Early variations in plasmodium falciparum dynamics in Nigerian children after treatment with two artemisinin-based combinations: implications on delayed parasite clearance

<p>Abstract</p> <p>Background</p> <p>Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent <it>Plasmodium falciparum </it>drug resistance. Artemether-lumefantrine (AL) and artesunate-amodiaquine (AA) are efficacious regimens that have been widely adopted in sub-Saharan Africa. However, most study designs ignore the effects of these regimens on peripheral parasitaemia in the first 24 hours of therapy. The study protocol was designed to evaluate more closely the early effects and the standard measures of efficacies of these two regimens.</p> <p>Methods</p> <p>In an open label, randomized controlled clinical trial, children aged 12 months to 132 months were randomized to receive AL (5-14 kg, one tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily) or artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) for three days. Peripheral blood smears were made hourly in the first 4 hours, 8 h, 16 h, 24 h, and daily on days 2-7, and on days 7, 14, 21, 28, 35, and 42 for microscopic identification and quantification of <it>Plasmodium falciparum</it>.</p> <p>Results</p> <p>A total of 193 children were randomized to receive either AL (97) or AA (96). In children that received both medications, early response of peripheral parasitaemia showed that 42% of children who received AL and 36.7% of those who received AA had an immediate rise in peripheral parasitaemia (0-4 h after treatment) followed by a rapid fall. The rise in parasitaemia was significant and seems to suggest a mobilization of asexual parasites from the deep tissues to the periphery. Days 3, 7, 14, 28, and 42 cure rates in the per protocol (PP) population were > 90% in both groups of children. Both drug combinations were well tolerated with minimal side effects.</p> <p>Conclusion</p> <p>The study showed the high efficacy of AL and AA in Nigerian children. In addition the study demonstrated the mobilisation of asexual parasites from the deep to the periphery in the early hours of commencing ACT treatment in a subset of patients in both study groups. It is unclear whether the early parasite dynamics discovered in this study play any role in the development of drug resistance and thus it is important to further evaluate this discovery. It may be useful for studies investigating delay in parasite clearance of artemisinin derivatives as a way of monitoring the development of resistance to artemisinin to assess the early effects of the drugs on the parasites.</p

A simple cost-effective high performance liquid chromatographic assay of sulphadoxine in whole blood spotted on filter paper for field studies

<p>Abstract</p> <p>Background</p> <p>Artesunate plus sulphadoxine-pyrimethamine is one of the four artemisinin-based combination therapies currently recommended by WHO as first-line treatment for falciparum malaria. Sulphadoxine-pyrimethamine is also used for intermittent preventive treatment for malaria in pregnancy. Drug use patterns and drug pharmacokinetics are important factors impacting the spread of drug resistant parasites hence it is imperative to monitor the effect of pharmacokinetic variability on therapeutic efficacy. Unfortunately, information on the pharmacokinetics of sulphadoxine in children and pregnant women with malaria is very limited. Methods for the assay of sulphadoxine-pyrimethamine have been previously reported, but they are not cost-effective and practicable in analytical laboratories in low resource areas where malaria is endemic. Efforts in this study were thus devoted to development and evaluation of a simple, cost-effective and sensitive method for quantification of sulphadoxine in small capillary samples of whole blood dried on filter paper.</p> <p>Methods</p> <p>Sulphadoxine was determined in whole blood by reversed-phase high performance liquid chromatography with UV detection at 340 nm. Sulisoxazole (SLX) was used as internal standard. Chromatographic separation was achieved using a Beckman Coulter ODS C₁₈and a mobile phase consisting of 0.05 M phosphate buffer-methanol-acetonitrile (70:17:13 V/V/V) containing 1% triethylamine solution.</p> <p>Results</p> <p>Standard curves from sulphadoxine-spiked blood added to filter paper were linear over the concentration range studied. Linear regression analysis yielded correlation coefficient r²> 0.99 (n = 6). Extraction recoveries were about 82-85%. The limit of quantification was 120 ng/ml while the within and between assay coefficient of variations were < 10%. The inter-day precision was < 5.8% and inter-day accuracy ranged from 4.1 to 5.3%. There was no interference from endogenous compounds or any of the commonly used anti-malarial, analgesic and anti-infective drugs with the peaks of SDX or the internal standard.</p> <p>Conclusion</p> <p>The recovery and accuracy of determination of SDX from whole blood filter paper samples using the method described in this study is satisfactory, thus making the method a valuable tool in epidemiological studies and therapeutic drug monitoring in developing endemic countries. Furthermore, the applicability of the method in studying the pharmacokinetic disposition of SDX in a patient suggests that the method is suitable in malaria endemic areas.</p

COVID-19 vaccine hesitancy and its determinants among sub-Saharan African adolescents.

COVID-19 vaccine hesitancy among adolescents poses a challenge to the global effort to control the pandemic. This multi-country survey aimed to assess the prevalence and determinants of COVID-19 vaccine hesitancy among adolescents in sub-Saharan Africa between July and December 2021. The survey was conducted using computer-assisted telephone interviewing among adolescents in five sub-Saharan African countries, Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania. A rural area and an urban area were included in each country (except Ghana, which only had a rural area), with approximately 300 adolescents in each area and 2662 in total. Sociodemographic characteristics and perceptions and attitudes on COVID-19 vaccines were measured. Vaccine hesitancy was defined as definitely not getting vaccinated or being undecided on whether to get vaccinated if a COVID-19 vaccine were available. Log-binomial models were used to calculate the adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) for associations between potential determinants and COVID-19 vaccine hesitancy. The percentage of COVID-19 vaccine hesitancy was 14% in rural Kersa, 23% in rural Ibadan, 31% in rural Nouna, 32% in urban Ouagadougou, 37% in urban Addis Ababa, 48% in rural Kintampo, 65% in urban Lagos, 76% in urban Dar es Salaam, and 88% in rural Dodoma. Perceived low necessity, concerns about vaccine safety, and concerns about vaccine effectiveness were the leading reasons for hesitancy. Healthcare workers, parents or family members, and schoolteachers had the greatest impacts on vaccine willingness. Perceived lack of safety (aPR: 3.52; 95% CI: 3.00, 4.13) and lack of effectiveness (aPR: 3.46; 95% CI: 2.97, 4.03) were associated with greater vaccine hesitancy. The prevalence of COVID-19 vaccine hesitancy among adolescents is alarmingly high across the five sub-Saharan African countries, especially in Tanzania. COVID-19 vaccination campaigns among sub-Saharan African adolescents should address their concerns and misconceptions about vaccine safety and effectiveness

Confirmation of emergence of mutations associated with atovaquone-proguanil resistance in unexposed Plasmodium falciparum isolates from Africa

BACKGROUND: In vitro and in vivo resistance of Plasmodium falciparum to atovaquone or atovaquone-proguanil hydrochloride combination has been associated to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and Tyr268Asn). However, little is known about the prevalence of codon-268 mutations in natural populations of P. falciparum without previous exposure to the drug in Africa. METHODS: The prevalence of codon-268 mutations in the cytb gene of African P. falciparum isolates from Nigeria, Malawi and Senegal, where atovaquone-proguanil has not been introduced for treatment of malaria was assessed. Genotyping of the cytb gene in isolates of P. falciparum was performed by PCR-restriction fragment length polymorphism and confirmed by sequencing. RESULTS: 295 samples from Nigeria (111), Malawi (91) and Senegal (93) were successfully analyzed for detection of either mutant Tyr268Ser or Tyr268Asn. No case of Ser268 or Asn268 was detected in cytb gene of parasites from Malawi or Senegal. However, Asn268 was detected in five out of 111 (4.5%) unexposed P. falciparum isolates from Nigeria. In addition, one out of these five mutant Asn268 isolates showed an additional cytb mutation leading to a Pro266Thr substitution inside the ubiquinone reduction site. CONCLUSION: No Tyr268Ser mutation is found in cytb of P. falciparum isolates from Nigeria, Malawi or Senegal. This study reports for the first time cytb Tyr268Asn mutation in unexposed P. falciparum isolates from Nigeria. The emergence in Africa of P. falciparum isolates with cytb Tyr268Asn mutation is a matter of serious concern. Continuous monitoring of atovaquone-proguanil resistant P. falciparum in Africa is warranted for the rational use of this new antimalarial drug, especially in non-immune travelers

Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo

Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical appliation of the reversal phenomenon

Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo

Resistance in Plasmodium falciparum to amodiaquine (AQ) can be reversed in vitro with with antihistaminic and tricyclic antidepressant compounds, but its significance in vivo is unclear. The present report presents the enhancement of the antimalarial efficacy of AQ by chlorpheniramine, an H1 receptor antagonist that reverses chloroquine (CQ) resistance in vitro and enhances its efficacy in vivo, in five children who failed CQ and/or AQ treatment, and who were subsequently retreated and cured with a combination of AQ plus CP, despite the fact that parasites infecting the children harboured mutant pfcrtT76 and pfmdr1Y86 alleles associated with AQ resistance. This suggests a potential clinical appliation of the reversal phenomenon

The continued impacts of the COVID-19 pandemic on education and mental health among sub-Saharan African adolescents

Purpose This multi-country survey assessed the levels and the determinants of the impacts of the pandemic on education and mental health among adolescents in sub-Saharan Africa and the potential factors that may exacerbate these adverse impacts. Methods A phone survey was conducted among adolescents in nine diverse areas in Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania between July and December 2021. Approximately 300 adolescents per area and 2803 adolescents in total were included. The survey collected information on adolescents’ sociodemographic characteristics, current COVID-19 preventive measures, and the impacts of the pandemic on daily activities, education, and mental health. Log-binomial models were used to calculate the adjusted prevalence ratios (aPRs) for determinants of education and mental health outcomes. Results Overall, 17% of the adolescents were not receiving any education. Compared to boys, girls were 15% more likely than boys to lack fully in-person education (aPR: 1.15; 95% CI: 1.02, 1.30). Rural residence was associated with 2.7 times the prevalence of not currently receiving any education (aPR: 2.68; 95% CI: 2.23, 3.22). Self-reported experience of the current impacts of the pandemic on daily activities was associated with a higher prevalence of possible psychological distress (aPR: 1.86; 95% CI: 1.55, 2.24), high anxiety level (aPR: 3.37; 95% CI: 2.25, 5.06), and high depression level (aPR: 3.01; 95% CI: 2.05, 4.41). Conclusions The COVID-19 pandemic presents continued challenges to adolescents’ education and mental health. Multi-sectoral efforts are needed to ensure that adolescents in sub-Saharan Africa do not fall further behind due to the pandemic