Preliminary insights on the metabolomics of Trichinella zimbabwensis infection in Sprague Dawley rats using GCxGC-TOF-MS (untargeted approach).

Trichinella infections have been documented globally and have been detected in wild and/or domestic animals except Antarctica. There is paucity of information in the metabolic responses of hosts during Trichinella infections and biomarkers for infection that can be used in the diagnosis of the disease. The current study aimed to apply a non-targeted metabolomic approach to identify Trichinella zimbabwensis biomarkers including metabolic response from sera of infected Sprague-Dawley rats. Fifty-four male Sprague-Dawley rats were randomly assigned into T. zimbabwensis infected group (n = 36) and the non-infected control (n = 18). Results from the study showed that the metabolic signature of T. zimbabwensis infection consists of enriched methyl histidine metabolism, disturbance of the liver urea cycle, impeded TCA cycle, and upregulation of gluconeogenesis metabolism. The observed disturbance in the metabolic pathways was attributed to the effects caused by the parasite during its migration to the muscles resulting in downregulation of amino acids intermediates in the Trichinella-infected animals, and therefore affecting energy production and degradation of biomolecules. It was concluded that T. zimbabwensis infection caused an upregulation of amino acids; pipecolic acid, histidine, and urea, and upregulation of glucose and meso-Erythritol. Moreover, T. zimbabwensis infection caused upregulation of the fatty acids, retinoic acid, and acetic acid. These findings highlight the potential of metabolomics as a novel approach for fundamental investigations of host-pathogen interactions as well as for disease progression and prognosis.

Environmental DNA in human and veterinary parasitology - Current applications and future prospects for monitoring and control.

Parasites are important pathogens with significant global economic, public and animal health impacts. Successful control or elimination of many parasitic diseases, not least neglected tropical parasites, will require scalable, sensitive and cost-effective monitoring tools. Environmental DNA (eDNA) methods, used extensively in ecology for biomonitoring in natural ecosystems, offer promising advantages such reduced costs and labor requirements for species monitoring. Yet, the use of eDNA-based methods in parasitology and disease surveillance, has only recently begun to be explored. With this review, we wish to give an up-to-date overview of current uses and limitations of eDNA in human and veterinary parasitology, and how existing challenges can be overcome to fully utilize the potential of eDNA for monitoring and control of parasitic diseases. We begin by systematically searching published literature to identify studies that apply eDNA methods in parasitology and synthesize the main findings from these studies. We find that eDNA applications in parasitology only account for a small proportion (73/1960) of all eDNA publications up to now, and even fewer (27/73) studies, that apply eDNA methods specifically for parasites of human or veterinary importance. The majority of studies concern snail-borne trematodes and their intermediate host snails, while a few apply eDNA for mosquito vector species detection. A strong geographical bias, with only very few studies undertaken on the African continent, where parasites are of the biggest public health concern, is also noted. Current obstacles hindering further advances of eDNA methods in parasitology include incomplete reference databases, and challenges related to real-time monitoring in remote areas, and in certain LMIC settings. Finally, we point to future opportunities for eDNA-based research in parasitology and highlight recent innovations in eDNA research, which could further develop its application for monitoring and control of parasitic diseases and vectors in the future.

Prevalence and molecular characterization of cystic hydatidosis in livestock slaughtered in southern Mozambique.

Hydatid disease is a parasitic zoonosis caused by genotypes of the genus Echinococcus. This disease inflicts economic loses in livestock and cause public health burden in resource poor mostly in developing countries. The aim of this study was to determine the prevalence and identity of the genotypes responsible for hydatid cysts in cattle, goats and pigs slaughtered at selected abattoirs of southern provinces of Mozambique. Cysts were collected from liver and lungs and hydatid confirmation was made by cystic membrane observation and visualization of protoscoleces by light microscope. Thirty-two hydatid cysts from 817 cattle and two from 68 pigs were collected from local slaughterhouses and slabs. DNA was extracted from protoscoleces of each cyst together with the cystic membrane and amplified based on the mitochondrial subunit 1 of the cox1 and nad1 gene. The overall prevalence of hydatid cysts was 3.9% in cattle, 2.9% in pigs and none of the goats were found with cysts. All cysts collected from cattle and pigs were identified as Echinococcus ortleppi (G5) with a minimum homology of 99% on BLAST analysis. Our results confirm the presence of E. ortleppi in cattle and pigs in southern Mozambique at a low prevalence and further studies are recommended to determine the risk factors favoring the transmission of this zoonotic parasite in the resource-poor livestock farming communities of this region.

Geography and ecology of invasive Pseudosuccinea columella (Gastropoda: Lymnaeidae) and implications in the transmission of Fasciola species (Digenea: Fasciolidae) - a review.

Pseudosuccinea columella is considered invasive and has become an important intermediate host of both Fasciola species in many regions of the world. This systematic review assessed the geographical distribution of P. columella, and its implications in the transmission of Fasciola hepatica and Fasciola gigantica, globally. A literature search was conducted on Google Scholar, JSTOR and PubMed databases using Boolean operators in combination with predetermined search terms for thematic analysis. Results show that P. columella has been documented in 22 countries from Europe (3), Africa (8), Oceania (2), North America (3) and South America (6). Furthermore, this snail species has shown to adapt to and inhabit a vast array of freshwater bodies including thermal lakes and ditches with acidic soils. Studies showed that P. columella transmits F. hepatica, with natural and experimental infections documented in sub-Saharan Africa, Europe, South America and North America. Experimental infection studies in Cuba showed the presence of P. columella populations resistant to F. hepatica infection. Furthermore, some populations of this invasive snail collected from F. hepatica endemic locations in Brazil, Venezuela, Australia, South Africa, Colombia and Argentina were found without Fasciola infection. As a result, the role played by this snail in the transmission of Fasciola spp. in these endemic areas is still uncertain. Therefore, further studies to detect natural infections are needed in regions/countries where the snail is deemed invasive to better understand the veterinary and public health importance of this snail species in Fasciola-endemic areas and determine the global dispersion of resistant populations of P. columella.

Genetic diversity of Rickettsia africae isolates from Amblyomma hebraeum and blood from cattle in the Eastern Cape province of South Africa.

Rickettsia africae is a re-emerging tick-borne pathogen causing African tick bite fever (ATBF) in humans. Amblyomma variegatum is the principal vector in most sub-Sahara African countries, whereas in South Africa it is A. hebraeum. Reports of high genetic heterogeneity among R. africae isolates in southern Africa have prompted the need for molecular investigations of isolates form South Africa. Therefore, this study aimed to determine the prevalence and genetic diversity of R. africae in A. hebraeum collected from cattle, grazing pasture, as well as from blood of cattle in the Eastern Cape Province of South Africa. Amblyomma hebraeum and blood from cattle were screened by PCR and the gltA, ompA, ompB, sca4, and 17kDa genes were sequenced for R. africae from samples collected from Caquba in Port St. Johns along the coastal region in the Eastern Cape province of South Africa. The overall proportion of adult A. hebraeum that were positive for the gltA and ompA genes was 0.63 (108/180). The overall proportion of nymphs positive for the gltA and ompA genes was 0.62 (23/37) and 0.22 (20/90) from cattle blood. A positive R. africae infection was inferred by analysis of 26 sequences of the ompA, gltA, ompB, 17kDa and sca4 genes. Neighbour-joining and Maximum Likelihood analysis revealed that the study isolates were closely related to R. africae isolates from South Africa deposited in GenBank, forming a clade that was separate from north, east and west African strains. This study provides new information on the epidemiology and phylogeny of R. africae isolated from A. hebraeum ticks in the Eastern Cape province of South Africa. The heterogeneity observed between R. africae isolates from South Africa deposited in GenBank and R. africae isolates from Africa retrieved from Genbank highlight the importance of differentiation and tracking of the genetic movement among R. africae isolates in southern Africa for the better characterisation of ATBF cases, especially in rural communities and travellers visiting the region.

Echinococcosis in humans and animals in Southern Africa Development Community countries: A systematic review.

