Assessment In Vitro of the Antimalarial and Transmission-Blocking Activities of Cipargamin and Ganaplacide in Artemisinin-Resistant Plasmodium falciparum.

Artemisinin resistance in Plasmodium falciparum has emerged and spread widely in the Greater Mekong Subregion, threatening current first-line artemisinin combination treatments. New antimalarial drugs are needed urgently. Cipargamin (KAE609) and ganaplacide (KAF156) are promising novel antimalarial compounds in advanced stages of development. Both compounds have potent asexual blood stage activities, inhibit P. falciparum gametocytogenesis, and reduce oocyst development in anopheline mosquitoes. In this study, we compared the asexual and sexual stage activities of cipargamin, ganaplacide, and artesunate in artemisinin-resistant P. falciparum isolates (n = 6; K13 mutations C580Y, G449A, and R539T) from Thailand and Cambodia. Asexual blood stage antimalarial activity was evaluated in a SYBR-green I-based 72-h in vitro assay, and the effects on male and female mature stage V gametocytes were assessed in the P. falciparum dual gamete formation assay. Ganaplacide had higher activities than cipargamin and artesunate, with mean (standard deviation [SD]) 50% inhibitory concentrations (IC50s) against asexual stages of 5.6 (1.2) nM and 6.9 (3.8) nM for male gametocytes and 47.5 (54.7) nM for female gametocytes. Cipargamin had a similar potency against male and female gametocytes, with mean (SD) IC50s of 115.6 (66.9) nM for male gametocytes, 104.9 (84.3) nM for female gametocytes, and 2.4 (0.7) nM for asexual stages. Both cipargamin and ganaplacide showed significant transmission-blocking activities against artemisinin-resistant P. falciparum in vitro.

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies.

BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). INTERPRETATION: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. FUNDING: No funding.

Ultrasound versus Computed Tomography Assessment of Focal Lung Aeration in Invasively Ventilated ICU Patients.

It is unknown whether and to what extent the penetration depth of lung ultrasound (LUS) influences the accuracy of LUS findings. The current study evaluated and compared the LUS aeration score and two frequently used B-line scores with focal lung aeration assessed by chest computed tomography (CT) at different levels of depth in invasively ventilated intensive care unit (ICU) patients. In this prospective observational study, patients with a clinical indication for chest CT underwent a 12-region LUS examination shortly before CT scanning. LUS images were compared with corresponding regions on the chest CT scan at different subpleural depths. For each LUS image, the LUS aeration score was calculated. LUS images with B-lines were scored as the number of separately spaced B-lines (B-line count score) and the percentage of the screen covered by B-lines divided by 10 (B-line percentage score). The fixed-effect correlation coefficient (ß) was presented per 100 Hounsfield units. A total of 40 patients were included, and 372 regions were analyzed. The best association between the LUS aeration score and CT was found at a subpleural depth of 5 cm for all LUS patterns (ß = 0.30, p < 0.001), 1 cm for A- and B1-patterns (ß = 0.10, p < 0.001), 6 cm for B1- and B2-patterns (ß = 0.11, p < 0.001) and 4 cm for B2- and C-patterns (ß = 0.07, p = 0.001). The B-line percentage score was associated with CT (ß = 0.46, p = 0.001), while the B-line count score was not (ß = 0.07, p = 0.305). In conclusion, the subpleural penetration depth of ultrasound increased with decreased aeration reflected by the LUS pattern. The LUS aeration score and the B-line percentage score accurately reflect lung aeration in ICU patients, but should be interpreted while accounting for the subpleural penetration depth of ultrasound.

Epidemiological Characteristics, Ventilator Management, and Clinical Outcome in Patients Receiving Invasive Ventilation in Intensive Care Units from 10 Asian Middle-Income Countries (PRoVENT-iMiC): An International, Multicenter, Prospective Study.

