6320 research outputs found
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Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses
No full textPolyelectrolyte microcapsules (MCs) are potent protein delivery vehicles which can be tailored with ligands to stimulate maturation of dendritic cells (DCs). We investigated the immune stimulatory capacity of monocyte-derived DC (Mo-DC) loaded with these MCs, containing p24 antigen from human immunodeficiency virus type 1 (HIV-1) alone [p24-containing MC (MCp24)] or with the Toll-like receptor ligand 3 (TLR3) ligand poly I:C (MCp24pIC) as a maturation factor. MO-DC, loaded with MCp24pIC, upregulated CCR7, CD80, CD83, and CD86 and produced high amounts of interleukin-12 (IL-12) cytokine, to a similar extent as MCp24 in the presence of an optimized cytokine cocktail. MO-DC from HIV-infected patients under highly active antiretroviral therapy (HAART) exposed to MCp24 together with cytokine cocktail or to MCp24pIC expanded autologous p24-specific CD4(+) and CD8(+) T-cell responses as measured by interferon-gamma (IFN-gamma) and IL-2 cytokine production and secretion. In vivo relevance was shown by immunizing C57BL/6 mice with MCp24pIC, which induced both humoral and cellular p24-specific immune responses. Together these data provide a proof of principle that both antigen and DC maturation signal can be delivered as a complex with polyelectrolyte capsules to stimulate virus-specific T cells both in vitro and in vivo. Polyelectrolyte MCs could be useful for in vivo immunization in HIV-1 and other infection
Trends in pregnancy outcomes in Malawian adolescents receiving antimalarial and hematinic supplements
No full textObjective. To describe pregnancy outcomes of adolescent and adult primigravidae receiving antimalarials and hematinic supplementation and compare findings with a survey in this area a decade earlier. Design. Cross-sectional surveys in intervention and control sites. Setting. Community, antenatal and delivery facilities in Chikwawa, Malawi. A rural area with year round malaria transmission. Methods. Data on antenatal attendance, uptake of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP), birthweight, malaria, anaemia, for 2,152 primigravidae. Outcome measures. Place of delivery, anaemia, malaria, birthweight. Results. Fewer adolescent than adult primigravidae received >/=2 IPTp-SP doses (66 vs. 77.2%, p < 0.001), although more attended for two or more antenatal visits (92.0 vs. 76.7%, p < 0.001). Only 24.1% of adolescent primigravidae attended for hospital delivery. Women resident in intervention sites receiving IPTp-SP community distribution were more likely to choose a community delivery (p < 0.01), and have higher uptake of IPTp-SP (p = 0.036) than women not resident in these villages. Postnatal malaria prevalence was low and did not differ by age or place of delivery. Postnatal anaemia and low birthweight prevalence were higher in adolescents with community deliveries. Maternal anaemia and low birthweight prevalence were lower amongst adolescents in this study compared to estimates from the same population a decade previously. Conclusions. Adolescents had higher anaemia risk, lower IPTp-SP uptake than adults and under a quarter had a hospital delivery. Pregnancy outcomes improved compared to the survey a decade earlier. Monitoring and surveillance is required to reinforce to policy makers the need to improve adolescent coverage for available intervention
The role of KIR gene content and HLA-C group in susceptibility to HTLV-1-associated myelopathy / tropical spastic paraparesis in Peru
No full textHuman T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) affects approximately 5% of HTLV-1-infected individuals. It is poorly understood why only some infected subjects develop this disease, but host genetic factors may determine susceptibility. The innate immune system may influence disease outcome in HTLV-1-infected subjects because of its role in early immune responses to viral infections. Variation in genes encoding killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) molecule ligands may affect the risk of HAM/TSP. We performed a two-stage case-control study to examine the distribution of KIR genes and HLA-Cw groups in Peruvian HTLV-1-infected HAM/TSP subjects and asymptomatic carriers. We also tested for epistatic effects between specific KIR genes and HLA-Cw groups. In the first stage, we found several trends towards association with HAM/TSP or proviral load (PVL). However, these results were not replicated in the second stage. In conclusion, this is the first report on KIR gene frequencies in the Peruvian population and may be of significance in hematopoietic stem-cell transplants. Our study did not reveal significant associations between KIR genes and HLA-Cw groups and HAM/TSP or PVL. However, since our study was only powered to detect larger effects, additional studies using larger cohorts are neede
