| 1. |
- Cagigi, Alberto, et al.
(författare)
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Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination
- 2021
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:22
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the presence and durability of antibodies against SARS-CoV-2 in the airways is required to provide insights into the ability of individuals to neutralize the virus locally and prevent viral spread. Here, we longitudinally assessed both systemic and airway immune responses upon SARS-CoV-2 infection in a clinically well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity, from asymptomatic infection to fatal disease. In addition, we evaluated how SARS-CoV-2 vaccination influenced the antibody responses in a subset of these individuals during convalescence as compared with naive individuals. Not only systemic but also airway antibody responses correlated with the degree of COVID-19 disease severity. However, although systemic IgG levels were durable for up to 8 months, airway IgG and IgA declined significantly within 3 months. After vaccination, there was an increase in both systemic and airway antibodies, in particular IgG, often exceeding the levels found during acute disease. In contrast, naive individuals showed low airway antibodies after vaccination. In the former COVID-19 patients, airway antibody levels were significantly elevated after the boost vaccination, highlighting the importance of prime and boost vaccinations for previously infected individuals to obtain optimal mucosal protection.
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| 2. |
- Friberg Hietala, Sofia, 1973, et al.
(författare)
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Population pharmacokinetics and pharmacodynamics of artemether and lumefantrine during combination treatment in children with uncomplicated falciparum malaria in Tanzania
- 2010
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Ingår i: Antimicrobial agents and chemotherapy. - 1098-6596. ; 54:11, s. 4780-4788
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Tidskriftsartikel (refereegranskat)abstract
- The combination of artemether and lumefantrine is currently the first line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were included in the model of the parasite dynamics. The population pharmacokinetics and pharmacodynamics of artemether dihydroartemisinin and lumefantrine were modeled in NONMEM. The distribution of artemether was described by a two-compartment model with a rapid absorption and elimination through metabolism to dihydroartemisinin. Dihydroartemisinin concentrations were adequately illustrated by a one compartment model. The pharmacokinetics of artemether was time dependent with typical oral clearance increasing from 2.6 L/h/kg on day one to 10 L/h/kg on day three. The pharmacokinetics of lumefantrine was sufficiently described by a one-compartment model with an absorption lag time. The typical value of CL/F was estimated to 77 mL/h/kg. The proposed semi-mechanistic model of parasite dynamics, while a rough approximation of the complex interplay between malaria parasite and the human host, adequately described the early effect of ARM and DHA concentrations on the parasite density in malaria patients. However the poor precision in some parameters illustrates the need for further data to support and refine this model. The patient study is registered at www.Clinical.Trials.gov, (NCT00336375).
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| 3. |
- Färnert, Anna, et al.
(författare)
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Transmission-dependent tolerance to multiclonal Plasmodium falciparum infection
- 2009
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Ingår i: Journal of Infectious Diseases. - Chicago : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 200:7, s. 1166-1175
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Tidskriftsartikel (refereegranskat)abstract
- Whether the number of concurrent clones in asymptomatic Plasmodium falciparum infections reflects the degree of host protection was investigated in children living in areas with different levels of transmission on the coast of Kenya. The number of concurrent clones was determined on the basis of polymorphism in msp2, which encodes the vaccine candidate antigen merozoite surface protein 2. In a low-transmission area, most children had monoclonal infections, and diversity did not predict a risk of clinical malaria. In an area of moderate transmission, asymptomatic infections with 2 clones were, compared with 1 clone, associated with an increased risk of subsequent malaria. In a comparative assessment in a high-transmission area in Tanzania, multiclonal infections conferred a reduced risk. The different nonlinear associations between the number of clones and malaria morbidity suggest that levels of tolerance to multiclonal infections are transmission dependent as a result of cumulative exposure to antigenically diverse P. falciparum infections.
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| 4. |
- Ivarsson, Anna Clara, et al.
