Fiona Allan

Diagnostics for schistosomiasis in Africa and Arabia: a review of present options in control and future needs for elimination.

Within the World Health Organization 2012-2020 roadmap for control and elimination of schistosomiasis, the scale-up of mass drug administration with praziquantel is set to change the epidemiological landscape across Africa and Arabia. Central in measuring progress is renewed emphasis upon diagnostics which operate at individual, community and environmental levels by assessing reductions in disease, infections and parasite transmission. However, a fundamental tension is revealed between levels for present diagnostic tools, and methods applied in control settings are not necessarily adequate for application in elimination scenarios. Indeed navigating the transition from control to elimination needs careful consideration and planning. In the present context of control, we review current options for diagnosis of schistosomiasis at different levels, highlighting several strengths and weaknesses therein. Future challenges in elimination are raised and we propose that more cost-effective diagnostics and clinical staging algorithms are needed. Using the Kingdom of Saudi Arabia as a contemporary example, embedding new diagnostic methods within the primary care health system is discussed with reference to both urogenital and intestinal schistosomiasis.

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial

Background Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. Methodology In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. Principal Findings The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0–19.7%) and 2.7% (range: 0–26.5%) in Unguja, and 8.9% (range: 0–31.8%) and 5.5% (range: 0–23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03–2.03). Decreasing adult age (OR: 1.04; CI: 1.02–1.06), being born in Pemba (OR: 1.48; CI: 1.02–2.13) or Tanzania (OR: 2.36; CI: 1.16–4.78), and use of freshwater (OR: 2.15; CI: 1.53–3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. Conclusions/Significance The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved.

Schistosomiasis collection at NHM (SCAN)

BackgroundThe Natural History Museum (NHM) is developing a repository for schistosomiasis-related material, the Schistosomiasis Collection at NHM (SCAN) as part of its existing Wolfson Wellcome Biomedical Laboratory (WWBL). This is timely because a major research and evaluation effort to understand control and move towards elimination of schistosomiasis in Africa has been initiated by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), resulting in the collection of many important biological samples, including larval schistosomes and snails. SCAN will collaborate with a number of research groups and control teams and the repository will acquire samples relevant to both immediate and future research interest. The samples collected through ongoing research and field activities, WWBL’s existing collections, and other acquisitions will be maintained over the long term and made available to the global research community for approved research purposes. Goals include: · Consolidation of the existing NHM schistosome and snail collections and transfer of specimens into suitable long-term storage systems for DNA retrieval, · Long-term and stable storage of specimens collected as part of on going field programmes initially in Africa especially relating to the SCORE research programmes, · Provision of access to snail and schistosome collections for approved research activities.

Use of sentinel snails for the detection of Schistosoma haematobium transmission on Zanzibar and observations on transmission patterns

Urogenital schistosomiasis is an important public health issue in Zanzibar. Transmission of the parasite to the human population is related to the distribution of the intermediate snail host, Bulinus globosus. We measured B. globosus abundance and Schistosoma haematobium prevalence within snails in a series of naturally occurring populations and compared prevalence detected by observing cercarial shedding for patent infections, and by PCR using DraI repeat. A total of 2146 B. globosus were collected throughout the study period from 2003 to 2007; of these 85 (3.96%) were shedding cercariae. The levels of infection detected by PCR were consistently higher (40-100 percent). Levels of exposure to miracidia in the field were measured using sentinel snails. B. globosus (a susceptible host) and B. nasutus (a non-susceptible host) were placed in cages at transmission sites for 72h to observe rates of penetration by miracidia. Both B. globosus and B. nasutus tested positive for S. haematobium by PCR (up to 24% infected) indicating frequent contamination of the waterbodies with S. haematobium miracidia. The use of sentinel snails coupled with PCR diagnostics could be a sensitive tool for mapping and monitoring transmission of schistosomiasis in areas of low prevalence.

Host choice and penetration by Schistosoma haematobium miracidia

Schistosome parasites commonly show specificity to their intermediate mollusc hosts and the degree of specificity can vary between parasite strains and geographical location. Here the role of miracidial behaviour in host specificity of Schistosoma haematobium on the islands of Zanzibar is investigated. In choice-chamber experiments, S. haematobium miracidia moved towards Bulinus globosus snail hosts in preference to empty chambers. In addition, miracidia preferred uninfected over patent B. globosus. This preference should benefit the parasite as patent snails are likely to have mounted an immune response to S. haematobium as well as providing poorer resources than uninfected snails. Miracidia also discriminated between the host B. globosus and the sympatric, non-host species Cleopatra ferruginea. In contrast, S. haematobium did not discriminate against the allopatric Bulinus nasutus. Penetration of the host by miracidia was investigated by screening snails 24 h after exposure using polymerase chain reaction (PCR) with S. haematobium specific DraI repeat primers. There was no difference in the frequency of penetration of B. globosus versus B. nasutus. These responses to different snail species may reflect selection pressure to avoid sympatric non-hosts which represent a transmission dead end. The distribution of B. nasutus on Unguja is outside the endemic zone and so there is less chance of exposure to S. haematobium, hence there will be little selection pressure to avoid this non-host snail.

