Response to Rift Valley Fever in Tanzania: Challenges and Opportunities

Rift Valley Fever (RVF) is an arthropod borne viral disease affecting livestock (cattle, sheep, goats and camels), wildlife and humans caused by Phlebovirus. The disease occurs in periodic cycles of 4-15 years associated with flooding from unusually high precipitations in many flood-prone habitats. Aedes and Culex spp and other mosquito species are important epidemic vectors. Because of poor living conditions and lack of knowledge on the pathogenesis of RVF, nomadic pastoralists and agro-pastoralists are at high risk of contracting the disease during epidemics. RVF is a professional hazard for health and livestock workers because of poor biosafety measures in routine activities including lack of proper Personal Protective Equipment (PPE). Direct exposure to infected animals can occur during handling and slaughter or through veterinary and obstetric procedures or handling of specimens in laboratory. The episodic nature of the disease creates special challenges for its mitigation and control and many of the epidemics happen when the governments are not prepared and have limited resource to contain the disease at source. Since its first description in 1930s Tanzania has recorded six epidemics, three of which were after independence in 1961. However, the 2007 epidemic was the most notable and wide spread with fatal human cases among pastoralists and agro-pastoralists concurrent with high livestock mortality. Given all the knowledge that exist on the epidemiology of the disease, still the 2006/2007 epidemic occurred when the government of Tanzania was not prepared to contain the disease at source. This paper reviews the epidemiology, reporting and outbreak investigation, public awareness, preparedness plans and policy as well as challenges for its control in Tanzania

'One Health' infectious diseases surveillance in Tanzania: Are we all on board the same flight?

Infectious diseases account for nearly 40% of the burden of human mortality and morbidity in low-income countries, of which 7% is attributable to zoonoses and 13% to recently emerging diseases from animals. One of the strategic approaches for effective surveillance, monitoring and control of infectious diseases compromising health in both humans and animals could be through a combination of multiple disciplines. The approach can be achieved through a joint effort from stakeholders comprising health professionals (medical and veterinary), social, economic, agricultural, environmental and other interested parties. With resource scarcity in terms of number of staff, skills and facility in low-income countries, participatory multi- sectoral and multidisciplinary approaches in limiting the burden of zoonotic diseases could be worthwhile. We review challenging issues that may limit the ‘One Health’ approach for infectious diseases surveillance in Tanzania with a focus on Health Policy and how best the human and animal health systems could be complemented or linked to suit the community in need for disease control under the theme’s context

Tuberculosis cross-species transmission in Tanzania: Towards a One-Health concept

For centuries, tuberculosis, which is a chronic infection caused by the bacillus Mycobacterium tuberculosis has remained a global health problem. The global burden of tuberculosis has increased, particularly in the Southern African region, mainly due to HIV, and inadequate health systems which has in turn given rise to emergent drug resistant tuberculosis (TB) strains. Bovine tuberculosis (BTB) has also emerged as a significant disease with the tendency for inter-species spread. The extent of interspecies BTB transmission both in urban and rural communities has not been adequately assessed. The phenomenon is of particular importance in rural communities where people share habitats with livestock and wildlife (particularly in areas near national parks and game reserves). Aerosol and oral intake are the major routes of transmission from diseased to healthy individuals, with health care workers often contracting infection nosocomially. Although TB control has increasingly been achieved in high-income countries, the disease, like other poverty-related infections, has continued to be a disaster in countries with low income economies. Transmission of infections occurs not only amongst humans but also between animals and humans (and occasionally vice versa) necessitating assessment of the extent of transmission at their interface. This review explores tuberculosis as a disease of humans which can cross-transmit between humans, livestock and wildlife. The review also addresses issues underlying the use of molecular biology, genetic sequencing and bioinformatics as t tools to understand the extent of inter-species cross-transmission of TB in a ‘One Health’ context

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Nonhuman primates across sub-Saharan Africa are infected with the yaws bacterium Treponema pallidum subsp. pertenue

Dear Editor, The bacterium Treponema pallidum (TP) causes human syphilis (subsp. pallidum; TPA), bejel (subsp. endemicum; TEN), and yaws (subsp. pertenue; TPE) (1). Although syphilis has reached a worldwide distribution (2), bejel and yaws have remained endemic diseases. Bejel affects individuals in dry areas of Sahelian Africa and Saudi Arabia, whereas yaws affects those living in the humid tropics (1). Yaws is currently reported as endemic in 14 countries, and an additional 84 countries have a known history of yaws but lack recent epidemiological data (3,4). Although this disease was subject to global eradication efforts in the mid-20th century, it later reemerged in West Africa, Southern Asia, and the Pacific region (5). New large-scale treatment options triggered the ongoing second eradication campaign, the goal of which is to eradicate yaws globally by 2020 (5). References: (1) Giacani, L. & Lukehart, S.A. The endemic treponematoses. Clin. Microbiol. Rev. 27, 89–115 (2014). (2) Arora, N. et al. Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat. Microbiol. 2, 16245 (2016). (3) Marks, M. Yaws: towards the WHO eradication target. Trans. R Soc. Trop. Med. Hyg. 110, 319–320 (2016). (4) World Health Organization. Eradication of yaws: procedures for verification and certification of interruption of transmission (World Health Organization, Geneva, 2018). (5) Asiedu, K., Fitzpatrick, C. & Jannin, J. Eradication of yaws: historical efforts and achieving WHO’s 2020 target. PLoS Negl. Trop. Dis. 8, e3016 (2014)

Strain diversity of Treponema pallidum subsp. pertenue suggests rare interspecies 4 transmission in African nonhuman primates

In our most recent study, we found that in Tanzania infection with Treponema pallidum (TP) subsp. pertenue (TPE) is present in four different monkey species. In order to gain information on the diversity and epidemiological spread of the infection in Tanzanian nonhuman primates (NHP), we identified two suitable candidate genes for multi-locus sequence typing (MLST). We demonstrate the functionality of the MLST system in invasively and non-invasively collected samples. While we were not able to demonstrate frequent interspecies transmission of TPE in Tanzanian monkeys, our results show a clustering of TPE strains according to geography and not host species, which is suggestive for rare transmission events between different NHP species. In addition to the geographic stability, we describe the relative temporal stability of the strains infecting NHPs and identified multi-strain infection. Differences between TPE strains of NHP and human origin are highlighted. Our results show that antibiotic resistance does not occur in Tanzanian TPE strains of nHp origin

Continent-wide genomic analysis of the African buffalo (<i>Syncerus caffer</i>)

AbstractThe African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest qualityde novogenome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided surprisingly little support for the currently described four subspecies, but indicated three main lineages, in Western/Central, Eastern and Southern Africa, respectively. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management

Identification of constrained sequence elements across 239 primate genomes

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3–9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals