Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 2; peer review: 1 approved with reservations]

BACKGROUND: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. METHODS: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. DISCUSSION: We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This study will generate new data to inform the design and sample size for definitive Phase III trial evaluation. REGISTRATION: ISRCTN49726849 (27th October 2017)

Do Dispersing Monkeys Follow Kin? Evidence from Gray-cheeked Mangabeys (Lophocebus albigena)

Among social vertebrates, immigrants may incur a substantial fitness cost when they attempt to join a new group. Dispersers could reduce that cost, or increase their probability of mating via coalition formation, by immigrating into groups containing first- or second-degree relatives. We here examine whether dispersing males tend to move into groups containing fathers or brothers in gray-cheeked mangabeys (Lophocebus albigena) in Kibale National Park, Uganda. We sampled blood from 21 subadult and adult male mangabeys in 7 social groups and genotyped them at 17 microsatellite loci. Twelve genotyped males dispersed to groups containing other genotyped adult males during the study; in only 1 case did the group contain a probable male relative. Contrary to the prediction that dispersing males would follow kin, relatively few adult male dyads were likely first- or second-degree relatives; opportunities for kin-biased dispersal by mangabeys appear to be rare. During 4 yr of observation, adult brothers shared a group only once, and for only 6 wk. Mean relatedness among adult males sharing a group was lower than that among males in different groups. Randomization tests indicate that closely related males share groups no more often than expected by chance, although these tests had limited power. We suggest that the demographic conditions that allow kin-biased dispersal to evolve do not occur in mangabeys, may be unusual among primates, and are worth further attention

Long-term Site Fidelity and Individual Home Range Shifts in Lophocebus albigena

We investigated long-term site fidelity of gray-cheeked mangabey (Lophocebus albigena) groups in Kibale National Park, Uganda. Concurrently, we monitored shifts in home range by individual females and subadult and adult males. We documented home range stability by calculating the area of overlap in successive years, and by recording the drift of each group’s monthly centroid from its initial location. Home ranges remained stable for 3 of our 4 groups (overlap over 10 yr >60%). Core areas were more labile, but group centroids drifted an average of only 530 m over the entire decade. Deviations from site fidelity were associated with dispersal or group fission. During natal dispersal, subadult males expanded their home ranges over many months, settling ≤4 home ranges away. Adult males, in contrast, typically dispersed within a few days to an adjacent group in an area of home range overlap. Adult males made solitary forays, but nearly always into areas used by their current group or by a group to which they had previously belonged. After secondary dispersal, they expanded their ranging in the company of their new group, apparently without prior solitary exploration of the new area. Some females also participated in home range shifts. Females shifted home ranges only within social groups, in association with temporary or permanent group splits. Our observations raise the possibility that male mangabeys use a finder-joiner mechanism when moving into new home ranges during secondary dispersal. Similarly, females might learn new resource locations from male immigrants before or during group fission

Grey Crowned Crane threat assessment around the wetlands of eastern Uganda

The Grey Crowned Crane Balearica regulorum was uplisted to globally Endangered in 2012. There is urgent need to determine the threats they face at local levels for their conservation. I conducted formal point-count surveys around the wetlands of eastern Uganda and observed no cranes. Groups of cranes were encountered when following directions from local inhabitants. Results from a questionnaire survey suggested that cranes make use of most of the wetlands in the region, and that the birds occur in small flocks averaging 6–8 individuals. Wetland loss through farming was reported to be the main threat, but I also documented poisoning, roost disturbance, and the collection of eggs and chicks. Rigorous conservation and education programs are needed to ensure the long-term survival of cranes and storks in this region.Keywords: agriculture, eastern Uganda, Grey Crowned Crane, wetland

Mangabey dispersal and conservation in Kibale National Park, Uganda

Dispersal is important for species persistence. However, little is known about dispersal in rainforest primates, particularly in cercopithecines. This study was conducted with the primary aim of documenting the frequency of dispersal events, fates and habitat preference of dispersers, and factors implicated in the movement of mangabey (Lophocebus albigena) males between social groups. Between July 1996 and December 1998, I captured, marked, and studied the movements of males in more than six social groups inhabiting the Kanyawara study area of Kibale National Park, Uganda. The social organization of mangabeys was rather fluid; males often moved far (\u3e200 m) from any group, and several males moved between groups over a relatively short period of time. Male emigration did not appear to be influenced by aggression; however, as males tended to move from groups with fewer estrous females to groups with more. Males emigrated singly, usually into adjacent groups, and spent variable periods (1 to 276 days) in transit. Lone males showed no different habitat preferences; males outside social groups used different habitat types with the same frequency as males within groups. Dispersing lone males did not appear to suffer higher foraging costs than non-dispersing males, since dispersers and non-dispersers traveled at the same rates and spent similar proportions of time feeding and foraging. Because a large number (41) of males was captured, this darting program permitted assessment of the performance of Telazol ® as an anesthetic for mangabeys, relative risk of darting in different habitats, the feasibility of radiotracking intensively (by homing) under rainforest conditions, as well as testing hypotheses about possible relationships between body size in mangabeys and habitat type. There were no adverse side effects associated with use of Telazol®; it was riskier capturing mangabeys in tall, primary forest than in regenerating or swamp forest; and standard radiotracking equipment could be used on daily basis with few breakdowns. Comparisons of measurements of adult males captured from logged and unlogged forest suggest that unlogged forest males weighed significantly more than males from logged forest. This underlines the importance of primary forest in the conservation of mangabeys

Modeling habitat suitability for Grey Crowned-cranes (Balearica regulorum gibbericeps) throughout Uganda

Grey Crowned-cranes occur throughout the mixed wetland-grassland habitats of Eastern and Southern Africa. Due primarily to loss of habitat, however, the species is in swift decline over much of its historic range. We present a prediction of habitat suitability throughout Uganda using a Maxent modeling approach, combining presence-only field data collected over the last few decades (1970 -2006) with remote sensing and climate derived variables. We ran six feature type models, with the Auto feature type model having the best fit to the data (AUC = 0.912). Our results provide detailed information regarding the characteristics of habitats used and highlight specific areas of high habitat suitability for the species. While wetlands were certainly important in the prediction (9.2% contribution), other variables (namely temperature seasonality) were more important within the model (19.5%). Areas of high habitat suitability (defined as > 0.6 probability of presence) accounted for only a small amount of the total area throughout the country (5.8 -6.9%), and were mainly found in the Southwestern corner of the country and along the Albert Nile River. These data provide a statistical basis for extrapolating into areas that have not been surveyed and provide valuable information for the future conservation of the species

Physical and mechanical properties of porcelain tiles made from raw materials in Uganda

This study was intended to determine the physicomechanical properties of porcelain tiles made from raw materials in Uganda, hitherto not used for the same. The raw materials were mixed in proportions of 40–60% clays, 30–40% feldspar and 10–30% sand, the goal was to identify a mixture with properties that meet the ISO 13006 standards after firing. Test tile samples were formulated at a pressure of 40 MPa and fired from 1050 to 1250 °C in steps of 50 °C. A firing rate of 40 °C per minute and a dwell time of 2 h were applied. The microstructures and phase analysis of the fired samples were studied using a scanning electron microscope (SEM) and X-ray diffractometer (XRD), respectively. The XRD analysis revealed mullite and quartz as crystalline phases present in the fired bodies. At 1150 °C, the SEM micrograph depicted few, short and thick mullite fibers. At 1200 °C, the mullite population increased. The nature of the fibers (long, fine and more interlocking) resulted in an increase in flexural strength. A further rise in temperature had no significant change on the nature of the fibers and flexural strength of the samples. The best properties; flexural strength (33 MPa) and water absorption (0.08%) were exhibited at 1200 °C by samples with 30–40% kaolin, 30–40% feldspar, 20% ball clay and 10% sand. The results indicate that these samples are comparable to the ISO 13006 standards for porcelain tiles which are ≥ 35±2 MPa flexural strength and <0.5% water absorption. The other mix proportions did not meet these standards, specifically in terms of flexural strength (<25 MPa)