scholarly journals Selection of Drug Resistance-Mediating Plasmodium falciparum Genetic Polymorphisms by Seasonal Malaria Chemoprevention in Burkina Faso

2014 ◽  
Vol 58 (7) ◽  
pp. 3660-3665 ◽  
Author(s):  
Anyirékun Fabrice Somé ◽  
Issaka Zongo ◽  
Yves-Daniel Compaoré ◽  
Souleymane Sakandé ◽  
François Nosten ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Control Measure ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Content Type ◽  
Development Of Resistance ◽  
Seasonal Malaria Chemoprevention ◽  
To Receive ◽  
Selection Of

ABSTRACTSeasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel subregion of Africa. Another strategy under study is SMC with dihydroartemisinin plus piperaquine (DP).Plasmodium falciparumsingle nucleotide polymorphisms (SNPs) inP. falciparumcrt(pfcrt),pfmdr1,pfdhfr, andpfdhpsare associated with decreased response to aminoquinoline and antifolate antimalarials and are selected by use of these drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs inP. falciparumisolated from children aged 3 to 59 months living in southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3 months in 2009. We compared SNP prevalence before the onset of SMC and 1 month after the third treatment inP. falciparumPCR-positive samples from 120 randomly selected children from each treatment arm and an additional 120 randomly selected children from a control group that did not receive SMC. The prevalence of relevant mutations was increased after SMC with AQ/SP. Significant selection was seen forpfcrt76T (68.5% to 83.0%,P= 0.04),pfdhfr59R (54.8% to 83.3%,P= 0.0002), andpfdhfr108N (55.0% to 87.2%,P= 0.0001), with trends toward selection ofpfmdr186Y,pfdhfr51I, andpfdhps437G. After SMC with DP, only borderline selection of wild-typepfmdr1D1246 (mutant; 7.7% to 0%,P= 0.05) was seen. In contrast to AQ/SP, SMC with DP did not clearly select for known resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the development of resistance to components of this regimen. (This study has been registered at ClinicalTrials.gov under registration no. NCT00941785.)

scholarly journals In VivoSelection of Plasmodium falciparumPfcrtandPfmdr1Variants by Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine in Burkina Faso

2014 ◽  
Vol 59 (1) ◽  
pp. 734-737 ◽  
Author(s):  
Vito Baraka ◽  
Halidou Tinto ◽  
Innocent Valea ◽  
Robert Fitzhenry ◽  
Christopher Delgado-Ratto ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Gene Polymorphisms ◽  
Content Type ◽  
Rational Use ◽  
Selection Of

ABSTRACTPlasmodium falciparumPfcrt-76 andPfmdr1-86 gene polymorphisms were determined during a clinical trial in Burkina Faso comparing the efficacies of dihydroartemisinin-piperaquine (DHA-PPQ) and artemether-lumefantrine (AL). Significant selection ofPfcrt-K76 was observed after exposure to AL and DHA-PPQ, as well as selection ofPfmdr1-N86 after AL but not DHA-PPQ treatment, suggesting reverse selection on thePfcrtgene by PPQ. These results support the rational use of DHA-PPQ in settings where chloroquine (CQ) resistance is high.

scholarly journals Gametocyte carriage after seasonal malaria chemoprevention in Plasmodium falciparum infected asymptomatic children

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Abdullahi Ahmad ◽  
Aurelia Prom ◽  
John Bradley ◽  
Mamadou Ndiath ◽  
Blessed Etoketim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Comparison Group ◽  
Conditional Logistic Regression ◽  
Gametocyte Carriage ◽  
Asymptomatic Children ◽  
Seasonal Malaria Chemoprevention ◽  
Before And After ◽  
Chi Squared ◽  
Comparison Groups ◽  
To Receive

