21 research outputs found
Investigating the associations between plasmodium infections and autoimmunity in sub-Saharan Africa
No full textAutoimmune diseases affect 5- 8% of the global population and are known to occur due to a misguided immune response towards the host, consequently affecting several organs. Importantly, infections are considered key environmental triggers of autoimmunity and contribute to the onset of autoimmune diseases, though this idea remains controversial. In this research, I focus on malaria, a disease caused by Plasmodium species, which has been linked to autoimmunity through the induction of anti-self-antibodies, with higher levels of autoantibodies associated with disease severity. By contrast, there is evidence suggesting that autoantibodies play a crucial role in anti-malarial protection, with increased autoantibodies shown to inhibit parasite growth. Thus, autoantibodies play a dual role in protection and pathology. However, this raises a crucial question on whether the induction of autoimmune antibodies during malaria increases predisposition to autoimmune disease later in life.
Herein, anti-citrullinated protein autoantibodies (ACPA) commonly associated with clinical diagnosis of rheumatoid arthritis and their corresponding native peptides were first screened using ELISA in mice infected with the model pathogen Plasmodium chabaudi. This approach was chosen to investigate whether Plasmodium triggers ACPA production, providing insights into the potential link between Plasmodium infections and autoimmunity. Subsequently, the impact of heightened antibody responses to both the native and citrullinated peptides on the development of a model of experimental arthritis in mice was assessed. Extending the findings to humans, serum samples obtained from individuals residing in areas with varying levels of malaria exposure were examined for the presence of autoimmune markers using ELISA and protein microarray assays. This was followed by assessing differential cellular immune phenotypes using flow cytometry.
Interestingly, increased levels of antibody responses to both the native and citrullinated peptides were observed in the P. chabaudi-infected mice with levels comparable to those observed in a chronic experimental arthritis model. However, despite the elevated autoantibodies, under the experimental conditions used in our study, infection-induced autoantibodies did not appear to influence the outcome of either acute or chronic experimental arthritis in mice.
Furthermore, expanding our findings to adults and children residing in malariaendemic areas, I observed that individuals living in high malaria transmission areas exhibited elevated antibody responses to both the native and citrullinated peptides compared to those in low transmission areas. Interestingly, a similar trend was observed in children, particularly children with uncomplicated and severe malaria who had increased levels of autoantibodies compared to healthy children. In addition, protein microarray data suggested that individuals from a high malaria transmission area had an overall increase in autoimmune reactivity. Notably, higher levels of antibodies against both the native and citrullinated peptides were also associated with increased frequency of atypical B cells (CD27⁻ CD21⁻CD11c⁺T-bet⁺) and a reduction in the levels of FOXP3 regulatory T cells.
My research indicates that Plasmodium infection leads to a broad spectrum of autoantibodies, including responses to both the native and citrullinated peptides as well as extracellular antigens, mirroring a profile of increased autoantibodies typically observed in autoimmune diseases. Moreover, in this study, I report the presence of elevated antibody responses to these peptides in both Plasmodium infected mice and humans residing in areas of high Plasmodium falciparum transmission. Notably, the pre-existing autoantibody response to these peptides from a single Plasmodium infection episode did not modulate susceptibility to experimental autoimmune arthritis. Thus, the effect and role of chronic exposures to P. falciparum infections on the risk of developing autoimmune diseases in people living in endemic areas cannot be ruled out and should be determined
Serological Profiling for Malaria Surveillance Using a Standard ELISA Protocol
No full textThe enzyme-linked immunosorbent assay (ELISA) is a reliable and relatively low-cost method for measuring soluble ligands such as antibodies and proteins in biological samples. For analysis of specific antibodies in serum, a capture antigen is immobilized onto a solid polystyrene surface from which it can capture the antibodies. The captured antibodies are subsequently detected using a secondary antibody conjugated to an enzyme. Detection is accomplished by addition of a colorimetric substrate, and the readout is absorbance (optical density). Here, we provide a detailed standardized ELISA protocol for the quantification of antibodies against malaria antigens
Molecular characterization and antibiotic resistance profiles of Salmonella isolated from fecal matter of domestic animals and animal products in Nairobi
No full textAbstract
Background
Salmonella has significant public health implications causing food borne and zoonotic diseases in humans. Treatment of infections due to Salmonella is becoming difficult due to emergence of drug resistant strains. There is therefore need to characterize the circulating non-typhoidal Salmonella (NTS) serovars in domestic animals and animal products in Kenya as well as determine their antibiotic resistance profiles.
