A New Test of a Theory about Old Mosquitoes

In vector control, it is widely accepted that killing adult mosquitoes would sharply reduce the proportion of old mosquitoes and cause the greatest changes to malaria transmission. The principle is based on a mathematical model of the sporozoite rate (the proportion of infective mosquitoes) that emphasized changes in mosquito age. Killing adult mosquitoes also reduces mosquito population densities, which are directly proportional to human biting rates (the number of bites, per person, per day). Eect sizes of vector control can be compared using sporozoite rates and human biting rates, which are commonly measured. We argue that human biting rates convey more use- ful information for planning, monitoring and evaluating vector control, and operational research should focus on understanding mosquito ecology

Will He Be There?: Mediating malaria, immobilizing science

This paper focuses on an unsettling example of experimental labour – the Human Landing Catch (HLC). The HLC is a cheap and reliable technique to produce data on mosquito densities in a defined area. It requires only a human volunteer to sit over night with his legs exposed, a headlamp to spot mosquitoes, and a rubber tube and plastic cup to catch them as they come to feed on him. The HLC formed the central methodological and operational strategy for a malaria control that took place in Dar es Salaam, funded by the Bill and Melinda Gates Foundation. This paper analyses the epistemic and economic value of this experimental scenario by examining in detail the work it entails. In conceptualizing the different species of productivity associated with the HLC, of particular interest is the surprising fact that he is there. This paper argues that the interplay of mobility and immobility offers a way to rethink the value of research within interlocking circulations of capital, science, mosquitoes and men

Agricultural dynamics and food security trends in Tanzania

ASC – Publicaties niet-programma gebonde

Pareto rules for malaria super-spreaders and super-spreading

Heterogeneity in transmission is a challenge for infectious disease dynamics and control. An 80-20 “Pareto” rule has been proposed to describe this heterogeneity whereby 80% of transmission is accounted for by 20% of individuals, herein called super-spreaders. It is unclear, however, whether super-spreading can be attributed to certain individuals or whether it is an unpredictable and unavoidable feature of epidemics. Here, we investigate heterogeneous malaria transmission at three sites in Uganda and find that super-spreading is negatively correlated with overall malaria transmission intensity. Mosquito biting among humans is 90-10 at the lowest transmission intensities declining to less than 70-30 at the highest intensities. For super-spreaders, biting ranges from 70-30 down to 60-40. The difference, approximately half the total variance, is due to environmental stochasticity. Super-spreading is thus partly due to super-spreaders, but modest gains are expected from targeting super-spreaders

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

Impact of seasonality and malaria control interventions on Anopheles density and species composition from three areas of Uganda with differing malaria endemicity

Background: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. This study examined the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control. Methods: From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction). Results: In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18–0.65, p = 0.001), but not Anopheles gambiae sensu stricto (s.s.) nor Anopheles arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49–0.94, p = 0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002–0.009, p < 0.001), and An. funestus sensu lato (s.l.) (3.90 vs 0.006, DR 0.001, 95% CI: 0.0005–0.004, p < 0.001), with a less pronounced decline in An. arabiensis (9.18 vs 2.00, DR 0.15 95% CI: 0.07–0.33, p < 0.001). Conclusions: LLIN distribution was associated with reductions in An. funestus s.l. in the lowest transmission site and An. gambiae s.s. in the moderate transmission site. In the highest transmission site, a combination of LLINs and multiple rounds of IRS was associated with the near collapse of An. gambiae s.s. and An. funestus s.l. Following IRS, An. arabiensis, a behaviourally resilient vector, became the predominant species, which may have implications for malaria vector control activities. Development of interventions targeted at outdoor biting remains a priority

Spatial variation and socio-economic determinants of Plasmodium falciparum infection in northeastern Tanzania

<p>Abstract</p> <p>Background</p> <p>Malaria due to <it>Plasmodium falciparum </it>is the leading cause of morbidity and mortality in Tanzania. According to health statistics, malaria accounts for about 30% and 15% of hospital admissions and deaths, respectively. The risk of <it>P. falciparum </it>infection varies across the country. This study describes the spatial variation and socio-economic determinants of <it>P. falciparum </it>infection in northeastern Tanzania.</p> <p>Methods</p> <p>The study was conducted in 14 villages located in highland, lowland and urban areas of Korogwe district. Four cross-sectional malaria surveys involving individuals aged 0-19 years were conducted during short (Nov-Dec) and long (May-Jun) rainy seasons from November 2005 to June 2007. Household socio-economic status (SES) data were collected between Jan-April 2006 and household's geographical positions were collected using hand-held geographical positioning system (GPS) unit. The effects of risk factors were determined using generalized estimating equation and spatial risk of <it>P. falciparum </it>infection was modelled using a kernel (non-parametric) method.</p> <p>Results</p> <p>There was a significant spatial variation of <it>P. falciparum </it>infection, and urban areas were at lower risk. Adjusting for covariates, high risk of <it>P. falciparum </it>infection was identified in rural areas of lowland and highland. Bed net coverage levels were independently associated with reduced risk of <it>P. falciparum </it>by 19.1% (95%CI: 8.9-28.2, p < 0.001) and by 39.3% (95%CI: 28.9-48.2, p < 0.001) in households with low and high coverage, respectively, compared to those without bed nets. Households with moderate and lower SES had risk of infection higher than 60% compared to those with higher SES; while inhabitants of houses built of mud walls were at 15.5% (95%CI: 0.1 - 33.3, p < 0.048) higher risk compared to those living in houses built by bricks. Individuals in houses with thatched roof had an excess risk of 17.3% (95%CI: 4.1 - 32.2, p < 0.009) compared to those living in houses roofed with iron sheet.</p> <p>Conclusions</p> <p>There was high spatial variation of risk of <it>P. falciparum </it>infection and urban area was at the lowest risk. High bed net coverage, better SES and good housing were among the important risk factors associated with low risk of <it>P. falciparum </it>infection.</p

Health research ethics in malaria vector trials in Africa

Malaria mosquito research in Africa as elsewhere is just over a century old. Early trials for development of mosquito control tools were driven by colonial enterprises and war efforts; they were, therefore, tested in military or colonial settings. The failure of those tools and environmental concerns, coupled with the desperate need for integrated malaria control strategies, has necessitated the development of new malaria mosquito control tools, which are to be tested on humans, their environment and mosquito habitats. Ethical concerns start with phase 2 trials, which pose limited ethical dilemmas. Phase 3 trials, which are undertaken on vulnerable civilian populations, pose ethical dilemmas ranging from individual to community concerns. It is argued that such trials must abide by established ethical principles especially safety, which is mainly enshrined in the principle of non-maleficence. As there is total lack of experience with many of the promising candidate tools (eg genetically modified mosquitoes, entomopathogenic fungi, and biocontrol agents), great caution must be exercised before they are introduced in the field. Since malaria vector trials, especially phase 3 are intrusive and in large populations, individual and community respect is mandatory, and must give great priority to community engagement. It is concluded that new tools must be safe, beneficial, efficacious, effective, and acceptable to large populations in the short and long-term, and that research benefits should be equitably distributed to all who bear the brunt of the research burdens. It is further concluded that individual and institutional capacity strengthening should be provided, in order to undertake essential research, carry out scientific and ethical review, and establish competent regulatory frameworks