Detection Rats Technology for Diagnosis of Tuberculosis in High-Risk Populations

Prevalence of tuberculosis (TB) in prisoners in Tanzania and other sub-Saharan African countries is considered to be higher than in other populations thus prisons are important source of TB transmission. Control of TB in prisons through appropriate screening and diagnosis is challenging in most low-income countries such as Tanzania that is among world’s 22 countries with high burden of TB. Commonly used TB diagnostic test (smear microscopy) have low sensitivity, and most advanced GeneXpert method is rather expensive for developing countries. SUA-APOPO TB detection rats’ technology is most promising and increases TB case detection by over 40% in hospitals in Dar es Salaam Tanzania and Maputo Mozambique. This paper reports on improved TB detection in a selected prison in Tanzania using TB detection rats. Sputum samples (n = 11,424) were collected from 5,840 patients whom 3,491 were men, 2,349 were women. Of these, 386 patients were children altogether seeking diagnosis of TB at Ukonga prison dispensary from January 2013 to October 2015) and Keko prison dispensary from February to October 2015). Samples were routinely examined by Ziehl Neelsen (ZN) staining and later tested by rats APOPO TB laboratory, Sokoine University of Agriculture, Morogoro. Rats’ positive samples were concentrated and confirmed by fluorescent microscopy (LED-FM) or ZN microscopy. A total of 709 individuals (12%) were diagnosed as smearpositive TB by the prison hospital, whereas rats detected an additional 302 TB patients. This increased the case detection in the prison population by 43%. The use of rats’ technology increased the prevalence of smear-positive TB in prisons from 12% to 17.3% (n = 1,011) that is higher than prevalence reported in prisons elsewhere using microscopy. This finding shows that detection rats’ technology can help reduce the burden of TB in developing countries. There is need to expand application of this technology to other risk populations including miners.This technology can improve workforce, livelihood and socio-economy by reducing TB related expenses

Using giant african pouched rats to detect human tuberculosis: a review

Despite its characteristically low sensitivity, sputum smear microscopy remains the standard for diagnosing tuberculosis (TB) in resource-poor countries. In an attempt to develop an alternative or adjunct to microscopy, researchers have recently examined the ability of pouched rats to detect TB-positive human sputum samples and the microbiological variables that affect their detection. Ten published studies, reviewed herein, suggest that the rats are able to detect the specific odor of Mycobacterium tuberculosis, which causes TB, and can substantially increase new-case detections when used for second-line TB screening following microscopy. Further research is needed to ascertain the rats' ability to detect TB in children and in HIV-positive patients, to detect TB when used for first-line screening, and to be useful in broad-scale applications where cost effectiveness is a major consideration

Leptospira Serovars for Diagnosis of Leptospirosis in Humans and Animals in Africa: Common Leptospira Isolates and Reservoir Hosts

The burden of leptospirosis in humans and animals in Africa is higher than that reported from other parts of the world. However, the disease is not routinely diagnosed in the continent. One of major factors limiting diagnosis is the poor availability of live isolates of locally circulating Leptospira serovars for inclusion in the antigen panel of the gold standard microscopic agglutination test (MAT) for detecting antibodies against leptospirosis. To gain insight in Leptospira serovars and their natural hosts occurring in Tanzania, concomitantly enabling the improvement of the MAT by inclusion of fresh local isolates, a total of 52 Leptospira isolates were obtained from fresh urine and kidney homogenates, collected between 1996 and 2006 from small mammals, cattle and pigs. Isolates were identified by serogrouping, cross agglutination absorption test (CAAT), and molecular typing. Common Leptospira serovars with their respective animal hosts were: Sokoine (cattle and rodents); Kenya (rodents and shrews); Mwogolo (rodents); Lora (rodents); Qunjian (rodent); serogroup Grippotyphosa (cattle); and an unknown serogroup from pigs. Inclusion of local serovars particularly serovar Sokoine in MAT revealed a 10-fold increase in leptospirosis prevalence in Tanzania from 1.9 % to 16.9 % in rodents and 0.26% to 10.75 % in humans. This indicates that local serovars are useful for diagnosis of human and animal leptospirosis in Tanzania and neighbouring countries

Phylogeography and cryptic diversity of the solitary-dwelling silvery mole-rat, genus Heliophobius (family: Bathyergidae)

Alongside the eusocial naked mole-rat, Heterocephalus glaber, Heliophobius argenteocinereus represents the second oldest lineage within the African mole-rat family Bathyergidae, and phylogenetically intermediate between the East African Het. glaber and the South African genera Bathyergus and Georychus. Across its geographic range, Hel.. argenteocinereus is widely distributed on both sides of the East African Rift System (EARS), and is a key taxon for understanding the phylogeographic patterns of divergence of the family as a whole. Phylogenetic analysis of 62 mitochondrial cyt b sequences, representing 48 distinct haplotypes from 26 geographic locations across the range of Heliophobius, consistently and robustly resolved six genetically divergent clades that we recognize as distinct evolutionary species. Early species descriptions of Heliophobius were synonymized into a monotypic taxonomy that recognized only Hel. argentocinereus. These synonyms constitute available names for these rediscovered cryptic lineages, for which combined morphological and genetic evidence for topotypical populations endorses the recognition of six to eight distinct taxa. Bayesian estimates of diver- gence times using the fossil Proheliophobius as a calibration for the molecular clock suggest that the adaptive radiation of the genus began in the early Miocene, and that cladogenesis, represented in the extant species, reflects a strident signa- ture of tectonic activity that forged the principal graben in the EARS.SYNTHESYS grant (BE-TAF-289), grants from the National Research Foundation, the University of Pretoria South Africa (to NCB) and the ERANDA and Bay Foundations (FC).http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1469-7998ab201