Methods
A total of 740 fecal samples were collected from cows ( n \u2009=\u2009150), pigs ( n \u2009=\u2009182), chicken ( n \u2009=\u2009191) and chicken eggs ( n \u2009=\u2009217) from various markets and abattoirs in Nairobi. The prevalence of NTS serovars using culture techniques and biochemical tests, antimicrobial sensitivity testing using disc diffusion method of the commonly prescribed antibiotics and phylogenetic relationships using 16S rRNA were determined.
Results
The results showed that the overall prevalence of Salmonella was 3.8, 3.6, 5.9 and 2.6% for pigs, chicken, eggs and cows respectively. Two serovars were isolated S. Typhimurium (85%) and S. Enteritidis (15%) and these two serovars formed distinct clades on the phylogenetic tree. Forty percent of the isolates were resistant to one or more antibiotics.
Conclusion
The isolation of Salmonella Typhimurium and Salmonella Enteritidis that are resistant to commonly used antibiotics from seemingly healthy animals and animal products poses a significant public health threat. This points to the need for regular surveillance to be carried out and the chain of transmission should be viewed to ascertain sources of contamination
Prospects for equitable growth in rural sub-Saharan Africa
No full textImproving agricultural technology equitably in Africa has been difficult in the past because of the vast differences, as well as weak institutions and infrastructure in its many regions. However, the prospects for equitable growth are good for several reasons. The distribution of land has not deteriorated, and there are few landless people in Africa. Technical packages do not favor large farms over small ones, and Africa's social institutions support people with a safety net for sources of income. The author, however, points out that equitable growth, though possible is not assured and several research and policy initiatives will be needed to capitalize on the potential. First, research must continue to focus on technology appropriate for small farms and crops. Policy makers must no longer withhold assistance from service enterprises or nonfarm activities of women. Rural infrastructure has to be upgraded, and finally, governments will need to monitor land tenure and tenancy.Economic Theory&Research,Agricultural Research,Crops&Crop Management Systems,Environmental Economics&Policies,Agricultural Knowledge&Information Systems
Additional file 2 of Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response
No full textAdditional file 2: Figure S2. Parasite growth based on qPCR outcome and location. Blood samples from C + 8 onwards after inoculation were assessed by qPCR to determine parasitaemia from individuals from low transmission (left panel, Kilifi North—N = 34) and high transmission (right panel, Kilifi South—N = 93 and Ahero—N = 15). Parasitaemia was determined by asexual 18S ribosomal RNA gene qPCR done in Kilifi. Blue line s represent individuals who required treatment and reached diagnosis threshold (Treated); green lines represent individuals who did not meet the diagnosis threshold but were qPCR positive (Untreated PCR +ve); orange lines representindividuals who were qPCR negative throughout monitoring (PCR −ve); and red dot denotes individuals who were febrile and who required treatment and reached diagnosis threshold (Febrile)
Additional file 4 of Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response
No full textAdditional file 4: Figure S4. Spearman correlations of qPCR metrics. Correlation matrix of qPCR metrics showed collinearity for phenotype (treated vs untreated), time to thresholds (1000 parasites/ml; 500 parasites/ml; 250 parasites/ml; 50 parasites/ml; 5 parasites/ml; and 1 parasite/ml) or to diagnosis, and mean qPCR/gradient/days of growing (maximum days consecutively growing; median days of growth; proportion of days growing) or decline (maximum days consecutively decline; median days of decline; proportion of days declining), and other parasite growth metrics. Inoculum represents peak at days from days 8.5 to 10 post-infection; proportion of days with parasite growth represents analysis of smoothed data; proportion of days with parasite growth represents analysis of raw data; and variability represents the summed/average day to day increase or decrease
Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response
No full textBackground
Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure.
