Bushfire-smoke trigger hospital admissions with cerebrovascular diseases: Evidence from 2019-20 bushfire in Australia.

INTRODUCTION: Exposure to ambient air pollution is strongly associated with increased cerebrovascular diseases. The 2019-20 bushfire season in Australia burnt 5.4 million hectares of land in New South Wales alone, with smoke so severe it affected cities in Argentina, 11,000 km away. The smoke emitted by bushfires consists of both gaseous and particle components. It is important to note that exposure to particulate matter has been shown to be linked to a heightened risk of stroke, which is the primary kind of cerebrovascular illness, as well as an increased likelihood of hospitalisations and mortality. However, the available data is inadequate in terms of documenting the response of patients diagnosed with a proven cerebrovascular illness to bushfire smoke. Additionally, there is a lack of information about the health effects associated with particulate matter throughout the bushfire season and on days when smoke was present in 2019 and 2020.Therefore, we aimed to determine the effects of (i) short-term air pollution triggered by bushfires and (ii) high smoke days in increasing the daily number of hospital admissions with cerebrovascular diseases. MATERIALS AND METHODS: Hospitalisation data were accessed from the admitted patient dataset from seven local Government areas of Hunter New England Local Health District. The bushfire period was defined from 1 October 2019 to 10 February 2020, and a same period from 2018-19 as the control. High bushfire smoke days were days when the average daily concentration of particulate matter was higher than the 95th percentile of the control period. Poisson regression models and fixed effect meta-analysis were used to analyse the data. RESULTS: In total, 275 patients with cerebrovascular admissions were identified, with 147 (53.5%) during the bushfire (2019-20) and 128 (46.5%) in the control period (2018-19). There was no significant increase in daily admissions for cerebrovascular disease (Incidence Rate Ratio, IRR: 1.04; 95% CI: 0.81-1.34; p-value: 0.73), acute stroke (IRR: 1.15; 95% CI: 0.88-1.50; p-value: 0.29) or acute ischaemic stroke (IRR: 1.18; 95% CI: 0.87-1.59; p-value: 0.28), over the entire bushfire period. However, the high bushfire smoke days were associated with increased acute ischaemic stroke-related hospital admissions across lead 0-3 and the highest cumulative effect was observed with lead 0 (IRR:1.52; 95% CI: 1.01-2.29; p-value: 0.04). In addition, during the bushfire period, particulate matter, both PM10 and PM2.5 (defined as particulates that have an effective aerodynamic diameter of 10, and 2.5 microns, respectively), were also associated with increased acute ischaemic stroke admissions with a lag of 0-3 days. DISCUSSION AND CONCLUSION: The results suggested a possible association between particulate matter and high smoke days with increased hospital admissions due to acute ischaemic stroke during the recent Australian bushfire season.

Effect of short-term exposure to air pollution on daily cardio- and cerebrovascular hospitalisations in areas with a low level of air pollution.

Exposure to air pollution is associated with increased cardio- and cerebrovascular diseases. However, the evidence regarding the short-term effect of air pollution on cardio- and cerebrovascular hospitalisations in areas with relatively low air pollution levels is limited. This study aims to examine the effect of short-term exposure to different air pollutants on hospital admissions due to cardio- and cerebrovascular diseases in rural and regional Australia with low air pollution. The study was conducted in five local Government areas of Hunter New England Local Health District (HNE-LHD). Hospitalisation data from January 2018 to February 2020 (820 days) were accessed from the HNE-LHD admitted patients' dataset. Poisson regression model was used to examine the association between the exposure (air pollutants) and outcome variables (hospitalisation due to cardio- and cerebrovascular disease). The concentrations of gaseous air pollutants, Sulphur Dioxide (SO2), Nitrogen Dioxide (NO2), Ozone (O3), Carbon Monoxide (CO), and Ammonia (NH3) were below national benchmark concentrations for every day of the study period. In single pollutant models, SO2 and NO2 significantly increased the daily number of cardio- and cerebrovascular hospitalisations. The highest cumulative effect for SO2 was observed across lag 0-3 days (Incidence Rate Ratio, IRR: 1.77; 95% Confidence Interval, CI: 1.18-2.65; p-value: 0.01), and for NO2, it was across lag 0-2 days (IRR: 1.13; 95% CI: 1.02-1.25; p-value: 0.02). In contrast, higher O3 was associated with decreased cardio- and cerebrovascular hospitalisations, with the largest effect observed at lag 0 (IRR: 0.94; 95% CI: 0.89-0.98; p-value: 0.02). In the multi-pollutant model, the effect of NO2 remained significant at lag 0 and corresponded to a 21% increase in cardio- and cerebrovascular hospitalisation (95% CI: 1-44%; p-value = 0.04). Thus, the study revealed that gaseous air pollutants, specifically NO2, were positively related to increased cardio- and cerebrovascular hospitalisations, even at concentrations below the national standards.

Endovascular thrombectomy for acute ischaemic stroke improves and maintains function in the very elderly: A multicentre propensity score matched analysis.

Introduction: The very elderly (⩾80 years) are under-represented in randomised endovascular thrombectomy (EVT) clinical trials for acute ischaemic stroke. Rates of independent outcome in this group are generally lower than the less-old patients but the comparisons may be biased by an imbalance of non-age related baseline characteristics, treatment related metrics and medical risk factors. Patients and methods: We compared outcomes between very elderly (⩾80) and the less-old (<80 years) using retrospective data from consecutive patients receiving EVT from four comprehensive stroke centres in New Zealand and Australia. We used propensity score matching or multivariable logistic regression to account for confounders. Results: We included 600 patients (300 in each age cohort) after propensity score matching from an initial group of 1270 patients. The median baseline National Institutes of Health Stroke Scale was 16 (11-21), with 455 (75.8%) having symptom free pre-stroke independent function, and 268 (44.7%) receiving intravenous thrombolysis. Good functional outcome (90-day modified Rankin Scale 0-2) was achieved in 282 (46.8%), with very elderly patients having less proportion of good outcome compared to the less-old (118 (39.3%) vs 163 (54.3%), p < 0.01). There was no difference between the very elderly and the less-old in the proportion of patients who returned to baseline function at 90 days (56 (18.7%) vs 62 (20.7%), p = 0.54). All-cause 90-day mortality was higher in the very elderly (75 (25%) vs 49 (16.3%), p < 0.01), without a difference in symptomatic haemorrhage (very elderly 11 (3.7%) vs 6 (2.0%), p = 0.33). In the multivariable logistic regression models, the very elderly were significantly associated with reduced odds of good 90-day outcome (OR 0.49, 95% CI 0.34-0.69, p < 0.01) but not with return to baseline function (OR 0.85, 90% CI 0.54-1.29, p = 0.45) after adjusting for confounders. Conclusion: Endovascular thrombectomy can be successfully and safely performed in the very elderly. Despite an increase in all-cause 90-day mortality, selected very elderly patients are as likely as younger patients with similar baseline characteristics to return to baseline function following EVT.

Ultra-Long Transfers for Endovascular Thrombectomy-Mission Impossible?: The Australia-New Zealand Experience.

BACKGROUND: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. METHODS: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). RESULTS: There were 131 patients; the median age was 64 [53-74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12-22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1-3] versus 3 [1-6] in the patients selected with noncontrast CT+CT angiography, P=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01-0.19]; P<0.01). CONCLUSIONS: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Gauging the skin resident Leishmania parasites through a loop mediated isothermal amplification (LAMP) assay in post-kala-azar dermal leishmaniasis.

