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There are currently no proven vaccines or drugs to prevent COVID-19. In this BBC World News interview, MORU’s Prof Sir Nick White explains why the only way to find out if chloroquine and hydroxychloriquine work against COVID-19 is via randomised, clinical trials and how the hype over chloroquine negatively affects people with lupus and rheumatoid arthritis.
Abstract Background The radical cure of Plasmodium vivax requires treatment with an 8-aminoquinoline drug, such as primaquine and tafenoquine, to eradicate liver hypnozoite stages, which can reactivate to cause relapsing infections. Safe treatment regimens require prior screening of patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency to avoid potential life-threatening drug induced haemolysis. Testing is rarely available in malaria endemic countries, but will be needed to support routine use of radical cure. This study investigates end-user perspectives in Bangladesh on the introduction of a quantitative G6PD test (SD Biosensor STANDARD™ G6PD analyser) to support malaria elimination. Methods The perspectives of users on the SD Biosensor test were analysed using semi-structured interviews and focus group discussions with health care providers and malaria programme officers in Bangladesh. Key emerging themes regarding the feasibility of introducing this test into routine practice, including perceived barriers, were analysed. Results In total 63 participants were interviewed. Participants emphasized the life-saving potential of the biosensor, but raised concerns including the impact of limited staff time, high workload and some technical aspects of the device. Participants highlighted that there are both too few and too many P. vivax patients to implement G6PD testing owing to challenges of funding, workload and complex testing infrastructure. Implementing the biosensor would require flexibility and improvisation to deal with remote sites, overcoming a low index of suspicion and mutual interplay of declining patient numbers and reluctance to test. This approach would generate new forms of evidence to justify introduction in policy and carefully consider questions of deployment given declining patient numbers. Conclusions The results of the study show that, in an elimination context, the importance of malaria needs to be maintained for both policy makers and the affected communities, in this case by ensuring P. vivax, PQ treatment, and G6PD deficiency remain visible. Availability of new technologies, such as the biosensor, will fuel ongoing debates about priorities for allocating resources that must be adapted to a constantly evolving target. Technical and logistical concerns regarding the biosensor should be addressed by future product designs, adequate training, strengthened supply chains, and careful planning of communication, advocacy and staff interactions at all health system levels.
The utility of an AMR dictionary as an educational tool to improve public understanding of antimicrobial resistance
Background: Communicating about antimicrobial resistance (AMR) to the public is challenging. Methods: We developed a dictionary of terms commonly used to communicate about AMR. For each term, we developed learning points to explain AMR and related concepts in plain language. We conducted a pilot evaluation in 374 high school students in Ubon Ratchathani, Thailand. In three 50-minute sessions, students were asked to answer five true/false questions using a paper-based questionnaire. The first session assessed their understanding of AMR at baseline, the second after searching the internet, and the third after the provision of the printed AMR dictionary and its web address. Results: We developed the AMR dictionary as a web-based application (www.amrdictionary.net). The Thai version of the AMR dictionary included 35 terms and associated learning points, seven figures displaying posters promoting AMR awareness in Thailand, and 66 recommended online videos. In the pretest, the proportion of correct responses to each question ranged from 10% to 57%; 10% of the students correctly answered that antibiotics cannot kill viruses and 57% correctly answered that unnecessary use of antibiotics makes them ineffective. After the internet searches, the proportions of correct answers increased, ranging from 62% to 89% (all p<0.001). After providing the AMR dictionary, the proportions of correct answers increased further, ranging from 79% to 89% for three questions (p<0.001), and did not change for one question (p=0.15). Correct responses as to whether taking antibiotics often has side-effects such as diarrhoea reduced from 85% to 74% (p<0.001). The dictionary was revised based on the findings and comments received. Conclusions: Understanding of AMR among Thai high school students is limited. The AMR dictionary can be a useful supportive tool to increase awareness and improve understanding of AMR. Our findings support the need to evaluate the effectiveness of communication tools in the real-world setting.
Rickettsial diseases are a group of vector-borne bacterial infections that cause acute febrile illness with potentially severe or fatal complications. These vector-borne diseases are prevalent in tropical and subtropical regions worldwide and disproportionately affect poorer communities but are scientifically underrecognized. Despite this, they are not included in the World Health Organization's list of neglected tropical diseases nor were they mentioned in Peter Hotez's recent reflections on "What constitutes a neglected tropical disease?" in PLOS Neglected Tropical Diseases . Here we present the case that rickettsial infections, as an overlooked cause of morbidity, mortality, and economic losses in marginalized populations, should be recognized as neglected tropical diseases. We describe how this oversight is the result of a number of factors and how it negatively impacts patient outcomes. We then propose measures to address the neglect of rickettsial infections in both scientific research and public health interventions.
