ABSTRACT
In a cross-sectional analysis of 354 Ugandan children (age 12-48 months) infected with Schistosoma mansoni, we assessed relationships between infection intensity and nutritional morbidities. Higher intensity was associated with an increased risk for anemia (RR = 1.05, 95% confidence interval [CI] 1.01-1.10) yet not associated with risk for underweight, stunting, or wasting.
Subject(s)
Anemia , Schistosomiasis mansoni , Child , Animals , Humans , Child, Preschool , Infant , Schistosomiasis mansoni/complications , Schistosomiasis mansoni/epidemiology , Uganda/epidemiology , Nutritional Status , Cross-Sectional Studies , Prevalence , Schistosoma mansoni , Anemia/epidemiology , Anemia/etiologyABSTRACT
Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.
ABSTRACT
Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.
Subject(s)
Anthelmintics , Helminthiasis , Schistosomiasis , Child , Humans , Child, Preschool , Praziquantel/therapeutic use , Schistosomiasis/drug therapy , Schistosomiasis/epidemiology , Schistosomiasis/prevention & control , Helminthiasis/drug therapy , Mass Drug Administration , Prevalence , World Health Organization , Anthelmintics/therapeutic useABSTRACT
BACKGROUND: There is a limited understanding of how diarrhoeal cases across other household members influence the likelihood of diarrhoea in young children (aged 1-4 years). METHODS: We surveyed 16,025 individuals from 3421 households in 17 villages in Uganda. Using logistic regressions with standard errors clustered by household, diarrhoeal cases within households were used to predict diarrhoeal outcomes in young children. Regressions were adjusted for socio-demographic, water, sanitation, and hygiene (WASH), and ecological covariates. Selection bias for households with (1632/3421) and without (1789/3421) young children was examined. RESULTS: Diarrhoeal prevalence was 13.7% (2118/16,025) across all study participants and 18.5% (439/2368) in young children. Young children in households with any other diarrhoeal cases were 5.71 times more likely to have diarrhoea than young children in households without any other diarrhoeal cases (95% CI: 4.48-7.26), increasing to over 29 times more likely when the other diarrhoeal case was in another young child (95% CI: 16.29-54.80). Diarrhoeal cases in older household members (aged ≥ 5 years) and their influence on the likelihood of diarrhoea in young children attenuated with age. School-aged children (5-14 years) had a greater influence on diarrhoeal cases in young children (Odds Ratio 2.70, 95% CI: 2.03-3.56) than adults of reproductive age (15-49 years; Odds Ratio 1.96, 95% CI: 1.47-2.59). Diarrhoeal cases in individuals aged ≥ 50 years were not significantly associated with diarrhoeal outcomes in young children (P > 0.05). These age-related differences in diarrhoeal exposures were not driven by sex. The magnitude and significance of the odds ratios remained similar when odds ratios were compared by sex within each age group. WASH factors did not influence the likelihood of diarrhoea in young children, despite influencing the likelihood of diarrhoea in school-aged children and adults. Households with young children differed from households without young children by diarrhoeal prevalence, household size, and village WASH infrastructure and ecology. CONCLUSIONS: Other diarrhoeal cases within households strongly influence the likelihood of diarrhoea in young children, and when controlled, removed the influence of WASH factors. Future research on childhood diarrhoea should consider effects of diarrhoeal cases within households and explore pathogen transmission between household members.
Subject(s)
Diarrhea , Sanitation , Adult , Aged , Child , Child, Preschool , Cross-Sectional Studies , Diarrhea/epidemiology , Humans , Hygiene , Infant , Uganda/epidemiology , WaterABSTRACT
Malaria-schistosomiasis coinfections are common in sub-Saharan Africa but studies present equivocal results regarding the interspecific relationships between these parasites. Through mixed-model analyses of a dataset of Ugandan preschool children, we explore how current coinfection and prior infection with either Schistosoma mansoni or Plasmodium species alter subsequent Plasmodium intensity, Plasmodium risk, and S mansoni risk. Coinfection and prior infections with S mansoni were associated with reduced Plasmodium intensity, moderated by prior Plasmodium infections, wealth, and host age. Future work should assess whether these interactions impact host health and parasite control efficacy in this vulnerable age group.
