Mechanistic studies of anti-malarial spiroindolones and synthesis and structure-activity relationship studies of an inhibitor of dengue proliferation

Master'sJOINT M.SC. IN INFECTIOUS DISEASES, VACCINOLOGY AND DRUG DISCOVER

Surveillance and response systems for elimination of tropical diseases : summary of a thematic series in infectious diseases of poverty

The peer-reviewed journal Infectious Diseases of Poverty provides a new platform to engage with, and disseminate in an open-access format, science outside traditional disciplinary boundaries. The current piece reviews a thematic series on surveillance-response systems for elimination of tropical diseases. Overall, 22 contributions covering a broad array of diseases are featured - i.e. clonorchiasis, dengue, hepatitis, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), H7N9 avian influenza, lymphatic filariasis, malaria, Middle East respiratory syndrome (MERS), rabies, schistosomiasis and tuberculosis (TB). There are five scoping reviews, a commentary, a letter to the editor, an opinion piece and an editorial pertaining to the theme "Elimination of tropical disease through surveillance and response". The remaining 13 articles are original contributions mainly covering (i) drug resistance; (ii) innovation and validation in the field of mathematical modelling; (iii) elimination of infectious diseases; and (iv) social media reports on disease outbreak notifications released by national health authorities. Analysis of the authors' affiliations reveals that scientists from the People's Republic of China (P.R. China) are prominently represented. Possible explanations include the fact that the 2012 and 2014 international conferences pertaining to surveillance-response mechanisms were both hosted by the National Institute of Parasitic Diseases (NIPD) in Shanghai, coupled with P.R. China's growing importance with regard to the control of infectious diseases. Within 4 to 22 months of publication, three of the 22 contributions were viewed more than 10 000 times each. With sustained efforts focusing on relevant and strategic information towards control and elimination of infectious diseases, Infectious Diseases of Poverty has become a leading journal in the field of surveillance and response systems in infectious diseases and beyond

Disease, activity and schoolchildren's health (DASH) in Port Elizabeth, South Africa: a study protocol

BACKGROUND: An in-depth epidemiological investigation on intestinal parasite infections in an impoverished area of Port Elizabeth, South Africa provides a unique opportunity for research on its impact on children's physical fitness, cognitive performance and psychosocial health. Additionally, we will screen risk factors for the development of diabetes and hypertension in adulthood. METHODS/DESIGN: A 2-year longitudinal cohort study will be conducted, consisting of three cross-sectional surveys (baseline and two follow-ups), in eight historically black and coloured (mixed race) primary schools located in different townships in Port Elizabeth, South Africa. Approximately 1000 Grade 4 primary schoolchildren, aged 8 to 12 years, will be enrolled and followed. At each survey, disease status, anthropometry and levels of physical fitness, cognitive performance and psychosocial health will be assessed. After each survey, individuals diagnosed with parasitic worm infections will be treated with anthelminthic drugs, while children with other infections will be referred to local clinics. Based on baseline results, interventions will be tailored to the local settings, embedded within the study and implemented in half of the schools, while the remaining schools will serve as controls. Implementation of the interventions will take place over two 8-week periods. The effect of interventions will be determined with predefined health parameters. DISCUSSION: This study will shed new light on the health burden incurred by children in deprived urban settings of South Africa and provide guidance for specific health interventions. Challenges foreseen in the conduct of this study include: (i) difficulty in obtaining written informed consent from parents/guardians; (ii) administration of questionnaires in schools where three languages are spoken (Afrikaans, Xhosa and English); (iii) challenges in grasping concepts of psychosocial health among schoolchildren using a questionnaire; and (iv) loss to follow-up due to the study setting where illiteracy, mobility and violence are common. Finally, designing the health interventions together with local principals and teachers will allow all concerned with the research to bolster a sense of community ownership and sustained use of the interventions after the study has ceased

Efficacy and Safety of Tribendimidine Against Clonorchis sinensis

In this randomized open-label trial, tribendimidine was shown to have an efficacy comparable to praziquantel for the treatment of Clonorchis sinensis infection. Patients treated with praziquantel experienced significantly more adverse events than tribendimidine recipient

Soil-transmitted helminth infections and physical fitness in school-aged Bulang children in southwest China: results from a cross-sectional survey

