Improving the cascade of global tuberculosis care: moving from the "what" to the "how" of quality improvement.

Tuberculosis is preventable, treatable, and curable, yet it has the highest mortality rate of infectious diseases worldwide. Over the past decade, services to prevent, screen, diagnose, and treat tuberculosis have been developed and scaled up globally, but progress to end the disease as a public health threat has been slow, particularly in low-income and middle-income countries. In these settings, low-quality tuberculosis prevention, diagnostic, and treatment services frustrate efforts to translate use of existing tools, approaches, and treatment regimens into improved individual and public health outcomes. Increasingly sophisticated methods have been used to identify gaps in quality of tuberculosis care, but inadequate work has been done to apply these findings to activities that generate population-level improvements. In this Personal View, we contend that shifting the focus from the "what" to the "how" of quality improvement will require National Tuberculosis Programmes to change the way they organise, use data, implement, and respond to the needs and preferences of people with tuberculosis and at-risk communities.

Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp.

Genotyping frequently is used to distinguish recrudescent from new infections in antimalarial drug efficacy trials, but methodology and interpretation of results have not been standardized. We compared the utility of polymorphisms within 3 Plasmodium falciparum genes during a longitudinal trial in Kampala, Uganda. Merozoite surface protein-1 (msp-1) and merozoite surface protein-2 (msp-2) revealed greater diversity than glutamate-rich protein. Genotypes based on msp-1, msp-2, and all 3 genes combined were compared for 394 initial and subsequent isolates. Classification of most episodes as due to recrudescence or reinfection was straightforward. In 24% (msp-1), 16% (msp-2), and 62% (3 genes combined) of samples, subsequent episodes contained identical and new alleles, however. Our analysis suggested that such episodes should be classified as reinfections and not recrudescence. Comparing the 3 studied genes, msp-2 results were most accurate, and analysis of this single gene effectively distinguished recrudescence from reinfection in our study population.

Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial.

BACKGROUND: New antimalarial treatments are urgently needed in sub-Saharan Africa. Improved therapies should decrease failure rates in the short term, but their effect on incidence of subsequent episodes of malaria is little studied. We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala, Uganda. METHODS: We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate. Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up. Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the total number of treatments for malaria per time at risk. Analyses were done per protocol. FINDINGS: 183 (61%) of 316 participants were diagnosed with at least one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs; all regimens were safe and well tolerated. Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215, 18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups. Overall, sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/ pyrimethamine alone and by 37% (12-54, p=0.007) compared with sulfadoxine/pyrimethamine plus artesunate. INTERPRETATION: Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria.