Unexpectedly long incubation period of Plasmodium vivax malaria, in the absence of chemoprophylaxis, in patients diagnosed outside the transmission area in Brazil

<p>Abstract</p> <p>Background</p> <p>In 2010, Brazil recorded 3343,599 cases of malaria, with 99.6% of them concentrated in the Amazon region. <it>Plasmodium vivax </it>accounts for 86% of the cases circulating in the country. The extra-Amazonian region, where transmission does not occur, recorded about 566 cases imported from the Amazonian area in Brazil and South America, from Central America, Asia and African countries. Prolonged incubation periods have been described for <it>P. vivax </it>malaria in temperate climates. The diversity in essential biological characteristics is traditionally considered as one possible explanation to the emergence of relapse in malaria and to the differences in the duration of the incubation period, which can also be explained by the use of chemoprophylaxis. Studying the reported cases of <it>P. vivax </it>malaria in Rio de Janeiro, where there is no vector transmission, has made it possible to evaluate the extension of the incubation period and to notice that it may be extended in some cases.</p> <p>Methods</p> <p>Descriptive study of every malaria patients who visited the clinic in the last five years. The mean, standard deviation, median, minimum and maximum of all incubation periods were analysed.</p> <p>Results</p> <p>From the total of 80 patients seen in the clinic during the study time, with confirmed diagnosis of malaria, 49 (63%) were infected with <it>P. vivax</it>. Between those, seven had an estimated incubation period varying from three to 12 months and were returned travellers from Brazilian Amazonian states (6) and Indonesia (1). None of them had taken malarial chemoprophylaxis.</p> <p>Conclusions</p> <p>The authors emphasize that considering malaria as a possible cause of febrile syndrome should be a post-travel routine, independent of the time elapsed after exposure in the transmission area, even in the absence of malaria chemoprophylaxis. They speculate that, since there is no current and detailed information about the biological cycle of human malaria plasmodia's in Brazil, it is possible that new strains are circulating in endemic regions or a change in cycle of preexisting strains is occurring. Considering that a prolonged incubation period may confer advantages on the survival of the parasite, difficulties in malaria control might arise.</p

Clara Cell 10-kDa Protein Gene Transfection Inhibits NF-κB Activity in Airway Epithelial Cells

Clara cell 10-kDa protein (CC10) is a multifunctional protein with anti-inflammatory and immunomodulatory effects. Induction of CC10 expression by gene transfection may possess potential therapeutic effect. Nuclear factor κB (NF-κB) plays a key role in the inflammatory processes of airway diseases.To investigate potential therapeutic effect of CC10 gene transfection in controlling airway inflammation and the underlying intracellular mechanisms, in this study, we constructed CC10 plasmid and transfected it into bronchial epithelial cell line BEAS-2B cells and CC10 knockout mice. In BEAS-2B cells, CC10's effect on interleukin (IL)-1β induced IL-8 expression was explored by means of RT-PCR and ELISA and its effect on NF-κB classical signaling pathway was studied by luciferase reporter, western blot, and immunoprecipitation assay. The effect of endogenous CC10 on IL-1β evoked IL-8 expression was studied by means of nasal explant culture. In mice, CC10's effect on IL-1β induced IL-8 and nuclear p65 expression was examined by immunohistochemistry. First, we found that the CC10 gene transfer could inhibit IL-1β induced IL-8 expression in BEAS-2B cells. Furthermore, we found that CC10 repressed IL-1β induced NF-κB activation by inhibiting the phosphorylation of IκB-α but not IκB kinase-α/β in BEAS-2B cells. Nevertheless, we did not observe a direct interaction between CC10 and p65 subunit in BEAS-2B cells. In nasal explant culture, we found that IL-1β induced IL-8 expression was inversely correlated with CC10 levels in human sinonasal mucosa. In vivo study revealed that CC10 gene transfer could attenuate the increase of IL-8 and nuclear p65 staining in nasal epithelial cells in CC10 knockout mice evoked by IL-1β administration.These results indicate that CC10 gene transfer may inhibit airway inflammation through suppressing the activation of NF-κB, which may provide us a new consideration in the therapy of airway inflammation

Magnesium induces neuronal apoptosis by suppressing excitability

In clinical obstetrics, magnesium sulfate (MgSO4) use is widespread, but effects on brain development are unknown. Many agents that depress neuronal excitability increase developmental neuroapoptosis. In this study, we used dissociated cultures of rodent hippocampus to examine the effects of Mg++ on excitability and survival. Mg++-induced caspase-3-associated cell loss at clinically relevant concentrations. Whole-cell patch-clamp techniques measured Mg++ effects on action potential threshold, action potential peak amplitude, spike number and changes in resting membrane potential. Mg++ depolarized action potential threshold, presumably from surface charge screening effects on voltage-gated sodium channels. Mg++ also decreased the number of action potentials in response to fixed current injection without affecting action potential peak amplitude. Surprisingly, Mg++ also depolarized neuronal resting potential in a concentration-dependent manner with a +5.2 mV shift at 10 mM. Voltage ramps suggested that Mg++ blocked a potassium conductance contributing to the resting potential. In spite of this depolarizing effect of Mg++, the net inhibitory effect of Mg++ nearly completely silenced neuronal network activity measured with multielectrode array recordings. We conclude that although Mg++ has complex effects on cellular excitability, the overall inhibitory influence of Mg++ decreases neuronal survival. Taken together with recent in vivo evidence, our results suggest that caution may be warranted in the use of Mg++ in clinical obstetrics and neonatology

