Claire J. Standley

An evaluation of urine-CCA strip test and fingerprick blood SEA-ELISA for detection of urinary schistosomiasis in schoolchildren in Zanzibar

To develop better monitoring protocols for detection of urinary schistosomiasis during ongoing control interventions, two commercially available diagnostic tests - the urine-circulating cathodic antigen (CCA) strip and the soluble egg antigen enzyme-linked immunosorbent assay (SEA-ELISA) - were evaluated for detection of Schistosoma haematobium infections in 150 schoolchildren from Zanzibar. The children originated from five primary schools representative of different levels of disease endemicity across the island; using standard urine filtration assessment with microscopy, mean prevalence of S. haematobium was 30.7% (95% confidence interval (CI)=23.4-38.7%) and a total of 35.3% (95% CI=27.7-43.5%) and 8.0% (95% CI=4.2-13.6%) children presented with micro- and macro-haematuria, respectively. Diagnostic scores of the urine-CCA strip were not satisfactory, a very poor sensitivity of 9% (95% CI=2-21%) was observed, precluding any further consideration. By contrast, the performance of the SEA-ELISA using sera from fingerprick blood was good; a sensitivity of 89% (95% CI=76-96%), a specificity of 70% (95% CI=60-79%), a positive predictive value of 57% (95% CI=45-69%) and a negative predictive value of 90% (95% CI=86-98%) were found. At the unit of the school, a positive linear association between prevalence inferred from parasitological examination and SEA-ELISA methods was found. The SEA-ELISA holds promise as a complementary field-based method for monitoring infection dynamics in schoolchildren over and above standard parasitological methods.

The path of least resistance: aggressive or moderate treatment?

The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance. Here, we summarize the very limited available empirical evidence across different pathogens and provide a conceptual framework describing the information required to effectively manage drug pressure to minimize resistance evolution.

Over-diagnosis of malaria by microscopy in the Kilombero Valley, Southern Tanzania: an evaluation of the utility and cost-effectiveness of rapid diagnostic tests

BackgroundEarly and accurate diagnosis of febrile patients is essential to treat uncomplicated malaria cases properly, prevent severe malaria, and avert unnecessary anti-malarial treatments. Improper use of anti-malarials increases the risk of adverse drug reaction and the evolution of drug/parasite resistance. While microscopy is the most common form of malaria diagnosis, concerns over its accuracy have prompted the incorporation of malaria rapid diagnostic tests (RDTs) into many national malaria control programmes.MethodsOver a three-month period, a direct comparison between microscopy and RDTs was made in a rural, private dispensary in the Kilombero Valley, Morogoro District, southern Tanzania, with the aim of estimating the extent of malaria over-diagnosis and over-treatment with anti-malarials. The study cohort was made up of patients referred by the dispensary’s clinician for malaria testing. One hundred percent of patients approached agreed to participate in this study and were then tested using both microscopy and RDTs. Using the results from the comparison of the two tests at this dispensary, the potential cost effectiveness of introducing RDTs to a neighbouring public health centre was estimated on the basis of this centre’s past malaria records spanning December 2007 to August 2011.ResultsAt the private dispensary, the apparent prevalence of malaria was 78% based on microscopy whereas the true prevalence, calculated using RDTs as the gold standard, was estimated at 14%. This discrepancy indicates that when using microscopy as the sole diagnostic test, malaria is being over-diagnosed by approximately a factor of five in this setting. At the public clinic, apparent malaria prevalence based on microscopy was 74%. If similar rates of over-diagnosis are assumed, 5,285 patients of the 6,769 patients positively diagnosed with malaria using microscopy were likely given unnecessary anti-malarials, and their true cause of illness was not addressed. The introduction of RDTs to the public clinic would be highly cost-efficient, with an estimated net saving of over 96 USD/month.ConclusionsCompared with RDTs, microscopy led to almost four out of five patients being over-diagnosed with malaria in this rural part of Tanzania. A policy that encompasses both the private and public sectors of health care is needed to ensure quality diagnostic testing for febrile patients. With estimated prevalence at 14%, RDT introduction is recommended given WHO findings that RDTs are predicted to be cost-effective in prevalence areas of less than 20%. The use of RDTs in malaria diagnosis would not only reduce government spending but would prove beneficial to ensuring appropriate care and treatment of febrile illness.

Integrated prevalence mapping of schistosomiasis, soil-transmitted helminthiasis and malaria in lakeside and island communities in Lake Victoria, Uganda

BackgroundIt is widely advocated that integrated strategies for the control of neglected tropical diseases (NTDs) are cost-effective in comparison to vertical disease-specific programmes. A prerequisite for implementation of control interventions is the availability of baseline data of prevalence, including the population at risk and disease overlap. Despite extensive literature on the distribution of schistosomiasis on the mainland in Uganda, there has been a knowledge gap for the prevalence of co-infections with malaria, particularly for island communities in Lake Victoria. In this study, nine lakeshore and island districts were surveyed for the prevalence of NTDs and malaria, as well as educational and health infrastructure.ResultsA total of 203 communities were surveyed, including over 5000 school-age children. Varying levels of existing health infrastructure were observed between districts, with only Jinja District regularly treating people for NTDs. Community medicine distributors (CMD) were identified and trained in drug delivery to strengthen capacity. Prevalence levels of intestinal schistosomiasis and soil-transmitted helminthiasis were assessed via Kato-Katz thick smears of stool and malaria prevalence determined by microscopy of fingerprick blood samples. Prevalence levels were 40.8%, 26.04% and 46.4%, respectively, while the prevalence of co-infection by Schistosoma mansoni and Plasmodium spp. was 23.5%. Socio-economic status was strongly associated as a risk factor for positive infection status with one or more of these diseases.ConclusionsThese results emphasise the challenges of providing wide-scale coverage of health infrastructure and drug distribution in remote lakeshore communities. The data further indicate that co-infections with malaria and NTDs are common, implying that integrated interventions for NTDs and malaria are likely to maximize cost-effectiveness and sustainability of disease control efforts.

Molecular epidemiology and phylogeography of Schistosoma mansoni around Lake Victoria.

Intestinal schistosomiasis continues to be a major public health problem in sub-Saharan Africa, and is endemic in communities around Lake Victoria. Interest is growing in the molecular evolution and population genetic structure of Schistosoma mansoni and we describe a detailed analysis of the molecular epidemiology and phylogeography of S. mansoni from Lake Victoria. In total, 388 cytochrome oxidase 1 (COI) sequences were obtained from 25 sites along the Ugandan, Tanzanian and Kenyan shorelines of Lake Victoria, and 122 unique barcodes were identified; 9 corresponded to previously discovered barcodes from Lakes Victoria and Albert. A subset of the data, composed of COI sequences from miracidia from 10 individual children, was used for population genetics analyses; these results were corroborated by microsatellite analysis of 4 isolates of lab-passaged adult worms. Overall, 12 barcodes were found to be shared across all 3 countries, whereas the majority occurred singly and were locally restricted. The population genetics analyses were in agreement in revealing high diversity at the level of the human host and negligible population structuring by location. The lack of correlation between genetic distance and geographical distance in these data may be attributed to the confounding influence of high intra-individual diversity as well as human migration between communities.

Zoonotic schistosomiasis in non-human primates: past, present and future activities at the human-wildlife interface in Africa.

Schistosomiasis is one of the worlds most widely distributed and prevalent parasitic diseases. Less widely recognized is that some species of Schistosoma, including several that commonly affect humans, also cause disease in other mammalian species; in particular, infections in non-human primates are known. With interest increasing in emerging zoonotic diseases, the status of schistosomiasis as a zoonotic infection is in need of re-appraisal, especially in light of advances in application of molecular screening and epidemiological tools where newly reported infections raise general animal welfare and conservation concerns. Focusing on Africa, this review provides a summary of the occurrence of schistosomiasis in non-human primates and discusses new ways in which surveillance for schistosomiasis should be integrated into more effective conservation management and disease control strategies. Emphasis is on the more common forms of human schistosomiasis, their clinical manifestations and epidemiological significance in terms of infection reservoir potential.

Environmental epidemiology of intestinal schistosomiasis and genetic diversity of Schistosoma mansoni infections in snails at Bugoigo village, Lake Albert

