Point-of-care ultrasound to inform antiviral treatment initiation in chronic hepatitis B virus infection in low-resource settings - the PUSH protocol.

BACKGROUND: Chronic Hepatitis B (CHB) is prevalent worldwide and most related deaths occur in low-resource settings. Antiviral treatment of CHB is indicated in those with significant liver disease and markers of viral replication. However, recommended diagnostics such as elastography (a non-invasive imaging measure of fibrosis/cirrhosis) or HBV viral load are often lacking in these settings, which creates barriers to treatment. Point-of-care clinical B-mode ultrasound (US) has potential to overcome implementation barriers in HBV care programs in low-resource settings. METHODS: We describe a Point-of-care US protocol for Hepatitis ("PUSH") to check for signs of cirrhosis and hepatocellular carcinoma in the liver of people with CHB. We performed a prospective observational study applying the protocol, first by trainee clinicians and then by trainers, in consecutive patients referred to our clinic for CHB treatment eligibility assessment. All patients additionally underwent physical examination, liver function tests (LFTs) and platelet counts. We describe the PUSH training approach and performance of the protocol. RESULTS: Four clinicians and 111 adult patients with HBV infection were included in the development of PUSH. Using US, liver complications of HBV were documented in 31 (27.9%) patients; including cirrhosis in 15 patients, HCC with cirrhosis in 13, and HCC without cirrhosis in 3. Patients with sonographic findings had significantly more clinical symptoms also their LFTs were higher and more frequently indicative for HBV treatment. Of 28 patients with sonographic diagnosis of cirrhosis, 23 (82.1%) showed a nodular liver surface, 24 (85.7%) a coarse echotexture, 20 (71.4%) scarce vessels, and 9 (32.1%) an enlarged caudate lobe. Overall concordance of the findings between assessment of trainees and experienced sonographers was high, ranging from 90 to 95%; trainees were not blinded to clinical and laboratory findings. CONCLUSION: Ultrasound can facilitate same-day initiation of antiviral therapy for chronic HBV monoinfection in a resource-limited setting and a streamlined protocol-driven liver ultrasound can be feasibly used by front line clinicians managing HBV.

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.

Case Report: Role of Point-of-Care Ultrasound in the Diagnosis of Bacillary Angiomatosis.

Clinical skin manifestations are commonly seen in resource-limited settings, but they are frequently misdiagnosed due to the lack of microbiological tests with ensuing stigma and long-term disability. The adoption of portable ultrasound devices, which extend physical examination in the hands of trained clinicians, has partially improved the situation. Specific protocols, such as focused assessment with sonography for HIV-associated tuberculosis (FASH), have led to simplified diagnostic pathways. Here we describe a case of bacillary angiomatosis in a patient with advanced HIV disease presenting with subacute unusual cutaneous lesions. The patient also presented with significant weight loss, anemia, and prostration. Highly sensitive rapid tests for tuberculosis and cryptococcosis were negative, and CD4 count was very low. Ultrasound scanning (US) and biopsy of the cutaneous lesions finally led to diagnosis and treatment. This report illustrates the benefits of integrating ultrasound-based protocols with clinical skills, as the diagnosis was suspected based on clinical presentation and US and confirmed by pathology. The importance of adoption of US protocols by infectious diseases clinicians is discussed.

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.

"Sponge pattern" of the spleen: a rarely described high-frequency ultrasound pattern in HIV-positive patients.

BACKGROUND: The spleen is frequently scanned in workup of infections. Hypoechoic splenic micro-abscesses are known signs of disseminated tuberculosis in HIV co-infected patients. The spleen of HIV patients is thus often scanned using high-frequency transducers. METHODS AND FINDINGS: We describe a reticulo-nodular "sponge pattern" in the spleen of an HIV-positive patient with Hodgkin's lymphoma. Disseminated throughout the spleen, very small (1.5-2.0 mm) hypoechoic lesions having a branching reticulo-nodular distribution were seen. The lesions partly, but not entirely, follow splenic vasculature. Review of stored images of other patients identified 15 more cases showing a similar pattern. All patients were HIV positive, almost all with CD4 counts below 200 cells/mm3. Seven (44%) were additionally diagnosed with HHV-8-associated diseases, but the pattern was seen with various underlying opportunistic infections. DISCUSSION AND CONCLUSION: After comparison with spleen microscopic anatomy, we hypothesize that the white pulp of spleens in our patients is hyperplastic or otherwise changed in consistency to be better visible by high-frequency ultrasound. Concomitant human herpesvirus-8 infection may be another cause of this visible white pulp. While we can only speculate about the etiology of the splenic "sponge pattern," it needs to be recognized as it may be misinterpreted as splenic micro-abscesses of disseminated infections, like tuberculosis in severely immune-compromised patients.

