Preventing malaria and anemia in pregnancy:
A case-control study of
intermittent preventative treatment on Bioko Island, Equatorial Guinea
Traveling Scholars Proposal
Josephine Czechowicz, SMSI
Dr. Yvonne Maldonado
Dr. Luis Benavente
April 17, 2006
Table of Contents
Relevant Experience / 4
Investigators / 5
Field Site / 6
Learning Objectives / 7
PROPOSAL
Abstract
Specific Aims / 8
9
Background and Significance / 9
Experimental Design
Interpretation of Results
Potential Sources of Error / 11
14
14
Relevance to Medicine / 15
Justification for Away Experience / 15
Bibliography / 16
Appendices
Appendix I: Questionnaires
English
Spanish Translations / 18
20
Appendix II: IRB Application Record / 22
Appendix III: Consent Forms / 23
Please see paper copy for signatures.
Relevant Experience
Prior Institutions: Carleton College
Major, Concentration: Biology, Biochemistry
Minor: Spanish
Degree: B.A. June 2004
Research Topic / Where and When / Duration in Months / Average hours per week / Scholarly Contributions / PublicationSynthesis of lead compounds for drugs against trypanosomes / -Carleton College Department of Chemistry
-Summer 2002, 2003
-Throughout 2003 academic year / Total of 10 months / Summer: 50h/week
Academic year: 10h/week / -Synthesized substrate analogue inhibitors
-Tested inhibitory kinetics / Abstract and Poster at American Chemical Society Conference, 2004
Antibiotic resistance of Streptococcus pneumoniae in Santiago, Chile / -Center for Vaccine Development Santiago, Chile
-Summer 2004 / 12 weeks / 40-50 hours per week / -Tested 404 isolates of S. pneumoniae for resistance to 16 antibiotics
-Generated antibiotic resistance profile for Santiago, Chile / -Abstracts and Posters: Northern California International Health Conference, Chilean Infectious Disease Conference
-Manuscript in preparation
Molecular mechanisms of ovarian cancer metastasis / -National Cancer Institute, NIH, lab of Dr. Elise Kohn
-2004-2005 / 1 year / 40-50 hours per week / -Investigated role of BAG-3 protein in apoptosis / -Abstract and Poster: Young Investigators Meeting, 2005
-Presentation: NIH Post-baccalaureate seminar series
-Publications: Pharmacogenomics, Women’s Health, manuscript in preparation
Investigators
Protocol Director: Josephine (JoAnn) Czechowicz
I am a first-year medical student. My main interests are women’s health, infectious disease, international health and pediatrics. Before coming to Stanford, I did research on drug design, molecular signaling and epidemiology. The project that intrigued me most was a study of antibiotic resistance I conducted as part of a Fogarty International Research Fellowship in Santiago, Chile. My work in Chile ignited my interested in international health.
Here at Stanford, I am pursuing a concentration in Women’s Health. I have already taken several classes in the concentration including Women and Health Care (the McGann lecture series) as well as Current Topics and Controversies in Women's Health and Sex-based Biology, Current Issues in Reproductive Health, and Mommies and Babies in the winter. I so enjoyed the Mommies and Babies class that I have applied for the TA position for next year. My interest in women’s health inspired me to found a new student group called “Women and Medicine” focused on educating my peers about major health issues pertinent to women in the US and around the world.
Stanford Advisor: Yvonne Maldonado, M.D.
Dr. Maldonado is Associate Professor of Pediatric Infectious Disease at Stanford. She has significant expertise in childhood infection and perinatal transmission of disease, most specifically HIV, but also malaria. Additionally, Dr. Maldonado has done a large amount of fieldwork, with field sites in Mexico and Zimbabwe. Dr. Maldonado is the founder and director of the Stanford Infectious Diseases and Immunology Center. She serves on federal, national and international advisory committees relevant to pediatric infectious diseases, pediatric vaccines and international health.
On-Site Advisor: Luis Benavente, M.D.
Dr. Luis Benavente has over 20 years of experience in public health, as well as maternal and child health. Accredited as a Specialist in Epidemiology, Luis has extensively published in epidemiology of nutritional disorders, nutrition and infection, and micronutrient deficiencies. He served as both Professor and Head of the Department of Public Health at the Universidad Peruana Cayetano Hereida, and worked at the Peruvian Institutes of Health in their Research Center for 13 years. Luis then went on to work with Project HOPE in Guatemala, Nicaragua, Peru and in the US from 1996-2002. Luis currently is the Senior Health Program Officer for Medical Care Development International. He holds a Medical Degree and a Masters of Science Degree in Microbiology and Immunology.
