The Plasmodium falciparum merozoite surface protein-1 19 KD antibody response in the Peruvian Amazon predominantly targets the non-allele specific, shared sites of this antigen

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>re-emerged in Iquitos, Peru in 1994 and is now hypoendemic (< 0.5 infections/person/year). Purportedly non-immune individuals with discrete (non-overlapping) <it>P. falciparum </it>infections can be followed using this population dynamic. Previous work demonstrated a strong association between this population's antibody response to <it>Pf</it>MSP1-19KD and protection against febrile illness and parasitaemia. Therefore, some selection for <it>Pf</it>MSP1-19KD allelic diversity would be expected if the protection is to allele-specific sites of <it>Pf</it>MSP1-19KD. Here, the potential for allele-specific polymorphisms in this population is investigated, and the allele-specificity of antibody responses to <it>Pf</it>MSP1-19KD are determined.</p> <p>Methods</p> <p>The 42KD region in <it>Pf</it>MSP1 was genotyped from 160 individual infections collected between 2003 and 2007. Additionally, the polymorphic block 2 region of <it>Pfmsp1 </it>(<it>Pfmsp1</it>-B2) was genotyped in 781 infection-months to provide a baseline for population-level diversity. To test whether <it>Pf</it>MSP1-19KD genetic diversity had any impact on antibody responses, ELISAs testing IgG antibody response were performed on individuals using all four allele-types of <it>Pf</it>MSP1-19KD. An antibody depletion ELISA was used to test the ability of antibodies to cross-react between allele-types.</p> <p>Results</p> <p>Despite increased diversity in <it>Pfmsp1</it>-B2, limited diversity within <it>Pfmsp1</it>-42KD was observed. All 160 infections genotyped were Mad20-like at the <it>Pfmsp1</it>-33KD locus. In the <it>Pfmsp1</it>-19KD locus, 159 (99.4%) were the Q-KSNG-F haplotype and 1 (0.6%) was the E-KSNG-L haplotype. Antibody responses in 105 individuals showed that Q-KNG and Q-TSR alleles generated the strongest immune responses, while Q-KNG and E-KNG responses were more concordant with each other than with those from Q-TSR and E-TSR, and vice versa. The immuno-depletion ELISAs showed all samples responded to the antigenic sites shared amongst all allelic forms of <it>Pf</it>MSP1-19KD.</p> <p>Conclusions</p> <p>A non-allele specific antibody response in <it>Pf</it>MSP1-19KD may explain why other allelic forms have not been maintained or evolved in this population. This has important implications for the use of <it>Pf</it>MSP1-19KD as a vaccine candidate. It is possible that Peruvians have increased antibody responses to the shared sites of <it>Pf</it>MSP1-19KD, either due to exposure/parasite characteristics or due to a human-genetic predisposition. Alternatively, these allelic polymorphisms are not immune-specific even in other geographic regions, implying these polymorphisms may be less important in immune evasion that previous studies suggest.</p

Antibody response dynamics to the Plasmodium falciparum conserved vaccine candidate antigen, merozoite surface protein-1 C-terminal 19kD (MSP1-19kD), in Peruvians exposed to hypoendemic malaria transmission

<p>Abstract</p> <p>Background</p> <p>In high-transmission areas, developing immunity to symptomatic <it>Plasmodium falciparum </it>infections requires 2–10 years of uninterrupted exposure. Delayed malaria-immunity has been attributed to difficult-to-develop and then short-lived antibody responses.</p> <p>Methods</p> <p>In a study area with <0.5 <it>P. falciparum </it>infections/person/year, antibody responses to the MSP1-19kD antigen were evaluated and associations with <it>P. falciparum </it>infections in children and adults. In months surrounding and during the malaria seasons of 2003–2004, 1,772 participants received ≥6 active visits in one study-year. Community-wide surveys were conducted at the beginning and end of each malaria season, and weekly active visits were completed for randomly-selected individuals each month. There were 79 <it>P. falciparum </it>infections with serum samples collected during and approximately one month before and after infection. Anti-MSP1-19kD IgG levels were measured by ELISA.</p> <p>Results</p> <p>The infection prevalence during February-July was similar in children (0.02–0.12 infections/person/month) and adults (0.03–0.14 infections/person/month) and was negligible in the four-month dry season. In children and adults, the seroprevalence was maintained in the beginning (children = 28.9%, adults = 61.8%) versus ending malaria-season community survey (children = 26.7%, adults = 64.6%). Despite the four-month non-transmission season, the IgG levels in <it>Plasmodium</it>-negative adults were similar to <it>P. falciparum</it>-positive adults. Although children frequently responded upon infection, the transition from a negative/low level before infection to a high level during/after infection was slower in children. Adults and children IgG-positive before infection had reduced symptoms and parasite density.</p> <p>Conclusion</p> <p>Individuals in low transmission areas can rapidly develop and maintain αMSP1-19kD IgG responses for >4 months, unlike responses reported in high transmission study areas. A greater immune capacity might contribute to the frequent asymptomatic <it>P. falciparum </it>infections in this Peruvian population.</p

Toxicological, enzymatic, and molecular assessment of the insecticide susceptibility profile of triatoma infestans (Hemiptera: Reduviidae, Triatominae) populations from rural communities of Santa Cruz, Bolivia

