A Trial of the Efficacy, Safety and Impact on Drug Resistance of Four Drug Regimens for Seasonal Intermittent Preventive Treatment for Malaria in Senegalese Children

UNLABELLED: In the Sahel, most malaria deaths occur among children 1-4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. METHODS: 2102 children aged 6-59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. FINDINGS: The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76-1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30-0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. CONCLUSIONS: Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria

Skin biopsy in netherton syndrome: a histological review of a large series and new findings

Netherton syndrome (NS) is a severe genetic skin disorder, with often delayed or misleading clinical signs. The histological features of skin biopsies, usually described as a psoriasiform hyperplasia, have only been reported in isolated case reports or small case series. The aim of this study is to define, for the first time, the precise histological pattern of cutaneous lesions, in a large cohort of skin biopsies from confirmed NS patients. The study included 80 consecutive skin biopsies from 67 patients taken between January 1995 and June 2014. All were from confirmed NS patients with either a negative lympho-epithelial Kazal-type-related inhibitor (LEKTI) immunohistochemistry and/or molecular confirmation by identified mutation in SPINK5. In this cohort, the most frequent histological finding was also psoriasiform hyperplasia, but there were additional, less common, or previously unreported findings, including compact parakeratosis with large nuclei, subcorneum or intracorneum splitting, presence of clear cells in the upper epidermis or stratum corneum, dyskeratosis, dermal infiltrate with neutrophils and/or eosinophils, and dilated blood vessels in the superficial dermis. An early confirmation of the diagnosis of NS is essential for improved patient management. Thus, in the situation of a patient with an unknown skin disorder and non specific clinical presentation, the dermatopathologist may now be able to suggest the diagnosis of NS based on these newly reported characteristics. However, LEKTI immunohistochemistry remains the essential diagnostic investigation in cases with misleading or nonspecific histological features and is mandatory for the definitive diagnosis of NS in all patients

The endemic plants of Mozambique: diversity and conservation status

An annotated checklist of the 271 strict-endemic taxa (235 species) and 387 near-endemic taxa (337 species) of vascular plants in Mozambique is provided. Together, these taxa constitute c. 9.3% of the total currently known flora of Mozambique and include five strict-endemic genera (Baptorhachis, Emicocarpus, Gyrodoma, Icuria and Micklethwaitia) and two near-endemic genera (Triceratella and Oligophyton). The mean year of first publication of these taxa is 1959, with a marked increase in description noted following the onset of the two major regional floristic programmes, the “Flora of Tropical East Africa” and “Flora Zambesiaca”, and an associated increase in botanical collecting effort. New taxa from Mozambique continue to be described at a significant rate, with 20 novelties described in 2018. Important plant families for endemic and near-endemic taxa include Fabaceae, Rubiaceae and Euphorbiaceae s.s. There is a high congruence between species-rich plant families and endemism with the notable exceptions of the Poaceae, which is the second-most species rich plant family, but outside of the top ten families in terms of endemism, and the Euphorbiaceae, which is the seventh-most species rich plant family, but third in terms of endemism. A wide range of life-forms are represented in the endemic and near-endemic flora, with 49% being herbaceous or having herbaceous forms and 55% being woody or having woody forms. Manica Province is by far the richest locality for near-endemic taxa, highlighting the importance of the cross-border Chimanimani-Nyanga (Manica) Highlands shared with Zimbabwe. A total of 69% of taxa can be assigned to one of four cross-border Centres of Endemism: the Rovuma Centre, the Maputaland Centre sensu lato, and the two mountain blocks, Chimanimani-Nyanga and Mulanje-Namuli-Ribaue. Approximately 50% of taxa have been assessed for their extinction risk and, of these, just over half are globally threatened (57% for strict-endemics), with a further 10% (17% for strict-endemics) currently considered to be Data Deficient, highlighting the urgent need for targeted conservation of Mozambique’s unique flora. This dataset will be a key resource for ongoing efforts to identify “Important Plant Areas – IPAs” in Mozambique, and to promote the conservation and sustainable management of these critical sites and species, thus enabling Mozambique to meet its commitments under the Convention on Biological Diversity (CBD)

