Effect of mass dihydroartemisinin-piperaquine administration in southern Mozambique on the carriage of molecular markers of antimalarial resistance.

--- - Label: BACKGROUND NlmCategory: BACKGROUND content: Mass drug administration (MDA) can rapidly reduce the burden of Plasmodium falciparum (Pf). However, concerns remain about its contribution to select for antimalarial drug resistance. - Label: METHODS NlmCategory: METHODS content: We used Sanger sequencing and real-time PCR to determine the proportion of molecular markers associated with antimalarial resistance (k13, pfpm2, pfmdr1 and pfcrt) in Pf isolates collected before (n = 99) and after (n = 112) the implementation of two monthly MDA rounds with dihydroartemisinin-piperaquine (DHAp) for two consecutive years in Magude district of Southern Mozambique. - Label: RESULTS NlmCategory: RESULTS content: None of the k13 polymorphisms associated with artemisinin resistance were observed in the Pf isolates analyzed. The proportion of Pf isolates with multiple copies of pfpm2, an amplification associated with piperaquine resistance, was similar in pre- (4.9%) and post-MDA groups (3.4%; p = 1.000). No statistically significant differences were observed between pre- and post-MDA groups in the proportion of Pf isolates neither with mutations in pfcrt and pfmdr1 genes, nor with the carriage of pfmdr1 multiple copies (p>0.05). - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: This study does not show any evidence of increased frequency of molecular makers of antimalarial resistance after MDA with DHAp in southern Mozambique where markers of antimalarial resistance were absent or low at the beginning of the intervention

Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control.

BACKGROUND: As new combinations of interventions aiming at interrupting malaria transmission are under evaluation, understanding the associated economic costs and benefits is critical for decision-making. This study assessed the economic cost and cost-effectiveness of the Magude project, a malaria elimination initiative implemented in a district in southern Mozambique (i.e. Magude) between August 2015-June 2018. This project piloted a combination of two mass drug administration (MDA) rounds per year for two consecutive years, annual rounds of universal indoor residual spraying (IRS) and a strengthened surveillance and response system on the back of universal long-lasting insecticide treated net (LLIN) coverage and routine case management implemented by the National Malaria Control Program (NMCP). Although local transmission was not interrupted, the project achieved large reductions in the burden of malaria in the target district. METHODS: We collected weekly economic data, estimated costs from the project implementer perspective and assessed the incremental cost-effectiveness ratio (ICER) associated with the Magude project as compared to routine malaria control activities, the counterfactual. We estimated disability-adjusted life years (DALYs) for malaria cases and deaths and assessed the variation of the ICER over time to capture the marginal costs and effectiveness associated with subsequent phases of project implementation. We used deterministic and probabilistic sensitivity analyses to account for uncertainty and built an alternative scenario by assuming the implementation of the interventions from a governmental perspective. Economic costs are provided in constant US$2015. RESULTS: After three years, the Magude project averted a total of 3,171 DALYs at an incremental cost of$2.89 million and an average yearly cost of $20.7 per targeted person. At an average cost of$19.4 per person treated per MDA round, the social mobilization and distribution of door-to-door MDA contributed to 53% of overall resources employed, with personnel and logistics being the main cost drivers. The ICER improved over time as a result of decreasing costs and improved effectiveness. The overall ICER was $987 (CI95$1,404/DALY averted, three times the gross domestic product (GDP) per capita of Mozambique, but above the threshold of interventions considered highly cost-effective (one time the GDP per capita or $468/DALY averted) and above the recently suggested thresholds based on the health opportunity cost ($537 purchasing power parity/ DALY averted). A significantly lower ICER was obtained in the implementation scenario from a governmental perspective ($441/DALY averted). CONCLUSION: Despite the initial high costs and volume of resources associated with its implementation, MDA in combination with other existing malaria control interventions, can be a cost-effective strategy to drastically reduce transmission in areas of low to moderate transmission in sub-Saharan Africa. However, further studies are needed to understand the capacity of the health system and financial affordability to scale up such strategies at regional or national level

The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings

Transport and optical conductivity in the Hubbard model: A high-temperature expansion perspective

We derive analytical expressions for the spectral moments of the dynamical response functions of the Hubbard model using the high-temperature series expansion. We consider generic dimension d as well as the infinite-d limit, arbitrary electron density n, and both finite and infinite repulsion U. We use moment-reconstruction methods to obtain the one-electron spectral function, the self-energy, and the optical conductivity. They are all smooth functions at high temperature and, at large U, they are featureless with characteristic widths of the order of the lattice hopping parameter t. In the infinite-d limit, we compare the series expansion results with accurate numerical renormalization group and interaction expansion quantum Monte Carlo results. We find excellent agreement down to surprisingly low temperatures, throughout most of the bad-metal regime, which applies for T≳(1−n)D, the Brinkman-Rice scale. The resistivity increases linearly in T at high temperature without saturation. This results from the 1/T behavior of the compressibility or kinetic energy, which play the role of the effective carrier number. In contrast, the scattering time (or diffusion constant) saturates at high T. We find that σ(n,T)≈(1−n)σ(n=0,T) to a very good approximation for all n, with σ(n=0,T)∝t/T at high temperatures. The saturation at small n occurs due to a compensation between the density dependence of the effective number of carriers and that of the scattering time. The T dependence of the resistivity displays a kneelike feature which signals a crossover to the intermediate-temperature regime where the diffusion constant (or scattering time) starts increasing with decreasing T. At high temperatures, the thermopower obeys the Heikes formula, while the Wiedemann-Franz law is violated with the Lorenz number vanishing as 1/T2. The relevance of our calculations to experiments probing high-temperature transport in materials with strong electronic correlations or ultracold atomic gases in an optical lattice is briefly discussed