Effects of Allium Sativum Ethanolic Extract on Trypanosoma brucei brucei Parasites’ Morphometric Parameters and Clinical Outcome in White Albino Laboratory Rats

Background: Trypanosomosis affects humans as well as wild and domestic vertebrates, yet has no successful prophylaxis, chemotherapy nor cure.Objectives: The study was to investigate the effects of Allium sativum extract on Trypanosoma brucei brucei parasites’ morphometric parameters, parasitemia and the clinical outcome in white infected Albino laboratory rats in order to determine its trypanocidal effects.Methodology: The study was conducted at the department of Biological Sciences Laboratory of the Moi University Eldoret. Thirty two (32) mature rats randomly divided into four groups (M, N, P and Q) were kept in four (4) cages in a well ventilated room, with adequate light supply in the day.Sixteen (16) rats were infected with T. b. brucei (1.0 x 104 parasites per rat); eight (8) of which (Group N) were treated with the A. sativum ethanolic  extract on day 5 and day 9 after infection, while the other eight (8)rats (Group Q) received saline treatment on the same days.Sixteen (16) non-infected rats (controls) were also divided into two groups of eight rats each (P and M) and treated as in group N and Q, respectively. The rats were obtained from University of Nairobi, Chiromo Campus.Results: All infected rats became parasitemic two days after infection and reached peak levels on day 4 and 5 post infection. Parasitemia in saline treated infected rats fluctuated between 4025.5 ± 0.05 - 5544.4 ± 0.05 parasites per 200WBC whereas in the extract treated rats parasitemia declinedfrom 6976.6 ± 0.05 - 311.0 ± 0.05 parasites per 200WBC after the first treatment. Uninfected saline treated rats maintained normal Hb level (10.6g/L to 11.8g/L) as compared to the uninfected extract treated rats’ whose Hb levels was at 13.41g/L to 14.36g/L. The haemoglobin level changed to 8.0g/L four days after the infection in the group N rats before rising to 10.2g/L on day 8 post-infection following the extract treatments. Group Qrats’ Hb declined to 6.43g/L by the end of the study. RBC count of the infected saline treated rats declined to 3.38 x 106/μL as compared to 4.93-7.61 x 106/μL in the normal rats by 11 days postinfection. There was however no significant change in WBC, temperature and weight between the saline extract treated rats. The extract produced a shrinking effect on the parasite's body with some of the morphometric parameters appearing  significantly (P<0.05) reduced as observed under a microscope with ocular and stage micrometer scale. The mean nucleus, posterior ends to nucleus centre, the nucleus centre to the anterior end and the body length were reduced from 2.41μm to 1.42μm(P=0.00), 4.42μm to  3.68μm(P=0.017) , 4.65μm to 4.18μm(P=0.001) and 8.58μm to 7.19μm(P=0.001) respectively.Conclusion: In conclusion it was evident that, A. sativum ethanolic extract exhibited Trypanocidal effects that can be exploited to control clinical progression of Trypanosomosis in rats. In addition, the data presented demonstrates the plant extract had the potential to improve the red and white blood cell indices reducing parasitaemia following T. b. brucei infection. These findings suggest that, the garlic extract affected the plasma membrane of the parasites since shrinking was only possible with disrupted membrane biochemistry. Key words:  Trypanosoma brucei brucei, Allium Sativum, Parasitemia, Morphometric parameters

Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria.

Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and -140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria

Pilot assessment of the sensitivity of the malaria thin film

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Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA): a study protocol to investigate in vivo Plasmodium falciparum malaria parasite growth in the context of pre-existing immunity [version 2; peer review: 2 approved]

Malaria remains a major public health burden despite approval for implementation of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development of a more effective multi-stage vaccine. Adults in malaria endemic areas may have substantial immunity provided by responses to the blood stages of malaria parasites, but field trials conducted on several blood-stage vaccines have not shown high levels of efficacy. We will use the controlled human malaria infection (CHMI) models with malaria-exposed volunteers to identify correlations between immune responses and parasite growth rates in vivo. Immune responses more strongly associated with control of parasite growth should be prioritized to accelerate malaria vaccine development. We aim to recruit up to 200 healthy adult volunteers from areas of differing malaria transmission in Kenya, and after confirming their health status through clinical examination and routine haematology and biochemistry, we will comprehensively characterize immunity to malaria using >100 blood-stage antigens. We will administer 3,200 aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (PfSPZ Challenge) by direct venous inoculation. Serial quantitative polymerase chain reaction to measure parasite growth rate in vivo will be undertaken. Clinical and laboratory monitoring will be undertaken to ensure volunteer safety. In addition, we will also explore the perceptions and experiences of volunteers and other stakeholders in participating in a malaria volunteer infection study. Serum, plasma, peripheral blood mononuclear cells and whole blood will be stored to allow a comprehensive assessment of adaptive and innate host immunity. We will use CHMI in semi-immune adult volunteers to relate parasite growth outcomes with antibody responses and other markers of host immunity. / Registration: ClinicalTrials.gov identifier NCT02739763

Caregiver perceptions of children who have complex communication needs following a home-based intervention using augmentative and alternative communication in rural Kenya: an intervention note:Home-based intervention using AAC in rural Kenya

A high level of unmet communication need exists amongst children with developmental disabilities in sub-Saharan Africa. This study investigated preliminary evidence of the impact associated with a home-based, caregiver-implemented intervention employing AAC methods, with nine children in rural Kenya who have complex communication needs. The intervention used mainly locally-sourced low-tech materials, and was designed to make use of the child's strengths and the caregiver's natural expertise. A pretest-posttest design was used in the study. Data were gathered using an adapted version of the Communication Profile, which was based on the International Classification of Functioning, Disability, and Health (ICF) framework. The non-parametric Wilcoxon signed-rank test was applied to data from the first two sections of the Communication Profile-Adapted. Qualitative analysis was conducted on the final section. The data provided evidence of statistically significant positive changes in caregiver perceptions of communication at the levels of Body Structure and Function, and Activities for Communication. Also, analysis of the Participation for Communication section revealed some expansion to the children's social activities. The potential impact of the home-based intervention would benefit from investigation on a larger scale. Limitations of the study are discussed

The PI3Kδ inhibitor zandelisib on intermittent dosing in relapsed/refractory follicular lymphoma: Results from a global phase 2 study

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune‐related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2–8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9–80.4), the complete response (CR) rate was 38% (95% CI, 29.3–47.3), and the median DOR was 16.4 months (95% CI, 9.5–not reached). With a median follow‐up of 14.3 months (range, 1–30.5), the median progression‐free survival was 11.6 months (95% CI, 8.3–not reached). Twenty‐one patients (17%) discontinued therapy due to an adverse event. Grade 3–4 class‐related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non‐infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class‐related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B‐cell malignancies