Mutations in dhfr in Plasmodium falciparum infections selected by chlorproguanil-dapsone treatment.

Treatment with the novel antifolate drug combination chlorproguanil-dapsone effectively cleared asymptomatic Plasmodium falciparum infections in 246 (93.5%) of 263 children in the Usambara Mountains of Tanzania during the course of a 2-week follow-up. Samples from 71 recurrent infections, collected over a 9-week follow-up, showed selection for parasites with the triple mutant Ile(51)-Arg(59)-Asn(108) in dihydrofolate reductase. There was no selection for mutations in dihydropteroate synthetase, the target enzyme of dapsone. Search for complete identity in the highly polymorphic genes coding for merozoite surface proteins 1 and 2 in parasite samples collected before and after treatment indicated that the majority of recurrent parasitemias were new infections. These observations on selection in Tanzania and the lack of selection reported from a less endemic area suggest that the active metabolite of chlorproguanil, which has a short half-life in the blood, may persist in the liver, where it exerts selective pressure on growing preerythrocytic stages

Comparison of coverage with insecticide-treated nets in a Tanzanian town and villages where nets and insecticide are either marketed or provided free of charge

BACKGROUND: There is much emphasis on social marketing as a means of scaling up coverage with insecticide-treated nets and the question has arisen whether nets provided free-of-charge will be looked after by householders. METHODS: Over several years questionnaires and surveys of usage and condition of nets were carried out throughout a town and 15 villages in north-east Tanzania, where nets and insecticide have to be purchased and in 24 other villages where over 15000 nets had been donated and annual re-treatment is provided free-of-charge. RESULTS: There was very high population coverage in the town but, in the villages where nets have to be purchased, only 9.3% of people used nets which were intact and/or had been insecticide-treated and could, therefore, provide protection. However, where nets had been provided free, over 90% of the nets were still present and were brought for re-treatment several years later. CONCLUSION: In this part of Tanzania, social marketing has performed well in a town but very poorly in villages. However, the study showed that people look after and bring for re-treatment nets which had been provided free-of-charge

Mosquito Abundance, Bed net Coverage and Other Factors Associated with Variations in Sporozoite Infectivity Rates in Four Villages of Rural Tanzania.

Entomological surveys are of great importance in decision-making processes regarding malaria control strategies because they help to identify associations between vector abundance both species-specific ecology and disease intervention factors associated with malaria transmission. Sporozoite infectivity rates, mosquito host blood meal source, bed net coverage and mosquito abundance were assessed in this study. A longitudinal survey was conducted in four villages in two regions of Tanzania. Malaria vectors were sampled using the CDC light trap and pyrethrum spray catch methods. In each village, ten paired houses were selected for mosquitoes sampling. Sampling was done in fortnight case and study was undertaken for six months in both Kilimanjaro (Northern Tanzania) and Dodoma (Central Tanzania) regions. A total of 6,883 mosquitoes were collected including: 5,628 (81.8%) Anopheles arabiensis, 1,100 (15.9%) Culex quinquefasciatus, 89 (1.4%) Anopheles funestus, and 66 (0.9%) Anopheles gambiae s.s. Of the total mosquitoes collected 3,861 were captured by CDC light trap and 3,022 by the pyrethrum spray catch method. The overall light trap: spray catch ratio was 1.3:1. Mosquito densities per room were 96.5 and 75.5 for light trap and pyrethrum spray catch respectively. Mosquito infectivity rates between villages that have high proportion of bed net owners and those without bed nets was significant (P < 0.001) and there was a significant difference in sporozoite rates between households with and without bed nets in these four villages (P < 0.001). Malaria remains a major problem in the study areas characterized as low transmission sites. Further studies are required to establish the annual entomological inoculation rates and to observe the annual parasitaemia dynamics in these communities. Outdoor mosquitoes collection should also be considered

Median knock-down time as a new method for evaluating insecticide-treated textiles for mosquito control