(författare)
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Head-to-head comparison of two loop-mediated isothermal amplification (LAMP) kits for diagnosis of malaria in a non-endemic setting
- 2023
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Ingår i: Malaria Journal. - 1475-2875. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Light microscopy and rapid diagnostic tests (RDT) have long been the recommended diagnostic methods for malaria. However, in recent years, loop-mediated isothermal amplification (LAMP) techniques have been shown to offer superior performance, in particular concerning low-grade parasitaemia, by delivering higher sensitivity and specificity with low laboratory capacity requirements in little more than an hour. In this study, the diagnostic performance of two LAMP kits were assessed head-to-head, compared to highly sensitive quantitative real time PCR (qPCR), in a non-endemic setting. Methods: In this retrospective validation study two LAMP kits; Alethia® Illumigene Malaria kit and HumaTurb Loopamp™ Malaria Pan Detection (PDT) kit, were evaluated head-to-head for detection of Plasmodium-DNA in 133 biobanked blood samples from suspected malaria cases at the Clinical Microbiology Laboratory of Region Skåne, Sweden to determine their diagnostic performance compared to qPCR. Results: Of the 133 samples tested, qPCR detected Plasmodium DNA in 41 samples (defined as true positives), and the two LAMP methods detected 41 and 37 of those, respectively. The results from the HumaTurb Loopamp™ Malaria PDT kit were in complete congruence with the qPCR, with a sensitivity of 100% (95% CI 91.40–100%) and specificity of 100% (95% CI 96.07–100%). The Alethia® Illumigene Malaria kit had a sensitivity of 90.24% (95% CI 76.87–97.28) and a specificity of 95.65% (95% CI 89.24–98.80) as compared to qPCR. Conclusions: This head-to-head comparison showed higher performance indicators of the HumaTurb Loopamp™ Malaria PDT kit compared to the Alethia® illumigene Malaria kit for detection of malaria.
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| 5. |
- Asghar, Muhammad, et al.
(författare)
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Cellular aging dynamics after acute malaria infection : A 12-month longitudinal study
- 2018
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Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 17:1, s. 12702-12702
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Tidskriftsartikel (refereegranskat)abstract
- Accelerated cellular aging and reduced lifespan have recently been shown in birds chronically infected with malaria parasites. Whether malaria infection also affects cellular aging in humans has not been reported. Here, we assessed the effect of a single acute Plasmodium falciparum malaria infection on cellular aging dynamics in travelers prospectively followed over one year in Sweden. DNA and RNA were extracted from venous blood collected at the time of admission and repeatedly up to one year. Telomere length was measured using real-time quantitative PCR, while telomerase activity and CDKN2A expression were measured by reverse transcriptase (RT)-qPCR. Our results show that acute malaria infection affects cellular aging as reflected by elevated levels of CDKN2A expression, lower telomerase activity, and substantial telomere shortening during the first three months postinfection. After that CDKN2A expression declined, telomerase activity increased and telomere length was gradually restored over one year, reflecting that cellular aging was reversed. These findings demonstrate that malaria infection affects cellular aging and the underlying cellular mechanism by which pathogens can affect host cellular aging and longevity need to be elucidated. Our results urge the need to investigate whether repeated malaria infections have more pronounced and long-lasting effects on cellular aging and lifespan (similarly to what was observed in birds) in populations living in malaria endemic areas.
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| 6. |
- Asghar, Muhammad, et al.
(författare)
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Parallel telomere shortening in multiple body tissues owing to malaria infection
- 2016
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Ingår i: Proceedings of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2954 .- 0962-8452. ; 283:1836
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have shown associations between shorter telomere length in blood and weakened immune function, susceptibility to infections, and increased risk of morbidity and mortality. Recently, we have shown that malaria accelerates telomere attrition in blood cells and shortens lifespan in birds. However, the impact of infections on telomere attrition in different body tissues within an individual is unknown. Here, we tested whether malarial infection leads to parallel telomere shortening in blood and tissue samples from different organs. We experimentally infected siskins (Spinus spinus) with the avian malaria parasite Plasmodium ashfordi, and used real-time quantitative polymerase chain reaction (PCR) to measure telomere length in control and experimentally infected siskins. We found that experimentally infected birds showed faster telomere attrition in blood over the course of infection compared with control individuals (repeatedly measured over 105 days post-infection (DPI)). Shorter telomeres were also found in the tissue of all six major organs investigated (liver, lungs, spleen, heart, kidney, and brain) in infected birds compared with controls at 105 DPI. To the best of our knowledge, this is the first study showing that an infectious disease results in synchronous telomere shortening in the blood and tissue cells of internal organs within individuals, implying that the infection induces systemic stress. Our results have far-reaching implications for understanding how the short-term effects of an infection can translate into long-term costs, such as organ dysfunction, degenerative diseases, and ageing.
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| 7. |
- Bereczky, Sándor, et al.
