Two-Color Duplex Platform for Point-of-Care Differential Detection of Malaria and Typhoid Fever

Introduction: There is an urgent need for affordable point-of-care diagnostics for the differentiation of febrile illnesses and the confirmation of typhoid in endemic countries. Methodology: Blood samples were collected from febrile patients with clinical suspicion of typhoid and screened for typhoid fever using the Widal and Typhi Dri Dot tests, while stool and blood samples were screened for Salmonella Typhi using the culture method as well as PCR as a confirmatory test. Results: A high proportion of febrile patients from Lagos with clinical suspicion of typhoid fever reacted positively in a simple and rapid latex agglutination assay for typhoid fever, indicating that this illness is a common and presumably under-diagnosed health problem in this metropolis. Seropositivity was 19.2% in the rapid test compared with 22.9% in the classical Widal test. The confirmation of typhoid in these seropositive patients appeared cumbersome because of negative blood cultures and low DNA yield in molecular testing. A review of the literature revealed that in Nigeria seroprevalence rates can be high in the normal population and that pathogens other than S. Typhi are often isolated from the blood of seropositive febrile patients. Conclusion: The simplicity and the relatively high specificity (97.8%) of the rapid test as determined in a study performed in Indonesia calls for a further validation of this promising test for use in Africa.

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Redefining typhoid diagnosis: what would an improved test need to look like?

10.1101/19001958 ◽

2019 ◽

Author(s):

Richard Mather ◽

Heidi Hopkins ◽

Christopher M. Parry ◽

Sabine Dittrich

Keyword(s):

Typhoid Fever ◽

Diagnostic Test ◽

Clinical Medicine ◽

Point Of Care ◽

Treatment Algorithm ◽

Febrile Illness ◽

Diagnosis And Treatment ◽

Acute Febrile Illness ◽

Next Generation ◽

Antibiotic Overuse

IntroductionTyphoid fever is one of the most common bacterial causes of acute febrile illness in the developing world, with an estimated 10.9 million new cases and 116.8 thousand deaths in 2017. Typhoid point-of-care (POC) diagnostic tests are widely used but have poor sensitivity and specificity, resulting in antibiotic overuse that has led to the emergence and spread of multidrug resistant strains. With recent advances in typhoid surveillance and detection, this is the ideal time to produce a target product profile (TPP) that guides product development and ensure that a next-generation test meets the needs of users in the resource-limited settings where typhoid is endemic.MethodsA structured literature review was conducted to develop a draft TPP for a next-generation typhoid diagnostic test with minimal and optimal desired characteristics for 36 test parameters. The TPP was refined using feedback collected from a Delphi survey of key stakeholders in clinical medicine, microbiology, diagnostics and public and global health.ResultsA next-generation typhoid diagnostic test should improve patient management through the diagnosis and treatment of infection with acute Salmonella enterica serovars Typhi or Paratyphi with a sensitivity ≥90% and specificity ≥95%. The test would ideally be used at the lowest level of the healthcare system in settings without a reliable power or water supply and provide results in less than 15 minutes at a cost of <$1.00 USD.ConclusionThis report outlines the first comprehensive TPP for typhoid fever and is intended to guide the development of a next-generation typhoid diagnostic test. An accurate POC test will reduce the morbidity and mortality of typhoid fever through rapid diagnosis and treatment and will have the greatest impact in reducing antimicrobial resistance if it is combined with diagnostics for other causes of acute febrile illness in a treatment algorithm.

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Point-of-Care Ultrasound by Nonexpert Operators Demonstrates High Sensitivity and Specificity in Detecting Gallstones: Data from the Samoa Typhoid Fever Control Program

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.21-0973 ◽

2022 ◽

Author(s):

Seth Hoffman ◽

Sachin Desai ◽

Michael Sikorski ◽

Glenn Fatupaito ◽

Siaosi Tupua ◽

...

