Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.

BACKGROUND: Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether-lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate-amodiaquine; amodiaquine is a compound with anti-Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period. METHODS: We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate-amodiaquine (artesunate-amodiaquine group), as compared with those who were prescribed artemether-lumefantrine (artemether-lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group). RESULTS: Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether-lumefantrine and 71 were prescribed artesunate-amodiaquine. The characteristics of the patients in the artesunate-amodiaquine group were similar to those in the artemether-lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether-lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate-amodiaquine group (50.7%). In adjusted analyses, the artesunate-amodiaquine group had a 31% lower risk of death than the artemether-lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria. CONCLUSIONS: Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.

Detection of myocardial edema with low-b-value diffusion-weighted echo-planar imaging sequence in patients with acute myocarditis.

PURPOSE: To evaluate the performance of a low-b-value diffusion-weighted (DW) echo-planar (EP) imaging sequence for detection of regional and diffuse myocardial edema in patients with acute myocarditis. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained from all subjects. Thirteen patients with acute myocarditis and a control group of seven healthy adults underwent low-b-value (50 sec/mm(2)) DW cardiac magnetic resonance imaging. DW EP images were acquired in the four-chamber long-axis section and analyzed qualitatively and quantitatively. Short inversion time inversion-recovery (STIR) T2-weighted and late gadolinium chelate enhancement images were acquired in the same plane and analyzed. Late gadolinium chelate enhancement was used as the reference standard. Statistical analyses were performed with a receiver operating characteristic analysis and a nonparametric Wilcoxon test. RESULTS: Qualitative analysis showed myocardial high-signal-intensity areas in 100% (13 of 13) of patients on DW EP, 38% (five of 13) on STIR T2-weighted, and 100% (13 of 13) on late gadolinium chelate enhancement images. In eight patients (61%), high-signal-intensity areas were exhibited on DW EP images that were not detected on STIR T2-weighted images, but were colocalized with lesions detected on late gadolinium chelate enhancement images. Similar results were obtained by using an automatic analysis with dedicated cardiac software. The global myocardial signal intensity ratio was significantly higher (P = .03) in patients than in controls for DW EP (2.2 ± 0.4 [standard deviation] vs 1.1 ± 0.4, respectively), and exhibited no significant difference (P = .14) for STIR T2-weighted (1.7 ± 0.6 vs 1.4 ± 0.1, respectively) images. Sensitivity and diagnostic accuracy were higher for DW EP images than for STIR T2-weighted images (92% vs 54%, and 95% vs 70%, respectively), and specificity was the same (100% vs 100%). CONCLUSION: A low-b-value DW EP imaging sequence is a feasible alternative to the standard STIR T2-weighted sequence for detection of regional and global myocardium edema in patients with acute myocarditis. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13121811/-/DC1.

Peripherally inserted central catheter placement in cancer patients with profound thrombocytopaenia: a prospective analysis.

OBJECTIVE: No studies have specifically evaluated the safety of peripherally inserted central catheter (PICC) placement in patients with profound thrombocytopaenia. We prospectively determined the frequency of haemorrhagic complications of PICC placement in cancer patients with uncorrected profound thrombocytopaenia. METHODS: Profound thrombocytopaenia was defined as a platelet count <50 × 10(9)/l. No patients received transfusions before or after the procedure. Three types of adverse effects were analysed: minor oozing, mild haematoma and major haemorrhage. RESULTS: One hundred and forty-three PICC implantations in 101 cancer patients were prospectively included in the study: seven patients (7 %) had a solid tumour and 94 (93 %) a haematological malignancy. Among these 143 procedures in thrombocytopaenic patients, 93 (65 %) were performed with a platelet count 20-50 × 10(9)/l and 50 (35 %) had lower than 20 × 10(9)/l. No major haemorrhage was observed. Minor oozing was observed in six implantations (4 %) and mild haematoma in two (1.5 %), for a total of eight minor haemorrhagic adverse events (5.5 %). In patients with a platelet count <20 × 10(9)/l, 1/50 (2 %) had minor oozing and none had minor haematoma. CONCLUSIONS: In cancer patients with uncorrected profound thrombocytopaenia, the incidence of adverse events after PICC implantation was low, and was limited to minor haemorrhagic adverse events. KEY POINTS: • PICC placement has high technical success in profound thrombocytopaenic cancer patients. • Few adverse events are encountered after PICC placement, limited to minor haemorrhage. • PICC placement does not routinely require platelet transfusion in patients with thrombocytopaenia. • Such PICC placement still seems safe when the platelet count is <20 × 10 (9) /l.

Incidence of pulmonary cement embolism after real-time CT fluoroscopy-guided vertebroplasty.

PURPOSE: To prospectively evaluate the incidence of pulmonary cement embolism (PCE) after vertebroplasty in procedures performed under real-time computed tomographic (CT) fluoroscopy guidance. MATERIALS AND METHODS: A total of 85 vertebroplasties were performed in 51 consecutive patients (31 women, 20 men; mean age, 71.9 y; range, 48-92 y) in 51 sessions. The needle was inserted with guidance from intermittent single-shot CT scans, and intermittent CT fluoroscopy was used during cement injection only. To reduce the risk of extravertebral or extraosseous leakage, several procedures (cement injection stopping/slowing, needle position changes) were employed. The chest and treated bone were scanned immediately after vertebroplasty. These CT images included the entire thorax as well as the treated vertebrae. RESULTS: No cement emboli were observed on CT after vertebroplasty. After 85 vertebroplasty procedures, 44 extravertebral leaks were detected. Epidural leaks were observed on CT in six treated vertebrae (7%), in 12 cases in the anterior external venous plexus (14.1%), in five in the azygos vein (5.8%), in 19 in the disc space (22%), and in two in the foraminal space (2.3%). On a per-patient basis, the odds of leaks increased with the number of vertebroplasties (P = .05) and the volume of cement used (P = .0412). There was also a higher probability of leak (P < .05) for osteoporotic vertebral compression fractures (67.9%; 95% confidence interval, 47.7%-84.1%) than osteolytic spinal metastases (34.8%; 16.4%-57.3%). CONCLUSIONS: PCE did not occur after vertebroplasty under CT fluoroscopy guidance. Further larger prospective vertebroplasty studies are needed to compare the rates of PCE for CT versus conventional fluoroscopic guidance.

Availability, accessibility and use of antivenom for snakebite envenomation in Africa with proposed strategies to overcome the limitations.

Africa remains one of the regions with the highest incident and burden of snakebite. The goal of the World Health Organization to halve the global burden of snakebite by 2030 can only be achieved if sub-optimal access to antivenoms in the most affected regions is addressed. We identified upstream, midstream, and downstream factors along the antivenom value chain that prevent access to antivenoms in the African region. We identified windows of opportunities that could be utilized to ensure availability, accessibility, and affordability for snakebite endemic populations in Africa. These include implementation of multicomponent strategies such as intensified advocacy, community engagement, healthcare worker trainings, and leveraging the institutional and governance structure provided by African governments to address the challenges identified.

Snakebite envenoming at MSF: A decade of clinical challenges and antivenom access issues.

The medical humanitarian organization Médecins Sans Frontières (MSF) provides medical care in more than 70 countries and admits more than 7000 cases of snakebite in its facilities each year. We describe our activities against snakebite in three African countries: Central African Republic, South Sudan and Ethiopia, in which different models of care have been developed. A standard protocol using two different antivenoms depending on the patient's syndrome has been introduced, and a simple blood coagulation test is performed to detect venom-induced coagulopathy. Other services, including surgery for necrotizing wounds, are offered in the facilities where MSF admits a large number of snakebite patients. All services, including provision of antivenom, are offered free-of-charge in MSF-supported facilities. Community-based activities focusing on preventive measures and prompt transport to hospital have been developed in a few MSF projects. The provision of quality care and treatment, including effective antivenoms, without out-of-pocket payments by the patients, probably explains why MSF has admitted an increasing number of snakebite victims over the last years. This model requires significant resources and monitoring, including regular training of healthcare workers on treatment protocols and a considerable budget for antivenom procurement.

Liposomal amphotericin B as a treatment for human leishmaniasis.

INTRODUCTION: Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB), alone or in combination with other drugs, has been extensively studied as VL treatment, but data on routine field use are limited, and several challenges to patients' access to this life-saving drug remain. AREAS COVERED: This article provides a review of clinical studies on LAMB for VL and other forms of leishmaniasis. The current development of generic versions of LAMB and related challenges are also discussed. EXPERT OPINION: LAMB proved to be highly efficacious and safe in over 8000 VL patients treated by MÉdecins Sans Frontières in South Asia, and its use was feasible even at primary healthcare level. Despite requiring higher doses, LAMB is the drug of choice to treat vulnerable groups (e.g., pregnant or HIV positive) and relapsing VL patients in East Africa. LAMB should be included in national VL guidelines and registered in all VL endemic countries. Its cost should be further reduced and regulatory pathways to prove bioequivalence for generic LAMB products should be implemented.

Scaling-up malaria treatment: a review of the performance of different providers.

BACKGROUND: Despite great progress towards malaria control, the disease continues to be a major public health problem in many developing countries, especially for poor women and children in remote areas. Resistance to artemisinin combination therapy (ACT) emerged in East Asia. Its spread would threaten the only effective malaria treatment currently available. Improvement in availability of diagnosis as part of malaria control has highlighted the fact that many fevers are not due to malaria. These fevers also need to be promptly diagnosed and adequately treated in order to improve public health outcomes in developing countries. METHODS: This review looked for evidence for the most effective approach to deliver malaria treatment in developing countries, by public sector, formal and informal private sector, and community health workers (CHWs). The authors analysed 31 studies to assess providers based on six parameters: knowledge and practice of provider, diagnosis, referral practices, price of medicine, availability of ACT, and treatment coverage and impact on morbidity and mortality. RESULTS: The public sector has made progress in prevention and treatment in many countries, but facilities are inaccessible to some communities, and the sector suffers shortages of health workers and stock-outs of medicines. Despite wide outreach, the private sector, especially informal facilities, presents public health risks. This is due to an inability to diagnose and treat non-malarial fevers, and an innate motive to over-prescribe malaria treatment. The need to pay for treatment is a major factor in deterring poor women and children from accessing the medicines they need. A system that depends on ability to pay risks a repeat of the chloroquine story, where an effective and cheap anti-malarial drug was rendered useless partly due to under-treatment. CHWs have proved to be effective agents in providing correct diagnosis and treatment of malaria and other common fevers, even in remote areas. CONCLUSIONS: The evidence shows that there is no short-cut to investing in training and supervision of providers, or in treating malaria within a public health context rather than as a separate disease. The studies highlighted that all outlets face challenges in delivering their services, but that CHWs scored highly in almost all parameters. CHWs have proved to be effective agents in providing correct diagnosis and treatment of malaria and other common fevers, even in remote areas. Their role should be recognized and expanded.

Snakebite envenoming in humanitarian crises and migration: A scoping review and the Médecins Sans Frontières experience.

Snakebite envenoming is a public health concern in many countries affected by humanitarian crises. Its magnitude was recognized internationally but associations between snakebite peaks and humanitarian crises were never clearly established or analysed. This scoping review searched any available evidence of this hypothesized association between snakebite types of crises, through PubMed/Medline by two researchers. The search also included hand searching, and reports from humanitarian organizations working in this area. The scoping review yielded 41 results. None described a robust epidemiological link or evidence of causality. There is an evidence gap regarding our research question. Several publications however point or hint towards the occurrence of snakebite outbreaks during conflict, displacement, floods, and migration of impoverished agricultural workers. Non-systematic screening yielded another 11 publications (52 in total). We found Médecins Sans Frontières routine reports showing that 6469 patients were admitted in 2019 throughout its projects in 17 countries. The impact of snakebite was the highest in four countries particularly affected by humanitarian crises, South Sudan, Ethiopia, Central African Republic, and Yemen, with some hospitals receiving more than 1000 annual admissions. Time correlations with conflict and events are shown in Figures. We found no published epidemiological data formally showing any associations between humanitarian crises and snakebite incidence. However, the search publications showing peaks during crises, and monitoring curves in four countries point towards an increased risk during humanitarian crises. We call for urgent population-based studies and surveillance. Stakeholders should consider upgrading snakebite care and antivenom supply during humanitarian crises in snakebite-endemic countries.

Corrigendum to "Snakebite envenoming in humanitarian crises and migration: A scoping review and the Médecins Sans Frontières experience" [Toxicon: X 13 (March 2022) 100089].

[This corrects the article DOI: 10.1016/j.toxcx.2021.100089.].

Access to antivenoms in the developing world: A multidisciplinary analysis.

Access to safe, effective, quality-assured antivenom products that are tailored to endemic venomous snake species is a crucial component of recent coordinated efforts to reduce the global burden of snakebite envenoming. Multiple access barriers may affect the journey of antivenoms from manufacturers to the bedsides of patients. Our review describes the antivenom ecosystem at different levels and identifies solutions to overcome these challenges. At the global level, there is insufficient manufacturing output to meet clinical needs, notably for antivenoms intended for use in regions with a scarcity of producers. At national level, variable funding and deficient regulation of certain antivenom markets can lead to the procurement of substandard antivenom. This is particularly true when producers fail to seek registration of their products in the countries where they should be used, or where weak assessment frameworks allow registration without local clinical evaluation. Out-of-pocket expenses by snakebite victims are often the main source of financing antivenoms, which results in the underuse or under-dosing of antivenoms, and a preference for low-cost products regardless of efficacy. In resource-constrained rural areas, where the majority of victims are bitten, supply of antivenom in peripheral health facilities is often unreliable. Misconceptions about treatment of snakebite envenoming are common, further reducing demand for antivenom and exacerbating delays in reaching facilities equipped for antivenom use. Multifaceted interventions are needed to improve antivenom access in resource-limited settings. Particular attention should be paid to the comprehensive list of actions proposed within the WHO Strategy for Prevention and Control of Snakebite Envenoming.

[Which imaging in acute abdominal pain management?]. / Quelle imagerie dans les douleurs abdominales aiguës?

Acute abdominal pain is a frequent consultation cause with large causal diversity and possible severity that may lead to emergency surgery. Radiology development and availability have changed their management with possibility of rapid diagnostic. Computed tomography has become the gold standard in this setting, reducing AAS to very few indications. Ultrasound remains the first exploration for children and pregnant woman. Magnetic resonance imaging may be more attractive in the future, thanks to its lack of radiation.

Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial.

BACKGROUND: Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness. CONCLUSIONS/SIGNIFICANCE: Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms.

Exploring global and country-level barriers to an effective supply of leishmaniasis medicines and diagnostics in eastern Africa: a qualitative study.

OBJECTIVES: To understand stakeholders' perceptions of the access barriers to quality-assured diagnostics and medicines for leishmaniasis in the high-burden region of eastern Africa, and to identify key bottlenecks to improve the supply of commodities for neglected tropical diseases. DESIGN: Desk reviews and qualitative in-depth interview study with purposive sampling. METHODS: A landscape analysis through literature and desk review was performed. Next, 29 representatives from international organisations, non-governmental agencies, national control programmes from six countries (Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) and manufacturers were interviewed between May and July 2018. Participants were selected purposively and expanded through a snowballing technique.Data analysis was aided by NVivo, applying the framework method as a part of the thematic content analysis approach. RESULTS: The barriers along the visceral leishmaniasis (VL) supply chain were identified as emerging themes, grouped across supply chain activities and health systems component(s). Stakeholders expressed the perception of progress, but bottlenecks persist. VL medicines, in general, lack multisource production capacity and with small market volume, expansion of suppliers is difficult. Procurement is plagued by forecasting difficulties, complex regulatory policies and procedures, and distribution challenges. Weak communication and coordination across different levels resulted in shortages and loss of trust among different actors. Cross-cutting issues spanned from limited political and resource commitment due to low awareness and limited in-country capacity. However, study respondents were optimistic to pursue several remedies, most importantly to build bridges between supply and demand sides through continued dialogue and collaborations. Diagnostics supply has mostly been overlooked; thus, improved investment in this area is needed. CONCLUSIONS: Addressing supply barriers in eastern Africa requires consistent, specific efforts at the global and national levels, progressing from current partnerships and agreements. Priority actions include pooled procurement, improved forecast, and increased commitment and resources. Sustainability remains an elusive goal, yet to be integrated into discussions moving forward.

Why miltefosine-a life-saving drug for leishmaniasis-is unavailable to people who need it the most.