Abstract Background Treatment of clinical Plasmodium falciparum malaria with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) is associated with increased post-treatment gametocyte carriage. The effect of seasonal malaria chemoprevention (SMC) with SP and AQ on gametocyte carriage was assessed in asymptomatic P. falciparum infected children. Methods The study was carried out in eastern Gambia. Asymptomatic P. falciparum malaria infected children aged 24–59 months old who were eligible to receive SMC (SMC group) and children 5–8 years that were not eligible to receive SMC (comparison group) were recruited. Gametocytaemia was determined by molecular methods before and after SMC administration. Gametocyte carriage between the groups was compared using the chi-squared test and within-person using conditional logistic regression. Results During the 2017 and 2018 malaria transmission seasons, 65 and 75 children were recruited in the SMC and comparison groups, respectively. Before SMC administration, gametocyte prevalence was 10.7% (7/65) in the SMC group and 13.3% (10/75) in the comparison group (p = 0.64). At day 13 (IQR 12, 13) after SMC administration, this was 9.4% (5/53) in children who received at least the first dose of SMC treatment and 12.7% (9/71) for those in the comparison group (p = 0.57). Similarly, there was no difference in prevalence of gametocytes between children that adhered to all 3-day doses of SMC treatment 15.6% (5/32) and those in the comparison group (p = 0.68). In the SMC group, within-group gametocyte carriage was similar before and after SMC administration in children that received at least the first dose of SMC treatment (OR 0.6, 95% CI 0.14–2.51; p = 0.48) and in those that adhered to all 3-day doses of SMC treatment (OR 1.0, 95% CI 0.20–4.95; p = 1.0). Conclusion In this study with relative low gametocyte prevalence prior to SMC treatment, no evidence was observed that SMC treatment increased gametocyte carriage in asymptomatic P. falciparum malaria infected children.

scholarly journals Risk of Plasmodium falciparum infection in south-west Burkina Faso - potential impact of expanding eligibility for seasonal malaria chemoprevention

2021 ◽  
Author(s):  
Anne L Wilson ◽  
Steve W Lindsay ◽  
Alfred Tiono ◽  
Jean Baptiste Yaro ◽  
Hilary Ranson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Malaria Transmission ◽  
Malaria Control ◽  
Control Measures ◽  
Sub Saharan Africa ◽  
South West ◽  
Seasonal Malaria Chemoprevention ◽  
The Impact

Abstract Background Burkina Faso has one of the highest malaria burdens in sub-Saharan Africa despite the mass deployment of insecticide-treated nets (ITNs) and use of seasonal malaria chemoprevention (SMC) in children aged up to 5 years. Identification of risk factors for Plasmodium falciparum infection in rural Burkina Faso could help to identify and target malaria control measures. Methods A cross-sectional survey of 1,199 children and adults was conducted during the peak malaria transmission season in south-west Burkina Faso in 2017. Logistic regression was used to identify risk factors for microscopically confirmed P. falciparum infection. A malaria transmission dynamic model was used to determine the impact on malaria cases averted of administering SMC to children aged 5–15 year old. Results P. falciparum prevalence was 32.8% in the study population. Children aged 5 to < 10 years old were at 3.74 times the odds (95% CI = 2.68–5.22, p < 0.001) and children aged 10 to 15 years old at 3.14 times the odds (95% CI = 1.20–8.21, p = 0.02) of P. falciparum infection compared to children aged less than 5 years old. Administration of SMC to children aged up to 10 years is predicted to avert an additional 57 malaria cases per 1000 population per year (9.4% reduction) and administration to children aged up to 15 years would avert an additional 89 malaria cases per 1000 population per year (14.6% reduction) in the Cascades Region, assuming coverage of pyrethroid-piperonyl butoxide ITNs. Conclusion Malaria infections were high in all age strata, although highest in children aged 5 to 15 years, despite roll out of core malaria control interventions. Given the burden of infection in school-age children, extension of the eligibility criteria for SMC could help reduce the burden of malaria in Burkina Faso and other countries in the region.

Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial

1991 ◽  
Vol 75 (5) ◽  
pp. 731-739 ◽  
Author(s):  
J. Paul Muizelaar ◽  
Anthony Marmarou ◽  
John D. Ward ◽  
Hermes A. Kontos ◽  
Sung C. Choi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Control Group ◽  
Content Type ◽  
Cerebral Vasoconstriction ◽  
Number Of Patients ◽  
Severity Of Injury ◽  
Head Injured ◽  
Injured Patients ◽  
To Receive

✓ There is still controversy over whether or not patients should be hyperventilated after traumatic brain injury, and a randomized trial has never been conducted. The theoretical advantages of hyperventilation are cerebral vasoconstriction for intracranial pressure (ICP) control and reversal of brain and cerebrospinal fluid (CSF) acidosis. Possible disadvantages include cerebral vasoconstriction to such an extent that cerebral ischemia ensues, and only a short-lived effect on CSF pH with a loss of HCO3− buffer from CSF. The latter disadvantage might be overcome by the addition of the buffer tromethamine (THAM), which has shown some promise in experimental and clinical use. Accordingly, a trial was performed with patients randomly assigned to receive normal ventilation (PaCO2 35 ± 2 mm Hg (mean ± standard deviation): control group), hyperventilation (PaCO2 25 ± 2 mm Hg: HV group), or hyperventilation plus THAM (PaCO2 25 ± 2 mm Hg: HV + THAM group). Stratification into subgroups of patients with motor scores of 1–3 and 4–5 took place. Outcome was assessed according to the Glasgow Outcome Scale at 3, 6, and 12 months. There were 41 patients in the control group, 36 in the HV group, and 36 in the HV + THAM group. The mean Glasgow Coma Scale score for each group was 5.7 ± 1.7, 5.6 ± 1.7, and 5.9 ± 1.7, respectively; this score and other indicators of severity of injury were not significantly different. A 100% follow-up review was obtained. At 3 and 6 months after injury the number of patients with a favorable outcome (good or moderately disabled) was significantly (p < 0.05) lower in the hyperventilated patients than in the control and HV + THAM groups. This occurred only in patients with a motor score of 4–5. At 12 months posttrauma this difference was not significant (p = 0.13). Biochemical data indicated that hyperventilation could not sustain alkalinization in the CSF, although THAM could. Accordingly, cerebral blood flow (CBF) was lower in the HV + THAM group than in the control and HV groups, but neither CBF nor arteriovenous difference of oxygen data indicated the occurrence of cerebral ischemia in any of the three groups. Although mean ICP could be kept well below 25 mm Hg in all three groups, the course of ICP was most stable in the HV + THAM group. It is concluded that prophylactic hyperventilation is deleterious in head-injured patients with motor scores of 4–5. When sustained hyperventilation becomes necessary for ICP control, its deleterious effect may be overcome by the addition of THAM.

Influence of selection criteria on clients’ satisfaction with construction consultancy services in Nigeria

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Chukwuemeka Patrick Ogbu ◽  
Monday Omogiate Imafidon
Keyword(s):  
Selection Criteria ◽  
Client Satisfaction ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Firm Reputation ◽  
Content Type ◽  
Importance Index ◽  
Tender Evaluation ◽  
To Receive ◽  
Selection Of

Purpose To receive a satisfactory consultancy service, a construction client must first select suitable consultants. While numerous criteria for the selection of construction consultants have been suggested in the literature, their influence on client satisfaction has hardly been statistically established. This study aimed to reduce the criteria for the selection of construction consultants into a more manageable set of fewer factors and ascertain the influence of the factors on client satisfaction. Design/methodology/approach Data were gathered through a purposively administered cross-sectional survey of public sector clients in Nigeria. Analyzes were done using relative importance index, factor analysis and multiple regression analysis. Findings The results proved that the criteria for the selection of consultants can, in the order of decreasing influence on client satisfaction, be grouped into service delivery approach (SDA), relationship with the client, the caliber of personnel, firm reputation and firm certification. However, SDA is more influential on client satisfaction. All the factors were found to have significant statistical effects on clients’ overall satisfaction with consultancy services. Originality/value The study demonstrates the extent to which construction consultant selection criteria are relevant to client satisfaction. It shows that SDA is the most important predictor of clients’ satisfaction with consultancy services. The results are helpful for grouping consultant selection criteria in future studies, and in guiding clients on the weights to assign to consultant selection criteria during tender evaluation.

