bluuebunny/crossref_metadata_2025 huggingface dataset:
The Plant-Specific SR45 Protein Negatively Regulates Glucose and ABA Signaling during Early Seedling Development in Arabidopsis
Authors: Carvalho Raquel Fonseca , Carvalho Sofia Domingues , Duque Paula
Published: August 2010

The plant-specific SR45 belongs to the highly conserved family of serine/arginine-rich (SR) proteins, which play key roles in precursor-mRNA splicing and other aspects of RNA metabolism. An Arabidopsis (Arabidopsis thaliana) loss-of-function mutant, sr45-1, displays pleiotropic phenotypes, such as defects in flower and leaf morphology, root growth, and flowering time. Here, we show that the sr45-1 mutation confers hypersensitivity to glucose (Glc) during early seedling growth in Arabidopsis. Unlike wild-type plants, the sr45-1 mutant displays impaired cotyledon greening and expansion as well as reduced hypocotyl elongation of dark-grown seedlings when grown in the presence of low (3%) Glc concentrations. In addition, SR45 is involved in the control of Glc-responsive gene expression, as the mutant displays enhanced repression of photosynthetic and nitrogen metabolism genes and overinduction of starch and anthocyanin biosynthesis genes. Like many other sugar response mutants, sr45-1 also shows hypersensitivity to abscisic acid (ABA) but appears to be unaffected in ethylene signaling. Importantly, the sr45-1 mutant shows enhanced ability to accumulate ABA in response to Glc, and the ABA biosynthesis inhibitor fluridone partially rescues the sugar-mediated growth arrest. Moreover, three ABA biosynthesis genes and two key ABA signaling genes, ABI3 and ABI5, are markedly overinduced by Glc in sr45-1. These results provide evidence that the SR45 protein defines a novel player in plant sugar response that negatively regulates Glc signaling during early seedling development by down-regulating both Glc-specific ABA accumulation and ABA biosynthesis and signaling gene expression.
Evidence That High Activity of Vacuolar Invertase Is Required for Cotton Fiber and Arabidopsis Root Elongation through Osmotic Dependent and Independent Pathways, Respectively
Authors: Wang Lu , Li Xiao-Rong , Lian Heng , Ni Di-An , He Yu-ke , Chen Xiao-Ya , Ruan Yong-Ling
Published: August 2010

Vacuolar invertase (VIN) has long been considered as a major player in cell expansion. However, direct evidence for this view is lacking due, in part, to the complexity of multicellular plant tissues. Here, we used cotton (Gossypium spp.) fibers, fast-growing single-celled seed trichomes, to address this issue. VIN activity in elongating fibers was approximately 4-6-fold higher than that in leaves, stems, and roots. It was undetectable in fiberless cotton seed epidermis but became evident in initiating fibers and remained high during their fast elongation and dropped when elongation slowed. Furthermore, a genotype with faster fiber elongation had significantly higher fiber VIN activity and hexose levels than a slow-elongating genotype. By contrast, cell wall or cytoplasmic invertase activities did not show correlation with fiber elongation. To unravel the molecular basis of VIN-mediated fiber elongation, we cloned GhVIN1, which displayed VIN sequence features and localized to the vacuole. Once introduced to Arabidopsis (Arabidopsis thaliana), GhVIN1 complemented the short-root phenotype of a VIN T-DNA mutant and enhanced the elongation of root cells in the wild type. This demonstrates that GhVIN1 functions as VIN in vivo. In cotton fiber, GhVIN1 expression level matched closely with VIN activity and fiber elongation rate. Indeed, transformation of cotton fiber with GhVIN1 RNA interference or overexpression constructs reduced or enhanced fiber elongation, respectively. Together, these analyses provide evidence on the role of VIN in cotton fiber elongation mediated by GhVIN1. Based on the relative contributions of sugars to sap osmolality in cotton fiber and Arabidopsis root, we conclude that VIN regulates their elongation in an osmotic dependent and independent manner, respectively.
Finite Element Model of Polar Growth in Pollen Tubes
Authors: Fayant Pierre , Girlanda Orlando , Chebli Youssef , Aubin Carl-Éric , Villemure Isabelle , Geitmann Anja
Published: August 2010

Cellular protuberance formation in walled cells requires the local deformation of the wall and its polar expansion. In many cells, protuberance elongation proceeds by tip growth, a growth mechanism shared by pollen tubes, root hairs, and fungal hyphae. We established a biomechanical model of tip growth in walled cells using the finite element technique. We aimed to identify the requirements for spatial distribution of mechanical properties in the cell wall that would allow the generation of cellular shapes that agree with experimental observations. We based our structural model on the parameterized description of a tip-growing cell that allows the manipulation of cell size, shape, cell wall thickness, and local mechanical properties. The mechanical load was applied in the form of hydrostatic pressure. We used two validation methods to compare different simulations based on cellular shape and the displacement of surface markers. We compared the resulting optimal distribution of cell mechanical properties with the spatial distribution of biochemical cell wall components in pollen tubes and found remarkable agreement between the gradient in mechanical properties and the distribution of deesterified pectin. Use of the finite element method for the modeling of nonuniform growth events in walled cells opens future perspectives for its application to complex cellular morphogenesis in plants.
Network Analysis of Enzyme Activities and Metabolite Levels and Their Relationship to Biomass in a Large Panel ofArabidopsisAccessions
Authors: Sulpice Ronan , Trenkamp Sandra , Steinfath Matthias , Usadel Bjorn , Gibon Yves , Witucka-Wall Hanna , Pyl Eva-Theresa , Tschoep Hendrik , Steinhauser Marie Caroline , Guenther Manuela , Hoehne Melanie , Rohwer Johann M. , Altmann Thomas , Fernie Alisdair R. , Stitt Mark
Published: August 2010

Natural genetic diversity provides a powerful resource to investigate how networks respond to multiple simultaneous changes. In this work, we profile maximum catalytic activities of 37 enzymes from central metabolism and generate a matrix to investigate species-wide connectivity between metabolites, enzymes, and biomass. Most enzyme activities change in a highly coordinated manner, especially those in the Calvin-Benson cycle. Metabolites show coordinated changes in defined sectors of metabolism. Little connectivity was observed between maximum enzyme activities and metabolites, even after applying multivariate analysis methods. Measurements of posttranscriptional regulation will be required to relate these two functional levels. Individual enzyme activities correlate only weakly with biomass. However, when they are used to estimate protein abundances, and the latter are summed and expressed as a fraction of total protein, a significant positive correlation to biomass is observed. The correlation is additive to that obtained between starch and biomass. Thus, biomass is predicted by two independent integrative metabolic biomarkers: preferential investment in photosynthetic machinery and optimization of carbon use.
Continuous Characterization of the Planform Geometry and Curvature of Meandering Rivers
Authors: Güneralp İnci , Rhoads Bruce L.
Published: August 2010

The complex feedback between process and form that governs planform migration of meandering rivers is still incompletely understood. Current theoretical models aimed at predicting planform migration relate the rate of meander migration at a particular location to the channel curvature at and upstream of that location. However, these models are still incapable of reproducing complex forms of bend development, such as compound loops. Evaluation of such models requires a representation of planform curvature better than that provided by traditional methods where the curvature is calculated from directional change between the successive digitized points—an approach that provides a discrete representation of curvature dependent on the density of the digitized points used to characterize the channel planform. This article presents and evaluates a methodology that provides a continuous functional representation of the planform geometry and curvature of meandering rivers. The method involves the fitting of splines, specifically parametric cubic splines (PCSs), to discrete digitization data of the channel centerline (CL) and the arc‐length parameterization of the resulting composite curve. The arc‐length parameterized PCS‐interpolated curve is then used to compute analytically the channel CL location and curvature for any value of the streamwise axis. Evaluation of the method involves examination of the effects of digitization interval size and digitization error on the characterization of the planform geometry and curvature using PCS fitting. The derivation of curvature values from continuous planform function for any location and any spatial interval overcomes the reliance either on average bend curvature values or on discrete curvature values based on digitized points.
Computational Analysis of an Axial Flow Pediatric Ventricular Assist Device
Authors: Throckmorton Amy L. , Untaroiu Alexandrina , Allaire Paul E. , Wood Houston G. , Matherne Gaynell Paul , Lim David Scott , Peeler Ben B. , Olsen Don B.
Published: August 2010

Abstract: Longer‐term (>2 weeks) mechanical circulatory support will provide an improved quality of life for thousands of pediatric cardiac failure patients per year in the United States. These pediatric patients suffer from severe congenital or acquired heart disease complicated by congestive heart failure. There are currently very few mechanical circulatory support systems available in the United States as viable options for this population. For that reason, we have designed an axial flow pediatric ventricular assist device (PVAD) with an impeller that is fully suspended by magnetic bearings. As a geometrically similar, smaller scaled version of our axial flow pump for the adult population, the PVAD has a design point of 1.5 L/min at 65 mm Hg to meet the full physiologic needs of pediatric patients. Conventional axial pump design equations and a nondimensional scaling technique were used to estimate the PVAD's initial dimensions, which allowed for the creation of computational models for performance analysis. A computational fluid dynamic analysis of the axial flow PVAD, which measures approximately 65 mm in length by 35 mm in diameter, shows that the pump will produce 1.5 L/min at 65 mm Hg for 8000 rpm. Fluid forces (∼1 N) were also determined for the suspension and motor design, and scalar stress values remained below 350 Pa with maximum particle residence times of approximately 0.08 milliseconds in the pump. This initial design demonstrated acceptable performance, thereby encouraging prototype manufacturing for  experimental  validation.
Some Observations on the Wound Reactions of Ankyropteris corrugata
Authors: Holden H. S.
Published: August 2010

The tissues of the fossil fern Ankyropteris corrugata show well-marked reactions to wounding. In the root these, which consist of irregularly disposed wedges of meristematic tissue, are confined to the cortical parenchyma and may extend for some distance beyond the actual wound area. In the stem the wounds generally take the form of irregular cortical fissures. These are bordered on either side by a strip of meristem four to eight cells in depth. Anomalous secondary xylem which occurs in a stem in the neighbourhood of a bifurcation is also considered to be due probably to traumatic stimulus. In the petiole the wound reaction varies. Where the wound is superficial a pad of healing meristem is developed from the cortical cells. The parenchymatous cells are most active, but the sclerenchymatous cells may also undergo division. Exceptionally the superficial cells may be modified in a similar way to those of the normal epidermis, thus providing an example of “restitution.” Other wounds, termed “crush” wounds, are characterised by irregular cortical fissures. These become bordered or surrounded by a strip of meristematic cambiform cells. Where the wounds are deep-seated the vascular tissues may be involved in the reaction. The reaction in such cases takes the form of the development of secondary tracheids, usually short and of small calibre, which vary in position with that of the wound. There is some evidence that the phloem or phloem-parenchyma may also become meristematic under these conditions.

I am much indebted to Dr. D. H. Scott, F.R.S., for his kindly interest during this investigation. Acknowledgments are also due to the Keeper of the Department of Geology, British Museum (Natural History), and to Prof. M. Drummond of Glasgow University for facilities for studying the fossil plants in their respective departments.

The expenses incurred in this study have been met in part by a grant from the Royal Society.
A survey of bancroftian filariasis among South‐East Asian expatriate workers in Saudi Arabia
Authors: Omar Mohamed S.
Published: August 2010

In a survey of bancroftian filariasis among expatriate workers from five South‐East Asian countries (India, Bangladesh, Sri Lanka, Thailand and the Philippines) where human filariasis is endemic, 762 individuals were examined in the Abha area (Asir) of south‐western Saudi Arabia. A prevalence of microfilaraemia of 3.5% and a mean mf density of 6.0/20 mm3of blood was found among 259 Indian males only. In three out of 9 microfilaraemic cases, clinical signs suggestive of filariasis were observed. The only species identified was Wuchereria bancrofti showing strict nocturnal periodicity. Preliminary laboratory studies on the susceptibility of local mosquitoes to infection with W. bancrofti in which laboratory‐bred Culex (C.) pipiens was fed directly on a microfilaraemic volunteer from Madras, South India, revealed that this species was highly susceptible to the Madras strain of the parasite with an average infection rate of 57 (range 41–75)% and a worm burden of 3.5 L3/infective mosquito. This is the first report that local Cx. pipiens mosquitoes may act as a potential vector of introduced bancroftian filariasis in Saudi Arabia. The potential danger of bancroftian filariasis importation and, more importantly, the establishment of new self‐sustained foci of the disease is likely to depend upon the abundance of mf carriers and density of vector mosquitoes feeding on carriers.
Clinical investigation of a population recently infected with Schistosoma mansoni (Richard‐Toll, Senegal)
Authors: Kongs A. , Verlé P. , Dieng A. , Talla I. , Rouquet Ph.
Published: August 2010

Following the introduction of large‐scale irrigation, an exceptional epidemic of intestinal schistosomiasis occurred in northern Senegal when a non‐immune population was exposed to massive infection. Subjects infected with Schistosoma mansoni were followed up parasitologically and clinically from the onset of the epidemic. After the initial evaluation, patients received a health education session and were treated with praziquantel in a dose of 30 mg/kg.

One year after this treatment, S. mansoni eggs were found in the stools of 227/301 subjects (75%). Twenty‐three per cent of subjects excreted >400 eggs per gram (e.p.g.) and 11% excreted >1000 e.p.g. of faeces. Overall, the geometric mean was 191 e.p.g. of faeces in infected individuals. The prevalence of diarrhoea was reduced from 55 to 29%, the prevalence of bloody diarrhoea from 44 to 11% and the prevalence of abdominal discomfort from 66 to 41%. No hepatomegaly was found in these patients either before or one year after treatment. Splenomegaly was reduced from 30% (measured by ultrasound) to 3% (on clinical examination). Morbidity associated with S. mansoni infection was considerably reduced one year after treatment with praziquantel (30 mg/kg).
Parasite‐specific lactate dehydrogenase for the diagnosis of Plasmodium falciparum infection in an endemic area in West Uganda
Authors: Jelinek T. , Kilian A. H. D. , Henk M. , Mughusu E. B. , Nothdurft H. D. , Löscher T. , Knobloch J. , Sonnenburg F. v.
Published: August 2010

The measurement of parasite lactate dehydrogenase (pLDH) has been presented as an easy and rapid method for the diagnosis of malaria in humans. In order to evaluate the sensitivity and specificity of such a test we examined blood samples from 429 Ugandan patients. While pLDH activity was significantly linked to parasitaemia, sensitivity and specificity were found to be rather low at 58.8 and 62.2% respectively. The positive and negative predictive values failed to meet necessary standards. We conclude that the methods of measurement of pLDH activity in malaria infection, although potentially useful for the fast diagnosis of malaria, need to be improved to be of true value in endemic areas.
Necrotizing and suppurative lymphadenitis in Leishmania major infections
Authors: Gaafar A. , Ismail A. , Kadaro A. Y. El , Hashim Elsir , Khalil E. A. G. , Hassan A. M. El
Published: August 2010

The pathology of lymph nodes and subcutaneous nodules in 6 patients with cutaneous leishmaniasis (Oriental sore) due to Leishmania major is described in this paper. In 3 patients enlarged epitrochlear lymph nodes were found to be associated with primary skin lesions in the forearm. The lymph node in one patient showed a necrotizing granulomatous reaction that simulated tuberculous lymphadenitis. Leishmania parasites were, however, found in sections of the node, and staining for mycobacteria was negative. The second patient presented with an abscess and a discharging sinus in the epitrochlear region. Parasites were found in smears of the pus and cultures for bacteria were negative. The lesion healed with antimonial therapy. In the third patient the lesion resembled cat‐scratch disease and showed stellate abscesses and granulomas. Leishmania parasites were also identified in the sections. Sections of a subcutaneous nodule from the fourth patient showed a necrotizing granuloma. The lesion healed spontaneously and the patient became leishmanin‐positive. In two other patients fine needle aspiration of the subcutaneous nodules showed parasites, granuloma and necrosis.

We concluded that L. major disseminates from the primary cutaneous lesion via the lymphatics to the subcutaneous tissues and the regional lymph nodes. The subcutaneous nodules and lymphadenopathy may persist long after the primary lesion had healed. The primary lesion is sometimes inconspicuous. Necrotizing and suppurative lymphadenitis due to L. major have to be distinguished from other causes of necrosis and suppuration such as tuberculosis and cat‐scratch disease.
Promoting operational research on insecticide‐treated netting: a joint TDR/IDRC initiative and call for research proposals
Authors: Lengeler C. , Lines J. D. , Cattani J. , Feilden R. , Zimicki S. , de Savigny D.
Published: August 2010

The evidence in favour of insecticide‐treated nets for reducing mortality from malaria among Africa children is becoming compelling. In order to support the next step in the development of this promising intervention the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and the International Development Research Centre (IDRC) decided to launch a joint initiative on operational research. In the first step, 3 reviews on the essential aspects of net technology, programme implementation and programme promotion were commissioned and will be published soon as a book. Secondly, expert opinion was sought regarding priority topics for research. Finally, a first round of research projects was funded and a call for more proposals is being widely advertised.
Immunohistological studies on an Onchocerca volvulus ankyrin (EI)
Authors: Erttmann K. D. , Gallin M. Y. , Eggert P. , Büttner D. W.
Published: August 2010

The distribution of an Onchocerca volvulus ankyrin, designated EI, was studied in different O. volvulus stages and other helminths by immunohistochemistry using rabbit antibodies raised against the recombinant EI protein.

In adult O. volvulus the protein designated EI was localized to the extracellular clefts as well as to the cytoplasm adjacent to the cell membrane in the area of the basal labyrinth in hypodermis, intestine and uterus and to a lesser extent in oviduct and vas deferens. Neuronal cell bodies were also labelled. No labelling of the basal laminae, muscles or epithelia of ovary or testis was observed. Detection of the Ei protein was associated with embryonic development. Germ cells and early morulae showed no reaction; labelling was first seen in late morulae, corresponding to the stage of gastrulation, and increased in the following embryonic stages. In microfilariae the nerve ring and the cephalic space, which represents the anterior nerve‐enriched portion of the body, were labelled. In third‐stage larvae of O. volvulus labelling was associated with the hypodermis, and in those of Anisakis sp. the cytoplasm adjacent to the membrane of the excretory gland cell and the basal labyrinth of the hypodermis were labelled. Following anthelminthic treatment a disruption of the labelling pattern of the EI protein was observed in adult O. volvulus with leakage of the protein into neighbouring areas. Damage to the worm was associated with reduction and finally loss of EI protein labelling. No EI protein was detected in dead adult worms, embryos or microfilariae. Labelling of the same organs was observed in 8 other Onchocerca species and in several other nematodes, but no reaction was seen in trematodes. The results indicate that the EI protein is associated with neuronal structures of O. volvulus, that its presence is developmentally regulated and that it has cross‐reactive homologues in other nematodes. The results suggest that EI is a functional protein. It may be useful for the assessment of parasite damage and death as well as in the characterization of the filarial nervous system.
A coverage plan for health centres in Murewa District in Zimbabwe: an example of action research
Authors: Criel B. , Macq J. , Bossyns P. , Hongoro Ch.
Published: August 2010

Good access to health facilities providing good first‐level health care remains problematic in many developing countries. It is a hindrance to effective and efficient functioning of the hospital, as outpatient departments become overcrowded with patients from areas without health centres. In many cases the quality of care delivered to these patients is poor because within the district health system the hospital is not the best place for the supply of comprehensive, integrated and continuous care. Eventually, high hospital involvement in first‐level care can jeopardize the delivery of adequate referral care for those patients who desperately need the hospital's technology and expertise.

This paper provides an account of the way this problem was investigated and managed by the district health management team in the Murewa district in north‐east Zimbabwe. The design of a comprehensive ‘master plan’ or ‘coverage plan’ is presented as well as the problems and difficulties encountered. The Murewa experience highlights the relevance of a coverage plan for rational and coherent health infrastructure planning at district level. The approach followed by the Murewa team illustrates the use of action research as an integral part of the management of district health systems.
Prevalence of iodine deficiency disorders and goitre in Chad
Authors: Wyss K. , Guiral C. , Ndikuyeze A. , Malonga G. , Tanner M.
Published: August 2010

A nationwide sample survey was conducted in Chad to establish the prevalence of iodine deficiency disorders (IDD). The country was stratified into the Sahel zone and the Sudan zone, the latter including the city of N'Djamena. The analysis followed a stratification whereby the city of N'Djamena was also separately analysed. A total of 1171 people between 10 and 20 years of age were included in the survey. The overall weighted prevalence of goitre, evaluated by a clinical examination, was 63%. In the Sudan zone the prevalence was 70%, in the Sahel zone 64% and for the capital, N'Djamena, 25%. There were significant differences in the frequency of goitre between the three zones. Females ‐ as established in surveys from other areas and countries—had goitre significantly more often. The prevalence of cretinism varied between o and 1.2%, and was highest in the Sahel zone.

Amongst the sampled population of the Sudan zone, 33% had less than 20 μg/l of urinary iodine, indicating severe iodine deficiency. In the Sahel zone and in N'Djamena the figures reached 8 and 1%. There were high levels of thiocyanate anions in urine reaching medians between 21 and 27 mg/l in the geographical stratas. This probably decreases the bio‐availability of iodine. These data show that there is a high endemicity of goitre in Chad and provide a basis for interventions as part of a national action plan against IDD, which will be adapted to the social, cultural and economic situation of the country and to available health services.
Detection of circulating antigens in Gabonese patients with Loa loa filariasis
Authors: Walker‐Deemin A. , Kombila M. , Mouray H. , Rondi M. L. , Nguiri C. , Richard‐Lenoble D.
Published: August 2010

Circulating antigens were detected in sera of Gabonese patients with Loa loa filarial infection by co‐electrosyneresis (Co‐ES). The serum samples selected for this study were exposed to rabbit hyperimmune antifilarial antisera and human immune antisera: specific arcs were observed in 35/60 filarial patients, of whom 24/47 were microfilaraemic and 11/13 amicofilaraemic. The identity of rabbit hyperimmune antisera and loiasial immune sera was confirmed by the continuity of precipitation arcs. These preliminary studies were carried out to develop diagnostic tools for loiasis and to study the physiopathology of immune complexes
Health education for community‐based malaria control: an intervention study in Ecuador, Colombia and Nicaragua
Authors: Kroeger Axel , Meyer Regine , Mancheno Manuel , González Martha
Published: August 2010

A malaria study was undertaken in 98 rural communities of the Pacific coast of Ecuador (n=14), Colombia (n= 22) and Nicaragua (n= 62). In‐depth interviews on people's knowledge and practice regarding malaria aetiology, symptoms and treatment were conducted and complemented by formal household interviews. On the basis of this information, an educational programme was set up which included the training of village health promoters and community workshops organized by the health workers and used a set of methods of interactive learning. After the baseline survey the communities were paired and randomly allocated to the intervention and control groups. Malaria education took place only in the intervention communities.

At the start of the project people's knowledge about malaria‐transmitting mosquitoes and malaria symptoms was correct and widespread in those areas where the community exposure to formal health services was pronounced. However, knowledge of the recommended dose of chloroquine was poor everywhere, and self‐treatment of malaria episodes deficient.

The educational intervention achieved a high level of participant satisfaction which was expressed in a high and continuous attendance rate at the monthly workshops. The knowledge of malaria aetiology and symptoms was 33–61% better in the intervention group than in the control group. Knowledge of the recommended doses of chloroquine increased significantly (34% in Ecuador, 93% in Colombia but not in Nicaragua) and correct use of chloroquine in the treatment of malaria episodes also improved (26% in Ecuador, 85% in Colombia). In Nicaragua the results were less satisfactory due to the short period of promotional activities and the health services' policy of delivering only supervised treatment to the population. It is concluded that health education should play a major role in malaria control.
High acceptability of voluntary counselling and HIV‐testing but unacceptable loss to follow up in a prevention of mother‐to‐child HIV transmission programme in rural Malawi: scaling‐up requires a different way of acting
Authors: Manzi M. , Zachariah R. , Teck R. , Buhendwa L. , Kazima J. , Bakali E. , Firmenich P. , Humblet P.
Published: August 2010

Setting Thyolo District Hospital, rural Malawi.

Objectives In a prevention of mother‐to‐child HIV transmission (PMTCT) programme, to determine: the acceptability of offering ‘opt‐out’ voluntary counselling and HIV‐testing (VCT); the progressive loss to follow up of HIV‐positive mothers during the antenatal period, at delivery and to the 6‐month postnatal visit; and the proportion of missed deliveries in the district.

Design Cohort study.

Methods Review of routine antenatal, VCT and PMTCT registers.

Results Of 3136 new antenatal mothers, 2996 [96%, 95% confidence interval (CI): 95–97] were pre‐test counselled, 2965 (95%, CI: 94–96) underwent HIV‐testing, all of whom were post‐test counselled. Thirty‐one (1%) mothers refused HIV‐testing. A total of 646 (22%) individuals were HIV‐positive, and were included in the PMTCT programme. Two hundred and eighty‐eight (45%) mothers and 222 (34%) babies received nevirapine. The cumulative loss to follow up (n = 646) was 358 (55%, CI: 51–59) by the 36‐week antenatal visit, 440 (68%, CI: 64–71) by delivery, 450 (70%, CI: 66–73) by the first postnatal visit and 524 (81%, CI: 78–84) by the 6‐month postnatal visit. This left just 122 (19%, CI: 16–22) of the initial cohort still in the programme. The great majority (87%) of deliveries occurred at peripheral sites where PMTCT was not available.

