Milk, the forgotten antimalarial

It all begins in 1952 with the work of the Liverpool School of Tropical Medicine (BG Maegraith et al, British Medical Journal, 1952, 1382-3). They found that in rats inoculated with Plasmodium berghei and living on a diet of milk there was a strong suppression of the growth of the parasites. This was valid for retail whole cow’s milk, reconstituted dried milk from different origins and human milk. Most rats on normal laboratory diet died in a few days. The authors suggested that the milk might contain an inhibitory substance and that herein lies the explanation of the common observation that severe malaria is not often seen in very young infants. In these first experiments only blood-transmitted malaria had been studied.

 

The London School of Tropical Medicine followed-up on this early work (RS Bray et al., Brit Medical Journal, 1953, 1200-1) and confirmed that sporozoite-induced infections of Plasmodium cynomogi in monkeys behaved much the same as blood-induced infections. But after a return to normal diet a severe recrudescence took place.

At the same time work done by Wilson and Garnham on the shores of lake Victoria suggested that milk might be deficient in certain nutrients required by the parasite, but that these are present in any normal diet. For the first three months in life children are exclusively breast-fed and they stay malaria free. At the third or fourth month mothers usually start giving them a variety of foods in addition to the breastmilk, and these extras might supply the nutrients required by the parasite.

The National Institute for Medical Research (F Hawking et al., British Medical Journal, 1953 1201-2) finds that milks contains very little p-aminobenzoic acid (PABA), not more than 0.004 ppm. This substance is much more plentiful in some of the constituents of a good laboratory diet, where the vegetal components contain up to 60 ppm of PABA. In vitro Plasmodium requires PABA for satisfactory growth. Experiments were undertaken to study this possibility. Rats were maintained on different diets: normal diet, milk, milk with 1000 ppm of PABA. Only the rats on the milk diet stayed free of P. berghei on day 12.

 

In 1980 the University of Minnesota ( MJ Murray et al., British Medical Journal, 1980 1351-2) showed that milk had a salutary effect on amoebiasis. Milk-drinking African nomads showed an unusual freedom from infection with Entamoeba histolytica compared with similar nomads taking a mixed diet. The authors related this to a low content in iron in cow’s milk. A personal communication from Dr Patrick Ogwang informs that in Uganda malaria is highest in East and North Uganda where the staple food is cereals with high iron content, in western Uganda where milk and low iron foods are eaten most malaria is low. In the past however, people in East and North also kept cows (zebu) and took milk regularly and malaria was not as rampant.

In 1983 a five month study was undertaken in Brazil (JJ Ferraroni, Mem Inst Oswaldo Cruz, 78, 27-35, 1983) to test the effect of a total milk diet on the susceptibility of mice to various doses of a the rodent malaria P berghei. The development of humoral immunity was followed by quantitation of the specific serum immunoglobulins (IgG and IgM). High levels of IgG antibodies persisted for 150 days , IgM antibodies were only observed during the two first weeks of infection. The results indicated that a milk diet administered to mice as the only source of food protected them against fatal malaria infection regardless of the number of parasites inoculated. The acquired immunity was still present in the mice at 150 days post inoculation.

But these very promising treatments were ignored by Bigpharma and subsidized research. Obviously dairy milk or dried milk is not an interesting cash cow in the fight against malaria.

Only more recently, in the light of resistance to most, if not all, of the pharmaceutical molecules (chloroquine, amodiaquine, lumefantrine, chloroquine, sulfadoxine-pyrimethmine) some research groups have tried to better understand these fifty years old findings. And the proposed role for PABA (p-aminobenzoic acid) seems to be confirmed. (GA McConkey, Antimicrob Ag Chemotherapy, 1999, 43-1, 175-177) (W Krteschmar, Z Tropenmed Parasitol 1966,17-4, 375-90). Plasmodium generates it’s own PABA in its apicomplexan organelle, but not in quantities sufficient to guarantee survival and multiplication of trophozoites and schizonts in the infected erythrocyte (GA Kiczka et al., J Infect Dis. 2003, 188, 1776-82). And as the human body does not generate its own PABA or folates, but takes them essentially from green vegetables, the parasite has to rely on this supply. If the diet is exclusively on milk it has no chance to survive.

Pierre Lutgen


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