The taeniid Echinococcus is the causative agent of the zoonotic disease echinococcosis/hydatidosis and is associated with economic losses in livestock production. This review summarizes available scientific literature on circulating species of Echinococcus in humans, wild and domestic animals in countries of Southern Africa Development Community, and identifies knowledge gaps and recommend research priorities. Data were systematically accessed from Google Scholar, MEDLINE/PubMed and from library resources from December 2017 to June 2019. Meta-analysis was conducted in STATA program and heterogeneity and prevalence values were pooled by host species with 95% confidence interval. In intermediate hosts, the overall prevalence of Echinococcus by meat inspection was 10% (CI: 9-11%) in small ruminants, 7% (CI: 5-8%) in cattle, 1% (CI: 0-1%) in pigs and 9% (CI: 0-29%) in wild herbivores. In canids by CoproAg-ELISA and necropsy the prevalence was of 10% (CI: 8-10%) and 6% (CI: 3-10%) respectively. A high level of heterogeneity (I2 > 65%) was observed for all study groups. Echinococcus equinus, E. canadensis, E ortleppi and E. felidis were reported from wildlife and E. ortleppi, E. granulosus s. s. and E. canadensis from humans. There is paucity of research in echinococcosis and gaps in prevalence reports over time in both humans and animals in the SADC region and we recommend an increase in future studies on the epidemiology of disease, risk factors for transmission in animals and humans and its relation with human health specially in the advent of HIV pandemic following a "One Health" approach.

Comparison of praziquantel efficacy at 40 mg/kg and 60 mg/kg in treating Schistosoma haematobium infection among schoolchildren in the Ingwavuma area, KwaZulu-Natal, South Africa.

BACKGROUND: The World Health Organization recommends praziquantel (PZQ) (40 mg/kg body weight) for treating schistosomiasis. However, drug failure has been reported, prompting use of 60 mg/kg, for which results have been inconsistent. OBJECTIVES: To compare the efficacy of PZQ 40 mg/kg and 60 mg/kg in treating schoolchildren infected with Schistosoma haematobium. METHODS: The study was conducted during November 2017 - August 2018 in the Ingwavuma area, uMkhanyakude District, KwaZulu-Natal Province, South Africa. Children aged 10 - 15 years were screened for S. haematobium using a filtration technique. Infected children were randomly assigned to a dose of PZQ of 40 mg/kg or 60 mg/kg. Side-effects were recorded within 24 hours after treatment using questionnaires and direct observation. Four weeks after treatment, participants were retested for S. haematobium infection. Baseline and post-treatment mean egg counts were calculated. Cure rate (CR) and egg reduction rate (ERR) were used to determine PZQ efficacy, while repeated-measures analysis of variance determined the effect of both doses on infection intensity. A χ2 test was used to determine the association of side-effects with treatment, with a p-value ≤0.05. RESULTS: Forty-three and 36 children were treated with PZQ 40 mg/kg and 60 mg/kg, respectively. The 40 mg/kg group had a CR of 79.0% and an ERR of 97.2%, and the 60 mg/kg group a CR of 83.0% and an ERR of 98.3%. The effect of dose on infection intensity was not significantly different between the two groups (p>0.05). Abdominal pains, dizziness and fatigue were common among children who received PZQ 40 mg/kg, while headache, dizziness and nausea were common in the 60 mg/kg group. CONCLUSIONS: The efficacy of PZQ at 60 mg/kg was similar to that at 40 mg/kg. A dose >40 mg/kg therefore does not add value in treating S. haematobium infection. Transient side-effects (mostly dizziness) were observed more in the 60 mg/kg group than in the 40 mg/kg group. We recommend continued use of 40 mg/kg body weight for treating schistosomiasis.

A systematic review and meta-analysis of canine, feline and human Toxocara infections in sub-Saharan Africa.

Toxocariasis is an emerging zoonotic disease caused by Toxocara canis and T. cati. Toxocariasis and its etiological agents are of global public health importance, whose burden appears underestimated, especially in sub-Saharan Africa (SSA). The diversity in the transmission routes of these parasites contributes to disease prevalence and often hinders disease control measures. This study aimed to review the epidemiological distribution of Toxocara infections in SSA region. A systematic review and meta-analysis were performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). We identified 94 relevant, peer-reviewed articles, out of which, 75 articles were found eligible based on Toxocara infections in dogs, cats and humans. Overall, 27,102 samples were examined for T. canis in dogs, T. cati in cats and Toxocara serology in humans, out of which 6142 were positive for Toxocara infection: 3717 (13.7%) in dogs (faecal, 3487; necropsy, 180; hair, 50); 266 (1%) in cats (faecal, 101; necropsy, 165); and 2159 (8%) in humans (serology). Overall mean prevalences of 19% (95% confidence interval (CI): 14-23%), 9% (95% CI: 0-28%) and 36% (95% CI: 24-49%) were recorded in dogs, cats and humans, respectively. Substantial heterogeneity was observed between studies and subgroups (I2 = 99%, P < 0.01). Findings from the review showed that studies on the epidemiology of Toxocara infections in the SSA region are limited. We strongly recommend focused, collaborative and coordinated studies to determine Toxocara spp. prevalence in various hosts, including food animals and the environment, through a 'One Health' approach across SSA countries.

Fasciola species and their vertebrate and snail intermediate hosts in East and Southern Africa: a review.

A systematic review was conducted focusing on the distribution of Fasciola species and their snail intermediate hosts (IHs) in East and Southern Africa. The reviewed literature showed that both Fasciola hepatica and F. gigantica are present in East and Southern Africa, and infect a wide range of domestic and wild ruminants. Fasciola gigantica was reported in six East African and five Southern African countries, where Radix natalensis (found in low altitudes) was reported to be the main IH. Fasciola hepatica was reported in Tanzania and Ethiopia (East Africa), and in South Africa and Zimbabwe (Southern Africa), where Galba truncatula (found in high altitudes) was documented as the IH in all countries except in Zimbabwe. Both Fasciola species were documented in Tanzania, Ethiopia, Zimbabwe and South Africa. An overlap of the two was observed in areas with an intermediate altitude in Ethiopia and South Africa, where Pseudosuccinea columella was widespread and assumed to transmit both species. Pseudosuccinea columella has been reported in South Africa and Namibia, and proven to transmit F. gigantica in South Africa; its role in Namibia in the transmission of Fasciola species has not been reported. Other lymnaeid species such as R. rubiginosa were reported in South Africa, and R. auricularia in South Africa and Botswana; their role in the transmission of Fasciola species has not been proven. Future studies should aim to determine the role of P. columella in the geographical spread of the two species in East and Southern African countries.

Molecular detection of natural infection of Lymnaea (Pseudosuccinea) columella (Gastropoda: Lymnaeidae) with Fasciola gigantica (Digenea: Fasciolidae) from two provinces of South Africa.

The main intermediate host of Fasciola gigantica in sub-Saharan Africa is Lymnaea (Radix) natalensis. Lymnaea (Pseudosuccinea) columella is capable of transmitting both F. gigantica and F. hepatica and has been reported to be present in South Africa. To date, no natural infection with F. gigantica has been reported despite the wide distribution of the snail. The aim of this study was to confirm whether L. (P.) columella was transmitting F. gigantica and/or F. hepatica in selected locations of KwaZulu-Natal and Eastern Cape provinces of South Africa. Lymnaea (Pseudosuccinea) columella snails were collected from two locations in two provinces of South Africa and screened for cercariae shedding. This was followed by humanely sacrificing the screened snails, and whole tissue of each individual snail was homogenized and amplified using primers designed to amplify the ITS-1 region of Fasciola spp. No cercariae were shed from the screened snails and molecular analysis showed that snails from the two locations were infected with F. gigantica. This study confirms natural infection of L. (P.) columella with F. gigantica in South Africa, where F. gigantica and F. hepatica have already been reported to coexist. Although L. (P.) columella is able to transmit the two species, surprisingly no infection with F. hepatica was detected from the screened snails. The natural intermediate host of F. gigantica in southern Africa, including South Africa, is Lymnaea (Radix) natalensis and comparative studies are needed to determine the competence of the two snail species in the transmission of F. gigantica.

Molecular identification of hookworm isolates from stray dogs, humans and selected wildlife from South Africa.

There is a paucity of information on hookworm species in humans, domestic animals and wildlife in southern Africa. Our study aimed to identify hookworm species from stray dogs, humans, and selected wildlife from South Africa. A total of 356 faecal samples were screened for the presence of hookworm-like eggs and subsequently coproculture from the positive samples was carried out to obtain larvae. Hookworm-like eggs were detected in 23.03% (82/356) of samples. Of these samples, 78/296 were from dogs, 3/50 from humans and 1/10 from wildlife. DNA was then isolated from the larvae of 55 positive samples, which were subjected to polymerase chain reaction (PCR), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing of the nuclear ribosomal internal transcribed spacer (ITS1) and 5.8S rRNA region. Presence of Ancylostoma caninum, A. braziliense and A. ceylanicum-like species was recorded in stray dogs and A. caninum was recorded in wildlife and humans, using PCR-RFLP. Although PCR-RFLP results pointed to the presence of A. ceylanicum, we did not get a sequence that matched with A. ceylanicum from GenBank. This may have been due to the low proportion of A. ceylanicum larvae in our samples. Twenty-two of the 27 positive amplicons from stray dogs matched with A. caninum, three with A. braziliense and two had mixed infections of A. braziliense and A. caninum. Sequences from a lion and three humans matched with A. caninum. This is the first confirmation of a patent A. caninum infection in humans as evidenced by the presence of eggs in faeces, with the subsequent larvae from coproculture being identified as A. caninum.

Prevalence and molecular identification of Trichinella species isolated from wildlife originating from Limpopo and Mpumalanga provinces of South Africa.

Trichinella species are widely distributed on all continents with the exception of Antarctica, although the full spectrum of Trichinella species found in sub-Saharan African countries, and their hosts, has not been fully documented. This study was conducted to determine the prevalence of Trichinella in wildlife from the Greater Kruger National Park (GKNP) and adjacent areas located in the Limpopo and Mpumalanga provinces of South Africa, and to identify the species and/or genotypes of Trichinella larvae isolated from muscle tissues, using molecular techniques. A review of Trichinella spp. and their wildlife hosts reported during 1964-2011 was also conducted and the results were compared with our current study. Ninety samples representing 15 mammalian, two bird and three reptile species were screened for Trichinella infection during 2012-2016, using artificial digestion. Isolates detected were identified using a multiplex polymerase chain reaction (PCR) amplification of the internal transcriber spacers ITS1 and ITS2, and expansion segment V (ESV) regions of ribosomal DNA, followed by molecular analysis of the sequences. Twenty samples from seven wildlife species were positive for Trichinella spp. larvae, with an overall prevalence of 21.1% (20/90). The prevalence was higher in carnivores (18.9%, 18/90) than in omnivores (2.2%, 2/90). Analysis of sequences showed that eight of the isolates - two from spotted hyaena (Crocuta crocuta) (2/8), three from lion (Panthera leo) (3/13), one from leopard (Panthera pardus) (1/6), one from small spotted genet (Genetta genetta) (1/2) and one Nile monitor lizard (Varanus niloticus) (1/2) - conformed to Trichinella zimbabwensis. One isolate from a hyaena was grouped under the encapsulated species clade comprising T. nelsoni and genotype Trichinella T8 reported to be present in South Africa. This is the first report confirming natural infection by T. zimbabwensis in hyaena, leopard, genet and Nile monitor lizard, adding to the body of knowledge on the epidemiology of Trichinella infections in the Greater Kruger National Park of South Africa. Ten Trichinella-like larval isolates recovered after digestion from four wildlife species in this study (2012-2016) revealed inconclusive results due to DNA degradation resulting from poor storage or too few larvae for analysis, in comparison to 20 unidentified isolates from five wildlife species during the 1964-2011 period.

Validation of a urine circulating cathodic antigen cassette test for detection of Schistosoma haematobiumin uMkhanyakude district of South Africa.

Circulating cathodic antigen (CCA) tests for schistosomiasis are fast and less complicated allowing making them good candidates for routine qualitative screening for schistosomiasis at point of care. The urine-CCA has been evaluated for detection of S. mansoni with promising results. Its specificity and consistency in detecting S. haematobium infection in different endemic regions has been variable. This study validated a rapid urine-CCA cassette test for qualitative detection of S. haematobium infection in an S. haematobium endemic area with low S. mansoni prevalence. Microscopic examination for the standard urine filtration technique was used to validate the commercially available urine-CCA cassette test (rapid medical diagnostics ®). The validation was done in a sample of primary school pupils (n = 420) aged 10-15 years in schools in the Jozini Municipality, KZN. There was a relationship between infection intensity and a positive urine-CCA test. Using the urine filtration method as the gold standard, the prevalence for S. haematobium was 40%, the accuracy of the CCA kit was 54.8%, sensitivity was 68.1% while the specificity was 45.8%. The positive predictive value was 45.82% while the negative predictive value was 68.05%. Both the urine filtration and the urine-CCA methods detected heavy (≥50 eggs/10 mL urine) and light infections at statistically significant levels. The overall accuracy, sensitivity and specificity of the urine-CCA cassette test were low. The urine-CCA cassette test performed much better for heavy infections than low infections (p < 0.05) implying that the kit may not be suitable for low endemic areas.