The endemic plants of Mozambique: diversity and conservation status

An annotated checklist of the 271 strict-endemic taxa (235 species) and 387 near-endemic taxa (337 species) of vascular plants in Mozambique is provided. Together, these taxa constitute c. 9.3% of the total currently known flora of Mozambique and include five strict-endemic genera (Baptorhachis, Emicocarpus, Gyrodoma, Icuria and Micklethwaitia) and two near-endemic genera (Triceratella and Oligophyton). The mean year of first publication of these taxa is 1959, with a marked increase in description noted following the onset of the two major regional floristic programmes, the “Flora of Tropical East Africa” and “Flora Zambesiaca”, and an associated increase in botanical collecting effort. New taxa from Mozambique continue to be described at a significant rate, with 20 novelties described in 2018. Important plant families for endemic and near-endemic taxa include Fabaceae, Rubiaceae and Euphorbiaceae s.s. There is a high congruence between species-rich plant families and endemism with the notable exceptions of the Poaceae, which is the second-most species rich plant family, but outside of the top ten families in terms of endemism, and the Euphorbiaceae, which is the seventh-most species rich plant family, but third in terms of endemism. A wide range of life-forms are represented in the endemic and near-endemic flora, with 49% being herbaceous or having herbaceous forms and 55% being woody or having woody forms. Manica Province is by far the richest locality for near-endemic taxa, highlighting the importance of the cross-border Chimanimani-Nyanga (Manica) Highlands shared with Zimbabwe. A total of 69% of taxa can be assigned to one of four cross-border Centres of Endemism: the Rovuma Centre, the Maputaland Centre sensu lato, and the two mountain blocks, Chimanimani-Nyanga and Mulanje-Namuli-Ribaue. Approximately 50% of taxa have been assessed for their extinction risk and, of these, just over half are globally threatened (57% for strict-endemics), with a further 10% (17% for strict-endemics) currently considered to be Data Deficient, highlighting the urgent need for targeted conservation of Mozambique’s unique flora. This dataset will be a key resource for ongoing efforts to identify “Important Plant Areas – IPAs” in Mozambique, and to promote the conservation and sustainable management of these critical sites and species, thus enabling Mozambique to meet its commitments under the Convention on Biological Diversity (CBD)

Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial.

BACKGROUND: In the Sahel and sub-Sahelian regions of Africa, malaria transmission is highly seasonal. During a short period of high malaria transmission, mortality and morbidity are high in children under age 5 years. We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection. METHODS: We did a randomised, placebo-controlled, double-blind trial of the effect of intermittent preventive treatment on morbidity from malaria in three health-care centres in Niakhar, a rural area of Senegal. 1136 children aged 2-59 months received either one dose of artesunate plus one dose of sulfadoxine-pyrimethamine or two placebos on three occasions during the malaria transmission season. The primary outcome was a first or single episode of clinical malaria detected through active or passive case detection. Primary analysis was by intention-to-treat. This study is registered with , number NCT00132561. FINDINGS: During 13 weeks of follow-up, the intervention led to an 86% (95% CI 80-90) reduction in the occurrence of clinical episodes of malaria. With passive case detection, protective efficacy against malaria was 86% (77-92), and when detected actively was 86% (78-91). The incidence of malaria in children on active drugs was 308 episodes per 1000 person-years at risk, whereas in those on placebo it was 2250 episodes per 1000 person-years at risk. 13 children were not included in the intention-to-treat analysis, which was restricted to children who received a first dose of antimalarial or placebo. There was an increase in vomiting in children who received the active drugs, but generally the intervention was well tolerated. INTERPRETATION: Intermittent preventive treatment could be highly effective for prevention of malaria in children under 5 years of age living in areas of seasonal malaria infection