The future of public health doctoral education in Africa: transforming higher education institutions to enhance research and practice.

The African Union and the Africa Centers for Disease Control and Prevention issued a Call to Action in 2022 for Africa's New Public Health Order that underscored the need for increased capacity in the public health workforce. Additional domestic and global investments in public health workforce development are central to achieving the aspirations of Agenda 2063 of the African Union, which aims to build and accelerate the implementation of continental frameworks for equitable, people-centred growth and development. Recognising the crucial role of higher education and research, we assessed the capabilities of public health doctoral training in schools and programmes of public health in Africa across three conceptual components: instructional, institutional, and external. Six inter-related and actionable recommendations were derived to advance doctoral training, research, and practice capacity within and between universities. These can be achieved through equitable partnerships between universities, research centres, and national, regional, and global public health institutions.

The Continued Impacts of the COVID-19 Pandemic on Education and Mental Health Among Sub-Saharan African Adolescents.

PURPOSE: This multicountry 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 2,803 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% confidence interval [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). DISCUSSION: The COVID-19 pandemic presents continued challenges to adolescents' education and mental health. Multisectoral efforts are needed to ensure that adolescents in sub-Saharan Africa do not fall further behind due to the pandemic.

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.

The age of opportunity: prevalence of key risk factors among adolescents 10-19 years of age in nine communities in sub-Saharan Africa.

OBJECTIVE: To measure health-related behaviours and risk factors among sub-Saharan African adolescents. METHODS: Cross-sectional study in nine communities in Burkina Faso, Ethiopia, Eswatini, Ghana, Nigeria, Tanzania and Uganda between 2015 and 2017. Community-representative samples of males and females 10-19 years of age were selected. All communities used a uniform questionnaire that was adapted from the WHO Global School-based Student Health Survey. Weighted prevalence estimates and 95% confidence intervals were calculated for each indicator and stratified by age and sex using SAS version 9.4. All prevalence estimates were pooled across communities through random-effects meta-analyses in Stata version 14. RESULTS: A total of 8075 adolescents participated in the study. We observed a high prevalence of inadequate fruit consumption (57-63%) and low physical activity (82-90%); a moderate prevalence of inadequate vegetable consumption (21-31%), unprotected last sex (38-45%), age at first sex <15 years (21-28%) and bullying and physical fighting (12-35%); and a low prevalence of mental health risk factors (1-11%) and alcohol and substance use risk factors (0-6%). We observed a moderate to high prevalence of daily soft drink consumption (21-31%) for all adolescents. Among sexually active adolescents 15-19 years, 37% of females reported ever being pregnant and 8% of males reported to have ever made someone pregnant. Bullying (23%) and physical fighting (35%) were more common among younger male adolescents . The prevalence of low mood was generally higher among older (15-19 years) than younger adolescents (10-14 years). The proportion of adolescents reporting alcohol, drug or cigarette use was very small, with the exception of khat use in Ethiopia. CONCLUSION: Overall, diet and physical activity, violence, sexual and reproductive health, and depression are important risk factors for these sub-Saharan African communities. These findings suggest that more evidence is needed including novel efforts for the collection of sensitive information, as well as a need to move towards community-tailored interventions to reach adolescent populations with varying needs.

OBJECTIF: Mesurer les comportements liés à la santé et les facteurs de risque chez les adolescents africains subsahariens. MÉTHODES: Etude transversale dans neuf communautés au Burkina Faso, en Ethiopie, à Eswatini, au Ghana, au Nigéria, en Tanzanie et en Ouganda entre 2015 et 2017. Des échantillons représentatifs de la communauté composés d'hommes et de femmes âgés de 10 à 19 ans ont été sélectionnés. Toutes les communautés ont utilisé un questionnaire uniforme adapté de l'Enquête Mondiale sur la Santé des Elèves de l'OMS. Les estimations de prévalence pondérée et les intervalles de confiance à 95% ont été calculés pour chaque indicateur et stratifiées par âge et sexe à l'aide de la version 9.4 de SAS. Toutes les estimations de prévalence ont été poolées dans les communautés via des méta-analyses à effets aléatoires dans Stata, version 14. RÉSULTATS: 8.075 adolescents ont participé à l'étude. Nous avons observé une prévalence élevée de consommation insuffisante de fruits (57-63%) et de faible activité physique (82-90%); une prévalence modérée de consommation insuffisante de légumes (21-31%), du dernier rapport sexuel non protégé (38-45%), du premier rapport sexuel à moins de 15 ans (21-28%) et de l'intimidation et des combats physiques (12-35%), une faible prévalence de facteurs de risque pour la santé mentale (1-11%) et de facteurs de risque pour la consommation d'alcool et de substances (0-6%). Nous avons observé une prévalence modérée à élevée de consommation quotidienne de boissons gazeuses (21-31%) chez tous les adolescents. Parmi les adolescents sexuellement actifs âgées de 15 à 19 ans, 37,0% des femmes ont déclaré avoir déjà été enceintes et 8,0% des hommes ont rapporté avoir déjà enceinté une femme. L'intimidation (23%) et les combats physiques étaient plus fréquents chez les adolescents plus jeunes (35%). La prévalence de la mauvaise humeur était généralement plus élevée chez les adolescents d'âge plus élevé (de 15 à 19 ans) que chez les plus jeunes (de 10 à 14 ans). La proportion d'adolescents déclarant avoir consommé de l'alcool, des drogues ou des cigarettes était très faible, à l'exception de la consommation de khat en Ethiopie. CONCLUSION: Dans l'ensemble, le régime alimentaire et l'activité physique, la violence, la santé sexuelle et reproductive et la dépression sont des facteurs de risque importants pour ces communautés d'Afrique subsaharienne. Ces résultats suggèrent que davantage de données sont nécessaires, notamment de nouveaux efforts pour la collecte d'informations sensibles, ainsi que la nécessité de passer à des interventions adaptées aux communautés pour atteindre les populations adolescentes avec des besoins variés.

Novel 4-aminoquinoline analogs highly active against the blood and sexual stages of Plasmodium in vivo and in vitro.

New drugs to treat malaria must act rapidly and be highly potent against asexual blood stages, well tolerated, and affordable to residents of regions of endemicity. This was the case with chloroquine (CQ), a 4-aminoquinoline drug used for the prevention and treatment of malaria. However, since the 1960s, Plasmodium falciparum resistance to this drug has spread globally, and more recently, emerging resistance to CQ by Plasmodium vivax threatens the health of 70 to 320 million people annually. Despite the emergence of CQ resistance, synthetic quinoline derivatives remain validated leads for new drug discovery, especially if they are effective against CQ-resistant strains of malaria. In this study, we investigated the activities of two novel 4-aminoquinoline derivatives, TDR 58845, N(1)-(7-chloro-quinolin-4-yl)-2-methyl-propane-1,2-diamine, and TDR 58846, N(1)-(7-chloro-quinolin-4-yl)-2,N(2),N(2)-trimethylpropane-1,2-diamine and found them to be active against P. falciparum in vitro and Plasmodium berghei in vivo. The P. falciparum clones and isolates tested were susceptible to TDR 58845 and TDR 58846 (50% inhibitory concentrations [IC(50)s] ranging from 5.52 to 89.8 nM), including the CQ-resistant reference clone W2 and two multidrug-resistant parasites recently isolated from Thailand and Cambodia. Moreover, these 4-aminoquinolines were active against early and late P. falciparum gametocyte stages and cured BALB/c mice infected with P. berghei. TDR 58845 and TDR 58846 at 40 mg/kg were sufficient to cure mice, and total doses of 480 mg/kg of body weight were well tolerated. Our findings suggest these novel 4-aminoquinolines should be considered for development as potent antimalarials that can be used in combination to treat multidrug-resistant P. falciparum and P. vivax.

Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolates from Nigeria and Brazil: the potential role of antimalarial drug selection pressure.

The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria.

Interaction between ciprofloxacin and chloroquine in mice infected with chloroquine resistant Plasmodium berghei: interaction between ciprofloxacin and chloroqune.

The increasing spread of chloroquine resistant malaria has intensified the search for new antimalarial treatment, especially drugs that can be used in combination. Ciprofloxacin (CFX) a fluoroquinolone commonly used to treat bacterial infections has been shown to possess significant antimalarial activity both in vitro and in vivo. Thus efforts in this study were devoted to evaluating the antimalarial activity of combination of chloroquine (CQ) with varying doses (10, 20, 40 80, 160 mg/kg body weight) of CFX in groups of 35 mice inoculated intraperitoneally with 10(7) chloroquine resistant strain Plasmodium berghei ANKA. Parasitological activity and survival of the animals were assessed over 21 days. Parasitemia in non-treated control mice peaked at 78% on day 9 and none survived by day 10. However, the combination of CQ with 160 mg/kg body weight of CFX resulted in a reduction in parasitemia between days 9 and 14 and this was significantly lower than that obtained with CQ alone or CQ combined with the lower doses of CFX (p < 0.05). In addition, the combination of CQ with 160 mg/kg CFX significantly reduced mortality in the infected animals (p = 0.0002) compared with the other treatment groups. The results from this study support the potential usefulness of CFX in combination with antimalarial drugs for the treatment of chloroquine resistant human malaria.

Antitrypanosomal activity of some medicinal plants from Nigerian ethnomedicine.

Human African trypanosomiasis is a neglected tropical disease with complex clinical presentation, diagnosis, and difficult treatment. The available drugs for the treatment of trypanosomiasis are old, expensive, and less effective, associated with severe adverse reactions and face the problem of drug resistance. This situation underlines the urgent need for the development of new, effective, cheap, and safe drugs for the treatment of trypanosomiasis. The search for new antitrypanosomal agents in this study is based on ethnomedicine. In vitro antitrypanosomal activity of 36 plant extracts from 10 plant species from Nigerian ethnomedicine was evaluated against bloodstream forms of Trypanosoma brucei rhodesiense STIB 900. Cytotoxic activity was determined against mammalian L6 cells. Alamar blue assay was used to measure the endpoint of both antitrypanosomal and toxicity assays. The ethyl acetate extract of leaves of Ocimum gratissimum Linn. (Labiatae) showed the highest antitrypanosomal activity (IC(50) of 2.08 ± 0.01 µg/ml) and a high selective index of 29. Furthermore, the hexane, ethyl acetate, or methanol extracts of Trema orientalis (L.) Blume (Ulmaceae), Pericopsis laxiflora (Benth. ex Baker) Meeuwen, Jatropha curcas Linn. (Euphorbiaceae), Terminalia catappa Linn. (Combretaceae), and Vitex doniana Sweet (Verbenaceae) displayed remarkable antitrypanosomal activity (IC(50) 2.1-17.2 µg/ml) with high selectivity indices (20-80) for trypanosomes. The antitrypanosomal activity of T. catappa and T. orientalis against T. brucei rhodesiense (STIB 900) is being reported for the first time in Nigerian ethnomedicine, and these plants could be a potential source of antitrypanosomal agents.

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

BACKGROUND: Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum 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. METHODS: 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 Plasmodium falciparum. RESULTS: 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. CONCLUSION: 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.

Rapid detection of lactate dehydrogenase and genotyping of Plasmodium falciparum in saliva of children with acute uncomplicated malaria.

The diagnosis of malaria in biological fluids other than blood using non-invasive, rapid diagnostic techniques provides a valuable approach in case management and epidemiological studies of malaria. Rapid detection of Plasmodium falciparum lactate dehydrogenase (pLDH) in saliva samples from 130 of 144 children with microscopically confirmed P. falciparum infection was evaluated using Optimal-IT dipsticks. Genotyping of parasites was also performed in saliva and blood samples from a cohort of patients by polymerase chain reaction (PCR). The sensitivity of the dipstick in whole-blood, whole-saliva, or supernatant of spun saliva samples was 97.2%, 77.9%, and 48.4%, respectively. The sensitivity of the dipstick in whole-saliva samples was significantly higher than in supernatant of spun saliva samples (P < 0.0005). Mutant T76 allele was detectable in 60% and 57% of blood and saliva samples, respectively. This finding shows rapid detection of pLDH in patient saliva.

Comparison of SYBR Green I-, PicoGreen-, and [3H]-hypoxanthine-based assays for in vitro antimalarial screening of plants from Nigerian ethnomedicine.

The standard method for in vitro antimalarial drug screening is based on the isotopic assay which is expensive and utilizes radioactive materials with limited availability, safety, and disposal problems in developing countries. The use of non-radioactive DNA stains SYBR Green I (SG) and PICO green (PG) for antimalarial screening had been reported. However, the use of the two DNA stains for antimalarial screening of medicinal plants has not been compared. Thus, this study compared SG, PG with the [(3)H]-hypoxanthine (HP) incorporation assays for in vitro antimalarial screening of medicinal plants. The 50% inhibitory concentration (IC(50)) values obtained using the three methods for antimalarial activity of medicinal plants and standard antimalarial drugs were similar. Data generated from this study suggests that the non-radioactive micro-flourimetric assay is sufficiently sensitive to reproducibly identify plant extracts with antimalarial activity from those lacking activity. The HP-based assay exhibited the most robust signal-to-noise ratio of 100, compared with signal-to-noise ratios of 7 for SG and 8 for PG. The SG-based assay is less expensive than the PG- and HP-based assays. SG appears to be a cost-effective alternative for antimalarial drug screening and a viable technique that may facilitate antimalarial drug discovery process especially in developing countries.

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

BACKGROUND: 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. METHODS: 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 C18 and a mobile phase consisting of 0.05 M phosphate buffer-methanol-acetonitrile (70:17:13 V/V/V) containing 1% triethylamine solution. RESULTS: 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. CONCLUSION: 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.

Potential contribution of prescription practices to the emergence and spread of chloroquine resistance in south-west Nigeria: caution in the use of artemisinin combination therapy.

BACKGROUND: Prescription practices have been shown to influence the emergence of anti-malarial drug resistance. Thus efforts in this study were devoted to evaluating the prescribing practices prior to introduction of the artemisinin based combination therapy (ACT) in Nigeria and its potential contribution to emergence of chloroquine resistant malaria in south-west Nigeria, in order to forestall a similar situation with the ACT. METHODS: A retrospective quantitative study was designed to examine case records of patients treated for malaria in either a government or a private hospital in Ibadan, south-west Nigeria, over a 20-year period, cutting across three phases of resistance to chloroquine in Nigeria: pre-resistance, emerging resistance and dissemination of resistance. Patient prescriptions were examined for use of anti-malarial drugs, sub-therapeutic doses of chloroquine, co-administration of anti-histamines with chloroquine. Descriptive statistics of frequency and percentage were used to describe trends in the parameters assessed using EPI-info. RESULTS: Case record files of 2,529 patients were examined. Chloroquine was the main drug used in treatment of malaria throughout the periods studied, with frequency of prescription at both sites ranging from 91.4% to 98.3% during the pre-resistance years. It was administered as standard doses during the pre resistance years. Anti-histamines, especially promethazine, were routinely co-administered with chloroquine at this period too. However, the practice of prescribing sub-therapeutic doses of chloroquine at the private health care facility coincided with the latter phase of emerging resistance and phase of dissemination of resistance. Frequency of prescription of sub-therapeutic doses increased from 6.7% in 1983 (pre-resistance years) to 43.6% in 1997 (dissemination of resistance phase) at the private health care facility. Frequency of co-administration of anti-histamines with chloroquine also reduced during the period of dissemination of resistance. CONCLUSION: The results from this study describe a lack of adherence to national treatment guidelines, especially in the private sector, and a relationship between prescription practices and dissemination of drug resistant falciparum malaria. As Nigeria adopts the use of ACT, there is an urgent need to improve malaria treatment practices in Nigeria in order to prolong the clinical shelf-life of the combination.

