A comprehensive resource describing innovative technologies and digital health tools that can revolutionize the delivery of health care in low- to middle- income countries, particularly in remote ...rural impoverished communities Revolutionizing Tropical Medicine offers an up-to-date guide for healthcare and other professionals working in low-resource countries where access to health care facilities for diagnosis and treatment is challenging. Rather than suggesting the expensive solution of building new bricks and mortar clinics and hospitals and increasing the number of doctors and nurses in these deprived areas, the authors propose a complete change of mindset. They outline a number of ideas for improving healthcare including rapid diagnostic testing for infectious and non-infectious diseases at a point-of-care facility, together with low cost portable imaging devices. In addition, the authors recommend a change in the way in which health care is delivered. This approach requires task-shifting within the healthcare provision system so that nurses, laboratory technicians, pharmacists and others are trained in the newly available technologies, thus enabling faster and more appropriate triage for people requiring medical treatment. This text: * Describes the current burden of communicable and non-communicable diseases in low- to middle-income countries throughout the world * Describes the major advances in healthcare outcomes in low-to middle-income countries derived from implementation of the United Nations/World Health Organisation's 2000 Millennium Development Goals * Provides a review of inexpensive rapid diagnostic point-of-care tests for infectious diseases in low-resource countries, particularly for people living in remote rural areas * Provides a review of other rapid point-of-care services for assessing hematological function, biochemical function, renal function, hepatic function and status including hepatitis, acid-base balance, sickle cell disease, severe acute malnutrition and spirometry * Explores the use of low-cost portable imaging devices for use in remote rural areas including a novel method of examining the optic fundus using a smartphone and the extensive value of portable ultrasound scanning when x-ray facilities are not available * Describes the use of telemedicine in the clinical management of both children and adults in remote rural settings * Looks to the future of clinical management in remote impoverished rural settings using nucleic acid identification of pathogens, the use of nanoparticles for water purification, the use of drones, the use of pulse oximetry and the use of near-infrared spectroscopy * Finally, it assesses the potential for future healthcare improvement in impoverished areas and how the United Nations/World Health Organization 2015 Sustainable Development Goals are approaching this. Written for physicians, infectious disease specialists, pathologists, radiologists, nurses, pharmacists and other health care workers, as well as government healthcare managers, Revolutionizing Tropical Medicine is a new up- to-date essential and realistic guide to treating and diagnosing patients in low-resource tropical countries based on new technologies.
Background
Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use antibodies to detect either HRP‐2 antigen or pLDH antigen, and can improve access to diagnostics in developing ...countries.
Objectives
To assess the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria by type and brand.
Search methods
We undertook a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; IndMED; to January 14, 2010.
Selection criteria
Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in P. falciparum endemic areas.
Data collection and analysis
For each study, a standard set of data was extracted independently by two authors, using a tailored data extraction form. Comparisons were grouped hierarchically by target antigen, and type and brand of RDT, and combined in meta‐analysis where appropriate.
Main results
We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP‐2 (fromP. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta‐analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively.
Overall for HRP‐2, the meta‐analytical average sensitivity and specificity (95% CI) were 95.0% (93.5% to 96.2%) and 95.2% (93.4% to 99.4%), respectively.
For pLDH antibody‐based RDTs verified with microscopy, we identified 17 evaluations of Type 4 RDTs and three evaluations of Type 5 RDTs. In meta‐analyses, average sensitivity for Type 4 tests was 91.5% (84.7% to 95.3%) and average specificity was 98.7% (96.9% to 99.5%). For Type 5 tests, average sensitivity was 98.4% (95.1% to 99.5%) and average specificity was 97.5% (93.5% to 99.1%).
Overall for pLDH, the meta‐analytical average sensitivity and specificity (95% CI) were 93.2% (88.0% to 96.2%) and 98.5% (96.7% to 99.4%), respectively.
For both categories of test, there was substantial heterogeneity in study results. Quality of the microscopy reference standard could only be assessed in 40% of studies due to inadequate reporting, but results did not seem to be influenced by the reporting quality.
Overall, HRP‐2 antibody‐based tests (such as the Type 1 tests) tended to be more sensitive and were significantly less specific than pLDH‐based tests (such as the Type 4 tests). If the point estimates for Type 1 and Type 4 tests are applied to a hypothetical cohort of 1000 patients where 30% of those presenting with symptoms have P. falciparum, Type 1 tests will miss 16 cases, and Type 4 tests will miss 26 cases. The number of people wrongly diagnosed with P. falciparum would be 34 with Type 1 tests, and nine with Type 4 tests.
Authors' conclusions
The sensitivity and specificity of all RDTs is such that they can replace or extend the access of diagnostic services for uncomplicated P. falciparum malaria. HRP‐2 antibody types may be more sensitive but are less specific than pLDH antibody‐based tests, but the differences are small. The HRP‐2 antigen persists even after effective treatment and so is not useful for detecting treatment failures.