Miltefosine, the only oral drug approved for the treatment of leishmaniasis-a parasitic disease transmitted by sandflies-is considered as a success story of research and development (R&D) by a public-private partnership (PPP). It epitomises the multiple market failures faced by a neglected disease drug: patients with low ability to pay, neglect by authorities and uncertain market size. Originally developed as an anticancer agent in the 1990s, the drug was registered in India in 2002 to treat the fatal visceral leishmaniasis. At the time, miltefosine was considered a breakthrough in the treatment, making it feasible to eliminate a regional disease. Today, access to miltefosine remains far from secure. The initial PPP agreement which includes access to the public sector is not enforced. The reality on the ground has been challenging: shortages due to inefficient supply chains, and use of a substandard product which led to a high number of treatment failures and deaths. Miltefosine received orphan drug status in the USA; when it was registered there in 2014, a priority review voucher (PRV) was awarded. The PRV, meant to facilitate drug development for neglected disease, was subsequently sold to another company for US$125 million without, to date, any apparent impact on drug access. At the heart of these concerns are questions on how to protect societal benefit of a drug developed with public investment, while clinicians worldwide struggle with its lack of affordability, limited availability and sustainability of access. This article analyses the reasons behind the postregistration access failure of miltefosine and provides the lessons learnt.

Uncharted territory of the epidemiological burden of cutaneous leishmaniasis in sub-Saharan Africa-A systematic review.

INTRODUCTION: Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis, with 0.7 to 1.2 million cases per year globally. However, the burden of CL is poorly documented in some regions. We carried out this review to synthesize knowledge on the epidemiological burden of CL in sub-Saharan Africa. METHODS: We systematically searched PubMed, CABI Global health, Africa Index Medicus databases for publications on CL and its burden. There were no restrictions on language/publication date. Case series with less than ten patients, species identification studies, reviews, non-human, and non-CL focused studies were excluded. Findings were extracted and described. The review was conducted following PRISMA guidelines; the protocol was registered in PROSPERO (42016036272). RESULTS: From 289 identified records, 54 met eligibility criteria and were included in the synthesis. CL was reported from 13 of the 48 sub-Saharan African countries (3 eastern, nine western and one from southern Africa). More than half of the records (30/54; 56%) were from western Africa, notably Senegal, Burkina Faso and Mali. All studies were observational: 29 were descriptive case series (total 13,257 cases), and 24 followed a cross-sectional design. The majority (78%) of the studies were carried out before the year 2000. Forty-two studies mentioned the parasite species, but was either assumed or attributed on the historical account. Regional differences in clinical manifestations were reported. We found high variability across methodologies, leading to difficulties to compare or combine data. The prevalence in hospital settings among suspected cases ranged between 0.1 and 14.2%. At the community level, CL prevalence varied widely between studies. Outbreaks of thousands of cases occurred in Ethiopia, Ghana, and Sudan. Polymorphism of CL in HIV-infected people is a concern. Key information gaps in CL burden here include population-based CL prevalence/incidence, risk factors, and its socio-economic burden. CONCLUSION: The evidence on CL epidemiology in sub-Saharan Africa is scanty. The CL frequency and severity are poorly identified. There is a need for population-based studies to define the CL burden better. Endemic countries should consider research and action to improve burden estimation and essential control measures including diagnosis and treatment capacity.

Knowledge, attitude and practices of snakebite management amongst health workers in Cameroon: Need for continuous training and capacity building.

BACKGROUND: Snakebite has only recently been recognized as a neglected tropical disease by the WHO. Knowledge regarding snakebites and its care is poor both at the population level, and at the health care staff level. The goal of this study was to describe the level of knowledge and clinical practice regarding snakebite among health care staff from Cameroon. METHODS: A two-day training dedicated to snakebite and its care was organized in 2015 in Yaoundé, capital city of Cameroon. A total of 98 health care staff from all over Cameroon attended the training. Prior to and after the training, an evaluation quantified the attendees' level of knowledge. Pre- and post-training evaluations were compared to assess knowledge improvement. RESULTS: Overall, prior to the training knowledge regarding snakebite and care was poor, and wrong beliefs that "pierre noire" or tourniquet were useful in case of snakebite were common. Knowledge was statistically improved after the training. CONCLUSION: Trainings dedicated to all type of health care staff towards snakebite to improve care are needed, this training must take into consideration the context and the targeted population.