The Use of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium vivax Malaria

The long-standing dearth of knowledge surrounding Plasmodium vivax, the most widely distributed of the malaria species, merits urgent attention. A growing awareness of the true burden of this parasite and its potential to cause severe disease, and the identification of increasing parasite resistance in many areas of the world to chloroquine, the mainstay of vivax treatment, underscores the need to identify new and effective treatment strategies. Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line treatment for P. falciparum malaria and would offer logistic benefits in areas of co-endemicity. However, while ACTs show high and similar efficacy against the blood stages of P. vivax, neither ACTs nor chloroquine are active against vivax hypnozoites and must be complemented with a full course of primaquine to eradicate dormant vivax hypnozoites and prevent relapses. Artemether-lumefantrine (AL), the most commonly deployed ACT, has shown rapid clearance of P. vivax parasitemia and fever. The relatively short half-life of lumefantrine would appear beneficial in terms of reducing risk of resistance when compared to other ACTs. However, it has a shorter capability to suppress vivax relapses or prevent de novo infections, which generally translates into comparatively lower in vivo short-term measures of efficacy (e.g., day 28 or day 42 uncorrected cure rates). Assuming that the different artemisinin derivatives have equivalent efficacy against vivax, differences between AL and other ACTs may be restricted to the duration of plasma therapeutic levels of the partner drug, a variable of limited clinical relevance, particularly in regions with low vivax transmission rates or in cases where primaquine is added to the regimen to prevent relapses. More rigorous assessment of the use of ACTs in general, and AL in particular, for the treatment of P. vivax infections, either alone or in combination with primaquine, is merited. In the meantime, AL treatment of vivax malaria may be a pragmatic choice for areas with chloroquine-resistant P. vivax, and in co-endemic areas where AL is already used routinely against P. falciparum and parasitological differentiation is not routinely performed or only clinical diagnosis is used

The perks of prognostic biomarkers: A paradigm switch in the triage of sick febrile patients

Fever is indisputably one of the most common symptoms triggering the quest for health care provision, globally, but particularly so in low and middle-income countries (LMIC), where infectious diseases remain highly prevalent, and where fever is a well-known cause of premature mortality. The epidemiology of fever is highly variable, with a myriad of different potential etiologies, and heavily dependent on a variety of parameters, including among others, the age of the individual affected, the presence of concomitant conditions, the geographical distribution and circulation of different pathogens, and the implementation of different control measures destined to decrease the risk of certain diseases

Estimating the hidden magnitude of the malaria community burden

The second push for global malaria eradication, launched more than a decade ago,1 has motivated a renewed interest in the understanding of malaria transmission, and in the strategies required to interrupt it. In this respect, in order to eliminate malaria from a given geographical area, rapid detection and treatment of the clinical cases is rarely sufficient. In settings where transmission intensity is sufficiently high, populations exposed to continuous infective mosquito bites progressively develop a tolerance to malaria infections during the first few years of their life. This tolerance protects them against malaria disease, but not necessarily against the infection itself

Malaria, immunity and mental disorders: A plausible relationship?

Malaria is the most common and dangerous parasitic disease, being responsible every year for nearly half a million deaths, and an estimated 219 million clinical cases, globally [1]. The devastating short-term effects that an acute malarial infection can have on any given individual have been historically well characterized, and there are also abundant data on the subacute and chronic sequelae derived from severe malarial episodes, which are understandable in the context of the sudden and profound insult that such an aggressive infection may have in the central nervous system and other key organs

La desesperante rutina de la malaria en África Subsahariana

La malaria ha estado con nosotros desde tiempos inmemoriales, siendo históricamente, una de las principales causas de enfermedad y muerte a nivel global. A pesar de que su transmisión está actualmente circunscrita a zonas endémicas situadas entre ambos trópicos -siendo esta la causa de que erróneamente se la considere una enfermedad “tropical”-la malaria llegó a afectar a la práctica totalidad del planeta. Hoy en día, los clínicos que trabajan en zonas no endémicas suelen desconocer esta enfermedad, y rara vez la incluyen en el diagnóstico diferencial del síndrome febril. Sin embargo, en zonas endémicas, la malaria se mantiene como una de las enfermedades más habituales y temidas. En este breve artículose describe mi experiencia personal como pediatra e investigador trabajando con esta enfermedad, en un hospital distrital del sur de Mozambique.Malaria has been with us since ancient times, historically being one of the leading causes of illness and death globally. Despite the fact that its transmission is currently limited to endemic areas located between the two tropics -this being the reason why it is mistakenly considered a "tropical" disease -malaria has historically affected the vast majority of theplanet. Today, clinicians working in non-endemic areas are often unaware of this disease, and rarely include it in the differential diagnosis of patients with fever. However, in endemic areas, malaria remains one of the most common and feared diseases. This short article describes my personal experience as a pediatrician and researcher working with this disease in a district hospital in southern Mozambique

Reappraising the cardiosafety of dihydroartemisinin-piperaquine

The arsenal of efficacious drugs for the treatment of malaria remains small and is clearly insufficient to tackle the global burden of malaria, with more than 216 million clinical episodes and nearly half a million deaths annually.1 Among the new antimalarials that have been developed in the past decade, the artemisinin-based combination dihydroartemisinin–piperaquine is one of the most promising, on account of its good efficacy and tolerability, simplified dose schedule (ie, once daily for 3 days), and long post-treatment prophylactic effect.2 The only brand of dihydroartemisinin–piperaquine that has been registered under stringent regulatory authority is Eurartesim (licensed by the European Medicines Agency [EMA] in 2011), although at least three other brands exist: Duo-cotecxin (also prequalified by WHO), D-ARTEPP, and Arterakine. Dihydroartemisinin–piperaquine is not only used as a treatment of uncomplicated malaria but also has been proposed as an alternative to sulphadoxine–pyrimethamine for intermittent preventive treatment of malaria during pregnancy,3 or as a suitable drug for the mass treatment of entire populations as part of malaria-elimination endeavours

"Resistance" to diagnostics: A serious biological challenge for malaria control and elimination

Delay in diagnosis and treatment is the leading cause of death in malaria patients. The recommendation issued in 2010 by the World Health Organization (WHO) to reserve malaria treatment to parasitologically confirmed malaria infections has boosted the use of malaria rapid diagnostic tests (RDTs), which have now become a critical component of management and surveillance of malaria. Indeed, it has been estimated that over 280 million RDTs are now used annually, at a cost of hundreds of millions of euros [1]. Beyond their use as a diagnostic tool for patients with suspected malaria, the detection of Plasmodium antigens in blood samples is also used in in vitro tests of sensitivity to antimalarial drugs, as a marker of clinical severity and to verify the elimination of the parasite after treatment, although the decay of parasite antigens may take longer than the clearance of parasitaemia.2 p

Widening the options for recurrent malaria.

The global need for new antimalarial drugs and new combinations is enormous and urgent,1, 2 but their successful delivery needs resilience to overcome the barriers imposed by expensive and lengthy clinical development plans. Attention is often directed to areas such as southeast Asia, where some antimalarial combinations are failing but transmission intensities are much lower than in sub-Saharan African countries. Children in Africa have frequent and life-threatening malaria infections as they grow up, and these need to be treated safely

Primaquine for all: is it time to simplify malaria treatment in co-endemic areas?

In most areas endemic for malaria, the major species are Plasmodium falciparum and Plasmodium vivax. Falciparum malaria is more often lethal, develops resistance to drugs easily, and is responsible for most of the malaria burden in Africa. However, particularly in this second era of malaria elimination efforts,1 P vivax requires increasing attention2 because of the intrinsic challenges related to its control. This species can lead to severe or even life-threatening disease,3 can present variable evidence of resistance to chloroquine in relation to geographical area,4 and has few drug options to prevent relapse. Prevention of relapse is essential because up to 80% of reported cases of P vivax malaria could result from hypnozoite-derived relapses, rather than from newly acquired infections.5 The triggers of relapse are not sufficiently understood, but 8-aminoquinolines (such as primaquine, or the newly registered tafenoquine) are the only effective drugs enabling radical cure

Mortality, morbidity, and hospitalisations due to influenza lower respiratory tract infections, 2017: an analysis for the Global Burden of Disease Study 2017

Background: Although the burden of influenza is often discussed in the context of historical pandemics and the threat of future pandemics, every year a substantial burden of lower respiratory tract infections (LRTIs) and other respiratory conditions (like chronic obstructive pulmonary disease) are attributable to seasonal influenza. The Global Burden of Disease Study (GBD) 2017 is a systematic scientific effort to quantify the health loss associated with a comprehensive set of diseases and disabilities. In this Article, we focus on LRTIs that can be attributed to influenza. Methods: We modelled the LRTI incidence, hospitalisations, and mortality attributable to influenza for every country and selected subnational locations by age and year from 1990 to 2017 as part of GBD 2017. We used a counterfactual approach that first estimated the LRTI incidence, hospitalisations, and mortality and then attributed a fraction of those outcomes to influenza. Findings: Influenza LRTI was responsible for an estimated 145 000 (95% uncertainty interval [UI] 99 000–200 000) deaths among all ages in 2017. The influenza LRTI mortality rate was highest among adults older than 70 years (16·4 deaths per 100 000 [95% UI 11·6–21·9]), and the highest rate among all ages was in eastern Europe (5·2 per 100 000 population [95% UI 3·5–7·2]). We estimated that influenza LRTIs accounted for 9 459 000 (95% UI 3 709 000–22 935 000) hospitalisations due to LRTIs and 81 536 000 hospital days (24 330 000–259 851 000). We estimated that 11·5% (95% UI 10·0–12·9) of LRTI episodes were attributable to influenza, corresponding to 54 481 000 (38 465 000–73 864 000) episodes and 8 172 000 severe episodes (5 000 000–13 296 000). Interpretation: This comprehensive assessment of the burden of influenza LRTIs shows the substantial annual effect of influenza on global health. Although preparedness planning will be important for potential pandemics, health loss due to seasonal influenza LRTIs should not be overlooked, and vaccine use should be considered. Efforts to improve influenza prevention measures are needed