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

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

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

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

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

Pneumonia in Bhutanese children: what we know, and what we need to know.

Background Pneumonia is the single largest cause of death in under-five children worldwide. We conducted a systematic review to identify the knowledge gaps around childhood pneumonia in Bhutan. Methods We searched PubMed, ScienceDirect and Google scholar from conception to 3rd December 2018, World Health Organization, UNICEF, Bhutan’s Ministry of Health and other local databases for relevant reports. We included any report describing pneumonia in Bhutanese children with regards to the burden of the disease, aetiology, related risk factors, clinical and prognostic characteristics, surveillance systems and national preventive strategies. Two review authors identified the records. We summarized the findings narratively. Results We included 44 records. Although with notable decreasing trends, pneumonia is still accountable for a high burden and mortality rate in Bhutanese children. The national surveillance system focuses mainly on influenza identification but has recently introduced other viral aetiology to monitor. We found very scarce or no data with regard to the bacterial aetiology, related risk factors and clinico-radiological and prognostic characteristics. Conclusion There is a dearth of data regarding the epidemiological, microbiological, clinical and radiological characteristics of pneumonia in children in Bhutan, leading to challenges while implementing evidence-based management and effective national preventive strategies

Global, regional, and national burden of meningitis, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

Background: Acute meningitis has a high case-fatality rate and survivors can have severe lifelong disability. We aimed to provide a comprehensive assessment of the levels and trends of global meningitis burden that could help to guide introduction, continuation, and ongoing development of vaccines and treatment programmes. Methods: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study estimated meningitis burden due to one of four types of cause: pneumococcal, meningococcal, Haemophilus influenzae type b, and a residual category of other causes. Cause-specific mortality estimates were generated via cause of death ensemble modelling of vital registration and verbal autopsy data that were subject to standardised data processing algorithms. Deaths were multiplied by the GBD standard life expectancy at age of death to estimate years of life lost, the mortality component of disability-adjusted life-years (DALYs). A systematic analysis of relevant publications and hospital and claims data was used to estimate meningitis incidence via a Bayesian meta-regression tool. Meningitis deaths and cases were split between causes with meta-regressions of aetiological proportions of mortality and incidence, respectively. Probabilities of long-term impairment by cause of meningitis were applied to survivors and used to estimate years of life lived with disability (YLDs). We assessed the relationship between burden metrics and Socio-demographic Index (SDI), a composite measure of development based on fertility, income, and education. Findings: Global meningitis deaths decreased by 21·0% from 1990 to 2016, from 403 012 (95% uncertainty interval [UI] 319 426–458 514) to 318 400 (265 218–408 705). Incident cases globally increased from 2·50 million (95% UI 2·19–2·91) in 1990 to 2·82 million (2·46–3·31) in 2016. Meningitis mortality and incidence were closely related to SDI. The highest mortality rates and incidence rates were found in the peri-Sahelian countries that comprise the African meningitis belt, with six of the ten countries with the largest number of cases and deaths being located within this region. Haemophilus influenzae type b was the most common cause of incident meningitis in 1990, at 780 070 cases (95% UI 613 585–978 219) globally, but decreased the most (–49·1%) to become the least common cause in 2016, with 397 297 cases (291 076–533 662). Meningococcus was the leading cause of meningitis mortality in 1990 (192 833 deaths [95% UI 153 358–221 503] globally), whereas other meningitis was the leading cause for both deaths (136 423 [112 682–178 022]) and incident cases (1·25 million [1·06–1·49]) in 2016. Pneumococcus caused the largest number of YLDs (634 458 [444 787–839 749]) in 2016, owing to its more severe long-term effects on survivors. Globally in 2016, 1·48 million (1·04—1·96) YLDs were due to meningitis compared with 21·87 million (18·20—28·28) DALYs, indicating that the contribution of mortality to meningitis burden is far greater than the contribution of disabling outcomes. Interpretation: Meningitis burden remains high and progress lags substantially behind that of other vaccine-preventable diseases. Particular attention should be given to developing vaccines with broader coverage against the causes of meningitis, making these vaccines affordable in the most affected countries, improving vaccine uptake, improving access to low-cost diagnostics and therapeutics, and improving support for disabled survivors. Substantial uncertainty remains around pathogenic causes and risk factors for meningitis. Ongoing, active cause-specific surveillance of meningitis is crucial to continue and to improve monitoring of meningitis burdens and trends throughout the world

Making sense of emerging evidence on the non-specific effects of the BCG vaccine on malaria risk and neonatal mortality

Vaccines are, indisputably, one of the greatest public health interventions, with a substantial positive impact on child survival. The remarkable declines in child mortality observed during the last quarter of a century, whereby global under 5 deaths were essentially halved, go hand in hand with the estimated 2–3 million child deaths prevented by vaccines annually.1 The premise for this is clear: vaccines directly prevent a variety of life-threatening diseases. Vaccines can also be held directly responsible for the eradication of smallpox, the first and only infectious disease extinguished by the action of humans and are paving the way for the disappearance of other terrible infections such as polio, measles or rubella