the more cynical microbiologists Louis Pasteur, Charles
Edouard Chamberland and Pierre Paul Émile Roux.
Robert Koch, one of the most influential microbiologists
of his time, however, remained sceptical until 1887.
Nevertheless in some quarters the miasma theory persisted
and as late as 1895 the American R. C. Newton, a
supporter of Tommasi-Crudeli, wrote that ‘Aerial and
aquatic transportation of malaria has been proved’ [17].
(This paper is worth reading in full because, although
based on what we now know to be false premises, it
contains a mass of interesting information about the
prevention of malaria such as the use of screens or mosquito
nets to exclude insects, closing doors at night and
lighting fires out of doors). Laveran was awarded the
Nobel Prize for Medicine in 1907 and his discoveries
are described in some detail by the Sergent brothers
[18] and Bruce-Chwatt [19] as well as in the various histories
of malaria listed above.
What was remarkable about Laveran’s discovery was
that it was without precedent as no protozoan had previously
been found inhabiting any kind of human blood
cell. Unbeknown to Laveran or the Italian malariologists,
however, the Russian physiologist, Vassily Danilewsky
had been examining the blood of birds and reptiles in
the Ukraine and had discovered a number of parasites
including trypanosomes and others that he identified as
‘pseudovacules’. Anyone who has studied blood parasites
will immediately recognise his description of ‘pseudovacuoles’
as unstained malaria parasites. By 1885 Danilewsky
had recognised the three most common genera
of intraerythrocytic blood parasites of birds now known
as Plasmodium, Haemoproteus and Leucocytozoon but,
as he had published much of his work in Russian, it was
not until his three volume book La Parasitologie Comparée
du Sang had been published in French in 1889
that this information became widely available [20].
Thereafter there began searches for other malaria parasites
in reptiles, birds and mammals and this was facilitated
by the accidental discovery of a methylene blueeosin
stain by Dimitri Leonidovitch Romanowsky in
1891 [6]. Romanowsky’s stains became popular at the
beginning of the twentieth century and remain the basis
of blood stains such as Leishman’s, Giemsa’s and
Wright’s to the present day. These stains colour the
nucleus of the parasite red and the cytoplasm blue permitting
their easy identification and are used not only
for malaria parasites but also for trypanosomes, leishmanias
and filarial worms. Romanowsky’s discovery is one
of the most significant technical advances in the history
of parasitology.
Meanwhile the Italian workers, now convinced that
malaria was caused by a parasite, took up the challenge
with vigour and Marchiafava and Bignami, using a combination
of eosin-based blood stains and the oilimmersion
microscope objective developed by the Carl
Zeiss Company in 1882-4, observed amoeboid movement
of the organism. This left them in no doubt that
they were dealing with a protozoan parasite that invaded
red blood cells, grew within the cells and produced
daughter cells that invaded fresh blood cells [21]. Thereafter
the Italian views dominated malaria research and,
based on observations of the erythrocytic stages of the
parasite, Golgi between 1885-6 differentiated between
tertian (48 hour periodicity) and quartan (72 hour periodicity)
malaria [22] and in 1889-1890 Golgi and
Marchiafava further described the differences between
mild Spring malaria (benign tertian) and severe Summer-Autumn
(malignant tertian) malaria [23].
By this time it had also become clear that the paroxsms
characteristic of malaria coincided with the bursting
of infected red blood cells and the release of the
products of multiplication something that Laveran, who
had also realised that in the case of malignant tertian
malaria the brain was involved, had proposed [24]. Thus
by 1890 it was known that malaria was caused by a protozoan
parasite that invaded and multiplied in red blood
cells and, after a lot of confusion, that there were three
species with specific periodicities and other characteristics
responsible for benign tertian (Haemamoeba vivax),
malignant tertian (Laverania malariae) and quartan
(Haemamoeba malariae) malaria now respectively Plasmodium
vivax, P. falciparum and P. malariae. The
situation as it existed in 1900 is beautifully summarised
by Grassi in his monograph, Studi di uno Zoologo Sulla
Malaria [25] and, although more details have since
been added, this work remains as relevant today as it
was 110 years ago. In 1918, John Stephens, working in
West Africa, discovered a fourth species which
resembled P. vivax which he described as P. ovale in
1922 [26].