<p>Abstract</p> <p>Background</p> <p>Insecticide treated bed nets are major tools for the Roll Back Malaria campaign. There are two types of Long-Lasting Insecticide-treated Nets (LNs) on the market: coated nets and insecticide-incorporated nets. Nets provided to this market need a recommendation from the World Health Organization to be purchased by donors and NGOs. During laboratory study (phase I), the first step consists in evaluating the wash resistance of a new LN product. When insecticide-incorporated nets are washed, it takes time to regenerate the insecticidal activity, i.e. insecticide must migrate to the net surface to be accessible to mosquitoes. The interval of time required for regeneration must be carefully determined to ensure the accuracy of further results. WHOPES procedures currently recommend the determination of the regeneration time by using mortality data. However, as mortality cannot exceed 100%, a LN that regenerates a surface concentration exceeding the dosage for 100% mortality, will have its regeneration time underestimated.</p> <p>Methods</p> <p>The Median Knock Down Time (MKDT) was determined as function of insecticide dosage on an inert surface, glass, and on polyester nettings using an acetone solution or a simple emulsion. Dosage response was also established for mortality data. The same method was then applied to a commercially polyethylene netting, currently under WHOPES evaluation, to determine the dynamics of regeneration as function of repeated washings. The deltamethrin content of these nets was estimated by Capillary Gas Chromatography (GC-ECD).</p> <p>Results</p> <p>MKDT was a linear function of log insecticide dosage on glass as on nettings. Mortality data were either 0 or 100% for most concentrations except for a narrow range. MKDT was log linear function of total deltamethrin content in a commercial polyethylene net exposed to washings. The regeneration time of this net increased with the number of washes and MKDT became higher. A new, easy and rapid method to determine MKDT is suggested.</p> <p>Discussion</p> <p>The MKDT is linearly correlated to log dosage on a given substrate and shows no saturation as mortality data do. It is suited to determine regeneration time of a product that is exposed to a stress, like washing or heating, where the process impacts on the bio-availability of the insecticide. Mortality data are useful for measuring product efficacy, whereas MKDT are better to measure dynamics of surface concentration like regeneration after a stressing process. Change in MKDT can be used to illustrate the loss of insecticide due to washing, but the slope of the curve is product and surface-dependent.</p

Reliability and validity of skin temperature measurement by telemetry thermistors and a thermal camera during exercise in the heat

Abstract. New technologies afford convenient modalities for skin temperature (T SKIN ) measurement, notably involving wireless telemetry and non-contact infrared thermometry. The purpose of this study was to investigate the validity and reliability of skin temperature measurements using a telemetry thermistor system (TT) and thermal camera (TC) during exercise in a hot environment. Each system was compared against a certified thermocouple, measuring the surface temperature of a metal block in a thermostatically controlled waterbath. Fourteen recreational athletes completed two incremental running tests, separated by one week. Skin temperatures were measured simultaneously with TT and TC compared against a hard-wired thermistor system (HW) throughout rest and exercise. Post hoc calibration based on waterbath results displayed good validity for TT (mean bias [MB] = -0.18°C, typical error [TE] = 0.18°C) and reliability (MB = -0.05°C, TE = 0.31°C) throughout rest and exercise. Poor validity (MB = -1.4°C, TE = 0.35°C) and reliability (MB = -0.65°C, TE = 0.52°C) was observed for TC, suggesting it may be best suited to controlled, static situations. These findings indicate TT systems provide a convenient, valid and reliable alternative to HW, useful for measurements in the field where traditional methods may be impractical

