Visceral leishmaniasis in the hills of western Nepal: A transmission assessment.

In Nepal, visceral leishmaniasis (VL) has been targeted for elimination as a public health problem by 2026. Recently, increasing numbers of VL cases have been reported from districts of doubtful endemicity including hills and mountains, threatening the ongoing VL elimination program in Nepal. We conducted a multi-disciplinary, descriptive cross-sectional survey to assess the local transmission of Leishmania donovani in seven such districts situated at altitudes of up to 1,764 meters in western Nepal from March to December 2019. House-to-house surveys were performed for socio-demographic data and data on past and current VL cases. Venous blood was collected from all consenting individuals aged ≥2 years and tested with the rK39 RDT. Blood samples were also tested with direct agglutination test, and a titer of ≥1:1600 was taken as a marker of infection. A Leishmania donovani species-specific PCR (SSU-rDNA) was performed for parasite species confirmation. We also captured sand flies using CDC light traps and mouth aspirators. The house-to-house surveys documented 28 past and six new VL cases of which 82% (28/34) were without travel exposure. Overall, 4.1% (54/1320) of healthy participants tested positive for L. donovani on at least one serological or molecular test. Among asymptomatic individuals, 17% (9/54) were household contacts of past VL cases, compared to 0.5% (6/1266) among non-infected individuals. Phlebotomus argentipes, the vector of L. donovani, was found in all districts except in Bajura. L. donovani was confirmed in two asymptomatic individuals and one pool of sand flies of Phlebotomus (Adlerius) sp. We found epidemiological and entomological evidence for local transmission of L. donovani in areas previously considered as non-endemic for VL. The national VL elimination program should revise the endemicity status of these districts and extend surveillance and control activities to curb further transmission of the disease.

Source Tracing of Leishmania donovani in Emerging Foci of Visceral Leishmaniasis, Western Nepal.

We sequenced Leishmania donovani genomes in blood samples collected in emerging foci of visceral leishmaniasis in western Nepal. We detected lineages very different from the preelimination main parasite population, including a new lineage and a rare one previously reported in eastern Nepal. Our findings underscore the need for genomic surveillance.

Extracorporeal life support and continuous renal replacement therapy in a patient with Enterovirus A71 associated cardiopulmonary failure: A case report.

RATIONALE: Hand-foot-mouth disease (HFMD) caused by Enterovirus A71, complicated by cardiopulmonary failure, is associated with a high mortality rate despite intensive treatment. To date, there is a paucity of clinical management data, regarding the use of extracorporeal life support (VA-ECMO) for Enterovirus-A71 associated cardiopulmonary failure reported. PATIENT CONCERNS: The patient in this study presented with severe HFMD complicated by cardiopulmonary failure, polymorphic ventricular tachycardia, and cardiac arrest. DIAGNOSES: Clinical presentations, laboratory data, and polymerase chain reaction (PCR) results from rectal swabs were used to confirm the diagnosis of severe HFMD caused by Enterovirus A71. INTERVENTIONS: The patient was managed with chest compression and an automatic external defibrillator, mechanical ventilation, intravenous immunoglobulin (IVIG), continuous renal replacement therapy (CRRT) and inotrope (milrinone). The patient did not respond to these interventions and subsequently required further management with VA-ECMO. OUTCOMES: The patient achieved a favorable outcomes. LESSONS: Our study highlights that extracorporeal membrane oxygenation and CRRT can enhance the survival outcomes of patients with severe HFMD with cardiopulmonary failure complications. Furthermore, we propose specific indications for the initiation of VA-ECMO.

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.

Correction: Doing our best and doing no harm: A focused ethnography of staff moral experiences of providing palliative care at a Médecins Sans Frontières pediatric hospital in Cox's Bazar, Bangladesh.

[This corrects the article DOI: 10.1371/journal.pone.0288938.].

The status of combination therapy for visceral leishmaniasis: an updated review.

For the past 15 years, trials of combination therapy options for visceral leishmaniasis have been conducted with the aim of identifying effective, and safe treatment regimens that were shorter than existing monotherapy regimens and could also prevent or delay the emergence of drug resistance. Although first-line treatment currently relies on combination therapy in east Africa, this is not true in Latin America owing to disappointing trial results, with lower than expected efficacy seen for the combination treatment group. By contrast, several effective combination therapy regimens have been identified through trials on the Indian subcontinent; yet, first-line therapy is still AmBisome monotherapy as the drug is part of a free donation programme and is highly effective in this region. Achieving a short all-oral combination treatment will require new chemical entities, several of which are currently under evaluation. Future studies should systematically include pharmacological substudies to ensure optimal dosing for all patient groups. To achieve maximal impact of new combination treatments, mechanisms to ensure drug availability and access after trials should be established. Enhancing the longevity of current and novel treatments will require effective systems for early detection of emerging drug resistance.

