Safety, Immunogenicity, and Protective Efficacy of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Malaria Transmission Season in Healthy African Adult Women of Childbearing Potential in Mali

Author(s):  
2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Protus Omondi ◽  
Marion Burugu ◽  
Damaris Matoke-Muhia ◽  
Edwin Too ◽  
Eva A. Nambati ◽  
...  

Abstract Background The efficacy and safety of artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DP) against asexual parasites population has been documented. However, the effect of these anti-malarials on sexual parasites is still less clear. Gametocyte clearance following treatment is essential for malaria control and elimination efforts; therefore, the study sought to determine trends in gametocyte clearance after AL or DP treatment in children from a malaria-endemic site in Kenya. Methods Children aged between 0.5 and 12 years from Busia, western Kenya with uncomplicated Plasmodium falciparum malaria were assigned randomly to AL or DP treatment. A total of 334 children were enrolled, and dried blood spot samples were collected for up to 6 weeks after treatment during the peak malaria transmission season in 2016 and preserved. Plasmodium falciparum gametocytes were detected by qRT-PCR and gametocyte prevalence, density and mean duration of gametocyte carriage were determined. Results At baseline, all the 334 children had positive asexual parasites by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) children had gametocytes by RT-qPCR. Gametocyte prevalence by RT-qPCR decreased from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4% (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The average duration of gametocyte carriage as estimated by qRT-PCR was slightly shorter in the AL group (4.5 days) than in the DP group (5.1 days) but not significantly different (p = 0.301). Conclusion The study identifies no significant difference between AL and DP in gametocyte clearance. Gametocytes persisted up to 42 days post treatment in minority of individuals in both treatment arms. A gametocytocidal drug, in combination with artemisinin-based combination therapy, will be useful in blocking malaria transmission more efficiently.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alfred Amambua-Ngwa ◽  
David Jeffries ◽  
Julia Mwesigwa ◽  
Aminata Seedy-Jawara ◽  
Joseph Okebe ◽  
...  

Abstract Malaria has declined significantly in The Gambia and determining transmission dynamics of Plasmodium falciparum can help targeting control interventions towards elimination. This can be inferred from genetic similarity between parasite isolates from different sites and timepoints. Here, we imposed a P. falciparum life cycle time on a genetic distance likelihood model to determine transmission paths from a 54 SNP barcode of 355 isolates. Samples were collected monthly during the 2013 malaria season from six pairs of villages spanning 300 km from western to eastern Gambia. There was spatial and temporal hierarchy in pairwise genetic relatedness, with the most similar barcodes from isolates within the same households and village. Constrained by travel data, the model detected 60 directional transmission events, with 27% paths linking persons from different regions. We identified 13 infected individuals (4.2% of those genotyped) responsible for 2 to 8 subsequent infections within their communities. These super-infectors were mostly from high transmission villages. When considering paths between isolates from the most distant regions (west vs east) and travel history, there were 3 transmission paths from eastern to western Gambia, all at the peak (October) of the malaria transmission season. No paths with known travel originated from the extreme west to east. Although more than half of all paths were within-village, parasite flow from east to west may contribute to maintain transmission in western Gambia, where malaria transmission is already low. Therefore, interrupting malaria transmission in western Gambia would require targeting eastern Gambia, where malaria prevalence is substantially higher, with intensified malaria interventions.


2018 ◽  
Vol 4 ◽  
Author(s):  
Hyon-Ok Kim ◽  
Tong-Chan Ko ◽  
Song-Su Kim ◽  
Song-Guk Im ◽  
Yun-Nam Kim

Abstract In Democratic People's Republic of Korea, only Plasmodium vivax malaria is prevalent, which is divided into two forms – long incubation form and short form. Among malaria cases reported in a year, long form accounts for 69% and short form 31%. Incubation period of short form ranges from 10 to 29 days (average 17 days) and long from 5·5 to 16 months (average 8–13 months). The most relapses (90%) were reported from May to September – malaria transmission season in the country. Result from preliminary mass chemoprevention in small size of population before transmission season to find appropriate method showed high protective efficacy in two regimens – one regimen given primaquine 0·25 mg base kg−1 day−1 for 14 days (95%) and another 0·5 mg base kg−1 day−1 for 7 days (94%). During the mass chemoprevention with primaquine, some adverse effects were reported but transient. We consider that mass chemoprevention with primaquine before transmission season is of great significance in disturbing the vivax malaria transmission, in which long incubation form is predominant in countries prevailing seasonal malaria.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Almahamoudou Mahamar ◽  
Djibrilla Issiaka ◽  
Ahamadou Youssouf ◽  
Sidi M. Niambele ◽  
Harouna M. Soumare ◽  
...  

Abstract Background More than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1, MSP-142 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-142 and CSP. Methods In 2017, a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 4–5 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled, 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP, MSP-142 and AMA1 by ELISA. Results The prevalence of antibodies to MSP-142 was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0%, ajusted odd ratio (aOR) = 1.06, 95% confidence intervals (CI 0.62–1.80), p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8%, aOR = 3.16, 95% CI 1.44–6.95, p = 0.004 for AMA-1; and 91.2 vs 81.9%, aOR = 3.14, 95% CI 1.70–5.76, p < 0.001 for CSP). Median antibody levels for anti-MSP-142 IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.64–1.15) and 0.95 ((0.68–1.15), respectively), anti-CSP (1.30 (1.00–1.56) and 1.17 (0.87–1.47)), and anti-AMA-1 (1.45 (1.24–1.68) and 1.41 (1.17–1.64)). Conclusion In an area of high seasonal malaria transmission, children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1, MSP-142 and CSP compared to children who had received SMC for only 2 years suggesting that children who have received SMC for 4 years may not be more at risk of malaria after the cessation of SMC than children who have received SMC for a shorter period.


