Ultrasononography in Managing Extrapulmonary Tuberculosis: A Randomized, Controlled, Parallel, Superiority, Open-Label Trial.

BACKGROUND: Patients with suspected extrapulmonary tuberculosis are often treated empirically. We hypothesized that extended focused assessment with sonography for human immunodeficiency virus (HIV) and tuberculosis (eFASH), in combination with other tests, would increase the proportion of correctly managed patients with suspected extrapulmonary tuberculosis. METHODS: This trial in adults with suspected extrapulmonary tuberculosis was performed in a rural and an urban hospital in Tanzania. Participants were randomized 1:1 to intervention or routine care, stratified by site and HIV status. All participants underwent clinical evaluation, chest radiography, and testing with sputum Xpert MTB/RIF and urine Xpert MTB/RIF Ultra assays. The intervention was a management algorithm based on results of eFASH plus microbiology, adenosine deaminase (ADA), and chest radiography. The primary outcome was the proportion of correctly managed patients. The presence of positive microbiological or ADA results defined definite tuberculosis. An independent end-point review committee determined diagnoses of probable or no tuberculosis. We evaluated outcomes using logistic regression models, adjusted for randomization stratification factors. RESULTS: From September 2018 to October 2020, a total of 1036 patients were screened and 701 were randomized (350 to the intervention and 351 to the control group). Of participants in the intervention group, 251 (72%) had a positive eFASH outcome. In 258 (74%) of the intervention and 227 (65%) of the control participants antituberculosis was initiated treatment at baseline. More intervention participants had definite tuberculosis (n = 124 [35%]), compared with controls (n = 85 [24%]). There was no difference between groups for the primary outcome (intervention group, 266 of 286 [93%]; control group, 245 of 266 [92%]; odds ratio, 1.14 [95% confidence interval: .60-2.16]; P = .68). There were no procedure-associated adverse events. CONCLUSIONS: eFASH did not change the proportion of correctly managed patients but increased the proportion of those with definite tuberculosis. CLINICAL TRIALS REGISTRATION: Pan African Registry: PACTR201712002829221.

Ultrasound in managing extrapulmonary tuberculosis: a randomized controlled two-center study.

BACKGROUND: Patients with clinically suspected tuberculosis are often treated empirically, as diagnosis - especially of extrapulmonary tuberculosis - remains challenging. This leads to an overtreatment of tuberculosis and to underdiagnosis of possible differential diagnoses. METHODS: This open-label, parallel-group, superiority randomized controlled trial is done in a rural and an urban center in Tanzania. HIV-positive and -negative adults (≥18 years) with clinically suspected extrapulmonary tuberculosis are randomized in a 1:1 ratio to an intervention- or control group, stratified by center and HIV status. The intervention consists of a management algorithm including extended focused assessment of sonography for HIV and tuberculosis (eFASH) in combination with chest X-ray and microbiological tests. Treatment with anti-tuberculosis drugs is started, if eFASH is positive, chest X-ray suggests tuberculosis, or a microbiological result is positive for tuberculosis. Patients in the control group are managed according national guidelines. Treatment is started if microbiology is positive or empirically according to the treating physician. The primary outcome is the proportion of correctly managed patients at 6 months (i.e patients who were treated with anti-tuberculosis treatment and had definite or probable tuberculosis, and patients who were not treated with anti-tuberculosis treatment and did not have tuberculosis). Secondary outcomes are the proportion of symptom-free patients at two and 6 months, and time to death. The sample size is 650 patients. DISCUSSION: This study will determine, whether ultrasound in combination with other tests can increase the proportion of correctly managed patients with clinically suspected extrapulmonary tuberculosis, thus reducing overtreatment with anti-tuberculosis drugs. TRIAL REGISTRATION: PACTR, Registration number: PACTR201712002829221, registered December 1st 2017.

Point-of-care ultrasound for tuberculosis and HIV-revisiting the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol and its differential diagnoses.

BACKGROUND: The 'Focused assessment with sonography for HIV-associated tuberculosis' (FASH) protocol has been applied and researched for over a decade in HIV-infected patients with suspected extra-pulmonary tuberculosis. Interpretation of target FASH features may be challenging as they can also indicate alternative opportunistic diseases. OBJECTIVES: The primary aim of the review was summarizing the accumulated evidence on the diagnostic accuracy of the FASH protocol including description of diagnoses of target FASH features. SOURCES: Literature was searched using PubMed, Google Scholar, and publications referencing the original FASH publications; data from identified studies were compiled with data from studies identified by a preceding Cochrane review. A meta-analysis was performed based on a generalized linearized mixed model. Data on differential diagnoses were compiled by literature review and retrospective evaluation of clinical data. CONTENT: We identified ten studies; abdominal target FASH features were most studied. Sensitivity and specificity estimates were 39% (95% CI 25-54) and 89% (95% CI 83-96) for enlarged lymph nodes (ten studies), and 30% (95% CI 16-45%) and 93% (95% CI 89-98%) for hypoechoic spleen lesions (eight studies). In people living with HIV differential diagnoses of target FASH features are multiple and primarily include other opportunistic infections and malignancies such as non-tuberculous mycobacterial infection, bacillary angiomatosis, hepato-splenic brucellosis, meliodiosis, visceral leishmaniasis, invasive fungal infections, and lymphoma as well as Kaposi sarcoma. Ultrasound-guided diagnostic sampling may assist obtention of a definitive diagnosis. IMPLICATIONS: On the basis of current evidence, although limited by methodology, and personal experience, we recommend basic ultrasound training, including the FASH protocol and ultrasound-guided diagnostic interventions, for all healthcare providers working with people living with HIV in resource-limited settings.

Ultrasound findings in Kaposi sarcoma patients: overlapping sonographic features with disseminated tuberculosis.

BACKGROUND: Focused Assessment with Sonography for HIV-associated TB (FASH) is a diagnostic tool for extra-pulmonary tuberculosis (TB) in symptomatic patients with advanced HIV. As Kaposi's sarcoma (KS) is also prevalent in this patient population, changes due to KS may mimic TB findings and clinical interpretation of target FASH findings can be challenging. We aimed to describe sonographic findings in patients with KS. METHODS: We performed a prospective observational study at Lighthouse clinic at Kamuzu Central Hospital, Lilongwe, Malawi, in consecutive patients with newly diagnosed KS, without known diagnosis of TB, referred for paclitaxel treatment. All patients underwent FASH and abdominal ultrasound to assess for effusions and changes in liver and spleen, as well as systematic sonographic assessment for lymphadenopathy. RESULTS: We included 30 patients. We found inguinal lymph nodes using ultrasound in 20 patients; in 3 (10%) additionally abdominal lymph nodes were found. Pathological effusions were seen in eight patients (27%): pericardial effusion in one (3%), pleural effusion in six (20%) and ascites in four (13%) patients. We found focal spleen lesions in three (10%) patients. Most of these lesions were echogenic, but in one patient, we saw hypoechoic lesions with an echogenic center. In three (10%) patients an unusual "sponge-like pattern" of the splenic vasculature was found. Six (20%) patients had echogenic focal lesions in the liver resembling hemangiomas, individual lesions showing a hypoechoic center. In two patients echogenic portal fields were seen. CONCLUSIONS: The majority of patients with newly diagnosed KS demonstrate sonographic features of disease, predominantly lymphadenopathy. Effusions were observed in a significant minority, as well as focal lesions in liver or spleen, which commonly resemble hemangiomas, but hypoechoic lesions were also observed and can easily be mistaken for extra-pulmonary TB. A 'sponge-like pattern' of the spleen should not be confused with micro-abscesses. In conclusion, this case series illustrates the diverse nature of ultrasound features in patients with KS, which can be difficult to distinguish from other opportunistic diseases, including TB.

Cross-cultural adaptation, translation, and validation of the functional assessment scale for acute hamstring injuries (FASH) questionnaire for French-speaking patients.

Study design: This consisted of a translation and validation study.Background: Acute hamstring injury is a frequent muscle strain in sports that require high explosive strength, impulsion or running phases. Therefore, the Functional Assessment Scale for Hamstring Injury questionnaire was developed to assess pain, physical activity level and ability to perform various exercises in patients with hamstring injuries. The Functional Assessment Scale for Hamstring Injury questionnaire is currently available in English, German, and Greek.Objectives: The goal of this study was to provide a cross-culturally adapted French-translation of the FASH questionnaire and to assess its psychometric performance.Methods: The French-translation and cross-cultural adaptation process were based on international recommendations, following six rigorous steps: (a) two initial translations from English to French; (b) synthesis of the two translations; (c) back-translations; (d) comparisons between the back-translations and the original questionnaire by an expert committee; (e) pretest; and (f) approval of the final French version of the Functional Assessment Scale for Hamstring Injury questionnaire. To validate this French version, 116 subjects (17 pathological patients, 19 patients with other muscle injury, 40 athletes at risk, and 40 healthy control athletes) were recruited to complete the Functional Assessment Scale for Hamstring Injury questionnaire. The Short Form Health Survey (SF-36) was used as a comparative questionnaire. The psychometric properties of the questionnaire were evaluated by determining the test-retest reliability after a 48-60-h interval, internal consistency, construct validity, and floor/ceiling effects.Results: All of the items of the Functional Assessment Scale for Hamstring Injury questionnaire were translated without any major difficulties. The questionnaire showed excellent discriminative power by obtaining significantly different scores from the four groups (p = 0.01). Regarding psychometric performances, the test-retest reliability was excellent (IntraClass Coefficient Correlation of 0.997). Very high internal consistency was also observed (Cronbach's alpha of 0.969). Correlations with the physical health subscales of the SF-36 were significant and considered to be strong, indicating an excellent convergent validity. The other subscales of the SF-36 (mental health) were weakly correlated with the FASH, reflecting good divergent validity. No floor or ceiling effects were observed.Conclusion: The French-translation of the Functional Assessment Scale for Hamstring Injury questionnaire and its cross-cultural adaptation can be considered to be successful. Functional Assessment Scale for Hamstring Injury-French questionnaire is now a reliable and valid tool for patients suffering from acute hamstring injury, and its application in clinical practice is particularly relevant.Implications for rehabilitationThe FASH-F can be considered to be discriminant, reliable and valid for the evaluation of the severity of symptoms and sports ability in individuals with hamstring injuries.FASH-F is now a reliable and valid tool for French-speaking patients suffering from acute hamstring injury, and its application in clinical practice is particularly relevant.A limitation of our study could be that the distribution between the different study groups was not homogeneous implying that our findings may not be fully representative of the general population.

Point-of-Care Ultrasound: A Useful Diagnostic Tool in Africa.

In resource limited settings with limited tests and diagnostic tools, most of diagnoses are based on clinical findings, and patients are managed empirically, e.g. with anti-tuberculosis drugs. This article aims at describing the use of point-of-care ultrasound in diagnosing the most important conditions in Africa, in addition to clinical work-up. Different protocols exist for the diagnosis of trauma-related disorders, tuberculosis, schistosomiasis, thromboembolism, causes of dyspnea, and non- traumatic shock. Point-of-care ultrasound might be a beneficial tool in Africa, aiding diagnostics and management of patients with these conditions. However, studies must be done to assess the impact of point-of-care ultrasound on mortality.

Sonography to Rule Out Tuberculosis in Sub-Saharan Africa: A Prospective Observational Study.

BACKGROUND: Patients with suspected tuberculosis are often overtreated with antituberculosis drugs. We evaluated the diagnostic value of the focused assessment with sonography for HIV-associated tuberculosis (FASH) in rural Tanzania. METHODS: In a prospective cohort study, the frequency of FASH signs was compared between patients with confirmed tuberculosis and those without tuberculosis. Clinical and laboratory examination, chest x-ray, Xpert MTB/RIF assay, and culture from sputum, sterile body fluids, lymph node aspirates, and Xpert MTB/RIF urine assay was done. RESULTS: Of 191 analyzed patients with a 6-month follow-up, 52.4% tested positive for human immunodeficiency virus, 21.5% had clinically suspected pulmonary tuberculosis, 3.7% had extrapulmonary tuberculosis, and 74.9% had extrapulmonary and pulmonary tuberculosis. Tuberculosis was microbiologically confirmed in 57.6%, probable in 13.1%, and excluded in 29.3%. Ten of eleven patients with splenic or hepatic hypoechogenic lesions had confirmed tuberculosis. In a univariate model, abdominal lymphadenopathy was significantly associated with confirmed tuberculosis. Pleural- and pericardial effusion, ascites, and thickened ileum wall lacked significant association. In a multiple regression model, abnormal chest x-ray (odds ratio [OR] = 6.19; 95% confidence interval [CI], 1.96-19.6; P < .002), ≥1 FASH-sign (OR = 3.33; 95% CI, 1.21-9.12; P = .019), and body temperature (OR = 2.48; 95% CI, 1.52-5.03; P = .001 per °C increase) remained associated with tuberculosis. A combination of ≥1 FASH sign, abnormal chest x-ray, and temperature ≥37.5°C had 99.1% sensitivity (95% CI, 94.9-99.9), 35.2% specificity (95% CI, 22.7-49.4), and a positive and negative predictive value of 75.2% (95% CI, 71.3-78.7) and 95.0% (95% CI, 72.3-99.3). CONCLUSIONS: The absence of FASH signs combined with a normal chest x-ray and body temperature <37.5°C might exclude tuberculosis.

Sound Around the World: Ultrasound for Tropical Diseases.

Ultrasound for diagnosis and staging of schistosomiasis and echinococcosis have paved the way over the past several decades for the application of ultrasound in tropical diseases. Until recently, the size and cost of ultrasound systems limited the application in low-resource settings. The increase in portable ultrasound systems has given more clinicians access to ultrasound, and clinically based protocols for the care of patients have emerged, such as focused assessment with sonography for HIV/TB and tropical cardiac ultrasound. This article explores the history and current use of ultrasound in these diseases and highlights their application in the care of patients.

Focused ultrasound to diagnose HIV-associated tuberculosis (FASH) in the extremely resource-limited setting of South Sudan: a cross-sectional study.

OBJECTIVE: Our cross-sectional study aimed at evaluating the diagnostic performance of Focused Assessment with Sonography for HIV-associated tuberculosis (FASH) to detect extrapulmonary tuberculosis in extremely resource-limited settings, with visceral leishmaniasis as a differential diagnosis with overlapping sonographic feature. DESIGN: Cross-sectional study. SETTING: Voluntary Counselling and Testing Centre (VCT) of Yirol Hospital, South Sudan. PARTICIPANTS: From May to November 2017, 252 HIV-positive patients out of 624 newly admitted to VCT Centre were registered for antiretroviral treatment. According to the number of trained doctors available to practise ultrasound (US) scan, a sample of 100 patients were screened using the FASH protocol. INTERVENTIONS: Following a full clinical examination, each patient was scanned with a portable US scanner in six different positions for pleural, pericardial, ascitic effusion, abdominal lymphadenopathy and hepatic/splenic microabscesses, according to the FASH protocol. A k39 antigen test for visceral leishmaniasis was also performed on patients with lymphadenopathy and/or splenomegaly. All demographic, clinical and HIV data, as well as FASH results and therapy adjustments, were recorded following the examination. RESULTS: The FASH protocol allowed the detection of pathological US findings suggestive of tuberculosis in 27 out of the 100 patients tested. Overall, FASH results supported tuberculosis treatment indication for 16 of 21 patients, with the treatment being based exclusively on FASH findings in half of them (8 patients). The group of FASH-positive patients had a significantly higher proportion of patients with CD4 count below 0.2 x109/L (n=22, 81%) as compared with FASH-negative patients (n=35, 48%) (p=0.003). Moreover, 48% (n=13) of FASH-positive patients had CD4 below 100 cells/mm3. All patients tested had a negative result on k39 antigen test. CONCLUSION: FASH was found to be a relevant diagnostic tool to detect signs of tuberculosis. Further research is needed to better define a patient profile suitable for investigation and also considering diagnostic accuracy.

Tuberculosis: Diagnostic Challenges in Rural Africa. / Tuberkulose: Diagnostische Herausforderungen im ländlichen Afrika

Tuberculosis (TB) remains among the top 10 infectious diseases with highest mortality globally since the 1990s despite effective chemotherapy. Among 10 million patients that fell ill with tuberculosis in the year 2017, 36 % were undiagnosed or detected and not reported; the number goes as high as 55 % in Tanzania, showing that the diagnosis of TB is a big challenge in the developing countries. There have been great advancements in TB diagnostics with introduction of the molecular tests such as Xpert MTB/RIF, loop-mediated isothermal amplification, lipoarabinomannan urine strip test, and molecular line-probe assays. However, most of the hospitals in Tanzania still rely on the TB score chart in children, the WHO screening questions in adults, acid-fast bacilli and chest x-ray for the diagnosis of TB. Xpert MTB/RIF has been rolled-out but remains a challenge in settings where the samples for testing must be transported over many kilometers. Imaging by sonography - nowadays widely available even in rural settings of Tanzania - has been shown to be a useful tool in the diagnosis of extrapulmonary tuberculosis. Despite all the efforts and new diagnostics, 30-50 % of patients in high-burden TB countries are still empirically treated for tuberculosis. More efforts need to be placed if we are to reduce the death toll by 90 % until 2030.

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.

Validation of the FASH (Functional Assessment Scale for Acute Hamstring Injuries) questionnaire for German-speaking football players.

BACKGROUND: The FASH (Functional Assessment Scale for Acute Hamstring Injuries) questionnaire has been recently developed as a disease-specific self-administered questionnaire for use in Greek, English, and German languages. Its psychometric qualities (validity and reliability) were tested only in Greek-speaking patients mainly representing track and field athletes. As hamstring injuries represent the most common football injury, we tested the validity and reliability of the FASH-G (G = German version) questionnaire in German-speaking footballers suffering from acute hamstring injuries. METHODS: The FASH-G questionnaire was tested for reliability and validity, in 16 footballers with hamstring injuries (patients' group), 77 asymptomatic footballers (healthy group), and 19 field hockey players (at-risk group). Known-group validity was tested by comparing the total FASH-G scores of the injured and non-injured groups. Reliability of the FASH-G questionnaire was analysed in 18 asymptomatic footballers using the intra-class coefficient. RESULTS: Known-group validity was demonstrated by significant differences between injured and non-injured participants (p < 0.001). The FASH-G exhibited very good test-retest reliability (intra-class correlation coefficient = 0.982, p < 0.001). Internal consistency was excellent (α = 0.938). Compared with the results presented in the original publication, no statistical differences were found between healthy athletes (p = 0.257), but patients' groups and at-risk groups presented scoring differences (p = 0.040 and <0.001, respectively). CONCLUSIONS: The FASH-G is a valid and reliable instrument to assess and determine the severity of hamstring injuries in German footballers.