Journal Article > ResearchFull Text
Proc Biol Sci. 2010 September 22; Volume 277 (Issue 1695); DOI:10.1098/rspb.2010.0536
Ferrari MJ, Djibo A, Grais RF, Bharti N, Grenfell BT, et al.
Proc Biol Sci. 2010 September 22; Volume 277 (Issue 1695); DOI:10.1098/rspb.2010.0536
Seasonally driven cycles of incidence have been consistently observed for a range of directly transmitted pathogens. Though frequently observed, the mechanism of seasonality for directly transmitted human pathogens is rarely well understood. Despite significant annual variation in magnitude, measles outbreaks in Niger consistently begin in the dry season and decline at the onset of the seasonal rains. We estimate the seasonal fluctuation in measles transmission rates for the 38 districts and urban centres of Niger, from 11 years of weekly incidence reports. We show that transmission rates are consistently in anti-phase to the rainfall patterns across the country. The strength of the seasonal forcing of transmission is not correlated with the latitudinal rainfall gradient, as would be expected if transmission rates were determined purely by environmental conditions. Rather, seasonal forcing is correlated with the population size, with larger seasonal fluctuation in more populous, urban areas. This pattern is consistent with seasonal variation in human density and contact rates due to agricultural cycles. The stronger seasonality in large cities drives deep inter-epidemic troughs and results in frequent local extinction of measles, which contrasts starkly to the conventional observation that large cities, by virtue of their size, act as reservoirs of measles.
Journal Article > ResearchFull Text
Proc Biol Sci. 2005 June 2; Volume 272 (Issue 1568); 1153-1161.; DOI:10.1098/rspb.2004.3026
Nash D, Nair SA, Mayxay M, Newton PN, Guthmann JP, et al.
Proc Biol Sci. 2005 June 2; Volume 272 (Issue 1568); 1153-1161.; DOI:10.1098/rspb.2004.3026
Neutral mutations may hitchhike to high frequency when they are situated close to sites under positive selection, generating local reductions in genetic diversity. This process is thought to be an important determinant of levels of genomic variation in natural populations. The size of genome regions affected by genetic hitchhiking is expected to be dependent on the strength of selection, but there is little empirical data supporting this prediction. Here, we compare microsatellite variation around two drug resistance genes (chloroquine resistance transporter (pfcrt), chromosome 7, and dihydrofolate reductase (dhfr), chromosome 4) in malaria parasite populations exposed to strong (Thailand) or weak selection (Laos) by anti-malarial drugs. In each population, we examined the point mutations underlying resistance and length variation at 22 (chromosome 4) or 25 (chromosome 7) microsatellite markers across these chromosomes. All parasites from Thailand carried the K76T mutation in pfcrt conferring resistance to chloroquine (CQ) and 2-4 mutations in dhfr conferring resistance to pyrimethamine. By contrast, we found both wild-type and resistant alleles at both genes in Laos. There were dramatic differences in the extent of hitchhiking in the two countries. The size of genome regions affected was smaller in Laos than in Thailand. We observed significant reduction in variation relative to sensitive parasites for 34-64 kb (2-4 cM) in Laos on chromosome 4, compared with 98-137 kb (6-8 cM) in Thailand. Similarly, on chromosome 7, we observed reduced variation for 34-69 kb (2-4 cM) around pfcrt in Laos, but for 195-268 kb (11-16 cM) in Thailand. Reduction in genetic variation was also less extreme in Laos than in Thailand. Most loci were monomorphic in a 12 kb region surrounding both genes on resistant chromosomes from Thailand, whereas in Laos, even loci immediately proximal to selective sites showed some variation on resistant chromosomes. Finally, linkage disequilibrium (LD) decayed more rapidly around resistant pfcrt and dhfr alleles from Laos than from Thailand. These results demonstrate that different realizations of the same selective sweeps may vary considerably in size and shape, in a manner broadly consistent with selection history. From a practical perspective, genomic regions containing resistance genes may be most effectively located by genome-wide association in populations exposed to strong drug selection. However, the lower levels of LD surrounding resistance alleles in populations under weak selection may simplify identification of functional mutations.