scholarly journals Evidence that seasonal malaria chemoprevention with SPAQ influences blood and pre-erythrocytic stage antibody responses of Plasmodium falciparum infections in Niger

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lamine Mahaman Moustapha ◽  
Rafiou Adamou ◽  
Maman Laminou Ibrahim ◽  
Mariama Abdoulaye Louis Padounou ◽  
Abdoulaye Diallo ◽  
...  

Abstract Background In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger. Methods This research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes. Results The analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p < 0.0001). Conclusion The research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity.

2020 ◽  
Author(s):  
Lamine Mahaman Moustapha ◽  
Rafiou Adamou ◽  
Maman Laminou Ibrahim ◽  
Mariama Abdoulaye Louis Padounou ◽  
Abdoulaye Diallo ◽  
...  

Abstract Background: In endemic areas, children develop slowly and naturally develop anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in young children in West Africa. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. We evaluated the effect of SMC with SPAQ on malaria antibody concentration in Niger.Methods: This survey was conducted in areas targeted with SMC since 2014 (Zinder district), without SMC (Dosso district), and with one year SMC 2016 (Gaya district). To assess the relationship between SMC and P. falciparum IgG antibody responses, we compared total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3-59 months across the three sites. Antibody concentrations were quantified using an enzyme-linked immunosorbent assay (ELISA) on the elution extracted from positive and negative RDT cassettes.Results: A total of 229 children aged 3-59 months were included in the analysis: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP=17.5µg/ml and GLURP-R2=14.3µg/ml) median antibody concentration observed were higher than in Gaya (CSP=7.7 µg/ml and GLURP-R2=6.5 µg/ml) and Dosso (CSP=4.5 µg/ml and GLURP-R2=3.6 µg/ml) (p<0.0001). Conclusion: We have some evidence that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of Plasmodium falciparum infections in Niger. Future studies are necessary to provide better understanding of the effect of on malaria immunity.


Blood ◽  
1985 ◽  
Vol 65 (4) ◽  
pp. 810-818 ◽  
Author(s):  
HC Chiu ◽  
AK Rao ◽  
C Beckett ◽  
RW Colman

Abstract An 82-year-old woman presented with extensive hematomas and melena associated with markedly decreased plasma factor V coagulant activity (FV:C). Using a competitive enzyme-linked immunosorbent assay developed in our laboratory, we made serial measurements of factor V antigen (FV:Ag) in plasma and found it to be normal or elevated. The patient's plasma was demonstrated to contain an IgG antibody that could neutralize FV:C in normal plasma. The antibody was of restricted heterogeneity (IgG1, IgG2,kappa). Circulating immune complexes containing antibody to factor V and FV:Ag were demonstrated directly in the plasma by immunoelectrophoresis with polyclonal monospecific antibody and with a monoclonal antibody using an enzyme-linked immunosorbent assay. Presence of neutralizing antibody could be demonstrated in vitro even at times when FV:C was within normal limits by heat inactivation of FV:C. Treatment with plasma and platelet transfusions as well as plasmapheresis induced definite but transient elevation of FV:C. Steroid therapy lowered the neutralizing antibody concentration and produced a rapid and persistent elevation of FV:C during two separate hospitalizations. This report describes a patient in whom levels of FV:Ag have been serially measured, and the presence of circulating immune complexes consisting of factor V and a neutralizing antibody have been directly demonstrated.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3936-3936 ◽  
Author(s):  
Nicolas Novitzky ◽  
Yunus Seth ◽  
Rosalia Mothupi

Abstract Splenectomy is very effective in patients with idiopathic thrombocytopenic purpura (ITP) unresponsive to steroids; however it is invasive and has been associated with longstanding immune suppression. We retrospectively reviewed the clinical outcome and laboratory parameters in 52 patients who had undergone splenectomy and had been followed up for a minimum of 5 years. We also studied the long term effectiveness of anti pneumococcal vaccination by testing antibody titres against 5 bacterial antigens. Hospital records of 52 individuals with ITP who required splenectomy were accessed. Of these 52, 47 patients were available for clinical review and consented to provide blood samples to have their laboratory parameters repeated. None of the patients had been treated with prophylactic antibiotics. Except for one, all had received anti pneumococcal vaccination before surgery. The serum anti pneumococcal IgG antibody titres were tested by enzyme linked immunosorbent assay and the results were related to a control group. The complication rate of surgery was 15%, but there was no mortality. Immediately post splenectomy all patients normalised their platelet counts but thrombocytopenia recurred in 6, who required further immunosuppression. Following splenectomy the median time to platelet recovery was 10 days (range 1–90). At 5 years from surgery, 92% remained in response and only 1 / 47 surviving subjects required continuing immunosuppression. In the intervening period subsequent to surgery 5 individuals died. Of these deaths, 4 were unrelated to ITP while 1 patient who had not received anti pneumococcal vaccination, developed rapidly fatal sepsis. At review, patients had significantly higher MCV (p= 0.001), lymphocyte count (p= 0.001) and lower IgM (p= 0.0001). Compared to control samples, of the 5 anti pneumococcal serotypes tested, only the 19F antibody titres were significantly reduced (15.07 ± 17.47 vs. 65.26 ± 79.35 pg/L; p= 0.03) in splenectomised subjects. Splenectomy is highly effective in ITP while the rate of short term complications and long term sequelae appear acceptable. In patients receiving vaccination, anti pneumococcal titres were well maintained and despite no antibiotic prophylaxis no patient in this group developed life threatening infections.