Pediatric Profound Dengue Shock Syndrome and Use of Point-of-Care Ultrasound During Mechanical Ventilation to Guide Treatment: Single-Center Retrospective Study, 2013-2021.

OBJECTIVES: Profound dengue shock syndrome (DSS) complicated by severe respiratory failure necessitating mechanical ventilation (MV) accounts for high case fatality rates among PICU-admitted patients. A major challenge to management is the assessment of intravascular volume, which can be hampered by severe plasma leakage and the use of MV. DESIGN: Retrospective cohort, from 2013 to 2021. PATIENTS: Sixty-seven children with profound DSS supported by MV, some of whom underwent bedside point-of-care ultrasound (POCUS) for assessment and monitoring of hemodynamics and fluid administration. SETTING: PICU of the tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data clinical and laboratory data during PICU stay. In particular, during use of MV (i.e., at times 0-, 6-, and 24-hr after commencement) and fluid resuscitation. The primary study outcome was 28-day in-hospital mortality, and the secondary outcomes were associations with changes in hemodynamics, blood lactate, and vasoactive-inotrope score (VIS). Patients had a median age of 7 years (interquartile range, 4-9). Use of POCUS during fluid management (39/67), as opposed to not using (28/67), was associated with lower mortality (6/39 [15%] vs. 18/28 [64%]; difference 49 % [95% CI, 28-70%], p < 0.001). Use of POCUS was associated with lower odds of death (adjusted odds ratio 0.17 [95% CI, 0.04-0.76], p = 0.02). The utilization of POCUS, versus not, was associated with greater use of resuscitation fluid, and reductions in VIS and pediatric logistic organ dysfunction (PELOD-2) score at 24 hours after MV and PICU discharge. CONCLUSIONS: In our experience of pediatric patients with profound DSS and undergoing MV (2013-2021), POCUS use was associated with lower odds of death, a higher volume of resuscitation fluid, and improvements in the blood lactate levels, VIS, and PELOD-2 score.

Point-of-care prognostication in moderate Covid-19: Analytical validation and prognostic accuracy of a soluble urokinase plasminogen activator receptor (suPAR) rapid test.

The soluble urokinase plasminogen activator receptor (suPAR) has been proposed as a biomarker for risk stratification of patients presenting with acute infections. However, most studies evaluating suPAR have used platform-based assays, the accuracy of which may differ from point-of-care tests capable of informing timely triage in settings without established laboratory capacity. Using samples and data collected during a prospective cohort study of 425 patients presenting with moderate Covid-19 to two hospitals in India, we evaluated the analytical performance and prognostic accuracy of a commercially-available rapid diagnostic test (RDT) for suPAR, using an enzyme-linked immunosorbent assay (ELISA) as the reference standard. Our hypothesis was that the suPAR RDT might be useful for triage of patients presenting with moderate Covid-19 irrespective of its analytical performance when compared with the reference test. Although agreement between the two tests was limited (bias = -2.46 ng/mL [95% CI = -2.65 to -2.27 ng/mL]), prognostic accuracy to predict supplemental oxygen requirement was comparable, whether suPAR was used alone (area under the receiver operating characteristic curve [AUC] of RDT = 0.73 [95% CI = 0.68 to 0.79] vs. AUC of ELISA = 0.70 [95% CI = 0.63 to 0.76]; p = 0.12) or as part of a published multivariable prediction model (AUC of RDT-based model = 0.74 [95% CI = 0.66 to 0.83] vs. AUC of ELISA-based model = 0.72 [95% CI = 0.64 to 0.81]; p = 0.78). Lack of agreement between the RDT and ELISA in our cohort warrants further investigation and highlights the importance of assessing candidate point-of-care tests to ensure management algorithms reflect the assay that will ultimately be used to inform patient care. Availability of a quantitative point-of-care test for suPAR opens the door to suPAR-guided risk stratification of patients with Covid-19 and other acute infections in settings with limited laboratory capacity.

Doing our best and doing no harm: A focused ethnography of staff moral experiences of providing palliative care at a Médecins Sans Frontières pediatric hospital in Cox's Bazar, Bangladesh.

INTRODUCTION: The Médecins Sans Frontières (MSF) Goyalmara Hospital in Cox's Bazar, Bangladesh is a referral centre offering the highest level of care available in the Rohingya camps for pediatrics and neonatology. Efforts are underway to integrate pediatric palliative care due to high mortality and medical complexity of patients, yet little is known about the experiences of staff delivering palliative and end-of-life care. The purpose of this study was to understand the moral experiences of MSF staff to inform program planning and implementation. METHODS: This focused ethnography was conducted between March-August 2021 at Goyalmara Hospital. Data collection involved participant-observation, individual interviews (22), focus group discussions (5), and analysis of documents including MSF clinical guidelines, admission and referral criteria, reports, and training materials. Data analysis followed a modified version of the Qualitative Analysis Guide of Leuven and data were coded using NVivo software. RESULTS: The prevailing understanding of pediatric palliative care among national and international staff was care that prioritized comfort for infants and children who were not expected to survive. Staff's views were informed by their sense of obligation to do no harm, to do their best on behalf of their patients, and religious beliefs about God's role in determining the child's outcome. The authority of doctors, international staff, as well as protocols and guidelines shaped palliative care decision-making. Staff saw clinical guidelines as valuable resources that supported a consistent approach to care over time, while others were concerned that palliative care guidelines were rigidly applied. CONCLUSION: When integrating palliative care into humanitarian programs, it is important to emphasize the active role of palliative care in reducing suffering. Advocacy for access to the highest level of care possible should continue alongside palliative care integration. While palliative care guidelines are valuable, it is essential to encourage open discussion of staff concerns and adapt care plans based on the family's needs and preferences.

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.

Perceptions of effective policy interventions and strategies to address antibiotic misuse within primary healthcare in India: A qualitative study.

Objectives: Antimicrobial resistance poses a major public health threat. Despite Indian retail sector antibiotic consumption per capita increasing by approximately 22% between 2008 and 2016, empirical studies that examine policy or behavioural interventions addressing antibiotic misuse in primary healthcare are scarce. Our study aimed to assess perceptions of interventions and gaps in policy and practice with respect to outpatient antibiotic misuse in India. Methods: We conducted 23 semi-structured, in-depth interviews with a variety of key informants with diverse backgrounds in academia, non-government organisations, policy, advocacy, pharmacy, medicine and others. Data were charted into a framework matrix and analysed using a hybrid, inductive and deductive thematic analysis. Themes were analysed and organised according to the socio-ecological model at various levels ranging from the individual to the enabling environment. Results: Key informants largely focused on the importance of adopting a structural perspective to addressing socio-ecological drivers of antibiotic misuse. There was a recognition that educational interventions targeting individual or interpersonal interactions were largely ineffective, and policy interventions should incorporate behavioural nudge interventions, improve the healthcare infrastructure and embrace task shifting to rectify staffing disparities in rural areas. Conclusions: Prescription behaviour is perceived to be governed by structural issues of access and limitations in public health infrastructure that create an enabling environment for antibiotic overuse. Interventions should move beyond a clinical and individual focus on behaviour change with respect to antimicrobial resistance and aim for structural alignment between existing disease specific programs and between the informal and formal sector of healthcare delivery in India.

Host Biomarkers Reflect Prognosis in Patients Presenting With Moderate Coronavirus Disease 2019: A Prospective Cohort Study.

Efficient resource allocation is essential for effective pandemic response. We measured host biomarkers in 420 patients presenting with moderate coronavirus disease 2019 and found that different biomarkers predict distinct clinical outcomes. Interleukin (IL)-1ra, IL-6, IL-10, and IL-8 exhibit dose-response relationships with subsequent disease progression and could potentially be useful for multiple use-cases.

Prevalence and determinants of asymptomatic Leishmania infection in HIV-infected individuals living within visceral leishmaniasis endemic areas of Bihar, India.

People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen's Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33-46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts <100 (OR 3.1; 95% CI 1.2-7.6) and CD4 counts 100-199 (OR = 2.1;95% CI:1.1-4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR = 1.9;95% CI:1.1-3.1). A total of 2.2% (n = 28) participants were positive by Leishmania antigen ELISA, detecting 20 additional participants to the asymptomatic cohort. Prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. Using the Leishmania antigen ELISA, prevalence increased to 9.0%. Patients with low CD4 counts and larger household size were found to have significantly higher risk of ALI. Trial Registration: Clinical Trial Registration CTRI/2017/03/008120.

Practical Methods to Permit the Analysis of Host Biomarkers in Resource-Limited Settings.

