The impact of economic recession on maternal and infant mortality: lessons from history.

BACKGROUND: The effect of the recent world recession on population health has featured heavily in recent international meetings. Maternal health is a particular concern given that many countries were already falling short of their MDG targets for 2015. METHODS: We utilise 20th century time series data from 14 high and middle income countries to investigate associations between previous economic recession and boom periods on maternal and infant outcomes (1936 to 2005). A first difference logarithmic model is used to investigate the association between short run fluctuations in GDP per capita (individual incomes) and changes in health outcomes. Separate models are estimated for four separate time periods. RESULTS: The results suggest a modest but significant association between maternal and infant mortality and economic growth for early periods (1936 to 1965) but not more recent periods. Individual country data display markedly different patterns of response to economic changes. Japan and Canada were vulnerable to economic shocks in the post war period. In contrast, mortality rates in countries such as the UK and Italy and particularly the US appear little affected by economic fluctuations. CONCLUSIONS: The data presented suggest that recessions do have a negative association with maternal and infant outcomes particularly in earlier stages of a country's development although the effects vary widely across different systems. Almost all of the 20 least wealthy countries have suffered a reduction of 10% or more in GDP per capita in at least one of the last five decades. The challenge for today's policy makers is the design and implementation of mechanisms that protect vulnerable populations from the effects of fluctuating national income.

The epidemiology of pregnancy outcomes in rural Burkina Faso.

OBJECTIVES: To describe levels and causes of pregnancy-related mortality and selected outcomes after pregnancy (OAP) in two districts of Burkina Faso. METHODS: A household census was conducted in the two study districts, recording household deaths to women aged 12-49 years from 2001 to 2006. Questions on pregnancy outcomes in the last 5 years for resident women of reproductive age were included, and an additional method - direct sisterhood - was added in part of the area. Adult female deaths were followed-up with verbal autopsies (VA) with household members. A probabilistic model for interpreting VA data (InterVA-M) was used to determine distributions of probable causes of death. An OAP survey was conducted among all women with an experience of pregnancy during the prior 12 months. It aimed to document physical and psychological disabilities, economic and social consequences and discomfort that women may suffer as a result of a pregnancy. RESULTS: The maternal mortality ratio (MMR) was 441 per 100 000 live births (95% CI: 397, 485), significantly higher in Diapaga [519 per 100 000 (95% CI: 454, 584)] than Ouargaye [353 per 100 000 (95% CI: 295, 411)]. MMRs were associated with wealth quintile, age and distance from a health facility. The causes of death showed higher than expected rates of sepsis (30%) and lower rates of haemorrhage (7%). A substantial proportion of all women had difficulty performing day-to-day tasks as a consequence of pregnancy. Women who had experienced stillbirths or Caesarean sections reported symptom-related indicators of poor physical health more frequently than women reporting uncomplicated deliveries, and were also more likely to be depressed. CONCLUSIONS: Expectations on the levels and causes of pregnancy-related mortality in Burkina Faso may need to be re-examined, and this could have programmatic implications; for example high levels of sepsis could prompt renewed efforts to reach women with skilled attendance at delivery and follow-up during the postpartum period. Further documentation of how complication-induced disabilities affect women and their families is needed. For mortality and morbidity outcomes, demonstrating variation between study districts is important to empower local decision makers with evidence of need at a subnational level.

Revealing the burden of maternal mortality: a probabilistic model for determining pregnancy-related causes of death from verbal autopsies.

