Rose McGready
Shoklo Malaria Research Unit, Maternal and Child Health, Faculty Member
Malaria in Southeast Asia frequently clusters along international borders. For example, while most of Thailand is malaria free, the border region shared with Myanmar continues to have endemic malaria. This spatial pattern is the result of... more
Malaria in Southeast Asia frequently clusters along international borders. For example, while most of Thailand is malaria free, the border region shared with Myanmar continues to have endemic malaria. This spatial pattern is the result of complex interactions between landscape, humans, mosquito vectors, and malaria parasites. An understanding of these complex ecological and socio-cultural interactions is important for designing and implementing malaria elimination efforts in the region. This article offers an ecological perspective on the malaria situation along the Thailand-Myanmar border. This border region is long (2000 km), mountainous, and the environment ranges from thick forests to growing urban settlements and wet-rice fields. It is also a biologically diverse region. All five species of malaria known to naturally infect humans are present. At least three mosquito vector species complexes, with widely varying behavioural characteristics, exist in the area. The region is also a hub for ethnic diversity, being home to over ten different ethnolinguistic groups, several of which have been engaged in conflict with the Myanmar government now for over half a century. Given the biological and ethnic diversity, as well as the complex socio-political context, malaria control and elimination in the region is challenging. Despite these complexities, multipronged approaches including collaborations with multiple local organizations, quick access to diagnosis and treatment, prevention of mosquito bites, radical cure of parasites, and mass drug administration appear to be drastically decreasing Plasmodium falciparum infections. Such approaches remain crucial as the region moves toward elimination of P. falciparum and potentially Plasmodium vivax.
Research Interests:
Artemether-lumefantrine is the most widely used antimalarial artemisinin-based combination treatment. Recent studies have suggested that day 7 plasma concentrations of the potent metabolite desbutyl-lumefantrine correlate better with... more
Artemether-lumefantrine is the most widely used antimalarial artemisinin-based combination treatment. Recent studies have suggested that day 7 plasma concentrations of the potent metabolite desbutyl-lumefantrine correlate better with treatment outcomes than lumefantrine. Low cure rates have been reported in pregnant women with uncomplicated falciparum malaria treated with artemether-lumefantrine in northwest Thailand. A simultaneous pharmacokinetic drug-metabolite model was developed based on dense venous and sparse capillary lumefantrine and desbutyl-lumefantrine plasma samples from 116 pregnant patients on the Thailand-Myanmar border. The best model was used to evaluate therapeutic outcomes with a time-to-event approach. Lumefantrine and desbutyl-lumefantrine concentrations, implemented in an EMAX model, both predicted treatment outcomes but lumefantrine provided better predictive power. A combined model including both lumefantrine and desbutyl-lumefantrine did not improve the mod...
Research Interests:
Estimating gestational age in resource-limited settings is prone to considerable inaccuracy because crown-rump length measured by ultrasound before 14 weeks gestation, the recommended method for estimating gestational age, is often... more
Estimating gestational age in resource-limited settings is prone to considerable inaccuracy because crown-rump length measured by ultrasound before 14 weeks gestation, the recommended method for estimating gestational age, is often unavailable. Judgements regarding provision of appropriate obstetric and neonatal care are dependent on accurate estimation of gestational age. We determined the accuracy of the Dubowitz Gestational Age Assessment, a population-specific symphysis-fundal height formula, and ultrasound biometry performed between 16 and 40 weeks gestation in estimating gestational age using pre-existing data from antenatal clinics of the Shoklo Malaria Research Unit on the Thai-Myanmar border, where malaria is endemic. Two cohorts of women who gave birth to live singletons were analysed: 1) 250 women who attended antenatal care between July 2001 and May 2006 and had both ultrasound crown-rump length (reference) and a Dubowitz Gestational Age Assessment; 2) 975 women attendin...
Research Interests:
Plasmodium falciparum infections adversely affect pregnancy. Anti-malarial treatment failure is common. The objective of this study was to examine the duration of persistent parasite carriage following anti-malarial treatment in... more
Plasmodium falciparum infections adversely affect pregnancy. Anti-malarial treatment failure is common. The objective of this study was to examine the duration of persistent parasite carriage following anti-malarial treatment in pregnancy. The data presented here are a collation from previous studies carried out since 1994 in the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border and performed using the same unique methodology detailed in the Materials and Methods section. Screening for malaria by microscopy is a routine part of weekly antenatal care (ANC) visits and therapeutic responses to anti-malarials were assessed in P. falciparum malaria cases. Women with microscopy confirmed P. falciparum malaria had a PCR blood spot from a finger-prick sample collected. Parasite DNA was extracted from the blood-spot samples using saponin lysis/Chelex extraction method and genotyped using polymorphic segments of MSP1, MSP2 and GLURP. Recurrent infections were classified by ge...