Mosquito nets in a rural area of Western Kenya: ownership, use and quality

<p>Abstract</p> <p>Background</p> <p>Insecticide-treated nets (ITNs) are regarded as one of the most effective strategies to prevent malaria in Africa. This study analyses the use and quality of nets owned by households in an area of high net coverage.</p> <p>Methods</p> <p>A structured questionnaire on ownership and use of nets was administered to the households of individuals sampled from a local health centre in south Kisii district, Kenya. A physical inspection of all the nets in the households was done and their conditions recorded on spot check forms designed for that purpose.</p> <p>Results</p> <p>Of the 670 households surveyed, 95% owned at least one net. Only 59% of household residents slept under a net during the night prior to the survey. 77% of those who slept under a net used an insecticide-treated net (ITN) or long-lasting insecticide-treated nets (LLIN). Out of 1,627 nets in the survey households, 40% were deemed to be of poor quality because of holes. Compared to other age groups, children aged 5-14 years were most likely to have slept under nets of poor quality (odds ratio 1.41; <it>p </it>= 0.007).</p> <p>Conclusions</p> <p>Although net ownership was high following increased delivery of ITNs, continuous promotion of effective maintenance and routine use is needed and efforts to replace damaged nets must be implemented.</p

ANKRD26 and Its Interacting Partners TRIO, GPS2, HMMR and DIPA Regulate Adipogenesis in 3T3-L1 Cells

Partial inactivation of the Ankyrin repeat domain 26 (Ankrd26) gene causes obesity and diabetes in mice and increases spontaneous and induced adipogenesis in mouse embryonic fibroblasts. However, it is not yet known how the Ankrd26 protein carries out its biological functions. We identified by yeast two-hybrid and immunoprecipitation assays the triple functional domain protein (TRIO), the G protein pathway suppressor 2 (GPS2), the delta-interacting protein A (DIPA) and the hyaluronan-mediated motility receptor (HMMR) as ANKRD26 interacting partners. Adipogenesis of 3T3-L1 cells was increased by selective down-regulation of Ankrd26, Trio, Gps2, Hmmr and Dipa. Furthermore, GPS2 and DIPA, which are normally located in the nucleus, were translocated to the cytoplasm, when the C-terminus of ANKRD26 was introduced into these cells. These findings provide biochemical evidence that ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenisis and identify new targets for the modulation of adipogenesis

Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

<p>Abstract</p> <p>Introduction</p> <p>Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature.</p> <p>Case presentation</p> <p>A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity.</p> <p>Conclusion</p> <p>We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity.</p

A powerful intervention: general practitioners' use of sickness certification in depression

&lt;b&gt;Background&lt;/b&gt; Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Defining the determinants of endurance running performance in the heat

In cool conditions, physiological markers accurately predict endurance performance, but it is unclear whether thermal strain and perceived thermal strain modify the strength of these relationships. This study examined the relationships between traditional determinants of endurance performance and time to complete a 5 km time trial in the heat. Seventeen club runners completed graded exercise tests (GXT) in hot (GXTHOT; 32°C, 60% RH, 27.2°C WBGT) and cool conditions (GXTCOOL; 13°C, 50% RH, 9.3°C WBGT) to determine maximal oxygen uptake (V̇O2max), running economy (RE), velocity at V̇O2max (vV̇O2max), and running speeds corresponding to the lactate threshold (LT, 2 mmol.l-1) and lactate turnpoint (LTP, 4 mmol.l-1). Simultaneous multiple linear regression was used to predict 5 km time, using these determinants, indicating neither GXTHOT (R2=0.72) or GXTCOOL (R2=0.86) predicted performance in the heat as strongly has previously been reported in cool conditions. vV̇O2max was the strongest individual predictor of performance, both when assessed in GXTHOT (r=-0.83) and GXTCOOL (r=-0.90). The GXTs revealed the following correlations for individual predictors in GXTHOT; V̇O2max r=-0.7, RE r=0.36, LT r=-0.77, LTP r=-0.78 and in GXTCOOL; V̇O2max r=-0.67, RE r=0.62, LT r=-0.79, LTP r=-0.8. These data indicate: (i) GXTHOT does not predict 5 km running performance in the heat as strongly as a GXTCOOL, (ii) as in cool conditions, vV̇O2max may best predict running performance in the heat.