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Cox M.P.,Massey University | Nelson M.G.,Massey University | Tumonggor M.K.,University of Arizona | Ricaut F.-X.,University Paul Sabatier | Sudoyo H.,Eijkman Institute for Molecular Biology
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

The settlement of Madagascar is one of the most unusual, and least understood, episodes in human prehistory. Madagascar was one of the last landmasses to be reached by people, and despite the island's location just off the east coast of Africa, evidence from genetics, language and culture all attests that it was settled jointly by Africans, and more surprisingly, Indonesians. Nevertheless, extremely little is known about the settlement process itself. Here, we report broad geographical screening of Malagasy and Indonesian genetic variation, from which we infer a statistically robust coalescent model of the island's initial settlement. Maximum-likelihood estimates favour a scenario in which Madagascar was settled approximately 1200 years ago by a very small group of women (approx. 30), most of Indonesian descent (approx. 93%). This highly restricted founding population raises the possibility that Madagascar was settled not as a large-scale planned colonization event from Indonesia, but rather through a small, perhaps even unintended, transoceanic crossing. © 2012 The Royal Society. Source

Ingram R.J.,Auckland City Hospital | Crenna-Darusallam C.,Eijkman Institute for Molecular Biology | Soebianto S.,Eijkman Oxford Clinical Research Unit | Noviyanti R.,University of Oxford | Baird J.K.,University of Oxford
Malaria Journal | Year: 2015

Background: Primaquine is the only drug available for preventing relapse following a primary attack by Plasmodium vivax malaria. This drug imposes several important problems: daily dosing over two weeks; toxicity in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency; partner blood schizontocides possibly impacting primaquine safety and efficacy; cytochrome P-450 abnormalities impairing metabolism and therapeutic activity; and some strains of parasite may be tolerant or resistant to primaquine. There are many possible causes of repeated relapses in a patient treated with primaquine. Case description: A 56-year-old Caucasian woman from New Zealand traveled to New Ireland, Papua New Guinea for two months in 2012. One month after returning home she stopped daily doxycycline prophylaxis against malaria, and one week later she became acutely ill and hospitalized with a diagnosis of Plasmodium vivax malaria. Over the ensuing year she suffered four more attacks of vivax malaria at approximately two-months intervals despite consuming primaquine daily for 14 days after each of those attacks, except the last. Genotype of the patient's cytochrome P-450 2D6 alleles (*5/*41) corresponded with an intermediate metabolizer phenotype of predicted low activity. Discussion: Multiple relapses in patients taking primaquine as prescribed present a serious clinical problem, and understanding the basis of repeated therapeutic failure is a challenging technical problem. This case highlights these issues in a single traveler, but these problems will also arise as endemic nations approach elimination of malaria transmission. © 2014 Ingram et al.; licensee BioMed Central. Source

Background: The persistence of influenza A virus H5N1 among poultry in Indonesia, along with increasing numbers of human infections by this virus, point to risk of a reassortment event with other prevalent influenza A subtypes in Indonesia. In the absence of cross-protective antibody to the emerging strain, the presence of cellular immunity might reduce the influenza illness to subclinical level and could dampen the pandemic. This study evaluated the degree of likely cross-protective T-cell mediated immunity against such hypothetical emerging influenza A strains. All 11 protein sequences from Indonesian H5N1 isolates were evaluated for the presence of T-cell epitopes restricted by Indonesian HLA types. Results: Among 4433 possible nonamer peptides, 225 were predicted as good CTL epitopes (score < 1%) by NetCTLpan and had strong binding affinity (IC50 < 50 nM) toward HLA molecules by IEDBann and netMHCann. Epitope conservation analysis revealed that at least 60% of the H5N1 Indonesian isolates contained the identical sequences of this 225 peptide set. Sixty-nine peptides were specific for H5N1 and 156 were cross-reactive with other subtypes. Significant numbers (184) of peptides bound to more than one HLA allele (promiscuous). Blast analysis showed that the majority (213) of peptides did not have similarity with the human self peptides likely to induce autoimmunity if used for vaccination. Certain peptides can act as a core for HLA Class II molecules, and some superimposed with the putative linear B-cell epitopes. Eighteen peptides emerged as likely vaccine components optimized to an Indonesian population but likely also to be effective among most other ethnic groups. Conclusions: Routine exposure to seasonal influenza A likely ensures some level of cross-protective immunity to H5N1 and most reassortment mutants. Identifying of such likely cross-reactive T-cell epitopes may aid in gauging the threat of potential outbreaks and composing the vaccines that could contain them. © 2011 Gustiananda; licensee Nikolai Petrovsky Publishing. Source