scholarly journals Molecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, China

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Ruimin Zhou ◽  
Chengyun Yang ◽  
Suhua Li ◽  
Yuling Zhao ◽  
Ying Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Henan Province ◽  
Nucleotide Polymorphisms ◽  
Combination Therapies ◽  
Antimalarial Drug Resistance ◽  
Single Nucleotide ◽  
Molecular Surveillance ◽  
Content Type

ABSTRACT Angola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as pfcrt, pfmdr1, pfdhfr, pfdhps, and K13. This study evaluated the drug resistance of the 180 imported Plasmodium falciparum isolates from Angola via nested PCR using Sanger sequencing. The prevalences of pfcrt C72V73M74N75K76, pfmdr1 N86Y184S1034N1042D1246, pfdhfr A16N51C59S108D139I164, and pfdhps S436A437A476K540A581 were 69.4%, 59.9%, 1.3% and 6.3%, respectively. Three nonsynonymous (A578S, M579I, and Q613E) and one synonymous (R471R) mutation of K13 were found, the prevalences of which were 2.5% and 1.3%, respectively. The single nucleotide polymorphisms (SNPs) in pfcrt, pfmdr1, pfdhfr, and pfdhps were generally shown as multiple mutations. The mutant prevalence of pfcrt reduced gradually, but pfdhfr and pfdhps still showed high mutant prevalence, while pfmdr1 was relatively low. The mutation of the K13 gene was rare. Molecular surveillance of artemisinin (ART) resistance will be used as a tool to evaluate the real-time efficacy of the artemisinin-based combination therapies (ACTs) and the ART resistance situation.

scholarly journals Associations between Malaria-Preventive Regimens and Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant Women

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Patience Nayebare ◽  
Victor Asua ◽  
Melissa D. Conrad ◽  
Richard Kajubi ◽  
Abel Kakuru ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Polymorphisms ◽  
Protective Efficacy ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Drug Susceptibility ◽  
Recent Trial ◽  
Content Type ◽  
High Level ◽  
Selection Of

ABSTRACT Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance, and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of Plasmodium falciparum genetic polymorphisms that alter susceptibility to these drugs. The prevalence of known genetic polymorphisms associated with altered drug susceptibility was determined in parasitemic samples, including 375 collected before IPTp drugs were administered, 125 randomly selected from those receiving SP, and 80 from those receiving DP. For women receiving DP, the prevalence of mixed/mutant sequences was greater in samples collected during IPTp than that in samples collected prior to the intervention for PfMDR1 N86Y (20.3% versus 3.9%; P < 0.001), PfMDR1 Y184F (73.0% versus 53.0%; P < 0.001), and PfCRT K76T (46.4% versus 24.0%; P < 0.001). Considering SP, prior to IPTp, the prevalence of all 5 common antifolate mutations was over 92%, and this prevalence increased following exposure to SP, although none of these changes were statistically significant. For two additional mutations associated with high-level SP resistance, the prevalence of PfDHFR 164L (13.7% versus 4.0%; P = 0.004), but not PfDHPS 581G (1.9% versus 3.0%; P = 0.74), was greater in samples collected during IPTp compared to those collected before the intervention. Use of IPTp in Uganda selected for parasites with mutations associated with decreased susceptibility to IPTp regimens. Thus, a potential drawback of IPTp is selection of parasites with decreased drug susceptibility.