BACKGROUND: Substantial reductions in maternal mortality are called for in Millennium Development Goal 5 (MDG-5), thus assuming that maternal mortality is measurable. A key difficulty is attributing causes of death for the many women who die unaided in developing countries. Verbal autopsy (VA) can elicit circumstances of death, but data need to be interpreted reliably and consistently to serve as global indicators. Recent developments in probabilistic modelling of VA interpretation are adapted and assessed here for the specific circumstances of pregnancy-related death. METHODS: A preliminary version of the InterVA-M probabilistic VA interpretation model was developed and refined with adult female VA data from several sources, and then assessed against 258 additional VA interviews from Burkina Faso. Likely causes of death produced by the model were compared with causes previously determined by local physicians. Distinction was made between free-text and closed-question data in the VA interviews, to assess the added value of free-text material on the model's output. RESULTS: Following rationalisation between the model and physician interpretations, cause-specific mortality fractions were broadly similar. Case-by-case agreement between the model and any of the reviewing physicians reached approximately 60%, rising to approximately 80% when cases with a discrepancy were reviewed by an additional physician. Cardiovascular disease and malaria showed the largest differences between the methods, and the attribution of infections related to pregnancy also varied. The model estimated 30% of deaths to be pregnancy-related, of which half were due to direct causes. Data derived from free-text made no appreciable difference. CONCLUSION: InterVA-M represents a potentially valuable new tool for measuring maternal mortality in an efficient, consistent and standardised way. Further development, refinement and validation are planned. It could become a routine tool in research and service settings where levels and changes in pregnancy-related deaths need to be measured, for example in assessing progress towards MDG-5.

The familial technique for linking maternal death with poverty.

BACKGROUND: Recognition of the synergy between health and poverty is now apparent in the development strategies of many low-income countries, and markers are needed to monitor progress towards poverty-relevant goals. Maternal mortality has been proposed as a possible candidate but evidence is lacking on the link with poverty at the level of individuals. We introduce a new approach to exploring the relation--the familial technique. METHODS: We used data from 11 household surveys in ten developing countries to create percentage distributions of women according to their poverty-related characteristics and survival status (alive, non-maternal death, maternal death). These women were identified as the sisters of the adult female respondents in the surveys, and were assigned the same poverty status as their respondent sibling. FINDINGS: The analysis showed significant associations, across a diverse set of countries, between women's poverty status (proxied by educational level, source of water, and type of toilet and floor) and survival. These associations indicated a gradient within and across the survival categories. With increasing poverty, the proportion of women dying of non-maternal causes generally increased, and the proportion dying of maternal causes increased consistently. Further analysis reported here for one of the countries--Indonesia, revealed that about 32-34% of the maternal deaths occurred among women from the poorest quintile of the population. The risk of maternal death in this country was around 3-4 times greater in the poorest than the richest group. INTERPRETATION: This new method makes efficient use of existing survey data to explore the relation between maternal mortality and poverty, and has wider potential for examining the poor-rich gap.

Patient preference in a randomized study comparing medical and surgical abortion at 10-13 weeks gestation.

The aim of this study was to assess women's preferences and acceptability of medical (MA) and surgical abortion (SA) at 10-13 weeks gestation. This was a partially randomized patient preference trial. Women were offered to enter the randomized arm of the trial. Those who expressed a strong preference for a method were entered into the preference arm. A total of 368 women were randomized (188 medical and 180 surgical) while 77 entered the preference arm (15 medical and 62 surgical). Prior to abortion, 253 women (72%) indicated a preference for MA while 98 (28%) showed a preference for surgery (p < .0001). Despite having a preference for a particular method, women were content with alternatives. Women were more likely to choose the same abortion method again if they had shown a preference for that method prior to abortion (p = .002 and .01 for MA and SA, respectively). The availability of MA is an important option for many women who wish to avoid surgery or anesthesia and should now be offered routinely in the late first trimester.

Do medical students want to learn about global health?

BACKGROUND: One objective of the United Nations Global Strategy for Women's and Children's Health relates to ensuring a sufficiently skilled workforce. To prepare future healthcare professionals for their role in the 21st century as members of this workforce, awareness of global health is essential, but few studies have explored student perspectives on such education. The main objectives of this study were to establish the views of medical students on learning about women's and children's health in low-income countries, to identify the nature and extent of learning already experienced, and to assess the demand for such learning. DESIGN: A questionnaire survey was conducted at three meetings of the International Federation of Medical Students Associations (IFMSA). Questionnaires were distributed to 500 participants from 75 countries and 336 medical schools, and 492 usable questionnaires were returned. Data were analysed using SPSS Version 20 and statistical analysis was undertaken using Fisher's exact test. RESULTS: There were 492 questionnaires included in the analysis. Forty-eight per cent of participants were from low-middle income countries and 52% were from high-income countries. Less than half (43%) of the respondents had received some teaching on women's and children's health in low-income countries. Teaching received was primarily (96%) through lectures in the second year of study. Ninety-one per cent of respondents thought such teaching would be important and stated that group work (66%) would be the preferred method. In total, only 14% thought they had received sufficient teaching on global health and on women's and children's health in low-income countries. CONCLUSIONS: This study has revealed a high demand among medical students for global health teaching, particularly on women's and children's health in low-income countries. The timing and methods of existing teaching on these topics does not match that desired by medical students. To help address this gap, a collaborative approach is proposed which includes students' views in the processes for revitalising medical curricula to meet the needs of the 21st century.

Incidence of adverse outcomes associated with gestational diabetes mellitus in low- and middle-income countries.

BACKGROUND: The contribution of medical conditions such as diabetes mellitus to maternal and neonatal ill-health in low- and middle-income countries is not well documented. OBJECTIVES: To ascertain the incidence of adverse outcomes associated with gestational diabetes mellitus (GDM) in these countries. SEARCH STRATEGY: Electronic databases were searched between 1990 and 2011. SELECTION CRITERIA: Observational, experimental, and quasi-experimental studies reporting adverse outcomes associated with GDM in mothers and their infants in low- and middle-income countries were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts were screened, and full-text articles were independently assessed by at least 2 reviewers. Characteristics of studies were tabulated and quality assessment performed. Median and interquartile range (IQR) were computed for each adverse outcome. MAIN RESULTS: 25 articles were included from an initial 1282 citations. High median incidences of cesarean (43.8%; IQR, 34.9%-65.9%), neonatal jaundice (17.1%; IQR, 8.5%-22.9%), and macrosomia (17.0%; IQR, 8.3%-32.5%) were reported in women with GDM. CONCLUSIONS: The high incidence of some complications of GDM is a concern and may indicate poorer care for women with GDM in low-resource settings. The wide IQRs found indicate uncertainty about the burden of GDM in these settings.

Lessons regarding the use of birth kits in low resource countries.

OBJECTIVE: To synthesise implementation lessons regarding birth kits in terms of the context, the user, requirements for use and the logistics of supplying kits. DESIGN: The scoping review was informed through a systematic literature review; a call for information distributed to experts in maternal and child health, relevant research centres and specialist libraries; a search of the web sites of groups working in the area of maternal and child health; and data extraction from DHS surveys. Data synthesis involved the production of a simple descriptive summary of the state of knowledge regarding birth kits. PARTICIPANTS: The 28 articles included in the review described a total of 21 birth kits used in 40 different countries and in many cases the kits were part of a package of interventions. FINDINGS: Although birth kits are available in more than 50 low resource countries, evidence regarding implementation is limited. Levels of birth kit use vary considerably (8-99%); with higher levels being reported where birth kits are distributed free as part of a research programme. Identifying the user of the birth kit was difficult in most reports and the evidence regarding training requirements for birth kit use was conflicting. Limited information exists regarding facilitators and barriers to birth kit use, and how birth kits fit within the wider service delivery of maternal and child health. CONCLUSION: Despite widespread use of birth kits, implementation lessons are hard to identify. The fact that birth kits are predominantly used in non-facility settings, and probably by non-skilled attendants, poses further challenges in synthesising the evidence. It would seem logical that government run programmes would increase utlisation rates; however in these countries national level data are not yet available. Such data are crucial to identifying how women obtain and use birth kits. The importance of context cannot be over emphasised, and better descriptive methods are needed to capture contextual factors that may impact on the implementation process. IMPLICATIONS FOR PRACTICE: Birth kits are a promising technology to achieve MDG 5, however further research is needed before making recommendations to scale up mother held birth kits or to expand kit contents.

Development of a proxy wealth index for women utilizing emergency obstetric care in Bangladesh.

There are increasing concerns regarding inequities in access to health care, and hence calls for routine data collection to improve monitoring. For many developing countries, such as Bangladesh, increasing the availability and uptake of emergency obstetric care (EmOC) is vital in improving maternal health. It is crucial, however, that women of all socio-economic status benefit from this. This paper describes the development and validation of a proxy wealth index for assessing women's socio-economic status in Bangladesh as they are admitted to hospital. Existing poverty assessment tools are unsuitable for use in this context as they are too lengthy or need to be administered at household or community level. We sought to develop a tool with a limited number of indicators to allow quick administration and avoid interference with treatment. We also aimed to develop a pragmatic tool to be able to calculate a score in the field. The steps, involving selecting and weighting indicators, assigning a proxy wealth score and validating the score, are outlined. Indicators were selected from the Bangladeshi Demographic and Health Survey (DHS) data, which allowed comparison of socio-economic status between women using EmOC and those in the wider population. The tool proved quick and easy to use and was acceptable to women and their families. The validity of the tool was established by means of factor analysis. Our comparison with DHS data suggested that women using EmOC were significantly wealthier than women in the wider population. The implications of this, as well as the strengths and limitations of the proxy wealth index, are discussed. The proxy wealth index offers potential as a pragmatic and quick means of assessing poverty status in a busy hospital setting. Such a tool may enable monitoring of equity in access to treatment and identification of those least able to afford treatment, to enable any mechanisms in place to pay for care to be applied in a timely fashion, so avoiding delays in treating life-threatening complications.

Evaluation of the delivery fee exemption policy in ghana: population estimates of changes in delivery service utilization in two regions.

SUMMARY OBJECTIVES: To determine changes in the proportion of deliveries at health facilities and the proportion attended by health professionals after delivery fee exemption implementation. DESIGN: Pre and post intervention implementation cluster-sampled household survey. SETTING: Central and Volta regions of Ghana. PARTICIPANTS: Women who had delivered in these regions during the fee exemption policy and an equivalent period of time prior to it. MAIN OUTCOME MEASURES: Place of delivery and person attending. RESULTS: After fee exemption implementation the likelihood of delivering in a health facility increased significantly in Central (OR 1.83, p<0.001) and Volta (OR 1.34, p<0.05) regions when accounting for the mothers' education and poverty levels and the clustered data. Results from Central Region showed increases in facility deliveries mainly occurred in health centres (from 13.7% to 22.3% of deliveries), and were attended by midwives (from 49.0% to 59.7%). There was evidence that after implementation some inequalities in the uptake of facility deliveries decreased. The greatest increase in the proportion of deliveries taking place in facilities occurred among women with the lowest levels of education (Central Region) and wealth (Volta Region). These changes reduced the differentials observed. CONCLUSIONS: After the implementation of fee exemption the proportion of deliveries in health facilities increased in both regions. Although changes cannot be directly attributed to delivery fee exemption, results demonstrating that the greatest increases in facility-based deliveries occurred among the poorest and least educated women are consistent with the expectation that the policy would particularly benefit women with the greatest financial barrier to health care and at the greatest risk of maternal mortality.

The effect of the national demonstration project Healthy Respect on teenage sexual health behaviour.

