The epidemiology of kuru: monitoring the epidemic from its peak to its end

Kuru is a fatal transmissible spongiform encephalopathy restricted to the Fore people and their neighbours in a remote region of the Eastern Highlands of Papua New Guinea. When first investigated in 1957 it was found to be present in epidemic proportions, with approximately 1000 deaths in the first 5 years, 1957–1961. The changing epidemiological patterns and other significant findings such as the transmissibility of kuru are described in their historical progression. Monitoring the progress of the epidemic has been carried out by epidemiological surveillance in the field for 50 years. From its peak, the number of deaths from kuru declined to 2 in the last 5 years, indicating that the epidemic is approaching its end. The mode of transmission of the prion agent of kuru was the local mortuary practice of transumption. The prohibition of this practice in the 1950s led to the decline in the epidemic, which has been prolonged into the present century by incubation periods that may exceed 50 years. Currently, the epidemiological surveillance is being maintained and further studies on human genetics and the past mortuary practices are being conducted in the kuru-affected region and in communities beyond it

A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea

Kuru is so far the principal human epidemic prion disease. While its incidence has steadily declined since the cessation of its route of transmission, endocannibalism, in Papua New Guinea in the 1950s, the arrival of variant Creutzfeldt–Jakob disease (vCJD), also thought to be transmitted by dietary prion exposure, has given kuru a new global relevance. We investigated all suspected cases of kuru from July 1996 to June 2004 and identified 11 kuru patients. There were four females and seven males, with an age range of 46–63 years at the onset of disease, in marked contrast to the age and sex distribution when kuru was first investigated 50 years ago. We obtained detailed histories of residence and exposure to mortuary feasts and performed serial neurological examination and genetic studies where possible. All patients were born a significant period before the mortuary practice of transumption ceased and their estimated incubation periods in some cases exceeded 50 years. The principal clinical features of kuru in the studied patients showed the same progressive cerebellar syndrome that had been previously described. Two patients showed marked cognitive impairment well before preterminal stages, in contrast to earlier clinical descriptions. In these patients, the mean clinical duration of 17 months was longer than the overall average in kuru but similar to that previously reported for the same age group, and this may relate to the effects of both patient age and PRNP codon 129 genotype. Importantly, no evidence for lymphoreticular colonization with prions, seen uniformly in vCJD, was observed in a patient with kuru at tonsil biopsy

On the determination of characteristics of the interior ocean dynamics from radar signatures of oceanic internal solitary waves

In this paper we discuss two different methods of inferring characteristics of the interior ocean dynamics from radar signatures of internal solitary waves visible on synthetic aperture radar (SAR) images. The first one consists in the recognition and the interpretation of sea surface patterns of internal solitary waves; the second one consists in the analysis of the modulation depth of the normalized radar backscattering cross section (NRCS) associated with internal solitary waves. For this purpose we consider a data set composed of SAR and in situ measurements carried out from 1991 to 1997 in the region of the Strait of Messina. The recognition and the interpretation of sea surface patterns of internal solitary waves in the Strait of Messina can be used to study characteristics of the density distribution in the area: The internal wave field varies with seasonal variations in the vertical density stratification and with remotely induced variations, i.e., variations induced by the larger-scale circulation, in the horizontal density distribution. In order to inquire into the possibility of inferring parameters of the interior ocean dynamics by analyzing the modulation of the NRCS associated with internal solitary waves, several numerical simulations are carried out using a radar imaging model. These simulations are performed by assuming different wind conditions and internal wave parameters. It is shown that an accurate knowledge of wind conditions is crucial for deriving internal wave parameters and hence parameters of the interior ocean dynamics from the modulation of measured NRCS associated with internal solitary waves

Visible Light Mediated Aryl Migration by Homolytic C−N Cleavage of Aryl Amines

The photocatalytic preparation of aminoalkylated heteroarenes from haloalkylamides via a 1,4‐aryl migration from nitrogen to carbon, conceptually analogous to a radical Smiles rearrangement, is reported. This method enables the substitution of amino groups in heteroaromatic compounds with aminoalkyl motifs under mild, iridium(III)‐mediated photoredox conditions. It provides rapid access to thienoazepinone, a pharmacophore present in multiple drug candidates for potential treatment of different conditions, including inflammation and psychotic disorders.Aminoalkylated heteroarenes are synthesized by a radical Smiles rearrangement of haloalkylamides through a key C−N cleavage under mild, iridium(III)‐mediated photoredox conditions. The method provides rapid access to the pharmaceutically relevant thienoazepinone scaffold.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/1/anie201806659_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/2/anie201806659.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/3/anie201806659-sup-0001-misc_information.pd

