Influence of Cyclophosphamide on the Haematological Profile of Laboratory Bred African Soft-furred Rats (Mastomys natalensis)

The African soft-furred rat (Mastomys natalensis) has been shown to be a possible model for propagation  of Trypanosoma brucei gambiense. This study aimed at determining the baseline biological reference values  and reproductive data of a laboratory bred Mastomys colony, which was established at TRC. In addition,  the effect of cyclophosphamide (an immunosuppressant) treatment (s) on the haematological profile  was investigated. The mean gestation period was 23 days and the mean litter size was eight. At birth, the  pups weighed 2.4±0.23 g and the weights increased to 78.0±10.6 g in males and 53.9±4.5 g in females by  90 days. The mean haematological values were significantly (p<0.05) higher in adults than juveniles.  However, there was no statistical difference of haematological values between the sexes.  Cyclophosphamide treatment caused a macrocytic hypochromic anaemia, which was noted 24 hours after  treatment and was more severe in animals treated more than once. Thus, in studies involving a disease that  causes anaemia, repeated cyclophosphamide treatment should be limited. Our study is a contribution to  the clinical and biological characterization of the disease pattern in this preferred rodent model of T. b.  gambiense.

Prevalence and Types of Coinfections in Sleeping Sickness Patients in Kenya (2000/2009)

The occurrence of coinfections in human African trypanosomiasis (HAT) patients was investigated using a retrospective data of hospital records at the National Sleeping Sickness Referral Hospital in Alupe, Kenya. A total of 31 patients, 19 males and 12 females, were diagnosed with HAT between the years 2000 and 2009. The observed co-infections included malaria (100%), helminthosis (64.5%), typhoid (22.5%), urinary tract infections (16.1%), HIV (12.9%), and tuberculosis (3.2%). The species of helminthes observed included Ancylostoma duodenale (38.7%), Ascaris lumbricoides (45.7%), Strongyloides stercoralis (9.7%), and Taenia spp. (3.2%). The patients were also infected with Entamoeba spp. (32.3%) and Trichomonas hominis (22.6%) protozoan parasites. The main clinical signs observed at the point of admission included headache (74.2%), fever (48.4%), sleep disorders (45.2%), and general body pain (41.9%). The HAT patients were treated with suramin (early stage, 9/31) and melarsoprol (late stage, 22/31). In conclusion, the study has shown that HAT patients have multiple co-infections which may influence the disease pathogenesis and complicate management of HAT

Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis

Novel drugs to treat human African trypanosomiasis (HAT) are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (NECT) to WHO Model Lists of Essential Medicines against second stage HAT, where parasites have invaded the central nervous system (CNS). The pharmacology of a potential orally available lead compound, N-methoxy-6-{5-[4-(N-methoxyamidino) phenyl]-furan-2-yl}-nicotinamidine (DB844), was evaluated in a vervet monkey model of second stage HAT, following promising results in mice. DB844 was administered orally to vervet monkeys, beginning 28 days post infection (DPI) with Trypanosoma brucei rhodesiense KETRI 2537. DB844 was absorbed and converted to the active metabolite 6-[5-(4-phenylamidinophenyl)-furanyl-2-yl]-nicotinamide (DB820), exhibiting plasma C(max) values of 430 and 190 nM for DB844 and DB820, respectively, after the 14th dose at 6 mg/kg qd. A 100-fold reduction in blood trypanosome counts was observed within 24 h of the third dose and, at the end of treatment evaluation performed four days post the last drug dose, trypanosomes were not detected in the blood or cerebrospinal fluid of any monkey. However, some animals relapsed during the 300 days of post treatment monitoring, resulting in a cure rate of 3/8 (37.5%) and 3/7 (42.9%) for the 5 mg/kg×10 days and the 6 mg/kg×14 days dose regimens respectively. These DB844 efficacy data were an improvement compared with pentamidine and pafuramidine both of which were previously shown to be non-curative in this model of CNS stage HAT. These data show that synthesis of novel diamidines with improved activity against CNS-stage HAT was possible

Use of the nested polymerase chain reaction for detection of Toxoplasma gondii in slaughterhouse workers in Thika District, Kenya

Background. The widely used methods of diagnosis of Toxoplasma gondii are serological. Current reports indicate a high seroprevalence of T. gondii in humans in Kenya. There is a need for more sensitive diagnostic tests, especially when the specific antibody titres are below detectable threshold levels. Use of the polymerase chain reaction (PCR) targeting the repetitive 529 base pair loci has been reported to be sensitive and specific.Objective. To detect T. gondii in a high-risk group of public health workers in Thika District, Kenya.Methods. In total, 87 human blood samples were collected from male slaughterhouse workers between 1 March 2013 and 25 June 2013. The DNA extracted was amplified by the nested PCR.Results. T. gondii was detected in 39.1% (34/87) of the workers. In the cow-sheep-goat slaughterhouses the prevalence ranged between 20% and 60%, while all the chicken slaughterhouse workers (6/6, 100%) tested positive. The difference in T. gondii positivity between the workers in the chicken slaughterhouse and those in the cattle-sheep-goat slaughterhouses was statistically significant (p=0.003).Conclusion. This study shows the presence of T. gondii in an asymptomatic high-risk group in Thika District, indicating the need for enhancement of public health awareness

A Fatal Outbreak of Campylobacter jejuni Enteritis in a Colony of Vervet Monkeys in Kenya

In a group of 50 wild-caught vervet monkeys trapped for experimental studies, 23 developed severe diarrhoea  during the quarantine period. While 10 of these responded well to routine treatment with metronidazole,  kaomycin and oral electrolytes, 13 initially showed slight improvement but later relapsed. Five of  these failed to respond altogether and were euthanised. Fresh faecal samples were collected from the surviving  eight monkeys and analysed for microbiology and drug sensitivity. Campylobacter jejuni, sensitive  to erythromycin, was isolated from all the faecal samples. Following treatment with erythromycin, seven  monkeys recovered fully within ten days but one died before the end of therapy. This study indicates that  wild non-human primates may play a significant role as a reservoir of C. jejuni, whereby they may act as  natural carriers of this human pathogen. Screening for Campylobacter sp in newly acquired monkeys is  advisable as part of the quarantine procedures.

Use of the nested polymerase chain reaction for detection of Toxoplasma gondii in slaughterhouse workers in Thika District, Kenya

Background. The widely used methods of diagnosis of Toxoplasma gondii are serological. Current reports indicate a high seroprevalence of T. gondii in humans in Kenya. There is a need for more sensitive diagnostic tests, especially when the specific antibody titres are below detectable threshold levels. Use of the polymerase chain reaction (PCR) targeting the repetitive 529 base pair loci has been reported to be sensitive and specific.Objective. To detect T. gondii in a high-risk group of public health workers in Thika District, Kenya.Methods. In total, 87 human blood samples were collected from male slaughterhouse workers between  1 March 2013 and  25 June 2013. The DNA extracted was amplified by the nested PCR.Results. T. gondii was detected in 39.1% (34/87) of the workers. In the cow-sheep-goat slaughterhouses the prevalence ranged between 20% and 60%, while all the chicken slaughterhouse workers (6/6, 100%) tested positive. The difference in T. gondii positivity between the workers in the chicken slaughterhouse and those in the cattle-sheep-goat slaughterhouses was statistically significant (p=0.003).Conclusion. This study shows the presence of T. gondiiin an asymptomatic high-risk group in Thika District, indicating the need for enhancement of public health awareness.

<i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis

Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops

Interspecies interactions and potential Influenza A virus risk in small swine farms in Peru

<p>Abstract</p> <p>Background</p> <p>The recent avian influenza epidemic in Asia and the H1N1 pandemic demonstrated that influenza A viruses pose a threat to global public health. The animal origins of the viruses confirmed the potential for interspecies transmission. Swine are hypothesized to be prime "mixing vessels" due to the dual receptivity of their trachea to human and avian strains. Additionally, avian and human influenza viruses have previously been isolated in swine. Therefore, understanding interspecies contact on smallholder swine farms and its potential role in the transmission of pathogens such as influenza virus is very important.</p> <p>Methods</p> <p>This qualitative study aimed to determine swine-associated interspecies contacts in two coastal areas of Peru. Direct observations were conducted at both small-scale confined and low-investment swine farms (n = 36) and in open areas where swine freely range during the day (n = 4). Interviews were also conducted with key stakeholders in swine farming.</p> <p>Results</p> <p>In both locations, the intermingling of swine and domestic birds was common. An unexpected contact with avian species was that swine were fed poultry mortality in 6/20 of the farms in Chancay. Human-swine contacts were common, with a higher frequency on the confined farms. Mixed farming of swine with chickens or ducks was observed in 36% of all farms. Human-avian interactions were less frequent overall. Use of adequate biosecurity and hygiene practices by farmers was suboptimal at both locations.</p> <p>Conclusions</p> <p>Close human-animal interaction, frequent interspecies contacts and suboptimal biosecurity and hygiene practices pose significant risks of interspecies influenza virus transmission. Farmers in small-scale swine production systems constitute a high-risk population and need to be recognized as key in preventing interspecies pathogen transfer. A two-pronged prevention approach, which offers educational activities for swine farmers about sound hygiene and biosecurity practices and guidelines and education for poultry farmers about alternative approaches for processing poultry mortality, is recommended. Virological and serological surveillance for influenza viruses will also be critical for these human and animal populations.</p

Taenia solium Infections in a Rural Area of Eastern Zambia-A Community Based Study

Taenia solium taeniosis/cysticercosis is a zoonotic infection endemic in many developing countries, with humans as the definitive host (taeniosis) and pigs and humans as the intermediate hosts (cysticercosis). When humans act as the intermediate host, the result can be neurocysticercosis, which is associated with acquired epilepsy, considerable morbidity and even mortality. In Africa, most studies have been carried out in pigs with little or no data in humans available. In this human study, conducted in a rural community in Eastern Zambia, prevalences for taeniosis and cysticercosis were determined at 6.3% and 5.8% respectively, indicating the hyperendemicity of the area. Cysticercosis infection was strongly related with age, with a significant increase in prevalence occurring in individuals from the age of 30 onward. A collected tapeworm was confirmed to be T. solium. Risk factors associated with the transmission and maintenance of the parasite such as free roaming pigs, households without latrines, backyard slaughter of pigs without inspection and consumption of undercooked pork were also present. The findings of this work have identified the need for further research in the transmission dynamics and the burden that this infection has on the resources of poor local people