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1.  Breadth of Anti-Merozoite Antibody Responses Is Associated With the Genetic Diversity of Asymptomatic Plasmodium falciparum Infections and Protection Against Clinical Malaria 
The breadth of antibody responses to vaccine candidate merozoite antigens was positively correlated with the number of Plasmodium falciparum clones in asymptomatic infections. In combination, high diversity of antibody responses and parasite populations predicted the highest protection against clinical malaria.
Background. Elucidating the mechanisms of naturally acquired immunity to Plasmodium falciparum infections would be highly valuable for malaria vaccine development. Asymptomatic multiclonal infections have been shown to predict protection from clinical malaria in a transmission-dependent manner, but the mechanisms underlying this are unclear. We assessed the breadth of antibody responses to several vaccine candidate merozoite antigens in relation to the infecting parasite population and clinical immunity.
Methods. In a cohort study in Tanzania, 320 children aged 1–16 years who were asymptomatic at baseline were included. We genotyped P. falciparum infections by targeting the msp2 gene using polymerase chain reaction and capillary electrophoresis and measured antibodies to 7 merozoite antigens using a multiplex assay. We assessed the correlation between the number of clones and the breadth of the antibody response, and examined their effects on the risk of malaria during 40 weeks of follow-up using age-adjusted multivariate regression models.
Results. The antibody breadth was positively correlated with the number of clones (RR [risk ratio], 1.63; 95% confidence interval [CI], 1.32–2.02). Multiclonal infections were associated with a nonsignificant reduction in the risk of malaria in the absence of antibodies (RR, 0.83; 95% CI, .29–2.34). The breadth of the antibody response was significantly associated with a reduced risk of malaria in the absence of infections (RR, 0.25; 95% CI, .09–.66). In combination, these factors were associated with a lower risk of malaria than they were individually (RR, 0.14; 95% CI, .04–.48).
Conclusions. These data suggest that malaria vaccines mimicking naturally acquired immunity should ideally induce antibody responses that can be boosted by natural infections.
PMCID: PMC3805176  PMID: 23983244
malaria; immunity; multiclonal infections; merozoite surface antigens; antibodies
2.  Does feeling respected influence return to work? Cross-sectional study on sick-listed patients’ experiences of encounters with social insurance office staff 
BMC Public Health  2013;13:268.
Previous research shows that how patients perceive encounters with healthcare staff may affect their health and self-estimated ability to return to work. The aim of the present study was to explore long-term sick-listed patients’ encounters with social insurance office staff and the impact of these encounters on self-estimated ability to return to work.
A random sample of long-term sick-listed patients (n = 10,042) received a questionnaire containing questions about their experiences of positive and negative encounters and item lists specifying such experiences. Respondents were also asked whether the encounters made them feel respected or wronged and how they estimated the effect of these encounters on their ability to return to work. Statistical analysis was conducted using 95% confidence intervals (CI) for proportions, and attributable risk (AR) with 95% CI.
The response rate was 58%. Encounter items strongly associated with feeling respected were, among others: listened to me, believed me, and answered my questions. Encounter items strongly associated with feeling wronged were, among others: did not believe me, doubted my condition, and questioned my motivation to work. Positive encounters facilitated patients’ self-estimated ability to return to work [26.9% (CI: 22.1-31.7)]. This effect was significantly increased if the patients also felt respected [49.3% (CI: 47.5-51.1)]. Negative encounters impeded self-estimated ability to return to work [29.1% (CI: 24.6-33.6)]; when also feeling wronged return to work was significantly further impeded [51.3% (CI: 47.1-55.5)].
Long-term sick-listed patients find that their self-reported ability to return to work is affected by positive and negative encounters with social insurance office staff. This effect is further enhanced by feeling respected or wronged, respectively.
PMCID: PMC3623723  PMID: 23522034
Encounters; Ethics; Long-term sickness absentees; Return to work; Social insurance office staff; Sweden
3.  Plasmodium falciparum Infection Patterns Since Birth and Risk of Severe Malaria: A Nested Case-Control Study in Children on the Coast of Kenya 
PLoS ONE  2013;8(2):e56032.
Children in malaria endemic areas acquire immunity to severe malaria faster than to mild malaria. Only a minority of children suffers from severe malaria and it is not known what determines this. The aim of this study was to establish how P. falciparum infections during the first years of life affect the risk of severe malaria. A matched case-control study was nested within a large birth cohort set up to study the immunoepidemiology of pneumococci on the Kenyan coast. Infection patterns in three-monthly blood samples in cohort children admitted to hospital with severe malaria were compared to controls matched on age, residential location and time of sampling. P. falciparum detected at least once from birth conferred an increased risk of severe malaria and particularly if multiclonal infections, as characterized by genotyping of a polymorphic antigen gene, were ever detected. The results show for the first time that children with severe malaria have more infections early in life compared to community controls. These findings provide important insights on the immunity to severe disease, knowledge essential for the development of a vaccine against severe malaria.
PMCID: PMC3572150  PMID: 23418502
4.  cis-{2,6-Bis[(di-tert-butyl­phosphan­yl)meth­yl]cyclo­hexyl-κ3 P,C 1,P′}chloridopalladium(II) 
The PdII atom in the title compound, [Pd(C24H49P2)Cl], has a distorted square-planar CClP2 coordination geometry with the P,C,P′-tridentate ligand forming two five-membered metallacycles. The cyclo­hexane ring is aligned with the PdII coordination plane due to C—H activation in an equatorial position, giving a tri-equatorial conformation of the cyclo­hexyl ring.
PMCID: PMC3588760  PMID: 23468725
5.  Plasmodium falciparum Line-Dependent Association of In Vitro Growth-Inhibitory Activity and Risk of Malaria 
Infection and Immunity  2012;80(5):1900-1908.
Plasmodium falciparum's ability to invade erythrocytes is essential for its survival within the human host. Immune mechanisms that impair this ability are therefore expected to contribute to immunity against the parasite. Plasma of humans who are naturally exposed to malaria has been shown to have growth-inhibitory activity (GIA) in vitro. However, the importance of GIA in relation to protection from malaria has been unclear. In a case-control study nested within a longitudinally followed population in Tanzania, plasma samples collected at baseline from 171 individuals (55 cases and 116 age-matched controls) were assayed for GIA using three P. falciparum lines (3D7, K1, and W2mef) chosen based on their erythrocyte invasion phenotypes. Distribution of GIA differed between the lines, with most samples inhibiting the growth of 3D7 and K1 and enhancing the growth of W2mef. GIA to 3D7 was associated with a reduced risk of malaria within 40 weeks of follow-up (odds ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.96; P = 0.04), whereas GIA to K1 and W2mef was not. These results show that GIA, as well as its association with protection from malaria, is dependent on the P. falciparum line and can be explained by differences in erythrocyte invasion phenotypes between parasite lines. Our study contributes knowledge on the biological importance of growth inhibition and the potential influence of P. falciparum erythrocyte invasion phenotypic differences on its relationship to protective immunity against malaria.
PMCID: PMC3347460  PMID: 22392930
6.  Respectful encounters and return to work: empirical study of long-term sick-listed patients' experiences of Swedish healthcare 
BMJ Open  2011;1(2):e000246.
To study long-term sick-listed patients' self-estimated ability to return to work after experiences of healthcare encounters that made them feel either respected or wronged.
A cross-sectional and questionnaire-based survey was used to study a sample of long-term sick-listed patients (n=5802 respondents). The survey included questions about positive and negative encounters as well as reactions to these encounters, such as ‘feeling respected’ and ‘feeling wronged’. The questionnaire also included questions about the effects of these encounters on the patients' ability to return to work.
Among patients who had experienced positive encounters, those who also felt respected (n=3327) demonstrated significantly improved self-estimated ability to return to work compared to those who did not feel respected (n=79) (62% (95% CI 60% to 64%) vs 34% (95% CI 28% to 40%)). Among patients with experiences of negative encounters, those who in addition felt wronged (n=993) claimed to be significantly more impeded from returning to work compared to those who did not feel wronged (n=410) (50% (95% CI 47% to 53%) vs 31% (95% CI 27% to 35%)).
The study indicates that positive encounters in healthcare combined with feeling respected significantly facilitate sickness absentees' self-estimated ability to return to work, while negative encounters combined with feeling wronged significantly impair it.
Article summary
Article focus
To what extent can positive and perceived respectful healthcare encounters influence long-term sick-listed patients' ability to return to work?
To what extent can negative and perceived unfair healthcare encounters influence long-term sick-listed patients' ability to return to work?
Key messages
Long-term sick-listed patients' self-estimated ability to return to work is significantly facilitated if healthcare encounters are perceived as respectful.
Long-term sick-listed patients' self-estimated ability to return to work is significantly impeded if healthcare encounters are perceived as unfair.
The net effect of feeling respected was highest among patients with somatic disorders, while the net effect of feeling wronged was highest among patients with psychiatric disorders.
Strengths and limitation of this study
The study sample was large and we obtained quite a high response rate.
The outcome measure was the respondents' self-estimated ability to return to work, not their actual ability.
The findings are based on the views of long-term sick-listed patients and so generalisation may not be possible.
PMCID: PMC3211048  PMID: 22021890
7.  Influences of Intermittent Preventive Treatment and Persistent Multiclonal Plasmodium falciparum Infections on Clinical Malaria Risk 
PLoS ONE  2010;5(10):e13649.
Intermittent preventive treatment (IPT) of malaria involves administration of curative doses of antimalarials at specified time points to vulnerable populations in endemic areas, regardless whether a subject is known to be infected. The effect of this new intervention on the development and maintenance of protective immunity needs further understanding. We have investigated how seasonal IPT affects the genetic diversity of Plasmodium falciparum infections and the risk of subsequent clinical malaria.
Material and Methods
The study included 2227 Ghanaian children (3–59 months) who were given sulphadoxine-pyrimethamine (SP) bimonthly, artesunate plus amodiaquine (AS+AQ) monthly or bimonthly, or placebo monthly for six months spanning the malaria transmission season. Blood samples collected at three post-interventional surveys were analysed by genotyping of the polymorphic merozoite surface protein 2 gene. Malaria morbidity and anaemia was monitored during 12 months follow-up.
Monthly IPT with AS+AQ resulted in a marked reduction in number of concurrent clones and only children parasite negative just after the intervention period developed clinical malaria during follow-up. In the placebo group, children without parasites as well as those infected with ≥2 clones had a reduced risk of subsequent malaria. The bimonthly SP or AS+AQ groups had similar number of clones as placebo after intervention; however, diversity and parasite negativity did not predict the risk of malaria. An interaction effect showed that multiclonal infections were only associated with protection in children without intermittent treatment.
Molecular typing revealed effects of the intervention not detected by ordinary microscopy. Effective seasonal IPT temporarily reduced the prevalence and genetic diversity of P. falciparum infections. The reduced risk of malaria in children with multiclonal infections only seen in untreated children suggests that persistence of antigenically diverse P. falciparum infections is important for the maintenance of protective malaria immunity in high transmission settings.
PMCID: PMC2965101  PMID: 21048970

Results 1-7 (7)