Longitudinal monitoring of pancreatic islet damage in streptozotocin-treated mice with optical coherence microscopy.

Pancreatic islets regulate glucose homeostasis in the body, and their dysfunction is closely related to diabetes. Islet transplantation into the anterior chamber of the eye (ACE) was recently developed for both in vivo islet study and diabetes treatment. Optical coherence microscopy (OCM) was previously used to monitor ACE transplanted islets in non-obese diabetic (NOD) mice for detecting autoimmune attack. In this study, OCM was applied to streptozotocin (STZ)-induced diabetic mouse models for the early detection of islet damage. A custom extended-focus OCM (xfOCM) was used to image islet grafts in the ACE longitudinally during STZ-induced beta cell destruction together with conventional bright-field (BF) imaging and invasive glucose level measurement. xfOCM detected local structural changes and vascular degradation during the islet damage which was confirmed by confocal imaging of extracted islet grafts. xfOCM detection of islet damage was more sensitive than BF imaging and glucose measurement. Longitudinal xfOCM images of islet grafts were quantitatively analyzed. All these results showed that xfOCM could be used as a non-invasive and sensitive monitoring method for the early detection of deficient islet grafts in the ACE with potential applications to human subjects.

Antivirulence Bispecific Monoclonal Antibody-Mediated Protection against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model.

Ventilator-associated pneumonia is an important clinical manifestation of the nosocomial pathogen Pseudomonas aeruginosa. We characterized the correlates of protection with MEDI3902, a bispecific human IgG1 monoclonal antibody that targets the P. aeruginosa type 3 secretion system PcrV protein and the Psl exopolysaccharide, in a rabbit model of ventilator-associated pneumonia using lung-protective, low-tidal-volume mechanical ventilation. Rabbits infused with MEDI3902 prophylactically were protected, whereas those pretreated with irrelevant isotype-matched control IgG (c-IgG) succumbed between 12 and 44 h postinfection (100% survival [8/8 rabbits] versus 0% survival [8/8 rabbits]; P < 0.01 by log rank test). Lungs from rabbits pretreated with c-IgG, but not those pretreated with MEDI3902, had bilateral, multifocal areas of marked necrosis, hemorrhage, neutrophilic inflammatory infiltrate, and diffuse fibrinous edema in alveolar spaces. All rabbits pretreated with c-IgG developed worsening bacteremia that peaked at the time of death, whereas only 38% of rabbits pretreated with MEDI3902 (3/8 rabbits) developed such high-grade bacteremia (two-sided Fisher's exact test, P = 0.026). Biomarkers associated with acute respiratory distress syndrome were evaluated longitudinally in blood samples collected every 2 to 4 h to assess systemic pathophysiological changes in rabbits pretreated with MEDI3902 or c-IgG. Biomarkers were sharply increased or decreased in rabbits pretreated with c-IgG but not those pretreated with MEDI3902, including the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen of <300, hypercapnia or hypocapnia, severe lactic acidosis, leukopenia, and neutropenia. Cytokines and chemokines associated with acute respiratory distress syndrome were significantly downregulated in lungs from rabbits pretreated with MEDI3902, compared with c-IgG. These results suggest that MEDI3902 prophylaxis could have potential clinical utility for decreasing the severity of P. aeruginosa ventilator-associated pneumonia.

A 62-year-old man with stridor and dyspnoea.

Stridor is a sign of vital emergency that immediately orientates towards a laryngeal or tracheal obstruction. This case report focuses on the management of stridor, which comprises emergency securing of airways and parallel aetiological investigations. https://bit.ly/39CTjOg.

High-speed combined reflectance confocal and moxifloxacin based two-photon microscopy.

Reflectance confocal microscopy (RCM) is a non-invasive high-resolution optical imaging technique used in clinical settings as a diagnostic method. However, RCM has limited diagnostic ability by providing non-specific morphological information only based on reflection contrast. Various multimodal imaging techniques have been developed to compensate the limitations of RCM, but multimodal techniques are often slow in imaging speed compared to RCM alone. In this report, we combined RCM with moxifloxacin based two-photon microscopy (TPM) for high-speed multimodal imaging. Moxifloxacin based TPM used clinically compatible moxifloxacin for cell labeling and could do non-invasive cellular imaging at 30 frames/s together with RCM. Performance of the combined microscopy was characterized in the imaging of mouse skin and cornea, in vivo. Detail tissue microstructures including cells, extra-cellular matrix (ECM), and vasculature were visualized. The combined microscopy was applied to human skin cancer specimens, and both cells and ECM in the skin cancer and normal skin regions were visualized at high imaging speeds. The combined microscopy can be useful in the clinical applications of RCM by providing multiple contrasts.

Efficacy of Active Immunization With Attenuated α-Hemolysin and Panton-Valentine Leukocidin in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia.

Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all 3 toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus (MRSA). Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all 3 toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only α-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.

An uncommon therapeutic option for a challenging cause of pleural effusion.

Can you diagnose this challenging cause of pleural effusion? http://bit.ly/2VVwZv3.

Treatment Efficacy of MEDI3902 in Pseudomonas aeruginosa Bloodstream Infection and Acute Pneumonia Rabbit Models.

Pseudomonas aeruginosa is a challenge for clinicians due to increasing drug resistance and dwindling treatment options. We report on the activity of MEDI3902, an antibody targeting type 3 secretion protein PcrV and Psl exopolysaccharide, in rabbit bloodstream and lung infection models. MEDI3902 prophylaxis or treatment was protective in both acute models and exhibited enhanced activity when combined with a subtherapeutic dose of meropenem. These findings further support MEDI3902 for the prevention or treatment of serious P. aeruginosa infections.

MEDI3902 Correlates of Protection against Severe Pseudomonas aeruginosa Pneumonia in a Rabbit Acute Pneumonia Model.

Pseudomonas aeruginosa is among the most formidable antibiotic-resistant pathogens and is a leading cause of hospital-associated infections. With dwindling options for antibiotic-resistant infections, a new paradigm for treatment and disease resolution is required. MEDI3902, a bispecific antibody targeting the P. aeruginosa type III secretion (T3S) protein PcrV and Psl exopolysaccharide, was previously shown to mediate potent protective activity in murine infection models. With the current challenges associated with the clinical development of narrow-spectrum agents, robust preclinical efficacy data in multiple animal species are desirable. Here, we sought to develop a rabbit P. aeruginosa acute pneumonia model to further evaluate the activity of MEDI3902 intervention. In the rabbit model of acute pneumonia, prophylaxis with MEDI3902 exhibited potent dose-dependent protection, whereas those receiving control IgG developed fatal hemorrhagic necrotizing pneumonia between 12 and 54 h after infection. Blood biomarkers (e.g., partial pressure of oxygen [pO2], partial pressure of carbon dioxide [pCO2], base excess, lactate, and creatinine) were grossly deranged for the vast majority of control IgG-treated animals but remained within normal limits for MEDI3902-treated animals. In addition, MEDI3902-treated animals exhibited a profound reduction in P. aeruginosa organ burden and a marked reduction in the expression of proinflammatory mediators from lung tissue, which correlated with reduced lung histopathology. These results confirm that targeting PcrV and Psl via MEDI3902 is a promising candidate for immunotherapy against P. aeruginosa pneumonia.

Chemical constituents of Geum urbanum L. roots.

A new dehydrodigallic acid derivative (1), along with 19 known compounds, including 6 phenolic derivatives, 2 steroids and 11 triterpenoids were isolated from the ethanol extract of the root of Geum urbanum. Herein, there is the first report of steroid and triterpene in Geum urbanum. The purified metabolites were characterised by NMR spectroscopic and mass spectrometric analyses. The identification of the known compounds (2-20) was based on the comparison of their NMR spectroscopic features with previously published data. The structural characteristics of compound 1 were elucidated by comprehensive 1D and 2D NMR spectroscopic methods and acid hydrolysis.

Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia.

The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. Tedizolid phosphate was administered to rabbits at 6 mg/kg of body weight intravenously twice daily, which yielded values of the 24-h area under the concentration-time curve approximating those found in humans. The overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P = 0.66 by the log-rank test versus the results obtained with tedizolid phosphate). These survival rates were significantly greater than the survival rates of 17% for rabbits treated with 30 mg/kg vancomycin twice daily (P = 0.003) and 17% for rabbits treated with saline (P = 0.002). The bacterial count in the lungs of rabbits treated with tedizolid phosphate was significantly decreased compared to that in the lungs of rabbits treated with saline, although it was not significantly different from that in the lungs of rabbits treated with vancomycin or linezolid. The in vivo bacterial production of alpha-toxin and Panton-Valentine leukocidin, two key S. aureus-secreted toxins that play critical roles in the pathogenesis of necrotizing pneumonia, in the lungs of rabbits treated with tedizolid phosphate and linezolid was significantly inhibited compared to that in the lungs of rabbits treated with vancomycin or saline. Taken together, these results indicate that tedizolid phosphate is superior to vancomycin for the treatment of S. aureus necrotizing pneumonia because it inhibits the bacterial production of lung-damaging toxins at the site of infection.