Building an African Leptospirosis Network

Although leptospirosis is a disease of global importance, local context is crucial to formulating effective intervention strategies. Factors including reservoir host species, pathogen type, environmental, and social settings generate context-specific epidemiologies. Diverse climatic zones, agricultural systems, urbanization patterns, and cultural practices in Africa are likely to drive considerable variation in leptospirosis epidemiology. There is growing evidence of a substantial burden of human leptospirosis in Africa that is difficult to quantify in part due to lack of surveillance and clinical awareness of leptospirosis. Leptospirosis is therefore rarely considered as a differential diagnosis for acute febrile illness, and there is little access to diagnostic services for leptospirosis on the continent. In 2016, a virtual network was founded focussing on improving awareness and understanding leptospirosis in Africa. We currently have 40 members from academia, clinical practice, government and non-governmental agencies and others. Current members are based predominantly in institutions outside the continent but increasingly colleagues based in public health, laboratories, veterinary, and academic institutions within Africa are joining. We will share our experiences of developing this network, and our plans for capacity building through identifying and addressing knowledge gaps in our understanding of leptospirosis in Africa

Isolation and Characterization of New Leptospira Genotypes from Patients in Mayotte (Indian Ocean)

Leptospirosis has been recognized as an increasing public health problem affecting poor people from developing countries and tropical regions. However, the epidemiology of leptospirosis remains poorly understood in remote parts of the world. In this study of patients from the island of Mayotte, we isolated 22 strains from the blood of patients during the acute phase of illness. The pathogenic Leptospira strains were characterized by serology and various molecular typing methods. Based on serological data, serogroup Mini appears to be the dominant cause of leptospirosis in Mayotte. Further molecular characterization of these isolates allowed the identification of 10 pathogenic Leptospira genotypes that could correspond to previously unknown serovars. Further progress in our understanding of the epidemiology of Leptospira circulating genotypes in highly endemic regions should contribute to the development of novel strategies for the diagnosis and prevention of this neglected emerging disease

Profiles of Volatile Biomarkers Detect Tuberculosis from Skin

Tuberculosis (TB) is an infectious disease that threatens >10 million people annually. Despite advances in TB diagnostics, patients continue to receive an insufficient diagnosis as TB symptoms are not specific. Many existing biodiagnostic tests are slow, have low clinical performance, and can be unsuitable for resource-limited settings. According to the World Health Organization (WHO), a rapid, sputum-free, and cost-effective triage test for real-time detection of TB is urgently needed. This article reports on a new diagnostic pathway enabling a noninvasive, fast, and highly accurate way of detecting TB. The approach relies on TB-specific volatile organic compounds (VOCs) that are detected and quantified from the skin headspace. A specifically designed nanomaterial-based sensors array translates these findings into a point-of-care diagnosis by discriminating between active pulmonary TB patients and controls with sensitivity above 90%. This fulfills the WHO's triage test requirements and poses the potential to become a TB triage test

Determination of Mycobacterium tuberculosis odour compounds detected by Cricetomys gambianus rats for diagnosis of pulmonary tuberculosis in low-income settings

PhD, ThesisNovel methods for rapid diagnosis of tuberculosis (TB) are urgently needed to complement the widely used smear microscopy in low income settings. Trained TB detection rats offer a promising tool for rapid diagnosis of TB in resource limited settings. The Mycobacterium tuberculosis (Mtb) specific volatile compounds detected by trained Cricetomys gambianus rats in sputum of TB patients are unknown. It is also not known whether rats detect odour signals from other mycobacteria and microorganisms related to Mtb, which cause pulmonary infections resembling TB. In this thesis I investigated Mtb-specific volatile compounds detected by trained rats and whether the target compounds are found in other mycobacterial species and related pulmonary pathogens. The ability of rats to discriminate cultures of different microorganisms, clinical sputa with different Mycobacterium spp., Mtb genotypes and other respiratory tract microorganisms was investigated. Finally, the ability of the rats to discriminate Mtb-specific odour compounds from shared compounds found in Mtb and other microorganisms was determined. Results show that Mtb produce specific volatile compounds which are not produced by other mycobacterial species, mycobacteria-related Nocardia spp. and Rhodococcus spp. and other microorganisms. Trained rats use these Mtb-specific compounds to distinguish TB-positive sputa from TB-negative sputa. Volatile compounds shared by Mtb and other mycobacteria and non-mycobacterial species are not detected by trained rats. A blend of Mtb-specific compounds is detected by rats better than individual compounds. Rats can discriminate cultures of Mtb from those of other microorganisms. Detection of Mtb cultures is influenced by growth stage. Rats detect more frequently TB-positive sputa than negative sputa spiked with Mtb or specific volatiles. Clinical sputa containing Mtb are well discriminated by rats from sputa containing other microorganisms. Sputa containing different Mtb genotypes are also detected. It is concluded that trained rats can reliably diagnose TB. Further studies are needed to determine the optimal combinations/ratios of Mtb-specific volatile compounds to yield similarly higher responses of rats as those of detection of typical TB-positive sputa. Future studies should assess detection of sputa with frequent nontuberculous mycobacterial species. Further investigations including recovery of dormant Mtb in sputum may give insights on actual cause of detection of false positive sputa currently judged by microscopy and conventional Mtb culture in which dormant Mtb cannot grow

