Genetic diversity of Plasmodium falciparum reticulocyte binding protein homologue-5, which is a potential malaria vaccine candidate: baseline data from areas of varying malaria endemicity in Mainland Tanzania.

Background: The limited efficacy of the two recently approved malaria vaccines, RTS,S/AS01 and R21/Matrix- M™, highlights the need for alternative vaccine candidate genes. Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 (Pfrh5) is a promising malaria vaccine candidate, given its limited polymorphism, its essential role in parasite survival, a lack of immune selection pressure and higher efficacy against multiple parasites strains. This study evaluated the genetic diversity of Pfrh5 gene among parasites from regions with varying malaria transmission intensities in Mainland Tanzania, to generate baseline data for this potential malaria vaccine candidate.

Prevalence and drivers of malaria infection among asymptomatic and symptomatic community members in five regions with varying transmission intensity in mainland Tanzania.

Background: Despite implementation of effective interventions in the past two decades, malaria is still a major public health problem in Tanzania. This study assessed the prevalence and drivers of malaria infections among symptomatic and asymptomatic members of selected communities from five regions with varying endemicity in mainland Tanzania.

Methods: A cross-sectional community survey was conducted in five districts, including one district/region in Kagera, Kigoma, Njombe, Ruvuma and Tanga from July to August 2023.

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.

Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania.

Background: Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES.

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.

Effectiveness and safety of intermittent preventive treatment with dihydroartemisinin-piperaquine or artesunate-amodiaquine for reducing malaria and related morbidities in schoolchildren in Tanzania: a randomised controlled trial.

Background: In high transmission settings, most school-aged children harbour malaria parasites without showing symptoms, often leading to anaemia and possibly impaired psychomotor and cognitive abilities. We aimed to assess the effectiveness and safety of intermittent preventive treatment for malaria in school-aged children (IPTsc) living in highly endemic areas.

Methods: We did an open-label randomised controlled trial in seven primary schools in northeastern Tanzania.

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.

Attributable risk factors for asymptomatic malaria and anaemia and their association with cognitive and psychomotor functions in schoolchildren of north-eastern Tanzania.

In Africa, children aged 5 to 15 years (school age) comprises more than 50% (>339 million) of the under 19 years population, and are highly burdened by malaria and anaemia that impair cognitive development. For the prospects of improving health in African citizens, understanding malaria and its relation to anaemia in school-aged children, it is crucial to inform targeted interventions for malaria control and accelerate elimination efforts as part of improved school health policy. We conducted a study to determine the risk factors for asymptomatic malaria and their association to anaemia.

Prevalence of asymptomatic malaria, submicroscopic parasitaemia and anaemia in Korogwe District, north-eastern Tanzania.

Background: Asymptomatic malaria infections largely remain undetected and act as a reservoir for continuous transmission. The study assessed the prevalence of submicroscopic asymptomatic malaria infections and anaemia in two rural low (300 m above sea level) and highland (700 m asl) settings of Korogwe District north-eastern Tanzania.

Methods: A cross-sectional malariometric survey involving individuals aged 0-19 years was conducted in June 2018 in the two rural villages.

Describing the current status of Plasmodium falciparum population structure and drug resistance within mainland Tanzania using molecular inversion probes.

High-throughput Plasmodium genomic data is increasingly useful in assessing prevalence of clinically important mutations and malaria transmission patterns. Understanding parasite diversity is important for identification of specific human or parasite populations that can be targeted by control programmes, and to monitor the spread of mutations associated with drug resistance. An up-to-date understanding of regional parasite population dynamics is also critical to monitor the impact of control efforts.

Effectiveness and safety of intermittent preventive treatment for malaria using either dihydroartemisinin-piperaquine or artesunate-amodiaquine in reducing malaria related morbidities and improving cognitive ability in school-aged children in Tanzania: A study protocol for a controlled randomised trial.

Background: In high transmission settings, up to 70% of school-aged children harbour malaria parasites without showing any clinical symptoms. Thus, epidemiologically, school aged children act as a substantial reservoir for malaria transmission. Asymptomatic infections induce inflammation leading to iron deficiency anaemia.

Herpes Simplex virus type 2 seroprevalence and risk factors among adolescents and youth with HIV-1 in Northern, Tanzania.

Introduction: Herpes Simplex virus type 2 (HSV-2) infection is associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition and transmission. Individuals co-infected with HIV-1 and HSV-2 may have longer lasting, more frequent and severe outbreaks of herpes symptoms. Previous studies have assessed HSV-2 seroprevalence and associated risk factors in adult populations.

Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo.

Sulfadoxine/pyrimethamine (SP) is still used for malaria control in sub-Saharan Africa; however, widespread resistance is a major concern. This study aimed to determine the dispersal and origin of sulfadoxine resistance lineages in the Democratic Republic of the Congo compared with East African Plasmodium falciparum dihydropteroate synthetase (Pfdhps) haplotypes. The analysis involved 264 isolates collected from patients with uncomplicated malaria from Tanzania, Uganda and DR Congo.