A mixed methods evaluation of Advanced Life Support in Obstetrics (ALSO) and Basic Life Support in Obstetrics (BLSO) in a resource-limited setting on the Thailand-Myanmar border
Background: Short emergency obstetric care (EmOC) courses have demonstrated improved provider confidence, knowledge and skills but impact on indicators such as maternal mortality and stillbirth is less substantial. This manuscript evaluates Advanced Life Support in Obstetrics (ALSO) and Basic Life Support (BLSO) as an adult education tool, in a protracted, post-conflict and resource-limited setting. Methods: A mixed methods evaluation was used. Basic characteristics of ALSO and BLSO participants and their course results were summarized. Kirkpatrick’s framework for assessment of education effectiveness included: qualitative data on participants’ reactions to training (level 1); and quantitative health indicator data on change in the availability and quality of EmOC and in maternal and/or neonatal health outcomes (level 4), by evaluation of the post-partum haemorrhage (PPH) related maternal mortality ratio (MMR) and stillbirth rate in the eight years prior and following implementation of ALSO and BLSO. Results: 561 Thailand-Myanmar border health workers participated in ALSO (n=355) and BLSO (n=206) courses 2008-2020. Pass rates on skills exceeded 90% for both courses while 50% passed the written ALSO test. Perceived confidence significantly improved for all items assessed. In the eight-year block preceding the implementation of ALSO and BLSO (2000-07) the PPH related MMR per 100,000 live births was 57.0 (95%CI 30.06-108.3)(9/15797) compared to 25.4 (95%CI 11.6-55.4)(6/23620) eight years following (2009-16), p=0.109. After adjustment, PPH related maternal mortality was associated with birth before ALSO/BLSO implementation aOR 3.825 (95%CI 1.1233-11.870), migrant (not refugee) status aOR 3.814 (95%CI 1.241-11.718) and attending ≤four antenatal consultations aOR 3.648 (95%CI 1.189-11.191). Stillbirth rate per 1,000 total births was 18.2 (95%CI 16.2-20.4)(291/16016) before the courses, and 11.1 (95%CI 9.8-12.5)(264/23884) after, p=0.038. Birth before ALSO/ BLSO implementation was associated with stillbirth aoR 1.235 (95%CI 1.018-1.500). Conclusions: This evaluation suggests ALSO and BLSO are sustainable, beneficial, EmOC trainings for adult education in protracted, post-conflict, resource-limited settings.
Theory of change: Drama and arts-based community engagement for malaria research and elimination in Cambodia
Background: Across the Greater Mekong Sub-region, malaria persists in isolated communities along international borders. Arts and drama have been used to reach to communities in Cambodia to engage them in malaria research, prevention and control. The “Village Drama Against Malaria” (VDAM) project was conducted in north eastern and western Cambodia: Stung Treng; Battambang and Pailin provinces during 2016 to 2019. In total, VDAM reached 55 rural villages, 2,378 student participants and 43,502 audience members. Methods: This article presents the results of two stakeholder-led evaluation workshops in which participants collaboratively developed theories of change to better understand the potential and actual impact of arts and drama-based activities on malaria in these communities. The workshops had a particular focus on identifying areas for monitoring and evaluation so that impact can be measured. Workshop participants included village malaria workers, community leaders, professional and student drama performers, and representatives from the local health authorities and the national malaria control programme. Results: Five broad areas were identified as relevant for monitoring and evaluation: logistical and practical challenges; embeddedness and reach of engagement; health knowledge and confidence of young people; effectiveness of communications; impact on malaria. These areas align well with the monitoring and evaluation conducted to date and point to additional opportunities for data collection. Conclusions: The findings from these workshops will inform future engagement strategies, for example, we may engage a smaller number of young people but over a longer period and more in-depth.
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.
BACKGROUND: Mass drug administration (MDA) has received growing interest to accelerate the elimination of multi-drug resistant malaria in the Greater Mekong Subregion. Targeted MDA, sometimes referred to as focal MDA, is the practice of delivering MDA to high incidence subpopulations only, rather than the entire population. The potential effectiveness of delivering targeted MDA was demonstrated in a recent intervention in Kayin State, Myanmar. Policymakers and funders need to know what resources are required if MDA, targeted or otherwise, is to be included in elimination packages beyond existing malaria interventions. This study aims to estimate the programmatic cost and the unit cost of targeted MDA in Kayin State, Myanmar. METHODS: We used financial data from a malaria elimination initiative, conducted in Kayin State, to estimate the programmatic costs of the targeted MDA component using a micro-costing approach. Three activities (community engagement, identification of villages for targeted MDA, and conducting mass treatment in target villages) were evaluated. We then estimated the programmatic costs of implementing targeted MDA to support P. falciparum malaria elimination in Kayin State. A costing tool was developed to aid future analyses. RESULTS: The cost of delivering targeted MDA within an integrated malaria elimination initiative in eastern Kayin State was approximately US$ 910,000. The cost per person reached, distributed among those in targeted and non-targeted villages, for the MDA component was US$ 2.5. CONCLUSION: This cost analysis can assist policymakers in determining the resources required to clear malaria parasite reservoirs. The analysis demonstrated the value of using financial data from research activities to predict programmatic implementation costs of targeting MDA to different numbers of target villages.