Rhinovirus-induced basic fibroblast growth factor release mediates airway remodeling features

BACKGROUND: Human rhinoviruses, major precipitants of asthma exacerbations, induce lower airway inflammation and mediate angiogenesis. The purpose of this study was to assess the possibility that rhinoviruses may also contribute to the fibrotic component of airway remodeling. METHODS: Levels of basic fibroblast growth factor (bFGF) mRNA and protein were measured following rhinovirus infection of bronchial epithelial cells. The profibrotic effect of epithelial products was assessed by DNA synthesis and matrix metalloproteinase activity assays. Moreover, epithelial cells were exposed to supernatants from cultured peripheral blood mononuclear cells, obtained from healthy donors or atopic asthmatic subjects and subsequently infected by rhinovirus and bFGF release was estimated. bFGF was also measured in respiratory secretions from atopic asthmatic patients before and during rhinovirus-induced asthma exacerbations. RESULTS: Rhinovirus epithelial infection stimulated mRNA expression and release of bFGF, the latter being positively correlated with cell death under conditions promoting rhinovirus-induced cytotoxicity. Supernatants from infected cultures induced lung fibroblast proliferation, which was inhibited by anti-bFGF antibody, and demonstrated increased matrix metalloproteinase activity. Rhinovirus-mediated bFGF release was significantly higher in an in vitro simulation of atopic asthmatic environment and, importantly, during rhinovirus-associated asthma exacerbations. CONCLUSIONS: Rhinovirus infection induces bFGF release by airway epithelium, and stimulates stroma cell proliferation contributing to airway remodeling in asthma. Repeated rhinovirus infections may promote asthma persistence, particularly in the context of atopy; prevention of such infections may influence the natural history of asthma

No more 'business as usual' with audit and feedback interventions: towards an agenda for a reinvigorated intervention

Background: Audit and feedback interventions in healthcare have been found to be effective, but there has been little progress with respect to understanding their mechanisms of action or identifying their key ‘active ingredients.’ Discussion: Given the increasing use of audit and feedback to improve quality of care, it is imperative to focus further research on understanding how and when it works best. In this paper, we argue that continuing the ‘business as usual’ approach to evaluating two-arm trials of audit and feedback interventions against usual care for common problems and settings is unlikely to contribute new generalizable findings. Future audit and feedback trials should incorporate evidence- and theory-based best practices, and address known gaps in the literature. Summary: We offer an agenda for high-priority research topics for implementation researchers that focuses on reviewing best practices for designing audit and feedback interventions to optimize effectiveness

Prospective study on severe malaria among in-patients at Bombo regional hospital, Tanga, north-eastern Tanzania

In Tanzania, malaria is the major cause of morbidity and mortality, accounting for about 30% of all hospital admissions and around 15% of all hospital deaths. Severe anaemia and cerebral malaria are the two main causes of death due to malaria in Tanga, Tanzania. This was a prospective observational hospital-based study conducted from October 2004 to September 2005. Consent was sought from study participants or guardians in the wards. Finger prick blood was collected from each individual for thick and thin smears, blood sugar levels and haemoglobin estimations by Haemocue machine after admission. A total of 494 patients were clinically diagnosed and admitted as cases of severe malaria. Majority of them (55.3%) were children below the age of 5 years. Only 285 out of the total 494 (57.7%) patients had positive blood smears for malaria parasites. Adults aged 20 years and above had the highest rate of cases with fever and blood smear negative for malaria parasites. Commonest clinical manifestations of severe malaria were cerebral malaria (47.3%) and severe anaemia (14.6%), particularly in the under-fives. Case fatality was 3.2% and majority of the deaths occurred in the under-fives and adults aged 20 years and above with negative blood smears. Proper laboratory diagnosis is crucial for case management and reliable data collection. The non-specific nature of malaria symptomatologies limits the use of clinical diagnosis and the IMCI strategy. Strengthening of laboratory investigations to guide case management is recommended

Coquillettidia (Culicidae, Diptera) mosquitoes are natural vectors of avian malaria in Africa

<p>Abstract</p> <p>Background</p> <p>The mosquito vectors of <it>Plasmodium </it>spp. have largely been overlooked in studies of ecology and evolution of avian malaria and other vertebrates in wildlife.</p> <p>Methods</p> <p><it>Plasmodium </it>DNA from wild-caught <it>Coquillettidia </it>spp. collected from lowland forests in Cameroon was isolated and sequenced using nested PCR. Female <it>Coquillettidia aurites </it>were also dissected and salivary glands were isolated and microscopically examined for the presence of sporozoites.</p> <p>Results</p> <p>In total, 33% (85/256) of mosquito pools tested positive for avian <it>Plasmodium </it>spp., harbouring at least eight distinct parasite lineages. Sporozoites of <it>Plasmodium </it>spp. were recorded in salivary glands of <it>C. aurites </it>supporting the PCR data that the parasites complete development in these mosquitoes. Results suggest <it>C. aurites</it>, <it>Coquillettidia pseudoconopas </it>and <it>Coquillettidia metallica </it>as new and important vectors of avian malaria in Africa. All parasite lineages recovered clustered with parasites formerly identified from several bird species and suggest the vectors capability of infecting birds from different families.</p> <p>Conclusion</p> <p>Identifying the major vectors of avian <it>Plasmodium </it>spp. will assist in understanding the epizootiology of avian malaria, including differences in this disease distribution between pristine and disturbed landscapes.</p