Malaria-induced reduction of fecundity during the first gonotrophic cycle of Anopheles Stephensi mosquitoes

Abstract. Anopheles stephensi mosquitoes which had fed upon mice infected with Plasmodium yoelii nigeriensis malaria parasites produced significantly fewer eggs than mosquitoes fed on an uninfected mouse. Fecundity reduction was more pronounced when the bloodmeal contained malaria gametocytes and the mosquitoes developed oocysts. Egg production and haematin excretion were correlated for uninfected bloodfed mosquitoes; the presence of P.y. nigeriensis in the blood affected this relationship. Reduced fecundity was associated with a significant reduction of bloodmeal size (measured by haematin excretion) in mosquitoes which ingested gametocytaemic blood. The bloodmeal size in mosquitoes fed on parasitaemic blood without gametocytes was not significantly reduced. The use of haematin assays for determination of bloodmeal size in mosquitoes is discussed.     

Dose dependent responses of cattle to Theileria parva stabilate

Dolan T. T., Young A.S., Losos G.J., McMillan I., Minder Ch.E. and Soulsby K. 1984. Dose dependent responses of Theileria parva stabilate. International Journal for Parasitology14: 89–95. A tick derived stabilate of Theileria parva (Maguga) was titrated in a large group of Boran (Bos indicus) cattle of the same age, sex and origin. The infectivity data was analysed using the independent action model. The cattle were identified as heterogeneous in their response to infection with 75% showing one ID₅₀ (0.0014) and 25% showing another (0.01). The disease responses of the cattle given different dose levels were compared for a variety of parameters. The results obtained showed these parameters to be dose dependent including the time to onset of piroplasm parasitaemia. The stabilate is of large volume and can be used for controlled challenge in immunity studies and for comparison of susceptibility between cattle of different breeds and from different epidemiological backgrounds.     

Babesia major: protection of intact calves against homologous challenge by the injection of irradiated piroplasms.

Blood from a splenectomized calf infected with Babesia major was divided into 20 ml aliquots which were γ-irradiated at doses of 0, 23.3, 27.3, 31.4, 35.4 and 39.5 krad and then inoculated into groups of three intact calves. Animals receiving non-irradiated blood had typical mild B. major reactions, but those receiving blood irradiated at 23.3, 27.3 and 31.4 krad and 2 of 3 receiving blood irradiated at 35.4 krad had minimal reactions. The remaining 4 animals had no detectable parasitaemic reactions. When the calves were challenged with a similar number (6.0 × 10⁹) of homologous parasites, they were all immune with the exception of the 4 animals which had not reacted initially. The immune status of individual cattle was reflected accurately in the results of the micro-ELISA test, which detected a significant rise in serum antibody titre of the 4 susceptible animals 7 days after challenge.     

Synthesis and antimalarial activity of novel chiral and achiral benzenesulfonamides bearing 1, 3, 4-oxadiazole moieties

A series of new benzenesulfonamides, most of which are chiral, incorporating 1, 3, 4-oxadiazole and amino acid moieties have been synthesized. Some of these compounds were screened for antimalarial activity and also evaluated for their ability to inhibit hem polymerization. The electrophoretic analysis indicated that one compound was effective in inhibiting the degradation of hemoglobin. The synthesized compounds were tested in mice infected with Plasmodium berghei. These derivatives have the potential for the development of novel antimalarial lead compounds.     

Exposure to nectar-realistic sugar concentrations negatively impacts the ability of the trypanosome parasite (Crithidia bombi) to infect its bumblebee host

1. The ideal conditions for a parasite are typically found with its preferred host. However, prior to transmission to a naïve host and successful infection, a parasite may have to withstand extrinsic environmental conditions. Some parasites have adapted to time away from hosts, for example, by co-opting vectors or by having drought-resistant growth stages. However, other parasites may have no obvious adaptations to persist during prolonged transmission cycles. Consequently, the environment may detrimentally impact parasite fitness and ultimately epidemiology. 2. Here, we investigate the impact of nectar-realistic sugar concentrations on the ability of the trypanosome parasite Crithidia bombi, which may be transmitted between conspecifics at flowers, to infect its bumblebee host Bombus terrestris and to reproduce during the infection (parasitaemia). Our results show, following 30 min exposure to our experimental nectars that as sugar concentration increases, infection prevalence and parasitaemia decrease. This is likely due to the increased osmotic stress C. bombi experiences in high sugar, aqueous environments. 3. Consequently, if C. bombi transmission is facilitated by nectar or a high-sugar environment, it may have a negative impact on parasite fitness.     

Evidence of an increased incidence of day 3 parasitaemia in Suriname: an indicator of the emerging resistance of Plasmodium falciparum to artemether

The emerging resistance to artemisinin derivatives that has been reported in South-East Asia led us to assess the efficacy of artemether-lumefantrine as the first line therapy for uncomplicated Plasmodium falciparum infections in Suriname. This drug assessment was performed according to the recommendations of the World Health Organization in 2011. The decreasing number of malaria cases in Suriname, which are currently limited to migrating populations and gold miners, precludes any conclusions on artemether efficacy because adequate numbers of patients with 28-day follow-up data are difficult to obtain. Therefore, a comparison of day 3 parasitaemia in a 2011 study and in a 2005/2006 study was used to detect the emergence of resistance to artemether. The prevalence of day 3 parasitaemia was assessed in a study in 2011 and was compared to that in a study in 2005/2006. The same protocol was used in both studies and artemether-lumefantrine was the study drug. Of 48 evaluable patients in 2011, 15 (31%) still had parasitaemia on day 3 compared to one (2%) out of 45 evaluable patients in 2005/2006. Overall, 11 evaluable patients in the 2011 study who were followed up until day 28 had negative slides and similar findings were obtained in all 38 evaluable patients in the 2005/2006 study. The significantly increased incidence of parasite persistence on day 3 may be an indication of emerging resistance to artemether.     

