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Journal of Chromatography. B,... Feb 2024To support the pharmacokinetic study of sulfadoxine (SD) and pyrimethamine (PM) in pregnant women and children, sensitive methods with small sample volume are desirable....
To support the pharmacokinetic study of sulfadoxine (SD) and pyrimethamine (PM) in pregnant women and children, sensitive methods with small sample volume are desirable. Here we report a method to determine SD and PM with microvolume plasma samples: 5 µL plasma samples were cleaned up by protein precipitation with acetonitrile. The deuterated analytes were used as the internal standards. The samples after cleanup were injected onto an ACE Excel SuperC column (50 × 2.1 mm, 1.7 μm, Hichrom Limited) connected to a Waters I class UPLC coupled with a Sciex Triple Quad 6500 Mass Spectrometer and eluted with water and acetonitrile both containing 0.1% formic acid in a gradient mode at 0.8mL/min. Detection utilized ESI as the ion source and MRM as the quantification mode. The precursor-to-product ion transitions m/z 311→245 for SD and 249→233 for PM were selected for quantification. The ion transitions for the corresponding internal standards were 315→249 for SD-d and 254→235 for PM-d. The simplest linear regression weighted by 1/x was used for the calibration curves. The calibration ranges were 1-200 µg/mL SD and 2 - 1000ng/mL PM. The mean (± standard deviation) recoveries were 94.3±3.2% (SD) and 97.0±1.5% (PM). The validated method was applied to analysis of 1719 clinical samples, demonstrating the method is suitable for the pharmacokinetic study with samples collected up to day 28 post-dose.
Topics: Pregnancy; Child; Humans; Female; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Pyrimethamine; Sulfadoxine; Acetonitriles
PubMed: 38309043
DOI: 10.1016/j.jchromb.2024.124030 -
Infection and Drug Resistance 2024Due to the increasing resistance of to chloroquine (CQ) in Sudan, a shift from CQ to artesunate combined with sulfadoxine/pyrimethamine as a first-line treatment for...
BACKGROUND
Due to the increasing resistance of to chloroquine (CQ) in Sudan, a shift from CQ to artesunate combined with sulfadoxine/pyrimethamine as a first-line treatment for uncomplicated falciparum malaria was adopted in 2004. This study aimed to determine the frequency distribution of K76T and N86Y mutations in chloroquine resistance transporter () and multidrug resistance 1 () genes as key markers of resistance to CQ among isolates from patients in Nyala district of South Darfur state, west of Sudan.
METHODS
A descriptive, cross-sectional study was conducted among 75 P. falciparum isolates from Sudanese patients diagnosed with falciparum malaria mono-infection. Parasite DNA was extracted from dried blood spots and amplified using a nested polymerase chain reaction (PCR). Then, restriction fragment length polymorphism (RFLP) was used to detect the genetic polymorphisms in codons 76 of and 86 of . PCR-RFLP products were analyzed using 1.5% gel electrophoresis to identify the genetic polymorphisms in the studied codons. The wild-type (pfcrt K76 and pfmdr1 N86), mutant ( 76T and 86Y) and mixed-type ( K76T and N86Y) alleles were expressed as frequencies and proportions.
RESULTS
The wild-type K76 allele was observed among 34.7% of isolates and the mutant 76T allele among 20% of isolates, while the mixed-type K76T allele was observed among 45.3% of isolates. On the other hand, 54.7% of isolates harbored the wild-type N86 allele and 5.3% of isolates had the mutant 86Y allele, while the mixed-type N86Y allele was observed among 40% of isolates.
CONCLUSION
The key molecular markers associated with CQ resistance ( 76T and 86Y) are still circulating in high frequency among isolates in South Darfur state, about twelve years after the official withdrawal of the drug as a treatment for uncomplicated falciparum malaria.
PubMed: 38283109
DOI: 10.2147/IDR.S439875 -
Malaria Journal Jan 2024Seasonal malaria chemoprevention (SMC) is an effective intervention to prevent malaria in children in locations where the burden of malaria is high and transmission is...
BACKGROUND
Seasonal malaria chemoprevention (SMC) is an effective intervention to prevent malaria in children in locations where the burden of malaria is high and transmission is seasonal. There is growing evidence suggesting that SMC with sulfadoxine-pyrimethamine and amodiaquine can retain its high level of effectiveness in East and Southern Africa despite resistance concerns. This study aims to generate evidence on the effectiveness of SMC when delivered under programmatic conditions in an area with an unknown anti-malarial drug resistance profile in the Northern Bahr el-Ghazal region of South Sudan.
METHODS
A non-randomized quasi experimental study was conducted to compare an intervention county with a control county. Five monthly SMC cycles were delivered between July and November 2022, targeting about 19,000 children 3-59 months old. Data were obtained from repeated cross-sectional household surveys of caregivers of children aged 3-59 months using cluster sampling. Wave 1 survey took place in both counties before SMC implementation; Waves 2 and 3 took place after the second and fourth monthly SMC cycles. Difference-in-differences analyses were performed by fitting logistic regression models with interactions between county and wave.
RESULTS
A total of 2760 children were sampled in the study across the three survey waves in both study counties. Children in the intervention arm had 70% lower odds of caregiver-reported fever relative to those in the control arm during the one-month period prior to Wave 2 (OR: 0.30, 95% CI 0.12-0.70, p = 0.003), and 37% lower odds in Wave 3 (OR: 0.63, 95% CI 0.22-1.59, p = 0.306) after controlling for baseline difference between counties in Wave 1. Odds of caregiver-reported RDT-confirmed malaria were 82% lower in the previous 1-month period prior to Wave 2 (OR: 0.18, 95% CI 0.07-0.49, p = 0.001) and Wave 3 (OR: 0.18, 95% CI 0.06-0.54, p = 0.003).
CONCLUSION
These results show high effectiveness of SMC using SPAQ in terms of reducing malaria disease during the high transmission season in children 3-59 month. Despite the promising results, additional evidence and insights from chemoprevention efficacy cohort studies, and analyses of relevant resistance markers, are required to assess the suitability of SMC for this specific context.
Topics: Child; Humans; Infant, Newborn; Chemoprevention; Cross-Sectional Studies; Malaria; Seasons; South Sudan
PubMed: 38267985
DOI: 10.1186/s12936-024-04853-x -
Journal of Public Health in Africa Dec 2023Blood group O is reported to confer some degree of protection from severe malaria in endemic setting. This protection is believed to be due to reduced and smaller...
Blood group O is reported to confer some degree of protection from severe malaria in endemic setting. This protection is believed to be due to reduced and smaller rosette formation in people of blood group O which can easily be cleared by the host immune system. Also, sickle cell trait (HbAS) is reported to disrupt the adhesion of infected erythrocytes to microvascular endothelial walls, which could protect pregnant women from placental malaria. We determined the association between HbAS and ABO blood group, and placental malaria amongst pregnant women of all parities. The study enrolled 221 pregnant women. Peripheral blood samples were taken for malaria smears, ABO blood grouping and haemoglobin (Hb) electrophoresis. A structured questionnaire was used to age, bed net usage, and the number of Sulphadoxine-pyrimethamine (SP) doses taken by a pregnant woman. Two hundred and twenty-one (221) pregnant women were enrolled and out of this number, 110 (49.8%) were primiparae and 111 (50.2%) multiparae, with a mean age of 23.7±5.2. Placental malaria (PM) prevalence by PCR detection was 19.4% (43/221). Of those who were malaria positive 58.1% (25/43) were primiparae. Primiparae who are of blood group O were more susceptible to PM [P=0.04, (OR); 2.85, 95% (Cl), 1.12-9.01]. But sickle cell trait did not reduce the prevalence of PM [P=0.84 (OR); 0.92, 95% (Cl), 0.43-1.99]. Non-blood group O primiparae women were protected against placental malaria. This could be why some primiparae women are protected from PM, just like multiparae women.
PubMed: 38259428
DOI: 10.4081/jphia.2024.2817 -
JMIR Research Protocols Jan 2024Seasonal malaria chemoprevention (SMC) is recommended by the World Health Organization for the sub-Sahel region in sub-Saharan Africa for preventing malaria in children...
BACKGROUND
Seasonal malaria chemoprevention (SMC) is recommended by the World Health Organization for the sub-Sahel region in sub-Saharan Africa for preventing malaria in children 3 months old to younger than 5 years. Since 2016, the Malian National Malaria Control Program has deployed SMC countrywide during its high malaria transmission season at a rate of 4 monthly cycles annually. The standard SMC regimen includes sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ). Resistance against SP is suspected to be rising across West Africa; therefore, assessing the effectiveness of an alternative antimalarial drug for SMC is needed to provide a second-line regimen when it is ultimately needed. It is not well understood whether SMC effectively prevents malaria in children aged 5 years or older.
OBJECTIVE
The primary goal of the study is to compare 2 SMC regimens (SP-AQ and dihydroartemisinin-piperaquine [DHA-PQ]) in preventing uncomplicated Plasmodium falciparum malaria in children 3 months to 9 years old. Secondly, we will assess the possible use of DHA-PQ as an alternative SMC drug in areas where resistance to SP or AQ may increase following intensive use.
METHODS
The study design is a 3-arm cluster-randomized design comparing the SP-AQ and DHA-PQ arms in 2 age groups (younger than 5 years and 5-9 years) and a control group for children aged 5-9 years. Standard SMC (SP-AQ) for children younger than 5 years was provided to the control arm, while SMC with SP-AQ was delivered to children aged 3 months to 9 years (arm 2), and SMC with DHA-PQ will be implemented in study arm 3 for children up to 9 years of age. The study was performed in Mali's Koulikoro District, a rural area in southwest Mali with historically high malaria transmission rates. The study's primary outcome is P falciparum incidence for 2 SMC regimens in children up to 9 years of age. Should DHA-PQ provide an acceptable alternative to SP-AQ, a plausible second-line prevention option would be available in the event of SP resistance or drug supply shortages. A significant byproduct of this effort included bolstering district health information systems for rapid identification of severe malaria cases.
RESULTS
The study began on July 1, 2019. Through November 2022, a total of 4556 children 3 months old to younger than 5 years were enrolled. Data collection ended in spring 2023, and the findings are expected to be published later in early 2024.
CONCLUSIONS
Routine evaluation of antimalarial drugs is needed to establish appropriate SMC age targets. The study goals here may impact public health policy and provide alternative therapies in the event of drug shortages or resistance.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04149106, https://clinicaltrials.gov/ct2/show/NCT04149106.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/51660.
PubMed: 38252481
DOI: 10.2196/51660 -
Chemosphere Mar 2024Sulfadoxine (SDX) is a broad-spectrum veterinary antibiotic, which was used alone for the treatment of various infections in the past, and detected ubiquitously in the...
Sulfadoxine (SDX) is a broad-spectrum veterinary antibiotic, which was used alone for the treatment of various infections in the past, and detected ubiquitously in the aqueous environment. However, understanding SDX's photo- and microbial degradation within the environment, especially in marine matrixes, remains limited. This research hones in on SDX's degradation dynamics in seawater. Photodegradation emerges as the dominant process, surpassing microbial degradation in speed and efficiency. Notably, 90% of SDX is photo-degraded within 12 h, while only 52% is removed via microbial degradation over two weeks. Time-of-flight mass spectrometry provides high-resolution molecular mass information on degradation products. The molecular structures of hydrolysis, photo-, and microbial degradation products are deduced from accurate precursor and fragment ion masses, alongside an integrated data processing workflow. Six hydrolysis products arise from the treatment, and photodegradation and microbial degradation yield nine and eighteen products, respectively. Molecular insights from these products inform plausible degradation pathways involving hydrolysis, photodegradation, and microbial degradation. Processes like bond cleavage, methylation, hydroxylation, oxidation, reduction, and methoxylation are identified and associated with degradation. This study presents a comprehensive workflow for acquiring and processing degradation product data linked to emerging organic pollutants. Moreover, it contributes to our comprehension of the environmental fate of veterinary drugs in marine ecosystems.
Topics: Sulfadoxine; Ecosystem; Mass Spectrometry; Chromatography, Liquid; Seawater; Photolysis; Kinetics
PubMed: 38242518
DOI: 10.1016/j.chemosphere.2024.141225 -
Journal of the Royal Society, Interface Jan 2024The emergence and spread of drug-resistant parasites have hindered efforts to eliminate malaria. Monitoring the spread of drug resistance is vital, as drug resistance...
