The short-term impact of Schistosoma mansoni infection on health-related quality of life: implications for current elimination policies.

The WHO aims to eliminate schistosomiasis as a public health problem by 2030. However, standard morbidity measures poorly correlate to infection intensities, hindering disease monitoring and evaluation. This is exacerbated by insufficient evidence on Schistosoma's impact on health-related quality of life (HRQoL). We conducted community-based cross-sectional surveys and parasitological examinations in moderate-to-high Schistosoma mansoni endemic communities in Uganda. We calculated parasitic infections and used EQ-5D instruments to estimate and compare HRQoL utilities in these populations. We further employed Tobit/linear regression models to predict HRQoL determinants. Two-thirds of the 560 participants were diagnosed with parasitic infection(s), 49% having S. mansoni. No significant negative association was observed between HRQoL and S. mansoni infection status/intensity. However, severity of pain urinating (ß = -0.106; s.e. = 0.043) and body swelling (ß = -0.326; s.e. = 0.005), increasing age (ß = -0.016; s.e. = 0.033), reduced socio-economic status (ß = 0.128; s.e. = 0.032), and being unemployed predicted lower HRQoL. Symptom severity and socio-economic status were better predictors of short-term HRQoL than current S. mansoni infection status/intensity. This is key to disentangling the link between infection(s) and short-term health outcomes, and highlights the complexity of correlating current infection(s) with long-term morbidity. Further evidence is needed on long-term schistosomiasis-associated HRQoL, health and economic outcomes to inform the case for upfront investments in schistosomiasis interventions.

Community tuberculosis screening, testing and care, Uganda.

Objective: To assess the effectiveness of a community-based tuberculosis and leprosy intervention in which village health teams and health workers conduct door-to-door tuberculosis screening, targeted screenings and contact tracing. Methods: We conducted a before-and-after implementation study in Uganda to assess the effectiveness of the community tuberculosis intervention by looking at reach, outputs, adoption and effectiveness of the intervention. Campaign 1 was conducted in March 2022 and campaign 2 in September 2022. We calculated percentages of targets achieved and compared case notification rates during the intervention with corresponding quarters in the previous year. We also assessed the leprosy screening. Findings: Over 5 days, campaign 1 screened 1 289 213 people (2.9% of the general population), of whom 179 144 (13.9%) fulfilled the presumptive tuberculosis criteria, and 4043 (2.3%) were diagnosed with bacteriologically-confirmed tuberculosis; 3710 (91.8%) individuals were linked to care. In campaign 2, 5 134 056 people (11.6% of the general population) were screened, detecting 428 444 (8.3%) presumptive tuberculosis patients and 8121 (1.9%) bacteriologically-confirmed tuberculosis patients; 5942 individuals (87.1%) were linked to care. The case notification rate increased from 48.1 to 59.5 per 100 000 population in campaign 1, with a case notification rate ratio of 1.24 (95% confidence interval, CI: 1.22-1.26). In campaign 2, the case notification rate increased from 45.0 to 71.6 per 100 000 population, with a case notification rate ratio of 1.59 (95% CI: 1.56-1.62). Of the 176 patients identified with leprosy, 137 (77.8%) initiated treatment. Conclusion: This community tuberculosis screening initiative is effective. However, continuous monitoring and adaptations are needed to overcome context-specific implementation challenges.

Prevalence and intensity of soil-transmitted helminth infections in Uganda: Results from population-based prevalence surveys in five districts.

