Publications

Ric Price and colleagues pool individual patient data from efficacy trials of dihydroartemisinin-piperaquine shared with WWARN (Worldwide Antimalarial Resistance Network) to examine the potential for underdosing in young children. Please see later in the article for the Editors' Summary

Neonatal hyperbilirubinemia (NH) is a frequent condition that, if left untreated, can lead to neurological disability and death. We assessed the prevalence of NH and associated neonatal and maternal risk factors in 362 mothers and 365 newborns in a semi-rural area of the Democratic Republic of Congo. In addition, we explored the knowledge and practices of mothers regarding this condition. We collected demographic data, anthropometric data, and obstetric and medical anamneses. We examined newborns at birth and at 24, 48, and 72 hours and measured bilirubin at birth in umbilical cord and capillary blood and thereafter in capillary blood. Hemoglobin, hematocrit, ABO group, Rhesus factor, glucose-6-phosphate dehydrogenase (G6PD) deficiency, Hemoglobin S (HbS), and malaria were assessed in mothers and newborns. Among 296 newborns (all time points available), 5.7% developed NH (95% CI: 3.4-9.0) between 24 and 72 hours according to National Institute for Health and Care Excellence (NICE) UK guidelines. There was a significantly higher risk in newborns with G6PD deficiency (homo- and hemizygous adjusted Odd Ratio [aOR]: 21.0, 95% CI: 4.1-105.9), preterm births (aOR: 6.1, 95% CI: 1.4-26.9), newborns with excessive birth weight loss (aOR: 5.8, 95% CI: 1.4-23.2), and hyperbilirubinemia at birth (aOR: 14.8, 95% CI: 2.7-79.6). Newborns with feto-maternal ABO incompatibility and G6PD deficiency had significantly higher bilirubin at birth than others. More than 60% of mothers had adequate knowledge of NH, but compliance with phototherapy in the absence of symptoms was low. Although risk factors for NH are common in this area, prevalence was not high, suggesting a need for better case definition. Implementation of point-of-care devices for diagnosis and awareness programs on risk prevention could help reduce neonatal morbidity and mortality associated with hyperbilirubinemia in these areas.

Warming global temperatures are affecting a range of aspects of wild populations, but the exact mechanisms driving associations between temperature and phenotypic traits may be difficult to identify. Here, we use a 36-year data set on a wild population of red deer to investigate the causes of associations between temperature and two important components of female reproduction: timing of breeding and offspring size. By separating within- versus between-individual associations with temperature for each trait, we show that within-individual phenotypic plasticity (changes within a female's lifetime) was entirely sufficient to generate the observed population-level association with temperature at key times of year. However, despite apparently adequate statistical power, we found no evidence of any variation between females in their responses (i.e. no "IxE" interactions). Our results suggest that female deer show plasticity in reproductive traits in response to temperatures in the year leading up to calving and that this response is consistent across individuals, implying no potential for either selection or heritability of plasticity. We estimate that the plastic response to rising temperatures explained 24% of the observed advance in mean calving date over the study period. We highlight the need for comparable analyses of other systems to determine the contribution of within-individual plasticity to population-level responses to climate change.

Female intrasexual competition can be intense in cooperatively breeding species, with the dominant breeder or matriarch limiting reproduction in subordinates via aggression, eviction or infanticide. In males, these tendencies bidirectionally link to testosterone, but in females, there has been no systematic investigation of androgen-mediated behaviour within and across generations. In 22 wild meerkat ( Suricata suricatta ) clans, we show that matriarchs 1) express peak androgen concentrations during late gestation, 2) when displaying peak feeding competition, dominance, and evictions, and 3) relative to subordinates, produce offspring that are more aggressive in early development. Late-gestation, antiandrogen treatment of matriarchs 4) reduced their dominance behaviour, was associated with infrequent evictions, decreased social centrality within the clan, 5) increased aggression in cohabiting subordinate dams, and 6) reduced their offspring’s aggression. These effects implicate androgen-mediated aggression in the operation of female sexual selection, and intergenerational transmission of ‘masculinised’ phenotypes in the evolution of meerkat cooperative breeding.

