CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches.

Copper is required for aerobic respiration by Mycobacterium tuberculosis and its human host, but this essential element is toxic in abundance. Copper nutritional immunity refers to host processes that modulate levels of free copper to alternately starve and intoxicate invading microbes. Bacteria engulfed by macrophages are initially contained within copper-limited phagosomes, which fuse with ATP7A vesicles that pump in toxic levels of copper. In this report, we examine how CtpB, a P-type ATPase in M. tuberculosis, aids in response to nutritional immunity. In vitro, the induced expression of ctpB in copper-replete medium inhibited mycobacterial growth, while deletion of the gene impaired growth only in copper-starved medium and within copper-limited host cells, suggesting a role for CtpB in copper acquisition or export to the copper-dependent respiration supercomplex. Unexpectedly, the absence of ctpB resulted in hypervirulence in the DBA/2 mouse infection model. As ctpB null strains exhibit diminished growth only in copper-starved conditions, reduced copper transport may have enabled the mutant to acquire a "Goldilocks" amount of the metal during transit through copper-intoxicating environments within this model system. This work reveals CtpB as a component of the M. tuberculosis toolkit to counter host nutritional immunity and underscores the importance of elucidating copper-uptake mechanisms in pathogenic mycobacteria.

Regional status, epidemiology and impact of Taenia solium cysticercosis in Western and Central Africa.

In West Africa, Taenia solium cysticercosis in both pigs and man has been reported in Benin, Burkina-Faso, Ghana, Ivory Coast, Senegal and Togo, and although official data are lacking, T. solium is anticipated to be present in most of the pig-raising regions of other West African countries as well. In some regions of Nigeria, the prevalence of porcine cysticercosis and human taeniosis is quite high (20.5 and 8.6%, respectively). Surprisingly, however, no cases of human cysticercosis have been reported, although epilepsy is very common. Large epidemiological surveys have only been carried out in Togo and Benin, where the prevalence of human cysticercosis was 2.4 and 1.3%, respectively. In Central Africa, porcine and human cysticercosis are (hyper)-endemic in Rwanda, Burundi, the Democratic Republic of Congo and Cameroon. The parasite also has been reported in pigs in Chad and Angola. Cysticercosis has been shown to be one of the major causes of epilepsy in Cameroon with figures as high as 44.6%. Cameroon is one of the few countries where the taeniosis-cysticercosis complex has been examined more in detail. In the Western province of Cameroon large scale surveys have shown that active cysticercosis is present in 0.4-3% of the local population and in 11% of the village pigs. However, the prevalence of adult T. solium was only 0.1%, which underscores the frequency of the T. solium paradox. Based on the available information, a very conservative economic estimate indicates that the annual losses due to porcine cysticercosis in 10 West and Central African countries amount to about 25 million Euro. The financial losses due to human cysticercosis are very difficult to estimate, but are certainly exceeded by the social impact of the disease, especially because of the particular perception of epilepsy in many African communities. It is concluded that the true prevalence of T. solium cysticercosis in pigs and humans in Central and West Africa remains underestimated because of unreliable slaughterhouse data and the lack of awareness and diagnostic facilities in the public health sector.

Neurocysticercosis and epilepsy in Cameroon.

During January 2002 the frequency of Taenia solium cysticercosis was studied in a series of 504 epileptic patients from 3 rural localities in the West and North-West provinces of Cameroon using an enzyme-linked immunosorbent assay for both circulating antigen (Ag-ELISA) and antibody (Ag-ELISA) detection. Taenia solium antigens were detected in the sera of 1.2% of the patients whereas specific antibodies against the parasite were present in 44.6% of the patients. Significantly less seropositive results in Ab-ELISA were recorded in Batibo than in Bandjoun and Bamendjou, whereas a borderline significant difference was recorded with increasing age. Furthermore, 56.2% of patients with late-onset epilepsy showed antibodies against cysticercosis. Taenia solium cysticercosis appears to be an important cause of epilepsy in Cameroon.