Virological Findings and Treatment Outcomes of Cases That Developed Dolutegravir Resistance in Malawi's National HIV Treatment Program.

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.

Implementing Advanced HIV Disease Care for Inpatients in a Referral Hospital in Malawi - Demand, Results and Cost Implications.

Setting: 100 bed medical ward in referral hospital, Lilongwe, Malawi. Objective: HIV positive patients admitted to hospital often have advanced HIV disease (AHD) and are at risk for mortality. WHO guidelines suggest a package of care for AHD; these are often not implemented, especially in inpatient settings. We describe an implementation model for AHD care, its outcomes in routine care and provide cost estimates. Design: An "AHD care room" was established staffed by HIV counselor, nurse, and clinical officer allowing Provider Initiated Testing and Counseling, diagnostic testing for AHD and ensuring availability of HIV and TB drugs for rapid treatment initiation. Results: In the observation period from January to December 2020, a total of 1549 medical inpatients were tested for HIV (coverage 77.1%); 69 tested positive (yield 4.5%). The total proportion of HIV positive was 32.3% (638 already on ART and 69 newly diagnosed). CD4+ testing was done in 460 medical inpatients (65.1%); 245 (53.2%) were below 200 cells/ml and thus met definition of AHD. A total of 238 received S-CrAg tests; 39 (16.3%) were positive; 62 (28.3%) of 219 U-LAM tests were positive. The cost per identification of HIV positive patient was US$ 110.8; per AHD diagnosis between US$ 17.1 to 78.9; per positive S-CrAg test US$ 18.5 and per positive U-LAM test US$ 17.5. Conclusion: Our model successfully implemented AHD services according to WHO guidelines and provides basic costing data. Similar services could be implemented in other hospitals in LMICs.

Developing Endemicity of Schistosomiasis, Corsica, France.

Urogenital schistosomiasis was diagnosed in a man from Germany who had never traveled outside Europe. He likely acquired the infection in Corsica, France, but did not swim in the Cavu River, which was linked to a previous outbreak. This case highlights that transmission of schistosomiasis in Corsica is ongoing.

Development of amoebic liver abscess in early pregnancy years after initial amoebic exposure: a case report.

BACKGROUND: Infection with Entamoeba histolytica and associated complications are relatively rare in developed countries. The overall low prevalence in the Western world as well as the possibly prolonged latency period between infection with the causing pathogen and onset of clinical symptoms may delay diagnosis of and adequate treatment for amoebiasis. Amoebic liver abscess (ALA) is the most common extraintestinal manifestation of invasive amoebiasis. Pregnancy has been described as a risk factor for development of invasive amoebiasis and management of these patients is especially complex. CASE PRESENTATION: A 30-year-old Caucasian woman in early pregnancy presented to our emergency department with abdominal pain alongside elevated inflammatory markers and liver function tests. Travel history revealed multiple journeys to tropic and subtropic regions during the past decade and a prolonged episode of intermittently bloody diarrhea during a five month stay in Indonesia seven years prior to admission. Sonographic and magnetic resonance imaging revealed a 5 × 4 cm hepatic abscess. After ultrasound-guided transcutaneous liver drainage, both abscess fluids and blood cultures showed neither bacterial growth nor microscopic signs of parasitic disease. Serological testing confirmed an infection with Entamoeba histolytica, which was treated with metronidazole, followed by eradication therapy with paromomycin. Subsequent clinical, laboratory and imaging follow-up exams showed regression of the ALA. In addition, the pregnancy completed without complications and a healthy baby boy was born 7 months after termination of treatment. CONCLUSIONS: This case of invasive amoebiasis in early pregnancy outside of endemic regions and several years after exposure demonstrates the importance of broad differential diagnostics in the context of liver abscesses. The complex interdisciplinary decisions regarding the choice of imaging techniques as well as interventional and antibiotic therapy in the context of pregnancy are discussed. Furthermore, we present possible explanations for pregnancy as a risk factor for an invasive course of amoebiasis.

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.

Case Report: Cysticercosis: Sonographic Diagnosis of a Treatable Cause of Epilepsy and Skin Nodules.

A case of disseminated cysticercosis of brain, muscle subcutaneous tissue is reported and the use of musculoskeletal ultrasound in the diagnosis of the condition emphasized.

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.

Chest ultrasonography in patients with HIV: a case series and review of the literature.

INTRODUCTION: Pulmonary disease is common in HIV-infected patients. Diagnostic means, however, are often scarce in areas where most HIV patients are living. Chest ultrasonography has recently evolved as a highly sensitive and specific imaging tool for diagnosing chest conditions such as pneumothorax, pneumonia and pulmonary edema in critically ill patients. This article addresses the issue of imaging and differentiating common pulmonary conditions in HIV-infected patients by chest ultrasonography. METHODS: We report chest ultrasound features of five different common pulmonary diseases in HIV-infected patients (bacterial pneumonia, Pneumocystis jirovecii pneumonia, tuberculosis, cytomegalovirus pneumonia and non-Hodgkin lymphoma) and review the respective literature. CONCLUSIONS: We observed characteristic ultrasound patterns especially in Pneumocystis jirovecii pneumonia and pulmonary lymphoma. Further exploration of chest ultrasonography in HIV-infected patients appears promising and may translate into new diagnostic approaches for pulmonary conditions in patients living with HIV.

Point-of-Care Ultrasound Assessment of Tropical Infectious Diseases--A Review of Applications and Perspectives.

The development of good quality and affordable ultrasound machines has led to the establishment and implementation of numerous point-of-care ultrasound (POCUS) protocols in various medical disciplines. POCUS for major infectious diseases endemic in tropical regions has received less attention, despite its likely even more pronounced benefit for populations with limited access to imaging infrastructure. Focused assessment with sonography for HIV-associated TB (FASH) and echinococcosis (FASE) are the only two POCUS protocols for tropical infectious diseases, which have been formally investigated and which have been implemented in routine patient care today. This review collates the available evidence for FASH and FASE, and discusses sonographic experiences reported for urinary and intestinal schistosomiasis, lymphatic filariasis, viral hemorrhagic fevers, amebic liver abscess, and visceral leishmaniasis. Potential POCUS protocols are suggested and technical as well as training aspects in the context of resource-limited settings are reviewed. Using the focused approach for tropical infectious diseases will make ultrasound diagnosis available to patients who would otherwise have very limited or no access to medical imaging.

Patterns of Hepatosplenic Brucella Abscesses on Cross-Sectional Imaging: A Review of Clinical and Imaging Features.

While diffuse involvement of liver and spleen is frequently seen in brucellosis, suppurative abscesses caused by Brucella are less common but well described. With the increased availability of cross-sectional imaging techniques, reports have become more frequent. Four patients with hepatosplenic abscesses caused by Brucella spp. are described and included in a review of 115 previously published cases. Clinical characteristics and patterns on ultrasound (US) and computed tomography imaging were analyzed. Furthermore, the proportion of patients with brucellosis affected by suppurative hepatosplenic lesions was estimated. Hepatosplenic abscesses were seen in 1.2% of patients with brucellosis and were mostly caused by Brucella melitensis. Imaging analysis revealed two main distinct patterns. Solitary abscesses involving liver more frequently than spleen, and showing characteristic central calcifications, characterize the first pattern. Multiple smaller abscesses, frequent spleen involvement, and absence of calcifications characterize the second pattern. Blood and aspirate cultures were frequently negative, however, the positivity rate increased over the past years. Indirect Coombs test was positive in 96%. Half of the patients were cured by antibiotic treatment; case fatality in this series was 1.9%. Hepatosplenic abscesses due to Brucella infections have characteristic imaging findings. Clinicians should be aware of these and the proactive use of cross-sectional imaging, particularly US, should be encouraged in endemic regions.

Focused assessment with sonography for HIV-associated tuberculosis (FASH): a short protocol and a pictorial review.

BACKGROUND: Ultrasound can rapidly identify abnormal signs, which in high prevalence settings, are highly suggestive of extra-pulmonary tuberculosis (EPTB). Unfortunately experienced sonographers are often scarce in these settings. METHODS: A protocol for focused assessment with sonography for HIV-associated tuberculosis (FASH) which can be used by physicians who are relatively inexperienced in ultrasound was developed. RESULTS: The technique as well as normal and pathological findings are described and the diagnostic and possible therapeutic reasoning explained. The protocol is intended for settings where the prevalence of HIV/TB co-infected patients is high. CONCLUSION: FASH is suitable for more rapid identification of EPTB even at the peripheral hospital level where other imaging modalities are scarce and most of the HIV and TB care will be delivered in the future.

Tuberculosis pericarditis with cardiac tamponade: management in the resource-limited setting.

We report a case of human immunodeficiency virus-associated pericardial tuberculosis complicated by cardiac tamponade. Emergency management and subsequent therapeutic interventions are described and then discussed with particular focus on resource-limited settings. The paucity of evidence to support clinical decisions is emphasized and the need for well designed diagnostic and therapeutic studies is highlighted.