scholarly journals Prevalence and factors associated with carriage of Pfmdr1 polymorphisms among pregnant women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and artemether-lumefantrine for malaria treatment in Burkina Faso

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Hamtandi Magloire Natama ◽  
Rouamba Toussaint ◽  
Djamina Line Cerine Bazié ◽  
Sékou Samadoulougou ◽  
Maminata Coulibaly-Traoré ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Burkina Faso ◽  
Pregnant Women ◽  
Mutant Allele ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Dried Blood Spots ◽  
Nucleotide Polymorphisms ◽  
High Coverage ◽  
Factors Associated

Abstract Background Single nucleotide polymorphisms occurring in the Plasmodium falciparum multidrug resistant gene 1 (pfmdr1) are known to be associated with aminoquinoline resistance and, therefore, represent key P. falciparum markers for monitoring resistance both in susceptible groups (children under 5 years old and pregnant women) and in the general population. This study aimed to determine prevalence and factors associated with the carriage of pfmdr1 N86Y, Y184F and D1246Y polymorphisms among pregnant women in a setting of high malaria transmission in Burkina Faso. Methods Plasmodium falciparum isolates were collected at the first antenatal care visit (ANC-1) as well as at delivery from pregnant women participating in the COSMIC trial (NTC01941264), which assessed malaria preventive interventions during pregnancy in the Nanoro Health District. Here, pregnant women received intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and malaria infections and/or diseases were treated using artemether-lumefantrine (AL) during the trial. Parasite DNA was extracted from dried blood spots and the presence of pfmdr1 mutations at positions 86, 184 and 1246 was determined using nested PCR, followed by restriction fragment length polymorphism (RFLP) analysis. Results A prevalence of 13.2% (20/151) and 12.1% (14/116) of the pfmdr1 86Y mutant allele was found at ANC-1 and at delivery, respectively, while no mutant allele was observed for Y184F and D1246Y codons at both ANC-1 and at delivery. There were no significant factors associated with pfmdr1 86Y mutant allele carriage at ANC-1. However, malaria infections at delivery with a parasite density above the median (2237.2 (IQR: 613.5–11,425.7) parasites/µl) was associated with an increase risk of pfmdr1 86Y mutant allele carriage (AOR = 5.5 (95% CI  1.07–28.0); P = 0.04). In contrast, both three or more IPTp-SP doses (AOR = 0.25 (95% CI 0.07–0.92); P = 0.04) and one or more AL treatment (AOR = 0.25 (95% CI 0.07–0.89); P = 0.03) during pregnancy were associated with a significant reduce risk of pfmdr1 86Y mutant allele carriage at delivery. Conclusion These findings suggest that both high coverage of IPTp-SP and the use of AL for the treatment of malaria infection/disease during pregnancy select for pfmdr1 N86 wild-type allele at delivery.

scholarly journals Polymorphism in PfMRP1 (Plasmodium falciparum Multidrug Resistance Protein 1) Amino Acid 1466 Associated with Resistance to Sulfadoxine-Pyrimethamine Treatment

2009 ◽  
Vol 53 (6) ◽  
pp. 2553-2556 ◽  
Author(s):  
Sabina Dahlström ◽  
M. Isabel Veiga ◽  
Andreas Mårtensson ◽  
Anders Björkman ◽  
J. Pedro Gil
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Antimalarial Activity ◽  
Intermittent Preventive Treatment ◽  
Genetic Alterations ◽  
Multidrug Resistance Protein ◽  
Nucleotide Polymorphisms ◽  
Resistance Protein ◽  
Selection Of

