Investigation of outbreaks complicated by universal exposure

Contains fulltext : 108433.pdf (publisher's version ) (Open Access)Outbreaks in which most or all persons were exposed to the same suspected source of infection, so-called universal exposure, are common. They represent a challenge for public health specialists because conducting analytical studies in such investigations is complicated by the absence of a nonexposed group. We describe different strategies that can support investigations of outbreaks with universal exposure. The value of descriptive epidemiology, extensive environmental investigation, and the hypothesis-generation phase cannot be overemphasized. An exposure that seems universal may in fact not be universal when additional aspects of the exposure are taken into account. Each exposure has unique characteristics that may not be captured when investigators rely on the tools readily at hand, such as standard questionnaires. We therefore encourage field epidemiologists to be creative and consider the use of alternative data sources or original techniques in their investigations of outbreaks with universal exposure

The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data.

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Mechanisms of Plasmodium-Enhanced Attraction of Mosquito Vectors

Item does not contain fulltextEvidence is accumulating that Plasmodium-infected vertebrates are more attractive to mosquitoes than noninfected hosts, particularly when high levels of gametocytes are present. Changes in host odour have been suggested as a likely target for parasite manipulation because olfactory cues are crucial to mosquitoes in search of a bloodmeal host. This review discusses two routes that may lead to such changes: (i) direct emission of volatile products from malaria parasites, and (ii) changes in skin microbial composition that could lead to changes in the vertebrate odour profile. Here we synthesize what is known and suggest how further research can increase our understanding of the mechanisms of parasite manipulation of host attractiveness

Duration of the mosquitocidal effect of ivermectin.

Contains fulltext : 110981.pdf (publisher's version ) (Open Access

Filter paper collection of Plasmodium falciparum mRNA for detecting low-density gametocytes

Contains fulltext : 107918.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Accurate sampling of sub-microscopic gametocytes is necessary for epidemiological studies to identify the infectious reservoir of Plasmodium falciparum. Detection of gametocyte mRNA achieves sensitive detection, but requires careful handling of samples. Filter papers can be used for collecting RNA samples, but rigorous testing of their capacity to withstand adverse storage conditions has not been fully explored. METHODS: Three gametocyte dilutions: 10/muL, 1.0/muL and 0.1/muL were spotted onto Whatman 903 Protein Saver Cards, FTA Classic Cards and 3MM filter papers that were stored under frozen, cold chain or tropical conditions for up to 13 weeks . RNA was extracted, then detected by quantitative nucleic acid sequence-based amplification (QT-NASBA) and reverse-transcriptase PCR (RT-PCR). RESULTS: Successful gametocyte detection was more frequently observed from the Whatman 903 Protein Saver Card compared to the Whatman FTA Classic Card, by both techniques (p < 0.0001). When papers were stored at higher temperatures, a loss in sensitivity was experienced for the FTA Classic Card but not the 903 Protein Saver Card or Whatman 3MM filter paper. The sensitivity of gametocyte detection was decreased when papers were stored at high humidity. CONCLUSIONS: This study indicates the Whatman 903 Protein Saver Card is better for Pfs25 mRNA sampling compared to the Whatman FTA Classic Card, and that the Whatman 3MM filter paper may prove to be a satisfactory cheaper option for Pfs25 mRNA sampling. When appropriately dried, filter papers provide a useful approach to Pfs25 mRNA sampling, especially in settings where storage in RNA-protecting buffer is not possible

Modelling mosquito infection at natural parasite densities identifies drugs targeting EF2, PI4K or ATP4 as key candidates for interrupting malaria transmission

Eradication of malaria requires a novel type of drug that blocks transmission from the human to the mosquito host, but selection of such a drug is hampered by a lack of translational models. Experimental mosquito infections yield infection intensities that are substantially higher than observed in natural infections and, as a consequence, underestimate the drug effect on the proportion of mosquitoes that become infected. Here we introduce a novel experimental and computational method to adequately describe drug efficacy at natural parasite densities. Parameters of a beta-binomial infection model were established and validated using a large number of experimental mosquito infections at different parasite densities. Analyses of 15 experimental and marketed drugs revealed a class-specific ability to block parasite transmission. Our results highlight the parasite's elongation factor EF2, PI4 kinase and the ATP4 sodium channel as key targets for interruption of transmission, and compounds DDD107498 and KAE609 as most advanced drug candidates

Submicroscopic Plasmodium falciparum gametocyte densities frequently result in mosquito infection.

Item does not contain fulltextSubmicroscopic Plasmodium falciparum gametocytemia (<5,000 gametocytes/mL) is common and may result in mosquito infection. We assessed the relation between gametocyte density and mosquito infection under experimental and field conditions using real-time quantitative nucleic acid sequence-based amplification (QT-NASBA) for gametocyte quantification. Serial dilutions of NF54 P. falciparum gametocytes showed a positive association between gametocyte density and the proportion of infected mosquitoes (beta=6.1; 95% confidence interval [CI], 2.7-9.6; P=0.001). Successful infection became unlikely below an estimated density of 250-300 gametocytes/mL. In the field, blood samples of 100 naturally infected children showed a positive association between gametocyte density and oocyst counts in mosquitoes (beta=0.38; 95% CI, 0.14-0.61; P=0.002). The relative contribution to malaria transmission was similar for carriers with submicroscopic and microscopic gametocytemia. Our results show that transmission occurs efficiently at submicroscopic gametocyte densities and that carriers harboring submicroscopic gametocytemia constitute a considerable proportion of the human infectious reservoir

malERA: An updated research agenda for characterising the reservoir and measuring transmission in malaria elimination and eradication

Contains fulltext : 181686.pdf (publisher's version ) (Open Access

Increased Plasmodium falciparum gametocyte production in mixed infections with P. malariae.

Item does not contain fulltextPlasmodium falciparum and P. malariae occur endemically in many parts of Africa. Observations from malariotherapy patients suggest that co-infection with P. malariae may increase P. falciparum gametocyte production. We determined P. falciparum gametocyte prevalence and density by quantitative nucleic acid sequence-based amplification (QT-NASBA) after antimalarial treatment of Kenyan children with either P. falciparum mono-infection or P. falciparum and P. malariae mixed infection. In addition, we analyzed the relationship between mixed species infections and microscopic P. falciparum gametocyte prevalence in three datasets from previously published studies. In Kenyan children, QT-NASBA gametocyte density was increased in mixed species infections (P = 0.03). We also observed higher microscopic prevalences of P. falciparum gametocytes in mixed species infections in studies from Tanzania and Kenya (odds ratio = 2.15, 95% confidence interval = 0.99-4.65 and 2.39, 1.58-3.63) but not in a study from Nigeria. These data suggest that co-infection with P. malariae is correlated with increased P. falciparum gametocytemia

Practical Implications of a Relationship between Health Management Information System and Community Cohort-Based Malaria Incidence Rates

Contains fulltext : 226128.pdf (Publisher’s version ) (Open Access