Sulfadoxine-Pyrimethamine (SP) resistance, and three microsatellites flanking each gene. In addition, we examined a neutral polymorphic gene (Pfg377). We compared the dhfr and dhps haplotypes in Jazan, using network analysis, to an existing similar data set of 94 P. falciparum isolates from eastern Sudan. In Jazan, double mutant dhfr allele (51I, 108N) occurred with a prevalence of 33%. The vast majority (99%) of dhps were wild-type alleles. The mean expected heterozygosity (H(e)) of microsatellites around mutant dhfr alleles (H(e)=0.312; n=60) was lower (P ≤ 0.05) than that around the wild-type allele (H(e)=0.834; n=116). Also, the mutant dhfr isolates showed high H(e) for dhps (H(e)=0.80) and the non-drug resistance locus Pfg377 (H(e)=0.63) indicative of selection for mutant dhfr only. The predominant double mutant dhfr haplotype in Jazan (73%), was prevalent among P. falciparum in east Africa. Network analysis suggests the mutant haplotype of dhfr gene was possibly introduced into Jazan from East Africa. The absence of mutations in dhps as well as triple mutant dhfr haplotype associated with SP failure support the current use of SP as a partner with artesunate as a first line therapy in Saudi Arabia. However, the close relationship between the major mutant dhfr haplotype in Sudan and Saudi Arabia, favour the hypothesis of recent migration as a source of the major resistant dhfr lineage. Thus, regular monitoring of the dhfr and dhps haplotypes is of high priority to guard possible importation of high level SP resistant lineages.

In vitro antibacterial activity of three medicinal plants-Boswellia (Luban) species

Objective To study in vitro antibacterial and antifungal activity of hot water and methanolic extracts of the three medicinal plants- Boswellia (Luban) species. Methods Three selected plants were collected from different localities of Soqotra (Republic of Yemen), Dohfar (Sultanate of Oman) and Republic of Somalia. The plants were dried and extracted with two different solvents (methanol and hot water) to yield six crude extracts. The obtained extracts were tested for their antibacterial activity against eleven different bacterial strains and two fungi using the standard well-diffusion and micro-dilution methods. The following microorganisms were used: methicillin-resistant Staphylococcus aureus (ATCC 6538), muti-drug resistant Pseudomonas aeruginosa (ATCC 27853), enterohemorrhagic Escherichia coli (0157 EHEC), Salmonella typhi, Proteus vulgaris, Klebsiella pneumoniae, Bacillus subtilus (ATCC 6059, reference strain), Streptococcus pneumoniae, Klebsella pneumonia, MRSA, Corynebacterium, Corynebacterium diphtheriae and two fungus: Candida maltosa and Candida albicans . Results The different extracts possessed different inhibitory activity against different types of bacterial species. The patterns of inhibition varied with the plant extract, the solvent used for extraction and the organisms tested. The antimicrobial activity exhibited by the methanolic extracts of Boswellia sacra from the Suqotra and Dhofar regions was greater than that of Boswellia frereana collected from Somalia. The methanolic extract of the oleo-gum-resin showed higher efficacy to inhibit all the tested bacterial strains than the methanolic extract of frankincense-resin . The Boswellia frereana collected from Somalia showed lower activity compared with the two other Boswellia species. The plant extracts showed bacteriostatic activity at lower concentrations and bactericidal activity at higher concentrations. Neither water nor methanolic extracts showed any activity against the fungi Candida maltosa and Candida albicans . Conclusions It can be concluded that the methanolic extracts of Boswellia (Luban) possess the highest antibacterial activity. Neither water nor methanolic extracts show any activity against Candida maltosa and Candida albicans.

Ecological and molecular studies on emerging schistosomiasis mansoni in Dhofar Governorate, Sultanate of Oman

The recent detection of some cases of autochtonous schistosomiasis mansoni in Dhofar, Oman, prompted a search for the transmission sites. The five field surveys we conducted from November 2000 to February 2002 provided ecological data on schistosomiasis in Dhofar. Twenty‐eight water bodies situated within 8–160 km from Salalah, the largest city of Dhofar and at altitudes of up to 900 m, were surveyed for freshwater snails. Biomphalaria arabica was found in 15 of them. Three sites (Tibraq, Siginitti and Arazat) had Schistosoma infected snails, the first snails shedding cercariae of this parasite ever collected in Oman. The parasite from Dhofar was analysed by Random Amplified Polymorphic DNA comparisons using 11 primers and 167 polymorphic fragments and had 87–88% similarity with Schistosoma mansoni from Guadeloupe, but only 37–38% similarity with S. rodhaini from Burundi. Thus, it is a strain of S. mansoni. During the November 2000 survey, the prosobranch snail Melanoides tuberculata was associated with B. arabica in 10 of the 13 B. arabica sites. Cercariae from other species of Digenea emerged from five of the B. arabica sites, including the three named above. This paper presents the first finding of S. mansoni in the Dhofar Governorate and represents an initial study of the biology of S. mansoni transmission. This parasite and its cycle need further biological and molecular characterization, and the clarification of its epidemiological status in Dhofar Governorate is an urgent task.

A new chronotype of Schistosoma mansoni: adaptive significance

Objectives  To optimise host‐to‐host transmission, digenean trematodes (parasites) synchronize their cercarial emission patterns with the aquatic activities of their vertebrate hosts. Schistosoma mansoni has a strictly diurnal shedding pattern involving two circadian chronotypes: an early shedding pattern with a mean peak occurring at 11:00 h and a late pattern with a mean peak occurring at 16:00 h. We analysed the cercarial emergence pattern of three schistosome populations from Oman where S. mansoni is resurgent.

Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection

Background The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers. Methods Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. Results Chronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade. Conclusion The upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis.