The investigators suggest use of doxycycline which is effect

The investigators suggest use of doxycycline, which is effective for both diseases, as a possible empirical treatment at the primary level of care. Because the consequences of an untreated true case of rickettsiosis or leptospirosis are much greater than are those of unnecessary treatment, Mayxay and colleagues suggest that treatment of many false positives is a reasonable method to minimise the number of true cases remaining untreated. Note that in real (ie, hospital) practice, when fully trained study physicians were in charge of clinical management, almost half the study patients with bacteraemia (not known at the moment of the clinical decision) were left with no effective antibiotic treatment, and so were most of those who were subsequently diagnosed with typhus or leptospirosis. Unfortunately, because of the difficulties in organisation of a proper follow-up, the outcome of a quarter of patients was unknown, and therefore the consequences of the missed treatment could not be assessed. Interestingly, in a similar study in Indonesia, no patient with leptospirosis or rickettsial fever was treated with doxycycline because of a low index of suspicion. Systematic treatment with doxycycline alone would eliminate some diseases while leaving other severe infections untreated, such as typhoid fever and other bacteraemias for which this order CGP 41251 antibiotic is ineffective. Although in Mayxay and colleagues\' study, typhoid fever and other bacteraemias were identified less frequently than other infections, this finding could be partly due to the logistical constraints (eg, sample transport to reference laboratory) acknowledged by the investigators, which could have affected the sensitivity of blood culture for and other bacteria. Use or no use of a combined therapeutic approach (doxycycline plus another antibiotic) would be dependent on both an accurate cost-effectiveness analysis and the level of care, with additional consideration that other bacterial infections, such as pneumonia, that are less likely to yield a microbiological isolation in blood, are also difficult for rural health workers to diagnose clinically (cough was common in some of the confirmed causes). Other possible bacterial causes, such as urinary infections, were not specifically targeted. Studies of causes of non-malarial febrile illness with rigorous microbiological methods and clinical assessment are urgently needed in different epidemiological contexts to provide the best available evidence to inform a clinical management that remains largely empirical. Equally, research in diagnostics should focus on accurate, point-of-care techniques, not only for malaria, but also for non-malarial febrile illness, according to local epidemiology. In addition to diagnostics, which could ideally combine the most common local causes in the same device, another line of investigation concerns possible generic biomarkers of bacterial infection or clinical severity. Mayxay and colleagues noted, for example, that C-reactive protein (CRP) concentrations of 5 mg/L or more had some predictive potential for a bacterial infection, although CRP was higher than cotyledon cutoff in 71% of the identified viral causes and therefore might not contribute much to more focused treatment.
Access to essential medicines can be a formidable challenge in the wake of natural disasters where supply chains and health services might be severely affected. The devastating floods in Pakistan in 2010 affected most of the country from north to south, displacing more than 20 million people and damaging over 500 health facilities. This immense natural disaster, covering 2·4 million hectares of land at its highest, posed a substantial challenge to the provision of health services from the first rains in July until the flood waters receded in January the following year. In response to the flood, the WHO Pakistan Health Cluster established a coordinating body in Islamabad and set up regional hubs to provide essential medicines to affected populations, engaging 69 implementing partners from various non-governmental organisations. Almost 1200 mobile and 165 static health facilities in the four affected regions were established.