Vaccinations in patients with immune-mediated inflammatory diseases
No full textPatients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individual
Short, highly effective and inexpensive standardized treatment of multidrug-resistant tuberculosis
No full textRATIONALE: Based on expert opinion, the global guidelines for management of multidrug-resistant tuberculosis impose lengthy and often poorly tolerated treatments. OBJECTIVES: This observational study evaluates the effectiveness of standardized regimens for patients with proven multidrug-resistant tuberculosis previously untreated with second-line drugs in low-income countries. METHODS: Consenting patients were sequentially assigned to one of six standardized treatment regimens. Subsequent cohorts were treated with regimens adapted according to results in prior cohorts, striving to minimize failure and default, while reducing total treatment duration without increasing relapse frequency. Measurements and results: We report the treatment outcome of all patients with laboratory-confirmed multidrug-resistant tuberculosis enrolled from May 1997 to December 2007. The final most effective treatment regimen required a minimum of nine months duration with gatifloxacin, clofazimine, ethambutol, and pyrazinamide throughout, supplemented by prothionamide, kanamycin, and high-dose isoniazid during an intensive phase of a minimum of four months, giving a relapse-free cure of 87.9% (95% confidence interval 82.7% to 91.6%) among 206 patients. Major adverse drug reactions were infrequent and manageable. Compared to the 221 patients treated with regimens based on ofloxacin and commonly prothionamide throughout, the hazard ratio of any adverse outcome was 0.39 (95% confidence interval 0.26-0.59). CONCLUSIONS: Serial regimen formulation guided by overall treatment effectiveness ultimately resulted in treatment outcomes comparable to those obtained with first-line treatment. Confirmatory formal trials in populations with high levels of human immunodeficiency virus co-infection and in populations with a higher initial prevalence of resistance to second-line drugs are require
Taenia solium cysticercosis in the Democratic Republic of Congo: how does pork trade affect the transmission of the parasite?
No full textBACKGROUND: Taenia solium, a zoonotic parasite that is endemic in most developing countries where pork is consumed, is recognised as the main cause of acquired epilepsy in these regions. T. solium has been reported in almost all of the neighboring countries of Democratic Republic of Congo (DRC) but data on the current prevalence of the disease in the country itself are lacking. This study, focusing on porcine cysticercosis (CC), makes part of a first initiative to assess whether cysticercosis is indeed actually present in DRC. METHODS: An epidemiological study on porcine CC was conducted (1) on urban markets of Kinshasa where pork is sold and (2) in villages in Bas-Congo province where pigs are traditionally reared. Tongue inspection and ELISA for the detection of circulating antigen of the larval stage of T. solium were used to assess the prevalence of active CC in both study sites. FINDINGS: The overall prevalence of pigs with active cysticercosis did not significantly differ between the market and the village study sites (38.8 [CI 95%: 34-43] versus 41.2% [CI 95%: 33-49], respectively). However, tongue cysticercosis was only found in the village study site together with a significantly higher intensity of infection (detected by ELISA). INTERPRETATION: Pigs reared at village level are sold for consumption on Kinshasa markets, but it seems that highly infected animals are excluded at a certain level in the pig trade chain. Indeed, preliminary informal surveys on common practices conducted in parallel revealed that pig farmers and/or buyers select the low infected animals and exclude those who are positive by tongue inspection at village level. This study provides the only recent evidence of CC presence in DRC and gives the first estimates to fill an important gap on the African taeniasis/cysticercosis distribution ma
Factors associated with parent-child communication about HIV/AIDS in the United States and Kenya: a cross-cultural comparison
