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Introduction: Fever is managed using synthetic drugs such as aspirin, paracetamol among others. Synthetic drugs are associated with many side effects. Herbal medicines form alternative therapy since they possess fewer side effects and are readily available . This study aimed to determine antipyretic potential of DCM extracts of E. globulus and S. didymobotrya in Swiss albino rats., Materials and Methods: The plant leaves samples were obtained from Embu County, Kenya. Dichloromethane solvent was used to extract bioactive constituents from the plant samples. Three grams of DCM leaf extracts of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) samples were obtained and analyzed to determine quantitative phytochemical composition at ICIPE laboratory using GC-MS. Albino rats were used in the antipyretic activity study. Nine groups of five experimental animals were used in each test: Positive control, normal control, negative control and experimental (25, 50, 100, 150, 200 and 250 mg/kg body weight extracts) groups. Pyrexia was induced by injection of turpentine in albino rats intraperitoneally. One hour later, the pyretic animals received the leaf extracts at various dose levels, reference drug (aspirin100 mg/kg body) or the vehicle (DMSO)., Results: Results of antipyretic in vivo bioscreening revealed that E. globulus and S. didymobotrya possess potent antipyretic activity which was comparable to that of the reference drug aspirin. Both extracts exhibited highest antipyretic activity at a dose of 250 mg/kg bw. Results of the GC-MS revealed that these plants possess bio-compounds such as Terpinolene, Alpha-pinene, Borneol, Globulol and Terpineols that are associated with antipyretic activity., Conclusions: In conclusion, this study revealed that these plants are endowed with bioactive compounds such as terpenoids, and flavonoids that possess antipyretic activity in rats., (© 2019 The Author(s).)

Background: Accurate diagnosis of malaria is key to proper management and control and an ideal diagnostic parameter that correlates to disease outcome is required. The former would be helpful in correctly identifying patients that need hospitalisation versus those that can be managed at home. This study determined how well the density estimates by microscopy, qPCR and Pf HRP-2 correlate to malaria severity., Materials and Methods: Patients aged ≤ 5 yrs with severe (n = 60, Hb ≤ 6 g/dl) and mild (n = 60, Hb > 6 g/dl) malaria were enrolled to take part in a case control study at Kisumu District Hospital, Western Kenya. Parasite load was determined by microscopy, qPCR targeting the 18s rRNA gene and Pf HRP-2 antigen ELISA., Results: The median parasite load and the 25 th and the 75 th percentile by microscopy in children with severe malaria (SM) was 49,958 parasites/μl (12,013-128,695) compared to 24,233 (6,122-103,886) in the group with mild malaria (MM), P = 0.10. By qPCR, the translated median parasite density was 31,550 parasites/μl (4,106-196,640) in the SM group compared to 24,365 parasites/μl (5,512-93,401) in the MM group (P = 0.73). According to Pf HRP-2, the translated median parasite load in children with SM was 628,775 parasites/μl (332,222-1.165x106) compared to 150,453 (94,292-399,100) in children with MM (P < 0.0001)., Conclusions: Unlike microscopy and qPCR, the parasite load detected by Pf HRP-2 correlates with disease severity. Because of its unique attributes, Pf HRP-2 is able to account for trophozoites and schizonts that are sequestered away from peripheral circulation. Because it persists in circulation, it also serves as an indicator of the magnitude of current and recent infections., Competing Interests: Competing Interests: No competing interests declared., (Copyright © 2014: Kituyi et al.)

The isolation and characterization of primary strains of human immunodeficiency virus (HIV) is a vital tool for assessing properties of viruses replicating in HIV-infected subjects. HIV-1 isolation was carried out from 30 HIV-1-infected patients from a Comprehensive Care Clinic (CCC) after informed consent. Virus was successfully isolated from 9 out of the 30 samples investigated. Seven of the isolates were from drug-naive patients while two were from patients on antiretroviral drugs. The isolates were biologically phenotyped through measurement of the syncytium-inducing capacity in MT2 cells. Six of the isolates exhibited syncytia induction (SI) associated with CXCR4 coreceptor usage while three of the isolates were non-syncytia-inducing (NSI) isolates associated with CCR5 coreceptor usage. In addition, the replication capacity of the isolates was further determined in established cell line CD4(+) C8166. Indirect immunofluorescence assay was used to check the antigen expression on the cells as a supplementary test. HIV-1 isolation success was 70% (7/10) and 20% (2/20) in naive and drug-experienced patients, respectively. The majority of the viral isolates obtained (6/9) were of the SI phenotype, though SI virus strains are rare among non-B subtypes. A significant correlation between virus isolation success and viral load was established. Coreceptor use data for heavily treatment-experienced patients with limited treatment options are scanty and this is the group with perhaps the most urgent need of novel antiretroviral agents.

The two classes of cytokines Th1 and Th2 determine the type of immune response elicited. The Th2 immune response is associated with successful pregnancy. Brucellosis is an intracellular bacterium that elicits the Th1 response and is known to cause spontaneous abortion in mammalian species. This study sought to determine if Brucella infection causes spontaneous abortion by causing the circulating cytokine profile be Th1 dominant during pregnancy. Forty-eight Swiss white mice were used in this murine model and the S19 strain of Brucella abortus was used in as the infective agent. Pregnant mice in the test group were injected intraperitoneally with 10(5-8) CFU of Brucella and cytokine profile evaluated over the three trimesters of pregnancy. Pregnant mice in the control group were left to go through normal pregnancy and their cytokine profile evaluated over the three trimesters of pregnancy. Cytokines in serum samples were analyzed by Cytometric Bead Array. The data was analyzed using the Paired T- test and p < 0.05 was considered significant. IFN-γ and TNF-α represented the Th1 cytokines while IL-4 and IL-5 represented the Th2 cytokines. None of the mice in the test group had spontaneous abortion. IFN-γ and TNF-α had no significant differences between cytokine levels for infected and uninfected groups in all 3 trimesters of pregnancy. IL-4 levels had significant differences in all three trimesters of pregnancy (t = 13, P = 0.036, 0.0071 and 0.0277). IL-5 levels had significant differences second trimester (t = 14, P = 0.0075). The cytokine profile was robustly Th2. In conclusion, Brucella abortus cannot cause spontaneous abortion by altering the mouse cytokine profile towards Th1 in pregnancy. Elevated IL-4 levels with corresponding suppression of IFN-γ can be used as a marker for successful pregnancy in Brucellosis.

Molecular tools continue to be important in the prevention and control of parasitic diseases. However, using these techniques directly in the field remains a major challenge. Therefore, the preservation of clinical samples collected from endemic field areas for later analysis remains an important preanalytical process. This study aimed at identifying a suitable protocol for stabilization and preservation of RNA and DNA in bioclinical specimens for Trypanosoma, Leishmania, and Plasmodium research. Both spiked and unspiked blood samples were preserved in 7 protocols (different media; storage temperatures). Samples were evaluated for possible degradation of DNA and RNA along the storage duration up to the 10th week. Nucleic acid targets were assessed as follows: (i) Trypanosoma and Plasmodium RNA analysis was done using real-time nucleic acid sequence-based amplification (RT-NASBA) for 18S rRNA and for stage-specific Pfs25 mRNA, respectively; (ii) Trypanosoma DNA assessment analysis was conducted by using a conventional PCR for 18S rDNA; (iii) Leishmania RNA analysis was performed with a quantitative NASBA for 18S rRNA and Leishmania DNA assessment with an RT-PCR for 18S rDNA. Findings suggested that a newly developed L3™ buffer proved to be reliable and suitable for both short- and long-term preservation of parasite nucleic acid material. This buffer is envisaged to be suitable for utilization in field situations where resources are limited., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Infections due to methicillin resistant S. aureus (MRSA) present global challenges to clinicians since therapeutic options are limited and suboptimal dosing contributes to heightened mortality and increased length of hospital stay particularly among the HIV infected patients., Objectives: To assess the prevalence and relative risk of MRSA infections in HIV infected patients., Design: Cross sectional analytical study., Setting: Kenya Medical Research Institute, Opportunistic Infection Laboratories in Nairobi., Subjects: Four hundred and thirty six male and female patients aged one to 65 years, of whom 220 were HIV-infected and 216 were non-infected., Results: There was 436 male (57.1%) and female (42.9%) respondents. The prevalence of MRSA was 26.3% with majority infecting the HIV infected patients (P=0.046). Likewise, the overall Staphylococcal infections were more common in HIV patients (P <0.001). The common test for MRSA oxacillin disk diffusion had a sensitivity and specificity of 100% and 92%., Conclusion: HIV is a predisposing factor to Staphylococcal infection and there are indications that treatment with beta-lactam antibiotics may no longer be relied on as sole empiric therapy for several ill HIV patients whose infections may be of MRSA in origin. There is need for an informed choice in administration of appropriate antibiotics in order to minimise treatment failures due to the multidrug resistance and Vanvomycin intermediate S. aureus (VISA) strains. Molecular epidemiology of MRSA strains in understanding new and emerging trends is recommended.

A total of 90 animals was immunized against East Coast fever (ECF) using Theileria parva (Marikebuni) stock on three large-scale farms in Kiminini Division, Trans-Nzoia District, North Rift, Kenya. Another 90 cattle served as non-immunized controls. Following immunization the number of cattle with significant indirect fluorescent antibody (IFA) titres increased from 43.9% to 84.4% and 6.7% of the cattle developed clinical ECF reactions. Two months after immunization, the immunized and non-immunized cattle were divided into two groups one of which was dipped every 3 weeks and the other dipped when total full body tick counts reached 100. All the animals were monitored for 51 weeks for incidences of ECF and other tick-borne diseases. Twenty-four cases of ECF were diagnosed among the non-immunized cattle compared to four cases among the immunized cattle; a difference that was significant (P > 0.05). There was no significant difference in the incidences of babesiosis and anaplasmosis between the immunized and non-immunized cattle.

Background: Surveillance data documenting tick and tick-borne disease (TBD) prevalence is needed to develop risk assessments and implement control strategies. Despite extensive research in Africa, there is no standardized, comprehensive review. Methods: Here we tackle this knowledge gap, by producing a comprehensive review of research articles on ticks and TBD between 1901 and 2020 in Chad, Djibouti, Ethiopia, Kenya, Tanzania, and Uganda. Over 8356 English language articles were recovered. Our search strategy included 19 related MeSH terms. Articles were reviewed, and 331 met inclusion criteria. Articles containing mappable data were compiled into a standardized data schema, georeferenced, and uploaded to VectorMap. Results: Tick and pathogen matrixes were created, providing information on vector distributions and tick–pathogen associations within the six selected African countries. Conclusions: These results provide a digital, mappable database of current and historical tick and TBD distributions across six countries in Africa, which can inform specific risk modeling, determine surveillance gaps, and guide future surveillance priorities. [ABSTRACT FROM AUTHOR]

Cattle and buffalo are the main species producing milk for human consumption. Minor milch species such as goat, sheep, camel, horse, yak, donkey, and reindeer make up a less significant portion of the total milk supply in the dairy sector as their production share is relatively small. However, in recent years, people have started to recognize the numerous health and nutritional benefits of milk from these minor milch species. There is a rich diversity of traditional dairy products in the world, among which the ethnic products made from the milk of minor dairy species have a solicitous place in their region of origin. The ingredients and composition of these products and the preparation methods impart their characteristic taste and flavour along with their typical nutritional and functional health benefits. Anti-microbial, probiotic, antioxidant, nutraceutical, and other health-promoting qualities are the few benefits of these products. However, lack of research and developmental activities, promotions and advertisements of ethnic milk products of minor milch species have led to their limited awareness among the consumers. In view of the above, the present review attempts to discuss some of the important ethnic milk products around the world from the milk of minor milch species. [ABSTRACT FROM AUTHOR]

Inflammation is the core contributor in the pathogenesis of various acute and chronic illness including appendicitis, bronchitis, arthritis, cancer and neurological diseases. NSAIDs, commonly used medications for inflammatory diseases, on prolonged use cause GI bleeding, ulcers and many more issues. Plant-based therapeutic agents including essential oils in combination with low-dose synthetic drugs have been shown to produce synergistic effects and reduce complications of synthetic drugs. This study was designed to evaluate the anti-inflammatory, analgesic and anti-pyretic properties of Eucalyptus globulus essential oil alone and in combination with flurbiprofen. GC–MS analysis was performed to screen chemical composition of oil. In vitro anti-inflammatory assay (membrane stabilization assay) and in vivo inflammatory acute (carrageenan and histamine-induced paw oedema) and chronic (cotton pellet-induced granuloma and Complete Freund's adjuvant-induced arthritis) models were performed to check anti-inflammatory properties. Acetic acid-induced algesia and yeast-induced pyrexia models were performed to check analgesic and anti-pyretic properties. qRT-PCR was performed to study the effect of treatments on the expression of inflammatory biomarkers. GC–MS analysis of E. globulus essential oil showed the presence of eucalyptol along with other active biomolecules. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better in vitro membrane stabilization effects as compared with groups treated with 500 mg/kg of E. globulus oil and 10 mg/kg of Flurbiprofen alone. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better anti-inflammatory, analgesic and antipyretic effects as compared to 500 mg/kg of E. globulus oil alone in all in vivo models. When comparison was done between 500 + 10 mg/kg of oil-drug combination-treated and 10 mg/kg Flurbiprofen-treated group, the former group showed significantly (p < 0.05) better anti-inflammatory and anti-pyretic effects, but there were non-significant differences in the analgesic model. Animal group treated with 10 mg/kg of Flurbiprofen showed significantly (p < 0.05) better anti-inflammatory and analgesic effects than group treated with 500 mg/kg of oil alone while, there were non-significant differences in anti-pyretic effects. qRT-PCR analysis showed significant (p < 0.05) down-regulation in the expression of IL-4 and TNF-α in serum samples of animals treated with 500 + 10 mg/kg of oil-drug combination as compared to the diseased control (arthritic) group. Overall, the current research demonstrates that Eucalyptus globulus essential oil in combination with flurbiprofen showed better anti-inflammatory, analgesic and anti-pyretic effects than oil and flurbiprofen alone which is attributed to the down-regulation of pro-inflammatory biomarkers (IL-4 and TNF-α). Further studies are required to formulate a stable dosage form and to check the anti-inflammatory efficacy in different inflammatory disorders. [ABSTRACT FROM AUTHOR]

The range of the protozoan parasite Theileria parva, which causes East Coast fever in cattle, has been expanding to countries where it has not previously been detected, as a result of cross-border domestic cattle movement. Countries where T. parva has not previously been observed until recently include Cameroon and South Sudan. This raises the issue of the conservation of the p104 antigen gene, on which the nested PCR assay that is widely used for T. parva surveillance in the blood of infected cattle is based. We sampled 40 isolates from six countries widely distributed across the geographical range of the parasite, including eastern, central and southern Africa, for p104 sequence polymorphism. These included parasites from both domestic cattle and the Cape buffalo (Syncerus caffer) wildlife reservoir. The most frequent allelic variants were present in cattle transmissible isolates from multiple widely separated geographical regions in Zambia, Uganda, Kenya, Tanzania, Rwanda and South Africa. These frequent p104 variants were also present in the three component stocks of the Muguga cocktail used for the infection and treatment live immunisation procedure to control T. parva in the field. Other isolates exhibited unique alleles. This includes some of the p104 sequences from Cameroon, which is outside the known range of the Rhipicephalus tick vector and whose origin is therefore unclear. The nested primer oligonucleotides used to generate the amplicons were universally conserved in cattle-derived parasites and a majority of buffalo-derived isolates across the geographical range of the parasite. However, some rare South African buffalo–derived isolates exhibited one or two mismatches with the primer sequences. It therefore remains possible that some p104 alleles may be so divergent that they do not amplify with the current diagnostic primers and are not detectable in surveys, hence the need for increasing knowledge of genetic heterogeneity of diagnostic targets. There was no evidence for positive selection among those p104 mutations that resulted in residue changes. Importantly, the data indicate that the p104-based PCR detection assay should be effective across the majority of the range of T. parva, and if the one or two mismatches are shown in future to result in the primers annealing less efficiently, then the assay can be further improved by introduction of degenerate bases to enable amplification of the less frequent South African buffalo–derived variant p104 genes. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Agricultural, Environmental & Veterinary Sciences is the property of Arab Journal of Sciences & Research Publishing (AJSRP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Difficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs. [ABSTRACT FROM AUTHOR]

