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Background Influenza B viruses can cause morbidity and mortality in humans but due to the lack of an animal reservoir are not associated with pandemics. Because of this, there is relatively limited genetic sequences available for influenza B viruses, especially from developing countries. Complete genome analysis of one influenza B virus and several gene segments of other influenza B viruses isolated from Uganda from May 2009 through December 2010 was therefore undertaken in this study. Methods Samples were collected from patients showing influenza like illness and screened for influenza A and B by PCR. Influenza B viruses were isolated on Madin-Darby Canine Kidney cells and selected isolates were subsequently sequenced and analyzed phylogenetically. Findings Of the 2,089 samples collected during the period, 292 were positive by PCR for influenza A or B; 12.3% of the PCR positives were influenza B. Thirty influenza B viruses were recovered and of these 25 that grew well consistently on subculture were subjected to further analysis. All the isolates belonged to the B/Victoria-lineage as identified by hemagglutination inhibition assay and genetic analysis except one isolate that grouped with the B-Yamagata-lineage. The Ugandan B/Victoria-lineage isolates grouped in clade 1 which was defined by the N75K, N165K and S172P substitutions in hemagglutinin (HA) protein clustered together with the B/Brisbane/60/2008 vaccine strain. The Yamagata-like Ugandan strain, B/Uganda/MUWRP-053/2009, clustered with clade 3 Yamagata viruses such as B/Bangladesh/3333/2007 which is characterized by S150I and N166Y substitutions in HA. Conclusion In general there was limited variation among the Ugandan isolates but they were interestingly closer to viruses from West and North Africa than from neighboring Kenya. Our isolates closely matched the World Health Organization recommended vaccines for the seasons.

There is an alarming rate of human African trypanosomiasis recrudescence in many parts of sub-Saharan Africa. Yet, the disease has no successful chemotherapy. Trypanosoma lacks the enzymatic machinery for the de novo synthesis of purine nucleotides, and is critically dependent on salvage mechanisms. Inosine 5′-monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide metabolism. Here, we characterize recombinant Trypanosoma brucei IMPDH (TbIMPDH) to investigate the enzymatic differences between TbIMPDH and host IMPDH. Size-exclusion chromatography and analytical ultracentrifugation sedimentation velocity experiments reveal that TbIMPDH forms a heptamer, different from type 1 and 2 mammalian tetrameric IMPDHs. Kinetic analysis reveals calculated Km values of 30 and 1300 μm for IMP and NAD, respectively. The obtained Km value of TbIMPDH for NAD is approximately 20–200-fold higher than that of mammalian enzymes and indicative of a different NAD binding mode between trypanosomal and mammalian IMPDHs. Inhibition studies show Ki values of 3·2 μm, 21 nM and 3·3 nM for ribavirin 5′-monophosphate, mycophenolic acid and mizoribine 5′-monophosphate, respectively. Our results show that TbIMPDH is different from its mammalian counterpart and thus may be a good target for further studies on anti-trypanosomal drugs.

The antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children. A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12-47 months in general good health.Children were randomised in a 1ratio1 fashion to receive either FMP1/AS02 (50 microg) or Rabipur(R) rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature >/=37.5 degrees C with asexual parasitaemia of >/=50,000 parasites/microL of blood) occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE) was measured over a six-month period following third vaccinations. 374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-1(42) antibody concentrations increased from1.3 microg/mL to 27.3 microg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: -26% to +28%; p-value = 0.7). FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-1(42) vaccine development should focus on other formulations and antigen constructs. Clinicaltrials.gov NCT00223990.

The parasite Plasmodium falciparum, like neoplastic cells, develops resistance to multiple structurally unrelated drugs. If the mechanisms by which P. falciparum and neoplastic cells become resistant are similar, then it may be possible to reverse the resistance in the two types of cells by the same pharmacological agents. Verapamil, a calcium channel blocker, completely reversed chloroquine resistance in two chloroquine-resistant P. falciparum clones from Southeast Asia and Brazil. Verapamil reversed chloroquine resistance at the same concentration (1$\\times $10$^{-6}$M) as that at which it reversed resistance in multidrug-resistant cultured neoplastic cells. This same concentration of verapamil had no effect on chloroquine-sensitive parasites. Hence, chloroquine resistance in P. falciparum may fit the criteria for the multidrug-resistant phenotype.

Chloroquine-resistant Plasmodium falciparum accumulate significantly less chloroquine than susceptible parasites, and this is thought to be the basis of their resistance. However, the reason for the lower accumulation of chloroquine was unknown. The resistant parasite has now been found to release chloroquine 40 to 50 times more rapidly than the susceptible parasite, although their initial rates of chloroquine accumulation are the same. Verapamil and two other calcium channel blockers, as well as vinblastine and daunomycin, each slowed the release and increased the accumulation of chloroquine by resistant (but not susceptible) Plasmodium falciparum. These results suggest that a higher rate of chloroquine release explains the lower chloroquine accumulation, and thus the resistance observed in resistant Plasmodium falciparum.

Exoantigens released by Leishmania promastigotes were the subject of a workshop held in Mombasa, Kenya. Investigators from the Walter Reed Army Institute of Research (Silver Spring, Maryland) met with scientists from government and academic institutes and industry to review the current global status of leishmaniasis and to explore the potential role of exoantigens in the detection of Leishmania in the vertebrate host and arthropod vector. Some encouraging data, particularly in the immunodiagnosis of leishmaniasis, were shared. The participants concluded that the meeting provided a unique opportunity for investigators working on various aspects of the problem to network and to forge productive collaborations that could potentially lead to the development of more-effective tools to counter this persistent and expanding threat. They recommended periodic meetings to assess interval progress, to revise timelines, and to set achievable goals. The meeting also highlighted the importance of Leishmania infection in the 21st century, with more movement of people from disease-endemic to non-disease-endemic countries. Increased incidence and geographic spread of leishmaniasis emphasize the need for better and more reliable detection methods. Exoantigen-based diagnostic devices hold promise in this direction.

Cellular responses to growth factors, hormones, and other agonists have been shown in many animal cell systems to be mediated by the signal transduction cascade controlled by phospholipase C. One such response, calcium mobilization, is regulated by the concerted effect of several specific inositol (poly)phosphates. Another response, protein phosphorylation, is regulated by other phospholipase C (PLC) hydrolysis products. Mature gametocytes are specialized cells primed for transformation into gametes immediately upon removal from the vertebrate bloodstream, thereby initiating the sexual cycle in a vector mosquito. This study showed that PLC hydrolysis products, inositol (1,4,5)triphosphate and diacylglycerol, are correlated with the initial events of flagellar development; they are implicated in synchronizing this crucial transformation for the parasite and hence the continued transmission of the parasite, which leads to this debilitating disease.

Many low- and middle-income countries are undergoing a nutrition transition associated with rapid social and economic transitions. We explore the coexistence of over and under- nutrition at the neighborhood and household level, in an urban poor setting in Nairobi, Kenya. Data were collected in 2010 on a cohort of children aged under five years born between 2006 and 2010. Anthropometric measurements of the children and their mothers were taken. Additionally, dietary intake, physical activity, and anthropometric measurements were collected from a stratified random sample of adults aged 18 years and older through a separate cross-sectional study conducted between 2008 and 2009 in the same setting. Proportions of stunting, underweight, wasting and overweight/obesity were dettermined in children, while proportions of underweight and overweight/obesity were determined in adults. Of the 3335 children included in the analyses with a total of 6750 visits, 46% (51% boys, 40% girls) were stunted, 11% (13% boys, 9% girls) were underweight, 2.5% (3% boys, 2% girls) were wasted, while 9% of boys and girls were overweight/obese respectively. Among their mothers, 7.5% were underweight while 32% were overweight/obese. A large proportion (43% and 37%%) of overweight and obese mothers respectively had stunted children. Among the 5190 adults included in the analyses, 9% (6% female, 11% male) were underweight, and 22% (35% female, 13% male) were overweight/obese. The findings confirm an existing double burden of malnutrition in this setting, characterized by a high prevalence of undernutrition particularly stunting early in life, with high levels of overweight/obesity in adulthood, particularly among women. In the context of a rapid increase in urban population, particularly in urban poor settings, this calls for urgent action. Multisectoral action may work best given the complex nature of prevailing circumstances in urban poor settings. Further research is needed to understand the pathways to this coexistence, and to test feasibility and effectiveness of context-specific interventions to curb associated health risks.