Subject(s)
Coinfection , Malaria , Plasmodium , Schistosomiasis mansoni , Animals , Child, Preschool , Coinfection/complications , Humans , Malaria/parasitology , Schistosoma haematobium , Schistosoma mansoni , Schistosomiasis mansoni/complications , Schistosomiasis mansoni/epidemiology , Schistosomiasis mansoni/parasitology , Uganda/epidemiologyABSTRACT
BACKGROUND: The interaction of socio-demographic and ecological factors with Schistosoma mansoni (S. mansoni) infection risk by age and the household clustering of infections between individuals are poorly understood. METHODS: This study examined 1,832 individuals aged 5-90 years across 916 households in Mayuge District, Uganda. S. mansoni infection status and intensity were measured using Kato-Katz microscopy. Socio-demographic and ecological factors were examined as predictors of infection status and intensity using logistic and negative binomial regression models, respectively, with standard errors clustered by household. A subgroup analysis of children was conducted to examine the correlation of infection status between children and their caretakers. FINDINGS: Infection varied within age groups based on the distance to Lake Victoria. Children aged 9-17 years and young adults aged 18-29 years who lived ≤0.50km from Lake Victoria were more likely to be infected compared to individuals of the same age who lived further away from the lake. Infections clustered within households. Children whose caretakers were heavily infected were 2.67 times more likely to be infected. CONCLUSION: These findings demonstrate the focality of schistosome transmission and its dependence on socio-demographic, ecological and household factors. Future research should investigate the sampling of households within communities as a means of progressing towards precision mapping of S. mansoni infections.
Subject(s)
Logistic Models , Schistosoma mansoni/pathogenicity , Schistosomiasis mansoni/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Child , Child, Preschool , Cross-Sectional Studies , Family Characteristics , Feces/parasitology , Female , Humans , Lakes , Male , Middle Aged , Risk Factors , Schistosomiasis mansoni/parasitology , Schools , Uganda/epidemiology , Young AdultABSTRACT
BACKGROUND: Health related quality of life measurements are vital elements of public health surveillance that uncover unmet health needs and predict the success of health interventions. We described health related quality of life measurements using the EuroQoL 5-dimension (EQ-VAS/EQ-5D) instrument and associated factors among patients with upper gastrointestinal bleeding (UGIB) and hepatic schistosomiasis at a rural health facility in the Albert Nile Basin, Uganda. METHODS AND MATERIALS: This was a cross-sectional study at Pakwach Health Centre IV. Participants included adult inpatients and outpatients with a history of UGIB and ultrasound evidence of hepatic schistosomiasis. We evaluated and recorded each participant's medical history, physical examination, laboratory tests results, ultrasound results, and endoscopy findings. We also recorded health related quality of life measurements using the EuroQoL 5-dimension instrument and derived disability weights from EQ-VAS and EQ-5D measurements. These were our dependent variables. Descriptive and inferential statistics were generated summarizing our findings. RESULTS: We found 103 participants had a history of upper gastrointestinal bleeding and hepatosplenic schistosomiasis. Sixty percent were between the ages of 30-49 years, 59% were females, 74% were farmers, 92% had splenomegaly, 88% had varices at endoscopy, 22% were medical emergencies with acute variceal upper gastrointestinal bleeding, and 62% had anemia. Measures of the different dimensions of health from 101 participants with patient reported outcomes revealed 77 (76%) participants experienced problems in self-care, 89 (88%) participants reported anxiety or depression, and 89 (88%) participants experienced pain or discomfort. The median EQ-VAS derived disability weights and median EQ-5D index-derived disability weights were 0.3 and 0.34, respectively. Acute upper gastrointestinal bleeding, praziquantel drug treatment, and age by decade predicted higher EQ-VAS derived disability weights (p value < 0.05). Under weight (Body mass index ≤ 18.5), acute upper gastrointestinal bleeding, ascites, age by decade, female gender, and praziquantel drug treatment predicted higher EQ-5D index- derived disability weights (p value < 0.05). CONCLUSION: Adult patients with upper gastrointestinal bleeding and hepatic schistosomiasis from this primary health facility experience poor health and considerable health loss. Several factors predicted increased health loss. These factors probably represent key areas of health intervention towards mitigating increased health loss in this population.
ABSTRACT
BACKGROUND: Over 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used "off label" in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis. METHODS: We will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12-47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters. DISCUSSION: The trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03640377 . Registered on 21 Aug 2018.
