Pregnancy and malaria: the perfect storm

Purpose of review Malaria in pregnancy continues to exert a toll on pregnant women and their offspring. Recent findings The burden of Plasmodium falciparum infection is especially large in Africa, and new data show lasting effects of maternal infection on the infant's neurocognitive development. Elsewhere, P. vivax infection causes relapsing infections that are challenging to prevent. Infection in first trimester of pregnancy is an area of increasing focus, and its adverse effects on pregnancy outcome are increasingly recognised. First-trimester infection is common and frequently acquired prior to conception. Although newer rapid diagnostic tests still have limited sensitivity, they may be useful in detection of early pregnancy malaria for treatment. Artemisinin-based combination therapies are efficacious in later pregnancy but have yet to be recommended in first trimester because of limited safety data. In Africa, intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine improves pregnancy outcomes, but sulfadoxine-pyrimethamine resistance is worsening. The alternative, IPTp with dihydroartemisinin-piperaquine, has greater antimalarial efficacy, but does not appear to improve pregnancy outcomes, because sulfadoxine-pyrimethamine has poorly understood nonmalarial benefits on birthweight. Summary Novel IPTp regimens must be combined with interventions to strengthen protection from malaria infection acquired before and in early pregnancy

Screening for infectious maternal morbidity - knowledge, attitudes and perceptions among healthcare providers and managers in Malawi: a qualitative study.

Maternal morbidity and mortality related to infection is an international public health concern, but detection and assessment is often difficult as part of routine maternity care in many low- and middle-income countries due to lack of easily accessible diagnostics. Front-line healthcare providers are key for the early identification and management of the unwell woman who may have infection. We sought to investigate the knowledge, attitudes, and perceptions of the use of screening tools to detect infectious maternal morbidity during and after pregnancy as part of routine antenatal and postnatal care. Enabling factors, barriers, and potential management options for the use of early warning scores were explored. Key informant interviews (n = 10) and two focus group discussions (n = 14) were conducted with healthcare providers and managers (total = 24) working in one large tertiary public hospital in Blantyre, Malawi. Transcribed interviews were coded by topic and then grouped into categories. Thematic framework analysis was undertaken to identify emerging themes. Most healthcare providers are aware of the importance of the early detection of infection and would seek to better identify women with infection if resources were available to do so. In current practice, an early warning score was used in the high dependency unit only. Routine screening was not in place in the antenatal or postnatal departments. Barriers to implementing routine screening included lack of trained staff and time, lack of thermometers, and difficulties with the interpretation of the early warning scores. A locally adapted early warning screening tool was considered an enabler to implementing routine screening for infectious morbidity. Local ownership and clinical leadership were considered essential for successful and sustainable implementation for clinical change. Although healthcare providers considered infection during and after pregnancy and childbirth a danger sign and significant morbidity, standardised screening for infectious maternal morbidity was not part of routine antenatal or postnatal care. The establishment of such a service requires the availability of free and easy to access rapid diagnostic testing, training in interpretation of results, as well as affordable targeted treatment. The implementation of early warning scores and processes developed in high-income countries need careful consideration and validation when applied to women accessing care in low resource settings

Awareness, attitudes and perceptions regarding HIV and PMTCT amongst pregnant women in Guinea-Bissau- a qualitative study.

BACKGROUND: The human immunodeficiency virus (HIV) continues to be a major cause of maternal and infant mortality and morbidity in sub-Saharan Africa. Prevention of mother-to-child transmission of HIV (PMTCT) strategies have proven effective in decreasing the number of children infected in utero, intrapartum and during the breastfeeding period. This qualitative study explores knowledge and perceptions of HIV amongst pregnant women, healthcare workers' experiences of the national PMTCT services, and barriers to PMTCT, during a period of programme scale-up in urban Guinea-Bissau (2010-11). METHODS: In-depth interviews were undertaken amongst 27 women and 19 key informants at local antenatal clinics and the national maternity ward in Bissau, Guinea-Bissau. RESULTS: Amongst women who had been tested for HIV, awareness and knowledge of HIV and PMTCT remained low. Testing without informed consent was reported in some cases, in particular when the test was performed around the time of delivery. Possible drivers of inadequate counselling included lack of confidentiality, suboptimal healthcare worker training, lack of time, and perceived occupational risk. Demand-side barriers to PMTCT included lack of HIV and PMTCT knowledge, customary and cultural beliefs associated with HIV and ill-health, HIV stigma and discrimination, and fear of partnership dissolution. CONCLUSIONS: Socio-cultural and operational challenges, including HIV testing without informed consent, present significant barriers to the scale-up of PMTCT services in Bissau. Strengthening local capacity for effective counselling and testing in the antenatal setting is paramount. Further research into local customary beliefs relating to HIV is warranted

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

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 μg/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

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)

Undernutrition and malaria in pregnancy – a dangerous dyad?

BACKGROUND: In low-resource settings, malaria and macronutrient undernutrition are major health problems in pregnancy, contributing significantly to adverse pregnancy outcomes such as preterm birth and fetal growth restriction. Affected pregnancies may result in stillbirth and neonatal death, and surviving children are at risk of poor growth and infection in infancy, and of non-communicable diseases in adulthood. Populations exposed to macronutrient undernutrition frequently reside in malaria-endemic areas, and seasonal peaks of low food supply and malaria transmission tend to coincide. Despite these geographic and temporal overlaps, integrated approaches to these twin challenges are infrequent. DISCUSSION: This opinion article examines the current evidence for malaria-macronutrition interactions and discusses possible mechanisms whereby macronutrient undernutrition and malaria may interact to worsen pregnancy outcomes. Macronutrient undernutrition dysregulates the immune response. In pregnant women, undernutrition may worsen the already increased susceptibility to malarial infection and could impair development of protective immunity to malaria, and is likely to exacerbate the impact of placental malaria on fetal growth. Malarial infection, in turn, can drive nutritional depletion; poor gestational weight gain and weight loss in pregnancy increases the risk of adverse pregnancy outcomes. Despite a commendable number of studies and trials that, in isolation, attempt to address the challenges of malaria and undernutrition in pregnancy, few dare to venture beyond the 'single disease - single solution' paradigm. We believe that this may be a lost opportunity: researching malaria-nutrition interactions, and designing and implementing integrated interventions to prevent and treat these commonly co-existing and intertwining conditions, may markedly reduce the high burden of preterm birth and fetal growth restriction in affected areas. CONCLUSION: We call for more collaboration between researchers studying malaria and nutrition in pregnancy, and propose a research agenda to address this important twin health problem.BioMed Central open acces

Nutritional status in tricuspid regurgitation: implications of transcatheter repair

Aims To characterize the prevalence and clinical relevance of malnutrition in patients undergoing transcatheter tricuspid valve edge-to-edge repair (TTVR). Methods and results Overall, 86 consecutive patients (mean age 78 ± 7 years) with moderate-to-severe tricuspid regurgitation (TR) at prohibitive surgical risk were analysed. Mini Nutritional Assessment (MNA), quality of life assessment, 6-min walk test distance and laboratory analyses were performed before and 1 month after TTVR. A total of 43 patients (50%) underwent concomitant transcatheter mitral valve repair. According to MNA, 81 patients (94%) were malnourished or at risk of malnutrition before TTVR. Following TTVR, MNA improved in 64 patients (74%). As compared to patients without MNA improvement, patients with increased MNA score had greater reductions in TR [regurgitation volume −17.0 (interquartile range, IQR −25.0; −7.0) mL vs. −26.4 (IQR −40.3; −14.5) mL, P < 0.001] and inferior vena cava diameter. Only patients with increased MNA score displayed a decrease in N-terminal pro-brain natriuretic peptide levels [−320 (IQR −1294; 105) pg/mL vs. +708 (IQR −342; 2708) pg/mL, P = 0.009], improvements in cholinesterase levels (0.0 ± 11.9 μmoL/L vs. +10.9 ± 16.7 μmoL/L, P < 0.001) and renal function during follow-up. Beneficial effects on quality of life scores and 6-min walk test distance following TTVR were observed exclusively in patients with improvement in MNA. During a median follow-up of 6 months, patients with worsened MNA had an increased risk of death and rehospitalization for heart failure. Conclusion Nutritional impairment is common and of prognostic importance in patients undergoing TTVR. Hepatorenal function modestly improves after successful TTVR. Further study of extracardiac implications of TR-associated right heart failure is warranted to improve care in this vulnerable patient population

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

HIV-1 and HIV-2 prevalence, risk factors and birth outcomes among pregnant women in Bissau, Guinea-Bissau: a retrospective cross-sectional hospital study

The human immunodeficiency virus (HIV) remains a leading cause of maternal morbidity and mortality in Sub-Saharan Africa. Prevention of mother-to-child transmission (PMTCT) has proven an effective strategy to end paediatric infections and ensure HIV-infected mothers access treatment. Based on cross-sectional data collected from June 2008 to May 2013, we assessed changes in HIV prevalence, risk factors for HIV, provision of PMTCT antiretroviral treatment (ART), and the association between HIV infection, birth outcomes and maternal characteristics at the Simão Mendes National Hospital, Guinea-Bissau’s largest maternity ward. Among 24,107 women, the HIV prevalence was 3.3% for HIV-1, 0.8% for HIV-2 and 0.9% for HIV-1/2. A significant decline in HIV-1, HIV-2, and HIV-1/2 prevalence was observed over time. HIV infection was associated with age and ethnicity. A total of 85% of HIV-infected women received ART as part of PMTCT, yet overall treatment coverage during labour and delivery declined significantly for both mothers and infants. Twenty-two percent of infants did not receive treatment, and 67% of HIV-2-infected mothers and 77% of their infants received ineffective non-nucleoside reverse transcriptase inhibitors for PMTCT. Maternal HIV was associated with low birth weight but not stillbirth. Inadequate continuity of care and ART coverage present challenges to optimal PMTCT in Guinea-Bissau