Trial: Malaria Chemoprevention Protects Children

by

The non-governmental organization Doctors Without Borders, or Medecins Sans Frontieres, has launched a new, malaria prevention campaign in several countries in sub-Saharan Africa aimed at protecting the illnesses’ most vulnerable population – children under the age of five. During the campaigns at the height of malaria season – from July to October – young children will be offered so-called chemoprevention drugs.

Small children are at highest risk of dying from malaria, a mosquito-borne parasitic illness that claimed the lives of some three-quarters of a million people in 2012, most of them children and babies in sub-Saharan Africa.

Doctors Without Borders, or MSF, is planning to roll out mass seasonal malaria chemoprevention campaigns, known as SMCs, in the Sahel sub-region to prevent new cases of the disease in countries where malaria is widespread. These nations include Senegal, Gambia, Niger, Burkino Faso and Mali.

In a 2013 SMC trial in Niger, the organization treated more than 200,000 children between the ages of three and 59 months with chemoprevention drugs.

Trials of the chemoprevention strategy in the last two years have shown a reduction of up to 83 percent in simple malaria cases; there’s a similar percentage reduction in the number of cases of severe malaria.

Estrella Lasry, tropical medicine adviser for the group, says the campaign was launched at the urging of the World Health Organization.

“And what we do is we give drugs once a month that protect and they protect the children for about a month during those four months of high transmission,” said Lasry.

In Niger, during a trial in 2013, the anti-malaria compounds were made available in remote locations at health facilities, in the homes of village chiefs and in areas where public health workers go door-to-door.

The organization deployed some 2,000 community health care workers to educate families about the benefits of chemoprevention and to encourage them to take their children to a distribution site.

Lasry says MSF chemoprevention campaigns do not use artemisinin-based drugs that are currently the “gold standard” to treat malaria infection.

“We try to use different drugs so that even if we can potentially cause resistance, we are not causing resistance to the most effective drugs we have for treatment,” she said.

If they find malaria in any of the children, Lasry says they treat it. But she says there’s a shortage of rapid diagnostic tests in Niger, for example, hampering efforts to treat malaria in endemic regions.

While not a “miracle cure,” officials say prevention drugs complement other malaria control strategies, including insecticide-treated bed nets.

Source: VOA News

Diagnostic Testing of Pediatric Fevers: Meta-Analysis of 13 National Surveys Assessing Influences of Malaria Endemicity and Source of Care on Test Uptake for Febrile Children under Five Years

by

In 2010, the World Health Organization revised guidelines to recommend diagnosis of all suspected malaria cases prior to treatment. There has been no systematic assessment of malaria test uptake for pediatric fevers at the population level as countries start implementing guidelines. We examined test use for pediatric fevers in relation to malaria endemicity and treatment-seeking behavior in multiple sub-Saharan African countries in initial years of implementation. [Read more…]

Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria

by

Human genetics and immune responses are considered to critically influence the outcome of malaria infections including life-threatening syndromes caused by Plasmodium falciparum. An important role in immune regulation is assigned to the apoptosis-signaling cell surface receptor CD95 (Fas, APO-1), encoded by the gene FAS.

Here, a candidate-gene association study including variant discovery at the FAS gene locus was carried out in a case-control group comprising 1,195 pediatric cases of severe falciparum malaria and 769 unaffected controls from a region highly endemic for malaria in Ghana, West Africa. We found the A allele of c.−436C>A (rs9658676) located in the promoter region of FAS to be significantly associated with protection from severe childhood malaria (odds ratio 0.71, 95% confidence interval 0.58–0.88, pempirical = 0.02) and confirmed this finding in a replication group of 1,412 additional severe malaria cases and 2,659 community controls from the same geographic area.

The combined analysis resulted in an odds ratio of 0.71 (95% confidence interval 0.62–0.80, p = 1.8×10−7, n = 6035). The association applied to c.−436AA homozygotes (odds ratio 0.47, 95% confidence interval 0.36–0.60) and to a lesser extent to c.−436AC heterozygotes (odds ratio 0.73, 95% confidence interval 0.63–0.84), and also to all phenotypic subgroups studied, including severe malaria anemia, cerebral malaria, and other malaria complications. Quantitative FACS analyses assessing CD95 surface expression of peripheral blood mononuclear cells of naïve donors showed a significantly higher proportion of CD69+CD95+ cells among persons homozygous for the protective A allele compared to AC heterozygotes and CC homozygotes, indicating a functional role of the associated CD95 variant, possibly in supporting lymphocyte apoptosis.

Author Summary

Severe malaria caused by infection with the protozoan parasite Plasmodium falciparum is a major health burden, causing approximately one million fatalities annually, predominantly among young children in Sub-Saharan Africa. The occurrence of severe malaria may depend on a complex interplay of transmission dynamics and the development of a protective immune response but also on heritable differences in the susceptibility to the disease.

In two large studies including a total of 2,607 affected children and 3,428 apparently healthy individuals from Ghana, West Africa, we investigated genetic variants of the FAS gene, which encodes CD95, a molecule critically involved in the programmed cell death of lymphocytes. We found that a single nucleotide variant in the FAS promoter was associated with a 29%–reduced risk of developing severe malaria. In individuals carrying two copies of the protective allele, a higher proportion of activated lymphocytes was found to express CD95. These findings indicate that a predisposition to an increased expression of CD95 may help to protect from severe malaria, possibly by rendering activated T-lymphocytes more susceptible to programmed cell death.

Citation: Schuldt K, Kretz CC, Timmann C, Sievertsen J, Ehmen C, et al. (2011) A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria. PLoS Genet 7(5): e1002066. doi:10.1371/journal.pgen.1002066

Editor: Daniel C. Jeffares, University College London, United Kingdom

Received: November 3, 2010; Accepted: March 18, 2011; Published: May 19, 2011

Copyright: © 2011 Schuldt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The work was supported by the German National Genome Research Network (NGFN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Authors: Kathrin Schuldt1,2*, Cosima C. Kretz3, Christian Timmann1,2, Jürgen Sievertsen1, Christa Ehmen1, Claudia Esser1, Wibke Loag4, Daniel Ansong5, Carmen Dering2, Jennifer Evans1, Andreas Ziegler2, Jürgen May4, Peter H. Krammer3, Tsiri Agbenyega5, Rolf D. Horstmann1

1 Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 2 Institute of Medical Biometry and Statistics, University at Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany, 3 Division of Immunogenetics, German Cancer Research Centre, Heidelberg, Germany, 4 Infectious Disease Epidemiology Group, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 5 School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Full text: A −436C>A Polymorphism in the Human FAS Gene Promoter Associated with Severe Childhood Malaria (PDF)

What age can be affected by malaria?

by

QUESTION:

A child of what age can be affected from cerebral malaria or malaria?

ANSWER:

People of all ages can be affected by malaria, which is what makes it such a public health burden in so many places.

Severe symptoms of the disease, such as the manifestation of cerebral malaria that you mention, can also be seen in children of all ages as well as adults. However, generally, younger children tend to have more serious attacks of malaria, and the disease is most deadly in children under the age of 5, who have not had a chance to build up natural, protective immunity to malaria. This lack of immunity is why malaria is also particularly severe in travellers, who have not been exposed during their childhood. Similarly, changes in the body’s immune response and blood chemistry during pregnancy make pregnant women, no matter what their age, very vulnerable to malaria infection.