Epidemiology, ventilator management, and outcome in patients receiving invasive ventilation in intensive care units (ICUs) in middle-income countries are largely unknown. PRactice of VENTilation in Middle-income Countries is an international multicenter 4-week observational study of invasively ventilated adult patients in 54 ICUs from 10 Asian countries conducted in 2017/18. Study outcomes included major ventilator settings (including tidal volume [V T ] and positive end-expiratory pressure [PEEP]); the proportion of patients at risk for acute respiratory distress syndrome (ARDS), according to the lung injury prediction score (LIPS), or with ARDS; the incidence of pulmonary complications; and ICU mortality. In 1,315 patients included, median V T was similar in patients with LIPS < 4 and patients with LIPS ≥ 4, but lower in patients with ARDS (7.90 [6.8-8.9], 8.0 [6.8-9.2], and 7.0 [5.8-8.4] mL/kg Predicted body weight; P = 0.0001). Median PEEP was similar in patients with LIPS < 4 and LIPS ≥ 4, but higher in patients with ARDS (five [5-7], five [5-8], and 10 [5-12] cmH2O; P < 0.0001). The proportions of patients with LIPS ≥ 4 or with ARDS were 68% (95% CI: 66-71) and 7% (95% CI: 6-8), respectively. Pulmonary complications increased stepwise from patients with LIPS < 4 to patients with LIPS ≥ 4 and patients with ARDS (19%, 21%, and 38% respectively; P = 0.0002), with a similar trend in ICU mortality (17%, 34%, and 45% respectively; P < 0.0001). The capacity of the LIPS to predict development of ARDS was poor (receiver operating characteristic [ROC] area under the curve [AUC] of 0.62, 95% CI: 0.54-0.70). In Asian middle-income countries, where two-thirds of ventilated patients are at risk for ARDS according to the LIPS and pulmonary complications are frequent, setting of V T is globally in line with current recommendations.

Lung Ultrasound for Detection of Pulmonary Complications in Critically Ill Obstetric Patients in a Resource-Limited Setting.

Critically ill parturients have an increased risk of developing pulmonary complications. Lung ultrasound (LUS) could be effective in addressing the cause of respiratory distress in resource-limited settings with high maternal mortality. We aimed to determine the frequency, timing of appearance, and type of pulmonary complications in critically ill parturients in an obstetric unit in Sierra Leone. In this prospective observational study, LUS examinations were performed on admission, after 24 and 48 hours, and in case of respiratory deterioration. Primary endpoint was the proportion of parturients with one or more pulmonary complications, stratified for the presence of respiratory distress. Secondary endpoints included timing and types of complications, and their association with "poor outcome," defined as a composite of transfer for escalation of care or death. Of 166 patients enrolled, 35 patients (21% [95% CI: 15-28]) had one or more pulmonary complications, the majority diagnosed on admission. Acute respiratory distress syndrome (period prevalence 4%) and hydrostatic pulmonary edema (4%) were only observed in patients with respiratory distress. Pneumonia (2%), atelectasis (10%), and pleural effusion (7%) were present, irrespective of respiratory distress. When ultrasound excluded pulmonary complications, respiratory distress was related to anemia or metabolic acidosis. Pulmonary complications were associated with an increased risk of poor outcome (odds ratio: 5.0; 95% CI: 1.7-14.6; P = 0.003). In critically ill parturients in a resource-limited obstetric unit, LUS contributed to address the cause of respiratory distress by identifying or excluding pulmonary complications. These were associated with a poor outcome.

A national survey of critical care services in hospitals accredited for training in a lower-middle income country: Pakistan.

PURPOSE: To describe the extent and variation of critical care services in Pakistan. MATERIALS AND METHODS: A cross-sectional survey was conducted in all intensive care units (ICUs) recognised for postgraduate training to determine administration, infrastructure, equipment, staffing, and training. RESULTS: There were 151 hospitals recognised for training, providing 2166 ICU beds and 1473 ventilators. Regional distribution of ICU beds per 100,000 population ranged from 1.0 in Sindh to none in Gilgit Baltistan (median 0.7). A senior clinician trained in critical care was available in 19 (12.1%) of units. One-to-one nurse-to-bed ratio during the day was available in 84 (53.5%) of units, dropping to 75 (47.8%) at night. Availability of 1:1 nursing also varied between provinces, ranging from 56.5% in Punjab compared to 0% in Azad Jamu Kashmir. Similarly, there was disparity in the availability of ventilators between provinces. All ICUs had basic infrastructure (electricity, running water, piped oxygen) and basic equipment (electronic monitoring and infusion pumps). CONCLUSION: Pakistan, a lower middle-income country, has an established network of critical care facilities with access to basic equipment, but inequalities in its distribution. Investment in critical care training for doctors and nurses is needed.