Field Site
Obstetrics and Family Planning Clinic, Malabo Regional Hospital
This facility is the central prenatal facility on Bioko Island, providing prenatal care to over 70% of the island’s pregnant women annually. The clinic staffs three obstetricians and typically sees 40-50 patients per day. The facility has agreed to provide me with access to patients upon check in and a private space for me to conduct malaria and anemia tests, as well interview my subjects.
Medical Care Development International (MCDI) and the Bioko Island Malaria Control Project (BIMCP)
The government of Equatorial Guinea, Medical Care Development International and Marathon Oil Corporation have developed and are actively engaged in a comprehensive malaria control project for Bioko Island, Equatorial Guinea. This joint effort is expected to contribute significantly to the overall health and quality of life of the people of Equatorial Guinea.
The malaria control program will adopt a strategic plan designed around three program goals:
· Reduce the transmission of the malaria parasite through mosquito control programs and improved preventive measures at the household and the community level
· Improve the health care delivery systems for malaria cases by establishing malaria treatment centers that will use standardized protocols, diagnosis and referrals
· Enhance surveillance systems and operational research to strengthen Equatorial Guinea’s capacity to conduct surveys and implement an effective reporting and monitoring system
My on-site collaborator in this project, Luis Benavente, is Senior Health Project Officer of MCDI. Our academic inquiry has the potential to positively impact the second and third of the goals of the BIMCP.
Learning Objectives
To understand the process of community-based research from conception to publication.
This objective will be attained through the process of completing the project. At present I have conceived of my project, set up collaboration with a community-based partner, written a research proposal, planned appropriate statistical analysis and filed for IRB approval. Once I arrive in Bioko, I will learn about the obstacles to research in a resource-poor setting and how to overcome them to complete my investigation. Finally, upon my return, I will work with my statistical partners, Dr. Meira Falcovitz-Halpern here at Stanford and Dr. Luis Benavente in Africa, to analyze my data. Finally Drs. Maldonado and Benavente will guide me through the preparation and submission of a manuscript.
To gain an inside perspective on the reality of public-private collaboration in humanitarian aid work.
Health economists have touted the Bioko Island Malaria Control Project as a model of public-private collaboration in humanitarian development. My research partner in this study, Medical Care Development International, is a major player in this project. Through my work with MCDI researchers, I will see first hand how development projects are planned and implemented in a public-private partnership.
To observe what comprises the standard of obstetric care in a resource-poor setting.
My data collection will be based at the obstetrics clinic of Malabo Regional Hospital. In addition to collecting data and interviewing patients, I will also have the opportunity to shadow Dr. Gloria Nsteng in clinic and on the labor and delivery ward of the hospital. Dr. Ntseng is the chief obstetrician and a Bioko native. My interactions and conversations with her will give me insight into the quality and delivery of obstetric care in the developing world.
Proposal
Preventing malaria and anemia in pregnancy:
A case-control study of
intermittent preventative treatment on Bioko Island, Equatorial Guinea
Abstract
Malaria during pregnancy poses great risks to both mother and child, the most common of which is anemia. Anemia increases the mother’s risk for placental abruption, preterm labor and maternal death and puts the developing baby at risk for low birth weight and miscarriage. One dose of intermittent preventative treatment (IPT) with the drug combination sulfadoxine-pyrimethamine during the first 26 weeks of pregnancy has been shown to decrease a woman’s risk of malaria by 85% and anemia by 50%. The life cycle of P. falciparum as well as socio-behavioral factors differ throughout sub-Saharan Africa. In order to optimize IPT delivery, the operational efficacy of IPT in preventing malaria and anemia must be assessed on a local level.
This case-control study examines a population of pregnant women in their third trimester on Bioko Island, Equatorial Guinea. We aim to determine whether treatment with at least one dose of IPT during the first two trimesters of pregnancy correlates with reduced proportions of malaria and anemia.
70 participants will be recruited for each of two groups: a study group that previously received at least one dose of IPT in the first two trimesters and a control group that received none. We will determine malaria infection status using an immunochromatographic test and measure hemoglobin levels with a HemoCue detector. Additionally, to better understand contributors to anemia other than malaria, we will gather information with a quantitative survey. The knowledge gained in this study will allow for more effective implementation of malaria prevention measures for pregnant women and ultimately better outcomes for women and children.
Specific Aims
· Specific Aim 1: To determine whether pregnant women in Malabo, Equatorial Guinea who have taken Intermittent Preventative Treatment (IPT) with sulfadoxine-pyrimethamine have lower proportions of malaria than those who have not taken IPT. Malaria status will be determined using a rapid Immunochromatographic Test (ICT).
