scholarly journals Case Report: Three's a crowd: a case report examining the diagnostic and pharmacokinetic challenges in HIV-tuberculous meningitis-malaria co-infection

2019 ◽  
Vol 3 ◽  
pp. 111
Author(s):  
Jayne Ellis ◽  
Prosperity C. Eneh ◽  
Kenneth Ssebambulidde ◽  
Morris K. Rutakingirwa ◽  
Mohammed Lamorde ◽  
...  
Keyword(s):  
Case Report ◽  
Treatment Guidelines ◽  
Plasma Concentrations ◽  
False Negative ◽  
Peripheral Blood Smear ◽  
Pharmacokinetic Studies ◽  
Global Public Health ◽  
Cytochrome P450 Enzymes ◽  
Negative Results ◽  
False Negative Results

In 2016, 10.4 million cases of tuberculosis (TB) were reported globally. Malaria also continues to be a global public health threat. Due to marked epidemiological overlap in the global burden of TB and malaria, co-infection does occur. An HIV-infected, 32-year-old male presented with a two-week history of headache with fevers to Mulago National Referral Hospital, Uganda. Five months prior, he was diagnosed with pulmonary TB. He endorsed poor adherence to anti-tuberculous medications. Mycobacterium tuberculosis in CSF was confirmed on Xpert MTB/RIF Ultra. On day 2, he was initiated on dexamethasone at 0.4mg/kg/day and induction TB-medications were re-commenced (rifampicin, isoniazid, ethambutol, pyrazinamide) for TBM. He continued to spike high-grade fevers, a peripheral blood smear showed P. falciparum parasites despite a negative malaria rapid diagnostic test (RDT). He received three doses of IV artesunate and then completed 3 days of oral artemether/lumefantrine. To our knowledge this is the first published case of HIV-TBM-malaria co-infection. TBM/malaria co-infection poses a number of management challenges. Due to potential overlap in symptoms between TBM and malaria, it is important to remain vigilant for co-infection. Access to accurate parasitological diagnostics is essential, as RDT use continues to expand, it is essential that clinicians are aware of the potential for false negative results. Anti-malarial therapeutic options are limited due to important drug-drug interactions (DDIs). Rifampicin is a potent enzyme inducer of several hepatic cytochrome P450 enzymes, this induction results in reduced plasma concentrations of several anti-malarial medications. Despite recognition of potential DDIs between rifampicin and artemisinin compounds, and rifampicin and quinine, no treatment guidelines currently exist for managing patients with co-infection. There is both an urgent need for the development of new anti-malarial drugs which do not interact with rifampicin and for pharmacokinetic studies to guide dose modification of existing anti-malarial drugs to inform clinical practice guidelines.

scholarly journals Case Report: Three's a crowd: a case report examining the diagnostic and pharmacokinetic challenges in HIV-tuberculous meningitis-malaria co-infection

2018 ◽  
Vol 3 ◽  
pp. 111
Author(s):  
Jayne Ellis ◽  
Prosperity C. Eneh ◽  
Kenneth Ssebambulidde ◽  
Morris K. Rutakingirwa ◽  
Mohammed Lamorde ◽  
...  
Keyword(s):  
Case Report ◽  
Treatment Guidelines ◽  
Plasma Concentrations ◽  
False Negative ◽  
Peripheral Blood Smear ◽  
Pharmacokinetic Studies ◽  
Global Public Health ◽  
Cytochrome P450 Enzymes ◽  
Negative Results ◽  
False Negative Results

In 2016, 10.4 million cases of tuberculosis (TB) were reported globally. Malaria also continues to be a global public health threat. Due to marked epidemiological overlap in the global burden of TB and malaria, co-infection does occur. An HIV-infected, 32-year-old male presented with a two-week history of headache with fevers to Mulago National Referral Hospital, Uganda. Five months prior, he was diagnosed with pulmonary TB. He endorsed poor adherence to anti-tuberculous medications. Mycobacterium tuberculosis in CSF was confirmed on Xpert MTB/RIF Ultra. On day 2, he was initiated on dexamethasone at 0.4mg/kg/day and induction TB-medications were re-commenced (rifampicin, isoniazid, ethambutol, pyrazinamide) for TBM. He continued to spike high-grade fevers, a peripheral blood smear showed P. falciparum parasites despite a negative malaria rapid diagnostic test (RDT). He received three doses of IV artesunate and then completed 3 days of oral artemether/lumefantrine. To our knowledge this is the first published case of HIV-TBM-malaria co-infection. TBM/malaria co-infection poses a number of management challenges. Due to potential overlap in symptoms between TBM and malaria, it is important to remain vigilant for co-infection. Access to accurate parasitological diagnostics is essential, as RDT use continues to expand, it is essential that clinicians are aware of the potential for false negative results. Anti-malarial therapeutic options are limited due to important drug-drug interactions (DDIs). Rifampicin is a potent enzyme inducer of several hepatic cytochrome P450 enzymes, this induction results in reduced plasma concentrations of several anti-malarial medications. Despite recognition of potential DDIs between rifampicin and artemisinin compounds, and rifampicin and quinine, no treatment guidelines currently exist for managing patients with co-infection. There is both an urgent need for the development of new anti-malarial drugs which do not interact with rifampicin and for pharmacokinetic studies to guide dose modification of existing anti-malarial drugs to inform clinical practice guidelines.