Despite the availability of highly sensitive polymerase chain reaction (PCR)-based methods, the dearth of remotely deployable diagnostic tools circumvents the early and accurate detection of individuals with post-kala-azar dermal leishmaniasis (PKDL). Here, we evaluate a design-locked loop-mediated isothermal amplification (LAMP) assay to diagnose PKDL. A total of 76 snip-skin samples collected from individuals with probable PKDL (clinical presentation and a positive rK39 rapid diagnostic test (RDT)) were assessed by microscopy, qPCR, and LAMP. An equal number of age and sex-matched healthy controls were included to determine the specificity of the LAMP assay. The LAMP assay with a Qiagen DNA extraction (Q-LAMP) showed a promising sensitivity of 72.37% (95% CI: 60.91-82.01%) for identifying the PKDL cases. LAMP assay sensitivity declined when the DNA was extracted using a boil-spin method. Q-qPCR showed 68.42% (56.75-78.61%) sensitivity, comparable to LAMP and with an excellent agreement, whereas the microscopy exhibited a weak sensitivity of 39.47% (28.44-51.35%). When microscopy and/or qPCR were considered the gold standard, Q-LAMP exhibited an elevated sensitivity of 89.7% (95% CI: 78.83-96.11%) for detection of PKDL cases and Bayesian latent class modeling substantiated the excellent sensitivity of the assay. All healthy controls were found to be negative. Notwithstanding the optimum efficiency of the LAMP assay towards the detection of PKDL cases, further optimization of the boil-spin method is warranted to permit remote use of the assay.

Transition in Incidence Rate of Hospitalised Stroke and Case Fatality Rate in the Hunter Region, Australia, 2001-2019: A Prospective Hospital-Based Study.

INTRODUCTION: Continuous surveillance of stroke admissions has been conducted in the Hunter region, Australia, over the past two decades. We aimed to describe the trends in incidence rates of hospitalised stroke and case-fatality rates in this region, 2001-2019. METHODS: From a hospital-based stroke registry, data for admitted adult stroke patients residing in the Hunter region were collected using ICD-10 codes for ischemic and haemorrhagic stroke. Negative binomial regression and logistic regression analysis were used to analyse trends for age-standardised and age-specific incidence rates of hospitalised stroke and 28-day case-fatality rates. RESULTS: A total of 14,662 hospitalisations for stroke in 13,242 individuals were registered. The age-standardised incidence rate declined from 123 per 100,000 population in the 2001-2005 epoch to 96 in the 2016-2019 epoch (mean annual change -2.0%, incidence rate ratio (IRR) = 0.980 [95%CI: 0.976-0.984]). Age-specific analyses identified significant reduction in the group aged 75-84 (1039 per 100,000 population in 2001-2005 to 633 in 2016-2019, annual change -3.5%, IRR= 0.965 [95%CI: 0.960-0.970]). The 28-day case-fatality rates fluctuated over time (18.5% in 2001-2005, 20.8% in 2010-2015, and 17.8% in 2016-2019).  Projected population aging suggests annual volume of patients with new stroke will increase by 77% by 2041 if incidence rates remain unchanged at the 2016-2019 level. CONCLUSION: Although age-standardised hospitalised stroke incidence rates have declined in the Hunter region, the health system will face an increase in stroke hospitalisations related to the aging population.

Impact of Testing on Sexually Transmitted Infections among Female Brothel Sex Workers in Bangladesh: A Randomized Controlled Trial.

Past studies that have designed interventions to reduce the prevalence of sexually transmitted infections (STIs) have typically provided onsite treatment to sex workers who tested positive, which were expensive and difficult to implement. The purpose of this study was to examine the effect of an intervention which tested for STIs and provided information on the closest treatment facility on reducing the prevalence of STIs among female brothel-based sex workers (BSWs) in Bangladesh. The study adopted a pre-post interventional design as well as a randomized controlled study design. A baseline sample and follow-up urine sample were collected to evaluate the prevalence of STIs among participants in the treatment, but not control group. A baseline survey and interviews were also conducted for both the groups. The study found a nonsignificant reduction from baseline to follow-up in STI prevalence among intervention participants (adjusted odds ratio [aOR]: 0.74; 95% CI: 0.38, 1.45). However, the participants in the intervention group were significantly more likely to have a repeat client (aOR: 1.60; 95% CI: 1.12, 2.29) and nonsignificantly less likely to engage with a client suspected of having an STI (aOR: 0.62; 95% CI: 0.39, 1.00) than participants in the control group. The intervention testing of STIs and providing information to the positive cases about nearest treatment facilities were not effective in reducing the prevalence of STIs among BSWs. Further study of the clinical and behavioral impacts of such efforts to reduce STIs among BSWs is warranted.

Effectiveness of interventions to improve rates of intravenous thrombolysis using behaviour change wheel functions: a systematic review and meta-analysis.

