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Dial N.J.,University of California at San Francisco | Ceesay S.J.,Medical Research Council Unit | Gosling R.D.,University of California at San Francisco | D'Alessandro U.,Medical Research Council Unit | Baltzell K.A.,University of California at San Francisco
Malaria Journal | Year: 2014

Background: Mass drug administration (MDA) is a strategy widely used in the control of human parasitic diseases but has been rarely attempted with malaria, the most common and dangerous parasitic disease in humans. MDA is an intervention strategy that involves simultaneously dispensing treatment to an entire population in a given geographic area. With some areas in sub-Saharan Africa documenting a decline in malaria transmission, the feasibility of MDA to further reduce malaria transmission is being considered. Understanding community perceptions of such an activity is vitally important for the design of the study and gaining the support of participants in order to maximize compliance and adherence. Methods. A qualitative study to assess factors likely to influence community acceptance of MDA in the seasonal and low malaria transmission setting of The Gambia was conducted. Using in-depth interviews, the perceptions, knowledge and attitudes of medical personnel and community members who have undergone MDA trials in The Gambia were investigated. Results: Several major themes emerged, namely: 1) the importance of timing of rounds of MDA doses for maximum participation; 2) the need to educate the target population with accurate information on the procedures, drug regimen, and possible side effects to enhance adherence; 3) the need for continuous sensitization meetings to maintain and increase uptake of MDA; and, 4) the importance for defining roles in the delivery and assessment of MDA, including existing healthcare structures. Discussion. To increase the likelihood of participation in MDA trials in this setting, activities should be undertaken just before and during the rainy season when community members are less mobile. Importantly, fears regarding blood sampling and side effects of the drug regimen need to be addressed prior to the start of the trial and repeated throughout the study period. Accurate and frequent communication is essential, and village leaders should consistently be included in sensitization meetings to enhance community participation. Additionally, village healthcare workers should be included in training and implementation, with supervision by a fieldworker permanently posted in every few villages during the trial. Future collaboration with Senegal may prove important for enhanced elimination efforts in The Gambia. © 2014 Dial et al.; licensee BioMed Central Ltd.


Manyando C.,Tropical Diseases Research Center | Njunju E.M.,Tropical Diseases Research Center | D'Alessandro U.,Institute of Tropical Medicine | D'Alessandro U.,Medical Research Council Unit | Van geertruyden J.-P.,University of Antwerp
PLoS ONE | Year: 2013

Introduction: Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group. Objective: We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis. Result: CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%-97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%-97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%-99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women. Conclusion: CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups. © 2013 Manyando et al.


Mehtala J.,Finnish National Institute for Health and Welfare | Antonio M.,Medical Research Council Unit | Kaltoft M.S.,Statens Serum Institute | O'Brien K.L.,Center for American Indian Health | Auranen K.,Finnish National Institute for Health and Welfare
Epidemiology | Year: 2013

BACKGROUND:: Vaccine-induced replacement by nonvaccine serotypes in pneumococcal colonization and disease poses a threat to the long-term effectiveness of pneumococcal vaccination. One of the main drivers for serotype replacement is likely to be the competitive interactions between pneumococcal serotypes. METHODS:: We used longitudinal datasets of pneumococcal colonization among infants (American Indian and The Gambia) and toddlers (Denmark) to study the strength and mechanism of competition between pneumococcal serotypes. We characterized the strength of competition as the relative reduction in the expected time spent colonized with two serotypes (double colonization) as compared with colonization with no competition. We also assessed the mechanism of competition, that is, whether reduction in double colonization is due to reduced rate of acquisition or enhanced clearance of colonization. The three datasets were analyzed assuming both perfect (100%) and imperfect (50%) sensitivity in detection of double colonization. RESULTS:: Each dataset showed strong between-serotype competition, and competition in acquisition was clearly identified. These findings remained in the secondary analysis assuming only 50% sensitivity to detect double colonization. Inferences about enhanced clearance due to competition were susceptible to the assumed sensitivity of detection. CONCLUSIONS:: Strong competition between pneumococcal serotypes can explain the prompt replacement by the nonvaccine serotypes in vaccinated persons and populations. The main mechanism of between-serotype interaction was identified as competition in acquisition, which suggests that replacement in pneumococcal disease depends largely on propensities of the replacing serotypes to cause disease through acquisition of colonization. Copyright © 2013 by Lippincott Williams & Wilkins.