1990 ◽  
Vol 25 (1-3) ◽  
pp. 237-242 ◽  
Author(s):  
Thor G. Theander ◽  
Lars Hviid ◽  
Yousif A. Abu-Zeid ◽  
NasrEldin H. Abdulhadi ◽  
Bakri O. Saeed ◽  
...  

Parasitology ◽  
2001 ◽  
Vol 123 (2) ◽  
pp. 113-123 ◽  
Author(s):  
A. OFOSU-OKYERE ◽  
M. J. MACKINNON ◽  
M. P. K. SOWA ◽  
K. A. KORAM ◽  
F. NKRUMAH ◽  
...  

A survey of Plasmodium falciparum infection and clone multiplicity in Ghanaian children was carried out to study the effect of the onset of the malaria transmission season on disease incidence. Fortnightly blood samples were collected from 40 children living in the rural town of Dodowa, between February and August 1998. P. falciparum parasite densities were calculated and PCR genotyping was carried out using the polymorphic MSP-1 and MSP-2 genes as target loci for the estimation of the number of parasite clones in each sample. The average clone number was estimated using maximum likelihood techniques and the minimum number of clones per patient was analysed for the effects of age, sex, season, minimum number of clones per child, level of parasitaemia and parasite genotype. The statistical analysis indicated that the more clones a child carried, the more likely they were to have a clinical malaria episode. This was true after adjusting for age and season effects and for the measured circulating parasitaemia. The probability of clinical disease also increased if the MSP-1 MAD 20 and the MSP-2 FC 27 alleles were present. This longitudinal analysis thus indicates that the probability of a Ghanaian child having a symptomatic malaria episode is positively associated with both increasing numbers and novel types of P. falciparum clones.


2004 ◽  
Vol 72 (11) ◽  
pp. 6492-6502 ◽  
Author(s):  
David R. Cavanagh ◽  
Daniel Dodoo ◽  
Lars Hviid ◽  
Jørgen A. L. Kurtzhals ◽  
Thor G. Theander ◽  
...  

ABSTRACT This longitudinal prospective study shows that antibodies to the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP-1) are associated with protection against clinical malaria in an area of stable but seasonal malaria transmission of Ghana. Antibodies to the block 2 region of MSP-1 were measured in a cohort of 280 children before the beginning of the major malaria transmission season. The cohort was then actively monitored for malaria, clinically and parasitologically, over a period of 17 months. Evidence is presented for an association between antibody responses to block 2 and a significantly reduced risk of subsequent clinical malaria. Furthermore, statistical survival analysis provides new information on the duration of the effect over time. The results support a conclusion that the block 2 region of MSP-1 is a target of protective immunity against P. falciparum and, thus, a promising new candidate for the development of a malaria vaccine.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jean Baptiste Yaro ◽  
Alphonse Ouedraogo ◽  
Z. Amidou Ouedraogo ◽  
Amidou Diarra ◽  
Malik Lankouande ◽  
...  

Abstract Background Progress in controlling malaria has stalled in recent years. Today the malaria burden is increasingly concentrated in a few countries, including Burkina Faso, where malaria is not declining. A cohort study was conducted to identify risk factors for malaria infection in children in southwest Burkina Faso, an area with high insecticide-treated net (ITN) coverage and insecticide-resistant vectors. Methods Incidence of Plasmodium falciparum infection was measured in 252 children aged 5 to 15 years, using active and passive detection, during the 2017 transmission season, following clearance of infection. Demographic, socio-economic, environmental, and entomological risk factors, including use of ITNs and insecticide resistance were monitored. Results During the six-month follow-up period, the overall incidence of P. falciparum infection was 2.78 episodes per child (95% CI = 2.66–2.91) by microscopy, and 3.11 (95% CI = 2.95–3.28) by polymerase chain reaction (PCR). The entomological inoculation rate (EIR) was 80.4 infective bites per child over the six-month malaria transmission season. At baseline, 80.6% of children were reported as sleeping under an ITN the previous night, although at the last survey, 23.3% of nets were in poor condition and considered no longer protective. No association was found between the rate of P. falciparum infection and either EIR (incidence rate ratio (IRR): 1.00, 95% CI: 1.00–1.00, p = 0.08) or mortality in WHO tube tests when vectors were exposed to 0.05% deltamethrin (IRR: 1.05, 95% CI: 0.73–1.50, p = 0.79). Travel history (IRR: 1.52, 95% CI: 1.45–1.59, p < 0.001) and higher socio-economic status were associated with an increased risk of P. falciparum infection (IRR: 1.05, 95% CI: 1.00–1.11, p = 0.04). Conclusions Incidence of P. falciparum infection remains overwhelmingly high in the study area. The study findings suggest that because of the exceptionally high levels of malaria transmission in the study area, malaria elimination cannot be achieved solely by mass deployment of ITNs and additional control measures are needed.


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