Finding out about the most important papers in a field gives us an idea about the subjects or research areas that are deemed to be important by the research community. The PageRank algorithm is an algorithm used to determine the influence of a node over a network (see this link). Using this algorithm, the top 12 articles of the field of MDR-TB was compiled. As older articles tend to gather more citations and hence more links in the network, this list could also be considered as a snapshot of the important articles that shaped the whole field of MDR-TB historically.

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Below is the list of the top articles and a brief description of what they are about. Note that the reports by WHO and CDC are general reports and hence no description is given.

  1. Gandhi NR 2006 Lancet. This is one of the earliest papers that described XDR-TB as a cause of death in patients with TB and HIV.
  2. Mitnick C 2003 New Engl J Med. A key paper that described the first community-based treatment of MDR-TB (see below).
  3. Laserson KF 2005, Int J Tuberc Lung D. This paper discussed treatment outcome definitions for MDR-TB, thus enabling the community to standardize the language used in research in the field.
  4. Orenstein EW 2009 Lancet Infect Dis. This article was a systematic review on treatment outcomes for patients treated with MDR-TB.
  5. Espinal MA 2000 JAMA-J Am Med Assoc. The inadequacy of standard TB therapy in multi-drug resistant cases was demonstrated in a large study.
  6. Leimane V, 2005, Lancet, V365, P318. This paper described the use of DOTS-PLUS strategy to counter MDR-TB in a highly affected country Latvia. DOTS-PLUS at the time was not yet rolled out across the world so this was one of the early demonstrations of its effectiveness.
  7. Kamerbeek J, 1997, J Clin Microbiol, V35, P907 is a key paper that described for the first time the technique of spoligotyping that allows for the determination of strain evolution.
  8. Johnston JC 2009 Plos One is an early article that attempted to measure treatment outcomes and risk factors for MDR-TB.
  9. WHO, 2012, Global Tuberculosis Report 2012, P1
  10. Center For Disease Control And Prevention (CDC), 2006, Mmwr-Morbid Mortal W, V55, P301
  11. Goble M 1993 New Engl J Med is a key paper that very early on described the treatment of patients with resistance to isoniazid and rifampicin.
  12. Ramaswamy S 1998 Tubercle And Lung Disease is an important paper that summarizes the molecular genetic basis of antimicrobial resistance in tb, paving the way for diagnostics and drug development.

One paper in this list, specifically that of Mitnick et al., also scored the highest in the network on another algorithm based on betweenness centrality. This means that this article exerts considerable influence over the flow of information in this network. In other words, in the case of this citation network, it links divergent parts of the network.

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Why is this paper so influential and who is C Mitnick?

The story of community-based treatment of MDR-TB

A closer look at a co-authorship network for MDR-TB reveals that this author is clustered within a community that is closely knit.

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If we zoom in, we can see more clearly the connections the author has within the community.

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Looking at the map view, we see that the community C Mitnick belongs to is mostly based on the east coast of the US (yellow circle). The map view also allows us to geographically view an author’s co-authorship network visually. We can see that there is a strong link with a latin American country, which can be zoomed in and identified as Peru.

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Of course, there are many ways to ascertain who is C Mitnick, based on the affiliation in the article as well as a quick Google search. These tools are however useful to give a visual representation of an author’s network that provides additional information about the author that cannot be deciphered easily otherwise.

More detail analysis shows that Carole Mitnick is a faculty at Harvard Medical School, hence the clustering together with many other authors based at Harvard such as MC Becerra, S Keshavjee and P Farmer. In 2003, Dr. Mitnick together with colleagues, led by principal investigator Dr. Paul Farmer published a seminal paper in the field of MDR-TB. This study described a ‘DOTS-Plus’ programme to treat seventy-five patients in Peru with long-standing disease due to drug-resistance. The difference to the standard DOTS programme that was implemented worldwide at the time were the addition of second-line medications, sputum culture monitoring, drug-susceptibility testing and directly observed therapy which was carried out once per day by a community health worker at the patient’s home. The results demonstrated that by moving treatment into the community, the organization (Socios En Salud/Partners in Health) was able to cut costs and reduced the hospital transmission of MDR-TB while obtaining a cure rate of 83 percent, which was as high as that seen previously in hospital settings.

This article was therefore instrumental in catalysing a change of policy regarding worldwide MDR-TB treatment by challenging the notion predominant at the time that treating MDR-TB was not cost-effective.