(författare)
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Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population
- 2007
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 9:1, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6–10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10–0.78 Cox regression) for 2–3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.
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| 8. |
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| 9. |
- Enweji, Nizar
(författare)
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Dynamics of Resistant Plasmodium falciparum Parasites
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Persistence of drug resistant Plasmodium falciparum is a major problem to management and control malaria in endemic areas. The focus of this thesis was to study the dynamics of resistant P. falciparum parasites. The study was performed in two African countries: 1) Sudan: Asar village in eastern Sudan, here we examined the persistence of drug sensitive and resistant P. falciparum genotypes among individuals with single-clone and multiple clones infection during the dry season. We genotyped microsatellite loci in the vicinity of the dihydrofolate reductase gene (dhfr) and the dihydropteroate synthase gene (dhps). Microsatellite investigation showed that asymptomatic parasitemia persisted in some patients for several months throughout the dry season and into the next transmission season. In some samples mixed infections were detected, and we noted several cases where the microsatellite haplotype varied from month to month, suggesting turnover of different parasite populations in the blood. This demonstrates that even during asymptomatic infections there can be dynamics within the parasite population in an individual. In addition, we calculated the parasite density throughout the dry season to the next transmission season by using allele-specific quantitative PCR. Parasite density during the dry season fluctuated, but was generally lower than in the first transmission season. A significant difference (P<0.05) between dry and first transmission season was found in regard to the parasite density, whereas no significant difference was observed when dry and second transmission season were compared (P>0.05). 2) Ethiopia: West Arsi zone, one of the malaria endemic zones of the Oromia region. In the first study we determined the prevalence of asymptomatic malaria carriages from November-December 2012. According to PCR the prevalence of sub-microscopic P. falciparum carriage was 19.2%, microscopy-based prevalence was 3.7% while the prevalence was 6.9% using RDT. Based on this, PCR was considered a better tool for measuring Plasmodium prevalence than microscopy and RDT. A second study addressed the genetic diversity of chloroquine resistance (CQR) in P. falciparum by analysing four microsatellite markers in and around the pfcrt gene. Although CQ was withdrawn for more than a decade, 100% of the parasites still carried the Pfcrt K76T mutation. Only the CVIET haplotype was identified. Based on combinations of MS markers, seven different Ethiopian CQR variants (E1-E7) were identified. Both intronic and MS flanking the pfcrt gene showed low levels of diversity.
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| 10. |
- Farouk, Salah E., et al.
(författare)
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Different antibody and cytokine-mediated responses to Plasmodium falciparum parasite in two sympatric ethnic tribes living in Mali
- 2005
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Ingår i: Microbes and infection. - : Elsevier SAS. - 1286-4579 .- 1769-714X. ; 7:1, s. 110-117
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Tidskriftsartikel (refereegranskat)abstract
- The Fulani are known to be less susceptible to Plasmodium falciparum malaria infections and to have lower parasitaemia despite living under similar malaria transmission intensity compared with other ethnic tribes. The aim of the present study was to examine whether the Fulani were more polarised towards Th2 as reflected by higher numbers of malaria-specific IL-4- and IL-10-producing cells and lower numbers of IFN-γ- and IL-12-producing cells as compared to their neighbour ethnic tribe, the Dogon of Mali. Total IgE and both anti-malaria IgE and IgG antibodies were measured by ELISA and the numbers of IL-4-, IFN-γ-, IL-10- and IL-12-producing cells were enumerated using enzyme-linked ImmunoSpot assay (ELISPOT). Numbers of parasite clones were detected by polymerase chain reaction (PCR). The study was performed outside the transmission period and all individuals included were asymptomatic. The results revealed that the Fulani were less parasitised, had fewer circulating parasite clones in their blood, had significantly higher anti-malaria IgG and IgE antibodies and higher proportions of malaria-specific IL-4- and IFN-γ-producing cells compared to the Dogon. The higher antigen-specific production of IL-4 among the Fulani was statistically significant both before and after adjustment for level of spontaneous cytokine production, while greater IFN-γ production only attained statistical significance after adjustment for spontaneous levels. Taken together, the association of higher anti-malarial IgE and IgG antibodies and increased numbers of specific IL-4- and IFN-γ-producing cells compared to the ethnic sympatric tribe, the Dogon, may assist in explaining the lower susceptibility to malaria observed in the Fulani.
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