Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria

With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso. An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline. MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies

An overview of the development challenges and constraints of the Niger Basin and possible intervention strategies

The Niger River Basin covers 7.5% of the African continent, and is shared between nine riparian countries. The basin countries can be categorized into water resources producers, consumers, both producers and consumers, and minimum contributors and consumers. As in the case for most transboundary rivers, upstream and downstream conflicts emanating from the development and utilization of the Niger River are inevitable and are expected to be intense, particularly given the escalating demands for water from the many uses and users. The basin is divided into four major sections, namely Upper Niger, Inland Delta, Middle Niger, and Lower Niger. But these divisions, though useful, are too generic to provide a complete understanding of biophysical, hydrological and socioeconomic processes impinging on the basin’s water resources, and to provide intervention recommendations. On average, the basin’s population is two-thirds (64%) rural and a significant part of the northern zones of the basin is unpopulated. People in the basin are engaged in various livelihood strategies such as dry- and wet-season cropping systems, pastoral systems, crop-livestock systems, and fishing. The dry-season livelihood systems include fadama (lowland or inland valleys) farming, recession flood farming, agroforestry, irrigated rice farming and fishing. Wet-season livelihood systems center mostly on cereal cropping and transhumance. The major crops grown in the basin are yam, cassava, rice, groundnut, millet, sorghum, plantain, cocoa, maize, sugarcane, and cotton. Agriculture represents a large part of the gross domestic product (GDP) of the Niger River Basin with crop production alone contributing 25-35% of the basin’s GDP, while livestock and fishery contribute 10-15% and 1-4%, respectively. All countries of the Niger Basin suffer from chronic and acute poverty and are ranked ‘poor’ by most poverty indicators (Human Development Index [HDI]), child mortality, life expectancy, Social Vulnerability Index, etc.). Several structural (social and institutional) factors hold a large segment of the basin’s population in the throes of poverty. Niger Basin’s challenge is to break this vicious circle by using resources to generate sustainable growth that is favorable to the poor. Some of the prominent water-related challenges are degradation of land and water resources, climate change and variability, vulnerability to disasters, inefficiency and poor performance of agriculture (rain-fed and irrigation), competing demands between sectors and water users and inadequate investment in water infrastructure. At a wider level, inadequate public services, institutional and governance failure, high population growth and urbanization, poor macro-economic performance, and unemployment have also undermined the development of the basin. The severity of these challenges varies from location to location in the basin. The basin’s development goals and objectives originate as a response to the development challenges and are articulated in various policy documents such as the Niger Basin Shared Vision (NBA PADD), poverty reduction strategy papers, United Nations (UN) Millennium Development Goals (MDGs), and the New Partnership for Africa’s Development (NEPAD), specifically the pillars 1, 2, 3 and 4 of the Comprehensive Africa Agriculture Development Programme (CAADP). The goals of the basin countries are eradicating extreme poverty and hunger; achieving universal primary education; promoting gender equality and empowerment of women; reducing child mortality; improving maternal health; combating Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS), malaria and other diseases; ensuring environmental sustainability; and developing a global partnership for development. viii The specific development objectives of the basin countries are the following: • Increase income, generate jobs, improve living standards, and alleviate poverty, especially among the poorest section of the population while at the same time safeguarding the environment including the sustainable management of the Niger Basin water resources. • Improve access to health and education services, and increase life expectancy. • Achieve political stability, good governance and an appropriate institutional framework. • Improve the investment climate for private-sector development where infrastructure plays a decisive part. • Develop infrastructures and the productive sector to ensure better productivity of factors of production and economic growth. • Reduce food imports, boost agricultural exports through stabilization, intensification and expansion of agricultural production. To realize the basin’s development goals and objectives the following water-centered intervention clusters needed to be synergistically pursued. • Ensuring right to secure access to water for the poor. • Developing new infrastructure. • Improving access to agricultural water management innovations. • Strengthening Niger Basin’s water governance. • Upgrading rain-fed systems. • Reducing the vulnerability of poor people to climate shocks and other hazards. • Minimizing degradation of the terrestrial and aquatic ecosystems. • Diversifying livelihood strategies

Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria

Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso. Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03). MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention. ClinicalTrials.gov NCT00354380

Smallholder shallow groundwater irrigation development in the upper east region of Ghana

In sub-Saharan Africa, there is paucity of information on the potential of groundwater resources. The limited available information paints a pessimistic view about groundwater resources. Due to its perceived inadequate availability, groundwater is associated with domestic use but the potential for using it for agriculture is not well reflected in the national irrigation policies. Contrary to official pessimism, farmers do use groundwater for agriculture in many countries of sub-Saharan Africa including Ghana. This paper analyzes the current extent of use, economics, socioeconomic impacts, and constraints and opportunities of shallow groundwater irrigation based on the experiences of smallholders in the three micro-watersheds of the White Volta Basin in the Upper East Region of Ghana

A double-masked placebo-controlled trial of azithromycin to prevent child mortality in Burkina Faso, West Africa: Community Health with Azithromycin Trial (CHAT) study protocol.

BACKGROUND:Biannual, mass azithromycin distribution has previously been shown to reduce all-cause child mortality in sub-Saharan Africa. Subgroup analysis suggested that the strongest effects were in the youngest children, leading to the hypothesis that targeting younger age groups might be an effective strategy to prevent mortality. We present the methods of two randomized controlled trials designed to evaluate mass and targeted azithromycin distribution for the prevention of child mortality in Burkina Faso, West Africa. METHODS/DESIGN:The Child Health with Azithromycin Treatment (CHAT) study consists of two nested, randomized controlled trials. In the first, communities are randomized in a 1:1 fashion to biannual, mass azithromycin distribution or placebo. The primary outcome is under-5 all-cause mortality measured at the community level. In the second, children attending primary healthcare facilities during the first 5-12 weeks of life for a healthy child visit (e.g., for vaccination) are randomized in a 1:1 fashion to a single orally administered dose of azithromycin or placebo. The primary outcome is all-cause mortality measured at 6 months of age. The trial commenced enrollment in August 2019. DISCUSSION:This study is expected to provide evidence on two health systems delivery approaches (mass and targeted treatment) for azithromycin to prevent all-cause child mortality. The results will inform global and national policies related to azithromycin for the prevention of child mortality. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT03676764. Registered on 19 September 2018; prospectively registered pre results

Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial.

IntroductionBiannual mass azithromycin distribution to children aged 1-59 months has been shown to reduce all-cause mortality. Children under 28 days of age were not treated in studies evaluating mass azithromycin distribution for child mortality due to concerns related to infantile hypertrophic pyloric stenosis (IHPS). Here, we report the design of a randomised controlled trial to evaluate the efficacy and safety of administration of a single dose of oral azithromycin during the neonatal period.Methods and analysisThe Nouveaux-nés et Azithromycine: une Innovation dans le Traitement des Enfants (NAITRE) study is a double-masked randomised placebo-controlled trial designed to evaluate the efficacy of a single dose of azithromycin (20 mg/kg) for the prevention of child mortality. Newborns (n=21 712) aged 8-27 days weighing at least 2500 g are 1:1 randomised to a single, directly observed, oral dose of azithromycin or matching placebo. Participants are followed weekly for 3 weeks after treatment to screen for adverse events, including IHPS. The primary outcome is all-cause mortality at the 6-month study visit.Ethics and disseminationThis study was approved by the Institutional Review Boards at the University of California, San Francisco in San Francisco, USA (Protocol #18-25027) and the Comité National d'Ethique pour la Recherche in Ouagadougou, Burkina Faso (Protocol #2018-10-123). The findings of this trial will be presented at local, regional and international meetings and published in open access peer-reviewed journals.Trial registration numberNCT03682653; Pre-results

Strong Gametocytocidal Effect of Methylene Blue-Based Combination Therapy against Falciparum Malaria: A Randomised Controlled Trial

With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB)-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso.An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS), MB-amodiaquine (AQ), and AS-AQ (local standard of care). Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days.The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline.MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies.(ClinicalTrials.gov) NCT00354380

Uncertain pasts and risk-sensitive futures in sub-Saharan urban transformation

This chapter explores the status and the scope for transition of risk- sensitive and transformative urban development in diverse cities of sub-Saharan Africa. Sub-Saharan Africa is important because of its large proportions of urban populations with high vulnerability and growing exposure to risks. High rates of urban growth pose increasing risks as we go into the future, yet there is also opportunity to reduce risk through integrating risk management into development. However, this opportunity space is often constrained by limited capacities to plan and manage the rapid urbanisation process, particularly in informal settlements. Limited capacities to prevent processes of risk accumulation pose threats to poverty reduction and sustainable development. In this context, there is an increasingly urgent need for squarely recognising and addressing the underlying vulnerabilities of urban populations and their root causes. Transitioning towards such sustainable urban pathways will require the strengthening of capacities and accountability of city authorities and broader governance systems, both formal and informal