Mapping schistosomiasis in the Sesse Islands
Mapping this island group for schistosomiasis poses a significant logistical challenge in terms of equipment and resources as only the main island (Kalangala) is directly accessible by ferry from the mainland, whilst all the others are reachable by small boat access alone. Many of the Sesse Islands, especially those in the south-east, are remote and poorly served, yet are inhabited by large numbers of people (and associated communities) typically engaged in the Lake Victoria fishery. Our survey has shown that far from being a uniformly low transmission zone, as had been assumed previously, the Sesse Islands display significant heterogeneities in terms of the prevalence of S. mansoni, with obvious implications for on-going treatment campaigns and revision of general advice for tourists visiting these islands. Rather surprisingly, the CCA urine lateral flow tests did not perform as well in this putative low transmission setting, in terms of diagnostic scores as compared to Kato-Katz thick smears, as had been the case in other regions of Lake Victoria where transmission was high .
The prevalence maps of the Sesse Islands clearly show that the northern islands in the archipelago, in northern Bufumira sub-county, appear a local hot spot for schistosomiasis. Much of the rest of the archipelago, and especially the southern and eastern out-lying islands, have much lower prevalence of the disease; these areas were also surveyed for snails, and Biomphalaria abundance observed to be low, although not absent. Unfortunately, owing to time and personnel constraints, snail surveys were not undertaken in Bufumira sub-county; therefore we cannot yet know whether the high prevalence observed there could be maintained through local transmission, or whether the children had acquired their infections elsewhere. Previous demographic surveys in Lake Victoria have revealed very high levels of itinerancy among the communities living along the lakeshore; in Kalangala District, in 2008, almost 60% of the 189 children surveyed had been born outside of the district, and as far afield as Tanzania . The World Health Organization has put a large emphasis on the need to create predictive maps, for example of expected schistosome distributions, but these need to be validated on the ground; Bufumira sub-county would be a crucial location for further malacological surveys in order to better understand the relationship between prevalence and snail distribution and thus create more accurate predictive maps. Vector Control Division will shortly be providing an updated atlas of the prevalence of intestinal schistosomiasis across the shoreline of Lake Victoria drawing further attention to disease heterogeneity at the local level.
Diagnostic comparisons and differences
Across the district, a number of sites had significant differences in the prevalence as ascertained by one diagnostic or another. For example, Site 11 would have been considered high prevalence on the basis of CCA results, and yet not a single positive Kato-Katz thick smear was observed. Conversely, two sites would have been considered absent of S. mansoni had only CCA tests been used, and yet had Kato-Katz prevalence of 23.1% and 10.0% respectively.
The variability of the CCA test in this setting is the cause of some concern, and indeed the diagnostic scores are generally lower than given in other studies [10–12]. Moreover, the results could be explained by the particular transmission dynamics of schistosomiasis in these islands. As we have shown, in many localities in the Sesse Islands there is a relative lack of intermediate host snails, as compared to other parts of the Ugandan shoreline. If the Sesse Islands themselves are not a high transmission zone, children may only be exposed to the parasite infrequently, resulting in long-term infection from single or infrequent exposure event(s). As these worms age, fecundity could decrease with senescence, reducing egg output intensity and in this scenario, a CCA test would be positive whereas the Kato-Katz thick smear might not reveal eggs.
Another factor to consider is that the CCA test is thought to be sensitive to differences in antigenicity of the parasite populations [3, 13]; it is plausible that changes in parasite genotypes (and phenotypes) across the lakeshore may result in altered performance of the CCA test. Similarly, if exposure is low, the diversity of the parasite genotypes present within an individual child may also be lower than in other regions, which too could alter the way in which the test reacts.
The SEA-ELISA results potentially reveal a further complication; the effect of prior treatment. As the egg antigens used in the ELISA may persist after the parasite is eliminated, for example post-treatment with praziquantel, individuals may test sera-positive despite not having an active infection. In the Sesse Islands, while treatment is far from ubiquitous, the district has been involved in the national control programme since 2005, and mass drug administration has been underway since then, particularly on the main island. In this survey, 49 out of 226 children (21.7%) interviewed on site reported having received praziquantel at some point. As such, whereas SEA-ELISA testing is an extremely sensitive and effective way of testing baseline prevalence in an un-surveyed area, its lack of discrimination between historical and current infections make it unsuitable for on-going monitoring, particularly where a treatment programme is in place.
Implications for treatment recommendations
The main aim in measuring prevalence of schistosomiasis in these various locations is to use the information to provide recommendations to the Vector Control Division's Ministry of Health, to streamline the delivery of praziquantel in their national treatment programme and to maximise its therapeutic coverage across the disease endemic landscape. Under-estimating the prevalence of intestinal schistosomiasis by locality leads to incorrect assessment of actual treatment needs, and since drug resources are finite, medications could be reassigned to other sites incorrectly. Conversely overestimating the prevalence of the disease by site could lead to increased drug wastage as treatments may be given to patients when not actually needed, but ethically, overtreatment is a more equitable position than omission of treatment .
Here, we have shown that SEA-ELISA is likely to overestimate present treatment needs as past treatment history likely confounds this assay, particularly in areas where mass drug distribution has taken place. However, we also show that CCA tests can often inaccurately estimate prevalence, at least when compared against Kato-Katz thick smears from a single stool sample. Nonetheless, the need for mapping prevalence can bring forward significant drug savings, as well as programmatic costs when set across a 5-year period of intervention. The Sesse Islands can be considered a further example of where good baseline information is needed to guide sensible decisions in meeting present and future local treatment needs. In this setting, and as a rough approximation, the raw costs of blanket annual mass drug administration for 5 years could be estimated as US$7593 (45 villages each having 250 children per village with an average dose of 2.7 tablets of praziquantel per child at US$0.05 per tablet). Simply by doing a local-scale rapid assessment survey such as this one, costs of drug procurement can be more than halved. Based on Kato-Katz prevalence, 13 schools require annual treatment; if the other 32 are all given a single dose, the cost is now US$3273.75, for the 5-year period. This value holds true for if 'trace' CCA calls are considered negative, as well. If 'trace' is considered infection-positive, the amount needed rises to US$4353.75, but this is still much less than the cost of blanket annual treatment. Of course, this does not take into account the cost of training, transport, monitoring and other supplementary activities. Nevertheless the point stands: regardless of diagnostic technique, implementing local-scale monitoring into control programme surveys can greatly reduce the cost of the intervention, by tailoring treatment regimes to local needs especially from longer term perspectives and provide evidence-based decision making.
As we have discussed, however, the difficulty lies with determining exactly what local treatment needs actually are, especially in the face of varying results from different diagnostics. Here, more thematic research is needed, for example in comparing the CCA tests against triplicate Kato-Katz thick smears from successive stools, as a more accurate 'gold' measure. Doing this could lead to a correction factor for the CCA test, to be used in rapid assessment settings where only single stool samples are examined. Alternatively, other eggs in stool detection methods could be explored, some of which have been shown to be potentially more sensitive than triple Kato-Katz thick smears for detecting parasite eggs [15, 16]. However, all alternative methods should be field-tested to determine efficacy and usability, even in remote settings, before being widely recommended and scaled-up for rapid mapping endeavours . For the meantime, we urge researchers to continue to test the CCA urine lateral flow test alongside Kato-Katz thick smears, in different epidemiological settings which may later allow a future meta-analysis of performance across transmission landscapes. In addition, it would be useful to explore in greater detail the effect of parasite genetic diversity on the diagnostic sensitivity of CCA tests; as our knowledge base grows regarding the molecular epidemiology of S. mansoni in Lake Victoria, we may be better placed to judge its effect on such diagnostic tools.