Meghna Desai

Bio: Meghna Desai is an academic researcher from Centers for Disease Control and Prevention. The author has contributed to research in topics: Malaria & Population. The author has an hindex of 31, co-authored 93 publications receiving 4151 citations. Previous affiliations of Meghna Desai include University of Amsterdam & University of Oxford.

Epidemiology and burden of malaria in pregnancy

Abstract: We reviewed evidence of the clinical implications and burden of malaria in pregnancy. Most studies come from sub-Saharan Africa, where approximately 25 million pregnant women are at risk of Plasmodium falciparum infection every year, and one in four women have evidence of placental infection at the time of delivery. P falciparum infections during pregnancy in Africa rarely result in fever and therefore remain undetected and untreated. Meta-analyses of intervention trials suggest that successful prevention of these infections reduces the risk of severe maternal anaemia by 38%, low birthweight by 43%, and perinatal mortality by 27% among paucigravidae. Low birthweight associated with malaria in pregnancy is estimated to result in 100 000 infant deaths in Africa each year. Although paucigravidae are most affected by malaria, the consequences for infants born to multigravid women in Africa may be greater than previously appreciated. This is because HIV increases the risk of malaria and its adverse effects, particularly in multigravidae, and recent observational studies show that placental infection almost doubles the risk of malaria infection and morbidity in infants born to multigravidae. Outside Africa, malaria infection rates in pregnant women are much lower but are more likely to cause severe disease, preterm births, and fetal loss. Plasmodium vivax is common in Asia and the Americas and, unlike P falciparum, does not cytoadhere in the placenta, yet, is associated with maternal anaemia and low birthweight. The effect of infection in the first trimester, and the longer term effects of malaria beyond infancy, are largely unknown and may be substantial. Better estimates are also needed of the effects of malaria in pregnancy outside Africa, and on maternal morbidity and mortality in Africa. Global risk maps will allow better estimation of potential impact of successful control of malaria in pregnancy.

Absence of Putative Artemisinin Resistance Mutations Among Plasmodium falciparum in Sub-Saharan Africa: A Molecular Epidemiologic Study

Abstract: Plasmodium falciparum parasites that are resistant to artemisinins have been detected in Southeast Asia. Resistance is associated with several polymorphisms in the parasite's K13-propeller gene. The molecular epidemiology of these artemisinin resistance genotypes in African parasite populations is unknown. We developed an assay to quantify rare polymorphisms in parasite populations that uses a pooled deep-sequencing approach to score allele frequencies, validated it by evaluating mixtures of laboratory parasite strains, and then used it to screen P. falciparum parasites from >1100 African infections collected since 2002 from 14 sites across sub-Saharan Africa. We found no mutations in African parasite populations that are associated with artemisinin resistance in Southeast Asian parasites. However, we observed 15 coding mutations, including 12 novel mutations, and limited allele sharing between parasite populations, consistent with a large reservoir of naturally occurring K13-propeller variation. Although polymorphisms associated with artemisinin resistance in P. falciparum in Southeast Asia are not prevalent in sub-Saharan Africa, numerous K13-propeller coding polymorphisms circulate in Africa. Although their distributions do not support a widespread selective sweep for an artemisinin-resistant phenotype, the impact of these mutations on artemisinin susceptibility is unknown and will require further characterization. Rapid, scalable molecular surveillance offers a useful adjunct in tracking and containing artemisinin resistance.

Profile: The KEMRI/CDC Health and Demographic Surveillance System—Western Kenya

Abstract: The KEMRI/Centers for Disease Control and Prevention (CDC) Health and Demographic Surveillance System (HDSS) is located in Rarieda, Siaya and Gem Districts (Siaya County), lying northeast of Lake Victoria in Nyanza Province, western Kenya. The KEMRI/CDC HDSS, with approximately 220 000 inhabitants, has been the foundation for a variety of studies, including evaluations of insecticide-treated bed nets, burden of diarrhoeal disease and tuberculosis, malaria parasitaemia and anaemia, treatment strategies and immunological correlates of malaria infection, and numerous HIV, tuberculosis, malaria and diarrhoeal disease treatment and vaccine efficacy and effectiveness trials for more than a decade. Current studies include operations research to measure the uptake and effectiveness of the programmatic implementation of integrated malaria control strategies, HIV services, newly introduced vaccines and clinical trials. The HDSS provides general demographic and health information (such as population age structure and density, fertility rates, birth and death rates, in- and out-migrations, patterns of health care access and utilization and the local economics of health care) as well as disease- or intervention-specific information. The HDSS also collects verbal autopsy information on all deaths. Studies take advantage of the sampling frame inherent in the HDSS, whether at individual, household/compound or neighbourhood level.

Polymorphisms in Plasmodium falciparum chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors That Affect Treatment Outcomes for P. falciparum Malaria After Artemether-Lumefantrine and Artesunate-Amodiaquine

Abstract: Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

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The Immune System in Pregnancy: A Unique Complexity

Abstract: Placental immune response and its tropism for specific viruses and pathogens affect the outcome of the pregnant woman's susceptibility to and severity of certain infectious diseases. The generalization of pregnancy as a condition of immune suppression or increased risk is misleading and prevents the determination of adequate guidelines for treating pregnant women during pandemics. There is a need to evaluate the interaction of each specific pathogen with the fetal/placental unit and its responses to design the adequate prophylaxis or therapy. The complexity of the immunology of pregnancy and the focus, for many years, on the concept of immunology of pregnancy as an organ transplantation have complicated the field and delayed the development of new guidelines with clinical implications that could help to answer these and other relevant questions. Our challenge as scientists and clinicians interested in the field of reproductive immunology is to evaluate many of the 'classical concepts' to define new approaches for a better understanding of the immunology of pregnancy that will benefit mothers and fetuses in different clinical scenarios.