Seroepidemiology of Foot and Mouth Disease using passive surveillance techniques in selected provinces of Lao PDR.
Foot and Mouth Disease (FMD) is a high-impact, contagious transboundary animal disease that is endemic in Southeast Asia. Abattoir samples were routinely collected in six selected provinces between March and December 2019. A total of 1280 samples of abattoir animals were tested for FMD Non-Structural Protein (NSP) antibodies to indicate natural infections. Overall, 22.8% were seropositive for FMD NSP antibodies while seroprevalence of cattle (n = 469), buffalo (n = 214), and pigs (n = 597) were 44.6%, 35.0%, and 1.3%, respectively. The highest seroprevalence destination province was Xiengkhouang (35.3% of 272 samples), followed by Savannakhet (27.0% of 244 samples). Risk factors for evidence of natural infection identified by a multivariate logistic regression model included age groups (p-value = 0.02) and origin provinces (p-value = 2.8 × 10-5) of the animals. There were significant differences of FMD NSP seroprevalence between age groups and origin provinces of the animals. The odds ratio of a seropositive result in the less than 1 year old group was 2.5 (95% CI; 1.4, 4.4) when compared to the 3-4 years old group, while the odds ratios for animals that originated from Khammouane and Xiengkhouang provinces were 4.5 (95% CI; 1.1, 18.7) and 2.4 (95% CI; 1.4, 4.1), respectively, when compared to Champasak province. Serotype-specific antibody ELISA for 44 NSP antibody-positive samples revealed evidence of FMD serotypes O and A virus circulation in some provinces. Despite the passive abattoir survey providing useful information on FMD virus previous exposure and geographic locations of the animals, timely information on FMD virus circulation and distribution is also crucial to an effective control program. Alternative approaches to increase the cost-effectiveness of the surveillance network are also discussed.
Diagnostic accuracy of the WHO clinical definitions for dengue and implications for surveillance: A systematic review and meta-analysis
Background Dengue is the world’s most common mosquito-borne virus but remains diagnostically challenging due to its nonspecific presentation. Access to laboratory confirmation is limited and thus most reported figures are based on clinical diagnosis alone, the accuracy of which is uncertain. This systematic review assesses the diagnostic accuracy of the traditional (1997) and revised (2009) WHO clinical case definitions for dengue fever, the basis for most national guidelines. Methodology/Principal findings PubMed, EMBASE, Scopus, OpenGrey, and the annual Dengue Bulletin were searched for studies assessing the diagnostic accuracy of the unmodified clinical criteria. Two reviewers (NR/SL) independently assessed eligibility, extracted data, and evaluated risk of bias using a modified QUADAS-2. Additional records were found by citation network analysis. A meta-analysis was done using a bivariate mixed-effects regression model. Studies that modified criteria were analysed separately. This systematic review protocol was registered on PROSPERO (CRD42020165998). We identified 11 and 12 datasets assessing the 1997 and 2009 definition, respectively, and 6 using modified criteria. Sensitivity was 93% (95% CI: 77–98) and 93% (95% CI: 86–96) for the 1997 and 2009 definitions, respectively. Specificity was 29% (95% CI: 8–65) and 31% (95% CI: 18–48) for the 1997 and 2009 definitions, respectively. Diagnostic performance suffered at the extremes of age. No modification significantly improved accuracy. Conclusions/Significance Diagnostic accuracy of clinical criteria is poor, with significant implications for surveillance and public health responses for dengue control. As the basis for most reported figures, this has relevance to policymakers planning resource allocation and researchers modelling transmission, particularly during COVID-19.
Laboratory informatics capacity for effective antimicrobial resistance surveillance in resource-limited settings.
Antimicrobial resistance (AMR) is a major threat to human health globally. Surveillance is a key activity to determine AMR burden, impacts, and trends and to monitor effects of interventions. Surveillance systems require efficient capture and onward sharing of high-quality laboratory data. Substantial investment is being made to improve laboratory capacity, particularly in low-income and middle-income countries (LMICs) with high disease burdens. However, building capacity for effective laboratory data management remains an under-resourced area, which, unless addressed, will limit progress towards comprehensive AMR surveillance in LMICs. The lack of a fit-for-purpose and open-source laboratory information management system software is of particular concern. In this Personal View, we summarise the technical requirements for microbiology laboratory data management, provide a snapshot of laboratory data management in LMIC laboratories, and describe the key steps required to improve the situation. Without action to improve information technology infrastructure and data management systems in microbiology laboratories, the ongoing efforts to develop capacity for AMR surveillance in LMICs might not realise their full potential.
