65 research outputs found
Associations of maternal iron deficiency with malaria infection in a cohort of pregnant Papua New Guinean women
Background: Iron deficiency (ID) is common in malaria-endemic settings. Intermittent preventative treatment of malaria in pregnancy (IPTp) and iron supplementation are core components of antenatal care in endemic regions to prevent adverse pregnancy outcomes. ID has been associated with reduced risk of malaria infection, and correspondingly, iron supplementation with increased risk of malaria infection, in some studies.
Methods: A secondary analysis was conducted amongst 1888 pregnant women enrolled in a malaria prevention trial in Papua New Guinea. Maternal ID was defined as inflammation-corrected plasma ferritin levels < 15 ÎĽg/L at antenatal enrolment. Malaria burden (Plasmodium falciparum, Plasmodium vivax) was determined by light microscopy, polymerase chain reaction, and placental histology. Multiple logistic and linear regression analyses explored the relationship of ID or ferritin levels with indicators of malaria infection. Models were fitted with interaction terms to assess for modification of iron-malaria relationships by gravidity or treatment arm.
Results: Two-thirds (n = 1226) and 13.7% (n = 258) of women had ID and peripheral parasitaemia, respectively, at antenatal enrolment (median gestational age: 22 weeks), and 18.7% (120/1,356) had evidence of malaria infection on placental histology. Overall, ID was associated with reduced odds of peripheral parasitaemia at enrolment (adjusted odds ratio [aOR] 0.50; 95% confidence interval [95% CI] 0.38, 0.66, P < 0.001); peripheral parasitaemia at delivery (aOR 0.68, 95% CI 0.46, 1.00; P = 0.050); and past placental infection (aOR 0.35, 95% CI 0.24, 0.50; P < 0.001). Corresponding increases in the odds of infection were observed with two-fold increases in ferritin levels. There was effect modification of iron-malaria relationships by gravidity. At delivery, ID was associated with reduced odds of peripheral parasitaemia amongst primigravid (AOR 0.44, 95% CI 0.25, 0.76; P = 0.003), but not multigravid women (AOR 1.12, 95% CI 0.61, 2.05; P = 0.720). A two-fold increase in ferritin associated with increased odds of placental blood infection (1.44, 95% CI 1.06, 1.96; P = 0.019) and active placental infection on histology amongst primigravid women only (1.24, 95% CI 1.00, 1.54; P = 0.052).
Conclusions: Low maternal ferritin at first antenatal visit was associated with a lower risk of malaria infection during pregnancy, most notably in primigravid women. The mechanisms by which maternal iron stores influence susceptibility to infection with Plasmodium species require further investigation
Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea
BACKGROUND: Fetal growth restriction (FGR) is associated with
increased infant mortality rates and ill-health in adulthood.
Evaluation of fetal growth requires ultrasound. As a result,
ultrasound-assisted evaluations of causes of FGR in
malaria-endemic developing countries are rare. We aimed to
determine factors associated with indicators of abnormal fetal
growth in rural lowland Papua New Guinea (PNG). METHODS: Weights
and growth of 671 ultrasound-dated singleton pregnancies (<25
gestational weeks) were prospectively monitored using estimated
fetal weights and birthweights. Maternal nutritional status and
haemoglobin levels were assessed at enrolment, and participants
were screened for malaria on several occasions. FGR was
suspected upon detection of an estimated fetal weight or
birthweight <10(th) centile (small-for-gestational age)
and/or low fetal weight gain, defined as a change in weight
z-score in the first quartile. Factors associated with fetal
weight and fetal weight gain were additionally assessed by
evaluating differences in weight z-scores and change in weight
z-scores. Log-binomial and linear mixed effect models were used
to determine factors associated with indicators of FGR. RESULTS:
SGA and low weight gain were detected in 48.3% and 37.0% of
pregnancies, respectively. Of participants, 13.8%, 21.2%, and
22.8% had a low mid-upper arm circumference (MUAC, <22 cms),
short stature (<150 cms) and anaemia (haemoglobin <90 g/L)
at first antenatal visit. 24.0% (161/671) of women had at least
one malaria infection detected in peripheral blood. A low MUAC
(adjusted risk ratio [aRR] 1.51, 95% CI 1.29, 1.76, P <
0.001), short stature (aRR 1.27, 95% CI 1.04, 1.55, P = 0.009),
and anaemia (aRR 1.27, 95% CI 1.06, 1.51, P = 0.009) were
associated with SGA, and a low body mass index was associated
with low fetal weight gain (aRR 2.10, 95% CI 1.62, 2.71, P <
0.001). Additionally, recent receipt of intermittent preventive
treatment in pregnancy was associated with increased weight
z-scores, and anaemia with reduced change in weight z-scores.
Malaria infection was associated with SGA on crude but not
adjusted analyses (aRR 1.13, 95% CI 0.95, 1.34, P = 0.172).
CONCLUSION: Macronutrient undernutrition and anaemia increased
the risk of FGR. Antenatal nutritional interventions and malaria
prevention could improve fetal growth in PNG
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 <11.0 g/dL) in a longitudinal cohort of
2,700 pregnant women residing in rural lowland Papua New Guinea
(PNG) from November 2009 until February 2013. Chewing habits and
participant characteristics were evaluated at first antenatal
visit and women were followed until delivery. RESULTS: 83.3%
[2249/2700] of pregnant women used AN, and most chewed on a
daily basis (86.2% [1939/2249]. Smoking and alcohol use was
reported by 18.9% (511/2700) and 5.0% (135/2688) of women,
respectively. AN use was not associated with pregnancy loss or
congenital abnormalities amongst women with a known pregnancy
outcome (n = 2215). Analysis of 1769 birthweights did not
demonstrate an association between AN and LBW (chewers: 13.7%
[200/1459] vs. non-chewers: 14.5% [45/310], P = 0.87) or reduced
mean birthweight (2957 g vs. 2966 g; P = 0.76). Women using AN
were more likely to be anaemic (haemoglobin <11 g/dL) at
delivery (75.2% [998/1314] vs. 63.9% [182/285], adjusted odds
ratio [95% CI]: 1.67 [1.27, 2.20], P < 0.001). Chewers more
commonly had male babies than non-chewers (46.1% [670/1455] vs.
39.8% [123/309], P = 0.045). CONCLUSIONS: AN chewing may
contribute to anaemia. Although not associated with other
adverse pregnancy outcome in this cohort gestational AN use
should be discouraged, given the potential adverse effects on
haemoglobin and well-established long-term health risk including
oral cancer. Future research evaluating the potential
association of AN use and anaemia may be warranted. TRIAL
REGISTRATION: ClinicalTrials.gov NCT01136850 (06 April 2010)
Risk factors and pregnancy outcomes associated with placental malaria in a prospective cohort of Papua New Guinean women
BACKGROUND: Plasmodium falciparum in pregnancy results in
substantial poor health outcomes for both mother and child,
particularly in young, primigravid mothers who are at greatest
risk of placental malaria (PM) infection. Complications of PM
include maternal anaemia, low birth weight and preterm delivery,
which contribute to maternal and infant morbidity and mortality
in coastal Papua New Guinea (PNG). METHODS: Placental biopsies
were examined from 1451 pregnant women who were enrolled in a
malaria prevention study at 14-26 weeks gestation. Clinical and
demographic information were collected at first antenatal clinic
visits and women were followed until delivery. Placental
biopsies were collected and examined for PM using histology. The
presence of infected erythrocytes and/or the malaria pigment in
monocytes or fibrin was used to determine the type of placental
infection. RESULTS: Of 1451 placentas examined, PM infection was
detected in 269 (18.5%), of which 54 (3.7%) were acute, 55
(3.8%) chronic, and 160 (11.0%) were past infections. Risk
factors for PM included residing in rural areas (adjusted odds
ratio (AOR) 3.65, 95% CI 1.76-7.51; p </= 0.001), being
primigravid (AOR 2.45, 95% CI 1.26-4.77; p = 0.008) and having
symptomatic malaria during pregnancy (AOR 2.05, 95% CI
1.16-3.62; p = 0.013). After adjustment for covariates, compared
to uninfected women, acute infections (AOR 1.97, 95% CI
0.98-3.95; p = 0.056) were associated with low birth weight
babies, whereas chronic infections were associated with preterm
delivery (AOR 3.92, 95% CI 1.64-9.38; p = 0.002) and anaemia
(AOR 2.22, 95% CI 1.02-4.84; p = 0.045). CONCLUSIONS: Among
pregnant PNG women receiving at least one dose of intermittent
preventive treatment in pregnancy and using insecticide-treated
bed nets, active PM infections were associated with adverse
outcomes. Improved malaria prevention is required to optimize
pregnancy outcomes
The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study
Abstract: Background: Iron deficiency (ID) has been associated with adverse pregnancy outcomes, maternal anaemia, and altered susceptibility to infection. In Papua New Guinea (PNG), monthly treatment with sulphadoxine-pyrimethamine plus azithromycin (SPAZ) prevented low birthweight (LBW; <2500 g) through a combination of anti-malarial and non-malarial effects when compared to a single treatment with SP plus chloroquine (SPCQ) at first antenatal visit. We assessed the relationship between ID and adverse birth outcomes in women receiving SPAZ or SPCQ, and the mediating effects of malaria infection and haemoglobin levels during pregnancy. Methods: Plasma ferritin levels measured at antenatal enrolment in a cohort of 1892 women were adjusted for concomitant inflammation using C-reactive protein and α-1-acid glycoprotein. Associations of ID (defined as ferritin <15 μg/L) or ferritin levels with birth outcomes (birthweight, LBW, preterm birth, small-for-gestational-age birthweight [SGA]) were determined using linear or logistic regression analysis, as appropriate. Mediation analysis assessed the degree of mediation of ID-birth outcome relationships by malaria infection or haemoglobin levels. Results: At first antenatal visit (median gestational age, 22 weeks), 1256 women (66.4%) had ID. Overall, ID or ferritin levels at first antenatal visit were not associated with birth outcomes. There was effect modification by treatment arm. Amongst SPCQ recipients, ID was associated with a 81-g higher mean birthweight (95% confidence interval [CI] 10, 152; P = 0.025), and a twofold increase in ferritin levels was associated with increased odds of SGA (adjusted odds ratio [aOR] 1.25; 95% CI 1.06, 1.46; P = 0.007). By contrast, amongst SPAZ recipients, a twofold increase in ferritin was associated with reduced odds of LBW (aOR 0.80; 95% CI 0.67, 0.94; P = 0.009). Mediation analyses suggested that malaria infection or haemoglobin levels during pregnancy do not substantially mediate the association of ID with birth outcomes amongst SPCQ recipients. Conclusions: Improved antenatal iron stores do not confer a benefit for the prevention of adverse birth outcomes in the context of malaria chemoprevention strategies that lack the non-malarial properties of monthly SPAZ. Research to determine the mechanisms by which ID protects from suboptimal foetal growth is needed to guide the design of new malaria prevention strategies and to inform iron supplementation policy in malaria-endemic settings. Trial registration: ClinicalTrials.gov NCT01136850
Microscopic and submicroscopic Plasmodium falciparum infection, maternal anaemia and adverse pregnancy outcomes in Papua New Guinea: a cohort study.
Infection during pregnancy with Plasmodium falciparum is associated with maternal anaemia and adverse birth outcomes including low birth weight (LBW). Studies using polymerase chain reaction (PCR) techniques indicate that at least half of all infections in maternal venous blood are missed by light microscopy or rapid diagnostic tests. The impact of these subpatent infections on maternal and birth outcomes remains unclear. In a cohort of women co-enrolled in a clinical trial of intermittent treatment with sulfadoxine-pyrimethamine (SP) plus azithromycin for the prevention of LBW (< 2500 g) in Papua New Guinea (PNG), P. falciparum infection status at antenatal enrolment and delivery was assessed by routine light microscopy and real-time quantitative PCR. The impact of infection status at enrolment and delivery on adverse birth outcomes and maternal haemoglobin at delivery was assessed using logistic and linear regression models adjusting for potential confounders. Together with insecticide-treated bed nets, women had received up to 3 monthly intermittent preventive treatments with SP plus azithromycin or a single clearance treatment with SP plus chloroquine. A total of 9.8% (214/2190) of women had P. falciparum (mono-infection or mixed infection with Plasmodium vivax) detected in venous blood at antenatal enrolment at 14-26 weeks' gestation. 4.7% of women had microscopic, and 5.1% submicroscopic P. falciparum infection. At delivery (n = 1936), 1.5% and 2.0% of women had submicroscopic and microscopic P. falciparum detected in peripheral blood, respectively. Submicroscopic P. falciparum infections at enrolment or at delivery in peripheral or placental blood were not associated with maternal anaemia or adverse birth outcomes such as LBW. Microscopic P. falciparum infection at antenatal enrolment was associated with anaemia at delivery (adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI] 1.09, 3.67; P = 0.025). Peripheral microscopic P. falciparum infection at delivery was associated with LBW (aOR 2.75, 95% CI 1.27; 5.94, P = 0.010) and preterm birth (aOR 6.58, 95% CI 2.46, 17.62; P < 0.001). A substantial proportion of P. falciparum infections in pregnant women in PNG were submicroscopic. Microscopic, but not submicroscopic, infections were associated with adverse outcomes in women receiving malaria preventive treatment and insecticide-treated bed nets. Current malaria prevention policies that combine insecticide-treated bed nets, intermittent preventive treatment and prompt treatment of symptomatic infections appear to be appropriate for the management of malaria in pregnancy in settings like PNG
The epidemiology of Plasmodium falciparum and Plasmodium vivax in East Sepik Province, Papua New Guinea, pre- and post-implementation of national malaria control efforts
Background
In the past decade, national malaria control efforts in Papua New Guinea (PNG) have received renewed support, facilitating nationwide distribution of free long-lasting insecticidal nets (LLINs), as well as improvements in access to parasite-confirmed diagnosis and effective artemisinin-combination therapy in 2011–2012.
Methods
To study the effects of these intensified control efforts on the epidemiology and transmission of Plasmodium falciparum and Plasmodium vivax infections and investigate risk factors at the individual and household level, two cross-sectional surveys were conducted in the East Sepik Province of PNG; one in 2005, before the scale-up of national campaigns and one in late 2012-early 2013, after 2 rounds of LLIN distribution (2008 and 2011–2012). Differences between studies were investigated using Chi square (χ2), Fischer’s exact tests and Student’s t-test. Multivariable logistic regression models were built to investigate factors associated with infection at the individual and household level.
Results
The prevalence of P. falciparum and P. vivax in surveyed communities decreased from 55% (2005) to 9% (2013) and 36% to 6%, respectively. The mean multiplicity of infection (MOI) decreased from 1.8 to 1.6 for P. falciparum (p = 0.08) and from 2.2 to 1.4 for P. vivax (p  50% of household members with Plasmodium infection).
Conclusion
After the scale-up of malaria control interventions in PNG between 2008 and 2012, there was a substantial reduction in P. falciparum and P. vivax infection rates in the studies villages in East Sepik Province. Understanding the extent of local heterogeneity in malaria transmission and the driving factors is critical to identify and implement targeted control strategies to ensure the ongoing success of malaria control in PNG and inform the development of tools required to achieve elimination. In household-based interventions, diagnostics with a sensitivity similar to (expert) microscopy could be used to identify and target high rate households
Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells
In persistent infections that are accompanied by chronic immune activation, such as human immunodeficiency virus, hepatitis C virus, and malaria, there is an increased frequency of a phenotypically distinct subset of memory B cells lacking the classic memory marker CD27 and showing a reduced capacity to produce antibodies. However, critical knowledge gaps remain on specific B cell changes and immune adaptation in chronic infections. We hypothesized that expansion of atypical memory B cells (aMBCs) and reduction of activated peripheral marginal zone (MZ)-like B cells in constantly exposed individuals might be accompanied by phenotypic changes that would confer a tolerogenic profile, helping to establish tolerance to infections. To better understand malaria-associated phenotypic abnormalities on B cells, we analyzed peripheral blood mononuclear cells from 55 pregnant women living in a malaria-endemic area of Papua Nueva Guinea and 9 Spanish malaria-naĂŻve individuals using four 11-color flow cytometry panels. We assessed the expression of markers of B cell specificity (IgG and IgM), activation (CD40, CD80, CD86, b220, TACI, and CD150), inhibition (PD1, CD95, and CD71), and migration (CCR3, CXCR3, and CD62l). We found higher frequencies of active and resting aMBC and marked reduction of MZ-like B cells, although changes in absolute cell counts could not be assessed. Highly exposed women had higher PD1+-, CD95+-, CD40+-, CD71+-, and CD80+-activated aMBC frequencies than non-exposed subjects. Malaria exposure increased frequencies of b220 and proapoptotic markers PD1 and CD95, and decreased expression of the activation marker TACI on MZ-like B cells. The increased frequencies of inhibitory and apoptotic markers on activated aMBCs and MZ-like B cells in malaria-exposed adults suggest an immune-homeostatic mechanism for maintaining B cell development and function while simultaneously downregulating hyperreactive B cells. This mechanism would keep the B cell activation threshold high enough to control infection but impaired enough to tolerate it, preventing systemic inflammation
Microsatellite Genotyping of Plasmodium vivax Isolates from Pregnant Women in Four Malaria Endemic Countries
Plasmodium vivax is the most widely distributed human parasite
and the main cause of human malaria outside the African
continent. However, the knowledge about the genetic variability
of P. vivax is limited when compared to the information
available for P. falciparum. We present the results of a study
aimed at characterizing the genetic structure of P. vivax
populations obtained from pregnant women from different malaria
endemic settings. Between June 2008 and October 2011 nearly 2000
pregnant women were recruited during routine antenatal care at
each site and followed up until delivery. A capillary blood
sample from the study participants was collected for genotyping
at different time points. Seven P. vivax microsatellite markers
were used for genotypic characterization on a total of 229 P.
vivax isolates obtained from Brazil, Colombia, India and Papua
New Guinea. In each population, the number of alleles per locus,
the expected heterozygosity and the levels of multilocus linkage
disequilibrium were assessed. The extent of genetic
differentiation among populations was also estimated. Six
microsatellite loci on 137 P. falciparum isolates from three
countries were screened for comparison. The mean value of
expected heterozygosity per country ranged from 0.839 to 0.874
for P. vivax and from 0.578 to 0.758 for P. falciparum. P. vivax
populations were more diverse than those of P. falciparum. In
some of the studied countries, the diversity of P. vivax
population was very high compared to the respective level of
endemicity. The level of inter-population differentiation was
moderate to high in all P. vivax and P. falciparum populations
studied
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