Billy Ngasala

Billy Ngasala
Muhimbili University of Health and Allied Sciences | MUHAS · Department of Parasitology and Medical Entomology

MD, PhD

About

102
Publications
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Introduction
Additional affiliations
October 2010 - present

Publications

Publications (102)
Article
Full-text available
Background Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods Individual patient data from eligible antimala...
Presentation
Full-text available
Background Lymphatic filariasis is a parasitic infection caused by filarial nematodes (Wuchereria bancrofi, Brugia malayi and Brugia timori), transmitted by mosquito vectors (Anopheles, Aedes, Culex, and Mansonia). Approximately, 120 million people are infected in 83 countries. Long-term infection can affect the lymphatic system resulting in lymph...
Article
Full-text available
Background: Artemisinin-based combination therapies (ACTs) are the global mainstay treatment of uncomplicated Plasmodium falciparum infections. Pf MDR1 and Pf CRT are two transmembrane transporters, associated with sensitivity to several antimalarials, found in the parasite food vacuole. Herein, we explore if their relatedness extends to overlappin...
Poster
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Introduction Schistosomiasis is a three-stage disease caused by trematode worms of the genus Schistosoma. Organ-specific morbidity, according to the infecting Schistosoma spp., can develop in chronic stages. Clinical manifestations are caused by inflammatory response of the host to the accumulation of parasite eggs in vessels and organs. Vascular...
Article
Introduction Entamoeba histolytica is a protozoan parasite with worldwide distribution, higher in countries with poor sanitation due to its oral-faecal way of transmission. It is the causative agent of amoebic colitis and extraintestinal amoebiasis, and accounts for 40 000–100 000 deaths yearly. Amoebiasis can be complicated by liver abscess in 9%...
Article
Full-text available
Background Since the World Health Organization recommended single low-dose (0.25mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant P. falciparum, several single-site studies have been conducted to assess its efficacy. Methods An individual patient meta-anal...
Article
Full-text available
Background. Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falcip-arum, several single-site studies have been conducted to assess efficacy. Methods. An individual patient m...
Article
Full-text available
Background: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods: Antimalarial studies typically report the...
Article
Full-text available
Background The Tanzanian National Malaria Control Programme (NMCP) and its partners have been implementing regular therapeutic efficacy studies (TES) to monitor the performance of different drugs used or with potential use in Tanzania. However, most of the recent TES focused on artemether–lumefantrine, which is the first-line anti-malarial for the...
Article
Full-text available
Background The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at...
Article
Background: Delayed parasite clearance and, consequently, reduced efficacy of artemisinin-based combination therapies have been linked with Plasmodium falciparum K13 gene SNPs in Southeast Asia. In Africa, significantly prolonged clearance has not yet been observed and the presently restricted variation in parasite clearance cannot be explained by...
Article
Prevalence of and risk factors associated with polymerase chain reaction (PCR)-determined Plasmodium falciparum positivity were assessed on day 3 after initiation of treatment, pre-implementation and up to 8 years post-deployment of artemether–lumefantrine as first-line treatment for uncomplicated malaria in Bagamoyo district, Tanzania. Samples ori...
Article
Full-text available
Tandem Oligonucleotide Repeat Cascade Amplification (TORCA) based on signal rather than target amplification under isothermal conditions was developed for nucleic acid assays. The initial signal was generated by hybridization of single stranded DNA targets to immobilized recognition probes followed by hybrid cleavage with specific restriction endon...
Article
Full-text available
Background: Plasmodium falciparum infections with slow parasite clearance following artemisinin-based therapies are widespread in the Greater Mekong Subregion. A molecular marker of the slow clearance phenotype has been identified: single genetic changes within the propeller region of the Kelch13 protein (pfk13; Pf3D7_1343700). Global searches have...
Article
Full-text available
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 c...
Article
Full-text available
Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the...
Data
External validation and alternative sampling matrix prediction-corrected visual predictive checks. External validation using prediction-corrected visual predictive check of sparse venous plasma sampling after intact tablets (A). Prediction-corrected visual predictive check of sparse venous plasma sampling data after dispersible tablets (B), sparse...
Data
Goodness-of-fit diagnostics for lumefantrine when fitting the final lumefantrine pharmacokinetic model. The black solid line, black dashed line, and open circles represent the line of identity, trend line, and observations, respectively. (TIF)
Data
Supplementary methods: Detailed technical information regarding the pharmacokinetic model building process, the pharmacokinetic-pharmacodynamic time-to-event model building process, and dose optimisations. (DOCX)
Data
Supplementary results: Detailed technical information on the pharmacokinetic model and dose optimisation results. (DOCX)
Data
In silico dose optimisations using Monte Carlo simulations (n = 2,000) with the lumefantrine model. The boxes and whiskers represent 25%–75% and 2.5%–97.5% of the data, respectively. The horizontal dashed-dotted grey line in the upper panel represents the median lumefantrine concentration at day 7 after standard treatment in a non-pregnant adult pa...
Data
Demographic summary of post-2013 studies meeting the original inclusion criteria. (DOCX)
Data
Goodness-of-fit diagnostics for lumefantrine and desbutyl-lumefantrine when fitting the final pharmacokinetic drug-metabolite model. Lumefantrine (top); desbutyl-lumefantrine (bottom). The black solid line, black dashed line, and open circles represent the line of identity, trend line, and observations, respectively. (TIF)
Data
External validation using prediction-corrected visual predictive check of the sparse venous plasma sampling. Open circles represent the observed sparsely sampled desbutyl-lumefantrine venous plasma concentration data. Solid lines represent the 5th, 50th, and 95th percentiles of the observed data. Grey shaded areas represent the 95% confidence inter...
Data
Demographic summary of studies included in the pooled analyses. (DOCX)
Article
Full-text available
Background: Microscopy remains the gold standard in the diagnosis of neglected tropical diseases. As resource limited, rural areas often lack laboratory equipment and trained personnel, new diagnostic techniques are needed. Low-cost, point-of-care imaging devices show potential in the diagnosis of these diseases. Novel, digital image analysis algor...
Article
Aim: To investigate the potential involvement of the hepatic ATP-binding cassette transporters MRP2 and MDR1 in the disposition of lumefantrine (LUM) among patients with uncomplicated Plasmodium falciparum malaria. Materials & methods: The tag SNPs MDR1/ABCB1 C3435T and MRP2/ABCC2 C1515Y were determined in two artemether-LUM clinical trials, inc...
Article
Full-text available
We assessed the temporal trend of artemether–lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007–2008, 2012–2013, and 2014. Patients with acute uncomplicated...
Article
Full-text available
Background: Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito vectors and in sub Saharan Africa it is caused by nematode Wuchereria bancrofti. The disease has been targeted for global elimination by using annual mass drug administration (MDA) strategy. On the other hand, vector control is known to play important complement...
Article
Full-text available
Background Emergence of Plasmodium falciparum resistance against artemisinin in Southeast Asia raises a serious concern about the long-term efficacy of artemisinin-based combination therapy (ACT) globally. In Africa, ACT has remained highly efficacious with a microscopy determined asexual parasites clearance occurring within 48 hours post-treatment...
Article
Full-text available
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 ag...
Article
Full-text available
Background The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission settings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. T...
Article
Full-text available
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...
Article
Full-text available
Background: This study assessed the safety of the new World Health Organization (WHO) recommendation of adding a single low-dose of primaquine (PQ) to standard artemisinin-based combination therapy (ACT), regardless of individual glucose-6-phosphate dehydrogenase (G6PD) status, for treatment of acute uncomplicated Plasmodium falciparum malaria in...
Article
Full-text available
Background: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual pa...
Article
Full-text available
Background Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual pati...
Data
Additional file 2: Figure S1. Relationship between gametocytaemia on enrolment and baseline haemoglobin concentration, parasitaemia and patient age. The predicted probability of gametocyte carriage at enrolment is plotted from the multivariate model; the line indicates the best fit, the shaded area the 95 % CI. Only patients from studies with gamet...
Data
Additional file 3: Table S2. Independent risk factors for the prevalence of gametocytaemia at enrolment in children aged 1–5 years. Logistic multivariable analysis by region with prevalence of gametocytaemia at enrolment as dependent variable. Nobs, Number of observations; Npos, Number of positive observations. The relationship between gametocyte p...
Data
Additional file 8: Table S7. Sensitivity analysis: variation in model coefficients after exclusion of individual studies. 1 Estimates as obtained in the final multivariate models and listed in main tables. 2 RSD, Relative standard deviation was calculated as a ratio of standard deviation to mean of the estimates (odds ratio or hazard ratio) calcula...
Data
Additional file 9: Figure S2. Development of gametocytaemia after treatment evaluated in patients with no gametocytaemia on enrolment and full 28-day follow-up. A: Development of gametocytaemia by artemisinin combination therapy. B: Development of gametocytaemia by treatment outcome. (TIF 284 kb)
Data
Additional file 4: Table S3. The effect of treatment dosing on the appearance of gametocytaemia in participants without microscopically detected gametocytaemia before treatment (time to gametocytaemia) and clearance of gametocytaemia in participants with gametocytaemia at enrolment (time to clearance). All analyses of time to clearance are adjusted...
Data
Additional file 7: Table S6. Factors associated with the development of gametocytaemia after enrolment in individuals who were gametocyte-free before treatment with artemisinin combination therapy. Cox regression model for time to gametocytaemia. Only patients with complete 28-day follow-up are included. (DOC 35 kb)
Data
Additional file 1: Table S1. Overview of all included studies. 1 The sensitivity of microscopy methods was classified into one of four categories: 1 = studies in which slides were specifically read for gametocytes, reviewing at least 100 microscopic high power fields or against ≥ 1000 white blood cells (WBC); 2 = microscopists specifically instruct...
Data
Additional file 5: Table S4. Factors associated with the clearance of gametocytaemia after enrolment in individuals who were gametocytaemic before treatment with artemisinin combination therapy. Nobs, Number of observations; N cleared, Number of patients with day of clearance of gametocytaemia recorded. Derived haemoglobin, conversion from haematoc...
Data
Full-text available
Additional file 6: Table S5. Risk of bias in individual studies included in the analysis. ACT, Artemisinin combination therapy. 1 For trials with non-ACTs, data were only analysed for gametocytaemia on enrolment and regimens, arms, randomization, concealment of treatment, sequence generation and treatment blinding are given as not applicable (NA)....
Article
Full-text available
BACKGROUND: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual pat...
Article
Full-text available
Background and objectives: Current tools struggle to detect drug resistant malaria parasites when infections contain multiple parasite clones, which is the norm in high transmission settings in Africa. Our aim was to develop and apply an approach for detecting resistance that overcomes the challenges of polyclonal infections without requiring a ge...
Article
Full-text available
Background Malaria is a public health problem in Tanzania affecting all age groups. It is known that school children are the age group most commonly infected with malaria parasites. Their infections are usually asymptomatic, go unnoticed and thus never get treated, result in anaemia, reduced ability to concentrate and learn in school and if fallen...
Article
Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to stu...
Article
Full-text available
Objectives Polymorphisms in the lysosomal transporter encoded by the pfcrt gene directly impact on Plasmodium falciparum susceptibility to aminoquinolines. The Lys76Thr mutation is the critical change conferring chloroquine resistance in vitro and in vivo, but always occurs with additional non-synonymous changes in the pfcrt coding sequence. We sou...
Article
Full-text available
Background: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentration threshold needs to be defined better, particul...
Article
Full-text available
Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan Afri...
Data