Verbal autopsy can consistently measure AIDS mortality: a validation study in Tanzania and Zimbabwe

BACKGROUND: Verbal autopsy is currently the only option for obtaining cause of death information in most populations with a widespread HIV/AIDS epidemic. METHODS: With the use of a data-driven algorithm, a set of criteria for classifying AIDS mortality was trained. Data from two longitudinal community studies in Tanzania and Zimbabwe were used, both of which have collected information on the HIV status of the population over a prolonged period and maintained a demographic surveillance system that collects information on cause of death through verbal autopsy. The algorithm was then tested in different times (two phases of the Zimbabwe study) and different places (Tanzania and Zimbabwe). RESULTS: The trained algorithm, including nine signs and symptoms, performed consistently based on sensitivity and specificity on verbal autopsy data for deaths in 15-44-year-olds from Zimbabwe phase I (sensitivity 79%; specificity 79%), phase II (sensitivity 83%; specificity 75%) and Tanzania (sensitivity 75%; specificity 74%) studies. The sensitivity dropped markedly for classifying deaths in 45-59-year-olds. CONCLUSIONS: Verbal autopsy can consistently measure AIDS mortality with a set of nine criteria. Surveillance should focus on deaths that occur in the 15-44-year age group for which the method performs reliably. Addition of a handful of questions related to opportunistic infections would enable other widely used verbal autopsy tools to apply this validated method in areas for which HIV testing and hospital records are unavailable or incomplete

Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance

BACKGROUND: Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. METHODS: The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. RESULTS: Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. CONCLUSION: Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women). Patients with hyperparasitaemia who receive outpatient treatments provide the greatest risk of selecting de-novo resistant parasites. This emphasizes the importance of ensuring that only quality-assured anti-malarial combinations are used, that treatment doses are optimized on the basis of pharmacodynamic and pharmacokinetic assessments in the target populations, and that patients with heavy parasite burdens are identified and receive sufficient treatment to prevent recrudescence