Area effects of bednet use in a malaria-endemic area in Papua New Guinea

Relationships between area coverage with insecticide-free bednets and prevalence of Plasmodium falciparum were investigated in 7 community-based surveys over a 33-month period in 1990-1993 in 6 villages in the Wosera area of Papua New Guinea. Spatial patterns in circumsporozoite rates for P. Falciparum, P. vivax isomorphs K210 and K247, and P. malariae, and the proportions of mosquito blood meals positive for specific human, goat, cat, dog and pig antigens were determined using ELISAs. P. falciparum prevalence in humans was better explained by bednet coverage in the immediate vicinity than by personal protection alone. Circumsporozoite rates for both P. falciparum and P. vivax were also inversely related to coverage with bednets. There was some increase in zoophagy in areas with high coverage, but relatively little effect on the human blood index or on overall mosquito densities. In this setting, protracted use of untreated bednets apparently reduces sporozoite rates, and the associated effects on prevalence are greater than can be accounted for by personal protection. Even at high bednet coverage most anophelines feed on human hosts, so the decreased sporozoite rates are likely to be largely due to reduction of mosquito survival. This finding highlights the importance of local vector ecology for outcomes of bednet programmes and suggests that area effects of untreated bednets should be reassessed in other setting

Genetic susceptibility, evolution and the kuru epidemic

The acquired prion disease kuru was restricted to the Fore and neighbouring linguistic groups of the Papua New Guinea highlands and largely affected children and adult women. Oral history documents the onset of the epidemic in the early twentieth century, followed by a peak in the mid-twentieth century and subsequently a well-documented decline in frequency. In the context of these strong associations (gender, region and time), we have considered the genetic factors associated with susceptibility and resistance to kuru. Heterozygosity at codon 129 of the human prion protein gene (PRNP) is known to confer relative resistance to both sporadic and acquired prion diseases. In kuru, heterozygosity is associated with older patients and longer incubation times. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are predominantly PRNP codon 129 heterozygotes and this group show marked Hardy–Weinberg disequilibrium. The deviation from Hardy–Weinberg equilibrium is most marked in elderly women, but is also significant in a slightly younger cohort of men, consistent with their exposure to kuru as boys. Young Fore and the elderly from populations with no history of kuru show Hardy–Weinberg equilibrium. An increasing cline in 129V allele frequency centres on the kuru region, consistent with the effect of selection in elevating the frequency of resistant genotypes in the exposed population. The genetic data are thus strikingly correlated with exposure. Considering the strong coding sequence conservation of primate prion protein genes, the number of global coding polymorphisms in man is surprising. By intronic resequencing in a European population, we have shown that haplotype diversity at PRNP comprises two major and divergent clades associated with 129M and 129V. Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history

Spatial and Temporal Variation in Abundance of Anopheles (Diptera: Culicidae) in a Malaria Endemic Area in Papua New Guinea

Abundance of anophelines in 10 villages in the Wosera area of Papua New Guinea was monitored during 1990-1993. Of 85,197 anophelines collected in 1,276 paired indoor and outdoor landing catches, 40.4% were Anopheles koliensis Owen, 36.7% An. punctulatus Donitz, 14.3% Art. karwari (James), 4.9% An. farauti s.l. Laveran, 3.1% An. longirostris Brug, and 0.7% An. bancroftii Giles. Maps of average indoor biting rates were produced using a Bayesian conditional autoregressive model which allowed for heterogeneities in sampling effort over time and space. Differences in spatial distributions among species were observed among and within villages and were related to the distribution of larval habitats and vegetation. Abundance of An. punctulatus and An. koliensis decreased with distance from the main waterway and probably from a sago swamp forest at 6 villages in North Wosera. Abundance of An. punctulatus was associated negatively with those of An. farauti s.l., An. longirostris, and An. bancroftii. The latter 3 species also had relatively low ratios of indoor-to-outdoor biting rates, and earlier biting times than An. punctulatus. Human blood indices of at least 0.79 were observed for all species except An. bancroftii. Abundance of all 6 species was correlated temporally with recent rainfall, but An. koliensis, An. kanvari, and An. longirostris showed greater temporal variability than the other species. An. punctulatus and An. koliensis tended to occur together in time and space (index of association, I = 0.85). Weaker associations were seen between An. farauti s.l. and An. longirostris (I = 0.44) and An. koliensis and An. kanvari (I = 0.34). The most frequently collected species occurred together and were concentrated near the Amugu river; the remaining species tended to occur together but in different parts of the Wosera area. The importance of understanding ecological requirements of the different Anopheles vectors and their association with key household and landscape features are discussed in relation to malaria transmission and contro