BACKGROUND: Despite being one of the few evidence-based treatments for acute ischemic stroke, intravenous thrombolysis has low implementation rates-mainly due to a narrow therapeutic window and the health system changes required to deliver it within the recommended time. This systematic review and meta-analyses explores the differential effectiveness of intervention strategies aimed at improving the rates of intravenous thrombolysis based on the number and type of behaviour change wheel functions employed. METHOD: The following databases were searched: MEDLINE, EMBASE, PsycINFO, CINAHL and SCOPUS. Multiple authors independently completed study selection and extraction of data. The review included studies that investigated the effects of intervention strategies aimed at improving the rates of intravenous thrombolysis and/or onset-to-needle, onset-to-door and door-to-needle time for thrombolysis in patients with acute ischemic stroke. Interventions were coded according to the behaviour change wheel nomenclature. Study quality was assessed using the QualSyst scoring system for quantitative research methodologies. Random effects meta-analyses were used to examine effectiveness of interventions based on the behaviour change wheel model in improving rates of thrombolysis, while meta-regression was used to examine the association between the number of behaviour change wheel intervention strategies and intervention effectiveness. RESULTS: Results from 77 studies were included. Five behaviour change wheel interventions, 'Education', 'Persuasion', 'Training', 'Environmental restructuring' and 'Enablement', were found to be employed among the included studies. Effects were similar across all intervention approaches regardless of type or number of behaviour change wheel-based strategies employed. High heterogeneity (I2 > 75%) was observed for all the pooled analyses. Publication bias was also identified. CONCLUSION: There was no evidence for preferring one type of behaviour change intervention strategy, nor for including multiple strategies in improving thrombolysis rates. However, the study results should be interpreted with caution, as they display high heterogeneity and publication bias.

Thrombolysis implementation intervention and clinical outcome: a secondary analysis of a cluster randomized trial.

BACKGROUND: Multiple studies have attempted to increase the rate of intravenous thrombolysis for ischemic stroke using interventions to promote adherence to guidelines. Still, many of them did not measure individual-level impact. This study aimed to make a posthoc comparison of the clinical outcomes of patients in the "Thrombolysis ImPlementation in Stroke (TIPS)" study, which aimed to improve rates of intravenous thrombolysis in Australia. METHODS: A posthoc analysis was conducted using individual-level patient data. Excellent (Three-month post treatment modified Rankin Score 0-2) and poor clinical outcome (Three-month post treatment modified Rankin Score 5-6) and post treatment parenchymal haematoma were the three main outcomes, and a mixed logistic regression model was used to assess the difference between the intervention and control groups. RESULTS: There was a non-significant higher odds of having an excellent clinical outcome of 57% (odds ratio: 1.57; 95% CI: 0.73-3.39) and 33% (odds ratio: 1.33; 95% CI: 0.73-2.44) during the active-and post-intervention period respectively, for the intervention compared to the control group. A non-significant lower odds of having a poor clinical outcome was also found in the intervention, relative to control group of 4% (odds ratio: 0.96; 95% CI: 0.56-2.07) and higher odds of having poor outcome of 44% (odds ratio: 1.44 95% CI: 0.61-3.41) during both active and post-intervention period respectively. Similarly, a non-significant lower odds of parenchymal haematoma was also found for the intervention group during the both active- (odds ratio: 0.53; 95% CI: 0.21-1.32) and post-intervention period (odds ratio: 0.96; 95% CI: 0.36-2.52). CONCLUSION: The TIPS multi-component implementation approach was not effective in reducing the odds of post-treatment severe disability at 90 days, or post-thrombolysis hemorrhage. TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.anzctr.org.au/ Unique Identifier: ACTRN12613000939796 .

Door-to-needle time for thrombolysis: a secondary analysis of the TIPS cluster randomised controlled trial.