Background: Water is the most abundant resource on earth, however water scarcity affects more than 40% of people worldwide. Access to safe drinking water is a basic human right and is a United Nations Sustainable Development Goal (SDG) 6. Globally, waterborne diseases such as cholera are responsible for over two million deaths annually. Cholera is a major cause of ill-health in Africa and Uganda. This study aimed to determine the physicochemical characteristics of the surface and spring water in cholera endemic communities of Uganda in order to promote access to safe drinking water.Methods: A longitudinal study was carried out between February 2015 and January 2016 in cholera prone communities of Uganda. Surface and spring water used for domestic purposes including drinking from 27 sites (lakes, rivers, irrigation canal, springs and ponds) were tested monthly to determine the vital physicochemical parameters, namely pH, temperature, dissolved oxygen, conductivity and turbidity.Results: Overall, 318 water samples were tested. Twenty-six percent (36/135) of the tested samples had mean test results that were outside the World Health Organization (WHO) recommended drinking water range. All sites (100%, 27/27) had mean water turbidity values greater than the WHO drinking water recommended standards and the temperature of above 17 °C. In addition, 27% (3/11) of the lake sites and 2/5 of the ponds had pH and dissolved oxygen respectively outside the WHO recommended range of 6.5-8.5 for pH and less than 5 mg/L for dissolved oxygen. These physicochemical conditions were ideal for survival of Vibrio. cholerae.Conclusions: This study showed that surface water and springs in the study area were unsafe for drinking and had favourable physicochemical parameters for propagation of waterborne diseases including cholera. Therefore, for Uganda to attain the SDG 6 targets and to eliminate cholera by 2030, more efforts are needed to promote access to safe drinking water. Also, since this study only established the vital water physicochemical parameters, further studies are recommended to determine the other water physicochemical parameters such as the nitrates and copper. Studies are also needed to establish the causal-effect relationship between V. cholerae and the physicochemical parameters. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Agricultural Chemistry & Biotechnology is the property of Egyptian National Agricultural Library (ENAL) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. Methods: A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. Results: In sequential analyses with 49–51 patients per arm, initial cure was 85% (95% CI: 73–92) in all arms. At D210, definitive cure was 87% (95% CI: 77–97) for AmBisome + SSG, 77% (95% CI 64–90) for AmBisome + miltefosine and 72% (95% CI 60–85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. Conclusion: No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. Trial Registration: The study was registered with ClinicalTrials.gov, number [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is a chronic physiological glucose metabolic disorder. It has affected millions of people all over the world thereby having a significant impact on quality of life. The management of diabetes includes both nonpharmacological and conventional interventions. Drawbacks in conventional therapy have led to seeking alternative therapy in herbal medicine. Therefore, the need to review, elucidate and classify their mode of action in therapy for diabetes disease arises. Materials and Methods: Comprehensive literature reports were used to review all conventional agents and herbal therapy used in the management of diabetes. An online database search was conducted for medicinal plants of African origin that have been investigated for their antidiabetic therapeutic potentials. Results: The results showed that of the documented sixty five plants used, fourteen inhibit intestinal absorption of glucose, three exhibit insulin-mimetic properties, seventeen stimulate insulin secretion from pancreatic beta cells, twelve enhance peripheral glucose uptake, one promotes regeneration of beta-cell of islets of Langerhans, thirteen ameliorate oxidative stress and twenty induces hypoglycemic effect (mode of action is still obscure). Thirteen of these plants have a duplicate mode of actions while one of them has three modes of actions. These agents have a similar mechanism of action as the conventional drugs. Conclusion: In conclusion, antidiabetic activities of these plants are well established; however, the molecular modulation remains unknown. It is envisaged that the use of herbal therapy will promote good health and improve the status of diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Anti-leishmanial drug regimens that include a single dose AmBisome® could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. Methodology: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome® for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome® 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1–5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. Principal Findings: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73–93%), 40% (95%CI 19–64%), and 58% (95%CI 41–73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. Conclusions: The tested AmBisome® regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. Trials Registration: www.clinicaltrials.govNCT00832208 Author Summary: Visceral leishmaniasis is a potentially fatal disease which affects 0.2–0.4 million people every year, principally in South-East Asia, Latin America or Eastern Africa. Currently the safest drug in use is AmBisome®, which cures 90% of patients in India at 5 mg/kg, and is even more effective at higher doses (10 mg/kg) or in combination with miltefosine or paromomycin. These regimens have been shown to be equally cost-effective in India. However, the drug requires a cold chain for storage and reconstitution prior to injection. Although it is licensed for use in eastern Africa, in practice it is mainly used as a second-line treatment. A small study carried out in Kenya indicated that a higher dose is necessary in eastern Africa in contrast to Asia. This study aimed to determine the minimum single dose that is safe and effective for treatment of eastern African VL patients so as to be used in simplified treatment regimens. However, the tested regimens were found to be ineffective, and an optimal single dose that could potentially be used in simplified treatment regimens was not identified. [ABSTRACT FROM AUTHOR]