The emergence and spread of drug-resistant parasites have hindered efforts to eliminate malaria. Monitoring the spread of drug resistance is vital, as drug resistance can lead to widespread treatment failure. We develop a Bayesian model to produce spatio-temporal maps that depict the spread of drug resistance, and apply our methods for the antimalarial sulfadoxine-pyrimethamine. We infer from genetic count data the prevalences over space and time of various malaria parasite haplotypes associated with drug resistance. Previous work has focused on inferring the prevalence of individual molecular markers. In reality, combinations of mutations at multiple markers confer varying degrees of drug resistance to the parasite, indicating that multiple markers should be modelled together. However, the reporting of genetic count data is often inconsistent as some studies report haplotype counts, whereas some studies report mutation counts of individual markers separately. In response, we introduce a latent multinomial Gaussian process model to handle partially reported spatio-temporal count data. As drug-resistant mutations are often used as a proxy for treatment efficacy, point estimates from our spatio-temporal maps can help inform antimalarial drug policies, whereas the uncertainties from our maps can help with optimizing sampling strategies for future monitoring of drug resistance.
Topics: Humans; Antimalarials; Bayes Theorem; Malaria, Falciparum; Malaria; Plasmodium falciparum; Mutation; Biomarkers; Protozoan Proteins
PubMed: 38228183
DOI: 10.1098/rsif.2023.0570 -
Lancet (London, England) Jan 2024The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium... (Randomized Controlled Trial)
Randomized Controlled Trial
Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial.
BACKGROUND
The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV.
METHODS
We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713.
FINDINGS
From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups.
INTERPRETATION
Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy.
FUNDING
European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency.
Topics: Female; Humans; Infant; Pregnancy; Antimalarials; Artemisinins; Chemoprevention; Folic Acid Antagonists; HIV Infections; Kenya; Malaria; Malawi; Piperazines; Placenta; Pregnancy Outcome; Pregnant Women; Quinolines; Trimethoprim, Sulfamethoxazole Drug Combination; Double-Blind Method
PubMed: 38224710
DOI: 10.1016/S0140-6736(23)02631-4 -
The Lancet. Infectious Diseases May 2024The cornerstone of malaria prevention in pregnancy, intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine, is contraindicated in women with HIV who are... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnant women with HIV from Gabon and Mozambique: a randomised, double-blind, placebo-controlled trial.
BACKGROUND
The cornerstone of malaria prevention in pregnancy, intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine, is contraindicated in women with HIV who are receiving co-trimoxazole prophylaxis. We assessed whether IPTp with dihydroartemisinin-piperaquine is safe and effective in reducing the risk of malaria infection in women with HIV receiving co-trimoxazole prophylaxis and antiretroviral drugs.
METHODS
For this randomised, double-blind, placebo-controlled clinical trial, women with HIV attending the first antenatal care clinic visit, resident in the study area, and with a gestational age up to 28 weeks were enrolled at five sites in Gabon and Mozambique. Participants were randomly assigned (1:1) to receive either IPTp with dihydroartemisinin-piperaquine at each scheduled antenatal care visit plus daily co-trimoxazole (intervention group) or placebo at each scheduled antenatal care visit plus daily co-trimoxazole (control group). Randomisation was done centrally via block randomisation (block sizes of eight), stratified by country. IPTp was given over 3 days under direct observation by masked study personnel. The number of daily IPTp tablets was based on bodyweight and according to the treatment guidelines set by WHO (target dose of 4 mg/kg per day [range 2-10 mg/kg per day] of dihydroartemisinin and 18 mg/kg per day [range 16-27 mg/kg per day] of piperaquine given once a day for 3 days). At enrolment, all participants received co-trimoxazole (fixed combination drug containing 800 mg trimethoprim and 160 mg sulfamethoxazole) for daily intake. The primary study outcome was prevalence of peripheral parasitaemia detected by microscopy at delivery. The modified intention-to-treat population included all randomly assigned women who had data for the primary outcome. Secondary outcomes included frequency of adverse events, incidence of clinical malaria during pregnancy, and frequency of poor pregnancy outcomes. All study personnel, investigators, outcome assessors, data analysts, and participants were masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT03671109.
FINDINGS
From Sept 18, 2019, to Nov 26, 2021, 666 women (mean age 28·5 years [SD 6·4]) were enrolled and randomly assigned to the intervention (n=332) and control (n=334) groups. 294 women in the intervention group and 308 women in the control group had peripheral blood samples taken at delivery and were included in the primary analysis. Peripheral parasitaemia at delivery was detected in one (<1%) of 294 women in the intervention group and none of 308 women in the control group. The incidence of clinical malaria during pregnancy was lower in the intervention group than in the control group (one episode in the intervention group vs six in the control group; relative risk [RR] 0·12, 95% CI 0·03-0·52, p=0·045). In a post-hoc analysis, the composite outcome of overall malaria infection (detected by any diagnostic test during pregnancy or delivery) was lower in the intervention group than in the control group (14 [5%] of 311 women vs 31 [10%] of 320 women; RR 0·48, 95% CI 0·27-0·84, p=0·010). The frequency of serious adverse events and poor pregnancy outcomes (such as miscarriages, stillbirths, premature births, and congenital malformations) did not differ between groups. The most frequently reported drug-related adverse events were gastrointestinal disorder (reported in less than 4% of participants) and headache (reported in less than 2% of participants), with no differences between study groups.
INTERPRETATION
In the context of low malaria transmission, the addition of IPTp with dihydroartemisinin-piperaquine to co-trimoxazole prophylaxis in pregnant women with HIV did not reduce peripheral parasitaemia at delivery. However, the intervention was safe and associated with a decreased risk of clinical malaria and overall Plasmodium falciparum infection, so it should be considered as a strategy to protect pregnant women with HIV from malaria.
FUNDING
European and Developing Countries Clinical Trials Partnership 2 (EDCTP2) and Medicines for Malaria Venture.
TRANSLATIONS
For the Portuguese and French translations of the abstract see Supplementary Materials section.
Topics: Humans; Female; Pregnancy; Mozambique; Quinolines; Artemisinins; Antimalarials; Double-Blind Method; Adult; HIV Infections; Gabon; Malaria; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult; Pregnancy Complications, Parasitic; Treatment Outcome; Pregnancy Complications, Infectious; Drug Combinations; Piperazines
PubMed: 38224706
DOI: 10.1016/S1473-3099(23)00738-7 -
Gates Open Research 2023The World Health Organization (WHO) recommends seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) for children aged 3 to 59...
A hybrid effectiveness-implementation study protocol to assess the effectiveness and chemoprevention efficacy of implementing seasonal malaria chemoprevention in five districts in Karamoja region, Uganda.
BACKGROUND
The World Health Organization (WHO) recommends seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SPAQ) for children aged 3 to 59 months, living in areas where malaria transmission is highly seasonal. However, due to widespread prevalence of resistance markers, SMC has not been implemented at scale in East and Southern Africa. An initial study in Uganda showed that SMC with SPAQ was feasible, acceptable, and protective against malaria in eligible children in Karamoja region. Nonetheless, exploration of alternative regimens is warranted since parasite resistance threats persist.
OBJECTIVE
The study aims to test the effectiveness of SMC with Dihydroartemisinin-piperaquine (DP) or SPAQ (DP-SMC & SPAQ-SMC), chemoprevention efficacy as well as the safety and tolerability of DP compared to that of SPAQ among 3-59 months old children in Karamoja region, an area of Uganda where malaria transmission is highly seasonal.
METHODS
A Type II hybrid effectiveness-implementation study design consisting of four components: 1) a cluster randomized controlled trial (cRCT) using passive surveillance to establish confirmed malaria cases in children using both SPAQ and DP; 2a) a prospective cohort study to determine the chemoprevention efficacy of SPAQ and DP (if SPAQ or DP clears sub-patent infection and provides 28 days of protection from new infection) and whether drug concentrations and/or resistance influence the ability to clear and prevent infection; 2b) a sub study examining pharmacokinetics of DP in children between 3 to <6 months; 3) a resistance markers study in children 3-59 months in the research districts plus the standard intervention districts to measure changes in resistance marker prevalence over time and finally; 4) a process evaluation.
DISCUSSION
This study evaluates the effects of SPAQ-SMC versus DP-SMC on clinical malaria in vulnerable children in the context of high parasite SP resistance, whilst informing on the best implementation strategies.
CONCLUSION
This study will inform malaria policy in high-burden countries, specifically on utility of SMC outside the sahel, and contribute to progress in malaria control.
Topics: Child, Preschool; Humans; Infant; Amodiaquine; Chemoprevention; Malaria; Prospective Studies; Randomized Controlled Trials as Topic; Seasons; Uganda
PubMed: 38196920
DOI: 10.12688/gatesopenres.14287.2