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International audience; Young children cannot easily produce sputum for diagnosis of pulmonary tuberculosis (TB). Alternatively, Mycobacterium tuberculosis complex bacilli can be detected in stool by using the Xpert MTB/RIF (Ultra) assay (Xpert). Published stool processing methods contain somewhat complex procedures and require additional supplies. The aim of this study was to develop a simple one-step (SOS) stool processing method based on gravity sedimentation only, similar to Xpert testing of sputum samples, for the detection of M. tuberculosis in stool samples. We first assessed whether the SOS stool method could provide valid Xpert results without the need for bead-beating, dilution, and filtration steps. We concluded that this was the case, and we then validated the SOS stool method by testing spiked stool samples. By using the SOS stool method, 27 of the 29 spiked samples gave valid Xpert results, and M. tuberculosis was recovered from all 27 samples. The proof of principle of the SOS stool method was demonstrated in routine settings in Addis Ababa, Ethiopia. Nine of 123 children with presumptive TB had M. tuberculosis-positive results for nasogastric aspiration (NGA) samples, and 7 (77.8%) of those children also had M. tuberculosis-positive Xpert results for stool samples. Additionally, M. tuberculosis was detected in the stool samples but not the NGA samples from 2 children. The SOS stool processing method makes use of the standard Xpert assay kit, without the need for additional supplies or equipment. The method can potentially be rolled out to any Xpert site, bringing a bacteriologically confirmed diagnosis of TB in children closer to the point of care.

INTRODUCTION: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. METHODS: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. RESULTS AND DISCUSSION: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI - evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. CONCLUSIONS: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point-of-care diagnostics, and efficacious and effective first-line regimens.

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria., Author summary Plasmodium vivax is the second most prevalent Plasmodium species amongst the five that can infect humans and cause malaria. The control and elimination of P. vivax is complicated by its specific biology, such as hard-to-detect low densities of blood-circulating parasites in infected individuals, the existence of persistent liver forms causing relapse, or the early appearance of sexual stages of the parasite during the course of an infection, which facilitates its transmission. These difficulties are reinforced by the fact that most antimalarial tools have been developed primarily for P. falciparum, the most prevalent malaria species, and are not always as effective for P. vivax. Current tools for the diagnosis of P. vivax are of limited effectiveness. Rapid diagnostic tests exist but show, in average, lower performance than similar test for P. falciparum. P. vivax diagnosis often relies on light microscopy which is challenging to maintain at a high quality and not sensitive enough to detect a large fraction of all infections. Recognizing that better diagnostic tools for P. vivax are needed, we report in this study the development of new target product profiles to define the specific characteristics of such tests. The establishment of these consensus-based documents is an important first step to guide research and development efforts toward better diagnostic solutions for P. vivax malaria and to accelerate the elimination of this species alongside P. falciparum.

Comment in : Screen-and-treat for chronic hepatitis B: an overdue issue for sub-Saharan Africa./Allain JP. Lancet Glob Health. 2016 Aug;4(8):e507-8. doi: 10.1016/S2214-109X(16)30140-1. PMID: 27443770; International audience; Background: Despite the introduction of immunisation for hepatitis B virus (HBV) in the 1990s, HBV-related morbidity and mortality remain high in sub-Saharan Africa. Identification and treatment of asymptomatic people with chronic HBV infection should reduce the disease burden. We therefore assessed the feasibility of a screen-and-treat programme for HBV infection in The Gambia, west Africa, and estimated the proportion of HBV-infected people who had significant liver disease in need of treatment.Methods: Between Dec 7, 2011, and Jan 24, 2014, individuals living in randomly selected communities in western Gambia were offered hepatitis B surface antigen (HBsAg) screening via a point-of-care test. The test was also offered to potential blood donors attending the central hospital in the capital, Banjul. HBsAg-positive individuals were invited for a comprehensive liver assessment and were offered treatment according to international guidelines. We defined linkage to care as visiting the liver clinic at least once. Eligibility for treatment was judged in accordance with the 2012 European Association for the Study of the Liver guidelines.Findings: HBsAg screening was accepted by 5980 (weighted estimate 68·9%, 95% CI 65·0-72·4) of 8170 adults from 27 rural and 27 urban communities and 5559 (81·4%, 80·4-82·3) of 6832 blood donors. HBsAg was detected in 495 (8·8%, 7·9-9·7) individuals in communities and 721 (13·0%, 12·1-13·9) blood donors. Prevalence was higher in men (239 [10·5%, 8·9-12·1] of 2328 men vs 256 [7·6%, 6·5-8·7] of 3652 women; p=0·004) and middle-aged participants. Linkage to care was high in the communities, with 402 (81·3%) of 495 HBsAg-positive individuals attending the clinic. However, only 300 (41·6%) of 721 HBsAg-positive people screened at the blood bank linked into care. Of those who attended the clinic, 18 (4·4%, 2·5-7·7) patients from the communities and 29 (9·7%, 6·8-13·6) from the blood bank were eligible for treatment. Male sex was strongly associated with treatment eligibility (odds ratio 4·35, 1·50-12·58; p=0·007).Interpretation: HBV infection remains highly prevalent in The Gambia. The high coverage of community-based screening, good linkage into care, and the small proportion of HBsAg carriers who need treatment suggest that large-scale screening and treatment programmes are feasible in sub-Saharan Africa.Funding: European Commission (FP7).