OBJECTIVE: The current study aimed to evaluate the effects of a multi-component in-hospital intervention on the door-to-needle time for intravenous thrombolysis in acute ischaemic stroke. DESIGN: This study was a post hoc analysis of door-to-needle time data from a cluster-randomised controlled trial testing an intervention to boost intravenous thrombolysis implementation. SETTING: The study was conducted among 20 hospitals from three Australian states. PARTICIPANT: Eligible hospitals had a Stroke Care Unit or staffing equivalent to a stroke physician and a nurse, and were in the early stages of implementing thrombolysis. INTERVENTION: The intervention was multifaceted and developed using the behaviour change wheel and informed by breakthrough collaborative methodology using components of the health behaviour change wheel. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome for this analysis was door-to-needle time for thrombolysis and secondary outcome was the proportion of patients received thrombolysis within 60 min of hospital arrival. RESULTS: The intervention versus control difference in the door-to-needle times was non-significant overall nor significant by hospital classification. To provide additional context for the findings, we also evaluated the results within intervention and control hospitals. During the active-intervention period, the intervention hospitals showed a significant decrease in the door-to-needle time of 9.25 min (95% CI: -16.93 to 1.57), but during the post-intervention period, the result was not significant. During the active intervention period, control hospitals also showed a significant decrease in the door-to-needle time of 5.26 min (95% CI: -8.37 to -2.14) and during the post-intervention period, this trend continued with a decrease of 12.13 min (95% CI: -17.44 to 6.81). CONCLUSION: Across these primary stroke care centres in Australia, a secular trend towards shorter door-to-needle times across both intervention and control hospitals was evident, however the TIPS (Thrombolysis ImPlementation in Stroke) intervention showed no overall effect on door-to-needle times in the randomised comparison. TRIAL REGISTRATION NUMBER: Trial Registration-URL: http://www.anzctr.org.au/ Unique Identifier: ACTRN 12613000939796.

Can a multicomponent multidisciplinary implementation package change physicians' and nurses' perceptions and practices regarding thrombolysis for acute ischemic stroke? An exploratory analysis of a cluster-randomized trial.

BACKGROUND: The Thrombolysis ImPlementation in Stroke (TIPS) trial tested the effect of a multicomponent, multidisciplinary, collaborative intervention designed to increase the rates of intravenous thrombolysis via a cluster randomized controlled trial at 20 Australian hospitals (ten intervention, ten control). This sub-study investigated changes in self-reported perceptions and practices of physicians and nurses working in acute stroke care at the participating hospitals. METHODS: A survey with 74 statements was administered during the pre- and post-intervention periods to staff at 19 of the 20 hospitals. An exploratory factor analysis identified the structure of the survey items and linear mixed modeling was applied to the final survey domain scores to explore the differences between groups over time. RESULT: The response rate was 45% for both the pre- (503 out of 1127 eligible staff from 19 hospitals) and post-intervention (414 out of 919 eligible staff from 18 hospitals) period. Four survey domains were identified: (1) hospital performance indicators, feedback, and training; (2) personal perceptions about thrombolysis evidence and implementation; (3) personal stroke skills and hospital stroke care policies; and (4) emergency and ambulance procedures. There was a significant pre- to post-intervention mean increase (0.21 95% CI 0.09; 0.34; p < 0.01) in scores relating to hospital performance indicators, feedback, and training; for the intervention hospitals compared to control hospitals. There was a corresponding increase in mean scores regarding perceptions about the thrombolysis evidence and implementation (0.21, 95% CI 0.06; 0.36; p < 0.05). Sub-group analysis indicated that the improvements were restricted to nurses' responses. CONCLUSION: TIPS resulted in changes in some aspects of nurses' perceptions relating to the evidence for intravenous thrombolysis and its implementation and hospital performance indicators, feedback, and training. However, there is a need to explore further strategies for influencing the views of physicians given limited statistical power in the physician sample. TRIAL REGISTRATION: ACTRN12613000939796, UTN: U1111-1145-6762.

Relationship between treatment regimens for visceral leishmaniasis and development of post-kala-azar dermal leishmaniasis and visceral leishmaniasis relapse: A cohort study from Bangladesh.