False Negative Carrier Screening in Spinal Muscular Atrophy

2019 ◽  
Vol 35 (4) ◽  
pp. 274-277
Author(s):  
Sophie Butcher ◽  
Melanie Smith ◽  
Ian R. Woodcock ◽  
Martin Delatycki ◽  
Monique M. Ryan ◽  
...  
Keyword(s):  
Case Report ◽  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Diagnostic Testing ◽  
False Negative ◽  
Carrier Screening ◽  
Carrier Testing ◽  
Clinical Suspicion ◽  
Negative Results ◽  
False Negative Results

We describe a case of spinal muscular atrophy diagnosed in an infant despite previous parental carrier testing suggesting low risk of the disease. This case report explains how this situation arose and illustrates that clinicians need to perform diagnostic testing in children where clinical suspicion for spinal muscular atrophy is high, regardless of the result of previous parental carrier testing, because of the risk of false negative results.

Be aware of Shiga-toxin 2f-producing Escherichia coli: case report and false-negative results with certain rapid molecular panels

2020 ◽  
Vol 98 (4) ◽  
pp. 115177
Author(s):  
Aurélie Cointe ◽  
André Birgy ◽  
Alice Pascault ◽  
Ferielle Louillet ◽  
Alice Dufougeray ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Case Report ◽  
Shiga Toxin ◽  
False Negative ◽  
Negative Results ◽  
False Negative Results

Clinical utility of stimulation tests in infants with suspected adrenal insufficiency (AI)

2019 ◽  
Vol 32 (5) ◽  
pp. 529-531
Author(s):  
Preneet Cheema Brar
Keyword(s):  
Adrenal Insufficiency ◽  
Clinical Utility ◽  
Plasma Concentrations ◽  
False Negative ◽  
Relative Adrenal Insufficiency ◽  
Term Infants ◽  
Negative Results ◽  
False Negative Results ◽  
Confirmatory Tests ◽  
Stimulation Tests

Abstract Diagnosis of adrenal insufficiency (AI) in infants can be difficult. While a low random cortisol can signal AI, often confirmatory tests are required when clinical suspicion is strong but the cortisol levels are equivocal. Several studies have demonstrated that in sick preterm infants, there is relative adrenal insufficiency (RAI) defined as an inadequate cortisol production relative to the degree of stress or illness, a condition which can last for several weeks, while in term infants the adrenal axis is mature at birth (Bagnoli F, Mori A, Fommei C, Coriolani G, Badii S, et al. ACTH and cortisol cord plasma concentrations in preterm and term infants. J Perinatol 2013;33:520–4). Adrenocorticotrophic hormone (ACTH) and corticotrophin releasing hormone (CRH) stimulation tests have been validated in infants in several studies. In light of recent reports of false-negative results of stimulation tests, it is imperative to highlight the pitfalls of these tests. The purpose of this communication is to bring attention to the accuracy of timing of these tests in infants.

Coagulation Testing Gone Awry; Effect of Direct Oral Anticoagulant (DOAC) Removal on Lupus Anticoagulant Assays

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S11-S11
Author(s):  
Daniel Casa ◽  
Morayma Reyes Gil
Keyword(s):  
Lupus Anticoagulant ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
False Negative ◽  
Plasma Samples ◽  
Negative Results ◽  
False Negative Results ◽  
Increased Risk ◽  
Before And After

