The WHO Maternal Near Miss Approach: Consequences at Malawian District Level

Introduction

WHO proposes a set of organ-failure based criteria for maternal near miss. Our objective was to evaluate what implementation of these criteria would mean for the analysis of a cohort of 386 women in Thyolo District, Malawi, who sustained severe acute maternal morbidity according to disease-based criteria.

Methods and Findings

A WHO Maternal Near Miss (MNM) Tool, created to compare disease-, intervention- and organ-failure based criteria for maternal near miss, was completed for each woman, based on a review of all available medical records. Using disease-based criteria developed for the local setting, 341 (88%) of the 386 women fulfilled the WHO disease-based criteria provided by the WHO MNM Tool, 179 (46%) fulfilled the intervention-based criteria, and only 85 (22%) the suggested organ-failure based criteria.

Conclusions

In this low-resource setting, application of these organ-failure based criteria that require relatively sophisticated laboratory and clinical monitoring underestimates the occurrence of maternal near miss. Therefore, these criteria and the suggested WHO approach may not be suited to compare maternal near miss across all settings.     

Development of an Electronic Medical Record Based Alert for Risk of HIV Treatment Failure in a Low-Resource Setting

Background

The adoption of electronic medical record systems in resource-limited settings can help clinicians monitor patients'' adherence to HIV antiretroviral therapy (ART) and identify patients at risk of future ART failure, allowing resources to be targeted to those most at risk.

Methods

Among adult patients enrolled on ART from 2005–2013 at two large, public-sector hospitals in Haiti, ART failure was assessed after 6–12 months on treatment, based on the World Health Organization''s immunologic and clinical criteria. We identified models for predicting ART failure based on ART adherence measures and other patient characteristics. We assessed performance of candidate models using area under the receiver operating curve, and validated results using a randomly-split data sample. The selected prediction model was used to generate a risk score, and its ability to differentiate ART failure risk over a 42-month follow-up period was tested using stratified Kaplan Meier survival curves.

Results

Among 923 patients with CD4 results available during the period 6–12 months after ART initiation, 196 (21.2%) met ART failure criteria. The pharmacy-based proportion of days covered (PDC) measure performed best among five possible ART adherence measures at predicting ART failure. Average PDC during the first 6 months on ART was 79.0% among cases of ART failure and 88.6% among cases of non-failure (p<0.01). When additional information including sex, baseline CD4, and duration of enrollment in HIV care prior to ART initiation were added to PDC, the risk score differentiated between those who did and did not meet failure criteria over 42 months following ART initiation.

Conclusions

Pharmacy data are most useful for new ART adherence alerts within iSanté. Such alerts offer potential to help clinicians identify patients at high risk of ART failure so that they can be targeted with adherence support interventions, before ART failure occurs.     

Performance of the 2007 WHO Algorithm to Diagnose Smear-Negative Pulmonary Tuberculosis in a HIV Prevalent Setting

Background

The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya.

Methods

PTB smear-negative adult suspects were included in a prospective diagnostic study (2009–2011). In addition, program data (2008–2009) were retrospectively analysed. At the first consultation, clinical examination, chest X-ray, and sputum culture (Thin-Layer-Agar and Lowenstein-Jensen) were performed. Patients not started on TB treatment were clinically re-assessed after antibiotic course. The algorithm performance was calculated using culture as reference standard.

Results

380 patients were included prospectively and 406 analyzed retrospectively. Culture was positive for MTB in 17.5% (61/348) and 21.8% (72/330) of cases. Sensitivity of the clinical-radiological algorithm was 55.0% and 31.9% in the prospective study and the program data analysis, respectively. Specificity, positive and negative predictive values were 72.9%, 29.7% and 88.6% in the prospective study and 79.8%, 30.7% and 80.8% in the program data analysis. Performing culture increased the number of confirmed TB patients started on treatment by 43.3% in the prospective study and by 44.4% in the program data analysis. Median time to treatment of confirmed TB patients was 6 days in the prospective study and 27 days in the retrospective study. Inter-reader agreement for X-ray interpretation between the study clinician and a radiologist was low (Kappa coefficient = 0.11, 95%CI: 0.09–0.12). In a multivariate logistic analysis, past TB history, number of symptoms and signs at the clinical exam were independently associated with risk of overtreatment.