Intestinal schistosomiasis continues to be hyper-endemic in the fishing community of Bugoigo located on the eastern shore of Lake Albert, Uganda. Our study aimed to identify the factors that determine the local distribution and abundance of Biomphalaria, as well as infection(s) with Schistosoma mansoni inclusive of their genetic diversity. In addition, a DNA barcoding approach was taken to genotype schistosome cercariae, exploring the micro-epidemiology of infections. Over a 3-week period in June-July 2010, several hundred Biomphalaria spp. were collected, together with environmental information, from 10 selected sites, representative of both putative wave-exposed (n=5) and wave-sheltered shorelines (n=5). A Mann-Whitney U-test and a generalized linear model were used to assess associations with snail abundance and parasite infections across the shoreline. Levels of local wave action were recorded over the 19-day period using digital accelerometers. The general absence of wave action on the sheltered shoreline likely helped to raise and focalize other environmental parameters, such as water conductivity by lack of mixing, that foster transmission of intestinal schistosomiasis. Over the study period, a total of 10 infected snails were encountered and a selection of schistosome cercariae from each infected snail was harvested for analysis by DNA barcoding. In total, 91 DNA barcodes were generated with 15 unique barcode types identified. Of these, 4 barcodes had been found previously in Lake Albert and (or) Victoria, the remaining 11 were newly encountered here and described. The distribution of DNA barcodes across infected snails and sampled locations revealed a complicated spatial sub-structuring. By shedding new light on the fine-scale patterning of infections, DNA barcoding has revealed a rather heterogeneous landscape of cercariae, likely inclusive of multi-miracidial infections within the snail, which will in turn interplay with human water contact activities to shape the genetic diversity of worm populations within infected people.

A fresh insight into transmission of schistosomiasis: a misleading tale of Biomphalaria in Lake Victoria.

Lake Victoria is a known hot-spot for Schistosoma mansoni, which utilises freshwater snails of the genus Biomphalaria as intermediate hosts. Different species of Biomphalaria are associated with varying parasite compatibility, affecting local transmission. It is thought that two species, B. choanomphala and B. sudanica, inhabit Lake Victoria; despite their biomedical importance, the taxonomy of these species has not been thoroughly examined. This study combined analysis of morphological and molecular variables; the results demonstrated that molecular groupings were not consistent with morphological divisions. Habitat significantly predicted morphotype, suggesting that the different Lake Victorian forms of Biomphalaria are ecophentoypes of one species. The nomenclature should be revised accordingly; the names B. choanomphala choanomphala and B. c. sudanica are proposed. From a public health perspective, these findings can be utilised by policy-makers for better understanding of exposure risk, resulting in more effective and efficient control initiatives.

The population genetic structure of Biomphalaria choanomphala in Lake Victoria, East Africa: implications for schistosomiasis transmission

BackgroundThe freshwater snail Biomphalaria acts as the intermediate host of Schistosoma mansoni, a globally important human parasite. Understanding the population structure of intermediate host species can elucidate transmission dynamics and assist in developing appropriate control methods.MethodsWe examined levels of population genetic structure and diversity in 29 populations of Biomphalaria choanomphala collected around the shoreline of Lake Victoria in Uganda, Kenya and Tanzania, where S. mansoni is hyper-endemic. Molecular markers were utilized to estimate the degree to which snail populations are genetically differentiated from one another.ResultsHigh levels of snail genetic diversity were found coupled with evidence of geographically-determined population structure but low levels of local inbreeding. The data are consistent with an effect of schistosome infection on population structure of intermediate host snails, but other factors, such as habitat and historical demographic changes, could also be important determinants of the degree of population genetic structure in Biomphalaria choanomphala.ConclusionsThe low stratification of populations and high genetic diversity indicates potentially less local compatibility with intermediate snail populations than previously theorized, and highlights the importance of coordinated parasite control strategies across the region.

Compatibility of Ugandan Schistosoma mansoni isolates with Biomphalaria snail species from Lake Albert and Lake Victoria.

In order to investigate the capacity of being intermediate host for Schistosoma mansoni, the Ugandan F1 generation of Biomphalaria snail species that were laboratory-bred from parent populations originally collected from either Lake Victoria or Lake Albert was challenged with sympatric and non-sympatric S. mansoni isolates. After a prepatent period of 20 days, a daily 10-hourly snail shedding for cercariae was done to determine the infection rate, cercarial production per hour and survival period of infected snails. The study suggests that when parasite strains from a different geographical origin is used for infection, survival of infected snails increase, leading to an increased transmission potential. Although earlier literature had indicated that the Lake Victoria Biomphalaria sudanica is refractory to S. mansoni, we showed that all Ugandan Biomphalaria spp., including B. sudanica from all locations, were highly susceptible to the S. mansoni isolates. Thus if B. choanomphala, which is an efficient intermediate host in Lake Victoria, is given an opportunity to occupy Lake Albert, it will most likely be compatible with the Albertine S. mansoni parasites. Equally, if B. stanleyi, currently restricted to Lake Albert invades Lake Victoria, it is likely to act as an efficient intermediate host. Future work should concentrate on intraspecific population-level differences in compatibility.