BACKGROUND: We investigated the relationship of treatment regimens for visceral leishmaniasis (VL) with post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis relapse (VLR) development. METHODS: Study subjects included cohorts of patients cured of VL since treatment with monotherapy by sodium stibogluconate (SSG), miltefosine (MF), paromomycin intramuscular injection (PMIM), liposomal amphotericin B [AmBisome (AMB)] in a single dose (SDAMB) and in multidose (MDAMB), and combination therapies by AMB+PMIM, AMB+MF, and PMIM+MF. Follow up period was 4 years after treatment. Cohorts were prospective except SSG (retrospective) and MF (partially retrospective). We compared incidence proportion and rate in 100-person-4year of PKDL and VLR by treatment regimens using univariate and multivariate analysis. FINDINGS: 974 of 984 enrolled participants completed the study. Overall incidence proportion for PKDL and VLR was 12.3% (95% CI, 10.4%-14.5%) and 7.0% (95% CI, 5.6%-8.8%) respectively. The incidence rate (95% CI) of PKDL and VLR was 14.0 (8.6-22.7) and 7.6 (4.1-14.7) accordingly. SSG cohort had the lowest incidence rate of PKDL at 3.0 (1.3-7.3) and VLR at 1.8 (0.6-5.6), followed by MDAMB at 8.2 (4.3-15.7) for PKDL and at 2.7 (0.9-8.4) for VLR. INTERPRETATION: Development of PKDL and VLR is related with treatment regimens for VL. SSG and MDAMB resulted in less incidence of PKDL and VLR compared to other treatment regimens. MDAMB should be considered for VL as a first step for prevention of PKDL and VLR since SSG is highly toxic and not recommended for VL.

Quality Assessment of Dried Blood Spots from Patients With Tuberculosis from 4 Countries.

BACKGROUND: Dried blood spot (DBS) sampling is a blood collection tool that uses a finger prick to obtain a blood drop on a DBS card. It can be used for therapeutic drug monitoring, a method that uses blood drug concentrations to optimize individual treatment. DBS sampling is believed to be a simpler way of blood collection compared with venous sampling. The aim of this study was to evaluate the quality of DBSs from patients with tuberculosis all around the world based on quality indicators in a structured assessment procedure. METHODS: Total 464 DBS cards were obtained from 4 countries: Bangladesh, Belarus, Indonesia, and Paraguay. The quality of the DBS cards was assessed using a checklist consisting of 19 questions divided into 4 categories: the integrity of the DBS materials, appropriate drying time, blood volume, and blood spot collection. RESULTS: After examination, 859 of 1856 (46%) blood spots did not comply with present quality criteria. In 625 cases (34%), this was due to incorrect blood spot collection. The DBS cards from Bangladesh, Indonesia, and Paraguay seemed to be affected by air humidity, causing the blood spots not to dry appropriately. CONCLUSIONS: New tools to help obtain blood spots of sufficient quality are necessary and environmental specific recommendations to determine plasma concentration correctly. In addition, 3% of the DBS cards were rejected because the integrity of the materials suggesting that the quality of plastic ziplock bags currently used to protect the DBS cards against contamination and humidity may not be sufficient.

Amphotericin B deoxycholate for relapse visceral leishmaniasis in Bangladesh: a cross-sectional study.

OBJECTIVE: Based on studies in India (as there was no studies from outside India) amphotericin B deoxycholate has been considered as a backup drug for treatment of visceral leishmaniasis. However, treatment response and adverse effect to anti-leishmanial drugs may vary across different populations and in Bangladesh the effect to amphotericin B deoxycholate for treatment of visceral leishmaniasis is still unknown. Therefore, there is a need to explore cure rate and adverse effects to amphotericin B deoxycholate to justify its use on visceral leishmaniasis patients in Bangladesh. RESULT: Here we report 34 visceral leishmaniasis patients who received treatment with amphotericin B deoxycholate in the Surya Kanta Kala-azar Research Centre from December 2011 to June 2015. The dose of the treatment was 1 mg/kg body weight for 15 days followed up until 12 months after treatment. Response to amphotericin B deoxycholate treatment was excellent as all 34 patients achieved a final cure. Hypokalaemia (47%), shivering (47%), vomiting (35%) and acidity (15%) were most common adverse events. However, we did not observe any serious adverse events. Amphotericin B deoxycholate for relapse visceral leishmaniasis was found to be highly effective and safe. Our study justified to include amphotericin B deoxycholate as a second line drug for visceral leishmaniasis in Bangladesh.

