Ultrasound versus Computed Tomography Assessment of Focal Lung Aeration in Invasively Ventilated ICU Patients.

It is unknown whether and to what extent the penetration depth of lung ultrasound (LUS) influences the accuracy of LUS findings. The current study evaluated and compared the LUS aeration score and two frequently used B-line scores with focal lung aeration assessed by chest computed tomography (CT) at different levels of depth in invasively ventilated intensive care unit (ICU) patients. In this prospective observational study, patients with a clinical indication for chest CT underwent a 12-region LUS examination shortly before CT scanning. LUS images were compared with corresponding regions on the chest CT scan at different subpleural depths. For each LUS image, the LUS aeration score was calculated. LUS images with B-lines were scored as the number of separately spaced B-lines (B-line count score) and the percentage of the screen covered by B-lines divided by 10 (B-line percentage score). The fixed-effect correlation coefficient (ß) was presented per 100 Hounsfield units. A total of 40 patients were included, and 372 regions were analyzed. The best association between the LUS aeration score and CT was found at a subpleural depth of 5 cm for all LUS patterns (ß = 0.30, p < 0.001), 1 cm for A- and B1-patterns (ß = 0.10, p < 0.001), 6 cm for B1- and B2-patterns (ß = 0.11, p < 0.001) and 4 cm for B2- and C-patterns (ß = 0.07, p = 0.001). The B-line percentage score was associated with CT (ß = 0.46, p = 0.001), while the B-line count score was not (ß = 0.07, p = 0.305). In conclusion, the subpleural penetration depth of ultrasound increased with decreased aeration reflected by the LUS pattern. The LUS aeration score and the B-line percentage score accurately reflect lung aeration in ICU patients, but should be interpreted while accounting for the subpleural penetration depth of ultrasound.

Point-of-Care Ultrasound in the Diagnosis of Melioidosis in Laos.

Melioidosis is endemic in many rural areas in Southeast Asia where facilities for culture and identification of Burkholderia pseudomallei are often limited. We performed a prospective observational study in patients presenting with fever to Mahosot Hospital, the primary referral hospital in Laos, to establish whether the detection of abscesses on ultrasound could support a presumptive diagnosis of melioidosis. All patients underwent ultrasound examination to detect abscesses in the liver, spleen, prostate, or, if indicated, subcutaneous tissue. We enrolled 153 patients, including 18 patients with melioidosis. Of these, 11 (61%) had an abscess at one or more sites, including five (28%) with splenic and/or liver abscesses. Absence of abscesses cannot rule out melioidosis, but the positive predictive value of abscesses for melioidosis was high at 93% (88-96%). Therefore, in endemic areas, the presence of abscesses in febrile patients should prompt empiric antibiotic therapy for melioidosis even in the absence of culture confirmation.

Cardiac ultrasound in resource-limited settings (CURLS): towards a wider use of basic echo applications in Africa.

BACKGROUND: Point-of-care ultrasound is increasingly being used as a diagnostic tool in resource-limited settings. The majority of existing ultrasound protocols have been developed and implemented in high-resource settings. In sub-Saharan Africa (SSA), patients with heart failure of various etiologies commonly present late in the disease process, with a similar syndrome of dyspnea, edema and cardiomegaly on chest X-ray. The causes of heart failure in SSA differ from those in high-resource settings. Point-of-care ultrasound has the potential to identify the underlying etiology of heart failure, and lead to targeted therapy. Based on a literature review and weighted score of disease prevalence, diagnostic impact and difficulty in performing the ultrasound, we propose a context-specific cardiac ultrasound protocol to help differentiate patients presenting with heart failure in SSA. RESULTS: Pericardial effusion, dilated cardiomyopathy, cor pulmonale, mitral valve disease, and left ventricular hypertrophy were identified as target conditions for a focused ultrasound protocol in patients with cardiac failure and cardiomegaly in SSA. By utilizing a simplified 5-question approach with all images obtained from the subxiphoid view, the protocol is suitable for use by health care professionals with limited ultrasound experience. CONCLUSIONS: The "Cardiac ultrasound for resource-limited settings (CURLS)" protocol is a context-specific algorithm designed to aid the clinician in diagnosing the five most clinically relevant etiologies of heart failure and cardiomegaly in SSA. The protocol has the potential to influence treatment decisions in patients who present with clinical signs of heart failure in resource-limited settings outside of the traditional referral institutions.

A Prospective Comparison of Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome Criteria, Universal Vital Assessment, and Modified Early Warning Score to Predict Mortality in Patients with Suspected Infection in Gabon.

The quick sequential organ failure assessment (qSOFA) score has been proposed for risk stratification of emergency room patients with suspected infection. Its use of simple bedside observations makes qSOFA an attractive option for resource-limited regions. We prospectively assessed the predictive ability of qSOFA compared with systemic inflammatory response syndrome (SIRS), universal vital assessment (UVA), and modified early warning score (MEWS) in a resource-limited setting in Lambaréné, Gabon. In addition, we evaluated different adaptations of qSOFA and UVA in this cohort and an external validation cohort from Malawi. We included 279 cases, including 183 with an ad hoc (suspected) infectious disease diagnosis. Overall mortality was 5%. In patients with an infection, oxygen saturation, mental status, human immunodeficiency virus (HIV) status, and all four risk stratification score results differed significantly between survivors and non-survivors. The UVA score performed best in predicting mortality in patients with suspected infection, with an area under the receiving operator curve (AUROC) of 0.90 (95% confidence interval [CI]: 0.78-1.0, P < 0.0001), outperforming qSOFA (AUROC 0.77; 95% CI: 0.63-0.91, P = 0.0003), MEWS (AUROC 0.72; 95% CI: 0.58-0.87, P = 0.01), and SIRS (AUROC 0.70; 95% CI: 0.52-0.88, P = 0.03). An amalgamated qSOFA score applying the UVA thresholds for blood pressure and respiratory rate improved predictive ability in Gabon (AUROC 0.82; 95% CI: 0.68-0.96) but performed poorly in a different cohort from Malawi (AUROC 0.58; 95% CI: 0.51-0.64). In conclusion, UVA had the best predictive ability, but multicenter studies are needed to validate the qSOFA and UVA scores in various settings and assess their impact on patient outcome.

Point-of-care lung ultrasound for the detection of pulmonary manifestations of malaria and sepsis: An observational study.

INTRODUCTION: Patients with severe malaria or sepsis are at risk of developing life-threatening acute respiratory distress syndrome (ARDS). The objective of this study was to evaluate point-of-care lung ultrasound as a novel tool to determine the prevalence and early signs of ARDS in a resource-limited setting among patients with severe malaria or sepsis. MATERIALS AND METHODS: Serial point-of-care lung ultrasound studies were performed on four consecutive days in a planned sub study of an observational cohort of patients with malaria or sepsis in Bangladesh. We quantified aeration patterns across 12 lung regions. ARDS was defined according to the Kigali Modification of the Berlin Definition. RESULTS: Of 102 patients enrolled, 71 had sepsis and 31 had malaria. Normal lung ultrasound findings were observed in 44 patients on enrolment and associated with 7% case fatality. ARDS was detected in 10 patients on enrolment and associated with 90% case fatality. All patients with ARDS had sepsis, 4 had underlying pneumonia. Two patients developing ARDS during hospitalisation already had reduced aeration patterns on enrolment. The SpO2/FiO2 ratio combined with the number of regions with reduced aeration was a strong prognosticator for mortality in patients with sepsis (AUROC 91.5% (95% Confidence Interval: 84.6%-98.4%)). CONCLUSIONS: This study demonstrates the potential usefulness of point-of-care lung ultrasound to detect lung abnormalities in patients with malaria or sepsis in a resource-constrained hospital setting. LUS was highly feasible and allowed to accurately identify patients at risk of death in a resource limited setting.

Potential Diagnostic Properties of Chest Ultrasound in Thoracic Tuberculosis-A Systematic Review.

Background: Chest ultrasound (CUS) has been shown to be a sensitive and specific imaging modality for pneumothorax, pneumonia, and pleural effusions. However, the role of chest ultrasound in the diagnosis of thoracic tuberculosis (TB) is uncertain. We performed a systematic search in the medical literature to better define the potential role and value of chest ultrasound in diagnosing thoracic tuberculosis. Aim: To describe existing literature with regard to the diagnostic value of chest ultrasound in thoracic tuberculosis. Methods: MEDLINE, EMBASE, and Scopus databases were searched for relevant articles. We included studies that used chest ultrasound for the diagnosis or management of any form of thoracic tuberculosis, including pulmonary, pleural, mediastinal, and military forms. Results: We identified five main fields of chest ultrasound application: (1) Detection, characterization, and quantification of TB; (2) detection of residual pleural thickening after evacuation; (3) chest ultrasound-guided needle biopsy; (4) identification of pathologic mediastinal lymph nodes in children; and (5) identification of parenchymal ultrasound patterns. Effusion was also detected, in early stages, with signs of organization in 24⁻100% of patients. A low to moderate (10⁻23%), false negative rate was reported for chest ultrasound-guided needle biopsy. CUS was able to identify mediastinal lymph nodes in as many as 67% of patients with negative chest radiography. Conclusions: Very few studies with important methodological limitations analyze the role of chest ultrasound in the diagnosis of TB. The scarce available data suggests potential targets of future diagnostic or feasibility trials, such as the detection of tuberculosis⁻related pleural effusion, residual pleural thickening, lymphadenopathy, TB parenchymal patterns, or the use of CUS in biopsy guidance.

Derivation and validation of a universal vital assessment (UVA) score: a tool for predicting mortality in adult hospitalised patients in sub-Saharan Africa.

BACKGROUND: Critical illness is a leading cause of morbidity and mortality in sub-Saharan Africa (SSA). Identifying patients with the highest risk of death could help with resource allocation and clinical decision making. Accordingly, we derived and validated a universal vital assessment (UVA) score for use in SSA. METHODS: We pooled data from hospital-based cohort studies conducted in six countries in SSA spanning the years 2009-2015. We derived and internally validated a UVA score using decision trees and linear regression and compared its performance with the modified early warning score (MEWS) and the quick sepsis-related organ failure assessment (qSOFA) score. RESULTS: Of 5573 patients included in the analysis, 2829 (50.8%) were female, the median (IQR) age was 36 (27-49) years, 2122 (38.1%) were HIV-infected and 996 (17.3%) died in-hospital. The UVA score included points for temperature, heart and respiratory rates, systolic blood pressure, oxygen saturation, Glasgow Coma Scale score and HIV serostatus, and had an area under the receiver operating characteristic curve (AUC) of 0.77 (95% CI 0.75 to 0.79), which outperformed MEWS (AUC 0.70 (95% CI 0.67 to 0.71)) and qSOFA (AUC 0.69 (95% CI 0.67 to 0.72)). CONCLUSION: We identified predictors of in-hospital mortality irrespective of the underlying condition(s) in a large population of hospitalised patients in SSA and derived and internally validated a UVA score to assist clinicians in risk-stratifying patients for in-hospital mortality. The UVA score could help improve patient triage in resource-limited environments and serve as a standard for mortality risk in future studies.

Application of the qSOFA score to predict mortality in patients with suspected infection in a resource-limited setting in Malawi.

PURPOSE: To determine the predictive value of qSOFA (quick Sequential Organ Failure Assessment) in Malawian patients with suspected infection. METHODS: Prospective observational study in a tertiary referral hospital in Malawi. RESULTS: Predictive ability of qSOFA was reasonable [AUROC 0.73 (95% CI 0.68-0.78)], increasing to 0.77 (95% CI 0.72-0.82) when classifying all patients with altered mental status as high risk. Adding HIV status as a variable to the qSOFA score did not improve predictive value. CONCLUSION: qSOFA is a simple tool that can aid risk stratification in resource-limited settings.

Ultrasound for patients in a high HIV/tuberculosis prevalence setting: a needs assessment and review of focused applications for Sub-Saharan Africa.

Ultrasound is increasingly used in point-of-care applications and has great potential to support the diagnosis of infectious diseases, especially in resource-limited settings. A cross-sectional study was performed involving 100 Malawian patients with a clinical indication for ultrasound. Furthermore, the literature on point-of-care ultrasound (POCUS) in Sub-Saharan Africa was reviewed to establish its applicability, most frequent indications, findings, and implications for treatment, and therefore relevance in POCUS curricula, with a main focus on infectious diseases. In Malawi, the main indications for ultrasound were weight loss, abdominal pain, and shortness of breath. Abnormal findings were observed in 77% of patients, the most common being enlarged abdominal lymph nodes (n=17), pericardial effusion (n=15), splenic microabscesses (n=15), and pleural effusion (n=14). POCUS led to a change in treatment in 72% of patients. The literature on the various POCUS applications used in Malawi was reviewed, including focused assessment with sonography for HIV-associated TB (FASH), heart, liver, kidney, deep venous thrombosis (DVT), and gynaecology. Based on disease prevalence, impact of POCUS on treatment, and technical difficulty, it is proposed that FASH, heart, and DVT are the most relevant POCUS applications in comparable Sub-Saharan African settings and should be incorporated in POCUS curricula.

The impact of HIV infection on blood leukocyte responsiveness to bacterial stimulation in asymptomatic patients and patients with bloodstream infection.

INTRODUCTION: HIV-induced changes in cytokine responses to bacteria may influence susceptibility to bacterial infections and the consequent inflammatory response. METHODS: We examined the impact of HIV on whole blood responsiveness to bacterial stimulation in asymptomatic subjects and patients with bacterial bloodstream infection (BSI). Whole blood was stimulated ex vivo with two bacterial Toll-like receptor agonists (lipopolysaccharide and lipoteichoic acid) and two pathogens (Streptococcus pneumoniae and non-typhoidal Salmonella), which are relevant in HIV-positive patients. Production of interferon-γ, tumour necrosis factor-α, interleukin-1ß and interleukin-6 was used as a read-out. RESULTS: In asymptomatic subjects, HIV infection was associated with reduced interferon-γ, release after stimulation and priming of the pro-inflammatory cytokine response to non-typhoidal Salmonella. In patients with BSI, we found no such priming effect, nor was there evidence for more profound sepsis-induced immunosuppression in BSI patients with HIV co-infection. CONCLUSIONS: These results suggest a complex effect of HIV on leukocyte responses to bacteria. However, in patients with sepsis, leukocyte responses were equally blunted in patients with and without HIV infection.

Bilateral pleural effusion in a HIV negative patient - TB or not TB?

Pleural tuberculosis is an infrequent cause of respiratory illness in Europe and usually presents unilaterally. We present the case of a young, immunocompetent sailor from the Phillippines, who presented with bilateral pleural fluid caused by Mycobacterium tuberculosis infection in the Netherlands. In addition challenges in the diagnostic process are discussed.

Impact of HIV infection on the haemostatic response during sepsis and malaria.

Patients positive for the human immunodeficiency virus (HIV) are more susceptible to sepsis and malaria, two conditions known to activate the coagulation system. As chronic HIV infection also influences haemostatic mechanisms, we determined the influence of HIV co-infection on coagulation, anticoagulation and the endothelium during sepsis or malaria. We performed a prospective observational study in 325 subjects with or without HIV infection (103 with sepsis, 127 with malaria and 95 asymptomatic controls) in an HIV endemic area in Central Africa. We measured plasma biomarkers indicative of activation of distinct haemostatic mechanisms. Sepsis and malaria had similar effects with elevated markers of coagulation, reduced anticoagulation markers and activation of endothelium. In particular, asymptomatic HIV infection reduced the plasma levels of the anticoagulant co-factor free protein S, and increased activation of the vascular endothelium, which were not normalized by combination antiretroviral therapy. HIV co-infection during sepsis and malaria caused more profound changes in free protein S and von Willebrand factor in sepsis and malaria, and ADAMTS13 in sepsis, while not influencing sepsis- or malaria-induced coagulation activation. These results show for the first time that HIV infection augments selective haemostatic changes during sepsis and malaria, which may contribute to the enhanced morbidity of these conditions in HIV patients.

The Impact of HIV Co-Infection on the Genomic Response to Sepsis.

HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis.

The impact of HIV on presentation and outcome of bacterial sepsis and other causes of acute febrile illness in Gabon.

PURPOSE: HIV, bacterial sepsis, malaria, and tuberculosis are important causes of disease in Africa. We aimed to determine the impact of HIV on the presentation, causes and outcome of bacterial sepsis and other acute febrile illnesses in Gabon, Central Africa. METHODS: We performed a prospective observational study in new adult admissions with fever or hypothermia (≥ 38 or <36 °C). Blood cultures, as well as HIV and malaria testing were performed in all patients. RESULTS: We enrolled 382 patients, including 77 (20.2%) with HIV infection. Malaria was the most frequent diagnosis (n = 130, 34%), and was associated with a more severe presentation in HIV patients. Sepsis was also common (n = 107, 28%), including 29 (7.6%) patients with culture confirmed bacterial bloodstream infection. Bacterial bloodstream infections were more frequent in HIV patients, in particular with S. pneumoniae. Tuberculosis was observed in 29 (7.6%) patients, and was also more common in HIV patients. The majority of HIV patients was newly diagnosed, and only 15 (19.5%) were using combination antiretroviral therapy. CONCLUSIONS: Our findings illustrate the impact of HIV co-infection on the burden of sepsis, malaria and tuberculosis in Gabon, as well as the need to scale up HIV counseling, testing and treatment.