Host biomarker testing can be used as an adjunct to the clinical assessment of patients with infections and might be particularly impactful in resource-constrained settings. Research on the merits of this approach at peripheral levels of low- and middle-income country health systems is limited. In part, this is due to resource-intense requirements for sample collection, processing, and storage. We evaluated the stability of 16 endothelial and immune activation biomarkers implicated in the host response to infection stored in venous plasma and dried blood spot specimens at different temperatures for 6 months. We found that -80°C storage offered no clear advantage over -20°C for plasma aliquots, and most biomarkers studied could safely be stored as dried blood spots at refrigeration temperatures (4°C) for up to 3 months. These results identify more practical methods for host biomarker testing in resource-limited environments, which could help facilitate research in rural and remote environments.

Facilitating Safe Discharge Through Predicting Disease Progression in Moderate Coronavirus Disease 2019 (COVID-19): A Prospective Cohort Study to Develop and Validate a Clinical Prediction Model in Resource-Limited Settings.

BACKGROUND: In locations where few people have received coronavirus disease 2019 (COVID-19) vaccines, health systems remain vulnerable to surges in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Tools to identify patients suitable for community-based management are urgently needed. METHODS: We prospectively recruited adults presenting to 2 hospitals in India with moderate symptoms of laboratory-confirmed COVID-19 to develop and validate a clinical prediction model to rule out progression to supplemental oxygen requirement. The primary outcome was defined as any of the following: SpO2 < 94%; respiratory rate > 30 BPM; SpO2/FiO2 < 400; or death. We specified a priori that each model would contain three clinical parameters (age, sex, and SpO2) and 1 of 7 shortlisted biochemical biomarkers measurable using commercially available rapid tests (C-reactive protein [CRP], D-dimer, interleukin 6 [IL-6], neutrophil-to-lymphocyte ratio [NLR], procalcitonin [PCT], soluble triggering receptor expressed on myeloid cell-1 [sTREM-1], or soluble urokinase plasminogen activator receptor [suPAR]), to ensure the models would be suitable for resource-limited settings. We evaluated discrimination, calibration, and clinical utility of the models in a held-out temporal external validation cohort. RESULTS: In total, 426 participants were recruited, of whom 89 (21.0%) met the primary outcome; 257 participants comprised the development cohort, and 166 comprised the validation cohort. The 3 models containing NLR, suPAR, or IL-6 demonstrated promising discrimination (c-statistics: 0.72-0.74) and calibration (calibration slopes: 1.01-1.05) in the validation cohort and provided greater utility than a model containing the clinical parameters alone. CONCLUSIONS: We present 3 clinical prediction models that could help clinicians identify patients with moderate COVID-19 suitable for community-based management. The models are readily implementable and of particular relevance for locations with limited resources.

AmBisome Monotherapy and Combination AmBisome-Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial.

BACKGROUND: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent. METHODS: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations. RESULTS: Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77-100%) in the monotherapy arm, and 96%, (72/75; 90-100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82-100%) in the monotherapy and 97% (59/61; 91-100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm. CONCLUSIONS: Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r).

Malaria vector control tools in emergency settings: What do experts think? Results from a DELPHI survey.

BACKGROUND: The use and implementation of novel tools for malaria control such as long lasting impregnated bednets (LLINs) and Indoor Residual Spraying (IRS) over the last decade has contributed to a substantial reduction in malaria burden globally. However numerous challenges exist particularly in relation to vector control in emergency settings. This study seeks to explore expert opinion on the utility of existing tools within the emergency context setting and to better understand the attitude towards emerging and innovative tools (including Genetically Modified Mosquitoes) to augment current approaches. METHODS: 80 experts in the field of malaria and vector control were invited to participate in a two-round Delphi survey. They were selected through a combination of literature (academic and policy publications) review and snowball sampling reflecting a range of relevant backgrounds including vector control experts, malaria programme managers and emergency response specialists. The survey was conducted online through a questionnaire including the possibility for free text entry, and concentrated on the following topics: 1. Utility and sustainability of current vector control tools, both in and outside emergency settings 2. Feasibility, utility and challenges of emerging vector control tools, both in and outside emergency settings 3. Current and unmet research priorities in malaria vector control and in malaria control in general. RESULTS: 37 experts completed the first round and 31 completed the second round of the survey. There was a stronger consensus about the increased utility of LLIN compared to IRS in all settings, while insecticide-treated covers and blankets ranked very high only in emergency settings. When considering the combination of tools, the ones deemed most interesting always involved LLINs and IRS regardless of the setting, and the acceptability and the efficacy at reducing transmission are essential characteristics. Regarding perceptions of tools currently under development, consensus was towards improvement of existing tools rather than investing in novel approaches and the majority of respondents expressed distrust for genetic approaches. CONCLUSION: Malaria vector control experts expressed more confidence for tools whose efficacy is backed up by epidemiological evidence, hence a preference for the improvement rather than the combination of existing tools. Moreover, while several novel tools are under development, the majority of innovative approaches did not receive support, particularly in emergency settings. Stakeholders involved in the development of novel tools should involve earlier and raise awareness of the potential effectiveness amongst a wider range of experts within the malaria community to increase acceptability and improve early adoption once the evidence base is established.

