A significantly greater proportion of patients in the tafenoquine group did not have malaria relapses compared to patients in the...
MedicalResearch.com Interview with:
Alfredo Mayor Aparicio PhD
Associate Research Professor
Barcelona Institute for Global Health
Medical Research: What is the background for this study? What are the main findings?
Dr. Mayor: The malaria parasite is a well-adapted pathogen which can persist and reappear in areas where infection is no longer circulating or at very low levels. Prevention of such reinfections and resurgences is critical for the current goal of malaria eradication. However, little is known about the determinants and consequences of malaria declines and resurgences. For this reason, understanding the relationship between malaria transmission, immunity and disease burdens is essential to rationalise malaria interventions aimed at reducing host-parasite encounters. We have described changes in prevalence among pregnant women delivering between 2003 and 2012 at antenatal clinics in Southern Mozambique, and showed that a reduction of malaria-specific immunity associated with drops in transmission is accompanied with an increase the severity of malaria infection among those women becoming infected. These results suggest that success of control and elimination activities may lead through a transitional period where infrequent infections will likely slowdown the rate of acquisition of host defenses and will be thus associated with more deleterious effects during pregnancy, thus requiring more precise diagnosis and surveillance methods, as well as improved prevention.
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MedicalResearch.com Interview with:
Dr. Martin N. Mwangi
Researcher
Division of Human Nutrition,
Nutrition and Health over the lifecourse
International Nutrition Unit
Wageningen University
The Netherlands
Medical Research: What is the background for this study?
Dr. Mwangi : Anemia in pregnancy is a moderate or severe health problem in more than 80 percent of countries worldwide, but particularly in Africa, where it affects 57 percent of pregnant women. Iron deficiency is the most common cause, but iron supplementation during pregnancy has uncertain health benefits. There is some evidence to suggest that iron supplementation may increase the risk of infectious diseases, including malaria.
Our main objective was to measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. We randomly assigned 470 pregnant Kenyan women living in a malaria endemic area to daily supplementation with 60 mg of iron (n = 237 women) or placebo (n = 233) until 1 month postpartum. All women received 5.7 mg iron/day through flour fortification during intervention and usual intermittent preventive treatment against malaria.
Medical Research: What are the main findings?
Dr. Mwangi : Overall, we found no effect of daily iron supplementation during pregnancy on risk of maternal Plasmodium infection. Iron supplementation resulted in an increased birth weight [5.3 ounces], gestational duration, and neonatal length; enhanced maternal and infant iron stores at 1 month after birth; and a decreased risk of low birth weight (by 58 percent) and prematurity. The effect on birth weight was influenced by initial maternal iron status. Correction of maternal iron deficiency led to an increase in birth weight by [8.4 ounces].
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MedicalResearch.com Interview with:
Manoj Duraisingh Ph.D.
John LaPorte Given Professor of Immunology and Infectious Diseases
Harvard T.H. Chan School of Public Health
Department of Immunology and Infectious Diseases
Boston, Massachusetts
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Duraisingh: The malaria parasite P. falciparum is one of the most important pathogens of humans, with enormous mortality resulting from blood-stage infections, when parasites replicate exponentially in red blood cells. Although anti-Plasmodial drugs are in clinical use, widespread and increasing parasite drug-resistance has contributed to an ongoing public health crisis, and we urgently need to find novel approaches to prevent and treat disease.
Targeting host red blood cell molecules presents an unexploited alternative. However, the highly differentiated and enucleated red blood cell poses a significant technical hurdle for genetic experimentation, due to the lack of a nucleus.
Here we have developed a novel, forward genetic screen to identify critical factors of malaria infection of red blood cells in an unbiased fashion. Our screen takes advantage of recent advances in human stem cell biology that enable the ex vivo culture of red blood cells from nucleated hematopoietic precursors which are amenable to in vitro genetics.
We have now identified a surface molecule CD55 (alias Decay-Accelerating Factor, DAF) as an essential host factor required for the invasion of red blood cells by P. falciparum. We demonstrate that this protein is required by all P. falciparum strains tested (laboratory and field) for invasion. Furthermore, we demonstrate that CD55 acts at the initial stage of invasion when the P. falciparum parasite attaches to the surface of the red blood cell.
Collectively, our findings indicate that CD55 is an ideal target for the development of new host-directed and vaccine therapeutics for malaria.
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MedicalResearch.com Interview with:
Mary J Hamel, M.D.
Chief, Strategic and Applied Sciences Unit,
And Deputy Branch Chief for Science, CDC Malaria Branch
US Centers for Disease Control and Prevention
1600 Clifton Rd, NE, MS A06
Atlanta GA 30333
Dr. Hamel was principal investigator at the Siaya site in western Kenya.
Medical Research: What is the background for this study? What are the main findings?
Dr. Hamel: Major progress has been made in malaria control during the past decade with the scale up of proven interventions including insecticide treated nets (ITNs), indoor residual spraying, effective diagnosis and treatment for malaria, and intermittent preventive treatment of malaria in pregnancy. Nonetheless, malaria remains a major cause of morbidity and mortality, and a leading cause of pediatric death worldwide. An estimated 198 million cases of malaria and 580,000 deaths occurred in 2013 – most of these in African children.
Now we face additional challenges in malaria control – the emergence of insecticide and drug resistance threatens some of our most effective interventions. New tools are needed to reach the goal of malaria elimination and eventual eradication. Vaccines are some of our most cost-effective interventions, and an effective malaria vaccine would be an important addition to our current malaria control tools.
This week, the RTS,S Clinical Trials Partnership published the final vaccine efficacy and safety results from the RTS,S/AS01 malaria vaccine phase 3 trial in the Lancet (Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial, http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60721-8/abstract). This large randomized controlled double-blind phase 3 clinical trial was conducted in 11 sites in 7 African countries across a range of malaria transmission levels. In all, 15,460 children and young infants were enrolled in two age-categories, those first vaccinated at 5-17 months of age (referred to as children), and those first vaccinated at 6-12 weeks of age (referred to as young infants) who received the RTS,S/AS01 vaccine along with their routine childhood immunizations. Participants were randomized into 3 groups – the first group received three doses of the RTS,S/AS01 vaccine followed 18 months later by a booster dose; the second group received three doses of the RTS,S/AS01 vaccine without a booster; and the third group received a comparator vaccine. All participants received an ITN. Children were followed for an average of 48 months and infants for an average of 38 months.
We found that vaccine efficacy was modest. Vaccine efficacy against clinical malaria in children was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was 32% with a booster and non-significant without. Efficacy results in young infants were lower than those in children– vaccine efficacy against clinical malaria was 36% with a booster and 28% without, and vaccine efficacy against severe malaria was non-significant.
However, impact, defined as the number of cases averted per 1000 participants vaccinated, was substantial in both age-categories, and highest where malaria burden was greatest. In children who received the booster, during 4 years follow-up, 1700 cases of clinical malaria were averted per 1000 children vaccinated. In young infants, during 3 years follow-up, nearly 1000 cases were averted per 1000 young infants vaccinated.
The safety findings were comparable overall in the different study arms, but two safety findings are notable. Meningitis occurred more frequently among children (but not young infants) who received RTS,S/AS01 than among those who received the comparator vaccines. There was no relationship between when the vaccine was administered and when meningitis occurred, most cases occurred in only two study sites, and the finding may be due to chance. If RTS,S/AS01 is licensed, post-licensing studies will be done to establish the significance of this finding. Both children and young infants experienced more episodes of fever and associated febrile convulsions during the 7 days following vaccination; convulsions occurred in 2.2 - 2.5/1000 vaccine doses. (more…)
MedicalResearch.com Interview with:
Amalia Z. Berna
CSIRO Food and Nutrition Flagship
Acton ACT 2601
MedicalResearch: What is the background for this study? What are the main findings?
Response: Globally an estimated 3.2 billion people in 97 countries are at risk of malaria and, in 2013, an estimated 198 million cases and 584,000 deaths were attributed to this infection. Accurate diagnosis of malaria is important to provide adequate treatment, conserve valuable drugs, and help prevent the emergence of resistant strains of the parasite. It is becoming important to be able to diagnose low level and asymptomatic cases, to support the drive towards local and/or global eradication.
Detection of volatile chemicals in expired breath has been used to diagnose or monitor a small number of diseases, including Helicobacter pylori infection, diabetes and lung inflammation but, if breath analysis is to be more broadly useful, we need to identify reliable biomarkers for a wider range of diseases and to develop more robust methods for breath analysis.
In collaboration with Professor James McCarthy of the QIMR Berghofer Institute and Associate Professor Kevin Saliba of the ANU, we found:
MedicalResearch.com: Interview with:
Dr. Simon Corrie PhD
The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Delivery of Drugs and Genes Group
Australian Infectious Diseases Research Centre, St. Lucia, Queensland, Australia
Medical Research: What is the background for this study? What are the main findings?
Dr. Corrie: P. falciparum malaria is a major cause of morbidity and mortality around the world, particularly in developing countries. Some estimates also suggest that in developing countries, children under 5 account for ~90% mortality. As malaria is treatable, positive detection is important rule out other causes, avoid over-treatment leading to resistance, and to guide appropriate treatment. Our focus is on developing diagnostic devices for infectious diseases, which do not require needles, lancets or laboratory processing.
These devices are “microprojection arrays”, silicon chips that can be applied to the skin to capture circulating protein biomarkers in the interstitial fluid of the skin. In this publication we:
(a) developed methods to improve the sensitivity of the devices for capturing HRP2,
(b) confirmed that HRP2 protein injected intravenously is detectable in skin fluid and
(c) showed that we could capture both HRP2 and total IgG (as a positive control for penetration into skin) at the same time.
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