Evaluation of Real-time PCR for Diagnosis of Post-Kala-azar Dermal Leishmaniasis in Endemic Foci of Bangladesh.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a sequel to visceral leishmaniasis (VL), which is found in VL-endemic countries including Bangladesh. Because of these enigmatic cases, the success of the National Kala-azar Elimination Program is under threat. To date, diagnostic methods for PKDL cases in endemic regions have been limited to clinical examination and rK39 test or microscopy, and a suitable and accurate alternative method is needed. In this study, we investigated the application of real-time polymerase chain reaction (PCR) as a potential method for diagnosis of PKDL in comparison with microscopy. METHODS: Ninety-one suspected macular PKDL cases from Mymensingh district, Bangladesh, were enrolled in the study after diagnosis by clinical examination and an rK39 strip test. All of them responded after completion of the treatment with miltefosine. During enrollment, a skin biopsy was done for each patient, and both microscopy and real-time PCR were performed for detection and quantification of Leishmania donovan body (LDB) and LD DNA, respectively. RESULTS: Real-time PCR detected 83 cases among all suspected PKDL patients, with an encouraging sensitivity of 91.2% (83.4%-96.1%), whereas microscopy showed 50.6% (39.9%-61.2%) sensitivity. Among all suspected PKDL cases, 42 cases were positive in both microscopy and qPCR, whereas 41 cases were detected as positive through qPCR only. CONCLUSIONS: This study provides evidence that real-time PCR is a promising tool for diagnosis of PKDL in endemic regions. In addition to diagnosis, the quantitative ability of this method could be further exploited for after-treatment prognosis and cure assessment of PKDL cases.

Managing Severe Tetanus without Ventilation Support in a Resource-limited Setting in Bangladesh.

Tetanus, a vaccine-preventable and potentially fatal disease, continues to remain prevalent in low- and middle-income countries. Furthermore, physicians are often unfamiliar with management of severe tetanus without ventilator support. Therefore, we proposed a modified treatment protocol that provides a low-cost and effective solution for the management of severe tetanus in resource-constrained settings. This is an observational study of 42 patients with severe tetanus treated during 2015-2016 at Surya Kanta Hospital, Bangladesh. This facility does not have an intensive care unit (ICU), and patients admitted here were provided treatment with the modified protocol. A total number of 42 patients with severe tetanus were treated with the modified protocol. Among them, 24 (57.1%) recovered completely, six (14.3%) recovered with the sequela, and 12 (28.6%) died. Among those who recovered with the sequela, four needed mechanical support during walking and two had a visual impairment. No significant adverse event was recorded during the treatment period. The results gathered during this case series provide a sustainable, low-cost, and effective solution to management of severe tetanus in resource-constrained settings where ICUs are unavailable.

Case Report: Treatment of Widespread Nodular Post kala-Azar Dermal Leishmaniasis with Extended-Dose Liposomal Amphotericin B in Bangladesh: A Series of Four Cases.

Post kala-azar dermal leishmaniasis (PKDL) is a skin manifestation which usually appears after visceral leishmaniasis. It is now proved that PKDL patients serve as a reservoir for anthropometric leishmanial transmission. Hence, to achieve the kala-azar elimination target set by the World Health Organization in the Indian Subcontinent, PKDL cases should be given priority. The goal of treatment for PKDL should be early reepithelizlization and rapid cure, but unfortunately this has been difficult to achieve, especially for patients with severe lesions. Therefore, we describe here four cases of PKDL who had widespread nodular and macular lesions and were treated with two cycles of LAmB doses with 20 mg/kg body weight divided into four equal doses (each dose contains 5 mg/kg) administered every alternate day. This treatment schedule achieved 100% treatment success with the minimal safety concern.

A comparative evaluation of the performance of commercially available rapid immunochromatographic tests for the diagnosis of visceral leishmaniasis in Bangladesh.

BACKGROUND: Accurate and early diagnosis of Visceral Leishmaniasis (VL) is a prerequisite for proper treatment and restricting disease propagation in enldemic foci. An rK39 antigen-based immunochromatographic test is now recommended for its diagnostic accuracy and operational feasibility at point of care. In endemic regions of Bangladesh, rK39 or rKE16 antigen-based Rapid Diagnostic Tests (RDTs) are routinely performed on whole blood for diagnosis of VL. However, manufacturer's instructions require use of serum. Therefore, we wanted to assess whether the diagnostic accuracy of these RDTs is as good on whole blood as on serum. METHODS: We evaluated and compared the sensitivity and specificity of five different commercially available RDTs on whole blood and on serum. We enrolled 30 VL patients, 35 endemic healthy controls and 30 Tuberculosis (TB) patients in our study from Mymensingh, a hyper-endemic region in Bangladesh. RESULTS: The sensitivity of all RDTs ranged between 96.67% (95% CI: 82.72-99.44%) and 100% (95% CI: 96.34-100%). The specificity ranged between 93.85% (95% CI: 84.97-98.26%) and 98.46% (95% CI: 91.69-99.74%), except for the Onsite leishmania Ab (Rev B) kit which showed markedly lower specificity (31.25-58.46 %). There was no significant difference in sensitivity and specificity between blood and serum. The Cohen kappa index (k >0.97) indicated excellent agreement. CONCLUSIONS: We conclude from the study that the use of blood for RDT in lieu of serum is appropriate for diagnosis of VL in peripheral endemic regions provided the manufacturer recommendations are followed and the RDT is of good quality.

First case of pulmonary tuberculosis and visceral leishmaniasis coinfection successfully treated with antituberculosis drug and liposomal amphotericin B.

KEY CLINICAL MESSAGE: Successful management of cases with visceral leishmaniasis (VL) and tuberculosis is a challenge for clinicians, because a guideline for that is currently unavailable. We report the first case in Bangladesh who developed VL during her treatment for pulmonary tuberculosis and was treated successfully with multidose liposomal amhptericin B for VL.

Efficacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: a feasibility study.

BACKGROUND: To rapidly reduce the burden of visceral leishmaniasis for national elimination programmes, an acceptable, safe, and effective treatment is needed that can be delivered at primary health-care centres. We aimed to assess the tolerability, safety, and cure rate of single-dose liposomal amphotericin B (AmBisome, Gilead, USA) for visceral leishmaniasis treatment in such a setting in Bangladesh. METHODS: We enrolled patients who had been diagnosed with visceral leishmaniasis at Muktagacha upazila (subdistrict) hospital, Bangladesh. Eligible participants were at least 5 years old and had a history of fever for more than 2 weeks, splenomegaly, rK39 rapid test positivity, and haemoglobin concentrations of at least 50 g/L. Participants were provided a one-off intravenous infusion of liposomal amphotericin B (10 mg/kg bodyweight). Clinical assessments were done during treatment, before hospital discharge, and on days 30 and 180 after treatment. Cure was defined as resolution of fever, decrease in spleen size, and an increase in haemoglobin by 10% compared with baseline or to at least 100 g/L. We estimated efficacy in terms of initial cure (at day 30) and final cure (at 6 months), and safety in all patients who were enrolled (intention-to-treat analysis). We also assessed efficacy in all patients who completed treatment and 6 month follow-up after treatment with or without visceral leishmaniasis relapse (per protocol analysis). We assessed acceptability in terms of proportion of patients who consented to treatment. This study was registered with the Australian New Zealand Clinical Trial Registry, number CTRN12612000367842. FINDINGS: Between March 5, and Aug 14, 2012, 329 (55%) of 594 cases of suspected visceral leishmaniasis were confirmed. Of these cases, five patients did not consent to treatment and 24 were ineligible for treatment. In the intention-to-treat analysis, 261 (87%) of 300 patients achieved initial cure and 290 (97%) achieved final cure. In the per-protocol analysis, 260 (88%) of 296 patients achieved initial cure and 289 (98%) achieved final cure. One patient did not start treatment owing to an allergic reaction to liposomal amphotericin B. During treatment or within 2 h afterwards, 79 (26%) patients developed fever, 109 (36%) had fever with rigor, and 56 (19%) had hypotension. No patients needed referral to a tertiary hospital for management of adverse events. INTERPRETATION: Treatment of visceral leishmaniasis in a primary health-care facility with single-dose liposomal amphotericin B could safely and effectively be adopted by the national visceral leishmaniasis elimination programme in Bangladesh. FUNDING: Neglected Tropical Diseases (WHO), Agencia Española de Cooperación Internacional.