Malaria infection is initiated when the insect vector injectsPlasmodium sporozoites into a susceptible vertebrate host. Sporozoites rapidly leave the circulatory system to invade hepatocytes, where further development generates the parasite form that invades and multiplies within erythrocytes. Previous experiments have shown that the thrombospondin-related adhesive protein (TRAP) plays an important role in sporozoite infectivity for hepatocytes. TRAP, a typical type-1 transmembrane protein, has a long extracellular region, which contains two adhesive domains, an A-domain and a thrombospondin repeat. We have generated recombinant proteins of the TRAP adhesive domains. These TRAP fragments show direct interaction with hepatocytes and inhibit sporozoite invasion in vitro. When the recombinant TRAP A-domain was used for immunoprecipitation against hepatocyte membrane fractions, it bound to ␣2-Heremans-Schmid glycoprotein/ fetuin-A, a hepatocyte-specific protein associated with the extracellular matrix. When the soluble sporozoite protein fraction was immunoprecipitated on a fetuin-A-adsorbed protein A column, TRAP bound this ligand. Importantly, anti-fetuin-A antibodies inhibited invasion of hepatocytes by sporozoites. Further, onset of malaria infection was delayed in fetuin-A-deficient mice compared to that in wild-type C57BL/6 mice when they were challenged with Plasmodium berghei sporozoites. These data demonstrate that the extracellular region of TRAP interacts with fetuin-A on hepatocyte membranes and that this interaction enhances the parasite's ability to invade hepatocytes.Malaria is a deadly parasitic disease which affects nearly 40% of the world's population. In any given year 300 to 500 million clinical cases occur, with more than a million deaths. Malaria is caused by species of the protozoan parasite Plasmodium. The infection is initiated when a female Anopheles mosquito injects Plasmodium sporozoites into a susceptible vertebrate host. The sporozoites migrate to the liver, where they undergo many rounds of schizogony in the hepatocytes. The resulting merozoites then invade and multiply within erythrocytes, causing the clinical symptoms of malaria.Understanding the pathogenesis of malaria requires a keen understanding of the molecular mechanisms used by Plasmodium to recognize and invade host cells. Invasion is mediated by interactions between specific parasite molecules and complementary ligands on the host cells. Plasmodium has three invasive stages: (i) sporozoites (sporogonic cycle), which invade the salivary glands of the mosquito; (ii) salivary gland sporozoites (exoerythrocytic cycle), which invade hepatocytes in the vertebrate; and (iii) merozoites (erythrocytic cycle), which invade erythrocytes. The invasion of hepatocytes by sporozoites has been known to require two parasite proteins: circumsporozoite protein (CS) and thrombospondin-related adhesive protein (TRAP) (6,28,30,33,34,44). These proteins are conserved in all Plasmodium species examined to date (26,40) and are present on the parasit...
Background Despite dramatic improvement in antiretroviral therapy (ART) access globally, people living with HIV who inject drugs continue to face barriers that limit their access to treatment. This paper explores barriers and facilitators to ART initiation among clients attending a methadone clinic in Dar es Salaam, Tanzania. Methods We interviewed 12 providers and 20 clients living with HIV at the Muhimbili National Hospital methadone clinic between January and February 2015. We purposively sampled clients based on sex and ART status and providers based on job function. To analyze interview transcripts, we adopted a content analysis approach. Results Participants identified several factors that hindered timely ART initiation for clients at the methadone clinic. These included delays in CD4 testing and receiving CD4 test results; off-site HIV clinics; stigma operating at the individual, social and institutional levels; insufficient knowledge of the benefits of early ART initiation among clients; treatment breakdown at the clinic level possibly due to limited staff; and initiating ART only once one feels physically ill. Participants perceived social support as a buffer against stigma and facilitator of HIV treatment. Some clients also reported that persistent monitoring and follow-up on their HIV care and treatment by methadone clinic providers led them to initiate ART. Conclusion Health system factors, stigma and limited social support pose challenges for methadone clients living with HIV to initiate ART. Our findings suggest that on-site point-of-care CD4 testing, a peer support system, and trained HIV treatment specialists who are able to counsel HIV-positive clients and initiate them on ART at the methadone clinic could help reduce barriers to timely ART initiation for methadone clients.
SummaryObjectivePrior studies have suggested that weight misperception – underestimating one's actual weight – may be associated with reduced engagement in weight loss programmes, decreasing the success of initiatives to address obesity and obesity‐related diseases. The purpose of this study was to examine the factors associated with weight misperception among Eastern Caribbean adults and its influence on engagement in weight control behaviour.MethodsData from the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study were analysed (adults aged 40 and older, residing in the US Virgin Islands, Puerto Rico, Barbados and Trinidad). Weight misperception is defined as participants who under‐assess their weight measured by body mass index (BMI). Multivariable logistic regression (n = 1,803 participants) was used to examine the association of weight misperception with BMI category, age, gender, education, history of non‐communicable disease and attempt to lose weight.ResultsWeight misperception was common, with 54% of overweight (BMI 25–29 kg m−2), and 23% of obese class I (BMI 30–34.9 kg m−2) participants under‐assessing their actual weight. Participants with higher levels of education, versus lower, had decreased odds of weight misperception (OR 0.5, p < 0.001). There were no significantly reduced odds of weight misperception in women versus men (OR 1.13, p = 0.367) or in individuals with history of diabetes versus none (OR 0.88, p = 0.418). Participants with weight misperception had 85% (p < 0.0001) lower odds of attempting weight loss than those with accurate weight perception.ConclusionWeight misperception is common among adults with overweight and obesity in the Eastern Caribbean and is associated with lower likelihood of attempting weight loss. Obesity interventions, targeting similar populations, should incorporate approaches for addressing weight misperception to achieve measurable success.
Background. The government of Tanzania launched an opioid treatment program (OTP), using methadone, in Dar es Salaam in February of 2011. Hepatitis C virus (HCV) is a leading cause of morbidity and mortality globally, especially among people who inject drugs (PWID). We conducted a cross-sectional study among PWID engaged in OTP in Dar es Salaam to describe the prevalence and predictors of HCV antibody serostatus. Methods. Routine programmatic data on patients enrolled in Muhimbili National Hospital’s OTP clinic from February 2011 to January 2013 were utilized. Multivariable Poisson regression was used to examine factors associated with HCV antibody serostatus. Results. A total of 630 PWID enrolled into the OTP clinic during the study period, seven percent of which were women. The overall seroprevalence of HCV antibody was 57% (95% Confidence interval: 53%-61%). In adjusted analysis, methadone patients who used heroin for 5-10 years (adjusted prevalence ratio; aPR=1.41; 95% CI: 1.10-1.81) and >10 years (aPR=1.48; 95% CI: 1.17-1.88) were more likely to be HCV antibody positive, compared to patients who used heroin for < 5 years. Patients who reported sharing needles or other equipment at their last injection (aPR=1.20; 95% CI: 1.01-1.41; p=0.022), being arrested (aPR=1.20; 95% CI: 1.04-1.40; p=0.012) and who were HIV-positive (aPR=1.84; 95% CI: 1.56-2.16; p<0.001) were also more likely to be HCV antibody positive than their counterparts. Conclusion. Our observed HCV antibody prevalence among PWID engaged in OTP is higher than previously reported estimates in Dar es Salaam. Predictors of HCV antibody serostatus in this sample were similar to those found among PWID in many other settings. Integrating HCV care and treatment into OTP clinics should be considered, leveraging lessons learned from the integration of HIV services into OTP. Global efforts to develop HCV care and treatment programs in low and middle-income countries are critical, especially among PWID who have a high burden of HCV.
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