Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Médecins Sans Frontières Experience in Guinea-Bissau and South Sudan.

Background: More than half of childhood tuberculosis cases remain undiagnosed yearly. The World Health Organization recommends the Xpert-Ultra assay as a first pediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra with stool and urine samples in presumptive pediatric tuberculosis cases in 2 high-tuberculosis-burden settings. Methods: This Médecins Sans Frontières cross-sectional multicentric study took place at Simão Mendes Hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal Hospital, South Sudan (April 2021 to June 2023). Children aged 6 months to 15 years with presumptive tuberculosis underwent clinical and laboratory assessment, with 1 respiratory and/or extrapulmonary sample (reference standard [RS]), 1 stool, and 1 urine specimen analyzed with Xpert-Ultra. Results: A total of 563 children were enrolled in the study, 133 from Bissau and 400 from Malakal; 30 were excluded. Confirmation of tuberculosis was achieved in 75 (14.1%), while 248 (46.5%) had unconfirmed tuberculosis. Of 553 with an RS specimen, the overall diagnostic yield was 12.4% (66 of 533). A total of 493 stool and 524 urine samples were used to evaluate the performance of Xpert-Ultra with these samples. Compared with the RS, the sensitivity and specificity of Xpert-Ultra were 62.5% (95% confidence interval, 49.4%-74%) and 98.3% (96.7%-99.2%), respectively, with stool samples, and 13.9% (7.5%-24.3%) and 99.4% (98.1%-99.8%) with urine samples. Nine patients were positive with stool and/or urine samples but negative with the RS. Conclusions: Xpert-Ultra in stool samples showed moderate to high sensitivity and high specificity compared with the RS and an added diagnostic yield when RS results were negative. Xpert-Ultra in stool samples was useful in extrapulmonary cases. Xpert-Ultra in urine samples showed low test performance. Clinical Trials Registration: NCT06239337.

Correction: Evaluation of a community-based HIV test and start program in a conflict affected rural area of Yambio County, South Sudan.

[This corrects the article DOI: 10.1371/journal.pone.0254331.].

Antibiotic susceptibility patterns of pathogens isolated from hospitalized patients with advanced HIV disease (AHD) in Bihar, India.

Objectives: To describe the prevalence of common bacterial pathogens and antibiotic susceptibility patterns amongst advanced HIV disease (AHD) patients admitted between May 2019 and March 2021 to a Médecins Sans Frontières (MSF)-supported AHD inpatient unit in Bihar, India. Methods: A retrospective analysis of routinely collected demographic, clinical and microbiological data. Antibacterial susceptibility testing was done by an accredited referral laboratory using the modified Kirby-Bauer disc diffusion method. Results: A total of 238 isolates from 577 patients were identified through culture testing. Patient median (IQR) age was 38 (31-45) years, and 75% were male. Predominant sample types included blood (600; 38%), urine (266; 17%) and sputum (178; 11%). Of the isolated bacteria, Escherichia coli (80; 13.9%) was the most prevalent, followed by Klebsiella pneumonia (54; 9.4%), Pseudomonas aeruginosa (22; 3.8%), Klebsiella oxytoca (10; 1.7%), Proteus mirabilis (9; 1.6%), and Acinetobacter baumannii (7; 1.2%). The resistance pattern showed that most bacterial isolates were highly resistant to commonly prescribed antibiotics such as third-generation cephalosporins, fluoroquinolones and co-trimoxazole. Most pathogens were moderately resistant to antibiotics from the WHO Watch group, such as meropenem and piperacillin/tazobactam. In contrast, isolates were more susceptible to aminoglycosides, such as amikacin, gentamicin and nitrofurantoin. Conclusions: In Bihar, inpatients with AHD displayed a concerning array of antibiotic-resistant infections. This study provides a starting point from which further work on antimicrobial resistance in this vulnerable cohort of patients can be conducted.

Point-of-care ultrasound for tuberculosis diagnosis in children: a Médecins Sans Frontières cross-sectional study in Guinea-Bissau.

OBJECTIVE: Description of tuberculosis (TB)-focused point-of-care ultrasound (POCUS) findings for children with presumptive TB. DESIGN: Cross-sectional study (July 2019 to April 2020). SETTING: Simão Mendes hospital in Bissau, a setting with high TB, HIV, and malnutrition burdens. PARTICIPANTS: Patients aged between 6 months and 15 years with presumptive TB. INTERVENTIONS: Participants underwent clinical, laboratory and unblinded clinician-performed POCUS assessments, to assess subpleural nodules (SUNs), lung consolidation, pleural and pericardial effusion, abdominal lymphadenopathy, focal splenic and hepatic lesions and ascites. Presence of any sign prompted a POCUS positive result. Ultrasound images and clips were evaluated by expert reviewers and, in case of discordance, by a second reviewer. Children were categorised as confirmed TB (microbiological diagnosis), unconfirmed TB (clinical diagnosis) or unlikely TB. Ultrasound findings were analysed per TB category and risk factor: HIV co-infection, malnutrition and age. RESULTS: A total of 139 children were enrolled, with 62 (45%) women and 55 (40%) aged <5 years; 83 (60%) and 59 (42%) were severely malnourished (SAM) and HIV-infected, respectively. TB confirmation occurred in 27 (19%); 62 (45%) had unconfirmed TB and 50 (36%) had unlikely TB. Children with TB were more likely to have POCUS-positive results (93%) compared with children with unlikely TB (34%). Common POCUS signs in patients with TB were: lung consolidation (57%), SUNs (55%) and pleural effusion (30%), and focal splenic lesions (28%). In children with confirmed TB, POCUS sensitivity was 85% (95% CI) (67.5% to 94.1%). In those with unlikely TB, specificity was 66% (95% CI 52.2% to 77.6%). Unlike HIV infection and age, SAM was associated with a higher POCUS-positivity. Cohen's kappa coefficient for concordance between field and expert reviewers ranged from 0.6 to 0.9. CONCLUSIONS: We found a high prevalence of POCUS signs in children with TB compared with children with unlikely TB. POCUS-positivity was dependent on nutritional status but not on HIV status or age. TB-focused POCUS could potentially play a supportive role in the diagnosis of TB in children. TRIAL REGISTRATION NUMBER: NCT05364593.

Evaluation of a community-based HIV test and start program in a conflict affected rural area of Yambio County, South Sudan.

BACKGROUND: Antiretroviral therapy (ART) coverage in South Sudan is around 10%. Access to HIV care in settings with low ART coverage or conflict affected is still low; innovative strategies are needed to increase access and ensure continuation of ART during instability. A pilot HIV test and start project was implemented in a conflict-affected area of South Sudan. In a retrospective analysis, we determined the feasibility and outcomes of this intervention. METHODS: Programme data from July 2015 to June 2018 was analysed. The project involved five mobile teams offering HIV counselling and testing (HCT) and same day ART initiation at community level. Baseline and follow-up information on clinical, immunological and viral load (VL) was routinely recorded, as well as treatment outcomes. A semi-qualitative study was conducted to assess acceptability of the program among beneficiaries and community members. RESULTS: By June 2018, 14824 people received counselling and testing for HIV and 498 (3.4%) tested positive. Out of those 395 (79.3%) started ART. A total of 72 ART patients were organized in 26 Community ART Groups (CAGs) and contingency plan was activated 9 times for 101 patients. Kaplan-Meier estimated retention in care (RIC) at 12 and 18 months was 80.6% [95% CI: 75.9-84.5%] and 69.9% [95% CI: 64.4-74.8%] respectively. RIC was significantly higher at 18 months in patients under community ART groups (CAGs) (90.9% versus 63.4% p<0.001) when compared to patients on regular follow up. VL suppression at 12 months was 90.3% and overall virological suppression reached 91.2%. A total of 279 persons were interviewed about the MSF program perception and acceptance: 98% had heard about the programme and 84% found it beneficial for the community, 98% accepted to be tested and only 4% found disadvantages to the programme. CONCLUSIONS: Our study shows that HCT and early ART initiation in conflict affected populations can be provided with good program outcomes. RIC and virological suppression are comparable with facility-based HIV programs and to those in stable contexts. This model could be extrapolated to other similar contexts with low access to ART and where security situation is a concern.

Sonographic findings in visceral leishmaniasis - A narrative review.

BACKGROUND: Visceral leishmaniasis (VL) is predominantly a neglected tropical parasitic disease but may also be acquired by travellers. We aimed at summarizing knowledge on sonographic presentation of VL to better understand sonographic features of VL. METHODS: PubMed was searched for studies and case reports presenting original data on sonographic findings of VL, published before August 13th, 2019. Demographic, clinical, and sonographic data were extracted and summarized in a qualitative approach. RESULTS: A total of 36 publications were included in this review; 27 of these were case reports and the remainder were prospective or retrospective studies. No study reported systematic cross-sectional comparative imaging. Overall, publications reported on 512 patients with VL of whom 12 were reported HIV-infected. Spleno- and hepatomegaly were the most frequently reported findings. Further relevant and repeatedly reported findings were splenic and hepatic lesions, abdominal lymphadenopathy, pleural and pericardial effusion and ascites. Reported focal splenic lesions were heterogeneous in size, shape, and echogenicity. Several publications reported gradual diminution and resolution of sonographic findings with VL treatment. CONCLUSION: Available literature on sonographic findings of VL is limited. Available reports indicate that spleno- and hepatomegaly, free fluid, abdominal lymphadenopathy, and focal splenic lesions may be common sonographic features in patients with VL. Because of the apparent overlap of sonographic features of VL, extrapulmonary tuberculosis and other conditions, interpretation of sonographic findings needs to be made with particular caution.

Lived experiences of palliative care among people living with HIV/AIDS: a qualitative study from Bihar, India.

OBJECTIVES: This study aimed to assess the lived experiences of palliative care among critically unwell people living with HIV/AIDS (PLHA), caregivers and relatives of deceased patients. It also aimed to understand the broader palliative care context in Bihar. DESIGN: This was an exploratory, qualitative study which used thematic analysis of semistructured, in-depth interviews as well as a focus group discussion. SETTING: All interviews took place in a secondary care hospital in Patna, Bihar which provides holistic care to critically unwell PLHA. PARTICIPANTS: We purposively selected 29 participants: 10 critically unwell PLHA, 5 caregivers of hospitalised patients, 7 relatives of deceased patients who were treated in the secondary care hospital and 7 key informants from community-based organisations. RESULTS: Critically ill PLHA emphasised the need for psychosocial counselling and opportunities for social interaction in the ward, as well as a preference for components of home-based palliative care, even though they were unfamiliar with actual terms such as 'palliative care' and 'end-of-life care'. Critically unwell PLHA generally expressed preference for separate, private inpatient areas for end-of-life care. Relatives of deceased patients stated that witnessing patients' deaths caused trauma for other PLHA. Caregivers and relatives of deceased patients felt there was inadequate time and space for grieving in the hospital. While both critically ill PLHA and relatives wished that poor prognosis be transparently disclosed to family members, many felt it should not be disclosed to the dying patients themselves. CONCLUSIONS: Despite expected high inpatient fatality rates, PLHA in Bihar lack access to palliative care services. PLHA receiving end-of-life care in hospitals should have a separate dedicated area, with adequate psychosocial counselling and activities to prevent social isolation. Healthcare providers should make concerted efforts to inquire, understand and adapt their messaging on prognosis and end-of-life care based on patients' preferences.

Quality of life perceptions amongst patients co-infected with Visceral Leishmaniasis and HIV: A qualitative study from Bihar, India.

BACKGROUND: Co-infection with Visceral Leishmaniasis (commonly known as Kala Azar, KA) and Human Immunodeficiency Virus (HIV) is increasingly being diagnosed among patients in Bihar. This qualitative study is the first assessment of self-reported quality of life among patients co-infected with KA-HIV in the Asian context. METHODS: We conducted semi-structured, in-depth interviews and adopted an inductive thematic analysis to generate evidence on the quality of life of patients co-infected with KA and HIV. Patients were purposively sampled until saturation was attained. RESULTS: We found that patients highly valued income or livelihood potential and health as indicators of a good quality life, and routinely went into debt accessing care in the private setup. This was due to perceptions of poor quality of care in the government setup and a lack of knowledge regarding available government services at the district level. KA symptoms were often misdiagnosed in the private sector as seasonal fever, while care providers found it difficult to disentangle the clinical symptoms of KA and HIV; hence, patients presented late to district hospitals. Patients perceived a high level of stigma, largely due to their HIV status, and routinely reported that HIV had "destroyed" their life. CONCLUSIONS: Inadequate social support and referral pathways that were not conducive to patient needs negatively impacted patients' quality of life. The dual burden of poverty interacting with the severity and chronicity of KA-HIV co-infection means financial support, increased community engagement, and collaborative decision making are crucial for co-infected patients. Increased provider awareness of co-infection and effective stigma-reduction interventions should be integrated to ensure that appropriate and effective access to care is possible for this vulnerable population. A sustainable long-term strategy requires a people-centered approach wherein the perceptions and life circumstances of patients are taken into account in the medical decision making process.

Refused and referred-persistent stigma and discrimination against people living with HIV/AIDS in Bihar: a qualitative study from India.

OBJECTIVES: This study aimed to explore barriers to accessing care, if any, among people living with HIV/AIDS (PLHA) in two districts of Bihar. We also aimed to assess attitudes towards PLHA among healthcare providers and community members. DESIGN: This qualitative study used an exploratory study design through thematic analysis of semistructured, in-depth interviews. SETTING: Two districts were purposively selected for the study, namely the capital Patna and a peripheral district located approximately 100 km from Patna, in order to glean insights from a diverse sample of respondents. PARTICIPANTS: Our team purposively selected 71 participants, including 35 PLHA, 10 community members and 26 healthcare providers. RESULTS: The overarching theme that evolved from these data through thematic coding identified that enacted stigma and discrimination interfere with each step in the HIV care continuum for PLHA in Bihar, India, especially outside urban areas. The five themes that contributed to these results include: perception of HIV as a dirty illness at the community level; non-consensual disclosure of HIV status; reliance on identifying PLHA to guide procedures and resistance to universal precautions; refusal to treat identified PLHA and referrals to other health centres for treatment; and inadequate knowledge and fear among health providers with respect to HIV transmission. CONCLUSIONS: The continued presence of discriminatory and stigmatising attitudes towards PLHA negatively impacts both disclosure of HIV status as well as access to care and treatment. We recognise a pressing need to improve the knowledge of HIV transmission, and implement universal precautions across all health facilities in the state, not just to reduce stigma and discrimination but also to ensure proper infection control. In order to improve treatment adherence and encourage optimal utilisation of services, it is imperative that the health system invest more in stigma reduction in Bihar and move beyond more ineffective, punitive approaches.

Implications of differentiated care for successful ART scale-up in a concentrated HIV epidemic in Yangon, Myanmar.

INTRODUCTION: National AIDS Programme in Myanmar has made significant progress in scaling up antiretroviral treatment (ART) services and recognizes the importance of differentiated care for people living with HIV. Indeed, long centred around the hospital and reliant on physicians, the country's HIV response is undergoing a process of successful decentralization with HIV care increasingly being integrated into other health services as part of a systematic effort to expand access to HIV treatment. This study describes implementation of differentiated care in Médecins Sans Frontières (MSF)-supported programmes and reports its outcomes. METHODS: A descriptive cohort analysis of adult patients on antiretroviral treatment was performed. We assessed stability of patients as of 31 December 2014 and introduced an intervention of reduced frequency of physicians' consultations for stable patients, and fast tract ART refills. We measured a number of saved physician's visits as the result of this intervention. Main outcomes, remained under care, death, lost to follow up, treatment failure, were assessed on 31 December 2015 and reported as rates for different stable groups. RESULTS: On 31 December 2014, our programme counted 16, 272 adult patients enrolled in HIV care, of whom 80.34% were stable. The model allowed for an increase in the average number of patients one medical team could care for - from 745 patients in 2011 to 1, 627 in 2014 - and, thus, a reduction in the number of teams needed. An assessment of stable patients enrolled on ART one year after the implementation of the new model revealed excellent outcomes, aggregated for stable patients as 98.7% remaining in care, 0.4% dead, 0.8% lost to follow-up, 0.8% clinical treatment failure and 5.8% with immunological treatment failure. CONCLUSIONS: Implementation of a differentiated model reduced the number of visits between stable clients and physicians, reduced the medical resources required for treatment and enabled integrated treatment of the main co-morbidities. We hope that these findings will encourage other stakeholders to implement innovative models of HIV care in Myanmar, further expediting the scale up of ART services, the decentralization of treatment and the integration of care for the main HIV co-morbidities in this context.