International audience; BACKGROUND: Volumetric capnography is technically more demanding but theoretically better than the time-based alveolar deadspace fraction (P(a)CO(2) - EtCO(2))/P(a)CO(2) as a bedside diagnostic tool for excluding pulmonary embolism (PE) in outpatients. OBJECTIVE: We compared both diagnostic accuracy in patients with a suspected PE and positive D-dimer enzyme-linked immunosorbent assay results. PATIENTS AND METHODS: In this clinical multicenter trial with prospective inclusion and 3-month follow-up, alveolar deadspace fraction was compared by receiver operating characteristic (ROC) analysis with other parameters derived from volumetric capnography. RESULTS: Capnography was performed in 239 patients, and 205 tests (86%) were conclusive. The incidence of PE was 33%. The alveolar deadspace fraction accuracy expressed with ROC curve analysis was 0.73 +/- 0.04. The diagnostic performances of parameters from volumetric capnography were not significantly better. Sixteen per cent [95% confidence interval (CI) 12-21%] of patients presented a (P(a)CO(2) - EtCO(2))/P(a)CO(2) ratio under the cut-off value of 0.15, with a low clinical probability. This combination excluded PE, with a sensitivity of 96% (95% CI 89-99%) and a negative likelihood ratio of 0.17 (95% CI 0.09-0.33%). CONCLUSION: Volumetric capnography failed to show superiority to alveolar deadspace fraction measurements [(P(a)CO(2) - EtCO(2))/P(a)CO(2)] for exclusion of PE in outpatients with positive D-dimer test results. Future studies should clarify the safety of excluding PE in patients combining low clinical probability with positive D-dimer results and (P(a)CO(2) - EtCO(2))/P(a)CO(2) ratios below the cut-off value of 0.15.

International audience; BACKGROUND: Using the intubation difficulty scale (IDS), we sought to confirm that obese patients are more difficult to intubate than lean patients. We assessed classical bedside tests and included neck circumference. METHODS: We prospectively compared the incidence of difficult tracheal intubation in 70 obese [body mass index (BMI) > or = 30 kg/m(2)] and 61 lean patients (BMI < 30 kg/m(2)). The IDS scores, categorized as difficult intubation (IDS > 5) or not (IDS < or = 5), and the patient data, were compared between lean and obese patients. Preoperative measurements [BMI, neck circumference (at the level of the thyroid cartilage), width of mouth opening, sternomental distance, and thyromental distance], medical history of obstructive sleep apnea syndrome, and several scores (Mallampati, Wilson, El Ganzouri) were recorded. The view during direct laryngoscopy was graded, and the IDS was recorded. We then compared patients with IDS < or = 5 and > 5, concerning each item. RESULTS: The results indicate that difficult tracheal intubation is more frequent in obese than in lean patients (14.3% vs 3%; P = 0.03). In the patients with IDS > 5, thyromental distance, BMI, large neck circumference, and higher Mallampati score were the only predictors of potential intubation problems. CONCLUSION: We found that problematic intubation was associated with thyromental distance, increasing neck circumference, BMI, and a Mallampati score of > or = 3. Neck circumference should be assessed preoperatively to predict difficult intubation.

Hepatitis B virus (HBV) infection is a leading cause of death in sub-Saharan Africa (SSA). Point-of-care tests for hepatitis B surface antigen (HBsAg) could be an ideal tool for a large-scale HBV screening/treatment program in SSA. Using data from the PROLIFICA (Prevention of Liver Fibrosis and Cancer in Africa) program, we conducted a cross-sectional study to assess the diagnostic accuracy of three point-of-care tests (Determine, Vikia, and Espline) for the detection of HBsAg in the field or a laboratory setting in the Gambia. In the field, we used finger-prick whole blood for the Determine and Vikia tests and dried blood spots for the reference standard test (AxSYM HBsAg enzyme-linked immunosorbent assay [ELISA]). In the laboratory we used serum for the Determine, Espline, and reference test (Architect chemiluminescent microparticle immunoassay). Of 773 participants recruited at the community and 227 known chronic HBV carriers (1,000 subjects in total), 293 were positive for HBsAg. The sensitivity and specificity of the Determine test were 88.5% and 100% in the field and 95.3% and 93.3% in the laboratory setting, respectively. The sensitivity and specificity were 90.0% and 99.8% for the Vikia test (in the field) and 93.9% and 94.7% for the Espline test (in the laboratory). There was no evidence that one kit was better than another. Most of the patients with false-negative results (18/19) were classified as inactive chronic carriers. In summary, the three point-of-care tests had acceptable ranges of diagnostic accuracy. These tests may represent accurate, rapid, and inexpensive alternatives to serology testing for the screening of HBV infection at field level in SSA.

BackgroundUser-friendly, accurate, point-of-care rapid tests to detect glucose-6-phosphate dehydrogenase deficiency (G6PDd) are urgently needed at peripheral level to safely recommend primaquine for malaria elimination.MethodsThe CareStart G6PD RDT (AccessBio, New Jersey, USA), a novel rapid diagnostic test and the most commonly used test, the fluorescent spot test (FST) were assessed against the quantitatively measured G6PD enzyme activity for detecting G6PDd. Subjects were healthy males and non-pregnant females aged 18 years or older residing in six villages in Pailin Province, western Cambodia.FindingsOf the 938 subjects recruited, 74 (7.9%) were severe and moderately severe G6PD deficient (enzyme activity ConclusionsThe CareStart G6PD RDT reliably detected moderate and severe G6PD deficient individuals (enzyme activity

The Aphasia Rapid Test (ART) is a 26-point scale developed as a bedside assessment to rate aphasia severity in acute stroke patients in 21 for poor outcome, with more than 90 % sensitivity and 80 % specificity. The ART is a simple, rapid and reproducible language task, useful in monitoring early aphasic changes in acute stroke patients and highly predictive of the 3-month verbal communication outcome. It should be easy to adapt to other languages. Electronic supplementary material The online version of this article (doi:10.1007/s00415-013-6943-x) contains supplementary material, which is available to authorized users.

Background Dengue diagnosis is complex and until recently only specialized laboratories were able to definitively confirm dengue infection. Rapid tests are now available commercially making biological diagnosis possible in the field. The aim of this study was to evaluate a combined dengue rapid test for the detection of NS1 and IgM/IgG antibodies. The evaluation was made prospectively in the field conditions and included the study of the impact of its use as a point-of-care test for case management as well as retrospectively against a panel of well-characterized samples in a reference laboratory. Methodology/Principal Findings During the prospective study, 157 patients hospitalized for a suspicion of dengue were enrolled. In the hospital laboratories, the overall sensitivity, specificity, PPV and NPV of the NS1/IgM/IgG combination tests were 85.7%, 83.9%, 95.6% and 59.1% respectively, whereas they were 94,4%, 90.0%, 97.5% and 77.1% respectively in the national reference laboratory at Institut Pasteur in Cambodia. These results demonstrate that optimal performances require adequate training and quality assurance. The retrospective study showed that the sensitivity of the combined kit did not vary significantly between the serotypes and was not affected by the immune status or by the interval of time between onset of fever and sample collection. The analysis of the medical records indicates that the physicians did not take into consideration the results obtained with the rapid test including for care management and use of antibiotic therapy. Conclusions In the context of our prospective field study, we demonstrated that if the SD Bioline Dengue Duo kit is correctly used, a positive result highly suggests a dengue case but a negative result doesn't rule out a dengue infection. Nevertheless, Cambodian pediatricians in their daily practice relied on their clinical diagnosis and thus the false negative results obtained did not directly impact on the clinical management., Author Summary Dengue is a potentially life-threatening viral disease. Symptoms are often not specific hence the importance to confirm the diagnosis during the early stage of the disease. Nevertheless, until recently only specialized laboratories were able to confirm dengue diagnosis. The discovery of the NS1 protein as a marker of infection has allowed the development of point-of-care tests for a rapid diagnosis confirmation. These tests have previously been evaluated by laboratories, but their performances have never been assessed in field conditions. In this study we evaluated the performance of SD Bioline Dengue Duo kit when tests were performed by hospital laboratories staff in a dengue hyper-endemic country. We also assessed the impact of the test results on the clinical management decision. The combination of NS1 test with antibodies detection improved the performance, though discordances on IgM and IgG results were observed between the hospitals and the national reference laboratories. Physicians treated patients according to their clinical diagnosis and did not take negative results into consideration.

International audience; PURPOSE: The study aimed to compare hemoglobin (Hb) values determined using the portable HemoCue system (HemoCue Hb 201+; HemoCue AB, Ängelholm, Sweden) with laboratory Hb level determination. MATERIALS AND METHODS: Adult patients hospitalized in our surgical intensive care unit who required an Hb level determination were included. To determine Hb level, one drop of arterial (A) or venous (V) blood was analyzed using HemoCue (HemoCue([A/V])), and also with an automated analyzer in the laboratory (Hb reference method, or Hb Lab([A/V])). Capillary blood (Cap) sample obtained simultaneously by fingerstick was analyzed using HemoCue (HemoCue([Cap])). Factors that could interfere with the accuracy of fingerstick measurements were also studied. Paired Hb level measurements were compared by Bland and Altman analysis (Hb Lab([A/V]) vs HemoCue([A/V]) and HemoCue([Cap])). RESULTS: One hundred fifty blood samples were obtained from 79 patients. The mean absolute differences between Hb Lab [A] and HemoCue [A], Hb Lab [V] and HemoCue [V] and Hb Lab [A/V] and HemoCue [Cap] were 0.1 g/dl (95% confidence interval, -1.9 to + 2.2 g/dl), 0.1 g/dl (95%CI, -2.5 to +2.6 g/dl) and 1.1 g/dl (95%CI, -3.6 to + 5.8 g/dl, respectively. Edema was the sole independent risk factor for discordance between HemoCue([Cap]) and Hb Lab([A/V]) (odds ratio, 6.65; 95% CI, 1.99-22.21; P < .001]. CONCLUSIONS: Hemoglobin level determination using HemoCue should not be used in critically patients, especially when capillary blood samples are used and/or in presence of edema.

International audience; OBJECTIVE: To assess the impact of clinical guidelines to improve appropriate use of routine laboratory tests and bedside chest radiographs in a medical intensive care. DESIGN: A two-year (Period-1: 2005, Period-2: 2006), retrospective, comparative study, before and after policy implementation. PATIENTS: All consecutive patients admitted during the study periods. SETTING: A university hospital 15-bed medical ICU. INTERVENTION: Multifaceted intervention combining a daily routine prescription help-guide developed by a multidisciplinary group and displayed at patient's bedside, educational sessions and feedbacks by information on volumes of prescription. Individual adaptation to patient's clinical status was allowed by protocol. ASSESSMENT: The overall number and cost of laboratory tests and chest radiographs during Period-2 (with the help guide; from 01 to 12-2006) were compared to Period-1 (from 01 to 12-2005). RESULTS: Patients' general characteristics were similar during the two periods. A relative reduction of routine laboratory tests performance was observed per patient-ICU-day, ranging from 38 to 71.5% depending on the type of tests (P < 0.001 in all cases). For chest radiographs, a 41% relative reduction was observed between the two periods (P < 0.001). Daily ICU laboratory tests and chest radiographs cost per patient decreased from 114 to 56 euros. An overall 300,000 euros ICU cost reduction was directly related to the protocol implementation. CONCLUSION: The implementation of a laboratory tests and chest radiographs prescription protocol within our ICU induced an important cost saving.