Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

Abstract

Background Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Methods Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. Results IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Conclusion Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.

High proportions of pfhrp2 gene deletion and performance of HRP2-based rapid diagnostic test in Plasmodium falciparum field isolates of Odisha

“…In spite of less number of samples collected during summer and winter (Table 1 ), the proportions of RDT negative for P. falciparum was higher in these periods compared to samples collected during the peak season of transmission in rain. This observation is consistent with the earlier reports of fall of sensitivity of RDT with decrease in transmission intensity [ 39 , 44 – 46 ]. Similar to present findings, high prevalence of PfHRP 2 -negative isolates in Mali has been recorded at the end of summer [ 39 ].…”

Immunity as a predictor of anti-malarial treatment failure: a systematic review

“…All eight included studies examined patients infected with P. falciparum, and included clinical efficacy cohort studies, randomized control trials and nested case–control studies. Participants were recruited with uncomplicated malaria in seven studies [ 22 – 28 ], one study included participants with uncomplicated and severe malaria [ 29 ], and two excluded patients with severe malaria from participation [ 25 , 28 ]. All studies included active follow-up of patients until at least day 28 (Table 2 ).…”

“…All studies included active follow-up of patients until at least day 28 (Table 2 ). The majority of the studies (n = 7) were conducted in Africa in children under 15 years old [ 22 – 28 ], with one conducted in Southeast Asia that reported only adult participants [ 29 ] (Table 2 ). First-line artemisinin derivatives, artemether (AM) and artesunate (AS), were assessed in two studies as either monotherapy (AM [ 28 , 29 ], AS [ 29 ]), in combination with lumefantrine (LM) [ 28 , 29 ] or with the antibiotic azithromycin (AZ) [ 29 ].…”

“…First-line artemisinin derivatives, artemether (AM) and artesunate (AS), were assessed in two studies as either monotherapy (AM [ 28 , 29 ], AS [ 29 ]), in combination with lumefantrine (LM) [ 28 , 29 ] or with the antibiotic azithromycin (AZ) [ 29 ]. The most common anti-malarial treatments studied were amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP), which were assessed as mono- or combination therapy in five of the eight studies [ 22 – 25 , 27 ]. A further two studies investigated the association between P. falciparum antibody responses and chloroquine treatment failure (CQ) [ 22 , 26 ] (Table 2 ).…”

Host immunity to Plasmodium falciparum and the assessment of emerging artemisinin resistance in a multinational cohort

“…The operational implications of an effect of host immunity on parasite clearance measures are that in populations with high levels of immunity and faster parasite clearance, early signs of low-grade drug resistance could go undetected, and conversely, that in populations with lower immunity and slower parasite clearance, a false impression of reduced drug efficacy could arise (16)(17)(18). The available immunological evidence for this comes from previous single-study-site investigations, predominantly in hightransmission settings in Africa, which have reported conflicting associations between immunity and treatment failure to historical first-line treatments (e.g., chloroquine, sulfadoxine-pyrimethamine) and ACTs (19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Of the four single-site studies looking at artemisinin derivatives, all examined ACT, where associations may be confounded by the partner drug, and all were performed in areas before the emergence of artemisinin resistance or in areas where resistance is yet to arise (24)(25)(26)(27).…”