· Specific Aim 2: To determine whether pregnant women in Malabo, Equatorial Guinea who have taken IPT have higher hemoglobin levels than those who have not taken IPT. Hemoglobin levels will be measured with a rapid HemoCue test.
· Specific Aim 3: To investigate factors other than malaria that contribute to maternal anemia among pregnant women on Bioko Island using a quantitative survey.
Hypothesis: Women who receive IPT with sulfadoxine-pyrimethamine during pregnancy will have lower proportions of malaria and higher average hemoglobin levels than those who do not receive IPT.
Background and Significance
Each year in sub-Saharan Africa, approximately 30 million pregnant women are at risk for contracting malaria and suffering its adverse consequences (World Health Organization/UNICEF, 2003). Pregnant women are particularly vulnerable to malaria and are more likely to be infected with the pathological P. falciparum than non-pregnant women [1]. The most common complication of malaria during pregnancy is maternal anemia. P. falciparum infection increases a woman’s risk of anemia by 450% [2]. Anemia secondary to malaria puts pregnant women at greater risk of other morbidities including placental abruption, placenta previa, premature labor and maternal death. Placental malaria, a condition in which parasites infect the placenta, poses further risks, particularly for the developing fetus [3, 4]. Malaria in pregnancy can result in poor fetal outcomes, specifically miscarriage, low birth weight, and neonatal mortality [5]. Pregnancy presents an important opportunity for health-related interventions that can simultaneously improve outcomes for both mother and child.
Numerous strategies have been employed to prevent maternal malaria including the use of insecticide-treated bed nets to prevent mosquito bites and indoor residual spraying. Both interventions have been shown to dramatically decrease the risk of malaria [6, 7]. Past pharmaceutical interventions have been controversial. Weekly prophylaxis with chloroquine was effective throughout the 1980s. However, the emergence of chloroquine resistant malaria has decreased the effectiveness of this option. Further, the logistic constraint of weekly drug administration has made chloroquine an unrealistic choice even in areas with little resistance [8].
Intermittent preventative treatment (IPT) with sulfadoxine-pyrimethamine (SP) has been proven to be a safe and effective treatment in many malaria-endemic areas. Three IPT doses of SP in Malawi were shown to decrease a woman’s risk of active parasitemia by 72% [9]. A more recent study conducted in Kenya showed that as little as one dose of SD-IPT in the first two trimesters of pregnancy decreased risk for malaria by 85%. The same study showed a beneficial effect of IPT usage on hemoglobin level, decreasing risk for anema by 50% [10]. In 2000, the WHO recommended that IPT be implemented in malaria endemic regions as the standard of care for prophylaxis during pregnancy (WHO, 2000). However, since the announcement of this policy, there has been little assesment of its effectiveness or implementation [11]. The life cycle of P. falciparum and numerous sociobehvioral parameters differ between different regions and climates, therefore local assessment of the operational efficacy of IPT is essential to determine optimal IPT implementation in a particular community.
Equatorial Guinea (EG) is a Central African country located on the Gulf of Guinea (Figure 1) consisting of a continental region and an island region. Bioko Island, 30km from the coast of Cameroon, is home to the EG capital, Malabo. Malaria on Bioko is holo- to hyper-endemic with an infection rate of approximately 50% among children [12]. The infection rate among pregnant women has not been directly measured but is estimated at 25% [13]. P. faliciparum infection is nine times more common on Bioko than infection with P. vivax. The life cycles of P. falciparum and P. vivax differ: P. falciparum infects and then is eliminated while vivax may become dormant and recur within a host [14].
A recent population-based study estimated the maternal anemia prevalence on Bioko to be approximately 75% [13]. Although the anemia rate among pregnant women is high, little research has been done to determine the contribution of malaria to anemia. Examining a possible correlation between IPT use and increased hemoglobin levels may provide insight into the contribution of malaria to the high anemia rate. Surveying the subjects on other possible contributors to anemia, may provide insight into other methods of combating maternal anemia (e.g. iron supplementation) if little correlation between ITP use and hemoglobin level is observed.
Figure 1. Relative location of Equatorial Guinea
Since 2003, a public-private partnership to eradicate malaria has existed between the EG Ministry of Health and Marathon Oil: the Bioko Island Malaria Control Project (BIMCP). The $8.3 million project has been implemented and assessed by Medical Care Development International (MCDI), a Washington DC-based non-profit organization. The main strategies of the program have been indoor residual spraying and improved prophylaxis distribution among children. The program was implemented in 2003 and has had tremendous success. In just one year, the prevalence of malaria among children fell by 33% [13]. There is a good deal of political will in support of malaria eradication on Bioko. Research in support of IPT would likely result in its implementation by BIMCP. Further, identifying major barriers to IPT access among women would allow for optimization of IPT delivery.