Are we prepared for emerging and re-emerging diseases? Experience and lessons from epidemics occurred in Tanzania during the last five decades

This paper reviews preparedness for containing and controlling emerging and re-emerging diseases drawing lessons from disease events that occurred in animal and human populations in the last five decades (1961-2011). A comprehensive analysis based on retrieval and analysis of grey and published literature as well as reported cases was carried out to document type and trend of occurrence of emerging and re-emerging infectious diseases in different parts of Tanzania. Overall, the majority of diseases reported in the country were viral in nature followed by bacterial diseases. The trend for the occurrence shows a number of new emerging diseases as well as re-occurrence of old diseases in both animal (domestic and wild) and human populations. In humans, the major disease epidemics reported in the last five decades include cholera, influenza A H1N1, plague and rubella. In animals, the major epidemic diseases reported were Contagious Bovine Pleuropneumonia, Contagious Caprine Pleuropneumonia, Peste des petits ruminants and Giraffe Ear and Skin Diseases. Some epidemics have been reported in both human and animal populations including Rift Valley fever and anthrax.  The emergence of the ‘fit-for purpose’ approaches and technologies such as the discipline of One Health, use of participatory epidemiology and disease surveillance and mobile technologies offers opportunity for optimal use of limited resources to improve early detection, diagnosis and response to disease events and consequently reduced impact of such diseases in animal and human populations

Sequence-based prediction for vaccine strain selection and identification of antigenic variability in foot-and-mouth disease virus

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence - by controlling for phylogenetic structure - for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease

Perfil da resposta imune humoral de bovinos após a revacinação com vacina anti-rábica inativada, preparada em células BHK contendo Hidróxido de Alumínio

The phenomenon of "in vivo" blocking effect of antigen, due to the presence of rabies specific neutralizing antibodies in previously vaccinated cattle, and its possible interference on the humoral immunologic response to revaccination was investigated in five zebu-crossbred bovines reared in field condition. The secondary vaccination was performed 180 days from the first immunization, using a commercial inactivated rabies vaccine prepared in BHK-21 cells. Serum samples were taken sequentially after each vaccine administration at intervals of 0 (zero), 24 and 72 hours, and after 7 and 14 days for the determination of neutralizing antibodies. The mean neutralizing antibody titer determined for sera taken immediately before the first vaccination was < 1:5, at 24 and 72 hours post-vaccination, < 1:6.25; the mean value found at 7 days post-vaccination was 1:144 ± 51;and 1:3,460 ± 1,329, at 14 days post-vaccination with mean titer of 1:58 ± 14; 24 hours after revaccination the mean titer was 1:129 ± 80, raising forwardly to1:277 ± 161, at 72 hours post-revaccination, and increasing levels > 1:6,400 and > 1:25,600 were found at 7 and 14 days post-revaccination, evidenciating a full anamnestic response. The blocking effect of antigen and the consequent fall in antibody levels shortly after the revaccination was not observed.O fenômeno do consumo de antígeno, devido apresentação de anticorpos neutralizantes específicos para a raiva, em bovinos previamente vacinados e a sua possível interferência na resposta imunológica humoral, decorrente de revacinação, foi investigado em cinco bovinos mestiços azebuados, criados em condições de campo. A revacinação foi realizada 180 dias após a primeira aplicação, utilizando uma vacina comercial inativada, preparada em células BHK-21. As amostras de soros foram obtidas em intervalos sequenciais de 0 (zero), 24 , 72 horas, sete e 14 dias, em cada vacinação e foram submetidas à prova de neutralização em camundongos para a pesquisa de anticorpos. O título médio de anticorpos neutralizantes, encontrado para o momento imediatamente antes da primeira vacinação foi < 1:5, 24 e 72 horas após a vacinação foi < 1:6, 25; no sétimo dia pós-vacinação o valor médio foi de 1:144 ± 51; aos 14 dias pós-vacinação, 1:3.460 ± 1.329. Todos os animais apresentaram títulos detectáveis no 180ª dia pós-vacinação, com um valor médio de 1:58 ± 14; no entanto, 24 horas após a dose revacinante, foi detectado um valor médio de 1:129 ± 80, ascendendo para 1:277 ± 161 no 3 S dia pós-vacinação, e níveis crescentes no 7 ! e no 14! pós-vacinação, com valores, respectivamente, superiores a 1:6.400 e1:25.600, indicando o estabelecimento de uma resposta anamnéstica plena. Não foi observado o efeito do consumo do antígeno e a consequente diminuição nos títulos de anticorpos, imediatamente após a revacinação

Safety, immunogenicity and antibody persistence of Rift Valley fever Virus clone 13 vaccine in sheep, goats and cattle in Tanzania

BACKGROUND : Vaccination is considered to be the best approach to control Rift Valley fever (RVF) in animals and consequently in humans. This study assessed the efficacy and safety of the RVF virus (RVFV) Clone 13 vaccine under field conditions. METHODOLOGY : A vaccine trial was conducted in sheep (230), goats (230), and cattle (140) in Ngorongoro district, Tanzania. Half of each of the animal species were vaccinated and the other half received the placebo. Animals were clinicallymonitored and bled before vaccination and at days 15, 30, 60, 180 and 360 (+/– 10) post-vaccination to measure Immunoglobulin M (IgM) and IgG antibody responses to RVFV. Survival analysis was conducted using cox-proportional hazard regression model to measure the time until an event of interest had occurred and to compare the cumulative proportion of events over time. RESULTS : Of 600 animals included in the study, 120 animals were lost during the study, leaving a total of 480 (243 in the vaccinated group and 237 in the control group) for complete follow-up sampling. There was no adverse reaction reported at the injection site of the vaccine/placebo in all animals. Abortions, deaths, or body temperature variations were not associated with vaccination (p > 0.05). By day 15 post-inoculation, the IgG seroconversion in vaccinated goats, cattle and sheep was 27.0% (n = 115), 20.0% (n = 70) and 10.4% (n = 115), respectively. By day 30 post-inoculation, it was 75.0% (n = 113), 74.1% (n = 112) and 57.1% (n = 70) in vaccinated sheep, goats and cattle, respectively. By day 60 post-inoculation, IgG seroconversion in sheep, goats and cattle was 88.1% (n = 109), 84.3% (n = 108) and 64.60% (n = 65), respectively. By day 180, the IgG seroconversion in sheep, goats and cattle was 88.0% (n = 108), 83.8% (n = 105) and 66.1% (n = 62), respectively. By day 360, the IgG seroconversion in sheep, goats and cattle was 87.2% (n = 94), 85.6% (n = 90) and 66.1% (n = 59), respectively. Only five animals from the vaccinated group were RVFV IgM positive, which included four sheep and a goat. CONCLUSION : RVFV Clone 13 vaccine was well tolerated by sheep, goats, and cattle. The vaccine induced detectable, but variable levels of IgG responses, and of different duration. The vaccine is considered safe, with high immunogenicity in sheep and goats and moderate in cattle.The Bill & Melinda Gates Foundation and United Kingdom (UK) aid from the UK Government through the Global Alliance for Livestock Veterinary Medicines.https://www.frontiersin.org/journals/veterinary-science#am2022Medical Virolog

Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania

SummaryThis study was part of a larger cross-sectional survey that was evaluating tuberculosis (TB) infection in humans, livestock and wildlife in the Serengeti ecosystem in Tanzania. The study aimed at evaluating the genetic diversity of Mycobacterium tuberculosis isolates from TB patients attending health facilities in the Serengeti ecosystem. DNA was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated TB patients aged ≥18 years. Spacer oligonucleotide typing (spoligotyping) and Mycobacterium Interspersed Repetitive Units and Variable Number Tandem Repeat (MIRU-VNTR) were used to genotype M. tuberculosis to establish the circulating lineages. Of the214 M. tuberculosis isolates genotyped, 55 (25.7%) belonged to the Central Asian (CAS) family, 52 (24.3%) were T family (an ill-defined family), 38 (17.8%) belonged to the Latin American Mediterranean (LAM) family, 25 (11.7%) to the East-African Indian (EAI) family, 25 (11.7%) comprised of different unassigned (‘Serengeti’) strain families, while 8 (3.7%) belonged to the Beijing family. A minority group that included Haarlem, X, U and S altogether accounted for 11 (5.2%) of all genotypes. MIRU-VNTR typing produced diverse patterns within and between families indicative of unlinked transmission chains. We conclude that, in the Serengeti ecosystem only a few successful families predominate namely CAS, T, LAM and EAI families. Other types found in lower prevalence are Beijing, Haarlem, X, S and MANU. The Haarlem, EAI_Somalia, LAM3 and S/convergent and X2 subfamilies found in this study were not reported in previous studies in Tanzania

Whole genome sequencing of Mycobacterium tuberculosis isolates and clinical outcomes of patients treated for multidrug-resistant tuberculosis in Tanzania.

BACKGROUND: Tuberculosis (TB), particularly multi- and or extensive drug resistant TB, is still a global medical emergency. Whole genome sequencing (WGS) is a current alternative to the WHO-approved probe-based methods for TB diagnosis and detection of drug resistance, genetic diversity and transmission dynamics of Mycobacterium tuberculosis complex (MTBC). This study compared WGS and clinical data in participants with TB. RESULTS: This cohort study performed WGS on 87 from MTBC DNA isolates, 57 (66%) and 30 (34%) patients with drug resistant and susceptible TB, respectively. Drug resistance was determined by Xpert® MTB/RIF assay and phenotypic culture-based drug-susceptibility-testing (DST). WGS and bioinformatics data that predict phenotypic resistance to anti-TB drugs were compared with participant's clinical outcomes. They were 47 female participants (54%) and the median age was 35 years (IQR): 29-44). Twenty (23%) and 26 (30%) of participants had TB/HIV co-infection BMI < 18 kg/m2 respectively. MDR-TB participants had MTBC with multiple mutant genes, compared to those with mono or polyresistant TB, and the majority belonged to lineage 3 Central Asian Strain (CAS). Also, MDR-TB was associated with delayed culture-conversion (median: IQR (83: 60-180 vs. 51:30-66) days). WGS had high concordance with both culture-based DST and Xpert® MTB/RIF assay in detecting drug resistance (kappa = 1.00). CONCLUSION: This study offers comparison of mutations detected by Xpert and WGS with phenotypic DST of M. tuberculosis isolates in Tanzania. The high concordance between the different methods and further insights provided by WGS such as PZA-DST, which is not routinely performed in most resource-limited-settings, provides an avenue for inclusion of WGS into diagnostic matrix of TB including drug-resistant TB

Exploring local knowledge and perceptions on zoonoses among pastoralists in northern and eastern Tanzania

Background: Zoonoses account for the most commonly reported emerging and re-emerging infectious diseases in Sub-Saharan Africa. However, there is limited knowledge on how pastoral communities perceive zoonoses in relation to their livelihoods, culture and their wider ecology. This study was carried out to explore local knowledge and perceptions on zoonoses among pastoralists in Tanzania. Methodology and principal findings: This study involved pastoralists in Ngorongoro district in northern Tanzania and Kibaha and Bagamoyo districts in eastern Tanzania. Qualitative methods of focus group discussions, participatory epidemiology and interviews were used. A total of 223 people were involved in the study. Among the pastoralists, there was no specific term in their local language that describes zoonosis. Pastoralists from northern Tanzania possessed a higher understanding on the existence of a number of zoonoses than their eastern districts' counterparts. Understanding of zoonoses could be categorized into two broad groups: a local syndromic framework, whereby specific symptoms of a particular illness in humans concurred with symptoms in animals, and the biomedical framework, where a case definition is supported by diagnostic tests. Some pastoralists understand the possibility of some infections that could cross over to humans from animals but harm from these are generally tolerated and are not considered as threats. A number of social and cultural practices aimed at maintaining specific cultural functions including social cohesion and rites of passage involve animal products, which present zoonotic risk. Conclusions: These findings show how zoonoses are locally understood, and how epidemiology and biomedicine are shaping pastoralists perceptions to zoonoses. Evidence is needed to understand better the true burden and impact of zoonoses in these communities. More studies are needed that seek to clarify the common understanding of zoonoses that could be used to guide effective and locally relevant interventions. Such studies should consider in their approaches the pastoralists' wider social, cultural and economic set up

Genetic diversity of Mycobacterium tuberculosis isolated from tuberculosis patients in the Serengeti ecosystem in Tanzania

This study was part of a larger cross-sectional survey that was evaluating tuberculosis (TB) infection in humans, livestock and wildlife in the Serengeti ecosystem in Tanzania. The study aimed at evaluating the genetic diversity of Mycobacterium tuberculosis isolates from TB patients attending health facilities in the Serengeti ecosystem. DNA was extracted from 214 sputum cultures obtained from consecutively enrolled newly diagnosed untreated TB patients aged 18 years. Spacer oligonucleotide typing (spoligotyping) and Mycobacterium Interspersed Repetitive Units and Variable Number Tandem Repeat (MIRU-VNTR) were used to genotype M. tuberculosis to establish the circulating lineages. Of the214 M. tuberculosis isolates genotyped, 55 (25.7%) belonged to the Central Asian (CAS) family, 52 (24.3%) were T family (an ill-defined family), 38 (17.8%) belonged to the Latin American Mediterranean (LAM) family, 25 (11.7%) to the East-African Indian (EAI) family, 25 (11.7%) comprised of different unassigned (‘Serengeti’) strain families, while 8 (3.7%) belonged to the Beijing family. A minority group that included Haarlem, X, U and S altogether accounted for 11 (5.2%) of all genotypes. MIRU-VNTR typing produced diverse patterns within and between families indicative of unlinked transmission chains. We conclude that, in the Serengeti ecosystem only a few successful families predominate namely CAS, T, LAM and EAI families. Other types found in lower prevalence are Beijing, Haarlem, X, S and MANU. The Haarlem, EAI_Somalia, LAM3 and S/convergent and X2 subfamilies found in this study were not reported in previous studies in Tanzania.WT087546MA and MUHAS Sida Sarec [000/3177].http://intl.elsevierhealth.com/journals/tubehb201

Knowledge, attitudes and practices regarding antimicrobial use and resistance among communities of Ilala, Kilosa and Kibaha districts of Tanzania.

BACKGROUND: Antimicrobial resistance (AMR) represents one of the biggest threats to health globally. This cross-sectional study determined knowledge, attitudes and practices (KAP) regarding antimicrobial use (AMU) and AMR among communities of Ilala, Kilosa and Kibaha in Tanzania. METHOD: A semi-structured questionnaire was used to collect socio-demographic and KAP data through face-to-face interviews. Responses related to the triad of KAP were assigned scores that were aggregated for each participant. Linear regression analysis was conducted to determine predictors of KAP scores. RESULTS: The study enrolled 828 participants from the three districts. A total of 816 (98.6%) were aware of antimicrobials, and 808 (99%, n = 816) reported to have used them. Antimicrobials were mainly used to treat cough (68.0%), urinary tract infections (53.4%), diarrhoea (48.5%) and wounds (45.2%). The most frequent sources of antimicrobials were health facility (65.0%, n = 820) and pharmacies/basic drug shops (53.7%). The median AMU knowledge score was 5 (IQR = 4, 7) and that of AMR was 26 (IQR=23, 29). The median AMU attitudes score was 32 (IQR: 29, 35) and that of AMR was 19 (IQR=17, 22). The median AMU practice score was 3 (IQR: 3, 3). The KAP scores were significantly influenced by increased participant's age (βadj=0.10; 95% CI: 0.05, 0.15) and level of education, being lower among those with primary education (βadj=5.32; 95% CI: 3.27, 7.37) and highest among those with college/university education (βadj=9.85; 95% CI: 6.04, 13.67). CONCLUSION: The study documented a moderate level of KAP regarding AMU and AMR in the study districts. The participant's age and level of education were significantly associated with participant's KAP scores. The observed inadequate knowledge, inappropriate attitude, and practices of AMU and AMR should be considered as alarming problems that require immediate actions including policy formulation and planning of community-based mitigation measures