Assessing spatiotemporal patterns of multidrug-resistant and drug-sensitive tuberculosis in a South American setting.

We examined the spatiotemporal distribution of laboratory-confirmed multidrug-resistant tuberculosis (MDR TB) cases and that of other TB cases in Lima, Peru with the aim of identifying mechanisms responsible for the rise of MDR TB in an urban setting. All incident cases of TB in two districts of Lima, Peru during 2005-2007 were included. The spatiotemporal distributions of MDR cases and other TB cases were compared with Ripley's K statistic. Of 11,711 notified cases, 1187 received drug susceptibility testing and 376 were found to be MDR. Spatial aggregation of patients with confirmed MDR disease appeared similar to that of other patients in 2005 and 2006; however, in 2007, cases with confirmed MDR disease were found to be more tightly grouped. Subgroup analysis suggests the appearance of resistance may be driven by increased transmission. Interventions should aim to reduce the infectious duration for those with drug-resistant disease and improve infection control.

Bacteriologic monitoring of multidrug-resistant tuberculosis patients in five DOTS-Plus pilot projects.

BACKGROUND: Multidrug-resistant tuberculosis programs in DOTS-Plus pilot sites in five countries. OBJECTIVES: To calculate sputum conversion time and its relationship to treatment outcome, document the frequency of culture reversions and examine concordance of smear and culture to assess the potential consequences of monitoring by smear microscopy alone. DESIGN: Retrospective cohort analysis of 1926 patients receiving individualized, second-line therapy. RESULTS: Among 1385 sputum culture-positive cases at baseline, 1146 (83%) experienced at least one culture conversion during treatment. Conversion, however, was not sustained in all patients: 201 (15%) experienced initial culture conversion and at least one subsequent culture reversion to positive; 1064 (77%) achieved sustained culture conversion. Median time to culture conversion was 3 months. Among 206 patients whose nal conversion occurred 7-18 months after the initiation of therapy, 71% were cured or had completed treatment. CONCLUSIONS: Prolonged treatment for patients with delayed conversion may be beneficial, as 71% of late converters still achieved cure or completed treatment. This has implications for programs with de ned end points for treatment failure. The interval between rst and nal conversion among patients whose initial con- version is not sustained raises concern with respect to the ongoing debate regarding duration of treatment and the definition of cure.

Programmatic implementation of rapid DST for Mycobacterium tuberculosis in Peru.

BACKGROUND: Performance characteristics of novel rapid drug susceptibility tests (DST) for Mycobacterium tuberculosis may change when moving from research to implementation in actual public health practice. We describe the performance characteristics of a direct, rapid DST when implemented in Lima, Peru. METHODS: A district laboratory validated conventional proportions and nitrate reductase methods. We collected data on samples submitted for DST from January 2005 to June 2007 and calculated frequency of testing and results, and median time to test results. RESULTS: A total of 4102 DSTs were performed by conventional DST and 895 by nitrate reductase. Results were obtained from 72.8% of samples by conventional DST and from 70.2% of those processed by Griess; respectively 26.4% and 31.5% were multidrug-resistant tuberculosis. The median time from sample collection to test result was 31 days for Griess vs. 99 days for conventional DST. CONCLUSIONS: Preliminary experience with the Griess method demonstrates favorable performance under program conditions.

Timely diagnosis of MDR-TB under program conditions: is rapid drug susceptibility testing sufficient?

Timely diagnosis and effective, safe treatment are essential to reduce transmission and improve outcomes for patients with tuberculosis. Aside from laboratory methods, many programmatic factors influence the overall turnaround time (TAT) in diagnosing multidrug-resistant tuberculosis (MDR-TB). We measured each step in the overall TAT required for MDR-TB in two of five health districts of Lima, Peru. The total TAT, from initial sputum specimen to diagnosis and appropriate treatment, was 5 months, almost twice as long as the bacteriological procedures per se. Expensive investments in laboratory technology may yield low returns unless the programmatic aspects of the diagnostic process are streamlined at the same time.

Agglutination of Plasmodium falciparum-infected erythrocytes from east and west African isolates by human sera from distant geographic regions.

Plasmodium falciparum-infected erythrocytes (PfE) were collected from acutely infected children in The Gambia and Tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. Sera collected from these countries, other African countries, Asia, and South America were used in the PfE microagglutination test to determine whether PfE from East and West Africa share surface antigens. From the patterns of agglutination reactivity, we identified extensive antigenic diversity in surface antigens, but obtained no evidence for greater differences between isolates from East or West Africa and those within one region. The majority of sera from immune adults from The Gambia, Tanzania, Sudan, Nigeria, or Ghana were pan-agglutinating, and agglutinated all PfE isolates from The Gambia and Tanzania. Some sera from immune adults of Irian Jaya also agglutinated each of the seven African isolates, while others agglutinated many but not all of the isolates, similar to sera from immune adults of Flores, Indonesia. In contrast, sera from nonimmune adults from Colombia agglutinated few of the African isolates. It was remarkable, however, that sera from nonimmune Colombians agglutinated any African isolates. Our results are consistent with the following conclusions: some PfE surface antigen(s) are very diverse; this diversity is a feature of the parasite worldwide; the repertoire of isolate-specific surface antigens, although large, includes antigens that are either identical or antigenically cross-reactive in geographically very distant parasite populations; and African adults have pan-agglutinating antibodies that may contribute to protective immunity. Such pan-agglutinating antibodies could reflect the accumulation of a large repertoire of isolate-specific antibodies. The contribution of antibody against any shared PfE surface antigen to the pan-agglutinating reactivities is unknown and awaits development of the appropriate reagents.