Research Interests:
Mental illness is a significant contributor to the global burden of disease, with prevalence highest in low- and middle-income countries. Rates are high in women of childbearing age, especially during pregnancy and the first year... more
Mental illness is a significant contributor to the global burden of disease, with prevalence highest in low- and middle-income countries. Rates are high in women of childbearing age, especially during pregnancy and the first year post-partum. Migrant and refugee populations are at risk of developing mental illness due to the multiple stresses associated with migration. The Thai-Myanmar border area is home to large populations of migrants and refugees as a result of long-standing conflict, poverty and unemployment in Myanmar. This study aims to explore perceptions of mental illness among pregnant migrants and refugees and antenatal clinic staff living and working along the Thai-Myanmar border. Thirteen focus group discussions were conducted with pregnant migrants, pregnant refugees and antenatal clinic staff. Focus groups were held in one large refugee camp and two migrant health clinics along the Thai-Myanmar border. Thematic analysis was used to identify and code themes emerging from the data. A total of 92 pregnant women and 24 antenatal clinic staff participated. Discussions centered around five main themes: symptoms of mental illness; causes of mental illness; suicide; mental illness during pregnancy and the post-partum period; and managing mental illness. Symptoms of mental illness included emotional disturbances, somatic symptoms and socially inappropriate behavior. The main causes were described as current economic and family-related difficulties. Suicide was frequently attributed to shame. Mental illness was thought to be more common during and following pregnancy due to a lack of family support and worries about the future. Talking to family and friends, medication and hospitalization were suggested as means of helping those suffering from mental illness. Mental illness was recognized as a concept by the majority of participants and there was a general willingness to discuss various aspects of it. More formal and systematic training including the development of assessment tools in the local languages would enable better ascertainment and treatment of mental illness in this population.
Research Interests:
To compare the pharmacokinetic properties of artesunate and dihydroartemisinin in the same women: i) pregnant with acute uncomplicated malaria on day 1 and 2, ii) pregnant with convalescent malaria on day 7 and iii) in a healthy state 3... more
To compare the pharmacokinetic properties of artesunate and dihydroartemisinin in the same women: i) pregnant with acute uncomplicated malaria on day 1 and 2, ii) pregnant with convalescent malaria on day 7 and iii) in a healthy state 3 months post-partum on day 1, 2 and 7. Nonlinear mixed-effects modelling was used to compare plasma concentration-time profiles of artesunate and dihydroartemisinin over 7 days of treatment following oral and intravenous artesunate administration to pregnant women with uncomplicated Plasmodium falciparum malaria during their second or third trimesters of pregnancy. The same women were restudied three months after delivery when fully recovered. Non-compartmental results of the same study have been published previously. Twenty pregnant patients on the Thailand-Myanmar border were studied and 15 volunteered to be restudied three months post-partum. Malaria and pregnancy had no effect on the pharmacokinetic properties of artesunate or dihydroartemisinin a...
Research Interests:
Research Interests: Southeast Asia, Malaria, Tropical Medicine, Lao PDR, Public Health, and 13 moreVietnam, Tropical medicine (Health Sciences), Humans, Fraud, Sesquiterpenes, Prevalence, Self medication, Cross Section, Public health systems and services research, Antimalarials, Active Ingredient, Cross Sectional Studies, and Mefloquine
Research Interests:
Research Interests: Africa, Global Health, Malaria, Travel, Humans, and 9 moreAsia, Fraud, Male, Sesquiterpenes, Adult, Antimalarials, Drug Costs, PLoS Med, and Drug Packaging
Research Interests:
Research Interests: Thailand, Refugees, Seasonality, Pregnancy, Humans, and 22 moreMultidrug Resistance, Hospitalization, Female, Male, Incidence, Sesquiterpenes, Aged, Prevalence, Middle Aged, Early Detection, Adult, Cross Section, Plasmodium falciparum, Antimalarials, Combination drug therapy, Diagnostic Test, Hospital Mortality, Tropical Climate, Cross Sectional Studies, Early Diagnosis, Confidence Interval, and Mefloquine
Research Interests: Tropical Medicine, Thailand, Treatment Outcome, Adolescent, Tropical medicine (Health Sciences), and 16 moreQuality Control, Humans, Child, Multidrug Resistance, Female, Male, Infant, Sesquiterpenes, Aged, Middle Aged, Adult, Public health systems and services research, Antimalarials, Tablets, Combination drug therapy, and Mefloquine
Research Interests:
Research Interests:
Research Interests: Soil, Malaria, Thailand, Adolescent, Plasmodium, and 21 moreBiological Sciences, Myanmar, Rural Health, Pregnancy, Humans, Low Birth Weight, Female, Animals, Young Adult, Anemia, Risk factors, Prevalence, Adult, Cross Section, Feces, Pregnant Women, Risk Factors, Antenatal Care, Helminths, Cross Sectional Studies, and Helminthiasis
Research Interests:
Research Interests: Treatment, Infectious Diseases, Biological Sciences, Spleen, Humans, and 22 moreChild, Resistance, Female, Animals, Drug Resistance, Male, Vascular endothelium, Life Cycle, Infectious, Sesquiterpenes, Middle Aged, Adult, Plasmodium falciparum, Antimalarials, Red blood cell, Protozoan Proteins, Erythrocytes, Rate, Antigen, Drug treatment, Splenectomy, and Host Defense
Research Interests: Cartography, Epidemiology, Africa, Reproduction, Medical Microbiology, and 19 moreTreatment, Developing Countries, Population Dynamics, Health, Public Health, Pregnancy, Population, Humans, Americas, Female, Animals, Asia, Clinical Sciences, Newborn Infant, Adult, Infant Mortality, Interventions, Gestation, and Pregnancy Outcome
The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai... more
The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai border districts. The children were evaluated for vaccination completion and timing, for six different vaccines: Bacille Calmette-Guerin (BCG); Oral Polio vaccine (OPV); Hepatitis B vaccine (HepB); Diphtheria, Pertussis and Tetanus vaccine (DTP); Measles Containing Vaccine or Measles, Mumps and Rubella vaccine (MMR); Tetanus and Diphtheria containing vaccine (Td). Vaccine coverage proportions for BCG, OPV3, DTP3, HepB3 and measles containing vaccine were 92.3, 85.3, 63.8, 72.2, and 90.9 % respectively. Most children were able to receive vaccines in a time appropriate manner. School-based immunization programs offer a suitable vaccine delivery mechanism for hard-to-reach populations. However, these data suggest overall low vaccine coverage in migrant populations. Further efforts toward improving appropriate vaccine coverage and methods of retaining documentation of vaccination in mobile migrant populations are necessary for improved health.