No full textThis study explored parent-child communication about HIV/AIDS among two populations disproportionately affected by HIV. Similar computer-assisted surveys were completed by parents of pre-teens, including 1,115 African American parents of 9-12-year-old children in southeastern US and 403 parents of 10-12-year-old children in Nyanza Province, Kenya. Multivariate analyses identified factors associated with parental report of ever talking to their child about HIV/AIDS. Twenty-nine percent of US parents and 40% in Kenya had never talked to their pre-teen about HIV/AIDS. In both countries, communication was more likely if parents perceived their child to be ready to learn about sex topics, had gotten information to educate their child about sex, and had greater sexual communication responsiveness (skill, comfort, and confidence communicating about sexuality). Programs are needed that help parents assess children's readiness to learn about sexual issues; access accurate information about adolescent sexual risks; and acquire the responsiveness needed to discuss sexual issues, including HIV/AID
Why the west is perceived as being unworthy of cooperation
No full textNatural selection generated a natural sense of justice. This natural sense of justice created a set of natural rights; rights humans accorded to each other in virtue of being members of the same tribe. Sharing the responsibility for natural rights between all members of the same tribe allowed humans to take advantage of all opportunities for cooperation. Human rights are the present day political emanation of natural rights. Theoretically, human rights are accorded by all humans to all humans in virtue of being humans; however, the idea that the corresponding responsibility is now shared among all humans is not broadly accepted. The natural sense of justice creates an ambiguity: on the one hand humans consider the nation they belong to as the social system that should guarantee their human rights (and likewise they do not consider themselves as having responsibility for the human rights of inhabitants of other nations); on the other hand, as cooperation between nations intensifies, expectations of global mutual responsibility increase as well. As the West does not feel responsible for the human rights of humans in the rest of the world, not even for their most basic survival needs, the West is perceived as unworthy of cooperation. If human rights are understood as conditions for the well-functioning communities, lifting the responsibility for the human rights of all humans to the global level can be understood as a condition to take full advantage of all opportunities globalization presents, or as a condition to adequately address all challenges globalization presents. However, this would have to happen without disregarding the particular feelings of mutual responsibility nations embody; we need a sliding scale of responsibility. The first step would be an acknowledgement that all humans are responsible for meeting the very basis survival needs of all humans, which could be achieved through a Framework Convention on Global Health and a Global Health Fun
Molecular epidemiology of Theileria parva in Zambia: the application of molecular biology techniques to analyse diversity in Theileria parva populations in Zambia
No full textTime for "test and treat" in prevention of mother-to-child transmission programs in low- and middle-income countries
No full textSignificant progress has been made in the prevention of mother-to-child transmission (PMTCT) of HIV. In 2008, an estimated 1.4 million pregnant women living with HIV in low- and middle-income countries (LMIC) gave birth and almost half of these accessed antiretroviral drugs to prevent HIV transmission to their infants, which ranged from single-dose nevirapine to full combination antiretroviral therapy (ART). Although this represents a significant increase in ART coverage, much more remains to be done in terms of HIV testing and counseling, establishment of ART eligibility, and postnatal treatment and care. In November 2009, the World Health Organization issued new PMTCT guidelines for LMIC, stressing the benefits of earlier initiation of ART during pregnancy and its continuation throughout the delivery and the breastfeeding periods. A key recommendation of these guidelines is to start ART for all HIV-positive pregnant women with a CD4 count below 350 cells/mm, irrespective of clinical stage. This makes access to CD4 testing more crucial than ever for the successful implementation of PMTCT programs, since clinical staging performs poorly in identifying pregnant women eligible for ART. However, there are still many barriers to accessing CD4 testing in remote health structures implementing antenatal care services, particularly in countries with a high HIV prevalence. In these settings, universal ART initiation among HIV-positive pregnant women, irrespective of CD4 cell count or clinical staging, is a potentially superior strategy for the prevention of vertical transmission and the improvement of mothers' healt