Naylor C.,Medical Research Council Unit | Petri W.A.,University of Virginia
Trends in Molecular Medicine | Year: 2015

Leptin is a regulatory hormone with multiple roles in the immune system. We favor the concept that leptin signaling 'licenses' various immune cells to engage in immune responses and/or to differentiate. Leptin is an inflammatory molecule that is capable of activating both adaptive and innate immunity. It can also 'enhance' immune functions, including inflammatory cytokine production in macrophages, granulocyte chemotaxis, and increased Th17 proliferation. Leptin can also 'inhibit' cells; CD4+ T cells are inhibited from differentiating into regulatory T cells in the presence of elevated leptin, while NK cells can exhibit impaired cytotoxicity under the same circumstances. Consequently, understanding the effect of leptin signaling is important to appreciate various aspects of immune dysregulation observed in malnutrition, obesity, and autoimmunity. Leptin signaling can regulate innate inflammatory responses, such as cytokine production in macrophages and mast cells, as well as leptin-mediated chemotaxis in granulocytes.Leptin signaling can regulate adaptive immunity. It is required for Th17 differentiation through upregulation of transcription of RORγt.Leptin signaling can suppress regulatory T cell (Treg) differentiation.Inhibition of the leptin receptor blocks macrophage microbicidal and phagocytic functions, as well as the maturation of dendritic cells.Leptin can inhibit natural killer (NK) cell activation under certain circumstances, a unique effect not observed in other cell types. © 2016.


Lindsey B.,Imperial College London | Kampmann B.,Imperial College London | Kampmann B.,Medical Research Council Unit | Jones C.,Imperial College London | Jones C.,St George's, University of London
Current Opinion in Infectious Diseases | Year: 2013

Purpose of Review: Following on from the success of maternal tetanus vaccination, recent research has shown that other vaccines given in pregnancy can protect against vaccine-preventable infections in early infancy. This review will outline these recent developments and highlight the impact on current clinical practice. RECENT FINDINGS: Maternal immunization provides protection to the newborn through the transfer of vaccine-induced IgG across the placenta, a process that is affected by multiple variables. The safety of newly recommended maternal vaccines has been further tested in recent studies. Maternal vaccination against influenza and pertussis is recommended in the United Kingdom and United States, with new studies indicating their efficacy. A number of additional maternal vaccines are also in the pipeline, which could be used to combat neonatal infection. Recent research findings have highlighted some of the reasons for the poor uptake of current recommendations among pregnant women. SUMMARY: Tetanus, influenza and pertussis vaccines are now recommended for use during pregnancy, with new vaccines, such as group B streptococcus and respiratory syncytial virus, being developed to prevent important neonatal infections in the future. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Noulin F.,Institute of Tropical Medicine | Noulin F.,Stem Cell Institute | Borlon C.,Institute of Tropical Medicine | Van Den Abbeele J.,Institute of Tropical Medicine | And 3 more authors.
Trends in Parasitology | Year: 2013

The development of a continuous Plasmodium vivax blood cycle in vitro was first attempted 100 years ago. Since then, and despite the use of different methods, only short-term cultures have been achieved so far. The available literature has been reviewed in order to provide a critical overview of the currently available knowledge on P. vivax blood cycle culture systems and identify some unexplored ways forward. Results show that data accumulated over the past century remain fragmented and often contradictory, making it difficult to draw conclusions. There is the need for an international consortium on P. vivax culture able to collect, update, and share new evidence, including negative results, and thus better coordinate current efforts towards the establishment of a continuous P. vivax culture. © 2013 Elsevier Ltd.


Battersby A.J.,Imperial College London | Kampmann B.,Imperial College London | Kampmann B.,Medical Research Council Unit | Burl S.,Imperial College London
Clinical and Developmental Immunology | Year: 2012

A potential role for vitamin D as a therapeutic immunomodulator in tuberculosis (TB) has been recognised for over 150 years, but has only recently returned to the centre of the research arena due to the increasing awareness of the global vitamin D deficiency epidemic. As early as birth a child is often deficient in vitamin D, which may not only affect their bone metabolism but also modulate their immune function, contributing to the increased susceptibility to many infections seen early in life. Recent studies have begun to explain the mechanisms by which vitamin D affects immunity. Antimicrobial peptides are induced in conjunction with stimulation of innate pattern recognition receptors enhancing immunity to particular infections. In contrast the role of vitamin D within the adaptive immune response appears to be more regulatory in function, perhaps as a mechanism to reduce unwanted inflammation. In this paper we focus on the effect of vitamin D on immunity to TB. Where much of the attention has been paid by past reviews to the role of vitamin D in adult TB patients, this paper, where possible, focuses on research in paediatric populations. Copyright © 2012 Anna Jane Battersby et al.


