Adaptive Feature Engineering Modeling for Ultrasound Image Classification for Decision Support

Ultrasonography is considered a relatively safe option for the diagnosis of benign and malignant cancer lesions due to the low-energy sound waves used. However, the visual interpretation of the ultrasound images is time-consuming and usually has high false alerts due to speckle noise. Improved methods of collection image-based data have been proposed to reduce noise in the images; however, this has proved not to solve the problem due to the complex nature of images and the exponential growth of biomedical datasets. Secondly, the target class in real-world biomedical datasets, that is the focus of interest of a biopsy, is usually significantly underrepresented compared to the non-target class. This makes it difficult to train standard classification models like Support Vector Machine (SVM), Decision Trees, and Nearest Neighbor techniques on biomedical datasets because they assume an equal class distribution or an equal misclassification cost. Resampling techniques by either oversampling the minority class or under-sampling the majority class have been proposed to mitigate the class imbalance problem but with minimal success. We propose a method of resolving the class imbalance problem with the design of a novel data-adaptive feature engineering model for extracting, selecting, and transforming textural features into a feature space that is inherently relevant to the application domain. We hypothesize that by maximizing the variance and preserving as much variability in well-engineered features prior to applying a classifier model will boost the differentiation of the thyroid nodules (benign or malignant) through effective model building. Our proposed a hybrid approach of applying Regression and Rule-Based techniques to build our Feature Engineering and a Bayesian Classifier respectively. In the Feature Engineering model, we transformed images pixel intensity values into a high dimensional structured dataset and fitting a regression analysis model to estimate relevant kernel parameters to be applied to the proposed filter method. We adopted an Elastic Net Regularization path to control the maximum log-likelihood estimation of the Regression model. Finally, we applied a Bayesian network inference to estimate a subset for the textural features with a significant conditional dependency in the classification of the thyroid lesion. This is performed to establish the conditional influence on the textural feature to the random factors generated through our feature engineering model and to evaluate the success criterion of our approach. The proposed approach was tested and evaluated on a public dataset obtained from thyroid cancer ultrasound diagnostic data. The analyses of the results showed that the classification performance had a significant improvement overall for accuracy and area under the curve when then proposed feature engineering model was applied to the data. We show that a high performance of 96.00% accuracy with a sensitivity and specificity of 99.64%) and 90.23% respectively was achieved for a filter size of 13 × 13

Expression of "Plasmodium Falciparum Var" Genes in Naturally Infected Children from Tanzania

Plasmodium falciparum is the most pathogenic malarial parasite and a major cause of morbidity and mortality among young children in sub-Saharan Africa. The virulence of P. falciparum has been linked to its expression of variant surface antigens (VSAs) on the surface of infected red blood cells. These VSAs subvert acquisition of protective immunity and mediate cytoadherence of infected erythrocytes to the microvasculature lining of various endothelial cell receptors. It causes sequestration of infected erythrocytes in post capillary venules of the vital organs such as the brain or placenta. Cytoadherence causes retention and accumulation of the infected erythrocytes to endothelial membranes of deep postvenous capillaries leading to occlusion of micro-vessels. This result in obstruction of free blood flow with serious pathological consequences associated with severe malaria. Sequestration facilitates parasite multiplication and enables the parasites to avoid the passage of infected erythrocytes through the spleen, where deformed erythrocytes are removed from blood circulations. This cytoadherence is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is a VSA family encoded by ~ 60 highly polymorphic var genes per haploid genome, expressed on the surface of infected red blood cells. PfEMP1 is expressed in a mutually exclusive manner, and switching the expression creates extensive antigenic variation and the potential for multiple adhesion profile. Antigenic variation is a strategy employed by P. falciparum to avoid antibody-mediated destruction by alternating expression of individual var genes each of which encodes an antigenically distinct form of PfEMP1. Sequence analysis of the var gene repertoire of the 3D7 clone revealed genetic structuring in which var genes fall into 3 distinct groups (A, B, and C) and two intermediate groups (B/A and B/C) based on chromosomal location, gene orientation and the 5' flanking sequences. It has been postulated that this genetic organization helps to restrict recombination within a specific group of genes and leads to their structural and functional specialization for binding to different endothelial receptors. The sequences of var genes vary substantially within and between the parasites genome. This has been clearly indicated by the fact that there is minimal overlap in the var gene repertoire between isolates due to high inter-genic and intra-genic recombination within the var gene family. Despite the complex nature of this molecule, the var gene still remains the best defined factor contributing to malaria pathogenesis. Different research groups have attempted to define the repertoire of var gene from different isolates, and reported vast global var gene diversity. Only a tip of iceberg of the var genes diversity is currently in view. The big challenge to date is to understand how the var gene diversity and selection pressure influence malaria pathogenesis in order to device a control strategy based on interference with PfEMP1 expression. Clinical and sero-epidemiological studies have suggested that severe disease is attributed by the parasite expressing a restricted and antigenically conserved subset of VSAs which are frequently recognized by sera from semi-immune individuals, proposing that expression of a particular VSA may be associated with disease manifestation. Pregnancy associated malaria (PAM) is well understood and has often been linked with the expression of a var gene called var2csa which is unusually conserved across parasite isolates and binds a low sulfated form of chondroitin sulfate A (CSA) in the placenta. Different studies have attempted to link a particular var gene expression with a disease phenotype. It is becoming evident that var group A and B/A are involved in severe childhood malaria. Protective immunity to severe malaria develops earlier in childhood after only few severe episodes pointing to a relatively conserved target antigen. This phenomenon makes it theoretically possible to protect non immune children against severe and complicated malaria by accelerating acquisition of PfEMP1 specific immunity. Given the proposed importance of immunity to PfEMP1 in protection against malaria, it is essential that we gain a better understanding of var gene expression during infection. Despite substantial contribution of var genes to malaria pathogenesis and parasites survival, few studies on var gene transcription during natural infections have been carried out in field isolates. This is mainly attributed to technical difficulties, and the complexity and immense diversity interfering with most study design. For this thesis, two studies on var gene expression in naturally infected children with severe P. falciparum malaria from Tanzania were conducted. In the first study, the transcription levels of var gene groups were compared in children with severe, uncomplicated and asymptomatic malaria by using quantitative real-time PCR. Transcripts of var group A and B genes were up-regulated in children with severe malaria compared to patients with uncomplicated malaria. In general, the transcript abundances of var group A and B genes were higher for children with clinical malaria than for children with asymptomatic infections. var group C was not linked with any disease phenotype. In the second study, the genetic diversity of expressed P. falciparum var genes in children with severe malaria from Tanzania was determined. The var transcripts isolated from children with severe malaria (Blantyre score ≤ 3) were compared with isolates from children with asymptomatic malaria. Diversity patterns of dominant full-length var transcripts were determined by isolation of mRNA followed by magnetic bead capture through an ATS-anchor and reversetranscription into var cDNA. The different PCR amplified expressed sequence tags were cloned and sequenced. Large sequence diversity of the amplified var DBL-1α and the 5’ non-coding regions was observed and minimal overlapping was evident among the isolates providing strong evidence that the transcribed var gene repertoire is immense. var DBL-1α sequences isolated from AM were more diverse with more singletons (P<0.05) compared with DBL-1α sequences from SM. Unique var sequences that were exclusively expressed with P. falciparum isolated from children with SM were found. Despite the fact that var gene diversity is unlimited, transcripts from SM isolates were more restricted, supporting the hypothesis that certain PfEMP1 repertoires are involved in triggering severe infections

Morphological re-description and molecular identification of Tabanidae (Diptera) in East Africa

Biting flies of the family Tabanidae are important vectors of human and animal diseases across continents. However, records of Africa tabanids are fragmentary and mostly cursory. To improve identification, documentation and description of Tabanidae in East Africa, a baseline survey for the identification and description of Tabanidae in three eastern African countries was conducted. Tabanids from various locations in Uganda (Wakiso District), Tanzania (Tarangire National Park) and Kenya (Shimba Hills National Reserve, Muhaka, Nguruman) were collected. In Uganda, octenol baited F-traps were used to target tabanids, while NG2G traps baited with cow urine and acetone were employed in Kenya and Tanzania. The tabanids were identified using morphological and molecular methods. Morphologically, five genera (Ancala, Tabanus, Atylotus, Chrysops and Haematopota) and fourteen species of the Tabanidae were identified. Among the 14 species identified, six belonged to the genus Tabanus of which two (T. donaldsoni and T. guineensis) had not been described before in East Africa. The greatest diversity of tabanid species were collected from the Shimba Hills National Reserve, while collections from Uganda (around the shores of Lake Victoria) had the fewest number of species. However, the Ancala genus was found in Uganda, but not in Kenya or Tanzania. Maximum likelihood phylogenies of mitochondrial cytochrome c oxidase 1 (COI) genes sequenced in this study show definite concordance with morphological species identifications, except for Atylotus. This survey will be critical to building a complete checklist of Tabanidae prevalent in the region, expanding knowledge of these important vectors of human and animal diseases

Dengue and Chikungunya Fever among Viral Diseases in Outpatient Febrile Children in Kilosa District Hospital, Tanzania.

Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria. A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2-13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used. A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35-3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus. Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended

Prevalence of Bacterial Febrile Illnesses in Children in Kilosa District, Tanzania.

