Protection

I came to know that thalassemia is a genetic mutation that provides protection against malaria. Can it also provides protection against dengue fever; the problem that we are facing in our area?
 

HI, I study medicine and I got really curious about this fact that thal ppl dont get affected from malaria...where did you hear about it? i have studied microbiology but never heard of it...could you please give me the name of the book or website you got the info cuz I would like to read more about it...thnx, anisa

Hi to both. Thalassemia does not give protection for dengue fever. It is actually a very dangerous disease for thals and must be treated with special attention. You can see a brief article at http://www.ncbi.nlm.nih.gov/pubmed/16856431

There are many misconceptions about thal and malaria. I have explained this in depth previously at a post at http://www.thalassemiapatientsandfriends.com/index.php/topic,474.msg3506.html#msg3506

There is an excellent article about thalassemias and malaria by Dr Weatherall at http://www.mjhid.org/article/view/5228/html_2

Thalassemia and P. falciparum malaria
Although the malaria hypothesis, as first proposed by Haldane, was first developed to explain the high frequency of the thalassemias it has taken many years to confirm that Haldane was correct.  There is now extensive evidence to suggest that the mild forms of a thalassemia reach their extraordinary high frequencies due to protection against P. falciparum and at least some suggestive evidence that the same applies to the b thalassemias.
a+ thalassemia The a+ thalassemias, which are most commonly due to deletions of one of the linked a globin genes, -a/aa, are the commonest monogenic diseases in the world population.  They occur in a broad band stretching through sub-Saharan Africa and the Mediterranean, through the Middle East and the Indian subcontinent to Southeast Asia.  The frequency in these regions varies fro 5-40% although in parts of Northern India and Papua New Guinea close on 80% of the population are carriers [16].
Extensive population studies in the Southwest Pacific showed a strong correlation between the distribution of a+ thalassemia and malaria, and related molecular analyses indicated that the particular form of a+ thalassemia in these populations is different to that and the Asian mainland [17].  An unusual feature of the distribution of a+ thalassemia in this region is that it is also found in Fiji in the west and Tahiti in the east and in other populations in which malaria has never been recorded.  However in these regions all the a+ thalassemias can be accounted for by a single mutation which was first identified in Vanuatu, suggesting that their occurrence in these areas has been the result of population migration and founder effect [18].
These findings were later augmented by case control studies in Papua New Guinea where it was found that, compared with normal children, the risk of being admitted to hospital with severe malaria was significantly reduced, both for a+ thalassemia homozygotes and heterozygotes [19].  More recently these findings have been replicated in several African populations and it is now absolutely clear that the a+ thalassemias do offer protection against P. falciparum [20,21].  Both cellular and immune mechanisms have been found that may offer at least a partial explanation to the protective effect of a+ thalassemia against malaria.  The red cells of individuals with a+ thalassemia bind more malaria-immune globulin than normal and appear to be more susceptible to phagocytosis in vitro [22].  In particular, they are less able than normal to form rosettes, an in vitro phenomena whereby uninfected red cells bind to infected cells.  This may affect a reduced expression of complement receptor 1 (CR1) expression on a thalassemic red cells [23]. These cells are also less able to adhere to human umbilical vein endothelial cells [24].  Taken together it does appear that a thalassemic red cells may be less able to sequester in blood vessels, an important mechanism for virulence of infection.  It has also been suggested recently that the relatively high red cell counts in this condition may offer some degree of protection against the profound anemia of malaria in early life [25].  We will consider other possible immune mechanisms mediated by a+ thalassemia in a later section.
b thalassemia  With the exception of a small-scale case control study in Liberia, which suggested that the b thalassemia trait is protective against severe malaria, there have been no large-scale studies of this type [26].  There is however a considerable body of epidemiological data relating the frequency of b thalassemia to malaria transmission that indicates that it too may be a protective polymorphism against malaria, a conclusion that is strengthened by the pattern of haplotype analysis of the b globin genes in relationship to different b thalassemia mutations [16].  Furthermore, work in both human blood cells [27] and in the cells of transgenic mice carrying human g globin genes[28], it has been found that red cells which contain human fetal hemoglobin are associated with ineffective development of P. falciparum or P. yoelli.  Since there is clear evidence that the rate of decline of fetal hemoglobin production after birth is delayed in b thalassemia heterozygotes [16] this could offer a further mechanism of protection during the first year of life.

Thals can and do get malaria, but it is usually milder. During epidemics, while non-carriers died, minors lived, which explains the high percentages of thal carriers found in high malaria zones like Maldives and Southeast Asia.