While vocal tract resonances or formants are key acoustic parameters that define differences between phonemes in human speech, little is known about their function in animal communication. Here, we used playback experiments to present red deer stags with re-synthesized vocalizations in which formant frequencies were systematically altered to simulate callers of different body sizes. In response to stimuli where lower formants indicated callers with longer vocal tracts, stags were more attentive, replied with more roars and extended their vocal tracts further in these replies. Our results indicate that mammals other than humans use formants in vital vocal exchanges and can adjust their own formant frequencies in relation to those that they hear.

The dhps sequences of 55 Plasmodium vivax isolates (39 from Thailand and 16 from elsewhere) revealed mutant Pvdhps at codons 383 and/or 553 (A --> G) in 33 isolates, all from Thailand. Mutations of Pvdhps and Pvdhfr were correlated. Multiple mutations were associated with high-grade sulfadoxine-pyrimethamine resistance.

Studies were conducted to determine how malaria parasites are cleared from the blood after antimalarial treatment. Neither artesunate nor quinine decreased parasitized red cell deformability or increased antibody binding. In acute falciparum malaria, ring-infected erythrocyte surface antigen (RESA) was observed in erythrocytes without malaria parasites (RESA-red blood cell [RBC]), indicating prior parasitization. In uncomplicated malaria, RESA-RBC numbers increased significantly (P = .002) within 24 h of starting artesunate but rose much more slowly (7 days) after quinine treatment. In severe malaria, RESA-RBC increased significantly (P = .001) within hours of starting artesunate but not with quinine treatment (P = .43). RESA-RBCs were not produced after drug treatment of malaria parasite cultures in vitro. Rapid malaria parasite clearance after treatment with artemisinin derivatives results mainly from the extraction of drug-affected parasites from host erythrocytes—presumably by the spleen. This explains why the fall in hematocrit after treatment of hyperparasitemia is often less than that predicted from loss of parasitized cells.

Journal Article Pharmacokinetics of oral artesunate in children with moderately severe Plasmodium falciparum malaria Get access Delia B. Bethell, Delia B. Bethell 1Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Viet Nam2Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Paktiya Teja-Isavadharm, Paktiya Teja-Isavadharm 3Department of Immunology, AFRIMS, Bangkok, Thailand Search for other works by this author on: Oxford Academic PubMed Google Scholar Cao Xuan Thanh Phuong, Cao Xuan Thanh Phuong 4Dong Nai Paediatric Centre, Bien Hoa, Dong Nai Province, Viet Nam Search for other works by this author on: Oxford Academic PubMed Google Scholar Pham Thi Thu Thuy, Pham Thi Thu Thuy 5Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Viet Nam Search for other works by this author on: Oxford Academic PubMed Google Scholar Ta Thi Tuyet Mai, Ta Thi Tuyet Mai 4Dong Nai Paediatric Centre, Bien Hoa, Dong Nai Province, Viet Nam Search for other works by this author on: Oxford Academic PubMed Google Scholar Tran Thi Nhu Thuy, Tran Thi Nhu Thuy 4Dong Nai Paediatric Centre, Bien Hoa, Dong Nai Province, Viet Nam Search for other works by this author on: Oxford Academic PubMed Google Scholar Nguyen Thi Thanh Ha, Nguyen Thi Thanh Ha 4Dong Nai Paediatric Centre, Bien Hoa, Dong Nai Province, Viet Nam Search for other works by this author on: Oxford Academic PubMed Google Scholar Pham Tung Phuong, Pham Tung Phuong 4Dong Nai Paediatric Centre, Bien Hoa, Dong Nai Province, Viet Nam Search for other works by this author on: Oxford Academic PubMed Google Scholar Dennis Kyle, Dennis Kyle 3Department of Immunology, AFRIMS, Bangkok, Thailand Search for other works by this author on: Oxford Academic PubMed Google Scholar Nicholas P.J. Day, Nicholas P.J. Day 1Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Viet Nam2Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Nicholas J. White Nicholas J. White 1Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Viet Nam2Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, UK Address for correspondence: Professor N. J. White, Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Cho Quan Hospital, 190/5 Ben Ham Tu.Q5, Ho Chi Minh City, Viet Nam. Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 91, Issue 2, March-April 1997, Pages 195–198, https://doi.org/10.1016/S0035-9203(97)90222-4 Published: 01 April 1997 Article history Received: 27 February 1996 Revision received: 28 August 1996 Accepted: 10 October 1996 Published: 01 April 1997