Rijken M.J.,Shoklo Malaria Research Unit | McGready R.,Shoklo Malaria Research Unit | McGready R.,University of Oxford | McGready R.,Mahidol University | And 8 more authors.
The Lancet Infectious Diseases | Year: 2012

Most pregnant women at risk of for infection with Plasmodium vivax live in the Asia-Pacific region. However, malaria in pregnancy is not recognised as a priority by many governments, policy makers, and donors in this region. Robust data for the true burden of malaria throughout pregnancy are scarce. Nevertheless, when women have little immunity, each infection is potentially fatal to the mother, fetus, or both. WHO recommendations for the control of malaria in pregnancy are largely based on the situation in Africa, but strategies in the Asia-Pacific region are complicated by heterogeneous transmission settings, coexistence of multidrug-resistant Plasmodium falciparum and Plasmodium vivax parasites, and different vectors. Most knowledge of the epidemiology, effect, treatment, and prevention of malaria in pregnancy in the Asia-Pacific region comes from India, Papua New Guinea, and Thailand. Improved estimates of the morbidity and mortality of malaria in pregnancy are urgently needed. When malaria in pregnancy cannot be prevented, accurate diagnosis and prompt treatment are needed to avert dangerous symptomatic disease and to reduce effects on fetuses. © 2012 Elsevier Ltd. Source

Karafet T.M.,University of Arizona | Hallmark B.,University of Arizona | Cox M.P.,University of Arizona | Sudoyo H.,Eijkman Institute for Molecular Biology | And 4 more authors.
Molecular Biology and Evolution | Year: 2010

The early history of island Southeast Asia is often characterized as the story of two major population dispersals: the initial Paleolithic colonization of Sahul ∼45 ka ago and the much later Neolithic expansion of Austronesian-speaking farmers ∼4 ka ago. Here, in the largest survey of Indonesian Y chromosomes to date, we present evidence for multiple genetic strata that likely arose through a series of distinct migratory processes. We genotype an extensive battery of Y chromosome markers, including 85 single-nucleotide polymorphisms/indels and 12 short tandem repeats, in a sample of 1,917 men from 32 communities located across Indonesia. We find that the paternal gene pool is sharply subdivided between western and eastern locations, with a boundary running between the islands of Bali and Flores. Analysis of molecular variance reveals one of the highest levels of between-group variance yet reported for human Y chromosome data (e.g., ΦST = 0.47). Eastern Y chromosome haplogroups are closely related to Melanesian lineages (i.e., within the C, M, and S subclades) and likely reflect the initial wave of colonization of the region, whereas the majority of western Y chromosomes (i.e., O-M119*, O-P203, and O-M95*) are related to haplogroups that may have entered Indonesia during the Paleolithic from mainland Asia. In addition, two novel markers (P201 and P203) provide significantly enhanced phylogenetic resolution of two key haplogroups (O-M122 and O-M119) that are often associated with the Austronesian expansion. This more refined picture leads us to put forward a four-phase colonization model in which Paleolithic migrations of hunter-gatherers shape the primary structure of current Indonesian Y chromosome diversity, and Neolithic incursions make only a minor impact on the paternal gene pool, despite the large cultural impact of the Austronesian expansion. © The Author 2010. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. Source

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