23 April 2019
No update planned
Other
Good evidence of benefit and further research is unlikely to change our confidence in the estimates of test accuracy. All eligible published studies found in the last search (14 Jan, 2010) were included.
Infectious diseases are a major global health issue. Diagnosis is a critical first step in effectively managing their spread. Paper-based microfluidic diagnostics first emerged in 2007 as a low-cost ...alternative to conventional laboratory testing, with the goal of improving accessibility to medical diagnostics in developing countries. In this review, we examine the advances in paper-based microfluidic diagnostics for medical diagnosis in the context of global health from 2007 to 2016. The theory of fluid transport in paper is first presented. The next section examines the strategies that have been employed to control fluid and analyte transport in paper-based assays. Tasks such as mixing, timing, and sequential fluid delivery have been achieved in paper and have enabled analytical capabilities comparable to those of conventional laboratory methods. The following section examines paper-based sample processing and analysis. The most impactful advancement here has been the translation of nucleic acid analysis to a paper-based format. Smartphone-based analysis is another exciting development with potential for wide dissemination. The last core section of the review highlights emerging health applications, such as male fertility testing and wearable diagnostics. We conclude the review with the future outlook, remaining challenges, and emerging opportunities.
Fast and widespread diagnosis is crucial to fighting against the outbreak of COVID‐19. This work surveys the landscape of available and emerging biosensor technologies for COVID‐19 testing. Molecular ...diagnostic assays based on quantitative reverse transcription polymerase chain reaction are used in most clinical laboratories. However, the COVID‐19 pandemic has overwhelmed testing capacity and motivated the development of fast point‐of‐care tests and the adoption of isothermal DNA amplification. Antigenic and serological rapid tests based on lateral‐flow immunoassays suffer from low sensitivity. Advanced digital systems enhance performance at the expense of speed and the need for large equipment. Emerging technologies, including CRISPR gene‐editing tools, benefit from high sensitivity and specificity of molecular diagnostics and the easy use of lateral‐flow assays. DNA sequencing and sample pooling strategies are highlighted to bring out the full capacity of the available biosensor technologies and accelerate mass testing.
Biosensors for COVID‐19 testing. The landscape of molecular diagnostics for infectious diseases is evolving rapidly to respond to the COVID‐19 outbreak. The sensitivity, specificity and speed of the tests vary depending on the biomarker (viral RNA, viral protein or antibodies against the virus), sample type (swab or blood) and detection method. Emerging diagnostic tools aim to circumvent roadblocks encountered at each step.
Abstract
The 14
th
experimental campaign from the Korea Superconducting Tokamak Advanced Research (KSTAR) device has passed since the first experimental campaign was carried out in 2008. The basic ...diagnostic systems such as magnetic diagnostics, interferometer, inspection illuminator, visible spectrometer, ECE radiometer have been used for the first plasma experiment in KSTAR. Currently more than 50 diagnostic systems have been continuously installed including improved basic diagnostics and advanced imaging diagnostics in KSTAR. A recent progress and future plan of diagnostics for KSTAR are briefly discussed.
Aneurysms-osteoarthritis syndrome (AOS) is a new autosomal dominant syndromic form of thoracic aortic aneurysms and dissections characterised by the presence of arterial aneurysms and tortuosity, ...mild craniofacial, skeletal and cutaneous anomalies, and early-onset osteoarthritis. AOS is caused by mutations in the SMAD3 gene.
A cohort of 393 patients with aneurysms without mutation in FBN1, TGFBR1 and TGFBR2 was screened for mutations in SMAD3. The patients originated from The Netherlands, Belgium, Switzerland and USA. The clinical phenotype in a total of 45 patients from eight different AOS families with eight different SMAD3 mutations is described. In all patients with a SMAD3 mutation, clinical records were reviewed and extensive genetic, cardiovascular and orthopaedic examinations were performed.
Five novel SMAD3 mutations (one nonsense, two missense and two frame-shift mutations) were identified in five new AOS families. A follow-up description of the three families with a SMAD3 mutation previously described by the authors was included. In the majority of patients, early-onset joint abnormalities, including osteoarthritis and osteochondritis dissecans, were the initial symptom for which medical advice was sought. Cardiovascular abnormalities were present in almost 90% of patients, and involved mainly aortic aneurysms and dissections. Aneurysms and tortuosity were found in the aorta and other arteries throughout the body, including intracranial arteries. Of the patients who first presented with joint abnormalities, 20% died suddenly from aortic dissection. The presence of mild craniofacial abnormalities including hypertelorism and abnormal uvula may aid the recognition of this syndrome.
The authors provide further insight into the phenotype of AOS with SMAD3 mutations, and present recommendations for a clinical work-up.