BACKGROUND: Soil-transmitted helminth (STH) infections are caused by roundworms (Ascaris lumbricoides), whipworms (Trichuris trichiura), and hookworms (Necator americanus and Ancylostoma duodenale). In Uganda, baseline surveys conducted during the late 1990s and early 2000s suggested STH infections were common, with prevalence >50% among surveyed schoolchildren. In 2003, a national program was launched with mass preventative chemotherapy (PC) and health education for children 1-14 years old. Little evidence is available to show the impact of national deworming. METHODS: We conducted population-based, cross-sectional household surveys in five districts (Buikwe, Kassanda, Kiryandongo, Kisoro, and Rubanda) in March and May 2022. Our primary objective was to estimate STH prevalence by species due to infections of any intensity and infections of moderate-to-heavy intensity among preschool-aged children (PSAC, 1-4 years old), school-aged children (SAC, 5-14 years old), and women of reproductive age (WRA, 15-49 years old). Laboratory technicians used duplicate Kato-Katz microscopy to determine fecal egg count. RESULTS: Overall, 3,352 PSAC; 3,884 SAC; and 1,226 WRA provided stool samples. The prevalence of any infection remained high in Kisoro at or above ~50% within all risk groups. In other districts, the prevalence of any infection ranged from approximately 5 to 16% among PSAC, 6 to 23% among SAC, and 12 to 19% among WRA. Moderate-to-heavy intensity infection prevalence was highest in Kisoro (~15-26%), followed by Rubanda (<5%), and was ≤1% in other districts. A. lumbricoides and T. trichiura infections were largely confined to Kisoro and Rubanda, whereas hookworm was most common in other districts. CONCLUSIONS: The STH prevalence has decreased markedly in three districts in Uganda. Based on our findings, the national deworming program should consider decreasing PC distribution frequency in these districts per the World Health Organization guidelines. Efforts are needed to understand why the Kisoro and Rubanda districts did not demonstrate similar gains.

Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test 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'.

Addressing the Data Gaps on Child and Adolescent Tuberculosis.

The burden of tuberculosis (TB) among children and young adolescents (<15 years old) is estimated at 1.1 million; however, only 400,000 are treated for TB, indicating a large gap between the number who are cared for and the number estimated to have TB. Accurate data on the burden of pediatric TB is essential to guide action. Despite several improvements in estimating the burden of pediatric TB in the last decade, as well as enhanced data collection efforts, several data gaps remain, both at the global level, but also at the national level where surveillance systems and collaborative research are critical. In this article, we describe recent advances in data collection and burden estimates for TB among children and adolescents, and the remaining gaps. While data collection continues to improve, burden estimates must evolve in parallel, both in terms of their frequency and the methods used. Currently, at the global level, there is a focus on age-disaggregation of TB notifications, the collection of data on TB-HIV, multi-drug resistant (MDR)-TB and treatment outcomes, as well as estimates of the disease burden. Additional data from national surveillance systems or research projects on TB meningitis, as well as other forms of extra-pulmonary TB, would be useful. We must capitalize on the current momentum in child and adolescent TB to close the remaining data gaps for these age groups to better understand the epidemic and further reduce morbidity and mortality due to TB.

ABO Blood Groups Do Not Predict Schistosoma mansoni Infection Profiles in Highly Endemic Villages of Uganda.

Schistosoma mansoni is a parasite which causes significant public-health issues, with over 240 million people infected globally. In Uganda alone, approximately 11.6 million people are affected. Despite over a decade of mass drug administration in this country, hyper-endemic hotspots persist, and individuals who are repeatedly heavily and rapidly reinfected are observed. Human blood-type antigens are known to play a role in the risk of infection for a variety of diseases, due to cross-reactivity between host antibodies and pathogenic antigens. There have been conflicting results on the effect of blood type on schistosomiasis infection and pathology. Moreover, the effect of blood type as a potential intrinsic host factor on S. mansoni prevalence, intensity, clearance, and reinfection dynamics and on co-infection risk remains unknown. Therefore, the epidemiological link between host blood type and S. mansoni infection dynamics was assessed in three hyper-endemic communities in Uganda. Longitudinal data incorporating repeated pretreatment S. mansoni infection intensities and clearance rates were used to analyse associations between blood groups in school-aged children. Soil-transmitted helminth coinfection status and biometric parameters were incorporated in a generalised linear mixed regression model including age, gender, and body mass index (BMI), which have previously been established as significant factors influencing the prevalence and intensity of schistosomiasis. The analysis revealed no associations between blood type and S. mansoni prevalence, infection intensity, clearance, reinfection, or coinfection. Variations in infection profiles were significantly different between the villages, and egg burden significantly decreased with age. While blood type has proven to be a predictor of several diseases, the data collected in this study indicate that it does not play a significant role in S. mansoni infection burdens in these high-endemicity communities.

COVID-19 information dissemination in Uganda: Perspectives from sub-national health workers.