BACKGROUND: As part of the independent evaluation of Healthy Respect (a national demonstration project to improve teenage sexual health in Scotland) this study examined the effect of the school-based sexual health education intervention comprising multiprofessional classroom delivery and alongside drop-in clinics on teenage sexual behaviour outcomes. METHODS: Before-and-after cross-sectional surveys of secondary school pupils (average age 14 years and 6 months) were used in 10 Healthy Respect intervention schools in Lothian region and 5 comparison schools without intervention in Grampian region (2001 and 2003). RESULTS: By 2003, the proportion of pupils in Lothian feeling confident about getting condoms and using condoms properly significantly increased, more Lothian pupils (particularly boys) showed improved knowledge about condoms being protective against sexually transmitted infections. No further evidence of improved knowledge, attitudes, or intentions was evident after the intervention. Pupils in Lothian remained more likely to think using a condom would be embarrassing (especially girls), would reduce sexual enjoyment (especially boys), and intentions about condom use (as closer predictors of actual behaviour change) showed no significant improvement. More Lothian ( approximately 24%) than Grampian ( approximately 19%) pupils report having had sexual intercourse at age <16 years, both before and after the intervention, with no evidence of a significant reduction in Lothian by 2003. Overall differences in attitudes to condom use by gender were noted. Findings remain consistent in both unadjusted and adjusted comparisons. CONCLUSION: These findings demonstrate limited impact on sexual health behaviour outcomes, and raise questions about the likely and achievable sexual health gains for teenagers from school-based interventions.

A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs.

OBJECTIVE: To compare outpatient microwave endometrial ablation (MEA) in the postmenstrual phase to standard MEA treatment after drug preparation in a day case theatre environment. DESIGN: A randomised controlled trial. SETTING: A large United Kingdom teaching hospital. POPULATION: Two hundred and ten women complaining of excessive menstrual loss. METHODS: Two hundred and ten women with excessive menstrual loss were randomised. Ninety-seven women were treated as outpatients in the immediate post-menstrual phase and 100 were treated in an operating theatre after hormonal preparation. All procedures were commenced under local anaesthesia with or without conscious sedation. Analysis was by modified intention to treat. MAIN OUTCOME MEASURES: Primary outcome measures were satisfaction with treatment (measured at one year) and acceptability of treatment (measured at two weeks). Secondary outcome measures were menstrual outcome and financial cost. RESULTS: Significantly more women found treatment post-menses acceptable; 86 (89.5%) versus 76 (76.0%) [difference in proportions 13.6%, 95% CI (3.0%, 23.9%)]. Similar numbers in each arm were totally or generally satisfied with the treatment, 86 (92.5%) versus 84 (88.4%) [difference in proportions 4.1%, 95% CI (-4.7%, 12.9%)] while amenorrhoea rates at one year were comparable, 52 (55.9%) versus 60 (61.9%). [difference in proportions -5.9%, 95% CI (-19.8%, 7.6%)]. The mean health service costs were 124 pounds (95% CI 86-194 pounds) lower for the patients in the post-menses group. CONCLUSION: MEA performed under local anaesthesia (with or without conscious sedation) in the post-menstrual phase achieves high levels of satisfaction is very acceptable to patients and results in significantly reduced health service costs. Importantly menstrual outcomes are not affected by omission of drug preparation. There is now good evidence to support the use of MEA, without drug endometrial preparation, in the outpatient setting.

Psychological sequelae of medical and surgical abortion at 10-13 weeks gestation.

BACKGROUND: Although not much research comparing the emotional distress following medical and surgical abortion is available, few studies have compared psychological sequelae following both methods of abortion early in the first trimester of pregnancy. The aim of this review was to assess the psychological sequelae and emotional distress following medical and surgical abortion at 10-13 weeks gestation. METHODS: Partially randomized patient preference trial in a Scottish Teaching Hospital was conducted. The hospital anxiety and depression scales were used to assess emotional distress. Anxiety levels were also assessed using visual analog scales while semantic differential rating scales were used to measure self-esteem. A total of 368 women were randomized, while 77 entered the preference cohort. RESULTS: There were no significant differences in hospital anxiety and depression scales scores for anxiety or depression between the groups. Visual analog scales showed higher anxiety levels in women randomized to surgery prior to abortion (P < 0.0001), while women randomized to surgical treatment were less anxious after abortion (P < 0.0001). Semantic differential rating scores showed a fall in self-esteem in the randomized medical group compared to those undergoing surgery (P = 0.02). CONCLUSIONS: Medical abortion at 10-13 weeks is effective and does not increase psychological morbidity compared to surgical vacuum aspiration and hence should be made available to all women undergoing abortion at these gestations.