ABSTRACT Sulfadoxine-pyrimethamine (SP) remains widely recommended for intermittent preventive treatment against Plasmodium falciparum malaria for pregnant women and infants in Africa. Resistance to SP is increasing and associated primarily with mutations in the P. falciparum dhfr (Pfdhfr) and Pfdhps genes. This study aimed to explore the hypothetical association of genetic alterations in the P. falciparum multidrug resistance protein gene (Pfmrp1) with the in vivo response to SP by detecting the selection of single nucleotide polymorphisms (SNPs) following standard single-dose treatment administered to children with acute uncomplicated P. falciparum malaria in Tanzania. We detected significant selection of parasites carrying the Pfmrp1 1466K allele in samples from children with recrudescent infections, with 12 (100%) of 12 such samples being positive for this allele, compared to 52 (67.5%) of 77 baseline samples (P = 0.017), in parallel with the selection of the Pfdhfr Pfdhps quintuple mutant haplotype in cases of recrudescence (P = 0.001). There was no association between the 1466K SNP and the Pfdhfr Pfdhps quintuple mutation, indicating independent selections. Our data point for the first time to a role for a P. falciparum multidrug resistance protein homologue in the antimalarial activity of SP. Moreover, they add to the growing evidence of the potential importance of Pfmrp1 in antimalarial drug resistance.

scholarly journals An open label study of the safety and efficacy of a single dose of weekly chloroquine and azithromycin administered for malaria prophylaxis in healthy adults challenged with 7G8 chloroquine-resistant Plasmodium falciparum in a controlled human malaria infection model

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jeffrey Livezey ◽  
Patrick Twomey ◽  
Meshell Morrison ◽  
Susan Cicatelli ◽  
Elizabeth H. Duncan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
High Rate ◽  
Control Group ◽  
Infection Model ◽  
Post Challenge ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Malaria Chemoprophylaxis ◽  
To Receive

Abstract Background Malaria remains the top infectious disease threat facing the U.S. military in many forward operating environments. Compliance with malaria chemoprophylaxis remains a critical component in preventing malaria in the deployed Service Member. Studies of previous military operations show that compliance is consistently higher with weekly versus daily dosing regimens. Current FDA approved weekly chemoprophylaxis options have contraindications that can limit prescribing. The combination of chloroquine (CQ) with azithromycin (AZ) has previously been shown to be an efficacious treatment option for malaria, has pharmacokinetics compatible with weekly dosing, and has shown synergy when combined in vitro. Methods In this open label study, 18 healthy volunteers, aged 18–50 years (inclusive), were randomly assigned to receive either 300 mg CQ or 300 mg CQ and 2 gm azithromycin (CQAZ) of directly observed therapy, weekly for 3 weeks prior to undergoing mosquito bite challenge with chloroquine-resistant Plasmodium falciparum. Volunteers that remained asymptomatic and had no evidence of parasitaemia continued to receive weekly post-exposure chemoprophylaxis for 3 weeks following malaria challenge. The primary endpoint was the number of volunteers that remained asymptomatic and had no evidence of parasitaemia 28 days after the malaria challenge. Results All 6 (100%) volunteers randomized to the CQ control group became symptomatic with parasitaemia during the 28-day post-challenge period. Only 1/12 (8.3%) of volunteers in the CQAZ group developed symptoms and parasitaemia during the 28-day post-challenge period. However, after chemoprophylaxis was discontinued an additional 6 volunteers developed parasitaemia between days 28–41 after challenge, with 4 of 6 experiencing symptoms. 80% of subjects in the CQAZ group experienced treatment related gastrointestinal adverse events (including 13% that experienced severe nausea) compared to 38% in the CQ group. A comparison of the pharmacokinetics in the CQAZ group demonstrated higher azithromycin Cmax (p = 0.03) and AUC (p = 0.044) levels in those volunteers who never became parasitaemic compared to those who did. Conclusion Given the high rate of side effects and poor efficacy when administered for 3 weeks before and after challenge, the combination of weekly chloroquine and azithromycin is a suboptimal regimen combination for weekly malaria chemoprophylaxis. Trial registration ClinicalTrials.gov NCT03278808

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