Safety, tolerability and pharmacokinetic properties of coadministered azithromycin and piperaquine in pregnant Papua New Guinean women.

Aims: The aim of the present study was to investigate the safety, tolerability and pharmacokinetics of coadministered azithromycin (AZI) and piperaquine (PQ) for treating malaria in pregnant Papua New Guinean women.

Methods: Thirty pregnant women (median age 22 years; 16-32 weeks' gestation) were given three daily doses of 1 g AZI plus 960 mg PQ tetraphosphate with detailed monitoring/blood sampling over 42 days. Plasma AZI and PQ were assayed using liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively.

Insights into the naturally acquired immune response to Plasmodium vivax malaria.

Plasmodium vivax is the most geographically widespread of the malaria parasites causing human disease, yet it is comparatively understudied compared with Plasmodium falciparum. In this article we review what is known about naturally acquired immunity to P. vivax, and importantly, how this differs to that acquired against P.

Limited Degradation of the Plasmodium falciparum Gametocyte Marker pfs25 mRNA Exposed to Tropical Temperatures: Considerations for Malaria Transmission Field Studies.

An important aspect of many malaria molecular epidemiology and transmission studies is RNA-based detection of gametocytes. Ensuring RNA stability represents a challenge in tropical, resource-limited environments, as RNA may quickly degrade when samples are not preserved under adequate conditions. This study investigated the degradation of pfs25 messenger RNA (mRNA), the most widely used Plasmodium falciparum gametocyte marker, in whole blood spiked with cultured P.

Malaria transmission dynamics surrounding the first nationwide long-lasting insecticidal net distribution in Papua New Guinea.

Background: The major malaria vectors of Papua New Guinea exhibit heterogeneities in distribution, biting behaviour and malaria infection levels. Long-lasting, insecticide-treated nets (LLINs), distributed as part of the National Malaria Control Programme, are the primary intervention targeting malaria transmission. This study evaluated the impact of LLINs on anopheline density, species composition, feeding behaviour, and malaria transmission.

Evaluation of CDC light traps for mosquito surveillance in a malaria endemic area on the Thai-Myanmar border.

Background: Centers for Disease Control and Prevention miniature light traps (CDC-LT) baited with CO2 are a routine tool for adult mosquito sampling used in entomological surveys, and for monitoring and surveillance of disease vectors. The present study was aimed at evaluating the performance of baited and unbaited CDC-LT for indoor and outdoor trapping of endemic mosquito species in northwestern Thailand.

Methods: CDC-LT (n = 112) with and without dry ice baits were set both indoors and outdoors in 88 selected houses for stretches of 5 consecutive nights per month in 7 villages in Tha Song Yang district, Tak province between January 2011 and March 2013.

Acquisition and Longevity of Antibodies to Plasmodium vivax Preerythrocytic Antigens in Western Thailand.

Plasmodium vivax is now the dominant Plasmodium species causing malaria in Thailand, yet little is known about naturally acquired immune responses to this parasite in this low-transmission region. The preerythrocytic stage of the P. vivax life cycle is considered an excellent target for a malaria vaccine, and in this study, we assessed the stability of the seropositivity and the magnitude of IgG responses to three different preerythrocytic P.

A Toll-like receptor-1 variant and its characteristic cellular phenotype is associated with severe malaria in Papua New Guinean children.

Genetic factors are likely to contribute to low severe malaria case fatality rates in Melanesian populations, but association studies can be underpowered and may not provide plausible mechanistic explanations if significant associations are detected. In preparation for a genome-wide association study, 29 candidate single-nucleotide polymorphisms (SNPs) with minor allele frequencies >5% were examined in a case-control study of 504 Papua New Guinean children with severe malaria. In parallel, an immunological substudy was performed on convalescent peripheral blood mononuclear cells (PBMCs) from cases and controls.

True navigation in migrating gulls requires intact olfactory nerves.

During migratory journeys, birds may become displaced from their normal migratory route. Experimental evidence has shown that adult birds can correct for such displacements and return to their goal. However, the nature of the cues used by migratory birds to perform long distance navigation is still debated.

Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model.

Background: The undetectable hypnozoite reservoir for relapsing Plasmodium vivax and P. ovale malarias presents a major challenge for malaria control and elimination in endemic countries. This study aims to directly determine the contribution of relapses to the burden of P.

Accuracy of an HRP-2/panLDH rapid diagnostic test to detect peripheral and placental Plasmodium falciparum infection in Papua New Guinean women with anaemia or suspected malaria.

Background: The diagnosis of malaria during pregnancy is complicated by placental sequestration, asymptomatic infection, and low-density peripheral parasitaemia. Where intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine is threatened by drug resistance, or is inappropriate due to low transmission, intermittent screening and treatment (ISTp) with rapid diagnostic tests for malaria (RDT) could be a valuable alternative. Therefore, the accuracy of RDTs to detect peripheral and placental infection was assessed in a declining transmission setting in Papua New Guinea (PNG).

Significant geographical differences in prevalence of mutations associated with Plasmodium falciparum and Plasmodium vivax drug resistance in two regions from Papua New Guinea.

Background: Drug resistance remains a major obstacle to malaria treatment and control. It can arise and spread rapidly, and vary substantially even at sub-national level. National malaria programmes require cost-effective and timely ways of characterizing drug-resistance at multiple sites within their countries.

Development of vaccines for Plasmodium vivax malaria.

Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P.

Prevalence of malaria across Papua New Guinea after initial roll-out of insecticide-treated mosquito nets.

Objectives: To assess the population prevalence of malaria in villages across Papua New Guinea (PNG) following the first roll-out of free long-lasting insecticidal nets (LLIN).

Methods: Between October 2008 and August 2009, a household survey was conducted in 49 random villages in districts covered by the LLIN distribution campaign. The survey extended to 19 villages in sentinel sites that had not yet been covered by the campaign.

Azithromycin-containing intermittent preventive treatment in pregnancy affects gestational weight gain, an important predictor of birthweight in Papua New Guinea - an exploratory analysis.

In Papua New Guinea, intermittent preventive treatment with sulphadoxine-pyrimethamine and azithromycin (SPAZ-IPTp) increased birthweight despite limited impact on malaria and sexually transmitted infections. To explore possible nutrition-related mechanisms, we evaluated associations between gestational weight gain (GWG), enrolment body mass index (BMI) and mid-upper arm circumference (MUAC), and birthweight. We investigated whether the increase in birthweight associated with SPAZ-IPTp may partly be driven by a treatment effect on GWG.

Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea.

Background: Chewing areca nut (AN), also known as betel nut, is common in Asia and the South Pacific and the habit has been linked to a number of serious health problems including oral cancer. Use of AN in pregnancy has been associated with a reduction in mean birthweight in some studies, but this association and the relationship between AN chewing and other adverse pregnancy outcomes remain poorly understood.

Methods: We assessed the impact of AN chewing on adverse outcomes including stillbirth, low birthweight (LBW, <2,500 g) and anaemia at delivery (haemoglobin <11.

The Human Tau Interactome: Binding to the Ribonucleoproteome, and Impaired Binding of the Proline-to-Leucine Mutant at Position 301 (P301L) to Chaperones and the Proteasome.

The tau protein is central to the etiology of several neurodegenerative diseases, including Alzheimer's disease, a subset of frontotemporal dementias, progressive supranuclear palsy and dementia following traumatic brain injury, yet the proteins it interacts with have not been studied using a systematic discovery approach. Here we employed mild in vivo crosslinking, isobaric labeling, and tandem mass spectrometry to characterize molecular interactions of human tau in a neuroblastoma cell model. The study revealed a robust association of tau with the ribonucleoproteome, including major protein complexes involved in RNA processing and translation, and documented binding of tau to several heat shock proteins, the proteasome and microtubule-associated proteins.

Malaria Epidemiology and Control Within the International Centers of Excellence for Malaria Research.

Understanding the epidemiological features and metrics of malaria in endemic populations is a key component to monitoring and quantifying the impact of current and past control efforts to inform future ones. The International Centers of Excellence for Malaria Research (ICEMR) has the opportunity to evaluate the impact of malaria control interventions across endemic regions that differ in the dominant Plasmodium species, mosquito vector species, resistance to antimalarial drugs and human genetic variants thought to confer protection from infection and clinical manifestations of plasmodia infection. ICEMR programs are conducting field studies at multiple sites with the aim of generating standardized surveillance data to improve the understanding of malaria transmission and to monitor and evaluate the impact of interventions to inform malaria control and elimination programs.

Malaria Molecular Epidemiology: Lessons from the International Centers of Excellence for Malaria Research Network.

Molecular epidemiology leverages genetic information to study the risk factors that affect the frequency and distribution of malaria cases. This article describes molecular epidemiologic investigations currently being carried out by the International Centers of Excellence for Malaria Research (ICEMR) network in a variety of malaria-endemic settings. First, we discuss various novel approaches to understand malaria incidence and gametocytemia, focusing on Plasmodium falciparum and Plasmodium vivax.

Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens.

Background: Malaria is a major global cause of deaths and a vaccine is urgently needed.

Results: We have employed the P. falciparum merozoite antigens MSP2-3D7/FC27 and AMA1, used them in ELISA, and coupled them in different ways using surface plasmon resonance (SPR) and estimated affinity (measured as kd) of monoclonal as well as naturally-acquired polyclonal antibodies in human plasma.

Acquisition of Functional Antibodies That Block the Binding of Erythrocyte-Binding Antigen 175 and Protection Against Plasmodium falciparum Malaria in Children.

Background: The targets and mechanisms of human immunity to malaria are poorly understood, which poses a major barrier to malaria vaccine development. Antibodies play a key role in human immunity and may act by inhibiting receptor-binding functions of key merozoite invasion ligands. Antibodies to the major invasion ligand and vaccine candidate, erythrocyte-binding antigen 175 (EBA-175), have been linked with protection, but how these antibodies function has not been established.

Plasmodium vivax Diversity and Population Structure across Four Continents.

Plasmodium vivax is the geographically most widespread human malaria parasite. To analyze patterns of microsatellite diversity and population structure across countries of different transmission intensity, genotyping data from 11 microsatellite markers was either generated or compiled from 841 isolates from four continents collected in 1999-2008. Diversity was highest in South-East Asia (mean allelic richness 10.

Malaria preventive therapy in pregnancy and its potential impact on immunity to malaria in an area of declining transmission.

Background: Regular anti-malarial therapy in pregnancy, a pillar of malaria control, may affect malaria immunity, with therapeutic implications in regions of reducing transmission.

Methods: Plasma antibodies to leading vaccine candidate merozoite antigens and opsonizing antibodies to endothelial-binding and placental-binding infected erythrocytes were quantified in pregnant Melanesian women receiving sulfadoxine-pyrimethamine (SP) with chloroquine taken once, or three courses of SP with azithromycin.

Results: Malaria prevalence was low.