Conclusions  In a rural district hospital setting, at least 9 out of every 10 mothers attending antenatal services accepted VCT, of whom approximately one‐quarter were HIV‐positive and included in the PMTCT programme. The progressive loss to follow up of more than three‐quarters of this cohort by the 6‐month postnatal visit demands a ‘different way of acting’ if PMTCT is to be scaled up in our setting.
Trial participation and vaccine desirability for Vi polysaccharide typhoid fever vaccine in Hue City, Viet Nam
Authors: Kaljee Linda M. , Pham Van , Son Nguyen Dinh , Hoa Nguyen Thai , Thiem Vu Dinh , Canh Do Gia , Thoa Le Thi Kim , Ali Mohammad , Ochiai Rion Leon , Danovaro‐Holliday M. Carolina , Acosta Camilo J. , Stanton Bonita , Clemens John
Published: August 2010

Objectives  To identify demand for Vi typhoid fever vaccine for school‐age children; obstacles and enabling factors for vaccine delivery; and socio‐behavioural factors associated with trial participation and possible predictors of future vaccine acceptance, in Hue City, Viet Nam.

Methods  Pre‐ and post‐trial surveys of randomly selected households with children aged 6–17 years. Simple multinomial logistic analyses for ratios of relative risks (RRR) and significance on trial participation by demographics and variables related to typhoid fever, vaccination, and pre‐trial experiences with information and consents. Multiple logistic regressions to assess differences in participation based on child's characteristics.

Results  As many as 62.6% of households let all school age children participate, 10.2% let some participate, and 26.8% let none of their children participate in the trial. Factors associated with all children participating included past use of healthcare facilities (RRR, 0.45; 95% CI, 0.24–0.83), knowledge of vaccines (RRR, 0.17; 95% CI, 0.03–0.86), and perceived causes of typhoid fever (RRR, 0.90; 95% CI, 0.81–0.99). Factors associated with some children participating included utilization of healthcare facilities (RRR, 0.08; 95% CI, 0.01–0.66) and perceived severity of typhoid fever (RRR, 0.64; 95% CI 0.46–0.88). Participation was associated with satisfaction regarding pre‐vaccination information and consent procedures. Children and adolescents were active decision‐makers. Only 14 of 461 (2.2%) respondents would not use the Vi vaccine in the future for their child(ren).

Conclusions  Inter‐related factors contribute to participation in a clinical vaccine trial, which may differ from desire to participate in a public health campaign. Educational campaigns need to be targeted to children and adolescents, and consideration for assent procedures for minors. Obtaining informed consent may affect trial participation within a social and political system unaccustomed to these procedures.
Chloroquine prophylaxis against vivax malaria in pregnancy: a randomized, double‐blind, placebo‐controlled trial
Authors: Villegas Leopoldo , McGready Rose , Htway Mg , Paw Moo Kho , Pimanpanarak Mupawjay , Arunjerdja Ratree , Viladpai‐nguen Samuel Jacher , Greenwood Brian , White Nicholas J , Nosten François
Published: August 2010

Objective  To assess the safety of chloroquine (CQ) as prophylaxis against Plasmodium vivax infection during pregnancy.

Method  One thousand pregnant Karen women were enrolled in a randomized, double‐blind, placebo‐controlled trial of chemoprophylaxis with chloroquine (500 mg phosphate (or 300 mg base) weekly). Women received a median (range) chloroquine phosphate total dose of 9500 (1500–17 500) mg. The mothers were actively followed from inclusion to delivery and their infants until 12 months of age.

Results  Chloroquine prophylaxis completely prevented P. vivax episodes; 10.1% (95%CI: 7.3–14.5) of women in the placebo group experienced at least one episode of vivax malaria but no episode occurred in women in the CQ group. By contrast, the numbers of P. falciparum episodes were similar in each group: 7.4% (95%CI: 3.7–11.1) and 5.6% (95%CI: 3.3–7.9) in the placebo and CQ groups respectively (P = 0.56). Chloroquine prophylaxis was well tolerated and there was no difference in the proportions of reported side effects between CQ treated and placebo groups except for the duration of palpitations and sleeping disorders which were more frequent in those who had received CQ. Chloroquine prophylaxis had no impact on maternal anaemia, birth weight, gestational age, development of newborns or on growth, neurological development or visual acuity in infants at 1 year of age.

Conclusion  Chloroquine is safe and effective as prophylaxis against P. vivax during pregnancy in this population.
How much fat is necessary to optimize lumefantrine oral bioavailability?
Authors: Ashley Elizabeth A. , Stepniewska Kasia , Lindegårdh Niklas , Annerberg Anna , Kham Am , Brockman Al , Singhasivanon Pratap , White Nicholas J. , Nosten François
Published: August 2010

Background  Artemether–lumefantrine (AL) is the only fixed, artemisinin‐based combination antimalarial drug which is registered internationally and deployed on a large scale. Absorption of the hydrophobic lipophilic lumefantrine component varies widely between individuals and is greatly increased by fat coadministration; but patients with acute malaria are frequently nauseated and anorexic, making dietary advice difficult to comply with. The aim of this study was to describe the dose–response relationship between coadministration of fat and relative lumefantrine bioavailability, in order to determine the minimum amount of fat necessary to optimize absorption.

Method  We conducted a multiple crossover pharmacokinetic study in 12 healthy volunteers. This compared the area under the plasma concentration–time curve (AUC) for lumefantrine after administration of a single dose of AL in the fasting state given with 0, 10, 40, 150 and 500 ml of soya milk corresponding to 0, 0.32, 1.28, 4.8 and 16 g of fat. All volumes of milk supplements were tested in all subjects with a 3‐ to 4‐week washout period in‐between.

