Evidence of artemisinin partial resistance in northwestern Tanzania: clinical and molecular markers of resistance.

Background: In 2021, nationwide malaria molecular surveillance revealed a high prevalence of a validated artemisinin resistance marker, the kelch13 (k13) Arg561His mutation, in the Kagera region of northwestern Tanzania. We aimed to investigate the efficacy of artemether-lumefantrine and artesunate-amodiaquine and to confirm the presence of artemisinin partial resistance (ART-R) in the Karagwe district of this region.

Methods: This single-arm, therapeutic efficacy study was carried out at the Bukangara dispensary in the Karagwe district of the Kagera region in northwestern Tanzania.

High prevalence and risk of malaria among asymptomatic individuals from villages with high prevalence of artemisinin partial resistance in Kyerwa district of Kagera region, north-western Tanzania.

Background: Although Tanzania adopted and has been implementing effective interventions to control and eventually eliminate malaria, the disease is still a leading public health problem, and the country experiences heterogeneous transmission. Recent studies reported the emergence of parasites with artemisinin partial resistance (ART-R) in Kagera region with high prevalence (> 10.0%) in two districts of Karagwe and Kyerwa.

Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions among patients enrolled at 100 health facilities throughout Tanzania: February to July 2021.

Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results.

Prevalence of non-falciparum malaria infections among asymptomatic individuals in four regions of Mainland Tanzania.

Background: Recent studies point to the need to incorporate the detection of non-falciparum species into malaria surveillance activities in sub-Saharan Africa, where 95% of the world's malaria cases occur. Although malaria caused by infection with Plasmodium falciparum is typically more severe than malaria caused by the non-falciparum Plasmodium species P. malariae, P.

Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021.

Background: Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021.

Methods: A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021.

Evidence of artemisinin partial resistance in North-western Tanzania: clinical and drug resistance markers study.

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 from the north-western region, close to the border with Rwanda and Uganda.

Genetic polymorphism and evidence of signatures of selection in the circumsporozoite protein gene in Tanzanian regions with different malaria endemicity.

Background: In 2021 and 2023, the World Health Organization approved RTS, S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of circumsporozoite protein ( but polymorphisms in this gene raises concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission in mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country.

Malaria species prevalence among asymptomatic individuals in four regions of Mainland Tanzania.

Recent studies point to the need to incorporate non-falciparum species detection into malaria surveillance activities in sub-Saharan Africa, where 95% of malaria cases occur. Although infection is typically more severe, diagnosis, treatment, and control for , spp., and may be more challenging.

Malaria Species Positivity Rates Among Symptomatic Individuals Across Regions of Differing Transmission Intensities in Mainland Tanzania.

Background: 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.

Country wide surveillance reveals prevalent artemisinin partial resistance mutations with evidence for multiple origins and expansion of high level sulfadoxine-pyrimethamine resistance mutations in northwest Tanzania.

Background: Emergence of artemisinin partial resistance (ART-R) in is a growing threat to the efficacy of artemisinin combination therapies (ACT) and the efforts for malaria elimination. The emergence of Kelch13 (K13) R561H in Rwanda raised concern about the impact in neighboring Tanzania. In addition, regional concern over resistance affecting sulfadoxine-pyrimethamine (SP), which is used for chemoprevention strategies, is high.

Malaria species positivity rates among symptomatic individuals across regions of differing transmission intensities in Mainland Tanzania.

Recent data indicate that non- species may be more prevalent than previously realized in sub-Saharan Africa, the region where 95% of the world's malaria cases occur. Although spp., and are generally less severe than , treatment and control are more challenging, and their geographic distributions are not well characterized.

Performance of antigen detection for HRP2-based malaria rapid diagnostic tests in community surveys: Tanzania, July-November 2017.

Background: Malaria rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum histidine-rich protein 2 (HRP2) antigen are widely used for detection of active infection with this parasite and are the only practical malaria diagnostic test in some endemic settings. External validation of RDT results from field surveys can confirm appropriate RDT performance.

Methods: A community-based cross-sectional survey was conducted between July and November 2017 enrolling participants of all ages in households from 15 villages in four border regions of Tanzania: Geita, Kigoma, Mtwara and Ruvuma.

Potential Opportunities and Challenges of Deploying Next Generation Sequencing and CRISPR-Cas Systems to Support Diagnostics and Surveillance Towards Malaria Control and Elimination in Africa.

Recent developments in molecular biology and genomics have revolutionized biology and medicine mainly in the developed world. The application of next generation sequencing (NGS) and CRISPR-Cas tools is now poised to support endemic countries in the detection, monitoring and control of endemic diseases and future epidemics, as well as with emerging and re-emerging pathogens. Most low and middle income countries (LMICs) with the highest burden of infectious diseases still largely lack the capacity to generate and perform bioinformatic analysis of genomic data.

Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania.

Background: Histidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania.

Methods: A community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma.