Confirmed local endemicity and putative high transmission of Schistosoma mansoni in the Sesse Islands, Lake Victoria, Uganda

The Sesse Islands, in the Ugandan portion of Lake Victoria, have long been considered a low transmission zone for intestinal schistosomiasis. Based on observations of high prevalence of Schistosoma mansoni infection in the northern-most islands of this archipelago, a follow-up survey was conducted to ascertain whether transmission was endemic to this island group, combining parasitological and malacological surveys. Prevalence of intestinal schistosomiasis was again observed to be high, as was intensity of infections which, combined with low reported incidence of treatment, suggests that chemotherapy-based control initiatives are not being maximally effective in this region as high levels of population movement between islands and districts are confounding. The local disease transmission was confirmed by the observations of high abundance of Biomphalaria, as well as field-caught snails shedding S. mansoni cercariae. DNA sequencing of 12 cercariae revealed common mitochondrial cox1 haplotypes, as well as, novel ones, consistent with the high genetic diversity of this parasite in Lake Victoria. Intestinal schistosomiasis is firmly endemic in parts of the Sesse Islands and more broadly, this island group provides an insight into the future challenges to be faced by the Ugandan National Control Programme in regularly reaching these rather remote, inaccessible and largely itinerant communities

Translating from egg- to antigen-based indicators for Schistosoma mansoni elimination targets: A Bayesian latent class analysis study

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.Schistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations

Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test (POC-CCA) in two Schistosoma mansoni endemic areas in Uganda

Over 240 million people are infected with schistosomiasis. Detecting Schistosoma mansoni eggs in stool using Kato–Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity. The urine-based point-of-care circulating cathodic antigen test (POC-CCA) has higher sensitivity, but issues include specificity, discrepancy between batches and interpretation of trace results. A semi-quantitative G-score and latent class analyses making no assumptions about trace readings have helped address some of these issues. However, intra-sample and inter-sample variation remains unknown for POC-CCAs. We collected 3 days of stool and urine from 349 and 621 participants, from high- and moderate-endemicity areas, respectively. We performed duplicate Kato-Katzs and one POC-CCA per sample. In the high-endemicity community, we also performed three POC-CCA technical replicates on one urine sample per participant. Latent class analysis was performed to estimate the relative contribution of intra- (test technical reproducibility) and inter-sample (day-to-day) variation on sensitivity and specificity. Within-sample variation for Kato-Katzs was higher than between-sample, with the opposite true for POC-CCAs. A POC-CCA G3 threshold most accurately assesses individual infections. However, to reach the WHO target product profile of the required 95% specificity for prevalence and monitoring and evaluation, a threshold of G4 is needed, but at the cost of reducing sensitivity. This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’

Genome-wide analysis of Schistosoma mansoni reveals limited population structure and possible praziquantel drug selection pressure within Ugandan hot-spot communities

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment

Translating From Egg- to Antigen-Based Indicators for Schistosoma mansoni Elimination Targets: A Bayesian Latent Class Analysis Study

From Frontiers via Jisc Publications RouterHistory: received 2021-11-30, collection 2022, accepted 2022-01-12, epub 2022-02-18Publication status: PublishedSchistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations

Investigating portable fluorescent microscopy (CyScope®) as an alternative rapid diagnostic test for malaria in children and women of child-bearing age