Experimental evaluation of xenodiagnosis to detect trypanosomes at low parasitaemia levels in infected hosts

In Human African Trypanosomosis (HAT) endemic areas, there are a number of subjects that are positive to serological tests but in whom trypanosomes are difficult to detect with the available parasitological tests. In most cases and particularly in West Africa, these subjects remain untreated, thus posing a fundamental problem both at the individual level (because of a possible lethal evolution of the disease) and at the epidemiological level (since they are potential reservoirs of trypanosomes). Xenodiagnosis may constitute an alternative for this type of cases. The objective of this study was to update the use of xenodiagnosis to detect trypanosomes in infected host characterized by low parasitaemia levels. This was carried out experimentally by infecting cattle and pigs with Trypanosoma congolense and T. brucei gambiense respectively, and by feeding tsetse flies (Glossina morsitans submorsitans and G. palpalis gambiensis, from the CIRDES colonies) on these animals at a time when the observed blood parasitaemia were low or undetectable by the classical microscopic parasitological tests used for the monitoring of infected animals. Our results showed that: i) the G. p. gambiensis colony at CIRDES could not be infected with the T. b. gambiense stocks used; ii) midgut infections of G. m. submorsitans were observed with both T. congolense and T. b. gambiense; iii) xenodiagnosis remains positive even at very low blood parasitaemia for both T. congolense and T. b. gambiense; and iv) to implement T. b. gambiense xenodiagnosis, batches of 20 G. m. submorsitans should be dissected two days after the infective meal. These results constitute a first step toward a possible implementation of xenodiagnosis to better characterize the parasitological status of seropositive individuals and the modalities of parasite transmission in HAT foci.     

Physicochemical investigation and in vivo activity of anti-malarial drugs co-loaded in Tween 80 niosomes

Abstract

Drugs used for the treatment and prevention of malaria are often plagued by the problem of development of resistance. This has hampered their therapeutic efficiency and rendered them ineffective for monotherapy. However, if re-packaged and combined properly, many of these neglected anti-malarial drugs can possibly find their way back into the treatment regime. The present study evaluates the use of curcumin (CC) and primaquine (PRI) as an anti-malarial combination, packaged within niosomes, in comparison to their respective monotherapy options. It was observed that in Plasmodium berghei-infected mice, mice treated with a combination of 35?mg/kg of CC along with either 5?mg/kg or 1?mg/kg body weight of PRI demonstrated 100% anti-malarial activity and survivability beyond 20 days. The niosome-based PRI–CC combination therapy provided increased protection and survival rate that was associated with prevention in recrudescence. The findings of the study suggest that niosome-based PRI–CC combination therapy may be a promising approach in the treatment of malaria.     

DNA from pre-erythrocytic stage malaria parasites is detectable by PCR in the faeces and blood of hosts

Following the bite of an infective mosquito, malaria parasites first invade the liver where they develop and replicate for a number of days before being released into the bloodstream where they invade red blood cells and cause disease. The biology of the liver stages of malaria parasites is relatively poorly understood due to the inaccessibility of the parasites to sampling during this phase of their life cycle. Here we report the detection in blood and faecal samples of malaria parasite DNA throughout their development in the livers of mice and before the parasites begin their growth in the blood circulation. It is shown that parasite DNA derived from pre-erythrocytic stage parasites reaches the faeces via the bile. We then show that different primate malaria species can be detected by PCR in blood and faecal samples from naturally infected captive macaque monkeys. These results demonstrate that pre-erythrocytic parasites can be detected and quantified in experimentally infected animals. Furthermore, these results have important implications for both molecular epidemiology and phylogenetics of malaria parasites. In the former case, individuals who are malaria parasite negative by microscopy, but PCR positive for parasite DNA in their blood, are considered to be “sub-microscopic” blood stage parasite carriers. We now propose that PCR positivity is not necessarily an indicator of the presence of blood stage parasites, as the DNA could derive from pre-erythrocytic parasites. Similarly, in the case of molecular phylogenetics based on DNA sequences alone, we argue that DNA amplified from blood or faeces does not necessarily come from a parasite species that infects the red blood cells of that particular host.     

Experimental infection with the Toxoplasma gondii ME-49 strain in the Brazilian BR-1 mini pig is a suitable animal model for human toxoplasmosis

Toxoplasma gondii causes toxoplasmosis, a worldwide disease. Experimentation with pigs is necessary for the development of new therapeutic approaches to human diseases. BR-1 mini pigs were intramuscularly infected with T. gondii with tachyzoites (RH strain) or orally infected with cysts (ME-49 strain). Haematology and serum biochemistry were analysed and buffy coat cells were inoculated in mice to determine tachyzoite circulation. No alterations were observed in erythrocyte and platelet values; however, band neutrophils increased seven days after infection with ME-49. Serology of the mice inoculated with pig blood leucocytes revealed circulating ME-49 or RH strain tachyzoites in the pigs'' peripheral blood at two and seven or nine days post-infection. The tachyzoites were also directly observed in blood smears from the infected pigs outside and inside leucocytes for longer periods. Alanine-aminotransferase was high at days 21 and 32 in the RH infected pigs. After 90 days, the pigs were euthanised and their tissue samples were processed and inoculated into mice. The mice serology revealed the presence of parasites in the hearts, ileums and mesenteric lymph nodes of the pigs. Additionally, cysts in the mice were only observed after pig heart tissue inoculation. The infected pigs presented similar human outcomes with relatively low pathogenicity and the BR-1 mini pig model infected with ME-49 is suitable to monitor experimental toxoplasmosis.