BACKGROUND: In many places, health workers at the sub-national level are on the frontlines of disseminating information about coronavirus (COVID-19) to communities. To ensure communities are receiving timely and accurate information, it is vital health workers are kept abreast of the most recent recommendations, and guidance. METHODS: An electronic survey was implemented to provide insights about the dissemination and utilisation of information and evidence related to the COVID-19 pandemic by health workers engaged at sub-national levels of the Ugandan health system. The aim of this survey was to provide insights about the dissemination and utilisation of information and evidence related to the coronavirus (COVID-19) pandemic by individuals engaged at sub-national levels of the health system. RESULTS: Mass media and public health campaigns and outreach activities were deemed the most suitable means to reach communities with COVID-19 information. Given the reported disruption to public outreach campaigns, this is a particularly important consideration for the provision of information to communities. All materials should be adapted to the local context. The need for information on homecare of COVID-19 patients was highlighted, along with the need for updated local statistics as to COVID-19 cases to be relayed for health workers at sub-national levels. CONCLUSIONS: Understanding the sources of information used by health workers can facilitate the transfer of relevant and timely information, which in turn increases the use of such information by the Ugandan population. It is vital that these issues are continued to be monitored, and communication modes and content are actively responsive to the time- and place-specific needs of health workers and community members.

Schistosoma mansoni Infection as a Predictor of Low Aerobic Capacity in Ugandan Children.

Using the 20-meter shuttle run test (20mSRT) as a morbidity metric, we assessed whether Schistosoma mansoni infection was associated with decreased aerobic capacity in Ugandan children across a range of altitudes, either at low (∼600 m) or high (∼1,000 m) altitudes. A total of 305 children were recruited from six schools within the Buliisa District, Lake Albert, Uganda. A subset (n = 96) of these had been previously assessed and treated for schistosomiasis ± malaria 2 weeks prior. Fitness scores on the 20mSRT were translated into VO2max using a standardized equation. Unadjusted and multivariable-adjusted analyses were performed using VO2max as the primary outcome. Analysis of fitness scores from 304 children, inclusive of the subset follow-up cohort, revealed a median VO2max of 45.4 mL kg-1 min-1 (interquartile range: 42.9-48.0 mL kg-1 min-1). Children residing at high altitudes demonstrated increased aerobic capacities (46.3 versus 44.8 mL kg-1 min-1, P = 0.031). The prevalence of stunting, wasting, S. mansoni egg patent infection, malaria, giardiasis, anemia, and fecal occult blood were 36.7%, 16.1%, 44.3%, 65.2%, 21.4%, 50.6%, and 41.2%, respectively. Median VO2max was elevated in those previously treated, compared with those newly recruited (46.3 versus 44 mL kg-1 min-1, P < 0.001). Multivariable-adjusted analysis revealed a strong negative association between S. mansoni egg patent infection and VO2max at low altitude (beta coefficient: -3.96, 95% CI: -6.56 to -137, P = 0.004). This is the first study to document a negative association between S. mansoni infection and aerobic capacity at low altitudes using the 20mSRT.

Non-invasive surveillance of Plasmodium infection by real-time PCR analysis of ethanol preserved faeces from Ugandan school children with intestinal schistosomiasis.