Respiratory Support in COVID-19 Patients, with a Focus on Resource-Limited Settings.

The ongoing novel coronavirus disease (COVID-19) pandemic is threatening the global human population, including in countries with resource-limited health facilities. Severe bilateral pneumonia is the main feature of severe COVID-19, and adequate ventilatory support is crucial for patient survival. Although our knowledge of the disease is still rapidly increasing, this review summarizes current guidance on the best provision of ventilatory support, with a focus on resource-limited settings. Key messages include that supplemental oxygen is a first essential step for the treatment of severe COVID-19 patients with hypoxemia and should be a primary focus in resource-limited settings where capacity for invasive ventilation is limited. Oxygen delivery can be increased by using a non-rebreathing mask and prone positioning. The presence of only hypoxemia should in general not trigger intubation because hypoxemia is often remarkably well tolerated. Patients with fatigue and at risk for exhaustion, because of respiratory distress, will require invasive ventilation. In these patients, lung protective ventilation is essential. Severe pneumonia in COVID-19 differs in some important aspects from other causes of severe pneumonia or acute respiratory distress syndrome, and limiting the positive end-expiratory pressure level on the ventilator may be important. This ventilation strategy might reduce the currently very high case fatality rate of more than 50% in invasively ventilated COVID-19 patients.

Tools to accelerate falciparum malaria elimination in Cambodia: a meeting report.

Cambodia targets malaria elimination by 2025. Rapid elimination will depend on successfully identifying and clearing malaria foci linked to forests. Expanding and maintaining universal access to early diagnosis and effective treatment remains the key to malaria control and ultimately malaria elimination in the Greater Mekong Subregion (GMS) in the foreseeable future. Mass Drug Administration (MDA) holds some promise in the rapid reduction of Plasmodium falciparum infections, but requires considerable investment of resources and time to mobilize the target communities. Furthermore, the most practical drug regimen for MDA in the GMS-three rounds of DHA/piperaquine-has lost some of its efficacy. Mass screening and treatment benefits asymptomatic P. falciparum carriers by clearing chronic infections, but in its current form holds little promise for malaria elimination. Hopes that "highly sensitive" diagnostic tests would provide substantial advances in screen and treat programmes have been shown to be misplaced. To reduce the burden on P. falciparum and Plasmodium vivax infections in people working in forested areas novel approaches to the use of malaria prophylaxis in forest workers should be explored. During an October 2019 workshop in Phnom Penh researchers and policymakers reviewed evidence of acceptability, feasibility and effectiveness of interventions to target malaria foci and interrupt P. falciparum transmission and discussed operational requirements and conditions for programmatic implementation.

Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity.

Malaria is no longer a common cause of febrile illness in many regions of the tropics. In part, this success is a result of improved access to accurate diagnosis and effective anti-malarial treatment, including in many hard-to-reach rural areas. However, in these settings, management of other causes of febrile illness remains challenging. Health systems are often weak and other than malaria rapid tests no other diagnostics are available. With millions of deaths occurring annually due to treatable bacterial infections and the ever increasing spread of antimicrobial resistance, improvement in the management of febrile illness is a global public health priority. Whilst numerous promising point-of-care diagnostics are in the pipeline, substantial progress can be made in the interim with existing tools: C-reactive protein (CRP) is a highly sensitive and moderately specific biomarker of bacterial infection and has been in clinical use for these purposes for decades, with dozens of low-cost devices commercially available. This paper takes a health-economics approach to consider the possible advantages of CRP point-of-care tests alongside rapid diagnostic tests for malaria, potentially in a single multiplex device, to guide antimicrobial therapy for patients with febrile illness. Three rudimentary assessments of the costs and benefits of this approach all indicate that this is likely to be cost-effective when considering the incremental costs of the CRP tests as compared with either (i) the improved health outcomes for patients with bacterial illnesses; (ii) the costs of antimicrobial resistance averted; or (iii) the economic benefits of better management of remaining malaria cases and shorter malaria elimination campaigns in areas of low transmission. While CRP-guided antibiotic therapy alone cannot resolve all challenges associated with management of febrile illness in remote tropical settings, in the short-term a multiplexed CRP and malaria RDT could be highly cost-effective and utilize the well-established funding and distribution systems already in place for malaria RDTs. These findings should spark further interest amongst industry, academics and policy-makers in the development and deployment of such diagnostics, and discussion on their geographically appropriate use.

