Misago Seth

Dr. Misago Seth

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Research Focus & Metrics

Academic Career Length

17Years (2010-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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16 August 2024 in The Lancet Microbe
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Journal Article
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JJJonathan J Juliano
Jonathan J Juliano
DGDavid Giesbrecht
David Giesbrecht
ASAlfred Simkin
Alfred Simkin
AFAbebe A Fola
Abebe A Fola
BLBeatus M Lyimo
Beatus M Lyimo
DIDeus S Ishengoma
Deus S Ishengoma
The emergence of the artemisinin partial resistance (ART-R) mutation in the Plasmodium falciparum kelch13 gene (k13), Arg561His, in Rwanda and the regional presence of polymorphisms affecting sulfadoxine-pyrimethamine have raised concern in neighbouring Tanzania. The goal of this study was to assess the status of antimalarial resistance in Tanzania, with a focus on the border with Rwanda, to understand the distribution of the Arg561His mutation, partner drug resistance, and resistance to chemoprevention drugs. In this cross-sectional survey, capillary dried blood spots were collected from malaria positive asymptomatic individuals in the community and symptomatic individuals in health facilities aged 6 months and older, in 13 regions of mainland Tanzania from Jan 31 to June 26, 2021. Exclusion criteria included residence of the areas other than the target sites, presenting to the health facility for care and treatment of conditions other than malaria, and not providing informed consent. Samples were assessed for antimalarial resistance polymorphisms and genetic relatedness using molecular inversion probes targeting P falciparum and short-read whole-genome sequencing. The primary outcome was the prevalence of molecular markers of antimalarial resistance at the region level, as well as at the district level in Kagera, a region in the northwest of the country at the border with Rwanda. 6855 (88·1%) of 7782 capillary dried blood spot samples collected were successfully genotyped. The overall prevalence of k13 Arg561His in Kagera was 7·7% (90% CI 6·0-9·4; 50 of 649), with the highest prevalence in the districts near the Rwandan border (22·8% [31 of 136] in Karagwe, 14·4% [17 of 118]) in Kyerwa, and 1·4% [two of 144] in Ngara). k13 Arg561His was uncommon in the other regions. Haplotype analysis suggested that some of these parasites are related to isolates collected in Rwanda in 2015, supporting regional spread of Arg561His. However, a novel k13 Arg561His haplotype was observed, potentially indicating a second origin in the region. Other validated k13 resistance polymorphisms (one Arg622Ile and two Ala675Val isolates) were also identified. A region of prevalent dihydrofolate reductase Ile164Leu mutation, associated with sulfadoxine-pyrimethamine resistance, was also identified in Kagera (15·2% [12·6-17·8%]; 80 of 526). The mutant crt Lys76Thr mutation, associated with chloroquine and amodiaquine resistance, was uncommon, occurring only in 75 of 2861 genotyped isolates, whereases the wild-type mdr1 Asn86Tyr allele, associated with reduced sensitivity to lumefantrine, was found in 99·7% (3819 of 3830) of samples countrywide. These findings show that the k13 Arg561His mutation is common in northwest Tanzania and that multiple emergences of ART-R, similar as to what was seen in southeast Asia, have occurred. Mutations associated with high levels of sulfadoxine-pyrimethamine resistance are common. These results raise concerns about the long-term efficacy of artemisinin and chemoprevention antimalarials in the region. Understanding how multiple emergences interact with drivers of regional spread is essential for combating ART-R in Africa. This study was funded by the Bill & Melinda Gates Foundation and the National Institutes of Health.

22 November 2023 in The Journal of Infectious Diseases
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ZPZachary Popkin-Hall
Zachary Popkin-Hall
MSMisago Seth
Misago Seth
RMRashid A Madebe
Rashid A Madebe
RBRule Budodo
Rule Budodo
CBCatherine Bakari
Catherine Bakari
DIDeus S Ishengoma
Deus S Ishengoma
Recent data indicate that non-Plasmodium falciparum species may be more prevalent than thought in sub-Saharan Africa. Although Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax are less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized. We randomly selected 3284 of 12 845 samples collected from cross-sectional surveys in 100 health facilities across 10 regions of Mainland Tanzania and performed quantitative real-time PCR to determine presence and parasitemia of each malaria species. P. falciparum was most prevalent, but P. malariae and P. ovale were found in all but 1 region, with high levels (>5%) of P. ovale in 7 regions. The highest P. malariae positivity rate was 4.5% in Mara and 8 regions had positivity rates ≥1%. We only detected 3 P. vivax infections, all in Kilimanjaro. While most nonfalciparum malaria-positive samples were coinfected with P. falciparum, 23.6% (n = 13 of 55) of P. malariae and 14.7% (n = 24 of 163) of P. ovale spp. were monoinfections. P. falciparum remains by far the largest threat, but our data indicate that malaria elimination efforts in Tanzania will require increased surveillance and improved understanding of the biology of nonfalciparum species.

Verified
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AFAdam Fimbo
Adam Fimbo
OMOmary Mashiku Minzi
Omary Mashiku Minzi
BMBruno Mmbando
Bruno Mmbando
ABAbbie Barry
Abbie Barry
ANAlex Nkayamba
Alex Nkayamba
EAEleni Aklillu
Eleni Aklillu
Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1–6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.

7 June 2021 in Animals
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DMDaniel Mdetele
Daniel Mdetele
EKErick Komba
Erick Komba
MSMisago Seth
Misago Seth
Gerald MisinzoGerald Misinzo
Gerald Misinzo
RKRichard Kock
Richard Kock
BJBryony Anne Jones
Bryony Anne Jones
Peste des petits ruminants (PPR) is an important transboundary animal disease of domestic small ruminants, camels, and wild artiodactyls. The disease has significant socio-economic impact on communities that depend on livestock for their livelihood and is a threat to endangered susceptible wild species. The aim of this review was to describe the introduction of PPR to Tanzania and its subsequent spread to different parts of the country. On-line databases were searched for peer-reviewed and grey literature, formal and informal reports were obtained from Tanzanian Zonal Veterinary Investigation Centres and Laboratories, and Veterinary Officers involved with PPR surveillance were contacted. PPR virus (PPRV) was confirmed in northern Tanzania in 2008, although serological data from samples collected in the region in 1998 and 2004, and evidence that the virus was already circulating in Uganda in 2003, suggests that PPRV might have been present earlier than this. It is likely that the virus which became established in Tanzania was introduced from Kenya between 2006–7 through the cross-border movement of small ruminants for trade or grazing resources, and then spread to eastern, central, and southern Tanzania from 2008 to 2010 through movement of small ruminants by pastoralists and traders. There was no evidence of PPRV sero-conversion in wildlife based on sera collected up to 2012, suggesting that they did not play a vectoring or bridging role in the establishment of PPRV in Tanzania. PPRV lineages II, III and IV have been detected, indicating that there have been several virus introductions. PPRV is now considered to be endemic in sheep and goats in Tanzania, but there has been no evidence of PPR clinical disease in wildlife species in Tanzania, although serum samples collected in 2014 from several wild ruminant species were PPRV sero-positive. Similarly, no PPR disease has been observed in cattle and camels. In these atypical hosts, serological evidence indicates exposure to PPRV infection, most likely through spillover from infected sheep and goats. Some of the challenges for PPRV eradication in Tanzania include movements of small ruminants, including transboundary movements, and the capacity of veterinary services for disease surveillance and vaccination. Using wildlife and atypical domestic hosts for PPR surveillance is a useful indicator of endemism and the ongoing circulation of PPRV in livestock, especially during the implementation of vaccination to control or eliminate the disease in sheep and goats. PPR disease has a major socio-economic impact in Tanzania, which justifies the investment in a comprehensive PPRV eradication programme.

1 February 2024 in medRxiv
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Preprint
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DIDeus S. Ishengoma
Deus S. Ishengoma
CMCeline I. Mandara
Celine I. Mandara
CBCatherine Bakari
Catherine Bakari
AFAbebe A. Fola
Abebe A. Fola
RMRashid A. Madebe
Rashid A. Madebe
MWMarian Warsame
Marian Warsame
Background Artemisinin-based combination therapies (ACTs) are the recommended antimalarial drugs for the treatment of uncomplicated malaria. The recent emergence of artemisinin partial resistance (ART-R) in Rwanda, Uganda and Eritrea is of great concern. In Tanzania, a nationwide molecular malaria surveillance in 2021 showed a high prevalence of the Kelch13 (K13) 561H mutation in Plasmodium falciparum from the north-western region, close to the border with Rwanda and Uganda. This study was conducted in 2022 to evaluate the efficacy of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) for the treatment of uncomplicated falciparum malaria and to confirm the presence of ART-R in Tanzania. Methods This single-arm study evaluated the efficacy of AL and ASAQ in eligible children aged six months to 10 years at Bukangara Dispensary in Karagwe District, Kagera Region. Clinical and parasitological responses were monitored for 28 days according to standard WHO protocol. Mutations in K13 gene and extended haplotypes with these mutations were analysed using Sanger and whole genome sequencing data, respectively. Findings 176 children (88 in each AL and ASAQ group) were enrolled and all achieved the defined outcomes. PCR-corrected adequate clinical and parasitological response (ACPR) was 98.3% (95% CI: 90.8-100) and 100.0% (95% CI: 95.8-100) for AL and ASAQ, respectively. Parasitaemia on day 3 was observed in 11/88 (12.5%) and 17/88 (19.3%) in the AL and ASAQ groups, respectively. The half-life of parasitaemia was significantly higher (>6.5 hrs) in patients with parasitaemia on day 3 and/or mutations in K13 gene at enrolment. Most patients with parasitaemia on day 3 (8/11 = 72.7% in the AL group and 10/17 = 58.8% in the ASAQ group) had 561H mutation at enrolment. The parasites with K13 mutations were not similar to those from south-east Asia and Rwanda, but had the same core haplotype of a new 561H haplotype reported in Kagera in 2021. Interpretation These findings confirm the presence of ART-R in Tanzania. A context-specific strategy to respond to artemisinin partial resistance is urgently needed. Although both AL and ASAQ showed high efficacy, increased vigilance for reduced efficacy of these ACTs and detection of ART-R in other parts of the country is critical. Funding Bill and Melinda Gates Foundation to the World Health Organization (WHO, OPP 1209843) and the National Institute for Medical Research (NIMR, Inv. No. 002202), and US National Institute for Health (R01AI156267 to JAB, DSI and JJJ, and K24AI134990 to JJJ). Evidence before this study Artemisinin partial resistance (ART-R) is defined as delayed clearance after treatment with an artemisinin combination therapy (ACT) or artesunate monotherapy of a parasite strain carrying a validated marker of ART-R. At present, 13 different Kelch13 (K13) mutations have been validated as markers of ART-R. ART-R is confirmed in an area if a quality-controlled study using an ACT or artesunate monotherapy, finds more than 5% of patients have parasites with validated K13 mutations and delayed clearance as evidenced by either persistent parasitemia detected by microscopy on day 3 or a parasite clearance half-life of ≥5 hours. ART-R was first reported from Cambodia in 2008 and later from several countries in Southeast Asia. Published articles up to December 2023 were searched in PubMed with the terms; “artemisini n”, “artemisinin partial resistance”, “artemisinin-based combination therapies”, “Kelch 13” in combination with “Africa” or “Tanzania”. The publications confirmed the emergence of ART-R associated with mutations in K13: 561H in Rwanda, A675V and C469Y in Uganda and R622I in Eritrea. All these studies showed a high cure rate of the tested ACTs. The R622I mutant was not reported from Southeast Asia but is circulating in the Horn of Africa (Eritrea, Ethiopia, Sudan and Somalia). In Tanzania, a nationwide malaria molecular surveilla nce launched in January 2021 showed a high prevalence of 561H mutation in the north-western region of Kagera, close to the border with Rwanda and Uganda. Added value of this study The study documented delayed parasite clearance associated with pre-treatment validated K13 561H mutation. It confirms and provides evidence for the first-time of ART-R in Kagera region, north-western Tanzania, an area close to the border with Rwanda and Uganda. This makes Tanzania the fourth country in Africa with confirmed ART-R. The study documents presence of K13 mutation associated with ART-R suggesting that partial resistance to artemisinins is rapidly evolving and can still be found in more areas of Africa. Parasites with K13 mutations were not similar to those from south-east Asia and Rwanda, but had the same core haplotype of a new 561H haplotype reported in Kagera in 2021.The findings of this study furthermore show that both AL and ASAQ are highly effective. Implications of all the available evidence The emergence of confirmed ART-R in Africa, so far in four countries (Rwanda, Uganda, Eritrea and Tanzania), poses a serious threat to malaria control in Africa, which accounts for more than 95% of the global malaria burden. The current evidence of ART-R in Kagera region calls for an urgent response, including the development of a context-specific strategy based on the recently launched WHO strategy to respond to antimalarial drug resistance in Africa. The fact that ART-R has been confirmed in Kagera region, an area bordering Rwanda and Uganda, where resistance also has been reported, also calls for cross-border collaboration to harmonize strategies to combat this threat in the Great Lakes region of Africa. Nationwide studies on molecular markers in Tanzania, which revealed a high prevalence of K13 validated mutatio ns in the Kagera region, guided where to conduct the current study. This suggests that molecular marker surveillance could play an important role in conducting targeted antimalarial drug efficacy studies and confirming ART-R in other parts of Tanzania and beyond.

31 March 2018 in Microfluidics and Nanofluidics
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MSMisago Seth
Misago Seth
DMDaniel Mdetele
Daniel Mdetele
JBJoram Buza
Joram Buza