Research Interests:
Background. How antimalarial antibodies are acquired and maintained during pregnancy and boosted after reinfection with Plasmodium falciparum and Plasmodium vivax is unknown. Methods. A nested case-control study of 467 pregnant women (136... more
Background. How antimalarial antibodies are acquired and maintained during pregnancy and boosted after
reinfection with Plasmodium falciparum and Plasmodium vivax is unknown.
Methods. A nested case-control study of 467 pregnant women (136 Plasmodium-infected cases and 331 uninfected
control subjects) in northwestern Thailand was conducted. Antibody levels to P. falciparum and P. vivax
merozoite antigens and the pregnancy-specific PfVAR2CSA antigen were determined at enrollment (median 10
weeks gestation) and throughout pregnancy until delivery.
Results. Antibodies to P. falciparum and P. vivax were highly variable over time, and maintenance of high
levels of antimalarial antibodies involved highly dynamic responses resulting from intermittent exposure to infection.
There was evidence of boosting with each successive infection for P. falciparum responses, suggesting the
presence of immunological memory. However, the half-lives of Plasmodium antibody responses were relatively
short, compared with measles (457 years), and much shorter for merozoite responses (0.8–7.6 years), compared
with PfVAR2CSA responses (36–157 years). The longer half-life of antibodies to PfVAR2CSA suggests that antibodies
acquired in one pregnancy may be maintained to protect subsequent pregnancies.
Conclusions. These findings may have important practical implications for predicting the duration of vaccineinduced
responses by candidate antigens and supports the development of malaria vaccines to protect pregnant
women.
reinfection with Plasmodium falciparum and Plasmodium vivax is unknown.
Methods. A nested case-control study of 467 pregnant women (136 Plasmodium-infected cases and 331 uninfected
control subjects) in northwestern Thailand was conducted. Antibody levels to P. falciparum and P. vivax
merozoite antigens and the pregnancy-specific PfVAR2CSA antigen were determined at enrollment (median 10
weeks gestation) and throughout pregnancy until delivery.
Results. Antibodies to P. falciparum and P. vivax were highly variable over time, and maintenance of high
levels of antimalarial antibodies involved highly dynamic responses resulting from intermittent exposure to infection.
There was evidence of boosting with each successive infection for P. falciparum responses, suggesting the
presence of immunological memory. However, the half-lives of Plasmodium antibody responses were relatively
short, compared with measles (457 years), and much shorter for merozoite responses (0.8–7.6 years), compared
with PfVAR2CSA responses (36–157 years). The longer half-life of antibodies to PfVAR2CSA suggests that antibodies
acquired in one pregnancy may be maintained to protect subsequent pregnancies.
Conclusions. These findings may have important practical implications for predicting the duration of vaccineinduced
responses by candidate antigens and supports the development of malaria vaccines to protect pregnant
women.
Research Interests:
Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from... more
Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. We included 61 studies done between...
Research Interests: Africa, Global Health, Medical Microbiology, Tropical Medicine, Treatment Outcome, and 16 moreAdolescent, Humans, Child, Female, Asia, Male, Polymerase Chain Reaction, Neglected tropical diseases, Young Adult, Infant, Clinical Sciences, Aged, Middle Aged, Adult, Plasmodium falciparum, and Antimalarials
Research Interests:
The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of... more
The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals. The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear. In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine). In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine. Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand. Similar analysis revealed the around 70% of infecti...
Research Interests:
Malaria during pregnancy reduces birth weight, and low birth weight is a major determinant of infant mortality. The authors estimated the impact of malaria during pregnancy on infant mortality in a Karen population living in Thailand.... more
Malaria during pregnancy reduces birth weight, and low birth weight is a major determinant of infant mortality. The authors estimated the impact of malaria during pregnancy on infant mortality in a Karen population living in Thailand. Between 1993 and 1996, a cohort of 1,495 mothers and their infants was followed weekly from admission of the mother to antenatal clinics until
Research Interests:
Research Interests:
Research Interests:
Background: Inherited red blood cell disorders are prevalent in populations living in malaria endemic areas; G6PD deficiency is associated with oxidant-induced hemolysis and abnormal hemoglobin variants may cause chronic anemia. In... more
Background: Inherited red blood cell disorders are prevalent in populations living in malaria endemic areas; G6PD deficiency is associated with oxidant-induced hemolysis and abnormal hemoglobin variants may cause chronic anemia. In pregnant women, microcytic anemia caused by hemoglobinopathies mimics iron deficiency, complicating diagnosis and treatment. Anemia during pregnancy is associated with morbidity and mortality. The aim of this study was to characterize the prevalence of G6PD deficiency, hemoglobinopathies, ABO and Rhesus blood groups among the pregnant population living along the Thailand-Myanmar border. Pregnant women attending antenatal clinics in this area belong to several distinct ethnic groups. Methods: Data was available for 13,520 women attending antenatal care between July 2012 and September 2016. Screening for G6PD deficiency was done by fluorescent spot test routinely. G6PD genotyping and quantitative phenotyping by spectrophotometry were analyzed in a subsample...