Conclusion

The clinical-radiological algorithm is suboptimal to diagnose smear-negative PTB. Culture increases significantly the proportion of confirmed TB cases started on treatment. Better access to rapid MTB culture and development of new diagnostic tests is necessary.     

Appraisal of WHO Guidelines in Maternal Health Using the AGREE II Assessment Tool

In 2007, the World Health Organization (WHO) received a criticism for a lack of transparency and systematic methods in the development of guidelines, which were at that time perceived as substantially driven by expert opinion. In this paper we assessed the quality of maternal and perinatal health guidelines developed since then. We used the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool to evaluate the quality of methodological rigour and transparency of four different WHO guidelines published between 2007 and 2011. Our findings showed high scores among the most recent guidelines on maternal and perinatal health suggesting higher quality. However, there is still potential for improvement, especially in including different stakeholder views, transparency of guidelines regarding the role of the funding body and presentation of the guideline document.     

Population-Level Scale-Up of Cervical Cancer Prevention Services in a Low-Resource Setting: Development,Implementation, and Evaluation of the Cervical Cancer Prevention Program in Zambia

Background

Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries.

Methods

In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts.

Findings

Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25–49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women.

Interpretation

We creatively disrupted the ''no screening'' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps.     

The WHO Maternal Near-Miss Approach and the Maternal Severity Index Model (MSI): Tools for Assessing the Management of Severe Maternal Morbidity

Objectives

To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments.

Methods

In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity.

Results

Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56–114.6)). The maternal severity index (MSI) model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909–0.993)).

Conclusion

The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.     

Acceptability of Home-Assessment Post Medical Abortion and Medical Abortion in a Low-Resource Setting in Rajasthan,India. Secondary Outcome Analysis of a Non-Inferiority Randomized Controlled Trial

Background

Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education.

Objective

To investigate women’s acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India.

Design

Secondary outcome of a randomised, controlled, non-inferiority trial.

Setting

Outpatient primary health care clinics in rural and urban Rajasthan, India.

Population

Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin < 85mg/l and were below 18 years.

Methods

Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1:1) in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol), using opaque sealed envelopes. Blinding during outcome assessment was not possible.

Main Outcome Measures

Women’s acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups.

Results

731 women were randomized to the clinic follow-up group (n = 353) or home-assessment group (n = 378). 623 (85%) women were successfully followed up, of those 597 (96%) were satisfied and 592 (95%) found the abortion better or as expected, with no difference between study groups. The majority, 355 (57%) women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82%), in the home-assessment group preferred home-assessment in the future, as compared with 188 (70%) of women in the clinic follow-up group, who preferred clinic follow-up in the future (p < 0.001).

Conclusion

Home-assessment is highly acceptable among women in low-resource, and rural, settings. The choice to follow-up an early medical abortion according to women’s preference should be offered to foster women’s reproductive autonomy.

Trial Registration

ClinicalTrials.gov NCT01827995     

Familial Risk of Overweight and Obesity in the Canadian Population using the WHO/NIH Criteria