Regulation of expression of mas and fadD28, two genes involved in production of dimycocerosyl phthiocerol, a virulence factor of Mycobacterium tuberculosis.

Transcriptional regulation of genes involved in the biosynthesis of cell wall lipids of Mycobacterium tuberculosis is poorly understood. The gene encoding mycocerosic acid synthase (mas) and fadD28, an adjoining acyl coenzyme A synthase gene, involved in the production of a virulence factor, dimycocerosyl phthiocerol, were cloned from Mycobacterium bovis BCG, and their promoters were analyzed. The putative promoters were fused to the xylE reporter gene, and its expression was measured in Escherichia coli, Mycobacterium smegmatis, and M. bovis BCG. In E. coli, the fadD28 promoter was not functional but the mas promoter was functional. Both fadD28 and mas promoters were functional in M. smegmatis, at approximately two- and sixfold-higher levels, respectively, than the BCG hsp60 promoter. In M. bovis BCG, the fadD28 and mas promoters were functional at three- and fivefold-higher levels, respectively, than the hsp60 promoter. Primer extension analyses identified transcriptional start points 60 and 182 bp upstream of the translational start codons of fadD28 and mas, respectively. Both promoters contain sequences similar to the canonical -10 and -35 hexamers recognized by the sigma(70) subunit of RNA polymerase. Deletions of the upstream regions of both genes indicated that 324 bp of the fadD28 and 228 bp of the mas were essential for promoter activity. Further analysis of the mas promoter showed that a 213-bp region 581 bp upstream of the mas promoter acted as a putative transcriptional enhancer, promoting high-level expression of the mas gene when present in either direction. This represents the identification of a rare example of an enhancer-like element in mycobacteria.

Maternity satisfaction studies and their limitations: "What is, must still be best".

BACKGROUND: Health policymakers throughout the developed world are paying close attention to factors in maternity care that may influence women's satisfaction. This paper examines some of these factors in the light of observations from previous studies of satisfaction with health services. METHODS: The Scottish Birth Study, a cross-sectional questionnaire survey, sought the views of all women in Scotland delivering during a 10-day period in 1998. A total of 1,137 women completed and returned questionnaires (response rate = 69%). RESULTS: Women were overwhelmingly satisfied with their prenatal, intrapartum, and postnatal care. As is common in this type of study, reports of dissatisfaction were relatively low. However, differences occurred in satisfaction levels between subgroups; for example, the fewer the number of caregivers the woman had during childbirth, the more likely she was to be satisfied with the care received. A range of factors appeared to influence reported satisfaction levels, such as characteristics of the care provided and the woman's psychosocial circumstances. CONCLUSIONS: In addition to the inherent limitations of satisfaction studies found in the literature, problems may arise if such surveys are used uncritically to shape the future provision of maternity services, because service users tend to value the status quo over innovations of which they have no experience. Therefore, although satisfaction surveys have a role to play, we argue that they should only be used with caution, and preferably as part of an array of tools.

The creation of twin centile curves for size.