2002 ◽  
Vol 70 (2) ◽  
pp. 820-825 ◽  
Author(s):  
Niklas Ahlborg ◽  
Irene T. Ling ◽  
Wendy Howard ◽  
Anthony A. Holder ◽  
Eleanor M. Riley

ABSTRACT Vaccination of mice with the 42-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP142) or its 19-kDa C-terminal processing product (MSP119) can elicit protective antibody responses in mice. To investigate if the 33-kDa N-terminal fragment (MSP133) of MSP142 also induces protection, the gene segment encoding MSP133 was expressed as a glutathione S-transferase (GST) fusion protein. C57BL/6 and BALB/c mice were immunized with GST-MSP133 and subsequently challenged with the lethal P. yoelii YM blood stage parasite. GST-MSP133 failed to induce protection, and all mice developed patent parasitemia at a level similar to that in naive or control (GST-immunized) mice; mice immunized with GST-MSP119 were protected, as has been shown previously. Specific prechallenge immunoglobulin G (IgG) antibody responses to MSP1 were analyzed by enzyme-linked immunosorbent assay and immunofluorescence. Despite being unprotected, several mice immunized with MSP133 had antibody titers (of all IgG subclasses) that were comparable to or higher than those in mice that were protected following immunization with MSP119. The finding that P. yoelii MSP133 elicits strong but nonprotective antibody responses may have implications for the design of vaccines for humans based on Plasmodium falciparum or Plasmodium vivax MSP142.


1998 ◽  
Vol 5 (4) ◽  
pp. 479-485 ◽  
Author(s):  
Dan M. Granoff ◽  
Susan E. Maslanka ◽  
George M. Carlone ◽  
Brian D. Plikaytis ◽  
George F. Santos ◽  
...  

ABSTRACT The standardized enzyme-linked immunosorbent assay (ELISA) for measurement of serum immunoglobulin G (IgG) antibody responses to meningococcal C polysaccharide has been modified to employ assay conditions that ensure specificity and favor detection primarily of high-avidity antibodies. The modified and standard assays were used to measure IgG antibody concentrations in sera of toddlers vaccinated with meningococcal polysaccharide vaccine or a meningococcal C conjugate vaccine. The results were compared to the respective complement-mediated bactericidal antibody titers. In sera obtained after one or two doses of vaccine, the correlation coefficients, r, for the results of the standard assay and bactericidal antibody titers were 0.45 and 0.29, compared to 0.85 and 0.87, respectively, for the modified assay. With the standard assay, there were no significant differences between the geometric mean antibody responses of the two vaccine groups. In contrast, with the modified assay, 5- to 20-fold higher postvaccination antibody concentrations were measured in the conjugate than in the polysaccharide group. Importantly, the results of the modified assay, but not the standard ELISA, paralleled the respective geometric mean bactericidal antibody titers. Thus, by employing conditions that favor detection of higher-avidity IgG antibody, the modified ELISA provides results that correlate closely with measurements of antibody functional activity that are thought to be important in protection against meningococcal disease.


2020 ◽  
Author(s):  
Victor Yman ◽  
James Tuju ◽  
Michael T White ◽  
Gathoni Kamuyu ◽  
Kennedy Mwai ◽  
...  

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could dramatically improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111 Plasmodium falciparum proteins in travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a novel combination of five serological markers (GAMA, MSP1, MSPDBL1 C- and N-terminal, and PfSEA1) that detect exposure within the previous 3-months with >80% sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-individual variation in response kinetics, and minimal persistence over time. These serological exposure markers can be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination.


2020 ◽  
Vol 8 (11) ◽  
pp. 1722 ◽  
Author(s):  
Frank Msafiri ◽  
Agricola Joachim ◽  
Kathrin Held ◽  
Yuka Nadai ◽  
Raquel Matavele Chissumba ◽  
...  

Antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial were assessed in healthy African volunteers who had been primed three times with HIV-DNA (subtype A, B, C) and then randomized into two groups; group 1 was boosted twice with HIV-MVA (CRF01_AE) and group 2 with the same HIV-MVA coadministered with subtype C envelope (Env) protein (CN54rgp140/GLA-AF). The fine specificity of plasma Env-specific antibody responses was mapped after the final vaccination using linear peptide microarray technology. Binding IgG antibodies to the V1V2 loop in CRF01_AE and subtype C Env and Env-specific IgA antibodies were determined using enzyme-linked immunosorbent assay. Functional antibody-dependent cellular cytotoxicity (ADCC)-mediating antibody responses were measured using luciferase assay. Mapping of linear epitopes within HIV-1 Env demonstrated strong targeting of the V1V2, V3, and the immunodominant region in gp41 in both groups, with additional recognition of two epitopes located in the C2 and C4 regions in group 2. A high frequency of V1V2-specific binding IgG antibody responses was detected to CRF01_AE (77%) and subtype C antigens (65%). In conclusion, coadministration of CN54rgp140/GLA-AF with HIV-MVA did not increase the frequency, breadth, or magnitude of anti-V1V2 responses or ADCC-mediating antibodies induced by boosting with HIV-MVA alone.


2008 ◽  
Vol 15 (5) ◽  
pp. 863-871 ◽  
Author(s):  
Gunnstein Norheim ◽  
Abraham Aseffa ◽  
Mohammed Ahmed Yassin ◽  
Getahun Mengistu ◽  
Afework Kassu ◽  
...  

ABSTRACT Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease.


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