Objective: To determine the familial risk of overweight and obesity in Canada. Research Methods and Procedures: The sample was comprised of 15,245 participants from 6377 families of the Canada Fitness Survey. The risk of overweight and obesity among spouses and first‐degree relatives of individuals classified as underweight, normal weight, pre‐obese, or obese (Class I and II) according to the WHO/NIH guidelines for body mass index (BMI) was determined using standardized risk ratios. Results: Spouses and first‐degree relatives of underweight individuals have a lower risk of overweight and obesity than the general population. On the other hand, the risk of Class I and Class II obesity (BMI 35 to 39.9 kg/m²) in relatives of Class I obese (BMI 30 to 34.9 kg/m²) individuals was 1.84 (95% CI: 1.27, 2.37) and 1.97 (95% CI: 0.67, 3.25), respectively, in spouses, and 1.44 (95% CI:1.10, 1.78) and 2.05 (95% CI: 1.37, 2.73), respectively in first‐degree relatives. Further, the risk of Class II obesity in spouses and first‐degree relatives of Class II obese individuals was 2.59 (95% CI: ?0.91, 6.09) and 7.07 (95% CI: 1.48, 12.66) times the general population risk, respectively. Discussion: There is significant familial risk of overweight and obesity in the Canadian population using the BMI as an indicator. Comparison of risks among spouses and first‐degree relatives suggests that genetic factors may play a role in obesity at more extreme levels (Class II obese) more so than in moderate obesity.     

Case-Mix,Care Processes,and Outcomes in Medically-Ill Patients Receiving Mechanical Ventilation in a Low-Resource Setting from Southern India: A Prospective Clinical Case Series

Background

Mechanical ventilation is a resource intensive organ support treatment, and historical studies from low-resource settings had reported a high mortality. We aimed to study the outcomes in patients receiving mechanical ventilation in a contemporary low-resource setting.

Methods

We prospectively studied the characteristics and outcomes (disease-related, mechanical ventilation-related, and process of care-related) in 237 adults mechanically ventilated for a medical illness at a teaching hospital in southern India during February 2011 to August 2012. Vital status of patients discharged from hospital was ascertained on Day 90 or later.

Results

Mean age of the patients was 40 ± 17 years; 140 (51%) were men. Poisoning and envenomation accounted for 98 (41%) of 237 admissions. In total, 87 (37%) patients died in-hospital; 16 (7%) died after discharge; 115 (49%) were alive at 90-day assessment; and 19 (8%) were lost to follow-up. Weaning was attempted in 171 (72%) patients; most patients (78 of 99 [79%]) failing the first attempt could be weaned off. Prolonged mechanical ventilation was required in 20 (8%) patients. Adherence to head-end elevation and deep vein thrombosis prophylaxis were 164 (69%) and 147 (62%) respectively. Risk of nosocomial infections particularly ventilator-associated pneumonia was high (57.2 per 1,000 ventilator-days). Higher APACHE II score quartiles (adjusted HR [95% CI] quartile 2, 2.65 [1.19–5.89]; quartile 3, 2.98 [1.24–7.15]; quartile 4, 5.78 [2.45–13.60]), and new-onset organ failure (2.98 [1.94–4.56]) were independently associated with the risk of death. Patients with poisoning had higher risk of reintubation (43% vs. 20%; P = 0.001) and ventilator-associated pneumonia (75% vs. 53%; P = 0.001). But, their mortality was significantly lower compared to the rest (24% vs. 44%; P = 0.002).

Conclusions

The case-mix considerably differs from other settings. Mortality in this low-resource setting is similar to high-resource settings. But, further improvements in care processes and prevention of nosocomial infections are required.     

High-Resolution Microendoscopy for the Detection of Cervical Neoplasia in Low-Resource Settings

Cervical cancer is the second leading cause of cancer death among women in developing countries. Developing countries often lack infrastructure, cytotechnologists, and pathologists necessary to implement current screening tools. Due to their low cost and ease of interpretation at the point-of-care, optical imaging technologies may serve as an appropriate solution for cervical cancer screening in low resource settings. We have developed a high-resolution optical imaging system, the High Resolution Microendoscope (HRME), which can be used to interrogate clinically suspicious areas with subcellular spatial resolution, revealing changes in nuclear to cytoplasmic area ratio. In this pilot study carried out at the women''s clinic of Princess Marina Hospital in Botswana, 52 unique sites were imaged in 26 patients, and the results were compared to histopathology as a reference standard. Quantitative high resolution imaging achieved a sensitivity and specificity of 86% and 87%, respectively, in differentiating neoplastic (≥CIN 2) tissue from non-neoplastic tissue. These results suggest the potential promise of HRME to assist in the detection of cervical neoplasia in low-resource settings.     