Whole genome resequencing of the human parasite Schistosoma mansoni reveals population history and effects of selection

Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5–147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20–90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16–19th Century Atlantic Slave Trade.

Development of novel multiplex microsatellite polymerase chain reactions to enable high-throughput population genetic studies of Schistosoma haematobium.

Human urogenital schistosomiasis caused by Schistosoma haematobium is widely distributed across Africa and is increasingly targeted for control and regional elimination. The development of new high-throughput, cost-effective molecular tools and approaches are needed to monitor and evaluate the impact of control programs on the parasite populations. Microsatellite loci are genetic markers that can be used to investigate how parasite populations change over time and in relation to external influences such as control interventions. Here, 18 existing S. haematobium microsatellite loci were optimised to enable simultaneous amplification across two novel multiplex microsatellite PCR’s, each containing nine loci. Methods were developed for the cost effective and rapid processing and microsatellite analysis of S. haematobium larval stages stored on Whatman-FTA cards and proved robust on miracidia and cercariae collected from Zanzibar and Niger. The development of these novel and robust multiplex microsatellite assays, in combination with an improved protocol to elute gDNA from Whatman-FTA fixed schistosome larval stages, enables the high-throughput population genetic analysis of S. haematobium. The molecular resources and protocols described here advance the way researchers can perform multi locus-based population genetic analyses of S. haematobium as part of the evaluation and monitoring of schistosomiasis control programmes.

Mapping freshwater snails in north-western Angola: distribution, identity and molecular diversity of medically important taxa.

BackgroundThis study was designed to determine the distribution and identity of potential intermediate snail hosts of Schistosoma spp. in Bengo, Luanda, Kwanza Norte and Malanje Provinces in north-western Angola. This is an area where infection with Schistosoma haematobium, causing urogenital schistosomiasis, is common but little is yet known about transmission of the disease. Angola has had a varied past with regard to disease control and is revitalising efforts to combat neglected tropical diseases.MethodsSnails were sampled from 60 water-contact points. Specimens of the genera Bulinus, Biomphalaria or Lymnaea were screened for trematode infections by inducing cercarial shedding. Snails were initially identified using shell morphology; subsequently a cytochrome c oxidase subunit 1 (cox1) gene fragment was amplified from a subset of snails from each site, for molecular identification. Cercariae were captured onto FTA cards for molecular analysis. Specimens of Bulinus angolensis collected from the original locality of the type specimen have been characterised and comparisons made with snails collected in 1957 held at the Natural History Museum, London, UK.ResultsIn total snails of nine genera were identified using morphological characteristics: Biomphalaria, Bulinus, Gyraulus, Lanistes, Lentorbis, Lymnaea, Melanoides, Physa and Succinea. Significant for schistosomiasis transmission, was the discovery of Bulinus globosus, B. canescens, B. angolensis, B. crystallinus and Biomphalaria salinarum in their type-localities and elsewhere. Bulinus globosus and B. angolensis occurred in two distinct geographical areas. The cox1 sequence for B. globosus differed markedly from those from specimens of this species collected from other countries. Bulinus angolensis is more closely related to B. globosus than originally documented and should be included in the B. africanus group. Schistosoma haematobium cercariae were recovered from B. globosus from two locations: Cabungo, Bengo (20 snails) and Calandula, Malanje (5 snails). Schistosoma haematobium cercariae were identified as group 1 cox1 corresponding to the type common throughout the African mainland.ConclusionsVarious freshwater bodies in north-western Angola harbour potential intermediate snail hosts for urogenital schistosomiasis, highlighting the need to map the rest of the country to identify areas where transmission can occur and where control efforts should be targeted. The molecular phylogeny generated from the samples confirmed that considerable variation exists in B. globosus, which is the primary snail host for S. haematobium in many regions of Africa.

DNA barcoding of the medically important freshwater snail 'Physa acuta' reveals multiple invasion events into Africa

The medically important freshwater snail Physa acuta is highly invasive and has been reported in several freshwater environments across Africa. To identify species and provide initial insights into the origins of P. acuta into African freshwater environments standard molecular barcoding analyses, using the mitochondrial cytochrome c oxidase subunit I gene (COI), was performed on P. acuta isolates from Angola, Burundi and South Africa. Phylogenetic analyses of isolates from Africa could not be distinguished from P. acuta populations from other countries. Comparisons of COI sequences between isolates of P. acuta showed there to be no geographically specific clusters and the African isolates were distributed across four distinct unrelated clades suggesting several independent invasion events. Haplotype analyses indicated that there were a high number of haplotypes with low variation between them, which led to significant differences in AMOVA analyses between countries. This was further evidence of multiple invasion events suggesting multiple novel haplotypes being continually and independently introduced to each country. This approach not only provides initial insight into the invasion of Africa by P. acuta but a molecular method to monitor and manage the use of an agent of biological control.