OBJECTIVE: To create twin centile charts for size. DESIGN: Retrospective study. SETTING: Aberdeen Maternity Hospital. METHODS: Ultrasound measurements of abdominal circumference (AC), biparietal diameter (BPD) and femur length (FL) for 1,011 twin pregnancies were extracted from a databank. The methodology is based on that described by Altman and Chitty [Br. J. Obstet. Gynaecol. 101 (1994) 29.]; only one measurement from each twin was used, polynomial regression models were fitted separately to the mean and standard deviation (SD) of the ultrasound parameter as functions of gestational age. The centiles were obtained assuming that at each gestation, the measurements had a normal distribution. RESULTS: The growth pattern of AC for twins appear to follow closely that of singletons until 32 weeks. Thereafter, there is a gradual but definite fall off in growth away from singleton standards. The pattern of growth of FL is largely similar to that of singletons. From mid to early third trimester, the BPD of twin babies was larger than that of singletons.

A randomized comparison of medical abortion and surgical vacuum aspiration at 10-13 weeks gestation.

BACKGROUND: Since 1991, mifepristone in combination with a prostaglandin analogue has been licensed for termination of pregnancy in the UK at up to 9 weeks amenorrhoea, and since 1995, beyond 13 weeks. Surgical methods are used almost exclusively at 10-13 weeks amenorrhoea. METHODS: A patient-centred, partially randomized, controlled trial was carried out. Those who expressed a strong preference for either medical (n = 15) or surgical (n = 62) abortion were allocated to that method. The remainder agreed to be randomized. The medical method (n = 188) was mifepristone 200 mg followed by misoprostol up to 3 doses, and surgery (n = 180) was by vacuum aspiration under general anaesthesia. Outcome measures included efficacy rates, medical complications within 8 weeks of the procedure, patient preferences and acceptability. RESULTS: Among women who underwent medical abortion, 5.4% required a second procedure compared with 2.1% who had surgery, although this difference was not statistically significant. Side effects experienced were higher in women who underwent medical abortion compared with those who underwent surgery. There were no significant differences in the rates of major complications up to 8 weeks. Prior to termination, 80% of women had a preference for a method, with 72% preferring medical and 28% preferring surgical abortion. Following abortion, 70% of those who underwent medical termination and 79% who underwent surgery would opt for the same method in the future. CONCLUSION: Medical abortion is safe and effective at 10-13 weeks gestation and should be considered an option for those women who wish to avoid surgery and anaesthesia.

Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells.

Infection with Helicobacter pylori, a Gram-negative, microaerophilic, flagellated bacteria that adheres to human gastric mucosa, is strongly associated with gastric ulcers and adenocarcinoma. The mechanisms through which gastric epithelial cells recognize this organism are unclear. In this study we evaluated the interactions between the Toll-like receptors (TLRs) and H. pylori-mediated NF-kappa B activation and the induction of chemokine mRNA expression. By reverse transcriptase-PCR we determined that MKN45 gastric epithelial cells express low but detectable amounts of TLR2, -4, and -5 but no MD-2. To determine which, if any, TLRs may play a role in the response of epithelial cells to H. pylori, HEK293 cells were cotransfected with the NF-kappa B-Luc reporter, CD14 and MD2 expression plasmids, and expression plasmids for TLR2, TLR4, or TLR5. Infection of the cultures with H. pylori (strain 26695) induced NF-kappa B activity in cells transfected with TLR2 and TLR5, but not TLR4. Consistent with the HEK293 experiments, H. pylori-induced NF-kappa B activation was decreased in MKN45 gastric epithelial cells by transfection of dominant-negative versions of TLR2 and TLR5 but not TLR4. Highly purified lipopolysaccharide from H. pylori strain 26695 activated NF-kappa B in HEK293 via TLR2 but not TLR4. Partially purified flagellin from H. pylori was also capable of inducing NF-kappa B activation in HEK cells transfected with TLR5. Additionally, chemokine gene expression was induced by H. pylori in HEK293 cells following stable transfection with TLR2 or TLR5 expression plasmids. These studies demonstrate that gastric epithelial cells recognize and respond to H. pylori infection at least in part via TLR2 and TLR5. Furthermore, the unique lipopolysaccharide of H. pylori is a TLR2, not a TLR4 agonist.