BackgroundSerum lipid profile changes have been observed during malaria infection. The underlying biological mechanisms remain unclear. The aim of this paper is to provide an overview on those serum lipid profile changes, and to discuss possible underlying biological mechanisms and the role of lipids in malaria pathogenesis.MethodsA systematic review and meta-analysis to determine lipid profile changes during malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to 11 July, 2013, that measured serum lipid parameters in malaria patients. Also, major trial registries were searched. Mean differences in lipid profile parameters were combined in fixed and random effects meta-analysis, with a separate analysis for different groups of controls (healthy, other febrile illnesses or very low parasitaemia). These parameters were also compared between severe malaria and uncomplicated malaria. Funnel plots were used to test for publication bias.ResultsOf 2,518 studies reviewed, 42 met the criteria for inclusion in the qualitative analysis, and of these, 15 reported the necessary data for inclusion in the meta-analysis for cholesterol; nine for high-density lipoprotein (HDL), eight for low-density lipoprotein (LDL), and nine for triglycerides, respectively. Total cholesterol, HDL and LDL concentrations were lower in malaria and other febrile diseases compared to healthy controls. The decline was more pronounced and statistically significant during malaria compared to other febrile diseases. These results were consistent across included studies. Triglycerides were raised compared to healthy controls, but not statistically significant when compared to symptomatic controls.ConclusionsThis meta-analysis suggests that the observed lipid profile changes are characteristic for malaria. Although a definite link with the pathogenesis of malaria cannot yet be demonstrated, plausible hypotheses of biological mechanisms involving host lipid alterations and the pathogenesis of malaria exist. An increased research effort to elucidate the precise pathways is warranted, since this could lead to better understanding of malaria pathophysiology and consequently to novel treatment approaches.

IntroductionPrompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity.Methods and FindingsPBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07–3.1%). On day 180, these cells were still present (median 0.06%, range 0.02–0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells.ConclusionThe presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35–40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity.

BackgroundArtemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike.MethodsA PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014.ResultsThe literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi.ConclusionACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority.Trial registrationCRD42014009103Electronic supplementary materialThe online version of this article (doi:10.1186/1475-2875-13-463) contains supplementary material, which is available to authorized users.

BackgroundRetention to HIV care is vital for patients’ survival, to prevent onward transmission and emergence of drug resistance. Travelling to receive care might influence adherence. Data on the functioning of and retention to HIV care in the Central African region are limited.MethodsThis retrospective study reports outcomes and factors associated with retention to HIV care at a primary HIV clinic in Lambaréné, Gabon. Adult patients who presented to this clinic between January 2010 and January 2012 were included. Outcomes were retention in care (defined as documented show-up for clinical visits, regardless of delay) or LTFU (defined as a patient not retained in care; on ART or ART naïve, not returning to care during the study period with a patient delay for scheduled visits of more than 6 months), and mortality. Cox regression analysis was used to assess factors associated with respective outcomes. Qualitative data on reasons for LTFU were obtained from focus-group discussions.ResultsOf 223 patients included, 67.3% were female. The mean age was 40.5 (standard deviation 11.4) years and the median CD4 count 275 (interquartile range 100.5–449.5) cells/μL. In total, 34.1% were lost to follow up and 8.1% died. Documented tuberculosis was associated with increased risk of being LTFU (adjusted hazard ratio (aHR) 1.80, 95% confidence interval (95% CI) 1.05–3.11, P = 0.03), whereas early starting anti-retroviral therapy (ART) was associated with a decreased risk of LTFU (aHR 0.43, 95%CI 0.24–0.76, P = 0.004), as was confirmed by qualitative data.ConclusionsRetention to HIV care in a primary clinic in Gabon is relatively poor and interventions to address this should be prioritized in the HIV program. Early initiation of ART might improve retention in care.

BackgroundMalaria is a potentially lethal illness for which preventive measures are not optimally used among all travellers. Travellers visiting friends and relatives in their country of origin (VFRs) are known to use chemoprophylaxis less consistently compared to tourist travellers. In this study, factors explaining the low use of chemoprophylaxis were pursued to contribute to improving uptake of preventive measures among VFRs.MethodsFollowing in-depth interviews with Ghanaians living in Amsterdam, a questionnaire was developed to assess which behavioural determinants were related to taking preventive measures. The questionnaire was administered at gates of departing flights from Schiphol International Airport, Amsterdam (the Netherlands) to Kotoka International Airport, Accra (Ghana).ResultsIn total, 154 questionnaires were eligible for analysis. Chemoprophylaxis had been started by 83 (53.9%) and bought by 93 (60.4%) travellers. Pre-travel advice had been obtained by 104 (67.5%) travellers. Those who attended the pre-travel clinic and those who incorrectly thought they had been vaccinated against malaria were more likely to use preventive measures. Young-, business- and long-term travellers, those who had experienced malaria, and those who thought curing malaria was easier than taking preventive tablets were less likely to use preventive measures.ConclusionAlmost half of the VFRs travelling to West Africa had not started chemoprophylaxis; therefore, there is room for improvement. Risk reduction strategies could aim at improving attendance to travel clinics and focus on young-, business and long term travellers and VFRs who have experienced malaria during consultation. Risk reduction strategies should focus on improving self-efficacy and conceptions of response efficacy, including social environment to aim at creating the positive social context needed.

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Travelers with medical conditions had a higher risk of obtaining TRD, predominantly gastrointestinal in nature.

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