BACKGROUND: As part of ongoing co-surveillance of intestinal schistosomiasis and malaria in Ugandan school children, a non-invasive detection method for amplification of Plasmodium DNA using real-time (rt)PCR analysis of ethanol preserved faeces (EPF) was assessed. For diagnostic tabulations, results were compared to rtPCR analysis of dried blood spots (DBS) and field-based point-of-care (POC) rapid diagnostic tests (RDTs). METHODS: A total of 247 school children from 5 primary schools along the shoreline of Lake Albert were examined with matched EPF and DBS obtained. Mean prevalence and prevalence by school was calculated by detection of Plasmodium DNA by rtPCR using a 18S rDNA Taqman® probe. Diagnostic sensitivity, specificity, positive and negative predictive values were tabulated and compared against RDTs. RESULTS: By rtPCR of EPF and DBS, 158 (63.9%; 95% CI 57.8-69.7) and 198 (80.1%, 95% CI 74.7-84.6) children were positive for Plasmodium spp. By RDT, 138 (55.8%; 95% CI 49.6-61.9) and 45 (18.2%; 95% CI 13.9-23.5) children were positive for Plasmodium falciparum, and with non-P. falciparum co-infections, respectively. Using RDT results as a convenient field-based reference, the sensitivity of rtPCR of EPF and DBS was 73.1% (95% CI 65.2-79.8) and 94.2% (95% CI 88.9-97.0) while specificity was 47.7% (95% CI 38.5-57.0) and 37.6% (95% CI 29.0-46.9), respectively. With one exception, school prevalence estimated by analysis of EPF was higher than that by RDT. Positive and negative predictive values were compared and discussed. CONCLUSIONS: In this high transmission setting, EPF sampling with rtPCR analysis has satisfactory diagnostic performance in estimation of mean prevalence and prevalence by school upon direct comparison with POC-RDTs. Although analysis of EPF was judged inferior to that of DBS, it permits an alternative non-invasive sampling regime that could be implemented alongside general monitoring and surveillance for other faecal parasites. EPF analysis may also have future value in passive surveillance of low transmission settings.

Impact of a national deworming campaign on the prevalence of soil-transmitted helminthiasis in Uganda (2004-2016): Implications for national control programs.

BACKGROUND: Soil-transmitted Helminths and Anemia potentially reduce and retard cognitive and physical growth in school-age children with great implications for national control programs in Africa. After 13 years of deworming and limited health education campaigns, a study was undertaken to evaluate the impact of deworming interventions on the prevalence and intensity of soil-transmitted helminthic infections in school-age children in Uganda. METHODOLOGY: A cross-sectional study was carried out in six regions of Uganda, where two districts were randomly selected per region based on the ecological zones in the country. Included in the study were the districts; Mpigi and Nakasongola from the Central; Nakapiripirit and Kotido from Karamoja; Arua and Yumbe from West Nile; Gulu and Alebtong from the North; Kaliro and Mbale from the East; Hoima and Bundibugyo in the West. Five schools were randomly selected from each district and in each school 50 children aged 6-14 years were randomly selected. Stool samples were taken each child and examined for the presence of helminthic infections. A short pretested questionnaire was administered to each participant to obtain their knowledge, attitude, and practice relating to STH infections, their control. General observations were made on environmental sanitation in the schools. The location of each school was geo-referenced using a GPS machine (Garmin®GPSMAP62, Garmin Ltd, Southampton, UK). RESULTS: In total, 4,285 children were assessed including 719(16.82%) from central region, 718(16.80%) from eastern region, 719 (16.82%) from northern region, 689 (18.82%) from Karamoja region, 717(16.77%) from West Nile region and 723(16.91%) from western region. The average age of the children was 12.6 years with a standard deviation, SD 1.8 years and the minimum age was 6 years and upper age limit of 12 years. The percentage of boys (50.1%) and girls (49.9%) was comparable. 8.8% (95% CI; 8.0-9.7) were infected with at least any one STH species. Hookworm was the most prevalent (7.7%; 95% CI; 6.9-8.5) followed by whipworms (Trichuris trichiura) (1.3%; 95% CI; 1.0-1.7) and roundworms (Ascaris lumbricoides) (0.5%; 95% CI; 0.3-0.7). Some children had Schistosoma mansoni, 13.0% (95% CI; 12.0-14.0). All the children knew what soil transmitted helminths were (62.8%, 95% CI: 61.3-64.2) and most common knowledge of information were from; home (39%, 95% CI: 37.1-40.8), media (radio& newspaper)(11%, 95% CI: 9.8-12.2), school(65.7%, 95% CI: 63.9-67.5) and friends(11.5%, 95% CI: 10.3-12.7). Majority were aware of how one gets infected with soil transmitted helminths through; eating contaminated food (77.5%, 95% CI: 76.0-79.1), walking barefoot (59.6%, 95% CI: 57.8-61.5), drinking contaminated water (52.9%, 95% CI: 51.0-54.8), playing in dirty places (21.8%, 95% CI: 20.2-23.3) and dirty hands (2.3%, 95% CI: 1.7-2.9). CONCLUSION: Semi-annual deworming campaigns have proved effective in significantly reducing helminthic infections in most of the districts in Uganda. Regular evaluations are vital to assess impact of the interventions and guide programme implementation. Our data shows that the prevalence of infection has been reduced to a level where STH morbidity is no longer of public health importance in most districts surveyed.

Surveillance of intestinal schistosomiasis during control: a comparison of four diagnostic tests across five Ugandan primary schools in the Lake Albert region.

Programmatic surveillance of intestinal schistosomiasis during control can typically use four diagnostic tests, either singularly or in combination, but these have yet to be cross-compared directly. Our study assembled a complete diagnostic dataset, inclusive of infection intensities, from 258 children from five Ugandan primary schools. The schools were purposely selected as typical of the endemic landscape near Lake Albert and reflective of high- and low-transmission settings. Overall prevalence was: 44.1% (95% CI 38.0-50.2) by microscopy of duplicate Kato-Katz smears from two consecutive stools, 56.9% (95% CI 50.8-63.0) by urine-circulating cathodic antigen (CCA) dipstick, 67.4% (95% CI 61.6-73.1) by DNA-TaqMan® and 75.1% (95% CI 69.8-80.4) by soluble egg antigen enzyme-linked immunosorbent assay (SEA-ELISA). A cross-comparison of diagnostic sensitivities, specificities, positive and negative predictive values was undertaken, inclusive of a latent class analysis (LCA) with a LCA-model estimate of prevalence by each school. The latter ranged from 9.6% to 100.0%, and prevalence by school for each diagnostic test followed a static ascending order or monotonic series of Kato-Katz, urine-CCA dipstick, DNA-TaqMan® and SEA-ELISA. We confirm that Kato-Katz remains a satisfactory diagnostic standalone in high-transmission settings but in low-transmission settings should be augmented or replaced by urine-CCA dipsticks. DNA-TaqMan® appears suitable in both endemic settings though is only implementable if resources permit. In low-transmission settings, SEA-ELISA remains the method of choice to evidence an absence infection. We discuss the pros and cons of each method concluding that future surveillance of intestinal schistosomiasis would benefit from a flexible, context-specific approach both in choice and application of each diagnostic method, rather than a single one-size fits all approach.

Intestinal schistosomiasis in Uganda at high altitude (>1400 m): malacological and epidemiological surveys on Mount Elgon and in Fort Portal crater lakes reveal extra preventive chemotherapy needs.

BACKGROUND: Intestinal schistosomiasis is of public health importance in Uganda but communities living above 1400 m are not targeted for control as natural transmission is thought unlikely. To assess altitudinal boundaries and at-risk populations, conjoint malacological and epidemiological surveys were undertaken on Mount Elgon (1139 m-3937 m), in Fort Portal crater lakes and in the Rwenzori Mountains (1123 m-4050 m). METHODS: Seventy freshwater habitats [Mount Elgon (37), Fort Portal crater lakes (23), Rwenzori Mountains (8) and Lake Albert (2)] were inspected for Biomphalaria species. Water temperature, pH and conductivity were recorded. A parasitological examination of 756 schoolchildren [Mount Elgon (300), Fort Portal crater lakes (456)] by faecal microscopy of duplicate Kato-Katz smears from two consecutive stool samples was bolstered by antigen (urine-CCA dipstick) and antibody (SEA-ELISA) diagnostic assays. RESULTS: Biomphalaria spp. was found up to 1951 m on Mount Elgon and 1567 m in the Fort Portal crater lakes. Although no snail from Mount Elgon shed cercariae, molecular analysis judged 7.1% of snails sampled at altitudes above 1400 m as having DNA of Schistosoma mansoni; in Fort Portal crater lakes three snails shed schistosome cercariae. Prevalence of intestinal schistosomiasis as measured in schoolchildren by Kato-Katz (Mount Elgon = 5.3% v. Fort Portal crater lakes = 10.7%), CCA urine-dipsticks (18.3% v. 34.4%) and SEA-ELISA (42.3% v. 63.7%) showed negative associations with increasing altitude with some evidence of infection up to 2000 m. CONCLUSIONS: Contrary to expectations, these surveys clearly show that natural transmission of intestinal schistosomiasis occurs above 1400 m, possibly extending up to 2000 m. Using spatial epidemiological predictions, this now places some extra six million people at-risk, denoting an expansion of preventive chemotherapy needs in Uganda.