Targeting Alpha Toxin To Mitigate Its Lethal Toxicity in Ferret and Rabbit Models of Staphylococcus aureus Necrotizing Pneumonia.

The role broad-spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on the healthy microbiome, has led to advances in pathogen-specific approaches for the prevention or treatment of serious bacterial infections. One approach in clinical testing is passive immunization with a monoclonal antibody (MAb) targeting alpha toxin for the prevention or treatment of Staphylococcus aureus pneumonia. Passive immunization with the human anti-alpha toxin MAb, MEDI4893*, has been shown to improve disease outcome in murine S. aureus pneumonia models. The species specificity of some S. aureus toxins necessitates testing anti-S. aureus therapeutics in alternate species. We developed a necrotizing pneumonia model in ferrets and utilized an existing rabbit pneumonia model to characterize MEDI4893* protective activity in species other than mice. MEDI4893* prophylaxis reduced disease severity in ferret and rabbit pneumonia models against both community-associated methicillin-resistant S. aureus (MRSA) and hospital-associated MRSA strains. In addition, adjunctive treatment of MEDI4893* with either vancomycin or linezolid provided enhanced protection in rabbits relative to the antibiotics alone. These results confirm that MEDI4893 is a promising candidate for immunotherapy against S. aureus pneumonia.

IVIG-mediated protection against necrotizing pneumonia caused by MRSA.

New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital-associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus.

Women's perspectives on termination service delivery in Vietnam: a cross-sectional survey in three provinces.

OBJECTIVE: To explore the perspectives of abortion service users regarding termination methods and abortion service delivery in Vietnam. MATERIALS AND METHODS: Structured exit interviews were conducted between August and November 2011 with women who underwent termination of pregnancy at 62 public health facilities in Hanoi, Khanh Hoa, and Ho Chi Minh City in Vietnam. All women presenting for termination during the study period were recruited to participate in the study. Following their abortion, women were asked about their perspectives on abortion service delivery and attributes of medical abortion (MA) versus manual vacuum aspiration (MVA). Multiple logistic regression was used to assess the association between current method uptake and each attribute. RESULTS: A total of 1,233 women were included in the survey: 541 (43.9%) from Hanoi, 163 (13.2%) from Khanh Hoa, and 529 (42.9%) from Ho Chi Minh: 23.1% underwent MA; 78.9% reported that women should be given a choice between MA and MVA; and 77.6% thought that abortion services were accessible. Among the 48% who responded, 30.1% thought that MA should be made available at primary/secondary health care facilities. Among women who had previously undergone both methods, women who reported that MA "feels more natural" (like a menstrual regulation/period) were more likely to choose MA for their current abortion (odds ratio 2.15, 95% confidence interval 1.26-3.69). CONCLUSION: MA uptake is significantly lower than MVA uptake. Further insights to women's perceptions of MA in Vietnam could help improve abortion service delivery in the country.

Attributes and perspectives of public providers related to provision of medical abortion at public health facilities in Vietnam: a cross-sectional study in three provinces.

BACKGROUND: The purpose of this study was to investigate attributes of public service providers associated with the provision of medical abortion in Vietnam. METHODS: We conducted a cross-sectional study via interviewer-administered questionnaire among abortion providers from public health facilities in Hanoi, Khanh Hoa, and Ho Chi Minh City in Vietnam between August 2011 and January 2012. We recruited abortion providers at all levels of Vietnam's public health service delivery system. Participants were questioned about their medical abortion provision practices and perspectives regarding abortion methods. RESULTS: A total of 905 providers from 62 health facilities were included, comprising 525 (58.0%) from Hanoi, 122 (13.5%) from Khanh Hoa, and 258 (28.5%) from Ho Chi Minh City. The majority of providers were female (96.7%), aged ≥25 years (94%), married (84.4%), and had at least one child (89%); 68.9% of providers offered only manual vacuum aspiration and 31.1% performed both medical abortion and manual vacuum aspiration. Those performing both methods included physicians (74.5%), midwives (21.7%), and nurses (3.9%). Unadjusted analyses showed that female providers (odds ratio 0.1; 95% confidence interval 0.01-0.30) and providers in rural settings (odds ratio 0.3; 95% confidence interval 0.08-0.79) were less likely to provide medical abortion than their counterparts. Obstetricians and gynecologists were more likely to provide medical abortion than providers with nursing/midwifery training (odds ratio 22.2; 95% confidence interval 3.81-129.41). The most frequently cited advantages of medical abortion for providers were that no surgical skills are required (61.7%) and client satisfaction is better (61.0%). CONCLUSION: Provision of medical abortion in Vietnam is lower than provision of manual vacuum aspiration. While the majority of abortion providers are female midwives in Vietnam, medical abortion provision is concentrated in urban settings among physicians. Individuals providing medical abortion found that the method yields high client satisfaction.