Anticipating the future: prognostic tools as a complementary strategy to improve care for patients with febrile illnesses in resource-limited settings.

In low-income and middle-income countries, most patients with febrile illnesses present to peripheral levels of the health system where diagnostic capacity is very limited. In these contexts, accurate risk stratification can be particularly impactful, helping to guide allocation of scarce resources to ensure timely and tailored care. However, reporting of prognostic research is often imprecise and few prognostic tests or algorithms are translated into clinical practice.Here, we review the often-conflated concepts of prognosis and diagnosis, with a focus on patients with febrile illnesses. Drawing on a recent global stakeholder consultation, we apply these concepts to propose three use-cases for prognostic tools in the management of febrile illnesses in resource-limited settings: (1) guiding referrals from the community to higher-level care; (2) informing resource allocation for patients admitted to hospital and (3) identifying patients who may benefit from closer follow-up post-hospital discharge. We explore the practical implications for new technologies and reflect on the challenges and knowledge gaps that must be addressed before this approach could be incorporated into routine care settings.Our intention is that these use-cases, alongside other recent initiatives, will help to promote a harmonised yet contextualised approach for prognostic research in febrile illness. We argue that this is especially important given the heterogeneous settings in which care is often provided for patients with febrile illnesses living in low-income and middle-income countries.

Evaluation of qPCR on blood and skin microbiopsies, peripheral blood buffy coat smear, and urine antigen ELISA for diagnosis and test of cure for visceral leishmaniasis in HIV-coinfected patients in India: a prospective cohort study.

INTRODUCTION: HIV coinfection presents a challenge for diagnosis of visceral leishmaniasis (VL). Invasive splenic or bone marrow aspiration with microscopic visualisation of Leishmania parasites remains the gold standard for diagnosis of VL in HIV-coinfected patients. Furthermore, a test of cure by splenic or bone marrow aspiration is required as patients with VL-HIV infection are at a high risk of treatment failure. However, there remain financial, implementation and safety costs to these invasive techniques which severely limit their use under field conditions. METHODS AND ANALYSIS: We aim to evaluate blood and skin qPCR, peripheral blood buffy coat smear microscopy and urine antigen ELISA as non-invasive or minimally invasive alternatives for diagnosis and post-treatment test of cure for VL in HIV-coinfected patients in India, using a sample of 91 patients with parasitologically confirmed symptomatic VL-HIV infection. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by The Liverpool School of Tropical Medicine, The Institute of Tropical Medicine in Antwerp, the University of Antwerp and the Rajendra Memorial Research Institute of Medical Science in Patna. Any future publications will be published in open access journals. TRIAL REGISTRATION NUMBER: CTRI/2019/03/017908.

Visceral Leishmaniasis-HIV Coinfection as a Predictor of Increased Leishmania Transmission at the Village Level in Bihar, India.

Background: Visceral leishmaniasis (VL) is on the verge of being eliminated as a public health problem in the Indian subcontinent. Although Post-kala-azar dermal leishmaniasis (PKDL) is recognized as an important reservoir of transmission, we hypothesized that VL patients co-infected with Human Immunodeficiency Virus (HIV) may also be important reservoirs of sustained leishmania transmission. We therefore investigated to what extent cases of PKDL or VL-HIV are associated with VL incidence at the village level in Bihar, India. Methods: VL, VL-HIV, and PKDL case data from six districts within the highly VL-endemic state of Bihar, India were collected through the Kala-Azar Management Information System for the years 2014-2019. Multivariate analysis was done using negative binomial regression controlling for year as a fixed effect and block (subdistrict) as a random effect. Findings: Presence of VL-HIV+ and PKDL cases were both associated with a more than twofold increase in VL incidence at village level, with Incidence Rate Ratios (IRR) of 2.16 (95% CI 1.81-2.58) and 2.37 (95% CI 2.01-2.81) for VL-HIV+ and PKDL cases respectively. A sensitivity analysis showed the strength of the association to be similar in each of the six included subdistricts. Conclusions: These findings indicate the importance of VL-HIV+ patients as infectious reservoirs for Leishmania, and suggest that they represent a threat equivalent to PKDL patients towards the VL elimination initiative on the Indian subcontinent, therefore warranting a similar focus.