Subject(s)
Anthelmintics , Schistosomiasis mansoni , Animals , Anthelmintics/adverse effects , Child , Child, Preschool , Clinical Trials, Phase II as Topic , Humans , Praziquantel/adverse effects , Randomized Controlled Trials as Topic , Schistosoma mansoni , Schistosomiasis mansoni/diagnosis , Schistosomiasis mansoni/drug therapy , Treatment OutcomeABSTRACT
Control and elimination of the parasitic disease schistosomiasis relies on mass administration of praziquantel. Whilst these programmes reduce infection prevalence and intensity, their impact on parasite transmission and evolution is poorly understood. Here we examine the genomic impact of repeated mass drug administration on Schistosoma mansoni populations with documented reduced praziquantel efficacy. We sequenced whole-genomes of 198 S. mansoni larvae from 34 Ugandan children from regions with contrasting praziquantel exposure. Parasites infecting children from Lake Victoria, a transmission hotspot, form a diverse panmictic population. A single round of treatment did not reduce this diversity with no apparent population contraction caused by long-term praziquantel use. We find evidence of positive selection acting on members of gene families previously implicated in praziquantel action, but detect no high frequency functionally impactful variants. As efforts to eliminate schistosomiasis intensify, our study provides a foundation for genomic surveillance of this major human parasite.
Subject(s)
Mass Drug Administration , Praziquantel/pharmacology , Schistosoma mansoni/genetics , Whole Genome Sequencing , Animals , Child , Female , Humans , Male , Schistosoma mansoni/drug effects , Schistosomiasis mansoni/drug therapy , UgandaABSTRACT
BACKGROUND: There is a general consensus that widespread use of praziquantel in populations where schistosomiasis is endemic prevents development of hepatic schistosomiasis and its complications. However, a few studies have reported discordant findings linking praziquantel to the occurrence of upper gastrointestinal bleeding (UGIB) in some patients with hepatic schistosomiasis and varices. OBJECTIVE: We explored if there was any causal association between recent praziquantel use (rPZQ) and upper gastrointestinal bleeding in hepatic schistosomiasis in rural Africa. PATIENTS AND METHODS: A quasi-experimental, retrospective case-controlled study was performed. It involved adult patients with past or acute UGIB, varices, periportal fibrosis, and/or cirrhosis. Cases had acute variceal bleeding while controls did not. The outcome was the frequency of lifetime episodes of UGIB and exposure was rPZQ (received praziquantel in the last 11 months from the date of enrollment). The data analysis included 2 × 2 tables, logistic regression, and propensity-score matching. Odds ratios (ORs), average treatment effects (ATEs), and their 95% confidence intervals (CIs) were used for inference. RESULTS: Over 6 weeks, we enrolled 19 cases with 92 lifetime episodes of UGIB, and 66 controls with 192 lifetime episodes of UGIB. Cases were more likely to experience UGIB than controls following rPZQ (92% vs. 62%; OR 7.6; 95% CI 3.4-17). Factors predictive of more lifetime episodes of UGIB at multivariable analysis included rPZQ (adjusted OR 13; 95% CI 2.9-53), relative leukocytosis (adjusted OR 26; 95% CI 7.6-89), large varices (adjusted OR 5.0; 95% CI 1.7-15), a family member with hepatosplenic schistosomiasis (adjusted OR 19; 95% CI 7.4-51), advanced periportal fibrosis (adjusted OR 8.0; 95% CI 2.6-22), ascites (adjusted OR 14; 95% CI 4.3-47), and jaundice (adjusted OR 32; 95% CI 7.8-128). While the ATE following rPZQ among the treated was 0.40 (95% CI 0.33-0.48). CONCLUSIONS: Our findings suggest the presence of a plausible causal association between recent praziquantel use and increased frequency of UGIB in our study population.