Piloting the effectiveness of pig health education in combination with oxfendazole treatment on prevention and/or control of porcine cysticercosis, gastrointestinal parasites, African swine fever and ectoparasites in Angónia District, Mozambique.

A community-based intervention combining health education (HE) and treatment of pigs for control of porcine cysticercosis (PC), gastrointestinal (GI) helminths, African swine fever (ASF) and external parasites was tested involving six villages of resource-poor smallholder pig farmers. Farmers and pigs of six rural villages were randomly allocated into group 1 (HE), which served as controls, and group 2 (HE + OFZ) pigs received a single oral dose of 30 mg/kg OFZ. Farmers were trained in pig health, housing and feeding. The proportion of farmers with confined pigs, the adoption rate of the introduced pig pen, the sero-prevalence of PC and ASF, the prevalence and intensity of GI nematodes and the prevalence of ectoparasites were measured at 9, 15 and 24 months after initiation and compared to a baseline survey to seek the effectiveness of the interventions. There was no clear effect of the intervention on the sero-prevalence of PC, but analysis of the rate of change in prevalence between the two groups showed significant effect with the rate of change to lower prevalence in the HE + OFZ group compared to the HE group. Although HE managed to improve the farmer's knowledge in the control and prevention of ASF and ectoparasites, there was no significant reduction in the sero-prevalence of ASF and the prevalence of ectoparasites throughout the two-year period. The reported ineffectiveness of the intervention in this study suggested that more research is needed to develop more effective methods for controlling PC, ASF and pig parasites.

Metabolic and adaptive immune responses induced in mice infected with tissue-dwelling nematode Trichinella zimbabwensis.

Tissue-dwelling helminths are known to induce intestinal and systemic inflammation accompanied with host compensatory mechanisms to counter balance nutritional and metabolic deficiencies. The metabolic and immune responses of the host depend on parasite species and tissues affected by the parasite. This study investigated metabolic and immuno-inflammatory responses of mice infected with tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60) female BALB/c mice aged between 6 to 8 weeks old were randomly assigned into T. zimbabwensis-infected and control groups. Levels of Th1 (interferon-γ) and Th17 (interleukin-17) cytokines, insulin and blood glucose were determined as well as measurements of body weight, food and water intake. Results showed that during the enteric phase of infection, insulin and IFN-γ levels were significantly higher in the Trichinella infected group accompanied with a reduction in the trends of food intake and weight loss compared with the control group. During systemic larval migration, trends in food and water intake were significantly altered and this was attributed to compensatory feeding resulting in weight gain, reduced insulin levels and increased IL-17 levels. Larval migration also induced a Th1/Th17 derived inflammatory response. It was concluded that T. zimbabwensis alters metabolic parameters by instigating host compensatory feeding. Furthermore, we showed for the first time that non-encapsulated T. zimbabwensis parasite plays a role in immunomodulating host Th1/Th17 type responses during chronic infection.

Differential immune responses in mice infected with the tissue-dwelling nematode Trichinella zimbabwensis.

