Impact of intermittent preventive treatment with dihydroartemisinin-piperaquine on malaria in Ugandan schoolchildren: a randomized, placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment (IPT) in schoolchildren offers a promising option for malaria control. However, the optimal drug and dosing regimens for IPT remain to be determined. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 740 schoolchildren aged 6-14 years living in a setting of high malaria transmission in Uganda. Enrolled children were randomized to dihydroartemisinin-piperaquine (DP) given once a month (IPTm), DP given once a school term (4 treatments over 12 months, IPTst), or placebo and followed for 12 months. The primary outcome was the incidence of malaria over 12 months. Secondary outcomes included parasite prevalence and anemia over 12 months. Analyses were conducted on an intention-to-treat basis. RESULTS: In the placebo arm, the incidence of malaria was 0.34 episodes per person-year and the prevalence of parasitemia and anemia was 38% and 20%, respectively. IPTm reduced the incidence of malaria by 96% (95% confidence interval [CI], 88%-99%, P < .0001), the prevalence of asymptomatic parasitemia by 94% (95% CI, 92%-96%, P < .0001), and the prevalence of anemia by 40% (95% CI, 19%-56%, P < .0001). IPTst had no significant effect on the incidence of symptomatic malaria or the prevalence of anemia, but reduced the prevalence of asymptomatic parasitemia by 54% (95% CI, 47%-60%, P < .0001). CONCLUSIONS: Monthly IPT with DP offered remarkable protection against clinical malaria, parasitemia, and anemia in schoolchildren living in a high-malaria-transmission setting. CLINICAL TRIALS REGISTRATION: NCT01231880

"They don't care what happens to us." The situation of double orphans heading households in Rakai District, Uganda

<p>Abstract</p> <p>Background</p> <p>This article is based on information collected about the situation of double orphans who are heading households in Rakai District, Uganda. The information will be used as justification and guidance for planning actions to improve the situation of these and similar children. This research is thus the first step in an Action Research approach leading to specific interventions. The aim of this article is to describe the situation of these orphaned children, with an emphasis on the psychosocial challenges they face.</p> <p>Methods</p> <p>The study involved interviews, focus group discussions, observations and narratives. Forty-three heads of sibling-headed households participated. Information derived from informal discussions with local leaders is also included. The responses were analyzed using a modified version of Giorgi's psychological phenomenological method as described by Malterud <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p> <p>Results</p> <p>Factors such as lack of material resources, including food and clothes, limited possibilities to attend school on a regular basis, vast responsibilities and reduced possibilities for social interaction all contribute to causing worries and challenges for the child heads of households. Most of the children claimed that they were stigmatized and, to a great extent, ignored and excluded from their community. The Local Council Secretary ("Chairman") seemed to be the person in the community most responsible and helpful, but some chairmen seemed not to care at all. The children requested counseling for themselves as well as for community members because they experienced lack of understanding from other children and from adult community members.</p> <p>Conclusion</p> <p>The children experienced their situation as a huge and complex problem for themselves as well as for people in their villages. However, the situation might improve if actions focused on practical and psychological issues as well as on sensitization about the children's situation could be initiated. In addition to the fact that these children need adult guidance to become citizens who act in accordance with the expectations in their communities, material aid is important in order to reduce the children's experiences of being "different" and constantly experiencing survival anxieties.</p> <p indent="1"><it>Before my parents died, I was schooling without facing any problems and my heart was at rest. When they died I went to live with Jjajja [grandmother]. She fell very sick and I came out of school for a full term to look after her. I was treating Jjajja but she was not getting better. She died...so...I got my schoolmates' books and copied notes that they had taken while I was away from school...I face the problem of not having good friends. Some see me as a disease...other people are not bad. Some call me names and say that I am stupid, that I probably inherited the stupidity from my mother or father...Ever since my parents died, I have not had peace. I spend most of the time thinking, crying and struggling within myself asking God why He really had to do such a thing and saying to myself that: "God, help me overcome these problems!"</it></p> <p indent="1"><it>Girl, 15</it>.</p

Improving access to health care for malaria in Africa: a review of literature on what attracts patients