Falciparum but not vivax malaria increases the risk of hypertensive disorders of pregnancy in women followed prospectively from the first trimester.
BackgroundMalaria and hypertensive disorders of pregnancy (HDoP) affect millions of pregnancies worldwide, particularly those of young, first-time mothers. Small case-control studies suggest a positive association between falciparum malaria and risk of pre-eclampsia but large prospective analyses are lacking.MethodsWe characterized the relationship between malaria in pregnancy and the development of HDoP in a large, prospectively followed cohort. Pregnant women living along the Thailand-Myanmar border, an area of low seasonal malaria transmission, were followed at antenatal clinics between 1986 and 2016. The relationships between falciparum and vivax malaria during pregnancy and the odds of gestational hypertension, pre-eclampsia, or eclampsia were examined using logistic regression amongst all women and then stratified by gravidity.ResultsThere were 23,262 singleton pregnancies in women who presented during the first trimester and were followed fortnightly. Falciparum malaria was associated with gestational hypertension amongst multigravidae (adjusted odds ratio (AOR) 2.59, 95%CI 1.59-4.23), whereas amongst primigravidae, it was associated with the combined outcome of pre-eclampsia/eclampsia (AOR 2.61, 95%CI 1.01-6.79). In contrast, there was no association between vivax malaria and HDoP.ConclusionsFalciparum but not vivax malaria during pregnancy is associated with hypertensive disorders of pregnancy.
Improved Detection of Intestinal Helminth Infections with a Formalin Ethyl-Acetate-Based Concentration Technique Compared to a Crude Formalin Concentration Technique
Intestinal helminth infections are the most prevalent neglected tropical diseases, predominantly affecting rural and marginalised populations. The mainstay of diagnosis is the microscopic examination of faecal samples to detect parasites in the form of eggs, larvae and cysts. In an effort to improve the standard of care, the comparative accuracy in detecting helminth infections of the hitherto used formalin-based concentration method (FC) was compared to a previously developed formalin ethyl-acetate-based concentration technique (FECT), prior to the systematic deployment of the latter at a research and humanitarian unit operating on the Thailand–Myanmar border. A total of 693 faecal samples were available for the comparison of the two diagnostic methods. The FECT was superior in detecting hookworm, Trichuris trichiura and small liver flukes. Interestingly, there was no significant difference for Ascaris lumbricoides, possibly due to the high observed egg density. Despite the minor increase in material cost and the fact that the FECT is somewhat more time consuming, this method was implemented as the new routine technique.
ABSTRACT We report 16 Burkholderia pseudomallei genomes, including 5 new multilocus sequence types, isolated from rivers in Laos. The environmental bacterium B. pseudomallei causes melioidosis, a serious infectious disease in tropical and subtropical regions. The isolates are geographically clustered in one clade from around Vientiane, Laos, and one clade from further south.
AbstractISARIC (International Severe Acute Respiratory and emerging Infections Consortium) partnerships and outbreak preparedness initiatives enabled the rapid launch of standardised clinical data collection on COVID-19 in Jan 2020. Extensive global uptake of this resource has resulted in a large, standardised collection of comprehensive clinical data from hundreds of sites across dozens of countries. Data are analysed regularly and reported publicly to inform patient care and public health response. This report is a part of a series and includes the results of data analysis on 8 April 2021.We thank all of the data contributors for their ongoing support.Report highlights includeData have been entered for 340,312 individuals from 1609 sites across 54 countries.The analysis detailed in this report only includes individuals:for whom data collection commenced on or before 1 February 2021.ANDwho have laboratory-confirmed or clinically-diagnosed SARS-COV-2 infection.For the 264,496 cases who meet eligibility criteria for this report:The median age is 61 years.The five most common symptoms at admission were shortness of breath, cough, history of fever, fatigue/malaise, and altered consciousness/confusion. Children and older adults were less likely to display typical symptoms, and around 40% of patients >80 years experienced confusion.A total of 19% of patients were admitted at some point during their illness into an intensive care unit.Antibiotic use is high (79.9% of patients received antibiotics - the choice of antibiotic and specific indication have not yet been determined.)Altered consciousness/confusion was also relatively frequent (28,190/130,157) and most common in elderly patients. Overall, elderly patients are less likely to present with URTI symptoms.To access previous versions of ISARIC COVID-19 Clinical Data Report please use the link below:https://isaric.org/research/covid-19-clinical-research-resources/evidence-reports/