An extensive burden of giardiasis associated with intestinal schistosomiasis and anaemia in school children on the shoreline of Lake Albert, Uganda.

BACKGROUND: Water-borne parasitic diseases associated with poverty still blight the lives of African school children. In Uganda, intestinal schistosomiasis is still common along the shoreline of Lake Albert, despite ongoing control, and co-infection with giardiasis and malaria is poorly described. To shed light on putative interactions between diseases, a prospective cross-sectional parasitological survey was undertaken in five primary schools. METHODS: Stool samples from 254 school children, aged 5-10 years, were examined by microscopy and rapid diagnostic tests (RDTs), with additional real-time PCR assays for detection of Giardia DNA. A finger-prick blood sample was also taken from each child and tested for malaria, and haemoblobin levels measured. Assocations between diseases and anaemia were assessed. RESULTS: Intestinal schistosomiasis (46.5%), giardiasis (41.6%) and malaria (56.2%) were common, and a quarter of children were anaemic (<115 g/L). Up to 87.0% of children were excreting Giardia DNA and the prevalence of heavy infection by real-time PCR (Ct≤19) was 19.5%, being positively associated with light, moderate and heavy egg-patent schistosomiasis, as well as with anaemia. CONCLUSIONS: In this setting, an extensive burden of giardiasis was revealed with heavy intensity infections associated with egg-patent intestinal schistosomiasis and anaemia. To improve child health, greater attention on giardiasis is needed along with exploring joined-up actions across diseases that promote better water hygiene and sanitation measures.

Mapping of Schistosomiasis and Soil-Transmitted Helminths in Namibia: The First Large-Scale Protocol to Formally Include Rapid Diagnostic Tests.

BACKGROUND: Namibia is now ready to begin mass drug administration of praziquantel and albendazole against schistosomiasis and soil-transmitted helminths, respectively. Although historical data identifies areas of transmission of these neglected tropical diseases (NTDs), there is a need to update epidemiological data. For this reason, Namibia adopted a new protocol for mapping of schistosomiasis and geohelminths, formally integrating rapid diagnostic tests (RDTs) for infections and morbidity. In this article, we explain the protocol in detail, and introduce the concept of 'mapping resolution', as well as present results and treatment recommendations for northern Namibia. METHODS/FINDINGS/INTERPRETATION: This new protocol allowed a large sample to be surveyed (N = 17,896 children from 299 schools) at relatively low cost (7 USD per person mapped) and very quickly (28 working days). All children were analysed by RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2, P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall prevalence of geohelminths, more particularly hookworm infection, was 12.2%, highly associated with presence of faecal occult blood (OR = 1.9, P<0.001). Prevalence maps were produced and hot spots identified to better guide the national programme in drug administration, as well as targeted improvements in water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen and microhaematuria for Schistosoma mansoni and S. haematobium, respectively) performed well, with sensitivities above 80% and specificities above 95%. CONCLUSION/SIGNIFICANCE: This protocol is cost-effective and sensitive to budget limitations and the potential economic and logistical strains placed on the national Ministries of Health. Here we present a high resolution map of disease prevalence levels, and treatment regimens are recommended.

Effect of water temperature and population density on the population dynamics of Schistosoma mansoni intermediate host snails.