Risk factors for repeat abortion and implications for addressing unintended pregnancy in Vietnam.

OBJECTIVE: To determine predictors of repeat abortion in 3 provinces in Vietnam. METHODS: In a cross-sectional study between August and December 2011, women who underwent abortion were interviewed after the procedure in 62 public health facilities in Hanoi, Khanh Hoa, and Ho Chi Minh City (HCMC). Information on sociodemographic factors, contraceptive and reproductive history and intentions, and opinions and experience of abortion services was collected. The primary outcome was repeat (≥2) abortions. RESULTS: Overall, 1224 women were interviewed: 534 from Hanoi, 163 from Khanh Hoa, and 527 from HCMC. The mean age and parity of the respondents were 29 years and 1.8, respectively, and 79.6% were married. Approximately half of the respondents were not using contraception before pregnancy. The prevalence of repeat abortion was 31.7%. In multivariate models, significant predictors of repeat abortion included living in Hanoi, higher parity, age 35 years or older, and having 2 or more daughters (versus 1) or no sons (versus 1) after controlling for parity (all P < 0.05). CONCLUSION: Repeat abortion remains high in Vietnam, fueled partly by inadequate contraceptive use. Son preference seems to be an important predictor of repeat abortion. Strengthening post-abortion contraceptive counseling and promoting long-acting contraceptive methods are essential to reduce repeat abortion.

Service users' attributes associated with the uptake of medical versus surgical abortion at public health facilities in Vietnam.

OBJECTIVE: To investigate the attributes of service users associated with uptake of medical abortion (MA) versus manual vacuum aspiration (MVA) at public health facilities in Vietnam. METHODS: Structured exit interviews were conducted among women who underwent termination at 62 public health facilities in Hanoi, Khanh Hoa, and Ho Chi Minh City (HCMC) between August and December 2011. Data on sociodemographic, abortion-related, and service-related factors were compared between women who underwent MVA versus MA. RESULTS: Overall, 1233 women completed the study survey: 541 (43.9%) from Hanoi; 163 (13.2%) from Khanh Hoa; and 529 (42.9%) from HCMC. Almost one-quarter of women (23.1%) had chosen MA. After controlling for sociodemographic factors, women living in Khanh Hoa (odds ratio [OR], 13.4; 95% confidence interval [CI], 5.3-33.8) and HCMC (OR, 5.8; 95% CI, 2.1-15.9) were more likely to have undergone MA than women in Hanoi. Older women were less likely to have undergone MA (P < 0.05), and those who had previously heard of MA were twice as likely to have undergone MA (P = 0.020). CONCLUSION: Uptake of MA was lower than that of MVA and varied by province. Women in Vietnam will make their own judgment about which method to choose if they have prior knowledge of both.

Identifying potential therapeutic targets of methicillin-resistant Staphylococcus aureus through in vivo proteomic analysis.

BACKGROUND: Detailed knowledge on protein repertoire of a pathogen during host infection is needed for both developing a better understanding of the pathogenesis and defining potential therapeutic targets. Such data, however, have been missing for Staphylococcus aureus, a major human pathogen. METHODS: We determined the surface proteome of methicillin-resistant S. aureus (MRSA) clone usa300 derived directly from murine systemic infectiON. RESULTS: The majority of the in vivo-expressed surface-associated proteins were lipoproteins involved in nutrient acquisition, especially uptake of metal ions. Enzyme-linked immunosorbent assay (ELISA) of convalescent human serum samples revealed that proteins that were highly produced during murine experimental infection were also produced during natural human infection. We found that among the 7 highly abundant lipoproteins only MntC, which is the manganese-binding protein of the MntABC system, was essential for MRSA virulence during murine systemic infection. Moreover, we show that MntA and MntB are equally important for MRSA virulence. CONCLUSIONS: Besides providing experimental evidence that MntABC might be a potential therapeutic target for the development of antibiotics, our in vivo proteomics data will serve as a valuable basis for defining potential antigen combinations for multicomponent vaccines.

Knowledge and provision practices regarding medical abortion among public providers in Hanoi, Khanh Hoa, and Ho Chi Minh City, Vietnam.

