Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination

Processamento da casca de mandioca na alimentação de ovinos: desempenho, características de carcaça, morfologia ruminal e eficiência econômica Processing of cassava peel in sheep feeding: performance, carcass characteristics, ruminal morphology and economic efficiency

Avaliou-se o efeito de diferentes formas de processamento da casca de mandioca na alimentação sobre o desempenho e as características de carcaça, a morfologia ruminal e a viabilidade técnico-econômica da criação de ovinos. Foram utilizados 20 ovinos machos da raça Santa Inês, desmamados, com peso inicial de 19,02±0,21 kg e 90 dias de vida. O delineamento experimental foi inteiramente casualizado com cinco repetições por dieta. Durante o período experimental de 84 dias, incluindo 14 dias de adaptação, os animais foram mantidos em sistema de semiconfinamento em pastagem de Brachiaria decumbens. Foram avaliadas quatro formas de processamento da casca de mandioca: desidratada triturada em peneira de 12 ou de 5 mm; úmida triturada e ensilada; e úmida triturada e hidrolisada com 0,5% de cal virgem (óxido de cálcio - CaO). O peso médio ao abate foi 30,72±1,46 kg. Não houve influência do tipo de processamento da casca sobre as características de desempenho analisadas, as características quantitativas de carcaça e a morfologia ruminal, sendo influenciado somente o rendimento de paleta. A casca de mandioca hidrolisada foi a que promoveu melhor eficiência econômica. Os tipos de processamento da casca de mandioca não alteram o desempenho, as características de carcaça, os rendimentos de corte e a morfologia ruminal dos ovinos Santa Inês.<br>The objective of this trial was to evaluate the effect of different forms of processing of cassava peel in sheep feeding on performance traits, carcass, morphology and rumen and economic technical feasibility. Twenty non-castrated male Santa Ines lambs of 19.02±0.21 kg of initial body weight and 90 days of age at the beginning of the study were used in this trial. The design was completely randomized design with five replications per treatment. During the experimental period of 84 days, including 14 days of adaptation, animals were kept in semi-confinement on Brachiaria decumbens. Four forms of cassava peel processing were evaluated: dried cassava peel ground through 12-mm sieve; dried cassava peel ground through 5-mm sieve; ground and ensiled cassava peel, and wet, ground hydrolyzed with 0.5% lime (calcium oxide - CaO). The average weight at slaughter was 30.72±1.46 kg. There was no influence of the type of processing on the performance variables analyzed, quantitative carcass characteristics or ruminal morphology; only the values of width and leg yield palette were influenced. Hydrolyzed cassava peel showed the best economic efficiency between treatments. The different methods of processing cassava peel do not affect performance, carcass characteristics, yield cuts or rumen morphology of Santa Ines sheep

Características quantitativas da carcaça de cordeiros de diferentes genótipos submetidos a duas dietas Quantitative traits of carcass from lambs of different genotypes submitted to two diets

Objetivou-se avaliar as características quantitativas de carcaça de cordeiros de diferentes genótipos recebendo diversos níveis de energia na dieta. Foram utilizados 54 cordeiros não-castrados, sendo 18 Santa Inês (SI), 18 F1Dorper × Santa Inês (Dp × SI) e 18 F1 Santa Inês × Sem Raça Definida (SI × SRD), com idade média de 150 dias e peso médio de 22,60 kg no início do experimento. As dietas continham 17% de proteína bruta e 2,40 Mcal/kg MS ou 2,90 Mcal/kg MS. Os cordeiros alimentados com a dieta contendo 2,90 Mcal/kg MS apresentaram maior peso corporal e de carcaça, área de olho-de-lombo, percentual de gordura interna, índice de musculosidade, índice de compacidade da carcaça, percentual de gordura e menor relação músculo:gordura. As carcaças desses cordeiros obtiveram também menores perdas por resfriamento e maior peso e percentual de paleta e perna. As carcaças dos cordeiros Dorper × Santa Inês foram superiores em espessura de gordura subcutânea, medida GR (gordura sobre a 12ª costela a 11 cm de distância da linha média lombo), percentual de gordura, relação músculo:osso, índice de musculosidade, peso e percentual de lombo. Os cordeiros Santa Inês apresentaram maior relação músculo:gordura. A dieta e o genótipo influenciam as características quantitativas de carcaça de cordeiros.<br>The objective of this study was to evaluate the quantitative carcass traits of lambs from different genotypes receiving different levels of energy in the diet. Fifty-four non-castrated lambs - 18 Santa Inês (SI), 18 F1Dorper × Santa Inês (Dp × SI) and 18 F1Santa Inês × No defined breed (SI × NDB) - of average 150 days old and 22.6-kg BW were used in the beginning of the experiment. Diets contained 17% crude protein and 2.40 Mcal/kg DM or 2.90 Mcal/kg DM. Lambs fed the diet containing 2.90 Mcal/kg DM showed higher final live and carcass weight, loin eye area, percentage of internal fat, muscularity index, compactness of the carcass index, percentage of fat and lower muscle:fat relation. These lambs' carcasses also presented lower percentage of cold loss and higher weight and percentage of shoulder and leg. Carcasses of Dp × SI lambs were superior in fat thickness, GR site, percentage of fat, muscle:bone relation, muscularity index, weight and percentage of loin. Santa Inês sheep showed higher muscle:fat relation. Both diet and genotype influence quantitative carcass traits of lambs