Pf7: an open dataset of genome variation in 20,000 worldwide samples.

We describe the MalariaGEN Pf7 data resource, the seventh release of genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit.

Efficacy and safety of artemisinin-based combination therapy, and molecular markers for artemisinin and piperaquine resistance in Mainland Tanzania.

Background: Artemisinin-based combination therapy (ACT) is the first-line anti-malarial treatment of uncomplicated malaria in most malaria endemic countries, including Tanzania. Unfortunately, there have been reports of artemisinin resistance and ACT failure from South East Asia highlighting the need to monitor therapeutic efficacy of ACT in these countries as recommended by World Health Organization.

Methods: Open-label single arm studies in mainland Tanzania were conducted in nine sentinel sites in 2011, 2012 and 2015 to assess the efficacy and safety of artemether/lumefantrine (AL) and artesunate/amodiaquine (ASAQ) using 28 days follow-up and dihydroartemisinin/piperaquine (DHAPQ) using 42 days follow-up.

High efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Muheza and Kigoma Districts, Tanzania.

Background: Artemether-lumefantrine (AL) is the recommended first-line artemisinin-based combination therapy (ACT) for the treatment of uncomplicated falciparum malaria in most of the malaria-endemic countries, including Tanzania. Recently, dihydroartemisinin-piperaquine (DP) has been recommended as the alternative anti-malarial to ensure effective case management in Tanzania. This study assessed the parasite clearance rate and efficacy of AL and DP among patients aged 6 months to 10 years with uncomplicated falciparum malaria in two sites with different malaria transmission intensity.

Trends of Plasmodium falciparum prevalence in two communities of Muheza district North-eastern Tanzania: correlation between parasite prevalence, malaria interventions and rainfall in the context of re-emergence of malaria after two decades of progressively declining transmission.

Background: Although the recent decline of malaria burden in some African countries has been attributed to a scale-up of interventions, such as bed nets (insecticide-treated bed nets, ITNs/long-lasting insecticidal nets, LLINs), the contribution of other factors to these changes has not been rigorously assessed. This study assessed the trends of Plasmodium falciparum prevalence in Magoda (1992-2017) and Mpapayu (1998-2017) villages of Muheza district, North-eastern Tanzania, in relation to changes in the levels of different interventions and rainfall patterns.

Methods: Individuals aged 0-19 years were recruited in cross-sectional surveys to determine the prevalence of P.

Relationships between sickle cell trait, malaria, and educational outcomes in Tanzania.

Background: Sickle Cell Trait (SCT) has been shown to be protective against malaria. A growing literature suggests that malaria exposure can reduce educational attainment. This study assessed the relationship and interactions between malaria, SCT and educational attainment in north-eastern Tanzania.

Deployment and use of mobile phone technology for real-time reporting of fever cases and malaria treatment failure in areas of declining malaria transmission in Muheza district north-eastern Tanzania.

Background: Early detection of febrile illnesses at community level is essential for improved malaria case management and control. Currently, mobile phone-based technology has been commonly used to collect and transfer health information and services in different settings. This study assessed the applicability of mobile phone-based technology in real-time reporting of fever cases and management of malaria by village health workers (VHWs) in north-eastern Tanzania.

Malaria Host Candidate Genes Validated by Association With Current, Recent, and Historical Measures of Transmission Intensity.

Background: Human malaria susceptibility is determined by multiple genetic factors. It is unclear, however, which genetic variants remain important over time.

Methods: Genetic associations of 175 high-quality polymorphisms within several malaria candidate genes were examined in a sample of 8096 individuals from northeast Tanzania using altitude, seroconversion rates, and parasite rates as proxies of historical, recent, and current malaria transmission intensity.

Profile of C-reactive protein, white cells and neutrophil populations in febrile children from rural north-eastern Tanzania.

Introduction: C-reactive protein (CRP), white blood cell (WBC) and absolute neutrophil counts (ANC) are important inflammatory biomarkers in the early diagnosis of infections. However, little is known on their profile and usefulness in fever case management in children attending outpatient clinic in rural north-eastern Tanzania.

Methods: Patients aged between 2 and 59 months presenting with fever at Korogwe District Hospital were enrolled.

Performance of health laboratories in provision of HIV diagnostic and supportive services in selected districts of Tanzania.

Background: Roll-out and implementation of antiretroviral therapy (ART) necessitated many countries in Sub-Saharan Africa to strengthen their national health laboratory systems (NHLSs) to provide high quality HIV diagnostic and supportive services. This study was conducted to assess the performance of health laboratories in provision of HIV diagnostic and supportive services in eight districts (from four regions of Iringa, Mtwara, Tabora and Tanga), after nine years of implementation of HIV/AIDS care and treatment plan in Tanzania.

Methods: In this cross-sectional study, checklists and observations were utilized to collect information from health facilities (HFs) with care and treatment centres (CTCs) for HIV/AIDS patients; on availability of laboratories, CTCs, laboratory personnel, equipment and reagents.

Acceptability of malaria rapid diagnostic tests administered by village health workers in Pangani District, North eastern Tanzania.

Background: Malaria continues to top the list of the ten most threatening diseases to child survival in Tanzania. The country has a functional policy for appropriate case management of malaria with rapid diagnostic tests (RDTs) from hospital level all the way to dispensaries, which are the first points of healthcare services in the national referral system. However, access to these health services in Tanzania is limited, especially in rural areas.