Treatment-seeking behaviour for febrile illnesses and its implications for malaria control and elimination in Savannakhet Province, Lao PDR (Laos): a mixed method study.

BACKGROUND: How people respond to febrile illness is critical to malaria prevention, control, and ultimately elimination. This article explores factors affecting treatment-seeking behaviour for febrile illnesses in a remote area of Lao PDR. METHODS: Household heads or their representatives (n = 281) were interviewed using a structured questionnaire. A total of twelve focus group discussions (FGDs) each with eight to ten participants were conducted in four villages. In addition, observations were recorded as field notes (n = 130) and were used to collect information on the local context, including the treatment seeking behaviour and the health services. RESULTS: Almost three-quarters (201/281) of respondents reported fever in past two months. Most (92%, 185/201) sought treatment of which 80% (149/185) sought treatment at a health centre. Geographic proximity to a health centre (AOR = 6.5; CI = 1.74-24.25; for those < 3.5 km versus those > 3.6 km) and previous experience of attending a health centre (AOR = 4.7; CI = 1.2-19.1) were strong predictors of visiting a health centre for febrile symptoms. During FGDs, respondents described seeking treatment from traditional healers and at health centre for mild to moderate illnesses. Respondents also explained how if symptoms, including fever, were severe or persisted after receiving treatment elsewhere, they sought assistance at health centres. Access to local health centres/hospitals was often constrained by a lack of transportation and an ability to meet the direct and indirect costs of a visit. CONCLUSION: In Nong District, a rural area bordering Vietnam, people seek care from health centres offering allopathic medicine and from spiritual healers. Decisions about where and when to attend health care depended on their economic status, mobility (distance to the health centre, road conditions, availability of transport), symptoms severity and illness recognition. Current and future malaria control/elimination programmes could benefit from greater collaboration with the locally accessible sources of treatments, such as health volunteers and traditional healers.

Addressing the information deficit in global health: lessons from a digital acute care platform in Sri Lanka.

Lack of investment in low-income and middle-income countries (LMICs) in systems capturing continuous information regarding care of the acutely unwell patient is hindering global efforts to address inequalities, both at facility and national level. Furthermore, this of lack of data is disempowering frontline staff and those seeking to support them, from progressing setting-relevant research and quality improvement. In contrast to high-income country (HIC) settings, where electronic surveillance has boosted the capability of governments, clinicians and researchers to engage in service-wide healthcare evaluation, healthcare information in resource-limited settings remains almost exclusively paper based. In this practice paper, we describe the efforts of a collaboration of clinicians, administrators, researchers and healthcare informaticians working in South Asia, in addressing the inequality in access to patient information in acute care. Harnessing a clinician-led collaborative approach to design and evaluation, we have implemented a national acute care information platform in Sri Lanka that is tailored to priorities of frontline staff. Iterative adaptation has ensured the platform has the flexibility to integrate with legacy paper systems, support junior team members in advocating for acutely unwell patients and has made information captured accessible to diverse stakeholders to improve service delivery. The same platform is now empowering clinicians to participate in international research and drive forwards improvements in care. During this journey, we have also gained insights on how to overcome well-described barriers to implementation of digital information tools in LMIC. We anticipate that this north-south collaborative approach to addressing the challenges of health system implementation in acute care may provide learning and inspiration to other partnerships seeking to engage in similar work.

The feasibility and acceptability of mass drug administration for malaria in Cambodia: a mixed-methods study.

Background: Mass drug administrations (MDAs) are part of the World Health Organization's Plasmodium falciparum elimination strategy for the Greater Mekong Subregion (GMS). In Cambodia, a 2015-2017 clinical trial evaluated the effectiveness of MDA. This article explores factors that influence the feasibility and acceptability of MDA, including seasonal timing, financial incentives and the delivery model. Methods: Quantitative data were collected through structured questionnaires from the heads of 163 households. Qualitative data were collected through 25 semi-structured interviews and 5 focus group discussions with villagers and local health staff. Calendars of village activities were created and meteorological and malaria treatment records were collected. Results: MDA delivered house-to-house or at a central point, with or without compensation, were equally acceptable and did not affect coverage. People who knew about the rationale for the MDA, asymptomatic infections and transmission were more likely to participate. In western Cambodia, MDA delivered house-to-house by volunteers at the end of the dry season may be most practicable but requires the subsequent treatment of in-migrants to prevent reintroduction of infections. Conclusions: For MDA targeted at individual villages or village clusters it is important to understand local preferences for community mobilisation, delivery and timing, as several models of MDA are feasible.

Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries.

Importance: The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs). Objective: To assess the association of qSOFA with excess hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria. Design, Settings, and Participants: Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas. Exposures: Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 [best] to 3 [worst]) or SIRS criteria (range, 0 [best] to 4 [worst]) within 24 hours of presentation to study hospital. Main Outcomes and Measures: Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary). Results: The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% [95% CI, 11%-14%]; odds ratio, 3.6 [95% CI, 3.0-4.2]) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% [95% CI, 4%-6%]; odds ratio, 2.8 [95% CI, 2.0-3.9]), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% [95% CI, 3%-6%]; odds ratio, 1.7 [95% CI, 1.4-2.0]) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve [AUROC], 0.70 [95% CI, 0.68-0.72]) was superior to that of both the baseline model (AUROC, 0.56 [95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 [95% CI, 0.57-0.62]; P < .001). Conclusions and Relevance: When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.

Traumatic brain injury (TBI) outcomes in an LMIC tertiary care centre and performance of trauma scores.

BACKGROUND: This study evaluates post-ICU outcomes of patients admitted with moderate and severe Traumatic Brain Injury (TBI) in a tertiary neurocritical care unit in an low middle income country and the performance of trauma scores: A Severity Characterization of Trauma, Trauma and Injury Severity Score, Injury Severity Score and Revised Trauma Score in this setting. METHODS: Adult patients directly admitted to the neurosurgical intensive care units of the National Hospital of Sri Lanka between 21st July 2014 and 1st October 2014 with moderate or severe TBI were recruited. A telephone administered questionnaire based on the Glasgow Outcome Scale Extended (GOSE) was used to assess functional outcome of patients at 3 and 6 months after injury. The economic impact of the injury was assessed before injury, and at 3 and 6 months after injury. RESULTS: One hundred and one patients were included in the study. Survival at ICU discharge, 3 and 6 months after injury was 68.3%, 49.5% and 45.5% respectively. Of the survivors at 3 months after injury, 43 (86%) were living at home. Only 19 (38%) patients had a good recovery (as defined by GOSE 7 and 8). Three months and six months after injury, respectively 25 (50%) and 14 (30.4%) patients had become "economically dependent". Selected trauma scores had poor discriminatory ability in predicting mortality. CONCLUSIONS: This observational study of patients sustaining moderate or severe TBI in Sri Lanka (a LMIC) reveals only 46% of patients were alive at 6 months after ICU discharge and only 20% overall attained a good (GOSE 7 or 8) recovery. The social and economic consequences of TBI were long lasting in this setting. Injury Severity Score, Revised Trauma Score, A Severity Characterization of Trauma and Trauma and Injury Severity Score, all performed poorly in predicting mortality in this setting and illustrate the need for setting adapted tools.

A short, structured skills training course for critical care physiotherapists in a lower-middle income country.

OBJECTIVES: The aim of this article is to describe the delivery and acceptability of a short, structured training course for critical care physiotherapy and its effects on the knowledge and skills of the participants in Sri Lanka, a lower-middle income country. METHODS: The two-day program combining short didactic sessions with small group workshops and skills stations was developed and delivered by local facilitators in partnership with an overseas specialist physiotherapist trainer. The impact was assessed using pre/post-course self-assessment, pre/post-course multiple-choice-question (MCQ) papers, and an end-of-course feedback questionnaire. RESULTS: Fifty-six physiotherapists (26% of critical care physiotherapists in Sri Lanka) participated. Overall confidence in common critical care physiotherapy skills improved from 11.6% to 59.2% in pre/post-training self-assessments, respectively. Post-course MCQ scores (mean score = 63.2) and percentage of passes (87.5%) were higher than pre-course scores (mean score = 36.6; percentage of passes = 12.5%). Overall feedback was very positive as 75% of the participants were highly satisfied with the course's contribution to improved critical care knowledge. CONCLUSIONS: This short, structured, critical care focused physiotherapy training has potential benefit to participating physiotherapists. Further, it provides an evidence that collaborative program can be planned and conducted successfully in a resource poor setting. This sustainable short course model may be adaptable to other resource-limited settings.

