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When we are ill, we trust that the medicines that we take will make us feel and be better. But what if our pills do not contain the ingredients listed on the packaging? The art exhibition ‘What’s in your medicines?’ explores how substandard and falsified (‘fake’) medicines can affect our health, by showcasing the striking and original artwork of 12 South East Asian artists.
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/
Glucose-6-phosphate dehydrogenase activity in individuals with and without malaria: Analysis of clinical trial, cross-sectional and case–control data from Bangladesh
Background Glucose-6-phosphate dehydrogenase (G6PD) activity is dependent upon G6PD genotype and age of the red blood cell (RBC) population, with younger RBCs having higher activity. Peripheral parasitemia with Plasmodium spp. induces hemolysis, replacing older RBCs with younger cells with higher G6PD activity. This study aimed to assess whether G6PD activity varies between individuals with and without malaria or a history of malaria. Methods and findings Individuals living in the Chittagong Hill Tracts of Bangladesh were enrolled into 3 complementary studies: (i) a prospective, single-arm clinical efficacy trial of patients (n = 175) with uncomplicated malaria done between 2014 and 2015, (ii) a cross-sectional survey done between 2015 and 2016 (n = 999), and (iii) a matched case–control study of aparasitemic individuals with and without a history of malaria done in 2020 (n = 506). G6PD activity was compared between individuals with and without malaria diagnosed by microscopy, rapid diagnostic test (RDT), or polymerase chain reaction (PCR), and in aparasitemic participants with and without a history of malaria. In the cross-sectional survey and clinical trial, 15.5% (182/1,174) of participants had peripheral parasitemia detected by microscopy or RDT, 3.1% (36/1,174) were positive by PCR only, and 81.4% (956/1,174) were aparasitemic. Aparasitemic individuals had significantly lower G6PD activity (median 6.9 U/g Hb, IQR 5.2–8.6) than those with peripheral parasitemia detected by microscopy or RDT (7.9 U/g Hb, IQR 6.6–9.8, p < 0.001), but G6PD activity similar to those with parasitemia detected by PCR alone (submicroscopic parasitemia) (6.1 U/g Hb, IQR 4.8–8.6, p = 0.312). In total, 7.7% (14/182) of patients with malaria had G6PD activity < 70% compared to 25.0% (248/992) of participants with submicroscopic or no parasitemia (odds ratio [OR] 0.25, 95% CI 0.14–0.44, p < 0.001). In the case–control study, the median G6PD activity was 10.3 U/g Hb (IQR 8.8–12.2) in 253 patients with a history of malaria and 10.2 U/g Hb (IQR 8.7–11.8) in 253 individuals without a history of malaria (p = 0.323). The proportion of individuals with G6PD activity < 70% was 11.5% (29/253) in the cases and 15.4% (39/253) in the controls (OR 0.7, 95% CI 0.41–1.23, p = 0.192). Limitations of the study included the non-contemporaneous nature of the clinical trial and cross-sectional survey. Conclusions Patients with acute malaria had significantly higher G6PD activity than individuals without malaria, and this could not be accounted for by a protective effect of G6PD deficiency. G6PD-deficient patients with malaria may have higher than expected G6PD enzyme activity and an attenuated risk of primaquine-induced hemolysis compared to the risk when not infected.
In this review for the Vivax malaria collection, Kamala Thriemer and colleagues explore efforts to eliminate P. vivax malaria.
Lorenz von Seidlein and Nicholas White introduce a Collection on Plasmodium vivax malaria.
Introduction: The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic.Areas covered: Here, the authors discuss the history of hydroxychloroquine and chloroquine, the in vitro data which led to their widespread repurposing and adoption in COVID-19 and their complex pharmacokinetics. The evidence for the use of these drugs is assessed through in vivo animal experiments and the wealth of conflicting data and interpretations published during COVID-19, including the more informative results from randomized controlled trials (RCTs). The safety aspects of these drugs, in particular cardiotoxicity, are then reviewed.Expert opinion: The evidence from clinical trials in COVID-19 supports the well-established safety record of the 4-aminoquinolines at currently recommended dosage. In hospitalized patients with severe COVID-19 RCTs show clearly that the 4-aminoquinolines are not beneficial. The only treatments with proven benefit at this stage of infection are immunomodulators (dexamethasone, IL-6 receptor antagonists). No antiviral drugs have proven life-saving in late-stage COVID-19.