ABSTRACT
BACKGROUND: Mass drug administration (MDA) is a cornerstone of control of parasitic helminths. In schistosomiasis-endemic areas with >50% of school-aged children infected, community-wide MDA with praziquantel is recommended by the World Health Organisation (WHO), with target coverage of >75%. Using data from a cluster-randomised trial of MDA treatment strategies, we aimed to describe the proportion of eligible residents who received MDA and predictors of treatment receipt, and to assess associations with helminth prevalence. METHODS: In the Koome islands of Lake Victoria, Uganda, where baseline schistosomiasis prevalence (by single stool sample, Kato Katz) was 52% overall (all ages) and 67% among school-aged children, we conducted a cluster-randomised trial of community-wide, intensive MDA (quarterly single-dose praziquantel 40mg/kg; triple-dose albendazole 400mg) versus standard, Uganda government intervention (annual single-dose praziquantel 40mg/kg; 6-monthly single-dose albendazole). Twenty-six fishing villages were randomised, 13 per trial arm, for four years. At each treatment round, praziquantel treatment and the first dose of albendazole treatment were directly observed by the study team, registers of village residents were updated and the proportion receiving treatment among those eligible recorded. RESULTS: During the four-year MDA, at each treatment round an average of 13,382 people were registered in the 26 villages (7,153 and 6,229 in standard and intensive intervention villages, respectively). Overall, the proportion of those eligible receiving praziquantel was lower than for albendazole (60% versus 65%), particularly in the standard arm (61% versus 71%) compared to the intensive arm (60% versus 62%). Albendazole receipt was lower when given concurrently with praziquantel. Absence was the commonest reason for non-receipt of treatment (81% albendazole, 77% praziquantel), followed by refusal (14% albendazole, 18% praziquantel). Proportions receiving treatment were lowest among school-aged children, but did not differ by sex. Longitudinal analysis of a subgroup of residents who did not move during the study period found that persistent non-receipt of treatment in this subgroup was rare. Refusal to receive treatment was highest among adults and more common among females. CONCLUSION: In schistosomiasis high-risk communities, a combination of approaches to increasing treatment coverage, such as extended periods of treatment delivery, and the provision of incentives, may be required to achieve WHO targets.
Subject(s)
Anthelmintics/administration & dosage , Mass Drug Administration/statistics & numerical data , Schistosomiasis/drug therapy , Schistosomiasis/epidemiology , Treatment Refusal/statistics & numerical data , Adolescent , Adult , Albendazole/administration & dosage , Animals , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Lakes , Linear Models , Male , Middle Aged , Praziquantel/administration & dosage , Prevalence , Residence Characteristics , Uganda/epidemiology , Young AdultABSTRACT
BACKGROUND: Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure. METHODS: We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test of cure was done in participants who were positive on both urine circulating cathodic antigen test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants. RESULTS: Single-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio, 0.65; 95% CI, 0.27 to 1.58); ERRs were 94% and 81% (difference, -13%; 95% CI, -48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA. CONCLUSIONS: In this schistosomiasis hot spot, there was little evidence of decreased praziquantel efficacy. However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era.
ABSTRACT
BACKGROUND: A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. METHODS: We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. RESULTS: Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. CONCLUSIONS: Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.
Subject(s)
Anthelmintics/therapeutic use , Praziquantel/therapeutic use , Schistosoma mansoni/drug effects , Schistosoma mansoni/genetics , Schistosomiasis mansoni/drug therapy , Animals , Child , Drug Resistance , Female , Genetic Variation , Genotype , Humans , Longitudinal Studies , Male , Mass Drug Administration , Phylogeny , Schistosoma mansoni/classification , Schistosoma mansoni/growth & development , Schistosomiasis mansoni/epidemiology , Schistosomiasis mansoni/parasitology , Uganda/epidemiologyABSTRACT
BACKGROUND: Despite decades of community-based mass drug administration (MDA) for neglected tropical diseases, it remains an open question as to what constitutes the best combination of community medicine distributors (CMDs) for achieving high (>65%/75%) treatment rates within a village. METHODS: Routine community-based MDA was evaluated in Mayuge District, Uganda. For one month, we tracked 6,148 individuals aged 1+ years in 1,118 households from 28 villages. Praziquantel, albendazole, and ivermectin were distributed to treat Schistosoma mansoni, lymphatic filariasis, and soil-transmitted helminths. The similarity/diversity between CMDs was observed and used to predict the division of labour and overall village treatment rates. The division of labour was calculated by dividing the lowest treatment rate by the highest treatment rate achieved by two CMDs within a village. CMD similarity was measured for 16 characteristics including friendship network overlap, demographic and socioeconomic factors, methods of CMD selection, and years as CMD. Relevant variables for MDA outcomes were selected through least absolute shrinkage and selection operators with leave-one-out cross validation. Final models were run with ordinary least squares regression and robust standard errors. RESULTS: The percentage of individuals treated with at least one drug varied across villages from 2.79-89.74%. The only significant predictor (p-value<0.05) of village treatment rates was the division of labour. The estimated difference between a perfectly equal (a 50-50 split of individuals treated) and unequal (one CMD treating no one) division of labour was 39.69%. A direct tie (close friendship) between CMDs was associated with a nearly twofold more equitable distribution of labour when compared to CMDs without a direct tie. CONCLUSIONS: An equitable distribution of labour between CMDs may be essential for achieving treatment targets of 65%/75% within community-based MDA. To improve the effectiveness of CMDs, national programmes should explore interventions that seek to facilitate communication, friendship, and equal partnership between CMDs.