Research Interests:
Conflict settings and refugee camps can be chaotic places, with large and rapid population movements, exacerbated public health problems, and ad hoc health services. Reproductive health care that includes family planning is of heightened... more
Conflict settings and refugee camps can be chaotic places, with large and rapid population movements, exacerbated public health problems, and ad hoc health services. Reproductive health care that includes family planning is of heightened importance in such settings, however, funding and resources tend to be constrained and geared towards acute health services such as trauma management and infectious disease containment. Here we report on the complexities and challenges of providing family planning in a post-emergency refugee setting, using the example of the largest refugee camp on the Thai-Myanmar border, in existence now for over 30 years. Data from 2009 demonstrates an upward trend in uptake of all contraceptives, especially long acting reversible contraception (LARC) and permanent methods (e.g. sterilization) over time. Increased uptake occurred during periods of time when there were boosts in funding or when barriers to access were alleviated. For example a surgeon fluent in lo...
Research Interests:
We were encouraged to see the review of malaria in pregnancy by Whitty et al. in the BJOG given the huge burden of this disease and the lack of therapeutic and prophylactic options. As stated by the authors the risk of significant... more
We were encouraged to see the review of malaria in pregnancy by Whitty et al. in the BJOG given the huge burden of this disease and the lack of therapeutic and prophylactic options. As stated by the authors the risk of significant morbidity and mortality from withholding a drug for treatment of this condition usually outweighs the risk of toxicity. However we would like to share the following comments. We question the notion that pregnant women with malaria in Africa are asymptomatic: in fact there are no large and detailed longitudinal studies to support this hypothesis and most papers on treatment trials report the presence of symptoms in infected women even in areas of high transmission. It is unlikely that a pregnant woman infected with Plasmodium falciparum will remain completely asymptomatic and more likely that she will have mild symptoms that will not be reported. Maternal mortality attributed to malaria is high in Africa a fact that is hard to reconcile with absence of symptoms. (excerpt)
Research Interests:
<p>The file is a SAV type file with all variables used in the analysis available in the dataset (syp_hivF1000.sav)</p
Research Interests:
Research Interests:
Research Interests:
Malaria misconceptions We have serious concerns about the content of three letters published on Nov 13. In the first Arthur Caplan refers to the recently published report of the US Institute of Medicine and writes: “there is concern that... more
Malaria misconceptions We have serious concerns about the content of three letters published on Nov 13. In the first Arthur Caplan refers to the recently published report of the US Institute of Medicine and writes: “there is concern that the artemisinin derivatives are associated with greatly increased rates of birth defects in pregnant women” quoting one of our publications. This is an error: in the cited study there was only one birth defect among singleton babies and the mother had been treated with quinine. The “international agreement” on the use of artemisinin in pregnancy demanded by Caplan was reached by WHO in 2003. It would be disastrous if artemisinin-based combination therapy (ACT) was compromised by fears of liability based on groundless allegations. (excerpt)
Research Interests:
Considering the uncertainty of safety of anti-malarial drugs in pregnancy, efficacy studies are one of the few sources of clinical safety data. Complete safety evaluation is not usually incorporated in efficacy studies due to financial... more
Considering the uncertainty of safety of anti-malarial drugs in pregnancy, efficacy studies are one of the few sources of clinical safety data. Complete safety evaluation is not usually incorporated in efficacy studies due to financial and human resource constraints. This review reports the methods used for the assessment of safety of artemisinin-based and quinine-based treatments in efficacy studies in pregnancy. Methodology of assessment and reporting of safety in efficacy studies of artemisinin-based and quinine-based treatment in pregnancy was reviewed using seven databases and two clinical trial registries. The protocol was registered to PROSPERO (CRD42017054808). Of 48 eligible efficacy studies the method of estimation of gestational age was reported in only 32 studies (67%, 32/48) and ultrasound was used in 18 studies (38%, 18/48). Seventeen studies (35%, 17/48) reported parity, 9 (19%, 9/48) reported gravidity and 13 (27%, 13/48) reported both. Thirty-eight studies (79%, 38/...
Research Interests:
Perinatal depression is an important contributor to maternal morbidity and mortality worldwide. Migrant women, particularly those resettling within low- and middle-income settings, are at increased risk of perinatal depression due to... more
Perinatal depression is an important contributor to maternal morbidity and mortality worldwide. Migrant women, particularly those resettling within low- and middle-income settings, are at increased risk of perinatal depression due to multiple stressors experienced before, during and after migration. Evidence on migrant perinatal mental health to date has focused largely on women in high-income destination countries, leaving the voices of displaced women in low-income settings unheard. This study addresses the current evidence gap by exploring the experiences of migrant women living on the Thai-Myanmar border. In-depth interviews were conducted with pregnant and post-partum labour migrant and refugee women on the Thai-Myanmar border who had been diagnosed with severe depression. An interview guide covering women's current and past life experiences, social support and the impact of depression on social and occupational functioning was used as a prompt. Thematic analysis was used t...
Research Interests:
Amodiaquine plus artesunate is the recommended antimalarial treatment in many malaria-endemic countries. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published... more
Amodiaquine plus artesunate is the recommended antimalarial treatment in many malaria-endemic countries. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over three days. Plasma concentration-time profiles for both parent drug and metabolite were characterized using nonlinear mixed-effects modelling. Amodiaquine pharmacokinetics was adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethyla...
Research Interests:
Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals, and breast milk... more
Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals, and breast milk excretion and thus infant exposure are not known. Healthy G6PD normal breastfeeding women with previous P.vivax infection and their healthy G6PD normal infants between 28 days and 2 years old were enrolled. Mothers took primaquine 0.5 mg/kg/day for 14 days. Primaquine and carboxyprimaquine concentrations were measured in maternal venous plasma, capillary plasma, and breast milk samples and infant capillary plasma samples taken on days 0, 3, 7, and 13. In 20 mother-baby pairs primaquine concentrations were below measurement thresholds in all but one infant capillary plasma sample (that contained primaquine 2.6 ng/mL) and carboxyprimaquine was likewise unmeasurable in the majority of infant samples (maximum value 25.8 ng/mL). The estimated primaquine dose r...
Research Interests:
Perinatal depression is a significant contributor to maternal morbidity. Migrant women in resource-poor settings may be at increased risk, yet little research has been conducted in low-income and middle-income settings. This prospective... more
Perinatal depression is a significant contributor to maternal morbidity. Migrant women in resource-poor settings may be at increased risk, yet little research has been conducted in low-income and middle-income settings. This prospective cohort study of migrant women on the Thai-Myanmar border aims to establish prevalence of perinatal depression, identify risk factors for perinatal depression and examine associations with infant outcomes. Participating women are labour migrants and refugees living on the Thai-Myanmar border. A total of 568 women were recruited in their first trimester of pregnancy and are being followed up to 1-year postpartum. At baseline, women in our study had a median age of 25 years, the predominant ethnicity was Sgaw Karen (48.9%), agriculture was the main employment sector (39.2%) and educational attainment was low with a median of 4 years of education. In the first trimester of pregnancy, a quarter (25.8%; 95% CI 22.3 to 29.5) of all women were depressed as d...
Research Interests:
During pregnancy, immunoglobulin G (IgG) is transferred from the mother to the fetus, providing protection from disease in early infancy. Plasmodium falciparum infections may reduce maternofetal antibody transfer efficiency, but... more
During pregnancy, immunoglobulin G (IgG) is transferred from the mother to the fetus, providing protection from disease in early infancy. Plasmodium falciparum infections may reduce maternofetal antibody transfer efficiency, but mechanisms remain unclear. Mother-cord paired serum samples collected at delivery from Papua New Guinea (PNG) and the Thailand-Myanmar Border Area (TMBA) were tested for IgG1 and IgG3 to four P. falciparum antigens and measles antigen, as well as total serum IgG. Multivariable linear regression was conducted to assess the association of peripheral P. falciparum infection during pregnancy or placental P. falciparum infection assessed at delivery with maternofetal antibody transfer efficiency. Path analysis assessed the extent to which associations between P. falciparum infection and antibody transfer were mediated by gestational age at delivery or levels of maternal total serum IgG. Maternofetal antibody transfer efficiency of IgG1 and IgG3 was lower in PNG c...
Research Interests:
Research Interests:
Data on the cost effectiveness of hepatitis B virus (HBV) screening and vaccination strategies for prevention of vertical transmission of HBV in resource limited settings is sparse. A decision tree model of HBV prevention strategies... more
Data on the cost effectiveness of hepatitis B virus (HBV) screening and vaccination strategies for prevention of vertical transmission of HBV in resource limited settings is sparse. A decision tree model of HBV prevention strategies utilised data from a cohort of 7071 pregnant women on the Thailand-Myanmar border using a provider perspective. All options included universal HBV vaccination for newborns in three strategies: (1) universal vaccination alone; (2) universal vaccination with screening of women during antenatal visits with rapid diagnostic test (RDT) plus HBV immune globulin (HBIG) administration to newborns of HBV surface antigen positive women; and (3) universal vaccination with screening of women during antenatal visits plus HBIG administration to newborns of women testing HBV e antigen positive by confirmatory test. At the time of the study, the HBIG after confirmatory test strategy was used. The costs in United States Dollars (US$), infections averted and incremental c...
Research Interests:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder in humans and appears to be protective against falciparum severe malaria. Controversially, it is also thought that Plasmodium vivax has driven the... more
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder in humans and appears to be protective against falciparum severe malaria. Controversially, it is also thought that Plasmodium vivax has driven the recent selection of G6PD alleles. We use an experimental approach to determine whether G6PD-MahidolG487A variant, a widespread cause of severe G6PD deficiency in Southeast Asia, provides a barrier against vivax malaria. Our results show that the immature reticulocytes (CD71+) targeted by P. vivax invasion are enzymatically normal even in hemizygous G6PD-Mahidol G487A mutants; thus allowing the normal growth, development and high parasite density in severely deficient samples.
Research Interests:
Malaria in pregnancy is preventable and contributes significantly to the estimated 5.5 million stillbirths and neonatal deaths that occur annually. The contribution of malaria in pregnancy in areas of low transmission has not been... more
Malaria in pregnancy is preventable and contributes significantly to the estimated 5.5 million stillbirths and neonatal deaths that occur annually. The contribution of malaria in pregnancy in areas of low transmission has not been quantified, and the roles of maternal anaemia, small-for-gestational-age status, and preterm birth in mediating the effect of malaria in pregnancy on stillbirth and neonatal death are poorly elucidated. We analysed observational data routinely collected at antenatal clinics on the Thai-Myanmar border (1986-2015). We used Cox regression and sequential mediation analysis to determine the effect of falciparum and vivax malaria in pregnancy on antepartum (death in utero) and intrapartum (death during labour) stillbirth and neonatal mortality as well as mediation through maternal anaemia, preterm birth, and small-for-gestational-age status. Of 61,836 women, 9350 (15%) had malaria in pregnancy, and 526 (0.8%) had stillbirths. In a sub-set of 9090 live born singl...
Research Interests:
This study aims to identify risk factors and the neurodevelopmental impact of neonatal hyperbilirubinemia in a limited-resource setting among a refugee and migrant population residing along the Thai-Myanmar border, an area with a high... more
This study aims to identify risk factors and the neurodevelopmental impact of neonatal hyperbilirubinemia in a limited-resource setting among a refugee and migrant population residing along the Thai-Myanmar border, an area with a high prevalence of glucose-6-phosphate dehydrogenase-deficiency. This is an analytic, observational, prospective birth cohort study including all infants of estimated gestational age equal to or greater than 28 weeks from mothers who followed antenatal care in the Shoklo Malaria Research Unit clinics. At birth, a series of clinical exams and laboratory investigations on cord blood will be carried out. Serum bilirubin will be measured in all infants during their first week of life. All the infants of the cohort will be clinically followed until the age of one year, including monitoring of their neurodevelopment. The strength of this study is the prospective cohort design. It will allow us to collect information about the pregnancy and detect all infants with...
Research Interests:
Research Interests: Evolutionary Biology, Genetics, Population Genetics, Biology, Malaria, and 15 moreThailand, Medicine, Population, Humans, Mutation, Animals, Drug Resistance, Single Nucleotide Polymorphism, Plasmodium falciparum, Antimalarials, Protozoan Proteins, Mutation Rate, Biochemistry and cell biology, Gene frequency, and Malaria Falciparum
Research Interests:
Research Interests: Environmental Health, Malaria, Adolescent, Medicine, Refugees, and 15 moreMyanmar, Population, Humans, Female, Mothers, Jaundice, Haemolysis, Middle Aged, Adult, Maternal Behavior, Health surveys, Cross Sectional Studies, Menthol, Glucosephosphate dehydrogenase deficiency, and Paediatrics and reproductive medicine
Research Interests:
During pregnancy a variety of immunological changes occur to accommodate the fetus. It is unknown whether these changes continue to affect humoral immunity postpartum or how quickly they resolve. IgG levels were measured to P. falciparum... more
During pregnancy a variety of immunological changes occur to accommodate the fetus. It is unknown whether these changes continue to affect humoral immunity postpartum or how quickly they resolve. IgG levels were measured to P. falciparum and P. vivax antigens in 201 postpartum and 201 controls over 12 weeks. Linear mixed-effects models assessed antibody maintenance over time and the effect of microscopically confirmed Plasmodium spp. infection on antibody levels, and whether this was different in postpartum women compared with control women. Postpartum women had reduced Plasmodium spp. antibody levels compared to controls at baseline. Over 12 weeks, mean antibody levels in postpartum women increased to levels observed in control women. Microscopically confirmed P. falciparum and P. vivax infections during follow-up were associated with an increase in species-specific antibodies with similar magnitudes of boosting observed in postpartum and control women. Antibodies specific for preg...
Research Interests:
Research Interests:
Research Interests:
Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs,... more
Doxycycline is highly effective, inexpensive with a broad therapeutic spectrum and exceptional bioavailability. However these benefits have been overshadowed by its classification alongside the tetracyclines - class D drugs, contraindicated in pregnancy and in children under 8 years of age. Doxycycline-treatable diseases are emerging as leading causes of undifferentiated febrile illness in Southeast Asia. For example scrub typhus and murine typhus have an unusually severe impact on pregnancy outcomes, and current mortality rates for scrub typhus reach 12-13% in India and Thailand. The emerging evidence for these important doxycycline-treatable diseases prompted us to revisit doxycycline usage in pregnancy and childhood. Areas Covered: A systematic review of the available literature on doxycycline use in pregnant women and children revealed a safety profile of doxycycline that differed significantly from that of tetracycline; no correlation between the use of doxycycline and teratoge...
Research Interests:
The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai... more
The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai border districts. The children were evaluated for vaccination completion and timing, for six different vaccines: Bacille Calmette-Guerin (BCG); Oral Polio vaccine (OPV); Hepatitis B vaccine (HepB); Diphtheria, Pertussis and Tetanus vaccine (DTP); Measles Containing Vaccine or Measles, Mumps and Rubella vaccine (MMR); Tetanus and Diphtheria containing vaccine (Td). Vaccine coverage proportions for BCG, OPV3, DTP3, HepB3 and measles containing vaccine were 92.3, 85.3, 63.8, 72.2, and 90.9 % respectively. Most children were able to receive vaccines in a time appropriate manner. School-based immunization programs offer a suitable vaccine delivery mechanism for hard-to-reach populations. However, these data suggest overall low vaccine coverage in migrant...
Research Interests:
Research Interests:
Research Interests: Thailand, Adolescent, Medicine, Humans, Antimicrobial Stewardship, and 15 moreEscherichia coli, Female, Male, Antibiotics, Aged, Middle Aged, Outpatients, Adult, Public health systems and services research, Retrospective Studies, Reproducibility of Results, Sensitivity and Specificity, Point of Care Testing, Beta Lactamases, and dysuria
Page 1. 8 Branum GD, Tyson GS, Branum MA, Meyers WC. Hepatic abscess: changes in etiology, diagnosis, and management. ... Photoallergy to quinine Mathieu Nacher MD PhD 1 Rose McGready MD PhD 2 Carit Lermoo2 JateeWichiponpiboon2 Franc-ois... more
Page 1. 8 Branum GD, Tyson GS, Branum MA, Meyers WC. Hepatic abscess: changes in etiology, diagnosis, and management. ... Photoallergy to quinine Mathieu Nacher MD PhD 1 Rose McGready MD PhD 2 Carit Lermoo2 JateeWichiponpiboon2 Franc-ois Nosten MD PhD 2 ...
Research Interests:
Malaria is increasing worldwide due to the emergence and spread of drug resistant strains. This poses major health and economic problems for the population living in endemic areas and increases the risk of infections in travelers. The... more
Malaria is increasing worldwide due to the emergence and spread of drug resistant strains. This poses major health and economic problems for the population living in endemic areas and increases the risk of infections in travelers. The diagnosis of malaria relies on a biological proof of infection by microscopy or with a rapid test. The treatment must be initiated without delay preferably with an artemisinin containing regimen. Uncomplicated malaria can be treated with oral drugs while severe infections will be hospitalized and treated with injectables. Special attention will be given to the most susceptible groups: children and pregnant women.