Methods
We analysed data from 142 Kenyan adults from three locations representing distinct areas of malaria endemicity (Ahero, Kilifi North and Kilifi South) enrolled in a CHMI study with Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify the in vivo outcomes that most closely reflected naturally acquired immunity, parameters based on qPCR measurements were compared with anti-schizont antibody levels and residence as proxy markers of naturally acquired immunity.
Results
Time to endpoint correlated more closely with anti-schizont antibodies and location of residence than other parasite parameters such as growth rate or mean parasite density. Compared to observational field-based studies in children where 0.8% of the variability in malaria outcome was observed to be explained by anti-schizont antibodies, in the CHMI model the dichotomized anti-schizont antibodies explained 17% of the variability.
Conclusions
The CHMI model is highly effective in studying markers of naturally acquired immunity to malaria.
Trial registration Clinicaltrials.gov number NCT02739763. Registered 15 April 201
Additional file 5 of Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response
No full textAdditional file 5: Table S1. Sub-group analysis of qPCR outcome in relation to anti-schizont antibody responses. Table S2. Parametric analysis of qPCR parameters with anti-schizont antibody responses and location
Malaria attributable fractions with changing transmission intensity: Bayesian latent class vs logistic models
No full textBACKGROUND: Asymptomatic carriage of malaria parasites is common in high transmission intensity areas and confounds clinical case definitions for research studies. This is important for investigations that aim to identify immune correlates of protection from clinical malaria. The proportion of fevers attributable to malaria parasites is widely used to define different thresholds of parasite density associated with febrile episodes. The varying intensity of malaria transmission was investigated to check whether it had a significant impact on the parasite density thresholds. The same dataset was used to explore an alternative statistical approach, using the probability of developing fevers as a choice over threshold cut-offs. The former has been reported to increase predictive power. METHODS: Data from children monitored longitudinally between 2005 and 2017 from Junju and Chonyi in Kilifi, Kenya were used. Performance comparison of Bayesian-latent class and logistic power models in estimating malaria attributable fractions and probabilities of having fever given a parasite density with changing malaria transmission intensity was done using Junju cohort. Zero-inflated beta regressions were used to assess the impact of using probabilities to evaluate anti-merozoite antibodies as correlates of protection, compared with multilevel binary regression using data from Chonyi and Junju. RESULTS: Malaria transmission intensity declined from over 49% to 5% between 2006 and 2017, respectively. During this period, malaria attributable fraction varied between 27–59% using logistic regression compared to 10–36% with the Bayesian latent class approach. Both models estimated similar patterns of fevers attributable to malaria with changing transmission intensities. The Bayesian latent class model performed well in estimating the probabilities of having fever, while the latter was efficient in determining the parasite density threshold. However, compared to the logistic power model, the Bayesian algorithm yielded lower estimates for both attributable fractions and probabilities of fever. In modelling the association of merozoite antibodies and clinical malaria, both approaches resulted in comparable estimates, but the utilization of probabilities had a better statistical fit. CONCLUSIONS: Malaria attributable fractions, varied with an overall decline in the malaria transmission intensity in this setting but did not significantly impact the outcomes of analyses aimed at identifying immune correlates of protection. These data confirm the statistical advantage of using probabilities over binary data. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-022-04346-9
Additional file 3 of Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response
No full textAdditional file 3: Figure S3. Anti-schizont antibody titres in relation to CHMI qPCR category outcomes. Violin plots of the anti-schizont antibody units (AU) measured from each of the 142 volunteers at screening by ELISA. Plasma samples obtained at screening from each individual volunteer were assessed for IgG specific responses to schizont extract. Indicated within each violin plot are boxplots with the median (dark solid line), minimum and maximum. Each individual is represented by each individual closed circle based on either low transmission (blue) or high transmission (peach)