Subject(s)
Anthelmintics/administration & dosage , Community Health Workers/statistics & numerical data , Elephantiasis, Filarial/drug therapy , Neglected Diseases/drug therapy , Schistosomiasis mansoni/drug therapy , Adolescent , Adult , Aged , Albendazole/administration & dosage , Animals , Child , Child, Preschool , Community Medicine/statistics & numerical data , Cross-Sectional Studies , Female , Humans , Infant , Ivermectin/administration & dosage , Male , Mass Drug Administration , Middle Aged , Praziquantel/administration & dosage , Rural Population , Uganda , Young AdultABSTRACT
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.
Subject(s)
Epidemiological Monitoring , Feces/parasitology , Malaria/diagnosis , Parasitology/methods , Plasmodium/isolation & purification , Real-Time Polymerase Chain Reaction/methods , Specimen Handling/methods , Child , Cross-Sectional Studies , DNA, Protozoan/genetics , DNA, Ribosomal/genetics , Female , Humans , Malaria/epidemiology , Male , Prevalence , RNA, Ribosomal, 18S/genetics , Schistosomiasis mansoni/complications , Sensitivity and Specificity , Uganda/epidemiologyABSTRACT
BACKGROUND: The most prevalent neglected tropical diseases are treated through blanket drug distribution that is reliant on lay community medicine distributors (CMDs). Yet, treatment rates achieved by CMDs vary widely and it is not known which CMDs treat the most people. METHODS: In Mayuge District, Uganda, we tracked 6779 individuals (aged 1+ years) in 1238 households across 31 villages. Routine, community-based mass drug administration (MDA) was implemented for schistosomiasis, lymphatic filariasis, and soil-transmitted helminths. For each CMD, the percentage of eligible individuals treated (offered and ingested medicines) with at least one drug of praziquantel, albendazole, or ivermectin was examined. CMD attributes (more than 25) were measured, ranging from altruistic tendencies to socioeconomic characteristics to MDA-specific variables. The predictors of treatment rates achieved by CMDs were selected with least absolute shrinkage and selection operators and then analyzed in ordinary least squares regression with standard errors clustered by village. The influences of participant compliance and the ordering of drugs offered also were examined for the treatment rates achieved by CMDs. RESULTS: Overall, only 44.89% (3043/6779) of eligible individuals were treated with at least one drug. Treatment rates varied amongst CMDs from 0% to 84.25%. Treatment rate increases were associated (p value< 0.05) with CMDs who displayed altruistic biases towards their friends (13.88%), had friends who helped with MDA (8.43%), were male (11.96%), worked as fishermen/fishmongers (14.93%), and used protected drinking water sources (13.43%). Only 0.24% (16/6779) of all eligible individuals were noncompliant by refusing to ingest all offered drugs. Distributing praziquantel first was strongly, positively correlated (p value < 0.0001) with treatment rates for albendazole and ivermectin. CONCLUSIONS: These findings profile CMDs who treat the most people during routine MDA. Criteria currently used to select CMDs-community-wide meetings, educational attainment, age, years as a CMD, etc.-were uninformative. Participant noncompliance and the provision of praziquantel before albendazole and ivermectin did not negatively impact treatment rates achieved by CMDs. Engaging CMD friend groups with MDA, selecting CMDs who practise good preventative health behaviours, and including CMDs with high-risk occupations for endemic infections may improve MDA treatment rates. Evidence-based guidelines are needed to improve the monitoring, selection, and replacement of CMDs during MDA.