Research Interests: Malaria, Medicine, Plasmodium, Travel, Pregnancy, and 15 moreHumans, Female, Animals, Drug Resistance, Chemoprevention, Infant, Clinical Sciences, Public health systems and services research, Antimalarials, Pregnant Women, Combination drug therapy, Artemisinin, Regimen, Child preschool, and Combination Therapy
Research Interests: Malaria, Humans, Hospitalization, Female, Male, and 15 moreIncidence, Aged, Early Detection, Adult, Cross Section, Antimalarials, Combination drug therapy, Diagnostic Test, Hospital Mortality, Cross Sectional Studies, Early Diagnosis, Artesunate, Confidence Interval, Combination Therapy, and Malaria Falciparum
Research Interests:
Research Interests: Obstetrics, Africa, Malaria, Medicine, Pregnancy, and 7 moreHumans, Female, Antimalarials, Wq, WC, Malaria Falciparum, and Medical and Health Sciences
Most evidence on the association between malaria in pregnancy and adverse pregnancy outcomes focuses on falciparum malaria detected at birth. We assessed the association between the number and timing of falciparum and vivax malaria... more
Most evidence on the association between malaria in pregnancy and adverse pregnancy outcomes focuses on falciparum malaria detected at birth. We assessed the association between the number and timing of falciparum and vivax malaria episodes during pregnancy on small-for-gestational-age (SGA) and preterm birth. We analysed observational data collected from antenatal clinics on the Thailand-Myanmar border (1986-2015). We assessed the effects of the total number of malaria episodes in pregnancy on SGA and the effects of malaria in pregnancy on SGA, very preterm birth, and late preterm birth, by the gestational age at malaria detection and treatment using logistic regression models with time-dependent malaria variables (monthly intervals). World Health Organisation definitions of very preterm birth (≥28 and <32 weeks) and late preterm birth (≥32 and <37 weeks) and international SGA standards were used. Of 50,060 pregnant women followed, 8221 (16%) had malaria during their pregnanc...
Research Interests:
development of therapeutic methods that are better than empiric antacid therapy for specific lesions may demand modification of our conclusions"." Finally, the paper chosen to support the authors' views reported a mortality... more
development of therapeutic methods that are better than empiric antacid therapy for specific lesions may demand modification of our conclusions"." Finally, the paper chosen to support the authors' views reported a mortality of 11% in a relatively young group of patients which was probably high then but has to be regarded as totally unacceptable now. M OKelly, MB BS Surgical Registrar Department of Surgery °L Morris, MB ChB, FRCS, MD, PhD, FRACS Professor University Department of Surgery (UNSW) The St George Hospital Belgrave Street, Kogarah, NSW 2217
Research Interests:
Research Interests:
Laos has the highest maternal mortality ratio in mainland Southeast Asia but there has been little research conducted with pregnant women. We aim to discuss ethical challenges in enrolling pregnant women in research as a part of large... more
Laos has the highest maternal mortality ratio in mainland Southeast Asia but there has been little research conducted with pregnant women. We aim to discuss ethical challenges in enrolling pregnant women in research as a part of large pregnancy cohort study in Laos. From 2013 to 2015, a prospective cohort study was conducted with 1000 pregnant women in a rural area of Vientiane, Laos, to determine whether fevers were associated with maternal morbidity and small for gestational age. Incidence of fever was 10% and incidence of small for gestational age was 12%. Level of education, cultural norms about family decision-making, and misconceptions about healthcare during pregnancy were three common issues encountered in enrolling pregnant women to this study. Only 47% of recruited women had completed primary school with no further education, which could affect the decisions women make to participate and remain in the study. Family decision-making is common in Laos; in some cases, we could...
Research Interests:
Research Interests:
Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from... more
Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. We included 61 studies done between...
Research Interests:
... BMJ 1956; i: 556. PubMed. 3 Mohazab HR, Spigos DG, Anciaux D, Nadimapalli V. Fetus papyraceus. Am J Roentgenology 1993; 160: 663-664. PubMed. 4 Livnat EJ, Burd L, Cadkin A, Keh P, Ward AB. Fetus papyreceus in twin pregnancy. Obstet... more
... BMJ 1956; i: 556. PubMed. 3 Mohazab HR, Spigos DG, Anciaux D, Nadimapalli V. Fetus papyraceus. Am J Roentgenology 1993; 160: 663-664. PubMed. 4 Livnat EJ, Burd L, Cadkin A, Keh P, Ward AB. Fetus papyreceus in twin pregnancy. Obstet Gynecol 1978; 51: 41-45. ...
Research Interests: Buddhism, Thailand, Adolescent, Medicine, Pregnancy, and 8 moreHumans, Female, Male, Lancet, Adult, Fetal death, The Lancet, and Medical and Health Sciences
While on holiday in France from my work in Thailand, I thought I had a left upper molar infection. I wished I’d stocked up on some antibiotics (far too easy to purchase in resource poor settings, where they can least afford problems with... more
While on holiday in France from my work in Thailand, I thought I had a left upper molar infection. I wished I’d stocked up on some antibiotics (far too easy to purchase in resource poor settings, where they can least afford problems with drug resistance). The next day I diagnosed left maxillary sinusitis. The following day the supposed sinusitis was now on the left side of my nose as a 1.5 cm, red, slightly raised, circular lesion. In Thailand superficial migrating skin lesions are caused by helminths. The commonest is cutaneous larva migrans, where humans are accidental …
Research Interests:
Background Toxoplasma gondii is a major problem for the sheep industry as it may cause reproduction problems. The importance of T. gondii in Norwegian goat herds is uncertain, but outbreaks of toxoplasmosis in dairy goat farms have been... more
Background Toxoplasma gondii is a major problem for the sheep industry as it may cause reproduction problems. The importance of T. gondii in Norwegian goat herds is uncertain, but outbreaks of toxoplasmosis in dairy goat farms have been recorded. The aim of this study was to describe the prevalence of T. gondii infection in Norwegian dairy goats by using serology. Findings Goat serum originally collected as part of two nationwide surveillance and control programmes between 2002 and 2008 were examined for T. gondii antibodies by using direct agglutination test. In total, 55 of 73 herds (75%) had one or more serologically positive animals, while 377 of 2188 (17%) of the individual samples tested positive for T. gondii antibodies. Conclusions This is the first prevalence study of T. gondii infection in Norwegian goats. The results show that Norwegian goat herds are commonly exposed to T. gondii. Nevertheless, the majority of goat herds have a low prevalence of antibody positive animals...
Research Interests:
Artemisinins, the most effective antimalarials available, are not recommended for falciparum malaria during the first trimester of pregnancy because of safety concerns. Therefore, quinine is used despite its poor effectiveness. Assessing... more
Artemisinins, the most effective antimalarials available, are not recommended for falciparum malaria during the first trimester of pregnancy because of safety concerns. Therefore, quinine is used despite its poor effectiveness. Assessing artemisinin safety requires weighing the risks of malaria and its treatment. We aimed to assess the effect of first-trimester malaria and artemisinin treatment on miscarriage and major congenital malformations. In this observational study, we assessed data from antenatal clinics on the Thai-Myanmar border between Jan 1, 1994, and Dec 31, 2013. We included women who presented to antenatal clinics during their first trimester with a viable fetus. Women were screened for malaria, and data on malaria, antimalarial treatment, and birth outcomes were collected. The relationship between artemisinin treatments (artesunate, dihydroartemisinin, or artemether) and miscarriage or malformation was assessed using Cox regression with left-truncation and time-varyi...
Research Interests:
Research Interests:
Neurological examination, including visual fixation and tracking of a target, is routinely performed in the Shoklo Malaria Research Unit postnatal care units on the Thailand-Myanmar border. We aimed to evaluate a simple visual newborn... more
Neurological examination, including visual fixation and tracking of a target, is routinely performed in the Shoklo Malaria Research Unit postnatal care units on the Thailand-Myanmar border. We aimed to evaluate a simple visual newborn test developed in Italy and performed by non-specialized personnel working in neonatal care units. An intensive training of local health staff in Thailand was conducted prior to performing assessments at 24, 48 and 72 hours of life in healthy, low-risk term singletons. The 48 and 72 hours results were then compared to values obtained to those from Italy. Parents and staff administering the test reported on acceptability. One hundred and seventy nine newborns, between June 2011 and October 2012, participated in the study. The test was rapidly completed if the infant remained in an optimal behavioral stage (7 ± 2 minutes) but the test duration increased significantly (12 ± 4 minutes, p < 0.001) if its behavior changed. Infants were able to fix a targe...
Research Interests: Thailand, Multidisciplinary, Italy, Myanmar, Humans, and 6 moreFemale, Male, Color Vision, PLoS one, Newborn Infant, and Observer Variation
Deployment of mefloquine-artesunate (MAS3) on the Thailand-Myanmar border has led to a sustained reduction in falciparum malaria, although antimalarial efficacy has declined substantially in recent years. The role of P. falciparum K13... more
Deployment of mefloquine-artesunate (MAS3) on the Thailand-Myanmar border has led to a sustained reduction in falciparum malaria, although antimalarial efficacy has declined substantially in recent years. The role of P. falciparum K13 mutations (a marker of artemisinin resistance) in reducing treatment efficacy remains controversial. Between 2003 and 2013, we studied the efficacy of MAS3 in 1005 patients with uncomplicated P. falciparum malaria in relation to molecular markers of resistance. PCR-adjusted cure rates declined from 100% in 2003 to 81.1% in 2013 as the proportions of isolates with multiple Pfmdr1 copies doubled from 32.4% to 64.7% and those with K13 mutations increased from 6.7% to 83.4%. K13 mutations conferring moderate artemisinin resistance (notably E252Q) predominated initially but these were later overtaken by propeller mutations associated with slower parasite clearance (notably C580Y). Infections with both multiple Pfmdr1 copy number and a K13 propeller mutat...
Research Interests:
During pregnancy immunolglobulin G (IgG) antibodies are transferred from mother to neonate across the placenta. Studies in high transmission areas have shown transfer of P. falciparum-specific IgG, but the extent and factors influencing... more
During pregnancy immunolglobulin G (IgG) antibodies are transferred from mother to neonate across the placenta. Studies in high transmission areas have shown transfer of P. falciparum-specific IgG, but the extent and factors influencing maternal-foetal transfer in low transmission areas co-endemic for both P. falciparum and P. vivax are unknown. Pregnant women were screened weekly for Plasmodium infection. Mother-neonate paired serum samples at delivery were tested for IgG to antigens from P. falciparum, P. vivax and other infectious diseases. Antibodies to malarial and non-malarial antigens were highly correlated between maternal and neonatal samples (median [range] spearman ρ = 0.78 [0.57-0.93]), although Plasmodium spp. antibodies tended to be lower in neonates than mothers. Estimated gestational age at last P. falciparum infection, but not P. vivax infection, was positively associated with antibody levels in the neonate (P. falciparum merozoite, spearman ρ median [range] 0.42 [0...