Abstract Background Direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban are widely used to treat those with or at risk for thromboembolic disease. However, DOACs have been shown to interfere with coagulation assays making their interpretations challenging. Importantly, lupus anticoagulant (LA) assays using the dilute Russell Viper Venom Time (dRVVT) to screen for patients at increased risk of thrombosis are particularly affected by DOACs leading to inaccurate results. DOAC removal agents are available to improve dRVVT specificity for LA and eliminate assay interferences. Aims To evaluate the performance of DOAC-Remove to accurately measure LA in patient plasma. Methods 10 LA positive and 10 LA negative samples without DOAC as well as normal pool plasma (NPP) were used as controls. We assessed 64 patient plasma samples including 39 patients on apixaban and 25 patients on rivaroxaban (anticoagulation was confirmed by chart review). LA testing by dRVVT was performed using Staclot® DRVV Screen and Staclot® DRVV Confirm reagents on STA R Max analyzer. DRVVT testing was performed before and after DOAC removal (DOAC-Remove, Aniara). DOAC plasma concentrations were measured using STA Liquid Anti-Xa assay. Acceptable DOAC removal was defined as an anti Xa level <0.03 IU/mL. Positive LA was defined as a screen ratio and mix ratio greater than 1.15. Results Positive and negative samples without DOAC remained the same after DOAC removal treatment. Factor levels in NPP were not affected by DOAC removal treatment. DOAC removal resulted in shortening of the dRVVT in 91% of the samples. Surprisingly, 6 cases showed prolongation in the dRVVT after DOAC removal. Before DOAC removal, 47 cases (24 apixaban and 23 rivaroxaban) tested positive and 17 tested negative (15 apixaban and 2 rivaroxaban). Following DOAC removal, 28 cases tested positive and 36 tested negative. As expected, many samples of patients on DOAC were found to be falsely positive (27/64; 15 on apixaban and 12 on rivaroxaban). Interestingly, 8 of 64 tests were found to be falsely negative. Of the 8 samples that were falsely negative, 7 were on apixaban and 1 on rivaroxaban. 9 samples that were negative before DOAC removal remained negative after DOAC removal, and 20 tests that were positive before DOAC removal remained positive after DOAC removal for a total of 29 results (45%) that remained unchanged. It was found that DOACs caused inaccurate results in 55% of cases. Conclusions Our study was able to demonstrate the effectiveness of DOAC-Remove to eliminate DOACs from patient plasma and provide accurate LA results. DOAC interference on LA assays predictably creates many false positive results, however, presence of DOACs can produce false negative results as well, underlying the importance of pretest screening for presence of anticoagulants in plasma samples.

Critical Evaluation of Impedance Phlebography for the Diagnosis of Deep Vein Thrombosis

1974 ◽  
Vol 31 (02) ◽  
pp. 273-278
Author(s):  
Kenneth K Wu ◽  
John C Hoak ◽  
Robert W Barnes ◽  
Stuart L Frankel
Keyword(s):  
Deep Vein Thrombosis ◽  
False Positive ◽  
False Negative ◽  
Critical Evaluation ◽  
Original Method ◽  
Vein Thrombosis ◽  
Negative Results ◽  
False Negative Results ◽  
Deep Vein ◽  
Positive Results

SummaryIn order to evaluate its daily variability and reliability, impedance phlebography was performed daily or on alternate days on 61 patients with deep vein thrombosis, of whom 47 also had 125I-fibrinogen uptake tests and 22 had radiographic venography. The results showed that impedance phlebography was highly variable and poorly reliable. False positive results were noted in 8 limbs (18%) and false negative results in 3 limbs (7%). Despite its being simple, rapid and noninvasive, its clinical usefulness is doubtful when performed according to the original method.

Scoring System for the Diagnosis of COVID-19

2020 ◽  
Vol 13 (1) ◽  
pp. 413-414 ◽  
Author(s):  
Mohamed Farouk Allam
Keyword(s):  
Scoring System ◽  
Clinical Symptoms ◽  
False Negative ◽  
Nasopharyngeal Swab ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Negative Results ◽  
False Negative Results ◽  
Symptoms And Signs

Due to the international spread of COVID-19, the difficulty of collecting nasopharyngeal swab specimen from all suspected patients, the costs of RT-PCR and CT, and the false negative results of RT-PCR assay in 41% of COVID-19 patients, a scoring system is needed to classify the suspected patients in order to determine the need for follow-up, home isolation, quarantine or the conduction of further investigations. A scoring system is proposed as a diagnostic tool for suspected patients. It includes Epidemiological Evidence of Exposure, Clinical Symptoms and Signs, and Investigations (if available). This scoring system is simple, could be calculated in a few minutes, and incorporates the main possible data/findings of any patient.

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