Results  A dose–response relationship was demonstrated between the volume of soya milk administered and lumefantrine bioavailability. AL administration with soya milk increased the lumefantrine AUC more than five fold. The population mean estimated volume of soya milk required to obtain 90% of maximum effect (in terms of lumefantrine AUC) was 36 ml (corresponding to 1.2 g of fat).

Conclusions  Coadministration of artemether–lumefantrine with a relatively small amount of fat (as soya milk) was required to ensure maximum absorption of lumefantrine in healthy adult volunteers.
Pharmacokinetic study of artemether–lumefantrine given once daily for the treatment of uncomplicated multidrug‐resistant falciparum malaria
Authors: Ashley Elizabeth A. , Stepniewska Kasia , Lindegårdh Niklas , McGready Rose , Annerberg Anna , Hutagalung Robert , Singtoroj Thida , Hla Gilvary , Brockman Al , Proux Stephane , Wilahphaingern Jahser , Singhasivanon Pratap , White Nicholas J. , Nosten François
Published: August 2010

Background  Adherence to antimalarial drug regimens is improved by simple dosing. If the fixed antimalarial drug combination artemether–lumefantrine (AL) could be given once daily, this should improve adherence and thus effectiveness and lower the risk of selecting for resistance.

Methods  In an open randomized study, 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice‐daily regimen or as a single daily dose for 3 days. The primary end point was a comparison of the areas under the plasma lumefantrine concentration–time curves (AUC). Secondary end points were the day 42 polymerase chain reaction (PCR)‐adjusted cure rates and the tolerability profiles.

Results  Lumefantrine pharmacokinetic profiles were obtained for 36 patients. The AUC(0→∞) of the once‐daily regimen was 30% lower than that in the conventional regimen (P = 0.011) with a median (range) value of 306 (114–5781) μg/ml h, compared with 432 (308–992) μg/ml h. There was no significant difference in the peak plasma concentrations reached. PCR‐adjusted cure rate estimates at day 42 of follow‐up were 94% (95% CI: 84–100) in the six‐dose arm and 85% (70–100) in the three‐dose arm (P = 0.3).

Conclusion  Artemether–lumefantrine efficacy is reduced by once‐daily dosing, because absorption of lumefantrine is dose limited. At currently recommended doses, this antimalarial should be given twice daily in a 3‐day regimen, with food containing fat.
Effect of haematinic supplementation and malaria prevention on maternal anaemia and malaria in western Kenya
Authors: Van Eijk Anna M. , Ayisi John G. , Slutsker Laurence , Ter Kuile Feiko O. , Rosen Daniel H. , Otieno Juliana A. , Shi Ya‐Ping , Kager Piet A. , Steketee Richard W. , Nahlen Bernard L.
Published: August 2010

Objective  To evaluate the effect of routine antenatal haematinic supplementation programmes and intermittent preventive treatment (IPT) with sulphadoxine–pyrimethamine (SP) in Kenya.

Methods  Anaemia [haemoglobin (Hb) <11 g/dl), severe anaemia (Hb <8 g/dl) and placental malaria were compared among women with known HIV status who delivered at a provincial hospital after study enrolment in the third trimester during three consecutive periods: period 1, no routine intervention (reference); period 2, routine haematinic supplementation (60 mg elementary iron three times/day, folic acid 5 mg once daily) and period 3, haematinics and IPT with SP.

Results  Among 3108 participants, prevalence of placental malaria, anaemia and severe anaemia postpartum was 16.7%, 53.6% and 12.7%, respectively. Compared with period 1, women in period 2 were less anaemic [adjusted odds ratio (AOR), 95% confidence interval anaemia: 0.56, 0.47–0.67; severe anaemia 0.37, 0.28–0.49] and shared a similar prevalence of placental malaria (AOR 1.07, 0.86–1.32). Women in period 3 were also less anaemic (AOR anaemia: 0.43, 0.35–0.53 and severe anaemia: 0.43, 0.31–0.59), and had less placental malaria (AOR 0.56, 0.42–0.73). The effect of intervention did not differ significantly by HIV status.

Conclusion  The haematinic supplementation programme was associated with significant reductions in anaemia in HIV‐seropositive and HIV‐seronegative women. The subsequent introduction of IPT was associated with halving of malaria, but no additional haematological benefit over haematinics.
The role of imported cases in the epidemiology of urban Plasmodium falciparum malaria in Quibdó, Colombia
Authors: Osorio L. , Todd J. , Pearce R. , Bradley D. J.
Published: August 2010

Objective  To assess the role of imported cases in the local epidemiology of malaria and population genetics of Plasmodium falciparum in an urban endemic area in Colombia.

Method  A total of 679 P. falciparum cases presenting in the city were interviewed, mapped, and genotyped using msp1 and msp2 molecular markers.

Results  Among the cases, 75% were classified as imported and harboured single‐clone infections. The P. falciparum parasite population had low genetic diversity with a preponderant haplotype (mean genetic diversity H = 0.36), even when microsatellite markers were used (H = 0.49), partly because of the small scale at which population movement was studied. Nevertheless, indigenous and potentially introduced cases were identified.