A wide range of insecticide resistance profiles has been reported across Bolivian domestic and sylvatic populations of Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae), including some with levels proven to be a threat for vector control. In this work, the insecticide profile of domestic T. infestans was studied with standardized toxicological bioassays, in an area that has not undergone consistent vector control. F1 first-instar nymphs hatched in laboratory from bugs captured in three communities from the Santa Cruz Department were evaluated with different insecticides. Moreover, the enzymatic activity of esterases and cytochrome P450 monooxygenases was measured in individual insects to evaluate the possible mechanism of metabolic resistance to pyrethroids. In addition, the DNA sequence of sodium channel gene (kdr) was screened for two point mutations associated with pyrethroid resistance previously reported in T. infestans. All populations showed reduced susceptibility to deltamethrin and α-cypermethrin, albeit the RR50 values varied significantly among them. Increased P450 monooxygenases and permethrate esterases suggest the contribution, as detoxifying mechanisms, to the observed resistance to deltamethrin in all studied populations. No individuals presented either mutation associated to resistance in the kdr gene. The level of susceptibility to α-cypermethrin, the insecticide used by the local vector control program, falls within an acceptable range to continue its use in these populations. However, the observed RR50 values evidence the possibility of selection for resistance to pyrethroids, especially to deltamethrin. Consequently, the use of pyrethroid insecticides should be closely monitored in these communities, which should be kept under entomological surveillance and sustained interventions.Fil: Santo Orihuela, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación de Plagas e Insecticidas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica. Cátedra de Química Analítica Instrumental; ArgentinaFil: Vassena, Claudia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación de Plagas e Insecticidas; Argentina. Universidad Nacional de San Martín; ArgentinaFil: Carvajal, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación de Plagas e Insecticidas; ArgentinaFil: Clark, Eva. University of Alabama at Birmingahm; Estados Unidos. Baylor College; Estados UnidosFil: Menacho, Silvio. Eiti Health Center; BoliviaFil: Bozo, Ricardo. Hospital Municipal Camiri; BoliviaFil: Gilman, Robert H.. University Johns Hopkins; Estados UnidosFil: Bern, Caryn. University of California; Estados UnidosFil: Marcet, Paula Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Científicas y Técnicas para la Defensa. Centro de Investigación de Plagas e Insecticidas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentin

A Positive Correlation between Atypical Memory B Cells and Plasmodium falciparum Transmission Intensity in Cross-Sectional Studies in Peru and Mali

transmission intensity correlates with atypical memory B cell expansion.. In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61–7.28]; U.S. mean: 1.4% [95% CI: 0.92–1.81]; p<0.0001) but lower than Malian adults (Mali mean 13.1% [95% CI: 10.68–15.57]; p = 0.0001). In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% [95% CI: 4.09–9.11]; no prior episodes mean: 3.1% [95% CI: 1.52–4.73]; p = 0.028). infection could contribute to our understanding of naturally-acquired malaria immunity

Additional value of biomechanical indices based on CTa for rupture risk assessment of abdominal aortic aneurysms

Objective Biomechanics for rupture risk prediction in abdominal aortic aneurysms (AAA) are gaining popularity. However, their clinical applicability is still doubtful as there is lack of standardization. This study evaluates the added value of biomechanical indices in rupture risk assessment. Methods This study included 175 asymptomatic, 11 sAAA and 45 ruptured aneurysms. 3D-geome-tries were reconstructed using computer tomography angiographies. Subsequently, finite element models were made to calculate peak wall stress (PWS), peak wall rupture index (PWRI) and the rupture risk equivalent diameter (RRED). The indices were determined with a dedicated software to facilitate standardization. Results SAAAs showed a trend towards higher PWS, PWRI and RRED compared to asymptomatic AAAs, but PWS (22.0±5.8 vs. 33.4±15.8 N/cm2), PWRI (0.52±0.2 vs. 1.01±0.64), and RRED (65±60 vs. 98±51 mm) were significantly (p = 0.001) higher in ruptured. However, after diameter-matching no significant differences were seen. The ROC-curves for the maximum diameter and all biomechanical indices were similar but it slightly increased when diameter and biomechanical indices were combined. Conclusions This study showed no added value for biomechanical indices in AAA rupture risk assessment. Additionally, the difficulty of such an assessment increases. However, as symptomatic aneurysms show a trend towards higher biomechanical indices with similar diameters the indices may provide information about aneurysm growth and development

Beginning to explore the experience of managing a direct payment for someone with dementia: The perspectives of suitable people and adult social care practitioners

Following legal improvements made around mental capacity together with the Health and Social Care Act, it is now possible for a direct payment to be paid to a 'Suitable Person' to manage on someone's behalf to purchase directly care and support services. People with dementia are a key group affected by this change in England of adult social care. We interviewed nine social care practitioners and seven Suitable People for people with dementia across five English local authorities to begin to examine their experiences of this new method of social care provision. Findings from thematic analyses suggest positive outcomes and multiple beneficiaries, but some challenges: potentially inappropriate processes, support planning, divergence in attitudes towards care and support outcomes. Implications for practice include obfuscation of recipients' and Suitable People's best interests and supporting practitioners to explore fully clients' aspirations for care and support

Resistance to the impact of interruptions during multitasking by healthy adults and dysexecutive patients

Two experiments (one with healthy adult volunteers and the other with controls and dysexecutive patients) assessed the impact of interruptions on a novel test of multitasking. The test involved switching repeatedly between four tasks (block construction, bead threading, paper folding, alphabetical searching) over a 10 minute period. In Experiment 1, there were 4 groups of 20 healthy participants. One group attempted multitasking with no interruption, a second group was interrupted early in the test, a third group late in the test and a fourth group was interrupted both early and late. Interruption involved carrying out a fifth, unexpected task for a period of one minute before returning to the four main tasks. There was no difference in multitasking performance between the groups. In Experiment 2 the participants were seven dysexecutive patients and 14 age-matched controls. A repeated measures approach was employed to assess the impact of two interruptions (early and late) for both groups. Contrary to predictions, the patients as well as controls were resistant to the effects of interruptions, despite their clearly impaired multitasking performance. These results suggest that the ability to deal with interruptions may be separable from the ability to organise and execute multiple tasks within a limited time frame