Keyword(s):

Typhoid Fever ◽

Point Of Care ◽

Control Program ◽

High Sensitivity ◽

Point Of Care Ultrasound ◽

Food Handlers ◽

Household Contacts ◽

Swat Team ◽

Pilot Feasibility Study ◽

Stool Cultures

Approximately 90% of chronic typhoid carriers with persistent Salmonella enterica serovar Typhi (S. Typhi) gallbladder infection have gallstones. In Samoa, where typhoid fever has been endemic for many decades, risk factors predisposing to the development of gallstones are increasing among adults. The Samoa Typhoid Fever Control Program dispatches a “Typhoid Epidemiologic SWAT Team” to perform a household investigation of every blood culture-confirmed case of acute typhoid fever. Investigations include screening household contacts to detect chronic carriers. Following limited training, two nonexpert ultrasound operators performed point-of-care ultrasound (POCUS) on 120 Samoan adults from August to September 2019 to explore the feasibility of POCUS to detect individuals with gallstones during household investigations and community screenings. POCUS scans from 120 Samoan adults in three cohorts (28 food handlers, two typhoid cases and their 18 household contacts, and 72 attendees at an ambulatory clinic) were reviewed by a board-certified radiologist who deemed 96/120 scans (80%) to be interpretable. Compared with the radiologist (gold standard), the nonexpert operators successfully detected 6/7 Samoans with gallstones (85.7% sensitivity) and correctly identified 85/89 without gallstones (95.5% specificity). The proportion (24/120) of uninterpretable scans from this pilot that used minimally trained clinicians (who are neither radiologists nor ultrasound technicians) indicates the need for additional training of POCUS operators. Nevertheless, this pilot feasibility study engenders optimism that in the Samoan setting nonexperts can be trained to use POCUS to diagnose cholelithiasis, thereby helping (along with stool cultures and Vi serology) to identify possible chronic S. Typhi carriers.

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Typhoid Fever Diagnosis in Endemic Countries: A Clog in the Wheel of Progress?

Medicina ◽

10.3390/medicina54020023 ◽

2018 ◽

Vol 54 (2) ◽

pp. 23 ◽

Cited By ~ 4

Author(s):

Olumide Ajibola ◽

Mari Mshelia ◽

Bashar Gulumbe ◽

Anthonius Eze

Keyword(s):

Typhoid Fever ◽

Sensitivity And Specificity ◽

New Technologies ◽

Point Of Care ◽

Multidrug Resistant ◽

Sub Saharan Africa ◽

Surveillance Systems ◽

Serological Tests ◽

Laboratory Surveillance ◽

Low Sensitivity

Typhoid fever causes significant morbidity and mortality in developing countries, with inaccurate estimates in some countries affected, especially those situated in Sub-Saharan Africa. Disease burden assessment is limited by lack of a high degree of sensitivity and specificity by many current rapid diagnostic tests. Some of the new technologies, such as PCR and proteomics, may also be useful but are difficult for low-resource settings to apply as point-of-care diagnostics. Weak laboratory surveillance systems may also contribute to the spread of multidrug resistant Salmonella serovar Typhi across endemic areas. In addition, most typhoid-endemic countries employ serological tests that have low sensitivity and specificity making diagnosis unreliable. Here we review currently available typhoid fever diagnostics, and advances in serodiagnosis of S. Typhi.

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Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever

Clinical and Vaccine Immunology ◽

10.1128/cvi.00311-09 ◽

2009 ◽

Vol 16 (11) ◽

pp. 1587-1594 ◽

Cited By ~ 37

Author(s):

Alaullah Sheikh ◽

M. Saruar Bhuiyan ◽

Farhana Khanam ◽

Fahima Chowdhury ◽

Amit Saha ◽

...

Keyword(s):

Typhoid Fever ◽

Salmonella Enterica ◽

Point Of Care ◽

Immunoglobulin A ◽

Unknown Origin ◽

Epidemiological Studies ◽

Peripheral Blood Lymphocytes ◽

Time Of Presentation ◽

Antibody Levels ◽

Difficult Cases

ABSTRACTMany currently available diagnostic tests for typhoid fever lack sensitivity and/or specificity, especially in areas of the world where the disease is endemic. In order to identify a diagnostic test that better correlates with typhoid fever, we evaluated immune responses toSalmonella entericaserovar Typhi (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh. We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We harvested peripheral blood lymphocytes and analyzed antibody levels in supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte-supernatant [ALS] assay), as well as in plasma on these days. We measured ALS reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever individuals into different groups (groups I to V) based on blood culture results, Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin A isotype were detectable at the time of presentation in the plasma of 81% of patients. The ALS assay, however, tested positive in all patients with documented or highly suspicious typhoid, suggesting that such a response could be the basis of improved diagnostic point-of-care-assay for serovar Typhi infection. It can be important for use in epidemiological studies, as well as in difficult cases involving fevers of unknown origin.

