The potential distribution of Bacillus anthracis suitability across Uganda using INLA.

To reduce the veterinary, public health, environmental, and economic burden associated with anthrax outbreaks, it is vital to identify the spatial distribution of areas suitable for Bacillus anthracis, the causative agent of the disease. Bayesian approaches have previously been applied to estimate uncertainty around detected areas of B. anthracis suitability. However, conventional simulation-based techniques are often computationally demanding. To solve this computational problem, we use Integrated Nested Laplace Approximation (INLA) which can adjust for spatially structured random effects, to predict the suitability of B. anthracis across Uganda. We apply a Generalized Additive Model (GAM) within the INLA Bayesian framework to quantify the relationships between B. anthracis occurrence and the environment. We consolidate a national database of wildlife, livestock, and human anthrax case records across Uganda built across multiple sectors bridging human and animal partners using a One Health approach. The INLA framework successfully identified known areas of species suitability in Uganda, as well as suggested unknown hotspots across Northern, Eastern, and Central Uganda, which have not been previously identified by other niche models. The major risk factors for B. anthracis suitability were proximity to water bodies (0-0.3 km), increasing soil calcium (between 10 and 25 cmolc/kg), and elevation of 140-190 m. The sensitivity of the final model against the withheld evaluation dataset was 90% (181 out of 202 = 89.6%; rounded up to 90%). The prediction maps generated using this model can guide future anthrax prevention and surveillance plans by the relevant stakeholders in Uganda.

Human eosinophils modulate peripheral blood mononuclear cell response to Schistosoma mansoni adult worm antigen in vitro.

High numbers of eosinophils are observed in parasitic infections and allergic diseases, where they are proposed to be terminally differentiated effector cells that play beneficial role in host defence, or cause harmful inflammatory response. Eosinophils have been associated with killing of schistosomulae in vitro, but there is growing evidence that eosinophils can play additional immuno-regulatory role. Here, we report results of a study that examines peripheral blood mononuclear cell (PBMC) cytokine responses to Schistosoma mansoni adult worm antigen (SWA) when stimulated alone or enriched with autologous eosinophils. Production of the Th-2 type cytokines interleukin (IL)-4, IL-5 and IL-13 was lower (P = 0·017, 0·018 and <0·001, respectively) in PBMC + eosinophil cultures than in PBMC-only cultures stimulated with SWA. Substantial levels of IL-13, IL-10, interferon gamma and tumour necrosis factor alpha were recorded in cultures of eosinophils, but none of these cytokines showed significant association with the observed eosinophil-induced drop in cytokine responses of PBMC. Transwell experiments suggested that the observed effect is due to soluble mediators that downmodulate production of Th-2 type cytokines. This study shows that eosinophils may down-modulate schistosome-specific Th-2 type cytokine responses in S. mansoni-infected individuals. The mechanism of this immune modulation remains to be elucidated.

Group M consensus Gag and Nef peptides are as efficient at detecting clade A1 and D cross-subtype T-cell functions as subtype-specific consensus peptides.

OBJECTIVE: Evaluating HIV-1 specific T-cell response in African populations is sometimes compromised by extensive virus diversity and paucity of non-clade B reagents. We evaluated whether consensus group M (ConM) peptides could serve as comparable substitutes for detecting immune responses in clade A and clade D HIV-1 infection. METHODS: Frequencies, breadths and polyfunctionality (≥ 3 functions: IFN-γ, IL-2, TNF-α and Perforin) of HIV-specific responses utilizing ConM, ConA and ConD Gag and Nef peptides was compared. RESULTS: Median genetic distances of infecting gag sequences from consensus group M were (8.9%, IQR 8.2-9.7 and 9%, IQR 3.3-10) for consensus A and D, respectively. Of 24 subjects infected with A and D clade virus, Gag responses were detected in comparable proportions of subjects when using ConM peptides 22/24, ConA peptides 17/24, and ConD peptides 21/24; p=0.12. Nef responses were also detected at similar proportions of subjects when using ConM peptides 15/23, ConA peptides 19/23, and ConD peptides 16/23, p=0.39. Virus-specific CD4+ and CD8+ T-cell polyfunctionality were also detected in similar proportions of infected individuals when using different peptide sets. CONCLUSIONS: These data support the use of consensus group M overlapping peptide sets as reagents for detecting HIV-specific responses in a clade A and D infected population, but underscore the limitations of utilizing these reagents when evaluating the breadth of virus-specific responses.

Pregnancy and helminth infections.

It has been proposed that helminth infection may be particularly detrimental during pregnancy, through adverse effects on maternal anaemia and on birth outcomes, and that anthelminthic treatment during pregnancy will therefore be particularly beneficial. However, the few treatment trials that have been conducted have given, but little support to this notion and further trials in settings of nutritional stress are needed. It has also been proposed that prenatal exposure to helminth infection has an important effect on the development of the foetal immune response. There is evidence that this may impact, long-term, upon responses to helminth and nonhelminth antigens, and to allergens. Exposure to helminths in utero may also have nonspecific effects that may modify the offspring's susceptibility to diseases mediated by inflammation, including metabolic disorders. The mechanisms of such effects are not known, but they deserve to be explored as current epidemiological findings suggest the possibility of primary prevention for inflammatory conditions such as allergy, through intervention during pregnancy.

Treatment of East Coast fever of cattle with a combination of parvaquone and frusemide.

Pulmonary oedema is a common sign of East Coast fever (ECF, Theileria parva infection) of cattle. A trial was conducted on farms in Uganda to compare a product containing both the antitheilerial compound parvaquone and the diuretic compound frusemide with one containing only parvaquone, in the treatment of ECF. The trial involved 40 clinical cases of ECF, some of them complicated by other infections, in cattle of all ages and on several farms. Confirmed cases were treated with either parvaquone+frusemide (P+F) or parvaquone alone (P). Survival after treatment with P+F was 77% compared with 71% with P. Five of the 10 fatalities were complicated cases. The cure rate for severe but uncomplicated ECF was 89% with P+F and 40% with P. Pulmonary signs were resolved within 24-48 h after treatment with P+F and clinical recovery was noticeably more rapid than with P. The antiparasitic effect of the two treatments was similar. P+F could be particularly useful when reporting, diagnosis or laboratory confirmation of ECF is delayed, because advanced cases are more likely to be encountered under these circumstances.