Performance of rapid diagnostic test, blood-film microscopy and PCR for the diagnosis of malaria infection among febrile children from Korogwe District, Tanzania.

Background: Rapid diagnostic tests (RDT) and light microscopy are still recommended for diagnosis to guide the clinical management of malaria despite difficult challenges in rural settings. The performance of these tests may be affected by several factors, including malaria prevalence and intensity of transmission. The study evaluated the diagnostic performance of malaria RDT, light microscopy and polymerase chain reaction (PCR) in detecting malaria infections among febrile children at outpatient clinic in Korogwe District, northeastern Tanzania.

Bloodstream bacterial infection among outpatient children with acute febrile illness in north-eastern Tanzania.

Background: Fever is a common clinical symptom in children attending hospital outpatient clinics in rural Tanzania, yet there is still a paucity of data on the burden of bloodstream bacterial infection among these patients.

Methods: The present study was conducted at Korogwe District Hospital in north-eastern Tanzania. Patients aged between 2 and 59 months with a history of fever or measured axillary temperature ≥37.

Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis.

Introduction: Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis.

Objective: To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine).

Methods: Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women.

"Every drug goes to treat its own disease…" - a qualitative study of perceptions and experiences of taking anti-retrovirals concomitantly with anti-malarials among those affected by HIV and malaria in Tanzania.

Background: Little is known about how people living with human immunodeficiency virus (HIV) experience malaria and the concomitant use of anti-malarial treatments with anti-retrovirals (ARVs). An understanding of how patients make sense of these experiences is important to consider in planning and supporting the clinical management and treatment for co-infected individuals.

Methods: A qualitative study was conducted in Tanzania alongside a clinical trial of concomitant treatment for HIV and malaria co-infection.

Therapeutic efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in North-Eastern Tanzania.

Background: The World Health Organization recommends that regular efficacy monitoring should be undertaken by all malaria endemic countries that have deployed artemisinin combination therapy (ACT). Although ACT is still efficacious for treatment of uncomplicated malaria, artemisinin resistance has been reported in South East Asia suggesting that surveillance needs to be intensified by all malaria endemic countries. This study assessed the efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Muheza district of north-eastern Tanzania, an area where the transmission has significantly declined in recent years.

Development and validation of climate and ecosystem-based early malaria epidemic prediction models in East Africa.

Background: Malaria epidemics remain a serious threat to human populations living in the highlands of East Africa where transmission is unstable and climate sensitive. An existing early malaria epidemic prediction model required further development, validations and automation before its wide use and application in the region. The model has a lead-time of two to four months between the detection of the epidemic signal and the evolution of the epidemic.

Aetiology of acute febrile episodes in children attending Korogwe District Hospital in north-eastern Tanzania.

Introduction: Although the burden of malaria in many parts of Tanzania has declined, the proportion of children with fever has not changed. This situation underscores the need to explore the possible causes of febrile episodes in patients presenting with symptoms at the Korogwe District Hospital (KDH).

Methods: A hospital based cross-sectional study was conducted at KDH, north-eastern Tanzania.

Independent origin of plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia.

Super-resistant Plasmodium falciparum threatens the effectiveness of sulfadoxine-pyrimethamine in intermittent preventive treatment for malaria during pregnancy. It is characterized by the A581G Pfdhps mutation on a background of the double-mutant Pfdhps and the triple-mutant Pfdhfr. Using samples collected during 2004-2008, we investigated the evolutionary origin of the A581G mutation by characterizing microsatellite diversity flanking Pfdhps triple-mutant (437G+540E+581G) alleles from 3 locations in eastern Africa and comparing it with double-mutant (437G+540E) alleles from the same area.

How experiences become data: the process of eliciting adverse event, medical history and concomitant medication reports in antimalarial and antiretroviral interaction trials.

Background: Accurately characterizing a drug's safety profile is essential. Trial harm and tolerability assessments rely, in part, on participants' reports of medical histories, adverse events (AEs), and concomitant medications. Optimal methods for questioning participants are unclear, but different methods giving different results can undermine meta-analyses.

Early infant diagnosis of HIV in three regions in Tanzania; successes and challenges.

Background: By the end of 2009 an estimated 2.5 million children worldwide were living with HIV-1, mostly as a consequence of vertical transmission, and more than 90% of these children live in sub-Saharan Africa. In 2008 the World Health Organization (WHO), recommended early initiation of Highly Active Antiretroviral Therapy (HAART) to all HIV infected infants diagnosed within the first year of life, and since 2010, within the first two years of life, irrespective of CD4 count or WHO clinical stage.

Declining burden of malaria over two decades in a rural community of Muheza district, north-eastern Tanzania.

Background: The recently reported declining burden of malaria in some African countries has been attributed to scaling-up of different interventions although in some areas, these changes started before implementation of major interventions. This study assessed the long-term trends of malaria burden for 20 years (1992-2012) in Magoda and for 15 years in Mpapayu village of Muheza district, north-eastern Tanzania, in relation to different interventions as well as changing national malaria control policies.

Methods: Repeated cross-sectional surveys recruited individuals aged 0 - 19 years from the two villages whereby blood smears were collected for detection of malaria parasites by microscopy.