Evaluation of the efficacy and safety of artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in Nigerian infants and children.

BACKGROUND: The six-dose regimen of artemether-lumefantrine (AL) is now considered the gold standard for the treatment of uncomplicated Plasmodium falciparum malaria. There are few reports evaluating co-artemether in very young Nigerian infants and children. Results of the evaluation of the six-dose regimen in very young infants and children in Nigeria are presented in this report. METHODS: As part of a larger African study, this open label, non-comparative trial, assessed the efficacy and safety of six-dose regimen of AL tablets in 103 Nigerian infants and children weighing between five and 25 kg suffering from acute uncomplicated malaria. Treatment was administered under supervision over three days with children as in-patients. 12-lead ECG tracings were taken pre-treatment and at day 3. RESULTS: Ninety-three infants and children completed the study as stipulated by the protocol. Mean fever and parasite clearance times for the intent to treat population (ITT) were 24.9 h +/- (1.28) and 26 h +/- (4.14) and the corresponding figures for the per-protocol population (PP) were 19.24 h +/- 13.9 and 25.62 h +/- 11.25 respectively. Day 14 cure rates for the ITT and PP were 95.1% and 100% respectively while day 28 cure rates were 91.3% and 95.7% respectively. The overall PCR corrected day 28 cure rate was 95.1% for the ITT. The six-dose regimen of AL was well tolerated with no drug-related serious adverse events. Although six patients recorded a QTc prolongation of > 60 ms on D3 over D0 recording, no patient recorded a QTc interval > 500 ms. CONCLUSION: The six-dose regimen of AL tablets is safe and effective for the treatment of acute uncomplicated malaria in Nigerian infants and children weighing between five and 25 kg. TRIAL REGISTRATION: NCT00709969.

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 application 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.

Dihydroartemisinin suppository in moderately severe malaria: comparative efficacy of dihydroartemisinin suppository versus intramuscular artemeter followed by oral sulfadoxine-pyrimethamine in the management of moderately severe malaria in Nigerian children.

We compared two dose forms of artemisinin derivatives, dihydroartemisinin suppository (DHA) and intramuscular artemether (ART), in children 6 months to 10 years of age with moderately severe malaria for which oral therapy was not appropriate. Children were randomly allocated to receive three daily doses of DHA or ART followed by a single oral dose of sulfadoxine-pyrimethamine on the third day of both treatment regimens and were monitored for parasitologic and clinical response for 14 days. At enrollment, parasite density was 1,640-523,333/microL (geometric mean parasite density [GMPD] = 58,129/microL) in patients treated with DHA, whereas that for children who received ART was 1,440-559,400/microL (GMPD = 60,387/microL). Mean parasite and fever clearance times were similar in both groups. Days 14 and 28 parasitologic cure rates were 100% (34 of 34) and 96.2% (25 of 26) versus 96.2% (25 of 26) and 91.7% (22 of 24) for children treated with DHA and ART, respectively. In conclusion, both treatment regimens were efficacious and well tolerated.

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.

The Anopheles gambiae genome: next steps for malaria vector control.

Malaria remains a major public health problem that is made worse by poor implementation of control measures, and by the spread of drug- and insecticide-resistant parasites and vectors, respectively. Availability of the Anopheles gambiae genome sequence will accelerate identification and exploitation of new target genes in this insect vector. This provides unique opportunities to improve on existing vector control tools and to generate new tools within a global partnership. However, significant capacity needs to be built for investigators in disease-endemic countries to exploit the genome data. When integrated with existing strategies, the new tools will form an effective package for selective vector control in an effort to prevent mortality and morbidity due to malaria.