OBJECTIVE: To assess public service providers' knowledge of medical abortion (MA) and practices, and perspectives on expanding the use of MA to primary and secondary health facilities in Vietnam. METHODS: A cross-sectional study was conducted via an interviewer-administered questionnaire among abortion providers (n=905) from public health facilities between August 2011 and January 2012. RESULTS: Overall, 31.1% of providers performed both surgical and medical abortions; 68.9% offered only surgical abortion. Providers were knowledgeable about the regimen/dosage of mifepristone plus misoprostol regimen; however, knowledge scores were low for gestational age limits for MA, adverse effects of the combined drug regimen, and safety and effectiveness of MA compared with surgical abortion. Knowledge scores were significantly lower among providers in rural areas than among those in urban settings. A large proportion of providers (82.9%) thought that MA should be expanded to primary and secondary health facilities. Perceived barriers to MA expansion included lack of knowledge and training, qualified staff, adequate drug supplies, equipment, or facilities, guidelines and protocols on MA, and patient awareness. CONCLUSION: Provision of MA in Vietnam was found to be disproportionate to surgical abortion provision and to vary by region. Knowledge of MA was moderate, but poorer among providers in rural settings.

Effects of linezolid on suppressing in vivo production of staphylococcal toxins and improving survival outcomes in a rabbit model of methicillin-resistant Staphylococcus aureus necrotizing pneumonia.

BACKGROUND: Linezolid is recommended for treatment of pneumonia and other invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). The premise underlying this recommendation is that linezolid inhibits in vivo production of potent staphylococcal exotoxins, including Panton-Valentine leukocidin (PVL) and α-hemolysin (Hla), although supporting evidence is lacking. METHODS: A rabbit model of necrotizing pneumonia using MRSA clone USA300 was used to compare therapeutic effects of linezolid (50 mg/kg 3 times/day) and vancomycin (30 mg/kg 2 times/day) administered 1.5, 4, and 9 hours after infection on host survival outcomes and in vivo bacterial toxin production. RESULTS: Mortality rates were 100% for untreated rabbits and 83%-100% for vancomycin-treated rabbits. In contrast, mortality rates were 25%, 50%, and 100% for rabbits treated with linezolid 1.5, 4, and 9 hours after infection, respectively. Compared with untreated and vancomycin-treated rabbits, improved survival of rabbits treated 1.5 hours after infection with linezolid was associated with a significant decrease in bacterial counts, suppressed bacterial production of PVL and Hla, and reduced production of the neutrophil-chemoattractant interleukin 8 in the lungs. CONCLUSIONS: Across the study interval, only early treatment with linezolid resulted in significant suppression of exotoxin synthesis and improved survival outcomes in a rabbit model of MRSA necrotizing pneumonia.

Multicentre studies of insecticide-treated durable wall lining in Africa and South-East Asia: entomological efficacy and household acceptability during one year of field use.

BACKGROUND: Indoor residual spraying (IRS) is a primary method of malaria vector control, but its potential impact is constrained by several inherent limitations: spraying must be repeated when insecticide residues decay, householders can tire of the annual imposition and campaign costs are recurrent. Durable lining (DL) can be considered an advanced form of long-lasting IRS where insecticide is gradually released from an aesthetically attractive wall lining material to provide vector control for several years. A multicentre trial was carried out in Equatorial Guinea, Ghana, Mali, South Africa and Vietnam to assess the feasibility, durability, bioefficacy and household acceptability of DL, compared to conventional IRS or insecticide-treated curtains (LLITCs), in a variety of operational settings. METHODS: This study was conducted in 220 households in traditional rural villages over 12-15 months. In all sites, rolls of DL were cut to fit house dimensions and fixed to interior wall surfaces (usually with nails and caps) by trained teams. Acceptability was assessed using a standardized questionnaire covering such topics as installation, exposure reactions, entomology, indoor environment, aesthetics and durability. Bioefficacy of interventions was evaluated using WHO cone bioassay tests at regular intervals throughout the year. RESULTS: The deltamethrin DL demonstrated little to no decline in bioefficacy over 12-15 months, supported by minimal loss of insecticide content. By contrast, IRS displayed a significant decrease in bioactivity by 6 months and full loss after 12 months. The majority of participants in DL households perceived reductions in mosquito density (93%) and biting (82%), but no changes in indoor temperature (83%). Among those households that wanted to retain the DL, 73% cited protective reasons, 20% expressed a desire to keep theirs for decoration and 7% valued both qualities equally. In Equatorial Guinea, when offered a choice of vector control product at the end of the trial (DL, IRS or LLITCs), DL consistently emerged as the most popular intervention regardless of the earlier household allocation. CONCLUSIONS: Just as long-lasting insecticidal nets overcame several of the technical and logistical constraints associated with conventionally treated nets and then went to scale, this study demonstrates the potential of DL to sustain user compliance and overcome the operational challenges associated with IRS.