Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country

Abstract

Multidrug-resistant tuberculosis (MDR-TB) is a major concern in countries of the former Soviet Union. The reported risk of resistance among tuberculosis (TB) cases in the Republic of Moldova is among the highest in the world. We aimed to produce high-resolution spatial maps of MDR-TB risk and burden in this setting. We analysed national TB surveillance data collected between 2007 and 2010 in Moldova. High drug susceptibility testing coverage and detailed location data permitted identification of subregional areas of higher MDR-TB risk. We investigated whether the distribution of cases with MDR-TB risk factors could explain this observed spatial variation in MDR-TB. 3447 MDR-TB cases were notified during this period; 24% of new and 62% of previously treated patients had MDR-TB. Nationally, the estimated annual MDR-TB incidence was 54 cases per 100 000 persons and >1000 cases per 100 000 persons within penitentiaries. We identified substantial geographical variation in MDR-TB burden and hotspots of MDR-TB. Locations with a higher percentage of previously incarcerated TB cases were at greater risk of being MDR-TB hotspots. Spatial analyses revealed striking geographical heterogeneity of MDR-TB. Methods to identify locations of high MDR-TB risk and burden should allow for better resource allocation and more appropriate targeting of studies to understand local mechanisms driving resistance.

Figure 1

Map of the Republic of Moldova. Borders of the administrative regions are shown which highlight the 4 municipalities (in black) and 2 semi-autonomous regions (in grey) [note that Moldova is largely rural and the 4 municipalities shown are the main urban and highest population density areas]. The total area of the country is approximately 34,000 square kilometres.

Figure 2

Number of tuberculosis (TB) cases confirmed to have multidrug-resistant tuberculosis (MDR-TB) as a percentage of those with sufficient drug susceptibility testing to diagnose MDR-TB by age, 2007–2010. Pale grey bars indicate new TB cases, darker grey bars indicate previously treated TB cases and white bars indicate all incident TB cases. Binomial confidence intervals are shown.

Figure 3

Maps of multidrug-resistant TB (MDR-TB) in the Republic of Moldova. Number of notified MDR-TB cases as a percentage of TB cases with drug susceptibility testing (DST) sufficient to diagnose MDR-TB among (a) new TB cases and (b) previously treated TB cases. Figures (c) and (d) show spatial clustering analysis (using Local Moran’s I) of data shown in (a) and (b) respectively showing localities which are part of a statistically significant spatial cluster of high MDR-TB risk localities (red spots) or statistically significant outliers (i.e. localities with high MDR-TB next to areas of low MDR-TB risk, green spots). Maps shown in panels (a) and (b) were produced using data by locality which was spatially smoothed using inverse distance weighting (see Methods and Appendix Methods). New cases represent transmission of MDR-TB while previously treated cases include both acquired and transmitted MDR-TB infection. Areas which have a high percentage of TB cases with MDR-TB Figure 3((a) and (b)) may not necessarily have high MDR-TB incidence (Figure 4(a) and (b)) and thus (Figure 3(a) and (b)) and (Figure 4(a) and (b)) have different interpretations. Locations in all panels are based on residential location and not location of diagnosis.

Figure 4

Annual notified MDR-TB incidence per 100,000 population among (a) new TB cases and (b) previously treated TB cases and annual estimated MDR-TB incidence per 100,000 population among (c) new TB cases and (d) previously treated cases. All maps were produced using data by locality which was spatially smoothed using inverse distance weighting (see Methods and Appendix Methods). New cases represent transmission of MDR-TB while previously treated cases include both acquired and transmitted MDR-TB infection. Areas which have a high percentage of TB cases with MDR-TB (Figure 3(a) and (b)) may not necessarily have high MDR-TB incidence (Figure 3(a) and (b)) and thus (Figure 3(a) and (b)) and (Figure 4(a) and (b)) have different interpretations. Estimated incidence (Figure 4(c) and (d)) assumes that the percentages shown in (Figure 3(a) and (b)) are applicable to all TB cases (including those without positive culture and DST results). Locations in all panels are based on residential location and not location of diagnosis.