BACKGROUND: Mathematical models can be used to identify areas at risk of increased or new schistosomiasis transmission as a result of climate change. The results of these models can be very different when parameterised to different species of host snail, which have varying temperature preferences. Currently, the experimental data needed by these models are available for only a few species of snail. The choice of density-dependent functions can also affect model results, but the effects of increasing densities on Biomphalaria populations have only previously been investigated in artificial aquariums. METHODS: Laboratory experiments were conducted to estimate Biomphalaria sudanica mortality, fecundity and growth rates at ten different constant water temperatures, ranging from 13-32°C. Snail cages were used to determine the effects of snail densities on B. sudanica and B. stanleyi mortality and fecundity rates in semi-natural conditions in Lake Albert. RESULTS: B. sudanica survival and fecundity were highest at 20°C and 22°C respectively. Growth in shell diameter was estimated to be highest at 23°C in small and medium sized snails, but the relationship between temperature and growth was not clear. The fecundity of both B. sudanica and B. stanleyi decreased by 72-75% with a four-fold increase in population density. Increasing densities four-fold also doubled B. stanleyi mortality rates, but had no effect on the survival of B. sudanica. CONCLUSIONS: The optimum temperature for fecundity was lower for B. sudanica than for previously studied species of Biomphalaria. In contrast to other Biomphalaria species, B. sudanica have a distinct peak temperature for survival, as opposed to a plateau of highly suitable temperatures. For both B. stanleyi and B. sudanica, fecundity decreased with increasing population densities. This means that snail populations may experience large fluctuations in numbers, even in the absence of any external factors such as seasonal temperature changes. Survival also decreased with increasing density for B. stanleyi, in contrast to B. sudanica and other studied Biomphalaria species where only fecundity has been shown to decrease.

Detection of persistent Plasmodium spp. infections in Ugandan children after artemether-lumefantrine treatment.

During a longitudinal study investigating the dynamics of malaria in Ugandan lakeshore communities, a consistently high malaria prevalence was observed in young children despite regular treatment. To explore the short-term performance of artemether-lumefantrine (AL), a pilot investigation into parasite carriage after treatment(s) was conducted in Bukoba village. A total of 163 children (aged 2-7 years) with a positive blood film and rapid antigen test were treated with AL; only 8.7% of these had elevated axillary temperatures. On day 7 and then on day 17, 40 children (26.3%) and 33 (22.3%) were positive by microscopy, respectively. Real-time PCR analysis demonstrated that multi-species Plasmodium infections were common at baseline, with 41.1% of children positive for Plasmodium falciparum/Plasmodium malariae, 9.2% for P. falciparum/ Plasmodium ovale spp. and 8.0% for all three species. Moreover, on day 17, 39.9% of children infected with falciparum malaria at baseline were again positive for the same species, and 9.2% of those infected with P. malariae at baseline were positive for P. malariae. Here, chronic multi-species malaria infections persisted in children after AL treatment(s). Better point-of-care diagnostics for non-falciparum infections are needed, as well as further investigation of AL performance in asymptomatic individuals.

Performance and safety of praziquantel for treatment of intestinal schistosomiasis in infants and preschool children.

BACKGROUND: In 2012 the WHO formally recognised that infants and preschool children are at significant risk of schistosomiasis and qualify for treatment with praziquantel (PZQ). Targeted surveys determining both the performance and safety of this drug are now needed in endemic areas. We have formally assessed parasitological cure and putative side-effects in a prospective cohort of Schistosoma mansoni-infected children (aged 5 months-7 years old) in lakeshore settings of Uganda. METHODOLOGY/PRINCIPAL FINDINGS: From a total of 369 children found to be egg-patent for intestinal schistosomiasis, 305 were followed-up three to four weeks after PZQ treatment and infection status re-assessed. Separately, a previously tested side-effect questionnaire was employed before and 24 hours after PZQ treatment to assess incidence and amelioration of symptoms in young children and their mothers. While the overall observed parasitological cure was 56.4%, a significant difference was found between a sub-set of children who had a history of multiple PZQ treatments (between one and four in an 18 month period), where cure rate was 41.7%, and those who had never received treatment (cure rate was 77·6%). PZQ proved to be safe, with only mild reported side effects which cleared within a month after treatment. Prevalence of reported symptoms was significantly lower in children than in mothers, and fewer side-effects were reported upon subsequent rounds of PZQ treatment. CONCLUSION/SIGNIFICANCE: Our findings show that PZQ treatment of young children resulted in satisfactory cure rates, and marked reduction in egg-output, with only mild and transient reported side-effects. However, the cure rate is clearly lower in younger children and those with history of previous treatment. Cure rate, but not egg reduction rate, was also lower in children with heavier pre-intervention infection intensity. With chemotherapy now recommended as a long-term strategy for disease control in young children, research into optimising the periodicity of targeted treatment strategies is now crucial.

Opt-out HIV testing during antenatal care: experiences of pregnant women in rural Uganda.