Background
Plasmodium vivax (P vivax) is a focus of malaria elimination. It is important because P vivax and Plasmodium falciparum infection are co‐endemic in some areas. There are asymptomatic ...carriers of P vivax, and the treatment for P vivax and Plasmodium ovale malaria differs from that used in other types of malaria. Rapid diagnostic tests (RDTs) will help distinguish P vivax from other malaria species to help treatment and elimination. There are RDTs available that detect P vivax parasitaemia through the detection of P vivax‐specific lactate dehydrogenase (LDH) antigens.
Objectives
To assess the diagnostic accuracy of RDTs for detecting P vivax malaria infection in people living in malaria‐endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria; and to identify which types and brands of commercial tests best detect P vivax malaria.
Search methods
We undertook a comprehensive search of the following databases up to 30 July 2019: Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Science Citation Index Expanded (SCI‐EXPANDED) and Conference Proceedings Citation Index‐Science (CPCI‐S), both in the Web of Science.
Selection criteria
Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction (PCR)) in blood samples from patients attending ambulatory health facilities with symptoms suggestive of malaria in P vivax‐endemic areas.
Data collection and analysis
For each included study, two review authors independently extracted data using a pre‐piloted data extraction form. The methodological quality of the studies were assessed using a tailored Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. We grouped studies according to commercial brand of the RDT and performed meta‐analysis when appropriate. The results given by the index tests were based on the antibody affinity (referred to as the strength of the bond between an antibody and an antigen) and avidity (referred to as the strength of the overall bond between a multivalent antibody and multiple antigens). All analyses were stratified by the type of reference standard. The bivariate model was used to estimate the pooled sensitivity and specificity with 95% confidence intervals (CIs), this model was simplified when studies were few. We assessed the certainty of the evidence using the GRADE approach.
Main results
We included 10 studies that assessed the accuracy of six different RDT brands (CareStart Malaria Pf/Pv Combo test, Falcivax Device Rapid test, Immuno‐Rapid Malaria Pf/Pv test, SD Bioline Malaria Ag Pf/Pv test, OnSite Pf/Pv test and Test Malaria Pf/Pv rapid test) for detecting P vivax malaria. One study directly compared the accuracy of two RDT brands. Of the 10 studies, six used microscopy, one used PCR, two used both microscopy and PCR separately and one used microscopy corrected by PCR as the reference standard. Four of the studies were conducted in Ethiopia, two in India, and one each in Bangladesh, Brazil, Colombia and Sudan.
The studies often did not report how patients were selected. In the patient selection domain, we judged the risk of bias as unclear for nine studies. We judged all studies to be of unclear applicability concern. In the index test domain, we judged most studies to be at low risk of bias, but we judged nine studies to be of unclear applicability concern. There was poor reporting on lot testing, how the RDTs were stored, and background parasitaemia density (a key variable determining diagnostic accuracy of RDTs). Only half of the included studies were judged to be at low risk of bias in the reference standard domain, Studies often did not report whether the results of the reference standard could classify the target condition or whether investigators knew the results of the RDT when interpreting the results of the reference standard. All 10 studies were judged to be at low risk of bias in the flow and timing domain.
Only two brands were evaluated by more than one study. Four studies evaluated the CareStart Malaria Pf/Pv Combo test against microscopy and two studies evaluated the Falcivax Device Rapid test against microscopy. The pooled sensitivity and specificity were 99% (95% CI 94% to 100%; 251 patients, moderate‐certainty evidence) and 99% (95% CI 99% to 100%; 2147 patients, moderate‐certainty evidence) for CareStart Malaria Pf/Pv Combo test.
For a prevalence of 20%, about 206 people will have a positive CareStart Malaria Pf/Pv Combo test result and the remaining 794 people will have a negative result. Of the 206 people with positive results, eight will be incorrect (false positives), and of the 794 people with a negative result, two would be incorrect (false negative).
For the Falcivax Device Rapid test, the pooled sensitivity was 77% (95% CI: 53% to 91%, 89 patients, low‐certainty evidence) and the pooled specificity was 99% (95% CI: 98% to 100%, 621 patients, moderate‐certainty evidence), respectively. For a prevalence of 20%, about 162 people will have a positive Falcivax Device Rapid test result and the remaining 838 people will have a negative result. Of the 162 people with positive results, eight will be incorrect (false positives), and of the 838 people with a negative result, 46 would be incorrect (false negative).
Authors' conclusions
The CareStart Malaria Pf/Pv Combo test was found to be highly sensitive and specific in comparison to microscopy for detecting P vivax in ambulatory healthcare in endemic settings, with moderate‐certainty evidence. The number of studies included in this review was limited to 10 studies and we were able to estimate the accuracy of 2 out of 6 RDT brands included, the CareStart Malaria Pf/Pv Combo test and the Falcivax Device Rapid test. Thus, the differences in sensitivity and specificity between all the RDT brands could not be assessed. More high‐quality studies in endemic field settings are needed to assess and compare the accuracy of RDTs designed to detect P vivax.