BACKGROUND: Increasing access to health care services is considered central to improving the health of populations. Existing reviews to understand factors affecting access to health care have focused on attributes of patients and their communities that act as 'barriers' to access, such as education level, financial and cultural factors. This review addresses the need to learn about provider characteristics that encourage patients to attend their health services. METHODS: This literature review aims to describe research that has identified characteristics that clients are looking for in the providers they approach for their health care needs, specifically for malaria in Africa. Keywords of 'malaria' and 'treatment seek*' or 'health seek*' and 'Africa' were searched for in the following databases: Web of Science, IBSS and Medline. Reviews of each paper were undertaken by two members of the team. Factors attracting patients according to each paper were listed and the strength of evidence was assessed by evaluating the methods used and the richness of descriptions of findings. RESULTS: A total of 97 papers fulfilled the inclusion criteria and were included in the review. The review of these papers identified several characteristics that were reported to attract patients to providers of all types, including lower cost of services, close proximity to patients, positive manner of providers, medicines that patients believe will cure them, and timeliness of services. Additional categories of factors were noted to attract patients to either higher or lower-level providers. The strength of evidence reviewed varied, with limitations observed in the use of methods utilizing pre-defined questions and the uncritical use of concepts such as 'quality', 'costs' and 'access'. Although most papers (90%) were published since the year 2000, most categories of attributes had been described in earlier papers. CONCLUSION: This paper argues that improving access to services requires attention to factors that will attract patients, and recommends that public services are improved in the specific aspects identified in this review. It also argues that research into access should expand its lens to consider provider characteristics more broadly, especially using methods that enable open responses. Access must be reconceptualized beyond the notion of barriers to consider attributes of attraction if patients are to receive quality care quickly

Yield and Mineral Composition among Mungbean [Vigna radiata (L.) R. Wilczek] Genotypes Grown in Different Agroecologies in East Africa

Mungbean [Vigna radiata (L.) R. Wilczek var. radiata] also referred to as green gram is a key crop especially in the marginal areas of East Africa. It is rich in micronutrients and protein and thus can help ameliorate malnutrition if incorporated into diets. 'is study was conducted to evaluate the performance of 26 fixed elite mungbean breeding genotypes for yield and micronutrient composition across di6erent locations in East Africa (Uganda, Kenya, and Tanzania). 'e genotypes displayed significant variability for nutritional, phenology, and yield-related traits across test environments. Significant genotype e6ects were observed for most of the traits except for average yield per plant and dry matter content (P < 0.05). Random effect of environment was significant for all traits, and significant GXE was observed for all traits except for dry matter and iron content (P < 0.05). Moderate to high broad-sense heritability (H2) was found among traits except for dry matter content which was low (H2 =10.4%). 'ere was a signi4cant and positive correlation between Fe and Zn (r =0.58), and Fe and Ca (r=0.46), indicating the potential to enhance these traits simultaneously through breeding and/or selection. However, the correlation between yield and nutrients (iron, zinc, and calcium) was negative. Environments KAT_SR_2019, KYM_LR_2020, and KYM_LR_2020 were found to be discriminating (informative) and representative of grain yield, calcium, and zinc content, respectively. Genotypes AVMU 1679, AVMU 1685, and AVMU 1686 combined both stability and high micronutrient content, while the high yielding and stable genotypes were AVMU 1689, AVMU 1681, and AVMU 16102. The identified genotypes need to be assessed for farmer preference in on-farm trials before they can be recommended for release as new varieties. Additionally, these genotypes will be useful in future breeding efforts as donors aimed at developing nutrient-dense and high yielding mungbean varieties

Candidate genes for field resistance to cassava brown streak disease revealed through the analysis of multiple data sources

Cassava (Manihot esculenta Crantz) is a food and industrial storage root crop with substantial potential to contribute to managing risk associated with climate change due to its inherent resilience and in providing a biodegradable option in manufacturing. In Africa, cassava production is challenged by two viral diseases, cassava brown streak disease (CBSD) and cassava mosaic disease. Here we detect quantitative trait loci (QTL) associated with CBSD in a biparental mapping population of a Tanzanian landrace, Nachinyaya and AR37-80, phenotyped in two locations over three years. The purpose was to use the information to ultimately facilitate either marker-assisted selection or adjust weightings in genomic selection to increase the efficiency of breeding. Results from this study were considered in relation to those from four other biparental populations, of similar genetic backgrounds, that were phenotyped and genotyped simultaneously. Further, we investigated the co-localization of QTL for CBSD resistance across populations and the genetic relationships of parents based on whole genome sequence information. Two QTL on chromosome 4 for resistance to CBSD foliar symptoms and one on each of chromosomes 11 and 18 for root necrosis were of interest. Of significance within the candidate genes underlying the QTL on chromosome 4 are Phenylalanine ammonia-lyase (PAL) and Cinnamoyl-CoA reductase (CCR) genes and three PEPR1-related kinases associated with the lignin pathway. In addition, a CCR gene was also underlying the root necrosis-resistant QTL on chromosome 11. Upregulation of key genes in the cassava lignification pathway from an earlier transcriptome study, including PAL and CCR, in a CBSD-resistant landrace compared to a susceptible landrace suggests a higher level of basal lignin deposition in the CBSD-resistant landrace. Earlier RNAscope®in situ hybridisation imaging experiments demonstrate that cassava brown streak virus (CBSV) is restricted to phloem vessels in CBSV-resistant varieties, and phloem unloading for replication in mesophyll cells is prevented. The results provide evidence for the involvement of the lignin pathway. In addition, five eukaryotic initiation factor (eIF) genes associated with plant virus resistance were found within the priority QTL regions

Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial

BACKGROUND: Paediatric dolutegravir doses approved by stringent regulatory authorities (SRAs) for children weighing 20 kg to less than 40 kg until recently required 25 mg and 10 mg film-coated tablets. These tablets are not readily available in low-resource settings where the burden of HIV is highest. We did nested pharmacokinetic substudies in patients enrolled in the ODYSSEY-trial to evaluate simplified dosing in children with HIV. METHODS: We did pharmacokinetic and safety substudies within the open-label, multicentre, randomised ODYSSEY trial (NCT02259127) of children with HIV starting treatment in four research centres in Uganda and Zimbabwe. Eligible children were randomised to dolutegravir in ODYSSEY and weighed 20 kg to less than 40 kg. In children weighing 20 kg to less than 25 kg, we assessed dolutegravir's pharmacokinetics in children given once daily 25 mg film-coated tablets (approved by the SRAs at the time of the study) in part one of the study, and 50 mg film-coated tablets (adult dose) or 30 mg dispersible tablets in part two of the study. In children weighing 25 kg to less than 40 kg, we also assessed dolutegravir pharmacokinetics within-subject on film-coated tablet doses of 25 mg or 35 mg once daily, which were approved by the SRAs for the children's weight band; then switched to 50 mg film-coated tablets once daily. Steady-state 24 h dolutegravir plasma concentration-time pharmacokinetic profiling was done in all enrolled children at baseline and 1, 2, 3, 4, 6, and 24 h after observed dolutegravir intake. Target dolutegravir trough concentrations (Ctrough) were based on reference adult pharmacokinetic data and safety was evaluated in all children in the corresponding weight bands who consented to pharmacokinetic studies and received the studied doses. FINDINGS: Between Sept 22, 2016, and May 31, 2018, we enrolled 62 black-African children aged from 6 years to younger than 18 years (84 pharmacokinetic-profiles). In children weighing 20 kg to less than 25 kg taking 25 mg film-coated tablets, the geometric mean (GM) Ctrough (coefficient of variation) was 0·32 mg/L (94%), which was 61% lower than the GM Ctrough of 0·83 mg/L (26%) in fasted adults on dolutegravir 50 mg once-daily; in children weighing 25 kg to less than 30 kg taking 25 mg film-coated tablets, the GM Ctrough was 0·39 mg/L (48%), which was 54% lower than the GM Ctrough in fasted adults; and in those 30 kg to less than 40 kg taking 35 mg film-coated tablets the GM Ctrough was 0·46 mg/L (63%), which was 45% lower than the GM Ctrough in fasted adults. On 50 mg film-coated tablets or 30 mg dispersible tablets, Ctrough was close to the adult reference (with similar estimates on the two formulations in children in the 20 to <25 kg weight band), with total exposure (area under the concentration-time curve from 0 h to 24 h) in between reference values in adults dosed once and twice daily, where safety data are reassuring, although maximum concentrations were higher in children weighing 20 kg to less than 25 kg than in the twice-daily adult reference. Over a 24-week follow-up period in 47 children on 30 mg dispersible tablets or 50 mg film-coated tablets, none of the three reported adverse events (cryptococcal meningitis, asymptomatic anaemia, and asymptomatic neutropenia) were considered related to dolutegravir. INTERPRETATION: Adult dolutegravir 50 mg film-coated tablets given once daily provide appropriate pharmacokinetic profiles in children weighing 20 kg or more, with no safety signal, allowing simplified practical dosing and rapid access to dolutegravir. These results informed the WHO 2019 dolutegravir paediatric dosing guidelines and have led to US Food and Drug Administration approval of adult dosing down to 20 kg. FUNDING: Paediatric European Network for Treatment of AIDS Foundation, ViiV Healthcare, UK Medical Research Council

Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial

Background: Paediatric dolutegravir doses approved by stringent regulatory authorities (SRAs) for children weighing 20 kg to less than 40 kg until recently required 25 mg and 10 mg film-coated tablets. These tablets are not readily available in low-resource settings where the burden of HIV is highest. We did nested pharmacokinetic substudies in patients enrolled in the ODYSSEY-trial to evaluate simplified dosing in children with HIV. Methods: We did pharmacokinetic and safety substudies within the open-label, multicentre, randomised ODYSSEY trial (NCT02259127) of children with HIV starting treatment in four research centres in Uganda and Zimbabwe. Eligible children were randomised to dolutegravir in ODYSSEY and weighed 20 kg to less than 40 kg. In children weighing 20 kg to less than 25 kg, we assessed dolutegravir's pharmacokinetics in children given once daily 25 mg film-coated tablets (approved by the SRAs at the time of the study) in part one of the study, and 50 mg film-coated tablets (adult dose) or 30 mg dispersible tablets in part two of the study. In children weighing 25 kg to less than 40 kg, we also assessed dolutegravir pharmacokinetics within-subject on film-coated tablet doses of 25 mg or 35 mg once daily, which were approved by the SRAs for the children's weight band; then switched to 50 mg film-coated tablets once daily. Steady-state 24 h dolutegravir plasma concentration-time pharmacokinetic profiling was done in all enrolled children at baseline and 1, 2, 3, 4, 6, and 24 h after observed dolutegravir intake. Target dolutegravir trough concentrations (Ctrough) were based on reference adult pharmacokinetic data and safety was evaluated in all children in the corresponding weight bands who consented to pharmacokinetic studies and received the studied doses. Findings: Between Sept 22, 2016, and May 31, 2018, we enrolled 62 black-African children aged from 6 years to younger than 18 years (84 pharmacokinetic-profiles). In children weighing 20 kg to less than 25 kg taking 25 mg film-coated tablets, the geometric mean (GM) Ctrough (coefficient of variation) was 0\ub732 mg/L (94%), which was 61% lower than the GM Ctrough of 0\ub783 mg/L (26%) in fasted adults on dolutegravir 50 mg once-daily; in children weighing 25 kg to less than 30 kg taking 25 mg film-coated tablets, the GM Ctrough was 0\ub739 mg/L (48%), which was 54% lower than the GM Ctrough in fasted adults; and in those 30 kg to less than 40 kg taking 35 mg film-coated tablets the GM Ctrough was 0\ub746 mg/L (63%), which was 45% lower than the GM Ctrough in fasted adults. On 50 mg film-coated tablets or 30 mg dispersible tablets, Ctrough was close to the adult reference (with similar estimates on the two formulations in children in the 20 to <25 kg weight band), with total exposure (area under the concentration-time curve from 0 h to 24 h) in between reference values in adults dosed once and twice daily, where safety data are reassuring, although maximum concentrations were higher in children weighing 20 kg to less than 25 kg than in the twice-daily adult reference. Over a 24-week follow-up period in 47 children on 30 mg dispersible tablets or 50 mg film-coated tablets, none of the three reported adverse events (cryptococcal meningitis, asymptomatic anaemia, and asymptomatic neutropenia) were considered related to dolutegravir. Interpretation: Adult dolutegravir 50 mg film-coated tablets given once daily provide appropriate pharmacokinetic profiles in children weighing 20 kg or more, with no safety signal, allowing simplified practical dosing and rapid access to dolutegravir. These results informed the WHO 2019 dolutegravir paediatric dosing guidelines and have led to US Food and Drug Administration approval of adult dosing down to 20 kg. Funding: Paediatric European Network for Treatment of AIDS Foundation, ViiV Healthcare, UK Medical Research Council