Abstract.We are using controlled human malaria infection (CHMI) by direct venous inoculation (DVI) of cryopreserved, infectious Plasmodium falciparum (Pf) sporozoites (SPZ) (PfSPZ Challenge) to try to reduce time and costs of developing PfSPZ Vaccine to prevent malaria in Africa. Immunization with five doses at 0, 4, 8, 12, and 20 weeks of 2.7 × 105 PfSPZ of PfSPZ Vaccine gave 65% vaccine efficacy (VE) at 24 weeks against mosquito bite CHMI in U.S. adults and 52% (time to event) or 29% (proportional) VE over 24 weeks against naturally transmitted Pf in Malian adults. We assessed the identical regimen in Tanzanians for VE against PfSPZ Challenge. Twenty- to thirty-year-old men were randomized to receive five doses normal saline or PfSPZ Vaccine in a double-blind trial. Vaccine efficacy was assessed 3 and 24 weeks later. Adverse events were similar in vaccinees and controls. Antibody responses to Pf circumsporozoite protein were significantly lower than in malaria-naïve Americans, but significantly higher than in Malians. All 18 controls developed Pf parasitemia after CHMI. Four of 20 (20%) vaccinees remained uninfected after 3 week CHMI (P = 0.015 by time to event, P = 0.543 by proportional analysis) and all four (100%) were uninfected after repeat 24 week CHMI (P = 0.005 by proportional, P = 0.004 by time to event analysis). Plasmodium falciparum SPZ Vaccine was safe, well tolerated, and induced durable VE in four subjects. Controlled human malaria infection by DVI of PfSPZ Challenge appeared more stringent over 24 weeks than mosquito bite CHMI in United States or natural exposure in Malian adults, thereby providing a rigorous test of VE in Africa.
Sensitive diagnostic tools are crucial for an accurate assessment of helminth infections in low-endemicity areas. We examined stool samples from Tanzanian individuals and compared the diagnostic accuracy of a real-time polymerase chain reaction (PCR) with the FLOTAC technique and the Kato–Katz method for hookworm and the Baermann method for Strongyloides stercoralis detection. Only FLOTAC had a higher sensitivity than the Kato–Katz method for hookworm diagnosis; the sensitivities of PCR and the Kato–Katz method were equal. PCR had a very low sensitivity for S. stercoralis detection. The cycle threshold values of the PCR were negatively correlated with the logarithm of hookworm egg and S. stercoralis larvae counts. The median larvae count was significantly lower in PCR false negatives than true positives. All methods failed to detect very low-intensity infections. New diagnostic approaches are needed for monitoring of progressing helminth control programs, confirmation of elimination, or surveillance of disease recrudescence.
High‐resolution pollen, macrofossil and charcoal data, combined with accelerator mass spectrometry 14C dating and multivariate analysis, were used to reconstruct Holocene vegetation and fire dynamics at Urio Quattrocchi, a small lake in the supra‐mediterranean belt in the Nebrodi Mountains of Sicily (Italy). The data suggest that after 10 000 cal a BP increasing moisture availability supported closed forests with deciduous (Quercus cerris, Fagus sylvatica and Fraxinus spp.) and evergreen (Quercus ilex) species. Species‐rich closed forest persisted until 6850 cal a BP, when Neolithic activities caused a forest decline and affected plant diversity. Secondary forest with abundant Ilex aquifolium recovered between 6650 and 6000 cal a BP, indicating moist conditions. From 5000 cal a BP, agriculture and pastoralism led to the currently fragmented landscape with sparse deciduous forests (Quercus cerris). The study suggests that evergreen broadleaved species were more important at elevations above 1000 m a.s.l. before ca. 5000 cal a BP than subsequently, which might reflect less human impact or warmer‐than‐today climatic conditions between 10 000 and 5000 cal a BP. Despite land use since Neolithic times, deciduous supra‐mediterranean forests were never completely displaced from the Nebrodi Mountains, because of favourable moist conditions that persisted throughout the Holocene. Reconstructed vegetation dynamics document the absence of any pronounced mid‐ or late‐Holocene ‘aridification’ trend at the site, an issue which is controversially debated in Italy and the Mediterranean region. Copyright © 2012 John Wiley & Sons, Ltd.
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