To improve diagnostic tools, immunotherapies and vaccine development for trichinellosis surveillance and control there is a need to understand the host immune responses induced during infection with Trichinella zimbabwensis, a tissue-dwelling nematode. In this study, we sought to determine immune responses induced in mice during T. zimbabwensis infection. The parasite strain used (Code ISS1209) was derived from a naturally infected crocodile (Crocodylus niloticus) and is the main Trichinella species prevalent in southern Africa. Sixty 6- to 8-week-old female BALB/c mice were randomly assigned to two equal groups: T. zimbabwensis-infected (n= 30) and the non-infected control group (n= 30). Levels of serum tumour necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4) as well as parasite-specific IgM, IgG, IgG1, IgG2a, IgG2b and IgG3 antibody responses were determined using enzyme-linked immunosorbent assay (ELISA). The cytokines and antibodies provided information on T-helper 1 (Th1)- and Th2-type, T-regulatory and antibody responses. Results showed that during the intestinal stage of infection, higher levels of parasite-specific IgM, IgG, IgG1 (P <  0.05) and IL-10 and TNF-α (P <  0.001) were observed in the Trichinella-infected group compared with the non-infected control group. In the parasite establishment and tissue migration phases, levels of IgG1 and IgG3 were elevated (P <  0.001), while those of IgM (P <  0.01) declined on days 21 and 35 post infection (pi) compared to the enteric phase. Our findings show that distinct differences in Th1- and Th2-type and T-regulatory responses are induced during the intestinal, tissue migration and larval establishment stages of T. zimbabwensis infection.

Efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats.

Trichinellosis is a zoonotic disease caused by nematode species of the genus Trichinella. Anthelmintics targeting the intestinal adults and muscle-dwelling larvae of Trichinella spp. have been tested, with limited success. This study was aimed at determining the efficacy of maslinic acid and fenbendazole on muscle larvae of Trichinella zimbabwensis in laboratory rats. Forty-two Sprague-Dawley rats, with an average weight of 270 g and 180 g for males and females respectively, were infected with T. zimbabwensis larvae. Infected rats were randomly assigned to three groups which were subjected to single treatments with each of maslinic acid, fenbendazole and a combination of both on day 25 post-infection (pi), and three groups which were subjected to double treatments with each of these drugs and a combination on days 25 and 32 pi. The untreated control group received a placebo. In single-treatment groups, the efficacy of each treatment, measured by rate of reduction in muscle larvae, was significant (P0.05). We conclude that the efficacy of maslinic acid against larval stages of T. zimbabwensis in rats was comparable to that of fenbendazole, with no side-effects observed, making maslinic acid a promising anthelmintic against larval stages of Trichinella species.

The occurrence of Trichinella zimbabwensis in naturally infected wild crocodiles (Crocodylus niloticus) from the Kruger National Park, South Africa.

Trichinella zimbabwensis has been found naturally infecting crocodiles (Crocodylus niloticus) in Zimbabwe, Mozambique, Ethiopia and South Africa, as well as monitor lizards (Varanus niloticus) in Zimbabwe. The reports on natural infections were mostly accidental rather than structured surveys and involved very few animals. Previous surveillance studies in South Africa reported a 38.5% prevalence of T. zimbabwensis among wild crocodiles tested from the Mpumalanga province and Kruger National Park (KNP). No studies have been conducted to date on the geographical distribution and occurrence of T. zimbabwensis in wild crocodiles and varans in countries in southern Africa. Recent outbreaks of pansteatitis in crocodile populations of the KNP, South Africa, provided an opportunity to conduct a more structured survey aimed at elucidating the occurrence and distribution of T. zimbabwensis in culled wild crocodile populations within the KNP. Results from this study showed that T. zimbabwensis occurred in 10 out of 12 culled crocodiles form the KNP. The results also showed that the natural distribution of T. zimbabwensis in crocodiles includes all the major river systems in the KNP. The predilection sites of larvae in muscles followed a different pattern in naturally infected crocodiles compared to observations in experimentally infected mammalian hosts.

Anti-malarial drug formulations and novel delivery systems: a review.

Artemisinin combination therapies have decreased malaria associated morbidity and mortality in several parts of the world. On the other hand, malaria cases have increased in sub-Saharan Africa largely due to falciparum resistance to the most frequently used drugs (chloroquine and sulphadoxine/pyrimethamine (SP) combination). Therapeutic failure has also been attributed in part to adverse effects of anti-malarial drugs and patients' non-compliance due to inconvenient dosing schedules. We consider that formulation and evaluation of novel drug delivery systems is not only less expensive than developing new drugs, but may also improve delivery of anti-malarials at the desired rates. In this review we evaluate the therapeutic efficacy of existing anti-malarial drugs and assess the feasibility of developing novel formulations and delivery systems.