Artesunate is a key antimalarial drug in the treatment of multidrug-resistant Plasmodium falciparum malaria in southeast Asia. We investigated the distribution of counterfeit artesunate tablets by use of the validated, simple, and inexpensive Fast Red TR dye technique. We also aimed to identify distinguishing characteristics of the fake drugs. Of 104 shop-bought “artesunate” samples from Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, 38% did not contain artesunate. Characteristics such as cost and physical appearance of the tablets and packaging reliably predicted authenticity. The illicit trade in counterfeit antimalarials is a great threat to the lives of patients with malaria. The dye test will assist national malaria control authorities in urgently needed campaigns to stop this murderous trade.

After cryopreservation of semen from men with testicular tumours or Hodgkin's disease the success rate of artificial insemination of their partners was analysed. The cumulative probability of pregnancy at 6 months was 45%. The chance of pregnancy was greater when timing of ovulation was predicted with measurements of urinary luteinising hormone. Sperm density and sperm motility were also important in predicting the likelihood of pregnancy.

Melioidosis is an infectious disease with a propensity for relapse, despite prolonged antibiotic eradication therapy for 12 to 20 weeks. A pharmacokinetic (PK) simulation study was performed to determine the optimal dosing of cotrimoxazole (trimethoprim-sulfamethoxazole [TMP-SMX]) used in current eradication regimens in Thailand and Australia. Data for bioavailability, protein binding, and coefficients of absorption and elimination were taken from published literature. Apparent volumes of distribution were correlated with body mass and were estimated separately for Thai and Australian populations. In vitro experiments demonstrated concentration-dependent killing. In Australia, the currently used eradication regimen (320 [TMP]/1,600 [SMX] mg every 12 h [q12h]) was predicted to achieve the PK-pharmacodynamic (PD) target (an area under the concentration-time curve from 0 to 24 h/MIC ratio of >25 for both TMP and SMX) for strains with the MIC 90 of Australian strains (≤1/19 mg/liter). In Thailand, the former regimen of 160/800 mg q12h would not be expected to attain the target for strains with an MIC of ≥1/19 mg/liter, but the recently implemented weight-based regimen (<40 kg [body weight], 160/800 mg q12h; 40 to 60 kg, 240/1,200 mg q12h; >60 kg, 320/1,600 mg q12h) would be expected to achieve adequate concentrations for strains with an MIC of ≤1/19 mg/liter. The results were sensitive to the variance of the PK parameters. Prospective PK-PD studies of Asian populations are needed to optimize TMP-SMX dosing in melioidosis.

Melioidosis is common in north-eastern Thailand, but is reported rarely from the adjacent areas of central Thailand, although rice farming is common to both regions. Quantitative soil cultures for Burkholderia pseudomallei were therefore prepared on 12 rice farms in both regions. B. pseudomallei was isolated from a similar proportion of rice fields in the central region () and in the north-east (). Within the culture-positive sites, the number of B. pseudomallei colony-forming units (cfu) per mL of soil/water supernatant was significantly higher in the north-east (median 230 cfu/mL; range 1–17 000) than in the central region (median 10 cfu/mL; range 1–600). As bacterial counts in the soil are probably related to the risk of developing melioidosis, differences in exposure to B. pseudomallei probably contribute to the considerable differences in the incidence of this disease between these 2 adjacent regions.

Ex vivo conversion of the anti-influenza drug oseltamivir to its active metabolite can be inhibited by the esterase inhibitor dichlorvos or by using commercial fluoride-oxalate tubes. Oseltamivir and its active metabolite remain intact in plasma samples during a proposed virus heat inactivation step: incubation at 60°C for 45 min.

No abstract is provided for this article.