Application of a multidisciplinary approach to the systematics of Acomys (Rodentia: Muridae) from Northern Tanzania

The systematic status and geographic distribution of spiny mice of the genus Acomys I. Geoffroy, 1838 in Northern Tanzania is uncertain. This study assesses the systematic and geographic distribution of Acomys from Northern Tanzania using a multidisciplinary approach that includes molecular, cytogenetic, traditional and geometric morphometric analyses, and classical morphology of the same individuals. The molecular analysis was based on 1140 base pairs (bp) of the mitochondrial cytochrome b and 1297 bp of the nuclear interphotoreceptor retinoid binding protein (IRBP) gene sequences. These data were subjected to phylogenetic analyses using Maximum likelihood, Bayesian, Maximum parsimony, and Minimum evolution analyses. The cytogenetic analysis included G-banding of metaphase chromosomes. The morphometric analyses included univariate and multivariate analyses of traditional morphometric measurements of the cranium and mandible, and of geometric morphometric two-dimensional landmarks of the dorsal, ventral, and lateral views of the cranium, and lateral view of mandible that included thinplate spline (TPS) analysis. The classical morphology included examination of external, cranial and mandibular morphology. Results of all these multidisciplinary analyses were congruent and provide evidence for the occurrence of two sympatric species of Acomys in northern Tanzania, namely, the previously recorded A. wilsoni (2n = 62) and a newly recorded A. cf. percivali (2n = 58). These results that also represent the first reported mitochondrial cytochrome b and nuclear IRBP gene sequences and karyotype for A. cf. percivali, increases the number of species known to occur in Tanzania from four to five. However, the mitochondrial cytochrome b data that included GenBank sequences from the type locality in Kenya suggest that A. wilsoni may not be monophyletic. Ecologically, the two species seem to partition their niches with A. cf. percivali being found in well-covered habitats with thorn bushes, rocky and mountainous areas, and A. wilsoni being found in open semi-arid grasslands as well as in rice fields. The two species appear to be isolated by complex natural barriers formed by the Great East African Rift Valley whose geological features have generally been associated with active rodent speciation. However, the present results need further multidisciplinary investigation involving extensive sampling and examination of topotypical material

Application of a multidisciplinary approach to the systematics of Acomys (Rodentia: Muridae) from Northern Tanzania

The systematic status and geographic distribution of spiny mice of the genus Acomys I. Geoffroy, 1838 in Northern Tanzania is uncertain. This study assesses the systematic and geographic distribution of Acomys from Northern Tanzania using a multidisciplinary approach that includes molecular, cytogenetic, traditional and geometric morphometric analyses, and classical morphology of the same individuals. The molecular analysis was based on 1140 base pairs (bp) of the mitochondrial cytochrome b and 1297 bp of the nuclear interphotoreceptor retinoid binding protein (IRBP) gene sequences. These data were subjected to phylogenetic analyses using Maximum likelihood, Bayesian, Maximum parsimony, and Minimum evolution analyses. The cytogenetic analysis included G-banding of metaphase chromosomes. The morphometric analyses included univariate and multivariate analyses of traditional morphometric measurements of the cranium and mandible, and of geometric morphometric two-dimensional landmarks of the dorsal, ventral, and lateral views of the cranium, and lateral view of mandible that included thinplate spline (TPS) analysis. The classical morphology included examination of external, cranial and mandibular morphology. Results of all these multidisciplinary analyses were congruent and provide evidence for the occurrence of two sympatric species of Acomys in northern Tanzania, namely, the previously recorded A. wilsoni (2n = 62) and a newly recorded A. cf. percivali (2n = 58). These results that also represent the first reported mitochondrial cytochrome b and nuclear IRBP gene sequences and karyotype for A. cf. percivali, increases the number of species known to occur in Tanzania from four to five. However, the mitochondrial cytochrome b data that included GenBank sequences from the type locality in Kenya suggest that A. wilsoni may not be monophyletic. Ecologically, the two species seem to partition their niches with A. cf. percivali being found in well-covered habitats with thorn bushes, rocky and mountainous areas, and A. wilsoni being found in open semi-arid grasslands as well as in rice fields. The two species appear to be isolated by complex natural barriers formed by the Great East African Rift Valley whose geological features have generally been associated with active rodent speciation. However, the present results need further multidisciplinary investigation involving extensive sampling and examination of topotypical material