Background: East Coast fever (ECF) caused by Theileria parva is endemic in Rwanda. In this study, the antigenic and genetic diversity of T. parva coupled with immunization and field challenge were undertaken to provide evidence for the introduction of ECF immunization in Rwanda. Methods: Blood collected from cattle in the field was screened for T. parva using ELISA and PCR targeting the p104 gene. Tp1 and Tp2 gene sequences were generated from field samples and from Gikongoro and Nyakizu isolates. Furthermore, multilocus genotype data was generated using 5 satellite markers and an immunization challenge trial under field conditions using Muguga cocktail vaccine undertaken. Results: Out of 120 samples, 44 and 20 were positive on ELISA and PCR, respectively. Antigenic diversity of the Tp1 and Tp2 gene sequences revealed an abundance of Muguga, Kiambu and Serengeti epitopes in the samples. A further three clusters were observed on both Tp1 and Tp2 phylogenetic trees; two clusters comprising of field samples and vaccine isolates and the third cluster comprising exclusively of Rwanda samples. Both antigens exhibited purifying selection with no positive selection sites. In addition, satellite marker analysis revealed that field samples possessed both shared alleles with Muguga cocktail on all loci and also a higher proportion of unique alleles. The Muguga cocktail (Muguga, Kiambu and Serengeti) genotype compared to other vaccine isolates, was the most represented in the field samples. Further low genetic sub-structuring (FST = 0.037) coupled with linkage disequilibrium between Muguga cocktail and the field samples was observed. Using the above data to guide a field immunization challenge trial comprising 41 immunized and 40 control animals resulted in 85% seroconversion in the immunized animals and an efficacy of vaccination of 81.7%, implying high protection against ECF. Conclusions: Antigenic and genetic diversity analysis of T. parva facilitated the use of Muguga cocktail vaccine in field conditions. A protection level of 81.7% was achieved, demonstrating the importance of combining molecular tools with field trials to establish the suitability of implementation of immunization campaigns. Based on the information in this study, Muguga cocktail immunization in Rwanda has a potential to produce desirable results. [ABSTRACT FROM AUTHOR]