Two years after the introduction of provider-initiated, opt-out HIV counselling and testing during antenatal care (ANC) in Uganda, HIV testing uptake is still low. This study was carried out to explore pregnant women's experiences of, and views on, the policies for opt-out, and couple HIV testing, and to understand how the policy implementation could be improved in order to increase access to prevention of mother-to-child-transmission (PMTCT) services. The study was conducted at three ANC health facilities at different levels of care in rural eastern Uganda. Data were collected through sit-in observations during ANC and 18 semi-structured interviews with pregnant women receiving ANC, and thereafter analysed using latent content analysis. Pregnant women who received ANC from facilities that provided HIV testing on-site perceived HIV testing as compulsory without actually fully realizing the benefits of HIV testing and PMTCT. No referral for HIV testing or information about testing was given at ANC facilities that lacked HIV testing on-site. A major challenge of couple HIV testing was that pregnant women were made responsible for recruiting their spouses for testing, a precarious dilemma for many women who tried to fulfil health workers' requests without having the power to do so. In order to increase uptake of PMTCT services, the pre-test counselling in groups that precedes the provider-initiated HIV testing should be adjusted to inform women about the benefits of PMTCT. Further, if testing is perceived as compulsory it could potentially deter some women from seeking ANC services. In order to increase HIV testing of male partners new strategies are needed, for example peer-sensitization and male clinics. Moreover, to achieve the desired outcomes of the PMTCT programme, monitoring and evaluation should be built into the programme.

Genetic diversity of Ascaris in southwestern Uganda.

Despite the common occurrence of ascariasis in southwestern Uganda, helminth control in the region has been limited. To gain further insights into the genetic diversity of Ascaris in this area, a parasitological survey in mothers (n=41) and children (n=74) living in two villages, Habutobere and Musezero, was carried out. Adult Ascaris worms were collected from infected individuals by chemo-expulsion using pyrantel pamoate treatment. Genetic diversity within these worms was assessed by inspection of DNA sequence variation in a mitochondrial marker and length polymorphism at microsatellite loci. Overall prevalence of ascariasis was 42.5% in mothers and 30.4% in their children and a total of 98 worms was examined from 18 hosts. Sequence analysis of a portion of the mitochondrial cytochrome c oxidase subunit 1 gene revealed 19 different haplotypes, 13 of which had not been previously encountered. Microsatellite analysis using eight loci provided evidence for high gene flow between worm populations from the two villages but comparing these worms with others obtained in a prior study on Unguja, Zanzibar, confirmed little genetic exchange and mixing of worm populations between the two areas. By adding to our understanding of the genetic diversity of Ascaris in Africa, this study provides useful information for monitoring changes in parasite population structure in the face of ongoing and future control.

Schistosoma mansoni Infections in young children: when are schistosome antigens in urine, eggs in stool and antibodies to eggs first detectable?

BACKGROUND: in uganda, control of intestinal schistosomiasis with preventive chemotherapy is typically focused towards treatment of school-aged children; the needs of younger children are presently being investigated as in lakeshore communities very young children can be infected. In the context of future epidemiological monitoring, we sought to compare the detection thresholds of available diagnostic tools for Schistosoma mansoni and estimate a likely age of first infection for these children. METHODS AND FINDINGS: a total of 242 infants and preschool children (134 boys and 108 girls, mean age 2.9 years, minimum 5 months and maximum 5 years) were examined from Bugoigo, a well-known disease endemic village on Lake Albert. Schistosome antigens in urine, eggs in stool and host antibodies to eggs were inspected to reveal a general prevalence of 47.5% (CI(95) 41.1-54.0%), as ascertained by a positive criterion from at least one diagnostic method. Although children as young as 6 months old could be found infected, the average age of infected children was between 3»-3¾ years, when diagnostic techniques became broadly congruent. CONCLUSION: whilst different assays have particular (dis)advantages, direct detection of eggs in stool was least sensitive having a temporal lag behind antigen and antibody methods. Setting precisely a general age of first infection is problematic but if present Ugandan policies continue, a large proportion of infected children could wait up to 3-4 years before receiving first medication. To better tailor treatment needs for this younger ageclass, we suggest that the circulating cathodic antigen urine dipstick method to be used as an epidemiological indicator.