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  • WHO estimates that of people with tuberculosis are untreated

    2019-06-28

    WHO estimates that 30–50% of people with tuberculosis are untreated, in part because of underdiagnosis. Patients with undiagnosed (or diagnosed and untreated) tuberculosis are most likely to transmit infection, so strategies to reduce disease burden should focus on improving the pathway to care for patients. The past decade has seen welcome innovations in diagnostic technology, notably the Xpert MTB/RIF assay, which is significantly more sensitive than smear microscopy and provides rapid identification of rifampicin resistance. WHO has recently made recommendations on the use of the next-generation Xpert assay, the Xpert MTB/RIF Ultra, which has improved sensitivity. However, the pathway to care has many steps, and the systematic review and meta-analysis of sputum collection methods by Sumona Datta and colleagues, in this issue of , is a timely reminder that the diagnostic test is just one step. By examining the available evidence, Datta and colleagues show that two simple interventions increased the diagnostic performance of microbiological testing. Pooling of sputum samples collected over a Acitretin what of several hours increased the diagnostic performance of smear microscopy 1·6 times and of culture 1·7 times, compared with collection of a single timepoint or spot sample (the reference standard), while the delivery of standardised instruction before the provision of sputum samples increased the performance of smear microscopy 1·4 times compared with the standard of care. The implications of implementing these interventions require careful consideration. In 2010, WHO recommended the spot-spot algorithm, whereby patients with presumptive tuberculosis provide two, on demand, spot sputum samples on the day of presentation. The algorithm, based on a systematic review and meta-analysis of the literature, is intended to reduce loss to follow-up without compromising diagnosis. Although Datta and colleagues\' study did not address the incremental performance of collecting more than one sputum sample, pooling of sputum over a lengthy period requires additional clinic visits and is unlikely to be compatible with a spot-spot algorithm. Increased patient and health-care costs, and loss to follow up associated with these additional visits, would need to be balanced against increased diagnostic performance. Whether a pooled sample collected during the patient\'s visit to the health-care facility would show similar benefit Acitretin what remains to be shown. Similarly, important questions on sputum instruction remain. What are the current practices regarding instruction and what specific instructions would have the greatest effect? How should these instructions be presented? Written instructions in the form of a brochure probably have limited utility, particularly in areas where literacy is low. One study found a substantial increase in diagnostic performance for participants who viewed an instructional video. Implementation of a videographic intervention would allow presentation of other educational material as well. Cultural factors might require consideration: Khan and colleagues showed differences in the effectiveness of an instructional intervention depending on the sex of the participant with presumptive tuberculosis. Regardless of these considerations, an instructional intervention is an attractive strategy that would probably incur few additional costs and have minimal effect on health-care workers\' time.
    In their Article, Michael Head and colleagues provide a thorough analysis of patterns of malaria research investment in sub-Saharan Africa, which raises new questions about the appropriate distribution of this investment. They report that of 333 research awards meeting their inclusion criteria and totalling US$814·4 million, more than one third is received by three countries: Tanzania (13·2%), Uganda (12·0%), and Kenya (11·4%). Their findings show that some countries with high malaria burden, such as the Central African Republic or Sierra Leone, receive little funding for malaria research or malaria control. The same can be said for countries with high malaria mortality. The authors argue that “investment strategies should consider more equitable research and operational investments across countries to include currently neglected and susceptible populations”. Their use of the term equitable implies that there is an issue of fairness, not only one of efficacy, to be addressed in the distribution of research funding or a principle that investments in malaria research should be made where Unidirectional replication will generate the greatest return.