Antibiotic-resistant bacteria, also called “superbugs”, can at worst retrogress modern medicine to an era where even sore throats resulted in death. A solution is the development of novel types of antibiotics from untapped natural sources. Yet, no new class of antibiotic has been developed in clinical medicine in the last 30 years. Here, bacteria from insect-killing Steinernema roundworms found in the soils of Central Kenya were isolated and subjected to specific molecular identification. These were then assayed for production of antibiotic compounds with potential to treat methicillin-resistant Staphylococcus aureus infections. The bacteria were identified as Xenorhabdus griffiniae and produced cell free supernatants that inhibited S. aureus. Fermenting the bacteria for 4 days yielded a heat stable anti-staphylococcal class of compounds that at low concentrations also inhibited methicillin-resistant S. aureus. This class contained two major compounds whose identity remains unknown. Thus X. griffinae isolated from Steinernema roundworms in Kenya have antimicrobial potential and may herald novel and newly sourced potential medicines for treatment of the world’s most prevalent antibiotic resistant bacteria.

Antibiotic-resistant bacteria, also called “superbugs”, can at worst retrogress modern medicine to an era where even sore throats resulted in death. A solution is the development of novel types of antibiotics from untapped natural sources. Yet, no new class of antibiotic has been developed in clinical medicine in the last 30 years. Here, bacteria from insect-killing Steinernema roundworms in the soils of Central Kenya were isolated and subjected to specific molecular identification. These were then assayed for production of antibiotic compounds with potential to treat methicillin-resistant Staphylococcus aureus infections. The bacteria were identified as Xenorhabdus griffiniae and produced cell free supernatants that inhibited S. aureus. Fermenting the bacteria for 4 days yielded a heat stable anti-staphylococcal class of compounds that at low concentrations also inhibited methicillin-resistant S. aureus. This class contained two major compounds whose identity remains unknown. Thus X. griffinae isolated from Steinernema roundworms in Kenya have antimicrobial potential and may herald novel and newly sourced potential medicines for treatment of the world’s most prevalent antibiotic resistant bacteria.

The importance of ensuring food safety through the reduction of chemical residues in our food supply cannot be overemphasized. Food safety remains a major challenge confronting contemporary society. To ensure wholesomeness of food of animal origin, the level of drug residues must be below the maximum residue limits (MRLs) set by World Health Organization (WHO) and Food and Agriculture Organization (FAO). This calls for cost effective and efficient analytical methods for both quality assurance and monitoring. Diminazene aceturate is one of the few treatment drugs for animal trypanosomosis in the market. Because of its wide use in food producing animals, unwanted residues may be a risk to consumers. A competitive enzyme-linked immunosorbent assay (cELISA) for determination of diminazene residues in edible animal tissues after extraction in 0.1 M borax pH 9.7 is described. The assay has advantages of speed, high throughput and lower cost of analysis compared to the other conventional methods. The assay uses rabbit anti-diminazene polyclonal antibodies bound on a 96-well microtiter plate. Horseradish peroxidase-labeled diminazene and diminazene in a test sample were allowed to compete overnight at 4°C for the limited number of antibodies bound on the microtiter plate. After six washes with buffer, enzyme activity was determined by adding tetramethyl-benzidine and hydrogen peroxide as substrate. The assay detection limits for diminazene were 2.4 ng/g in muscle, 2.5 ng/g in liver and 2.2 ng/g in kidney while limits of quantification were 7.2 ng/g, 7.5 ng/g and 6.6 ng/g respectively. The recoveries for muscle liver and kidney spiked with 5 ng/g were 78%, 77% and 80% respectively while for 1,000 ng/g were 74%, 76.% and 84% respectively. The within-and between assay coefficients of variation (CV) were 2.4% and 15.5% respectively while assay specificity was above 99.9%. It is concluded that as a result of the good recoveries, high specificity and repeatability, the method could be used in the determination and monitoring of diminazene residues in tissues. These activities aimed at ensuring the safety of food of animal origin could play a major role in enhancing consumer confidence in these products which are very essential for health. Key words: Diminazene, Residues, cELISA, Animal tissues, Trypanosomosis, INTRODUCTION Antimicrobial drugs have been used for over fifty years in food producing animals to control, prevent and treat infections resulting in increased growth, feed efficiency and increased economic return [...]