The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

Effectiveness of Provider and Community Interventions to Improve Treatment of Uncomplicated Malaria in Nigeria: A Cluster Randomized Controlled Trial

The World Health Organization recommends that malaria be confirmed by parasitological diagnosis before treatment using Artemisinin-based Combination Therapy (ACT). Despite this, many health workers in malaria endemic countries continue to diagnose malaria based on symptoms alone. This study evaluates interventions to help bridge this gap between guidelines and provider practice. A stratified cluster-randomized trial in 42 communities in Enugu state compared 3 scenarios: Rapid Diagnostic Tests (RDTs) with basic instruction (control); RDTs with provider training (provider arm); and RDTs with provider training plus a school-based community intervention (provider-school arm). The primary outcome was the proportion of patients treated according to guidelines, a composite indicator requiring patients to be tested for malaria and given treatment consistent with the test result. The primary outcome was evaluated among 4946 (93%) of the 5311 patients invited to participate. A total of 40 communities (12 in control, 14 per intervention arm) were included in the analysis. There was no evidence of differences between the three arms in terms of our composite indicator (p = 0.36): stratified risk difference was 14% (95% CI -8.3%, 35.8%; p = 0.26) in the provider arm and 1% (95% CI -21.1%, 22.9%; p = 0.19) in the provider-school arm, compared with control. The level of testing was low across all arms (34% in control; 48% provider arm; 37% provider-school arm; p = 0.47). Presumptive treatment of uncomplicated malaria remains an ingrained behaviour that is difficult to change. With or without extensive supporting interventions, levels of testing in this study remained critically low. Governments and researchers must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines

Impact of gender on the decision to participate in a clinical trial: a cross-sectional study

Background In order for Informed Consent to be ethical and valid each clinical trial participant must be able to make a voluntary decision to participate, free from pressure or coercion. Nonetheless, many factors may influence the decision reached, and such influences may be different for male and female volunteers. Being aware of these differences may help researches develop better processes for obtaining consent that safeguard the right of autonomy for all participants. The goal of this study was to evaluate potential gender-based differences in the factors influencing clinical trial participation. Methods This cross-sectional study was conducted in the Northeast region of Minas Gerais, Brazil, in October 2011. A structured questionnaire was administered to 143 volunteers (48 male, 95 female) screened for participation in a clinical study of an investigational functional food with potential anthelminthic properties. Answers regarding their decision to participate in the study were compared, by gender, using chi-square and Mann Whitney tests. Odds ratios (OR) was used to measure association. Results A majority of subjects (58% of males, 59% of females) listed the desire to collaborate with the development of a product against parasitic worms as their main reason for participation. Females were significantly more likely to report a decision influenced by friends, family, or researchers (OR 3.14, 3.45, and 3.46 respectively, p \u3c 0.005). Females were also significantly more likely to report a decision influenced by general altruistic considerations (OR 8.45, p \u3c 0.005). There was no difference, by gender, in the report of decisions influenced by informational meetings, understanding of the disease, or the availability of medical treatments or exams. There was also no difference in knowledge of the rights of research participants. Conclusion Study results indicate that there is a strong difference between male and female participants regarding social influences on the decision to participate in clinical research. Further research into the impact this may have on autonomy is warranted

Assessment of the dissemination of COVID-19-related articles across social media: Altmetrics study

BACKGROUND: The use of social media assists in the distribution of information about COVID-19 to the general public and health professionals. Alternative-level metrics (ie, Altmetrics) is an alternative method to traditional bibliometrics that assess the extent of dissemination of a scientific article on social media platforms. OBJECTIVE: Our study objective was to characterize and compare traditional bibliometrics (citation count) with newer metrics (Altmetric Attention Score [AAS]) of the top 100 Altmetric-scored articles on COVID-19. METHODS: The top 100 articles with the highest AAS were identified using the Altmetric explorer in May 2020. AAS, journal name, and mentions from various social media platforms (Twitter, Facebook, Wikipedia, Reddit, Mendeley, and Dimension) were collected for each article. Citation counts were collected from the Scopus database. RESULTS: The median AAS and citation count were 4922.50 and 24.00, respectively. TheNew England Journal of Medicine published the most articles (18/100, 18%). Twitter was the most frequently used social media platform with 985,429 of 1,022,975 (96.3%) mentions. Positive correlations were observed between AAS and citation count (r CONCLUSIONS: Our research characterized the top 100 COVID-19-related articles by AAS in the Altmetric database. Altmetrics could complement traditional citation count when assessing the dissemination of an article regarding COVID-19. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/21408

The Right Tool for the Job: Detection of Soil-Transmitted Helminths in Areas Co-endemic for Other Helminths