<p>Abstract</p> <p>Background</p> <p>Prompt and correct diagnosis of malaria is crucial for accurate epidemiological assessment and better case management, and while the gold standard of light microscopy is often available, it requires both expertise and time. Portable fluorescent microscopy using the CyScope^®offers a potentially quicker, easier and more field-applicable alternative. This article reports on the strengths, limitations of this methodology and its diagnostic performance in cross-sectional surveys on young children and women of child-bearing age.</p> <p>Methods</p> <p>552 adults (99% women of child-bearing age) and 980 children (99% ≤ 5 years of age) from rural and peri-urban regions of Ugandan were examined for malaria using light microscopy (Giemsa-stain), a lateral-flow test (Paracheck-Pf^®) and the CyScope^®. Results from the surveys were used to calculate diagnostic performance (sensitivity and specificity) as well as to perform a receiver operating characteristics (ROC) analyses, using light microscopy as the gold-standard.</p> <p>Results</p> <p>Fluorescent microscopy (qualitative reads) showed reduced specificity (<40%), resulting in higher community prevalence levels than those reported by light microscopy, particularly in adults (+180% in adults and +20% in children). Diagnostic sensitivity was 92.1% in adults and 86.7% in children, with an area under the ROC curve of 0.63. Importantly, optimum performance was achieved for higher parasitaemia (>400 parasites/μL blood): sensitivity of 64.2% and specificity of 86.0%. Overall, the diagnostic performance of the CyScope was found inferior to that of Paracheck-Pf^®.</p> <p>Discussion</p> <p>Fluorescent microscopy using the CyScope^®is certainly a field-applicable and relatively affordable solution for malaria diagnoses especially in areas where electrical supplies may be lacking. While it is unlikely to miss higher parasitaemia, its application in cross-sectional community-based studies leads to many false positives (i.e. small fluorescent bodies of presently unknown origin mistaken as malaria parasites). Without recourse to other technologies, arbitration of these false positives is presently equivocal, which could ultimately lead to over-treatment; something that should be further explored in future investigations if the CyScope^®is to be more widely implemented.</p

Community involvement in health services at Namayumba and Bobi health centres: A case study

Background: Community involvement has been employed in the development of both vertical and horizontal health programmes. In Uganda, there is no empirical evidence on whether and how communities are involved in their health services. Aim and Setting: The aim of this study was to establish the existence of community involvement in health services and to identify its support mechanisms in Namayumba and Bobi health centres in Wakiso and Gulu districts, respectively. Methods: Participants were selected with the help of a community mobiliser. Key informants were selected purposively depending on their expertise and the roles played in their respective communities. The focus group discussions and key informant interviews were audio-recorded and transcribed verbatim. The transcripts were analysed manually for emerging themes and sub-themes. Results: Several themes emerged from the transcripts and we categorised them broadly into those that promote community involvement in health services and those that jeopardise it. Easy community mobilisation and several forms of community and health centre efforts promote community involvement, whilst lack of trust for health workers and poor communication downplay community involvement in their health services. Conclusion: Community involvement is low in health services in both Namayumba and Bobi health centres

Roles and challenges of family physicians in Uganda: A qualitative study.

BACKGROUND:The World Health report (2008), the World Health Assembly (2009) and the Declaration of Astana (2018) acknowledge the significant contribution of family physicians (FPs) in clinical and primary healthcare. Given the lack of resources and low numbers of FPs coupled with the contextual nature of family medicine (FM), the scope of practice of African FPs is likely to differ from that of colleagues in America and Europe. Thus, this study explored the roles of Ugandan FPs and the challenges they face. METHODS:This cross-sectional qualitative study was conducted through in-depth interviews with FPs who are working in Uganda. Participants who work in public and private healthcare systems including non-governmental organisations and in all geographical regions were purposively selected. Interviews were conducted from July 2016 to June 2017. Qualitative thematic content analysis of the transcripts was performed using a framework approach. RESULTS:The study team identified three and six thematic roles and challenges, respectively, from the interview transcripts. The roles were clinician, leadership and teaching and learning. Challenges included lack of common identity, low numbers of FPs, conflicting roles, unrealistic expectations, poor organisational infrastructure and lack of incentives. CONCLUSION:The major roles of FPs in Uganda are similar to those of their counterparts in other parts of the world. Family physicians provide clinical care for patients, including preventive and curative services; providing leadership, management and mentorship to clinical teams; and teaching and learning. However, their roles are exercised differently as a result of lack of proper institutionalisation of FM within the Uganda health system. Family physicians in Uganda have found many opportunities to contribute to healthcare leadership, education and service, but have not yet found a stable niche within the healthcare system