Subject(s)
Antiparasitic Agents/therapeutic use , Community Medicine/organization & administration , Delivery of Health Care/organization & administration , Elephantiasis, Filarial/drug therapy , Helminthiasis/drug therapy , Mass Drug Administration , Schistosomiasis/drug therapy , Soil/parasitology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Child , Child, Preschool , Community Medicine/standards , Community Medicine/statistics & numerical data , Delivery of Health Care/standards , Delivery of Health Care/statistics & numerical data , Efficiency, Organizational , Elephantiasis, Filarial/epidemiology , Elephantiasis, Filarial/transmission , Female , Helminthiasis/epidemiology , Helminthiasis/transmission , Humans , Infant , Male , Mass Drug Administration/methods , Mass Drug Administration/standards , Mass Drug Administration/statistics & numerical data , Middle Aged , Prevalence , Schistosomiasis/epidemiology , Schistosomiasis/transmission , Uganda/epidemiology , Work Performance , Young AdultABSTRACT
As part of an epidemiological survey for gastrointestinal parasites in school children across five primary schools on the shoreline of Lake Albert, the prevalence of giardiasis was 87.0% (nâ¯=â¯254) as determined by real-time PCR analysis of faecal samples with a genus-specific Giardia 18S rDNA probe. Faecal samples were further characterised with taxon assemblage-specific triose phosphate isomerase (TPI) Taqman® probes and by sequence characterisation of the ß-giardin gene. While less sensitive than the 18S rDNA assay, general prevalence by TPI probes was 52.4%, with prevalence by taxon assemblage of 8.3% (assemblage A), 35.8% (assemblage B) and 8.3% co-infection (A & B assemblages). While assemblage B was dominant across the sample, proportions of assemblages A and B, and co-infections thereof, varied by school and by age of child; mixed infections were particularly common at Runga school (ORâ¯=â¯6.9 [95% CI; 2.5, 19.3]) and in children aged 6 and under (ORâ¯=â¯2.7 [95% CI; 1.0, 7.3]). Infection with assemblage B was associated with underweight children (ORâ¯=â¯2.0 [95% CI; 1.0, 3.9]). The presence of each assemblage was also confirmed by sequence analysis of the ß-giardin gene finding sub-assemblage AII and further genetic diversity within assemblage B. To better explore the local epidemiology of giardiasis and its impact on child health, additional sampling of school children with assemblage typing would be worthwhile.
ABSTRACT
Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa, and a significant cause of morbidity; it is a priority for vaccine development. A controlled human infection model for Schistosoma mansoni (CHI-S) with potential to accelerate vaccine development has been developed among naïve volunteers in the Netherlands. Because responses both to infections and candidate vaccines are likely to differ between endemic and non-endemic settings, we propose to establish a CHI-S in Uganda where Schistosoma mansoni is endemic. As part of a "road-map" to this goal, we have undertaken a risk assessment. We identified risks related to importing of laboratory vector snails and schistosome strains from the Netherlands to Uganda; exposure to natural infection in endemic settings concurrently with CHI-S studies, and unfamiliarity of the community with the nature, risks and rationale for CHI. Mitigating strategies are proposed. With careful implementation of the latter, we believe that CHI-S can be implemented safely in Uganda. Our reflections are presented here to promote feedback and discussion.
ABSTRACT
In low-income countries, complex comorbidities and weak health systems confound disease diagnosis and treatment. Yet, data-driven approaches have not been applied to develop better diagnostic strategies or to tailor treatment delivery for individuals within rural poor communities. We observed symptoms/diseases reported within three months by 16 357 individuals aged 1+ years in 17 villages of Mayuge District, Uganda. Symptoms were mapped to the Human Phenotype Ontology. Comorbidity networks were constructed. An edge between two symptoms/diseases was generated if the relative risk greater than 1, Ï correlation greater than 0, and local false discovery rate less than 0.05. We studied how network structure and flagship symptom profiles varied against biosocial factors. 88.05% of individuals (14 402/16 357) reported at least one symptom/disease. Young children and individuals in worse-off households-low socioeconomic status, poor water, sanitation, and hygiene, and poor medical care-had dense network structures with the highest comorbidity burden and/or were conducive to the onset of new comorbidities from existing flagship symptoms, such as fever. Flagship symptom profiles for fever revealed self-misdiagnoses of fever as malaria and sexually transmitted infections as a potentially missed cause of fever in individuals of reproductive age. Network analysis may inform the development of new diagnostic and treatment strategies for flagship symptoms used to characterize syndromes/diseases of global concern.
Subject(s)
Communicable Diseases/epidemiology , Delivery of Health Care , Global Health , Rural Population , Adolescent , Adult , Child , Child, Preschool , Cluster Analysis , Comorbidity , Developing Countries , Female , Humans , Hygiene , Infant , Male , Middle Aged , Sanitation , Socioeconomic Factors , Uganda/epidemiology , Water Supply , Young AdultABSTRACT
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.