Takem E.N.,Medical Research Council Unit | D'Alessandro U.,Medical Research Council Unit | D'Alessandro U.,Institute of Tropical Medicine
Mediterranean Journal of Hematology and Infectious Diseases | Year: 2013

Pregnant women have a higher risk of malaria compared to non-pregnant women. This review provides an update on knowledge acquired since 2000 on P. falciparum and P.vivax infections in pregnancy. Maternal risk factors for malaria in pregnancy (MiP) include low maternal age, low parity, and low gestational age. The main effects of MIP include maternal anaemia, low birth weight (LBW), preterm delivery and increased infant and maternal mortality. P. falciparum infected erythrocytes sequester in the placenta by expressing surface antigens, mainly variant surface antigen (VAR2CSA), that bind to specific receptors, mainly chondroitin sulphate A. In stable transmission settings, the higher malaria risk in primigravidae can be explained by the non-recognition of these surface antigens by the immune system. Recently, placental sequestration has been described also for P.vivax infections. The mechanism of preterm delivery and intrauterine growth retardation is not completely understood, but fever (preterm delivery), anaemia, and high cytokines levels have been implicated. Clinical suspicion of MiP should be confirmed by parasitological diagnosis. The sensitivity of microscopy, with placenta histology as the gold standard, is 60% and 45% for peripheral and placental falciparum infections in African women, respectively. Compared to microscopy, RDTs have a lower sensitivity though when the quality of microscopy is low RDTs may be more reliable. Insecticide treated nets (ITN) and intermittent preventive treatment in pregnancy (IPTp) are recommended for the prevention of MiP in stable transmission settings. ITNs have been shown to reduce malaria infection and adverse pregnancy outcomes by 28-47%. Although resistance is a concern, SP has been shown to be equivalent to MQ and AQ for IPTp. For the treatment of uncomplicated malaria during the first trimester, quinine plus clindamycin for 7 days is the first line treatment and artesunate plus clindamycin for 7 days is indicated if this treatment fails; in the 2nd and 3rd trimester first line treatment is an artemisinin-based combination therapy (ACT) known to be effective in the region or artesunate and clindamycin for 7 days or quinine and clindamycin. For severe malaria, in the second and third trimester parenteral artesunate is preferred over quinine. In the first trimester, both artesunate and quinine (parenteral) may be considered as options. Nevertheless, treatment should not be delayed and should be started immediately with the most readily available drug.


Afolabi M.O.,Medical Research Council Unit
Molecular Therapy | Year: 2016

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2–6 years old in The Gambia; 5–17 months old in Burkina Faso; 5–12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity.Molecular Therapy (2016); doi:10.1038/mt.2016.83. © 2016 Official journal of the American Society of Gene & Cell Therapy


News Article | January 8, 2017
Site: www.techtimes.com

Anemia is generally perceived as a negative condition. New research, however, suggests that the same health condition, which could be accountable for severe long-term consequences, actually protects children against malaria. The research also points out that addressing the iron deficiency with supplements could also diminish or even completely neutralize its effects against the deadly virus. Iron deficiency is the most common condition caused by nutritional problems worldwide, and about 9.6 percent of the American population suffers from it. However, according to a new research, published in the journal EBioMedicine, the condition has proven to be beneficial against Malaria. The observational study indicates that iron supplementation increases the risk of malaria, although the underlying mechanism of this process is still unknown. "We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection.[...] Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria," noted the study. The researchers from University of North Carolina, in collaboration with the Medical Research Council Unit in The Gambia and the London School of Hygiene & Tropical Medicine, have investigated the red blood cells of 135 subjects between the ages of 6 months and 24 months in an area where the virus is highly active. The subjects were administered with micronutrient powder to combat the iron deficiency for 84 days, at the end of which they discovered that anemia reduced the blood-stage of malaria by 16 percent. This discovery implies that anemia represents a very powerful natural protector against malaria. Additionally, one of the hypotheses of the research is that the high prevalence of anemia within people from the African desert area is of genetic nature, while also being a signature of malaria. When anemic children were administered iron supplements for seven weeks, the progress of malaria retook its course, and its invasion at the blood level was reversed. Before conducting this research, the same team found that the reason why children seem to be so affected by the virus lies in their young red blood cells, which represent a perfect host for malaria. "This study is elegant in its simplicity, yet remains one of the most substantial and systematic attempts to unveil the cellular-level relationship between anemia, iron supplementation and malaria risk," noted Carla Cerami, M.D. Ph.D., lead scientist on the project at the MRC Unit in The Gambia. According to a WHO report released in 2016, there were 212 million reported cases of malaria in 2015 across the world, and the global incidence between 2010 and 2015 dropped by 21 percent. Additionally, due to the organized efforts to diminish the number of cases, the mortality among patients infected with the disease decreased by 29 percent within the same period. "Nevertheless, significant gaps in program coverage remain. Access to vector control has been greatly extended through mass-distribution campaigns; however, increasing the coverage of chemoprevention, diagnostic testing and treatment requires these interventions to be delivered through health systems that are frequently under-resourced and poorly accessible to those most at risk of malaria. Moreover, the potential for strengthening health systems in malaria endemic countries is often constrained by low national incomes and per capita domestic spending on health and malaria control," noted the report. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

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