Prevalence of extra-pulmonary tuberculosis in Africa: A systematic review and meta-analysis.

OBJECTIVE: The burden of extra-pulmonary tuberculosis (EPTB) is not well quantified in TB endemic countries such as those in sub-Saharan Africa. This study aimed to quantify that burden via a systematic review of the prevalence of EPTB in African countries. METHODS: Studies were retrieved by searching five databases; 105 studies published between 1990 and 2023 were included. The studies described the prevalence of EPTB among the general population (4 studies), TB patients (68) and patients with other conditions, including HIV (15), meningitis (3), renal failure (3) and other comorbidities, some of which are cancer (12). Due to the low number of studies reporting EPTB in patients with conditions other than TB, the meta-analysis was performed on studies reporting on EPTB among TB patients (68 studies). Meta-analysis was performed on the 68 studies (271,073 participants) using a random-effects model to estimate the pooled prevalence of EPTB. Meta-regression was used to explore possible explanations for heterogeneity according to regions and time periods. RESULTS: The pooled prevalence of EPTB among TB patients was 26% (95% CI 23-29%). There was substantial heterogeneity of prevalence for the five African regions. The Eastern region had the highest prevalence of 32% (95% CI 28-37%) and the lowest in Western Africa, 16% (95% CI 10-24%). There was no significant difference in the prevalence of EPTB between the 3 eleven-year time periods. CONCLUSIONS: Our systematic review and meta-analysis give insight into the burden of EPTB in Africa. This review could inform clinical and programmatic practices-a higher suspicion index for clinicians and more effort for better services. This could contribute to efforts aiming to end TB, which have historically been focused on PTB.Coordinated efforts that target both EPTB and PTB are needed.

Climatic requirements of the southern paralysis tick, Ixodes cornuatus, with a consideration of its host, Vombatus ursinus, and the possible geographic range of the tick up to 2090.

The southern paralysis tick, Ixodes cornuatus, is a tick of veterinary and medical importance in Australia. We use two methods, CLIMEX, and an envelope-model approach which we name the 'climatic-range method' to study the climatic requirements of I. cornuatus and thus to attempt to account for the geographic distribution of I. cornuatus. CLIMEX and our climatic-range method allowed us to account for 94% and 97% of the records of I. cornuatus respectively. We also studied the host preferences of I. cornuatus which we subsequently used in conjunction with our species distribution methods to account for the presence and the absences of I. cornuatus across Australia. Our findings indicate that the actual geographic distribution of I. cornuatus is smaller than the potential geographic range of this tick, and thus, that there are regions in Australia which may be suitable for I. cornuatus where this tick has not been recorded. Although our findings indicate that I. cornuatus might be able to persist in these currently unoccupied regions, our findings also indicate that the potential geographic range of I. cornuatus may shrink by 51 to 76% by 2090, depending on which climate change scenario comes to pass.

Climatic requirements of the eastern paralysis tick, Ixodes holocyclus, with a consideration of its possible geographic range up to 2090.

The eastern paralysis tick, Ixodes holocyclus, is an ectoparasite of medical and veterinary importance in Australia. The feeding of I. holocyclus is associated with an ascending flaccid paralysis which kills many dogs and cats each year, with the development of mammalian meat allergy in some humans, and with the transmission of Rickettsia australis (Australian scrub typhus) to humans. Although I. holocyclus has been well studied, it is still not known exactly why this tick cannot establish outside of its present geographic distribution. Here, we aim to account for the presence as well as the absence of I. holocyclus in regions of Australia. We modelled the climatic requirements of I. holocyclus with two methods, CLIMEX, and a new envelope-model approach which we name the 'climatic-range method'. These methods allowed us to account for 93% and 96% of the geographic distribution of I. holocyclus, respectively. Our analyses indicated that the geographic range of I. holocyclus may not only shift south towards Melbourne, but may also expand in the future, depending on which climate-change scenario comes to pass.

GPR183 Regulates Interferons, Autophagy, and Bacterial Growth During Mycobacterium tuberculosis Infection and Is Associated With TB Disease Severity.

Oxidized cholesterols have emerged as important signaling molecules of immune function, but little is known about the role of these oxysterols during mycobacterial infections. We found that expression of the oxysterol-receptor GPR183 was reduced in blood from patients with tuberculosis (TB) and type 2 diabetes (T2D) compared to TB patients without T2D and was associated with TB disease severity on chest x-ray. GPR183 activation by 7α,25-dihydroxycholesterol (7α,25-OHC) reduced growth of Mycobacterium tuberculosis (Mtb) and Mycobacterium bovis BCG in primary human monocytes, an effect abrogated by the GPR183 antagonist GSK682753. Growth inhibition was associated with reduced IFN-ß and IL-10 expression and enhanced autophagy. Mice lacking GPR183 had significantly increased lung Mtb burden and dysregulated IFNs during early infection. Together, our data demonstrate that GPR183 is an important regulator of intracellular mycobacterial growth and interferons during mycobacterial infection.