Category Archives: Neonatal

Could a Triple-Hit Hypothesis Explain the Pathway from Malaria in Pregnancy to Adverse Infant Neurodevelopmental Outcomes?

Harriet L. S. Lawford 1 , Mary C. Ghazawy 1 , Tessa R. Donaldson 2 , Jack Donaldson 3 , and  Samudragupta Bora 1 shared their researct at the Malaria World Congress in Melbourne this week and present their findings below.

  1. Mothers, Babies and Women’s Health Program, Mater Research Institute, Faculty of Medicine, The University of Queensland, Australia
  2. Department of Psychology, University of Canterbury, Christchurch, New Zealand
  3. Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

Each year, millions of pregnant women in malaria-endemic areas are at risk of Plasmodium falciparum infection and the development of placental malaria. Given that malaria in pregnancy is known to contribute to a number of perinatal and infant deaths, this suggests that a significant proportion of live-births may have been exposed to placental malaria in utero. Whilst the neurodevelopmental consequences of cerebral malaria in children have been widely documented, there has been little focus on the impact of placental malaria on infant neurodevelopment.

This research gap is critical to address. Placental malaria is associated with adverse birth outcomes including preterm birth, low birthweight and intrauterine growth restriction, which themselves are well recognized independent risk factors for adverse short-term and long-term neurodevelopment. Furthermore, the additive effects of prenatal environmental and social factors on infant neurodevelopment remain poorly understood. Hence, we propose a Triple-Hit Hypothesis to explain the potential pathway from placental malaria to poor infant neurodevelopmental outcomes.

As per our hypothesis, prenatal socioeconomic, environmental and maternal factors represent the first-hit that influences the risk of developing placental malaria. Poverty and low socioeconomic status are known to increase the likelihood of malaria infection, as well as negatively influence access to and uptake of malaria treatment and prevention tools. The use of sulfadoxine-pyrimethamine in resistant areas has been seen to increase placental inflammation and parasitisation, as well as the proportion of resistant parasites, which can lead to more severe placental infection. Lastly, maternal factors, including parity and age, are known to influence the likelihood of placental malaria; the risk of placental malaria among primigravidae is 2-4 times higher than multigravidae, and is seen to increase with decreasing age

The second-hit is represented by the direct activation of maternal immuno-inflammatory factors in response to placental malaria and resultant placental dysfunction. The infiltration of maternal immune and inflammatory factors and placental histopathological changes, such as thickening of the trophoblastic basement membrane, can cause mechanical blockage of materno-foetal oxygen and nutrient exchange, leading to hypoxic conditions and oxidative stress as well as impaired placental vascularisation. Evidence from the literature also suggests activation of complement and a TH1/TH2 imbalance, further contributing to the maternal immunological response.

The severity of placental infection represents the third-hit, wherein the risk of poor neurodevelopment is indirectly impacted by the increased likelihood of adverse birth outcomes associated with infection. Low birthweight, preterm birth and intrauterine growth restriction are themselves risk factors for adverse foetal brain development, and adversities include long-term volumetric brain reductions and cognitive, motor and behavioural deficits. Furthermore, research has shown a direct link between maternal inflammation, placental pathology and poor neurological and neurodevelopmental outcomes.

Taken together, this involvement of both direct and indirect pathways culminate in a unique foetal phenotype, where not only do we expect to see the adverse birth outcomes commonly associated with placental malaria, but also adversities including increased risks of neurological, cognitive and behavioural deficits that may impact the quality of life in this high-risk population. Validation of the link between placental malaria and adverse neurodevelopment is needed.

For feedback and any further information, please contact: harriet.lawford@mater.uq.edu.au.

Progress on Malaria in Pregnancy in 12 PMI Focus Countries

The challenges of implementing programs to control malaria in pregnancy based on experiences with US President’s Malaria Initiative Countries was presented at the Malaria World Congress in Melbourne this week. The team included Katherine Wolf, MCSP/Jhpiego, Marianne Henry, PMI/USAID, Lia Florey, PMI/USAID, Gabrielle Conecker, MCSP/Jhpiego, Betsy Hendrickson, MCSP/Jhpiego, Katherine Lilly, MCSP/Jhpiego, Nicholas
Furtado, GFATM, Maria Petro, GFATM, Susan Youll, PMI/USAID, and Julie Gutman, PMI/CDC, and their findings are shared below.

What is the danger of malaria in pregnancy (MiP)? Each year MIP is responsible for 20% of stillbirths in Sub-Saharan Africa, 100,000 Newborn deaths globally, 11% of newborn deaths in Africa and 10,000 maternal deaths globally. Four interventions are aimed at MIP, Intermittent Preventive Treatment in Pregnancy (IPTp), consistent use of insecticide treated nets, effective diagnosis and treatment and low-dose folic acid during antenatal care. IPTp with sulfadoxine-pyrimethamine reduces low birth weight by 29%, severe maternal anemia by 38% and neonatal mortality by 31%. What can be done?

  • Scale-up and full coverage of the WHO lifesaving interventions
  • Promote early and regular ANC
  • Preserve SP efficacy by avoiding its use for treating clinical cases of malaria
  • Reserve SP stocks for IPTp at ANC clinics

Methodology for MiP country review: Initial survey took place in 23 PMI countries. PMI resident advisors were surveyed, Qualitative and quantitative responses were collected and Input from NMCP/partners was obtained. Country selection resulted in 12 that were Tiptop-implementing countries, represented Geographic diversity, had varied IPTp coverage, and made clear progress or best practices to share.

Desk review including HMIS and house hold survey data, current studies and recent assessments, Selected interviews with PMI resident advisors, Jhpiego field staff and current/former NMCP staff. Analysis was a Review and clarification of qualitative and qualitative data.

The 12 countries included Angola, Benin, Burkina Faso, DRC, Ghana, Kenya, Liberia, Madagascar, Malawi, Nigeria, Senegal, and Zimbabwe (see map). The figure shows that none of these attained 80% of 2 doses of IPTp. The current recommendations are for monthly dosages from the 13th week of pregnancy. Often less that half of those receiving IPTp2 also got IPTp3.

Several health systems findings helped explain the IPT results. For Policy & Implementation, Countries reporting strong, coordinated leadership delivered
high IPTp coverage. With Community Engagement, countries reported a diversity of approaches to community health promotion and service delivery.

Concerning Service Delivery, Many countries struggle to implement MiP policies consistently and with quality in the private sector. Commodities were a challenge. Some countries continue to struggle with SP stockouts at facility level, whether ongoing or episodic. Monitoring and Evaluation processes need to catch up. Countries’ routine information systems are transitioning from tracking IPTp2 to IPTp3.
The team offered several Recommendations.

  1. Strengthen consistency of IPTp policies across malaria and reproductive health programs
  2. Scale up of evidence-based country appropriate
    community engagement strategies
  3. Alleviation of supply chain bottlenecks at peripheral level
  4. Inclusion and harmonization of key MIP indicators in routine information systems

For more information please visit www.mcsprogram.org, facebook.com/MCSPglobal and twitter.com/MCSPglobal

This presentation was made possible by the generous support of the American people through the United States Agency for International Development (USAID), under the terms of the Cooperative AgreementAID-OAA-A-14-00028. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government.

Challenges in achieving Maternal and Neonatal Tetanus Elimination: South Sudan Experience

Dr. Anthony Laku who is currently the Immunization Program Officer in the South Sudan Ministry of Health presented the status of efforts to eliminate maternal and neonatal tetanus (MNT) in South Sudan at the fourth meeting of the WHO Regional Immunization Technical Advisory Group held 5-7 December 2017 in Johannesburg, South Africa. A summary of key challenges is shared below.

General Challenges to health delivery in South Sudan include a Maternal Mortality Ratio of 2054 per 100,000 live births. Also ~56% of population are not reached by Health Facilities; 60% of roads not accessible for half of the year; 45% of people live without access to safe water; and 86% of women have no formal education.

Delivery of immunization is hampered by persistent insecurity and inaccessibility. As of 31st August 2017, 7.5 million people are affected, and 3.9 million people are displaced, of which 2 million are in neighboring countries. The health services have varying degrees of difficulty in reaching the displaced people with immunization services.

Key strategies to eliminate MNT are as follows:

  • Three doses to all Women of Reproductive Age (WRA) using supplementary immunization activities (SIAs)
  • Provision of at least two doses of tetanus containing vaccines (TT) to all pregnant women and in high-risk areas
  • Promotion of clean delivery services for all pregnant women, and
  • Effective surveillance for MNT

So far the results have been below the targets for elimination. For example, 61% of 80 counties had less than 80% coverage in the third Round of Tetanus Containing Vaccines SIAs with 27/80 counties not reached at all. There was low estimated routine immunization (Penta3) coverage of only 26% in 2016. A limited number of skilled staff were available to ensure clean cord delivery (5% skilled delivery) with challenging implication on MNT elimination validation.

The protracted civil crisis in the country creates an uphill task for reaching key global targets including MNT elimination. Weak economic status in the country has had a ripple effect on staff motivation and commitment (e.g. delayed salaries).

Additional strategies were adopted for coverage improvement in 2017. A “Hit and Run” strategy was developed for insecure areas. Periodic Intensification of Routine Immunization was used in areas of intermittent crisis and or with high buildup of unimmunized populations. Overall the MNT elimination strategic plan was updated for 2018–2022.

Funding gaps exist for this new strategic plan with only 21% of needed finance is pledged. One approach to funding is aligning MNT elimination with funding in related areas such as the RMNCAH and Nutrition strategy and the Human Resource for Health Strategy. Despite these challenges South Sudan is persisting in efforts to eliminate MNT.