HIV Coinfection Enhances Complement Activation During Sepsis.

BACKGROUND: Human immunodeficiency virus (HIV)-induced complement activation may play a role in chronic immune activation in patients with HIV infection and influence the complement system during acute illness. We determined the impact of HIV infection on the complement system in patients with asymptomatic HIV infection and HIV-infected patients with sepsis or malaria. METHODS: We performed a prospective observational study of 268 subjects with or without HIV infection who were asymptomatic, were septic, or had malaria. We measured complement activation products (C3bc and C4bc) and native complement proteins (C3 and C4). levels of mannose-binding lectin and C1q-C4 were measured to examine activation of the lectin and classical pathways, respectively. RESULTS: Asymptomatic HIV infection was associated with increased C4 activation, especially in patients with high HIV loads, and was accompanied by elevated C1q-C4 levels. Similarly, sepsis and malaria resulted in increased C4 activation and elevated C1q-C4 concentrations. HIV coinfection enhanced C4 activation and consumption in patients with sepsis; this effect was not detected in patients with malaria. Mannose-binding lectin deficiency (defined as a mannose-binding lectin level of <500 ng/mL) did not influence complement activation in any group. CONCLUSIONS: HIV activates the complement system, predominantly via the classical pathway, and causes increased C4 activation and consumption during sepsis. HIV-induced complement activation may contribute to tissue injury during chronic infection and acute intercurrent bacterial infections.

The effect of HIV infection on the host response to bacterial sepsis.

Bacterial sepsis is an important cause of morbidity and mortality in patients with HIV. HIV causes increased susceptibility to invasive infections and affects sepsis pathogenesis caused by pre-existing activation and exhaustion of the immune system. We review the effect of HIV on different components of immune responses implicated in bacterial sepsis, and possible mechanisms underlying the increased risk of invasive bacterial infections. We focus on pattern recognition receptors and innate cellular responses, cytokines, lymphocytes, coagulation, and the complement system. A combination of factors causes increased susceptibility to infection and can contribute to a disturbed immune response during a septic event in patients with HIV. HIV-induced perturbations of the immune system depend on stage of infection and are only in part restored by combination antiretroviral therapy. Immunomodulatory treatments currently under development for sepsis might be particularly beneficial to patients with HIV co-infection because many pathogenic mechanisms in HIV and sepsis overlap.

Clinical, environmental, and serologic surveillance studies of melioidosis in Gabon, 2012-2013.

Burkholderia pseudomallei, an environmental gram-negative bacillus, is the causative agent of melioidosis and a bio-threat agent. Reports of B. pseudomallei isolation from soil and animals in East and West Africa suggest that melioidosis might be more widely distributed than previously thought. Because it has been found in equatorial areas with tropical climates, we hypothesized that B. pseudomallei could exist in Gabon. During 2012-2013, we conducted a seroprevalance study in which we set up microbiology facilities at a large clinical referral center and prospectively screened all febrile patients by conducting blood cultures and testing for B. pseudomallei and related species; we also determined whether B. pseudomallei could be isolated from soil. We discovered a novel B. pseudomallei sequence type that caused lethal septic shock and identified B. pseudomallei and B. thailandensis in the environment. Our data suggest that melioidosis is emerging in Central Africa but is unrecognized because of the lack of diagnostic microbiology facilities.

Community-acquired bacterial bloodstream infections in HIV-infected patients: a systematic review.

Information on community-acquired bacterial bloodstream infections (BSIs) in individuals infected with human immunodeficiency virus (HIV) is limited. We conducted a systematic literature review. The case fraction of community-acquired bacterial BSIs in hospitalized patients is 20% and 30% in adults and children, respectively, compared to 9% in HIV-negative adults and children. Worldwide, the main pathogens of community-acquired BSI are nontyphoid salmonellae (NTS), Streptococcus pneumoniae, Escherichia coli, and Staphylococcus aureus, but regional differences are apparent, especially for S. pneumoniae. Compared to HIV-negative populations, HIV patients are particularly at risk to develop NTS bacteremia. Bacteremia incidence is related to immunosuppression, and antiretroviral therapy reduces the incidence of BSI in HIV patients (rate ratios, 0.63-0.02). Mortality rates varied between 7% and 46%. These results suggest that bacterial BSI is more likely to be found in HIV-positive than in HIV-negative patients upon hospitalization, and that causative pathogens vary by region.