Rapid Molecular Assays for the Detection of Yellow Fever Virus in Low-Resource Settings

Background

Yellow fever (YF) is an acute viral hemorrhagic disease transmitted by Aedes mosquitoes. The causative agent, the yellow fever virus (YFV), is found in tropical and subtropical areas of South America and Africa. Although a vaccine is available since the 1930s, YF still causes thousands of deaths and several outbreaks have recently occurred in Africa. Therefore, rapid and reliable diagnostic methods easy to perform in low-resources settings could have a major impact on early detection of outbreaks and implementation of appropriate response strategies such as vaccination and/or vector control.

Methodology

The aim of this study was to develop a YFV nucleic acid detection method applicable in outbreak investigations and surveillance studies in low-resource and field settings. The method should be simple, robust, rapid and reliable. Therefore, we adopted an isothermal approach and developed a recombinase polymerase amplification (RPA) assay which can be performed with a small portable instrument and easy-to-use lyophilized reagents. The assay was developed in three different formats (real-time with or without microfluidic semi-automated system and lateral-flow assay) to evaluate their application for different purposes. Analytical specificity and sensitivity were evaluated with a wide panel of viruses and serial dilutions of YFV RNA. Mosquito pools and spiked human plasma samples were also tested for assay validation. Finally, real-time RPA in portable format was tested under field conditions in Senegal.

Conclusion/Significance

The assay was able to detect 20 different YFV strains and demonstrated no cross-reactions with closely related viruses. The RPA assay proved to be a robust, portable method with a low detection limit (<21 genome equivalent copies per reaction) and rapid processing time (<20 min). Results from real-time RPA field testing were comparable to results obtained in the laboratory, thus confirming our method is suitable for YFV detection in low-resource settings.     

A Clinical Prediction Score in Addition to WHO Criteria for Anti-Retroviral Treatment Failure in Resource-Limited Settings - Experience from Lesotho

Objective

To assess the positive predictive value (PPV) of a clinical score for viral failure among patients fulfilling the WHO-criteria for anti-retroviral treatment (ART) failure in rural Lesotho.

Methods

Patients fulfilling clinical and/or immunological WHO failure-criteria were enrolled. The score includes the following predictors: Prior ART exposure (1 point), CD4-count below baseline (1), 25% and 50% drop from peak CD4-count (1 and 2), hemoglobin drop≥1 g/dL (1), CD4 count<100/µl after 12 months (1), new onset papular pruritic eruption (1), and adherence<95% (3). A nurse assessed the score the day blood was drawn for viral load (VL). Reported confidence intervals (CI) were calculated using Wilsons method.

Results

Among 1''131 patients on ART≥6 months, 134 (11.8%) had immunological and/or clinical failure, 104 (78%) had blood drawn (13 died, 10 lost to follow-up, 7 did not show up). From 92 (88%) a result could be obtained (2 samples hemolysed, 10 lost). Out of these 92 patients 47 (51%) had viral failure (≥5000 copies), 27 (29%) viral suppression (<40) and 18 (20%) intermediate viremia (40–4999). Overall, 20 (22%) had a score≥5. A score≥5 had a PPV of 100% to detect a VL>40 copies (95%CI: 84–100), and of 90% to detect a VL≥5000 copies (70–97). Within the score, adherence<95%, CD4-count<100/µl and papular pruritic eruption were the strongest single predictors. Among 47 patients failing, 8 (17%) died before or within 4 weeks after being switched. Overall mortality was 4 (20%) among those with score≥5 and 4 (5%) if score<5 (OR 4.3; 95%CI: 0.96–18.84, p = 0.057).

Conclusion

A score≥5 among patients fulfilling WHO-criteria had a PPV of 100% for a detectable VL and 90% for viral failure. In settings without regular access to VL-testing, this PPV may be considered high enough to switch this patient-group to second-line treatment without confirmatory VL-test.     

Miss Courtenay-Latimer on the Breeding of the Mountain Buzzard

[Breeding of the Mountain Buzzard ( Buteo oreophilus Hartert and Neumann). By Miss M. Courtenay-Latimer. 'Ostrich', Pretoria, Aug. 1941, pp. 20–23; 2 photos.]     

Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity

Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.     

Patterns and Outcomes of Induction of Labour in Africa and Asia: A Secondary Analysis of the WHO Global Survey on Maternal and Neonatal Health

Background

Labour induction should be performed where benefit outweighs potential harm, however epidemiology of induction in lower-income countries is not well described. We used the WHO Global Survey dataset to describe the epidemiology and outcomes of labour induction in 192,538 deliveries in 253 facilities across 16 countries in Africa and Asia.

Methods

Data was analyzed separately for Africa and Asia. Prevalence of indications, methods, success and characteristics associated with labour induction were determined. Multilevel logistic regression was used to determine the relationship between induction (with medical indication and elective) and maternal/perinatal outcomes.

Results

Induction accounted for 4.4% (Africa) and 12.1% (Asia) of deliveries. Oxytocin alone was the most common method (45.9% and 37.5%) and success rates were generally over 80%. Medically indicated inductions were associated with increased adjusted odds of Apgar <7 at 5 minutes, low birthweight, NICU admission and fresh stillbirth in both regions. The odds of caesarean section in Africa were reduced (Adj OR 0.61, 95%CI 0.42–0.88). Elective induction was associated with increased adjusted odds of NICU (Africa) and ICU (Asia) admissions.

Discussion

Induction was generally less common than in higher-income countries. Prostaglandin use was uncommon despite evidence supporting use. Induction for medical indications may be associated with poorer outcomes due to maternal baseline risks. Despite one-third of elective inductions occurring at <39 weeks, the risk of maternal, fetal and neonatal mortality was not elevated following elective inductions.     

Cost-Benefit Analysis in a Regulatory Setting

The purpose of requiring cost-benefit analysis is to produce better out-comes from regulatory processes. If implemented well, cost-benefit analysis and risk assessment can produce improvements at several levels, by encouraging regulators to consider unintended effects of regulations and thereby avoid making things worse, to find the least burdensome approach to a goal, and to balance the pluses and minuses involved in choosing a goal. Whether these improvements will occur depends in large part on how cost-benefit analysis is implemented. Guidelines for conducting cost-benefit analysis and procedures for considering evidence on costs and benefits play an important role. This article describes how guidelines and rules of process can affect outcomes, and the issues that cost-benefit guidelines need to cover. Guidelines can affect the bias of a regulatory process toward one set of stakeholders or another, make outcomes more predictable, define the information needed for decisions, and provide a basis for legal challenges. The questions that guidelines should address include: what are costs and benefits, what constitutes good economics, what are standards of proof, how should unquantified costs and benefits be treated, how should uncertainties of cost-benefit estimates be dealt with, and how should alternatives be generated? The article concludes with recommen dations about how the adoption of cost-benefit analysis can be made most effective and beneficial in regulatory processes.     

Setting SNAREs in a different wood

Vesicle traffic is essential for cell homeostasis, growth and development in plants, as it is in other eukaryotes, and is facilitated by a superfamily of proteins known as soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs). Although SNAREs are well-conserved across phylla, genomic analysis for two model angiosperm species available to date, rice and Arabidopsis, highlights common patterns of divergence from other eukaryotes. These patterns are associated with the expansion of some gene subfamilies of SNAREs, the absence of others and the appearance of new proteins that show no significant homologies to SNAREs of mammals, yeast or Drosophila. Recent findings indicate that the functions of these plant SNAREs also extend beyond the conventional 'housekeeping' activities associated with vesicle trafficking. A number of SNAREs have been implicated in environmental responses as diverse as stomata movements and gravisensing as well as sensitivity to salt and drought. These proteins are essential for signal transduction and response and, in most cases, appear also to maintain additional roles in membrane trafficking. One common theme to this added functionality lies in control of non-SNARE proteins, notably ion channels. Other examples include interactions between the SNAREs and scaffolding or other structural components within the plant cell.