Conclusion  Migration is a confounder in planning malaria control in this endemic urban area. Longitudinal studies which monitor the P. falciparum population in imported and autochthonous cases at larger spatial scales would be necessary to study the effect of population movement on malaria transmission and, with suitable molecular markers, on the spread of drug resistance.
What role do coagulation disorders play in the pathogenesis of leptospirosis?
Authors: Wagenaar J. F. P. , Goris M. G. A. , Sakundarno M. S. , Gasem M. H. , Mairuhu A. T. A. , De Kruif M. D. , Ten Cate H. , Hartskeerl R. , Brandjes D. P. M. , Van Gorp E. C. M.
Published: August 2010

Leptospirosis is a zoonosis of worldwide distribution, spread by the urine of infected animals. It is a major public health problem, especially in developing countries, where circumstances for transmission are most favourable. The clinical picture varies from mild disease to a severe illness with haemostatic derangements and multiorgan failure eventually leading to death. Although the haemorrhagic complications of severe disease are serious, the pathophysiology is scarcely elucidated. The complex mechanisms involved in inflammation‐induced coagulation activation are extensively studied in various infectious diseases, i.e. Gram‐negative sepsis. Tissue factor‐mediated coagulation activation, impairment of anticoagulant and fibrinolytic pathways in close concert with the cytokine network are thought to be important. But for human leptospirosis, data are limited. Because of the growing interest in this field, the impact of leptospirosis, and the availability of new therapeutic strategies, we reviewed the evidence regarding the role of coagulation in leptospirosis and provide suggestions for future research.
Community‐based study on knowledge, attitude and practice on the mode of transmission, prevention and treatment of the Buruli ulcer in Ga West District, Ghana
Authors: Renzaho Andre M. N. , Woods Paul V. , Ackumey Mercy M. , Harvey Simon K. , Kotin Jacob
Published: August 2010

Buruli ulcer disease (BUD), a devastating tropical disease caused by Mycobacterium ulcerans, occurs in more than 80% of the administrative districts of Ghana. To elucidate community perceptions and understanding of the aetiology of BUD, attitudes towards Buruli patients and treatment‐seeking behaviours, we conducted a survey with 504 heads of households and seven focus group discussions in Ga West District, Ghana. Although 67% of participants regarded BUD as a health problem, 53% did not know its cause. Sixteen per cent attributed the cause to drinking non‐potable water, 8.1% mentioned poor personal hygiene or dirty surroundings, and 5.5% identified swimming or wading in ponds as a risk factor. About 5.2% thought that witchcraft and curses cause BUD, and 71.8% indicated that BU sufferers first seek treatment from herbalists and only refer to the hospital as a last resort. The main reasons were prospects of prolonged hospital stay, cost of transport, loss of earnings and opportunity associated with parents attending their children's hospitalization over extended period, delays in being attended by medical staff, and not knowing the cause of the disease or required treatment. The level of acceptance of BUD sufferers was high in adults but less so in children. The challenge facing health workers is to break the vicious cycle of poor medical outcomes leading to poor attitudes to hospital treatment in the community. Because herbalists are often the first people consulted by those who contract the disease, they need to be trained in early recognition of the pre‐ulcerative stage of Buruli lesions.
Tuberculosis in intra‐urban settings: a Bayesian approach
Authors: Souza Wayner V. , Carvalho Marilia S. , Albuquerque Maria de Fátima P. M. , Barcellos Christovam C. , Ximenes Ricardo A. A.
Published: August 2010

Objective To model the effect of socio‐economic deprivation and a few transmission‐related indicators of the tuberculosis (TB) incidence at small area level, to discuss the potential of each indicator in targeting places for developing preventive action.

Methods Ecological spatial study of TB incidence in Olinda, a city in the north‐east of Brazil, during the period 1996–2000. Three socio‐economic indicators (mean number of inhabitants per household; percentage of heads of household with <1 year's formal education; percentage of heads of households with monthly income lower than the minimum wage) and two transmission‐related indicators (number of cases of retreatment; number of households with more than one case during the period under study), all calculated per census tract, were used. We adopted four different full hierarchical Bayesian models to estimate the relative risk of the occurrence of TB via Markov chain Monte Carlo.

Results The best specified model includes all the selected covariates and the spatially structured random effect. The gain in goodness‐of‐fit statistic when the spatial structure was included confirms the clustered spatial pattern of disease and poverty. In this model, the covariates within the non‐zero credibility interval were the number of persons per house, the number of cases of retreatment and the number of households with more than one case (all with relative risk ≥1.8) in each census tract.

Conclusions The possibility to estimate in the same framework both the contribution of covariates at ecological level and the spatial pattern should be encouraged in epidemiology, and may help with establishing Epidemiological Surveillance Systems on a territorial basis, that allows rational planning of interventions and improvement of the Control Programme effectiveness.
How to measure the prevalence of tuberculosis in a population
Authors: Van Der Werf Marieke J. , Borgdorff Martien W.
Published: August 2010

The World Health Assembly has defined targets for measuring performance of tuberculosis (TB) control programmes, which have been included in the framework of the Millennium Development Goals. To be able to measure progress towards these targets TB control programmes need epidemiological information. At the moment, surveillance data of countries with a high burden of TB are insufficient to assess performance of the TB control programme as a result of incompleteness or low quality. Several high‐burden countries have performed TB prevalence surveys to obtain epidemiological information. As a standardized method for TB prevalence surveys has not been defined, we discuss the different options for measuring prevalence and their advantages and disadvantages. Most surveys use comparable strategies. Alternatives strategies at lower cost need to be evaluated.