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni). Methods A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S. mansoni are co-endemic. One fecal sample from each participant was collected and transported to the field laboratory for analysis. Coprological diagnosis was performed on each fecal sample by three different methods: Formalin-Ether Sedimentation (FES), KK and the MM technique. The diagnostic sensitivity and negative predictive value (NPV) of each technique was calculated using the combination of all three techniques as the composite standard. In order to determine the agreement between the three techniques Fleiss´ kappa was used. Both the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) were calculated using the two quantification techniques (i.e., the MM and KK). Results Fecal samples from 1260 children were analyzed. The KK had higher diagnostic sensitivity than the MM for the detection of both A. lumbricoides (KK 97.3%, MM 69.5%) and hookworm (KK 95.1%, MM 80.8%). The CR of a single dose of mebendazole varied significantly between the KK and MM for both A. lumbricoides (p = 0.016) and hookworm (p = 0.000), with lower rates obtained with the KK. On the other hand, the FECR was very similar between both techniques for both A. lumbricoides and hookworm. Conclusion The MM did not add any diagnostic value over the KK in areas where both STHs and trematodes were co-endemic. The lower sensitivity of the MM would have an important impact on the administration of selective school-based treatment in this area since if only the MM were used, 36 (13.9%) children diagnosed with A. lumbricoides would have gone untreated. Author Summary Diagnosis of intestinal helminths and Schistosoma mansoni infections is based on the detection of eggs in feces. There are many techniques available for both detection and quantification of infection. For the quantification of helminth infections, the methods traditionally used are the Kato-Katz (KK) fecal think smear in humans, and the McMaster (MM) counting method in animals. Recently, the MM has been used for assessing the efficacy of benzimidazole drugs for treating soil-transmitted helminth (STH) infections in humans. In most parts of the world, however, STHs occur simultaneously with other helminth species, and the MM does not detect other helminth eggs. Therefore, in this study we sought to determine if the use of the MM in an area of Brazil were both STHs and S. mansoni are co-endemic, added any value to the current standard of diagnosis using the KK

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. METHODOLOGY/ PRINCIPAL FINDINGS: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. CONCLUSIONS/SIGNIFICANCE: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans

Substantial Contribution of Submicroscopical Plasmodium falciparum Gametocyte Carriage to the Infectious Reservoir in an Area of Seasonal Transmission

BACKGROUND: Man to mosquito transmission of malaria depends on the presence of the sexual stage parasites, gametocytes, that often circulate at low densities. Gametocyte densities below the microscopical threshold of detection may be sufficient to infect mosquitoes but the importance of submicroscopical gametocyte carriage in different transmission settings is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Membrane feeding experiments were carried out on 80 children below 14 years of age at the end of the wet season in an area of seasonal malaria transmission in Burkina Faso. Gametocytes were quantified by microscopy and by Pfs25-based quantitative nucleic acid sequence-based amplification assay (QT-NASBA). The children's infectiousness was determined by membrane feeding experiments in which a venous blood sample was offered to locally reared Anopheles mosquitoes. Gametocytes were detected in 30.0% (24/80) of the children by microscopy compared to 91.6% (65/71) by QT-NASBA (p<0.001). We observed a strong association between QT-NASBA gametocyte density and infection rates (p = 0.007). Children with microscopically detectable gametocytes were more likely to be infectious (68.2% compared to 31.7% of carriers of submicroscopical gametocytes, p = 0.001), and on average infected more mosquitoes (13.2% compared to 2.3%, p<0.001). However, because of the high prevalence of submicroscopical gametocyte carriage in the study population, carriers of sub-microscopical gametocytes were responsible for 24.2% of the malaria transmission in this population. CONCLUSIONS/SIGNIFICANCE: Submicroscopical gametocyte carriage is common in an area of seasonal transmission in Burkina Faso and contributes substantially to the human infectious reservoir. Submicroscopical gametocyte carriage should therefore be considered when implementing interventions that aim to reduce malaria transmission

Microproteinuria during Opisthorchis viverrini infection: A biomarker for advanced renal and hepatobiliary pathologies from chronic Opisthorchiasis

Approximately 680 million people are at risk of infection with Opisthorchis viverrini (OV) andClonorchis sinensis, with an estimated 10 million infected with OV in Southeast Asia alone. While opisthorchiasis is associated with hepatobiliary pathologies, such as advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA), animal models of OV infection show that immune-complex glomerulonephritis is an important renal pathology that develops simultaneously with hepatobiliary pathologies. A cardinal sign of immune-complex glomerulonephritis is the urinary excretion of immunoglobulin G (IgG) (microproteinuria). In community-based studies in OV endemic areas along the Chi River in northeastern Thailand, we observed that over half of the participants had urine IgG against a crude OV antigen extract (OV antigen). We also observed that elevated levels of urine IgG to OV antigen were not associated with the intensity of OV infection, but were likely the result of immune-complex glomerulonephritis as seen in animal models of OV infection. Moreover, we observed that urine IgG to OV antigen was excreted at concentrations 21 times higher in individuals with APF and 158 times higher in individuals with CCA than controls. We also observed that elevated urine IgG to OV antigen could identify APF+ and CCA+ individuals from non-cases. Finally, individuals with urine IgG to OV antigen had a greater risk of APF as determined by Odds Ratios (OR = 6.69; 95%CI: 2.87, 15.58) and a greater risk of CCA (OR = 71.13; 95%CI: 15.13, 334.0) than individuals with no detectable level of urine IgG to OV antigen. Herein, we show for the first time the extensive burden of renal pathology in OV endemic areas and that a urine biomarker could serve to estimate risk for both renal and hepatobiliary pathologies during OV infection, i.e., serve as a “syndromic biomarker” of the advanced pathologies from opisthorchiasis

Social factors influencing child health in Ghana

Objectives Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals’ target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. Methods ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. Results Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. Conclusions Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother’s health knowledge is emphasised