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Redefining typhoid diagnosis: what would an improved test need to look like?

BMJ Global Health ◽

10.1136/bmjgh-2019-001831 ◽

2019 ◽

Vol 4 (5) ◽

pp. e001831

Author(s):

Richard G Mather ◽

Heidi Hopkins ◽

Christopher M Parry ◽

Sabine Dittrich

Keyword(s):

Typhoid Fever ◽

Diagnostic Test ◽

Clinical Medicine ◽

Point Of Care ◽

Treatment Algorithm ◽

Febrile Illness ◽

Diagnosis And Treatment ◽

Acute Febrile Illness ◽

Next Generation ◽

Antibiotic Overuse

IntroductionTyphoid fever is one of the most common bacterial causes of acute febrile illness in the developing world, with an estimated 10.9 million new cases and 116.8 thousand deaths in 2017. Typhoid point-of-care (POC) diagnostic tests are widely used but have poor sensitivity and specificity, resulting in antibiotic overuse that has led to the emergence and spread of multidrug-resistant strains. With recent advances in typhoid surveillance and detection, this is the ideal time to produce a target product profile (TPP) that guides product development and ensure that a next-generation test meets the needs of users in the resource-limited settings where typhoid is endemic.MethodsA structured literature review was conducted to develop a draft TPP for a next-generation typhoid diagnostic test with minimal and optimal desired characteristics for 36 test parameters. The TPP was refined using feedback collected from a Delphi survey of key stakeholders in clinical medicine, microbiology, diagnostics and public and global health.ResultsA next-generation typhoid diagnostic test should improve patient management through the diagnosis and treatment of infection with acute Salmonella enterica serovars Typhi or Paratyphi with a sensitivity ≥90% and specificity ≥95%. The test would ideally be used at the lowest level of the healthcare system in settings without a reliable power or water supply and provide results in <15 min at a cost of <US$1.00.ConclusionThis report outlines the first comprehensive TPP for typhoid fever and is intended to guide the development of a next-generation typhoid diagnostic test. An accurate POC test will reduce the morbidity and mortality of typhoid fever through rapid diagnosis and treatment and will have the greatest impact in reducing antimicrobial resistance if it is combined with diagnostics for other causes of acute febrile illness in a treatment algorithm.

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Demonstration of a Low-Cost and Portable Optical Cavity-Based Sensor through Refractive Index Measurements

Sensors ◽

10.3390/s19092193 ◽

2019 ◽

Vol 19 (9) ◽

pp. 2193 ◽

Cited By ~ 2

Author(s):

Donggee Rho ◽

Caitlyn Breaux ◽

Seunghyun Kim

Keyword(s):

Refractive Index ◽

Detection Method ◽

Limit Of Detection ◽

Point Of Care ◽

Low Cost ◽

Optical Cavity ◽

Differential Detection ◽

Low Pass ◽

Portable System ◽

Simulation Results

An optical cavity-based sensor using a differential detection method has been proposed for point-of-care diagnostics. We developed a low-cost and portable optical cavity-based sensor system using a 3D printer and off-the-shelf optical components. In this paper, we demonstrate the sensing capability of the portable system through refractive index measurements. Fabricated optical cavity samples were tested using the portable system and compared to simulation results. A referencing technique and digital low pass filtering were applied to reduce the noise of the portable system. The measurement results match the simulation results well and show the improved linearity and sensitivity by employing the differential detection method. The limit of detection achieved was 1.73 × 10−5 Refractive Index Unit (RIU), which is comparable to other methods for refractive index sensing.

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Regulation of the gastrointestinal epithelial cell expression of CFTR protein by Salmonella enterica serovar Typhi, and its importance to infection and development of typhoid fever

Gastroenterology ◽

10.1016/s0016-5085(01)83516-2 ◽

2001 ◽

Vol 120 (5) ◽

pp. A706-A706

Author(s):

J LYCZAK ◽

G PIER

Keyword(s):

Epithelial Cell ◽

Typhoid Fever ◽

Salmonella Enterica ◽

Salmonella Enterica Serovar Typhi ◽

Cftr Protein ◽

Cell Expression

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