Improving ICU services in resource-limited settings: Perceptions of ICU workers from low-middle-, and high-income countries.

PURPOSE: To evaluate perceptions of intensive care unit (ICU) workers from low-and-middle income countries (LMICs) and high income countries (HICs). MATERIALS AND METHODS: A cross sectional design. Data collected from doctors using an anonymous online, questionnaire. RESULTS: Hundred seventy-five from LMICs and 43 from HICs participated. Barriers in LMICs were lack of formal training (Likert score median 3 [inter quartile range 3]), lack of nurses (3[3]) and low wages (3[4]). Strategies for LMICs improvement were formal training of ICU staff (4[3]), an increase in number of ICU nurses (4[2]), collection of outcome data (3[4]), as well as maintenance of available equipment [3(3)]. The most useful role of HIC ICU staff was training of LMIC staff (4[2]). Donation of equipment [2(4)], drugs [2(4)], and supplies (2[4]) perceived to be of limited usefulness. The most striking difference between HIC and LMIC staff was the perception on the lack of physician leadership as an obstacle to ICU functioning (4[3] vs. 0[2], p<0.005). CONCLUSION: LMICs ICU workers perceived lack of training, lack of nurses, and low wages as major barriers to functioning. Training, increase of nurse workforce, and collection of outcome data were proposed as useful strategies to improve LMIC ICU services.

Towards malaria elimination in Savannakhet, Lao PDR: mathematical modelling driven strategy design.

BACKGROUND: The number of Plasmodium falciparum malaria cases around the world has decreased substantially over the last 15 years, but with the spread of resistance against anti-malarial drugs and insecticides, this decline may not continue. There is an urgent need to consider alternative, accelerated strategies to eliminate malaria in countries like Lao PDR, where there are a few remaining endemic areas. A deterministic compartmental modelling tool was used to develop an integrated strategy for P. falciparum elimination in the Savannakhet province of Lao PDR. The model was designed to include key aspects of malaria transmission and integrated control measures, along with a user-friendly interface. RESULTS: Universal coverage was the foundation of the integrated strategy, which took the form of the deployment of community health workers who provided universal access to early diagnosis, treatment and long-lasting insecticidal nets. Acceleration was included as the deployment of three monthly rounds of mass drug administration targeted towards high prevalence villages, with the addition of three monthly doses of the RTS,S vaccine delivered en masse to the same high prevalence sub-population. A booster dose of vaccine was added 1 year later. The surveillance-as-intervention component of the package involved the screening and treatment of individuals entering the simulated population. CONCLUSIONS: In this modelling approach, the sequential introduction of a series of five available interventions in an integrated strategy was predicted to be sufficient to stop malaria transmission within a 3-year period. These interventions comprised universal access to early diagnosis and adequate treatment, improved access to long-lasting insecticidal nets, three monthly rounds of mass drug administration together with RTS,S vaccination followed by a booster dose of vaccine, and screening and treatment of imported cases.

Mass anti-malarial administration in western Cambodia: a qualitative study of factors affecting coverage.

BACKGROUND: Mass anti-malarial administration has been proposed as a key component of the Plasmodium falciparum malaria elimination strategy in the Greater Mekong sub-Region. Its effectiveness depends on high levels of coverage in the target population. This article explores the factors that influenced mass anti-malarial administration coverage within a clinical trial in Battambang Province, western Cambodia. METHODS: Qualitative data were collected through semi-structured interviews and focus group discussions with villagers, in-depth interviews with study staff, trial drop-outs and refusers, and observations in the communities. Interviews were audio-recorded, transcribed and translated from Khmer to English for qualitative content analysis using QSR NVivo. RESULTS: Malaria was an important health concern and villagers reported a demand for malaria treatment. This was in spite of a fall in incidence over the previous decade and a lack of familiarity with asymptomatic malaria. Participants generally understood the overall study aim and were familiar with study activities. Comprehension of the study rationale was however limited. After the first mass anti-malarial administration, seasonal health complaints that participants attributed to the anti-malarial as "side effects" contributed to a decrease of coverage in round two. Staff therefore adapted the community engagement approach, bringing to prominence local leaders in village meetings. This contributed to a subsequent increase in coverage. CONCLUSION: Future mass anti-malarial administration must consider seasonal disease patterns and the importance of local leaders taking prominent roles in community engagement. Further research is needed to investigate coverage in scenarios that more closely resemble implementation i.e. without participation incentives, blood sampling and free healthcare.

Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort.

Artemisinin-resistant falciparum malaria, defined by a slow-clearance phenotype and the presence of kelch13 mutants, has emerged in the Greater Mekong Subregion. Naturally acquired immunity to malaria clears parasites independent of antimalarial drugs. We hypothesized that between- and within-population variations in host immunity influence parasite clearance after artemisinin treatment and the interpretation of emerging artemisinin resistance. Antibodies specific to 12 Plasmodium falciparum sporozoite and blood-stage antigens were determined in 959 patients (from 11 sites in Southeast Asia) participating in a multinational cohort study assessing parasite clearance half-life (PCt1/2) after artesunate treatment and kelch13 mutations. Linear mixed-effects modeling of pooled individual patient data assessed the association between antibody responses and PCt1/2.P. falciparum antibodies were lowest in areas where the prevalence of kelch13 mutations and slow PCt1/2 were highest [Spearman ρ = -0.90 (95% confidence interval, -0.97, -0.65), and Spearman ρ = -0.94 (95% confidence interval, -0.98, -0.77), respectively]. P. falciparum antibodies were associated with faster PCt1/2 (mean difference in PCt1/2 according to seropositivity, -0.16 to -0.65 h, depending on antigen); antibodies have a greater effect on the clearance of kelch13 mutant compared with wild-type parasites (mean difference in PCt1/2 according to seropositivity, -0.22 to -0.61 h faster in kelch13 mutants compared with wild-type parasites). Naturally acquired immunity accelerates the clearance of artemisinin-resistant parasites in patients with falciparum malaria and may confound the current working definition of artemisinin resistance. Immunity may also play an important role in the emergence and transmission potential of artemisinin-resistant parasites.

An assessment of national surveillance systems for malaria elimination in the Asia Pacific.

BACKGROUND: Heads of Government from Asia and the Pacific have committed to a malaria-free region by 2030. In 2015, the total number of confirmed cases reported to the World Health Organization by 22 Asia Pacific countries was 2,461,025. However, this was likely a gross underestimate due in part to incidence data not being available from the wide variety of known sources. There is a recognized need for an accurate picture of malaria over time and space to support the goal of elimination. A survey was conducted to gain a deeper understanding of the collection of malaria incidence data for surveillance by National Malaria Control Programmes in 22 countries identified by the Asia Pacific Leaders Malaria Alliance. METHODS: In 2015-2016, a short questionnaire on malaria surveillance was distributed to 22 country National Malaria Control Programmes (NMCP) in the Asia Pacific. It collected country-specific information about the extent of inclusion of the range of possible sources of malaria incidence data and the role of the private sector in malaria treatment. The findings were used to produce recommendations for the regional heads of government on improving malaria surveillance to inform regional efforts towards malaria elimination. RESULTS: A survey response was received from all 22 target countries. Most of the malaria incidence data collected by NMCPs originated from government health facilities, while many did not collect comprehensive data from mobile and migrant populations, the private sector or the military. All data from village health workers were included by 10/20 countries and some by 5/20. Other sources of data included by some countries were plantations, police and other security forces, sentinel surveillance sites, research or academic institutions, private laboratories and other government ministries. Malaria was treated in private health facilities in 19/21 countries, while anti-malarials were available in private pharmacies in 16/21 and private shops in 6/21. Most countries use primarily paper-based reporting. CONCLUSIONS: Most collected malaria incidence data in the Asia Pacific is from government health facilities while data from a wide variety of other known sources are often not included in national surveillance databases. In particular, there needs to be a concerted regional effort to support inclusion of data on mobile and migrant populations and the private sector. There should also be an emphasis on electronic reporting and data harmonization across organizations. This will provide a more accurate and up to date picture of the true burden and distribution of malaria and will be of great assistance in helping realize the goal of malaria elimination in the Asia Pacific by 2030.