BACKGROUND: Chronic soil-transmitted helminth (STH) infections have been associated with reduced physical fitness, but available evidence is limited. The aim of this cross-sectional survey was to assess the feasibility of measuring children's physical fitness and to relate it to STH infections. Our study was carried out among school-aged children of the Bulang ethnic group in rural southwest People's Republic of China (P.R. China). Standardized, quality-controlled methods were employed to determine STH infections (Kato-Katz technique), haemoglobin levels, anthropometry (body weight and height) and physical fitness (20-m shuttle run test). RESULTS: A compliance of 87% suggested good acceptance of the methods used. Among 69 children with complete data records, infection prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm were 81%, 44% and 6%, respectively. The maximum volume of oxygen that can be utilized within 1 min during exhaustive exercise (VO2 max estimate) of T. trichiura-infected children was 1.94 ml kg1 min1 lower than that of their non-infected counterparts (P = 0.005). Until exhaustion, T. trichiura-infected children had completed 6.14 20-m laps less (P = 0.004). Additionally, the mean VO2 max estimate of stunted children was lowered by 1.63 ml kg1 min1 (P = 0.002) and they completed 5.32 20-m laps less (P = 0.001) compared to children of normal stature. No significant association between stunting and infection with any STH species could be established. CONCLUSIONS: Implementation of physical fitness tests in rural, resource-constraint settings is feasible. The physical fitness of children who are stunted or infected with STHs, particularly T. trichiura, is significantly impaired. We have launched a larger study and will determine the dynamics of school-aged children's physical fitness over a 7-month period after administration of anthelminthic drugs

Association between gastrointestinal tract infections and glycated hemoglobin in school children of poor neighborhoods in Port Elizabeth, South Africa

BACKGROUND: Low- and middle-income countries are facing a dual disease burden with infectious diseases (e.g., gastrointestinal tract infections) and non-communicable diseases (e.g., diabetes) being common. For instance, chronic parasite infections lead to altered immune regulatory networks, anemia, malnutrition, and diarrhea with an associated shift in the gut microbiome. These can all be pathways of potential relevance for insulin resistance and diabetes. The aim of this study was to investigate the association between common gastrointestinal tract infections and glycemia in children from non-fee paying schools in South Africa. METHODOLOGY: We conducted a cross-sectional survey among 9- to 14-year-old school children in Port Elizabeth. Stool and urine samples were collected to assess infection status with parasitic worms (e.g., Ascaris lumbricoides, Enterobius vermicularis, and Trichuris trichiura), intestinal protozoa (e.g., Cryptosporidium parvum and Giardia intestinalis), and the bacterium Helicobacter pylori. Glycated hemoglobin (HbA1c) was measured in finger prick derived capillary blood. All children at schools with a high prevalence of helminth infections and only infected children at the schools with low infection rates were treated with albendazole. The association of anthelmintic treatment with changes in HbA1c 6 months after the drug intervention was also investigated. FINDINGS: A high prevalence of 71.8% of prediabetes was measured in this group of children, with only 27.8% having HbA1c in the normal range. H. pylori was the predominant infectious agent and showed an independent positive association with HbA1c in a multivariable regression analysis (β = 0.040, 95% confidence interval (CI) 0.006-0.073, p<0.05). No association of HbA1c with either any other infectious agent or albendazole administration was found. CONCLUSION: The role of H. pylori in diabetes needs confirmation in the context of longitudinal treatment interventions. The specific effect of other gastrointestinal tract infections on glycemia remains unclear. Future studies should integrate the measurement of biomarkers, including immunological parameters, to shed light on the potential mediating mechanisms between parasite infections and diabetes

Intestinal parasites, growth and physical fitness of schoolchildren in poor neighbourhoods of Port Elizabeth, South Africa: a cross-sectional survey

BACKGROUND: As traditional lifestyle and diets change with social and economic development, disadvantaged communities in low- and middle-income countries increasingly face a double burden of communicable and non-communicable diseases. We studied the relationship between physical fitness and infections with soil-transmitted helminths (STHs), intestinal protozoa and Helicobacter pylori among schoolchildren in Port Elizabeth, South Africa. METHODS: We conducted a cross-sectional survey among 1009 children, aged 9 to 12 years, from eight primary schools in socioeconomically disadvantaged neighbourhoods of Port Elizabeth. Physical fitness was determined using field-deployable tests of the Eurofit fitness test battery. Stool samples were analysed with the Kato-Katz thick smear technique to diagnose STHs and with rapid diagnostic tests (RDTs) to detect intestinal protozoa and H. pylori infections. Haemoglobin (Hb) levels were assessed and anthropometric indicators determined. RESULTS: Complete data were available for 934 children (92 %). In two schools, high STH prevalences were found (Ascaris lumbricoides 60 and 72 %; Trichuris trichiura 65 % each). For boys and girls co-infected with A. lumbricoides and T. trichiura (n = 155) the maximal oxygen uptake (VO2 max) was estimated to be 50.1 and 47.2 ml kg(-1) min(-1), compared to 51.5 and 47.4 ml kg(-1) min(-1) for their non-infected peers (n = 278), respectively. On average, children without helminth infections had greater body mass (P = 0.011), height (P = 0.009) and a higher body mass index (P = 0.024) and were less often stunted (P = 0.006), but not significantly less wasted compared to their peers with a single or dual species infection. Among 9-year-old boys, a negative correlation between helminth infections and VO2 max, grip strength and standing broad jump distance was observed (P = 0.038). The overall mean Hb level was 122.2 g l(-1). In the two schools with the highest prevalence of STHs the Hb means were 119.7 and 120.5 g l(-1), respectively. CONCLUSIONS: Intestinal parasite infections appear to have a small but significant negative effect on the physical fitness of infected children, as expressed by their maximal oxygen uptake. We observed a clear impact on anthropometric indicators

Associations between selective attention and soil-transmitted helminth infections, socioeconomic status, and physical fitness in disadvantaged children in Port Elizabeth, South Africa: an observational study

BACKGROUND: Socioeconomically deprived children are at increased risk of ill-health associated with sedentary behavior, malnutrition, and helminth infection. The resulting reduced physical fitness, growth retardation, and impaired cognitive abilities may impede children's capacity to pay attention. The present study examines how socioeconomic status (SES), parasitic worm infections, stunting, food insecurity, and physical fitness are associated with selective attention and academic achievement in school-aged children. METHODOLOGY: The study cohort included 835 children, aged 8-12 years, from eight primary schools in socioeconomically disadvantaged neighborhoods of Port Elizabeth, South Africa. The d2-test was utilized to assess selective attention. This is a paper and pencil letter-cancellation test consisting of randomly mixed letters d and p with one to four single and/or double quotation marks either over and/or under each letter. Children were invited to mark only the letters d that have double quotation marks. Cardiorespiratory fitness was assessed via the 20 m shuttle run test and muscle strength using the grip strength test. The Kato-Katz thick smear technique was employed to detect helminth eggs in stool samples. SES and food insecurity were determined with a pre-tested questionnaire, while end of year school results were used as an indicator of academic achievement. PRINCIPAL FINDINGS: Children infected with soil-transmitted helminths had lower selective attention, lower school grades (academic achievement scores), and lower grip strength (all p<0.05). In a multiple regression model, low selective attention was associated with soil-transmitted helminth infection (p<0.05) and low shuttle run performance (p<0.001), whereas higher academic achievement was observed in children without soil-transmitted helminth infection (p<0.001) and with higher shuttle run performance (p<0.05). CONCLUSIONS/SIGNIFICANCE: Soil-transmitted helminth infections and low physical fitness appear to hamper children's capacity to pay attention and thereby impede their academic performance. Poor academic achievement will make it difficult for children to realize their full potential, perpetuating a vicious cycle of poverty and poor health. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN68411960

A call for citizen science in pandemic preparedness and response : beyond data collection

The COVID-19 pandemic has underlined the need to partner with the community in pandemic preparedness and response in order to enable trust-building among stakeholders, which is key in pandemic management. Citizen science, defined here as a practice of public participation and collaboration in all aspects of scientific research to increase knowledge and build trust with governments and researchers, is a crucial approach to promoting community engagement. By harnessing the potential of digitally enabled citizen science, one could translate data into accessible, comprehensible and actionable outputs at the population level. The application of citizen science in health has grown over the years, but most of these approaches remain at the level of participatory data collection. This narrative review examines citizen science approaches in participatory data generation, modelling and visualisation, and calls for truly participatory and co-creation approaches across all domains of pandemic preparedness and response. Further research is needed to identify approaches that optimally generate short-term and long-term value for communities participating in population health. Feasible, sustainable and contextualised citizen science approaches that meaningfully engage affected communities for the long-term will need to be inclusive of all populations and their cultures, comprehensive of all domains, digitally enabled and viewed as a key component to allow trust-building among the stakeholders. The impact of COVID-19 on people’s lives has created an opportune time to advance people’s agency in science, particularly in pandemic preparedness and response