Frank Hawking

Bio: Frank Hawking is an academic researcher from Medical Research Council. The author has contributed to research in topics: Trypanosomiasis & Tryparsamide. The author has an hindex of 8, co-authored 15 publications receiving 408 citations. Previous affiliations of Frank Hawking include National Institute for Medical Research.

Evidence for cyclic development and short-lived maturity in the gametocytes of Plasmodium falciparum.

Abstract: 1 1 In a previous paper (Hawking et al, 1968) it has been shown that with malaria parasites exhibiting a periodic synchronous asexual cycle (eg Plasmodium knowlesi; P cynomolgie and P cathemerium), the gametocytes show a 24 or 48 hour rhythm in their development to maturity and that this maturity is short lived (6–12 hours) 2 2 In the present work, exflagellation of the male gametocytes of Plasmodium falciparum was studied quantitatively in 4-hourly blood films taken from 5 infected children in Gambia, West Africa 3 3 In 2 cases there was clear evidence of a 48 hour cycle in the number of exflagellations observed; in 2 cases there was a “probable” cycle present, and in 1 case there was a “possible” cycle although the evidence is not decisive 4 4 It is concluded that the gametocytes of P falciparum probably resemble those of other periodic plasmodia in showing a (48 hour) rhythm of development to maturity (taking into account the well known irregularity of P falciparum) 5 5 The development of gametocytes of P falciparum was also studied in Aotus monkeys The classical view was confirmed that development from the merozoite takes more than 9 days and that there is no evidence for cell division during this process

The trypanocidal action of human serum and of baboon plasma

Abstract: 1. 1. Investigations have been made on the activity of normal human serum, and of baboon plasma in killing non-pathogenic trypanosomes such as Trypanosoma equiperdum. Baboon plasma is 5 times more active than human serum but otherwise its activity is qualitatively the same. 2. 2. The activity varies according to whether it is measured in vitro or in vivo (i.e. in mice). It is postulated that there are 2 closely related substances, A which acts in vitro and B which acts in vivo. Usually both substances are present but in suitable circumstances they can be obtained separately. Most human and baboon sera contain much B, but some contain very little A. Usually there is 20–40 times as much B as A. 3. 3. In vitro, there is a lag period of about 34 hour and then trypanocidal action is completed in less than 6 hours. In vivo the action is a little slower. 4. 4. Substance A is suppressed if the human serum is injected intravenously into rats and mice but B is made more active. The substances could not be removed from serum by absorption with large numbers of trypanosomes. 5. 5. Human serum and baboon plasma were fractionated by ion-exchange chromatography and by gel filtration using Sephadex G-150 and Sepharose 6B. The active fractions were further examined by Laurell immunoelectrophoresis. These techniques indicated that the active substances are α2 macroglobulins with molecular weight approximately 300,000. B has a slightly greater molecular weight and is slightly more acidic than A. It is postulated that both substances possess the same protein nucleus, but that they differ slightly in the configuration and/or composition. Some sera, which were initially inactive in vitro, yielded highly active fractions after gel filtration; this activation might be due to conversion of B into A or to removal of inhibitors which were masking A. 6. 6. When trypanosomes are exposed to serum there is a latent period of half an hour, after which the trypanosomes become distorted until they are almost globular. As shown by the electron microscope, there is progressive disintegration of the cytoplasm and large clear spaces appear beneath the pellicle. The other structures of the trypanosome persist unchanged for a long period, but ultimately the trypanosome disintegrates. 7. 7. As shown above the trypanocidal substances are α2 macroglobulins and they are probably synthesized in the liver (not in the spleen and lymph glands). Accordingly their activity is quite different from the standard immunological processes. Their action might be due to either a coincidental stimulation of the serum protein by the surface of the trypanosome, or it might be a biological mechanism to protect men and baboons from many species of African trypanosomes, or that it might be part of a properdin system against infections in general. 8. 8. The trypanocidal action of human serum has been used by Rickman and Robson (1970) in the Blood Incubation Infectivity Test to differentiate T. rhodesiense from T. brucei. Improved methods for conducting and interpreting this test will be described in a second communication.

Concentration of Bayer 205 (Germanin) in Human Blood and Cerebrospinal Fluid after Treatment.

Abstract: 1. 1. By means of the Wormall test, estimations were made on the concentration of Bayer 205 found in the plasma of African sleeping-sickness patients who had been treated with this compound. Big variations were found between one individual and another. 2. 2. In persons who had received a single intravenous dose of 1 gramme, the average concentration was about 3 mg. per 100 ml. after two days, and about 0·6 mg. after nine days. 3. 3. In persons who received courses of four doses, the concentrations reached depended more upon the individual peculiarities of the patient than upon the spacing of the doses. One day after the fourth dose, the concentration in the blood ranged from 4 to 15 mg. per 100 ml. After courses of five or six doses, Bayer 205 could be demonstrated in the blood of some patients up to eight or nine months later; in other patients it had disappeared within five months. 4. 4. Estimations were made on the cerebrospinal fluid. Although Bayer 205 was present in the plasma of these patients in considerable concentrations, it did not penetrate into the fluid in sufficient amounts to be detected by the chemical test. 5. 5. Since individuals vary so greatly in their tendency to retain Bayer 205 in their blood, it is strongly recommended that the treatment of European cases of sleeping-sickness be controlled by chemical estimations.

The differentiation of Trypanosoma rhodesiense from T. brucei by means of human serum

Abstract: 1. 1. A review is made of the Blood Incubation Infectivity Test (BIIT) introduced by Rickman and Robson (1970) to differentiate Trypanosoma rhodesiense from T. brucei in the laboratory. This test consists of incubating the trypanosomes with human blood and then injecting them into a rat; if the rat becomes infected, the trypanosomes are probably T. rhodesiense, and conversely. 2. 2. In the present paper it is shown that most of the effect of the human blood or serum is exerted after injection into the animal, and not during the previous incubation in vitro; moreover, the effect is proportional to the dose of blood per weight of animal. Accordingly, improved methods of conducting the test are recommended, especially the inoculation of the trypanosomes—blood mixture into 5 mice (rather than 1 rat), each animal to receive at least 0·4 ml. human blood per 20 g. weight. 3. 3. Further, the test should be interpreted according to statistical definitions of what is to be accepted as “serum-resistance”. Provisionally a strain which can infect 20% of the animals (treated with human blood as above) might well be regarded as “serum-resistant” (probably T. rhodesiense) and so potentially dangerous to man.

Transmission of Plasmodium knowlesi by Anopheles stephensi.

Abstract: 1. (1) A virulent strain of Plasmodium knowlesi has been transmitted through Anopheles stephensi (four times) and A. maculipennis atroparvus mosquitoes (once). A second strain has been transmitted through A. stephensi once. 2. (2) Oocysts developed on the midgut of the mosquitoes, but the sporozoites in the salivary glands were always scanty. 3. (3) The shortest pre-patent period observed was 6.8 days. 4. (4) There was no obvious change of virulence as a result of mosquito transmission.

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

Abstract: Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.

Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III.

Abstract: A recently discovered member of the human T-cell leukemia virus (HTLV) family of retroviruses has been etiologically linked to the acquired immune deficiency syndrome (AIDS). This virus, which has been designated HTLV-III, is tropic for OKT4-bearing (helper-inducer) T cells. Moreover, the virus is cytopathic for these cells. Suramin is a drug used in the therapy of Rhodesian trypanosomiasis and onchocerciasis, and it is known to inhibit the reverse transcriptase of a number of retroviruses. Suramin has now been found to block in vitro the infectivity and cytopathic effect of HTLV-III at doses that are clinically attainable in human beings.