Bacterial etiologies of non-malaria febrile illnesses have significantly become important due to high mortality and morbidity, particularly in children. Despite their importance, there are few reports on the epidemiology of these diseases in Tanzania, and the true burden of such illnesses remains unknown. This study aimed to identify the prevalence of leptospirosis, brucellosis, typhoid fever and urinary tract infections and their rate of co-infections with malaria. A cross-sectional study was conducted at Kilosa district hospital in Tanzania for 6 months. Febrile children aged from 2-13 years were recruited from the outpatient department. Patients were screened by serological tests such as IgM and IgG ELISA, and microscopic agglutination test. A total of 370 patients were enrolled; of these 85 (23.0%) had malaria parasites, 43 (11.6%) had presumptive acute leptospirosis and 26/200 (13%) had confirmed leptospirosis. Presumptive acute brucellosis due to B. abortus was identified among 26 (7.0%) of patients while B. melitensis was detected in 57 (15.4%) of the enrolled patients. Presumptive typhoid fever due to S. Typhi was identified in thirty eight (10.3%) of the participants and 69 (18.6%) had urinary tract infections. Patients presented with similar symptoms; therefore, the identification of these diseases could not be done based on clinical ground alone. Co-infections between malaria and bacterial febrile illnesses were observed in 146 patients (39.5%). Although antibacterials and/or anti-malarials were prescribed in most patients, some patients did not receive the appropriate treatment. The study has underscored the importance of febrile bacterial diseases including zoonoses such as leptospirosis and brucellosis infebrile children, and thus such illnesses should be considered by clinicians in the differential diagnoses of febrile diseases. However, access to diagnostic tests for discrimination of febrile illnesses is needed. This would allow febrile patients to receive the correct diagnoses and facilitation of accurate and prompt treatment

Simplified molecular detection of Leishmania parasites in various clinical samples from patients with leishmaniasis

<p>Abstract</p> <p>Background</p> <p>Molecular methods to detect <it>Leishmania </it>parasites are considered specific and sensitive, but often not applied in endemic areas of developing countries due to technical complexity. In the present study isothermal, nucleic acid sequence based amplification (NASBA) was coupled to oligochromatography (OC) to develop a simplified detection method for the diagnosis of leishmaniasis. NASBA-OC, detecting <it>Leishmania </it>RNA, was evaluated using clinical samples from visceral leishmaniasis patients from East Africa (n = 30) and cutaneous leishmaniasis from South America (n = 70) and appropriate control samples.</p> <p>Results</p> <p>Analytical sensitivity was 10 parasites/ml of spiked blood, and 1 parasite/ml of culture. Diagnostic sensitivity of NASBA-OC was 93.3% (95% CI: 76.5%-98.8%) and specificity was 100% (95% CI: 91.1%-100%) on blood samples, while sensitivity and specificity on skin biopsy samples was 98.6% (95% CI: 91.2%-99.9%) and 100% (95% CI: 46.3%-100%), respectively.</p> <p>Conclusion</p> <p>The NASBA-OC format brings implementation of molecular diagnosis of leishmaniasis in resource poor countries one step closer.</p

Experimental hut evaluation of a novel long-lasting non-pyrethroid durable wall lining for control of pyrethroid-resistant Anopheles gambiae and Anopheles funestus in Tanzania.

BACKGROUND: A novel, insecticide-treated, durable wall lining (ITWL), which mimics indoor residual spraying (IRS), has been developed to provide prolonged vector control when fixed to the inner walls of houses. PermaNet® ITWL is a polypropylene material containing non-pyrethroids (abamectin and fenpyroximate) which migrate gradually to the surface. METHODS: An experimental hut trial was conducted in an area of pyrethroid-resistant Anopheles gambiae s.l. and Anopheles funestus s.s. to compare the efficacy of non-pyrethroid ITWL, long-lasting insecticidal nets (LLIN) (Interceptor®), pyrethroid ITWL (ZeroVector®), and non-pyrethroid ITWL + LLIN. RESULTS: The non-pyrethroid ITWL produced relatively low levels of mortality, between 40-50% for An. funestus and An. gambiae, across all treatments. Against An. funestus, the non-pyrethroid ITWL when used without LLIN produced 47% mortality but this level of mortality was not significantly different to that of the LLIN alone (29%, P = 0.306) or ITWL + LLIN (35%, P = 0.385). Mortality levels for An. gambiae were similar to An. funestus with non-pyrethroid ITWL, producing 43% mortality compared with 26% for the LLIN. Exiting rates from ITWL huts were similar to the control and highest when the LLIN was present. An attempt to restrict mosquito access by covering the eave gap with ITWL (one eave open vs four open) had no effect on numbers entering. The LLIN provided personal protection when added to the ITWL with only 30% blood-fed compared with 69 and 56% (P = 0.001) for ITWL alone. Cone bioassays on ITWL with 30 min exposure after the trial produced mortality of >90% using field An. gambiae. CONCLUSIONS: Despite high mortality in bioassays, the hut trial produced only limited mortality which was attributed to pyrethroid resistance against the pyrethroid ITWL and low efficacy in the non-pyrethroid ITWL. Hut ceilings were left uncovered and may have served as a potential untreated refuge. By analogy to IRS campaigns, which also do not routinely treat ceilings, high community coverage with ITWL may still reduce malaria transmission. Restriction of eave gaps by 75% proved an inadequate barrier to mosquito entry. The findings represent the first 2 months after installation and do not necessarily predict long-term efficacy

Improving quality of medical certification of causes of death in health facilities in Tanzania 2014-2019

BACKGROUND: Monitoring medically certified causes of death is essential to shape national health policies, track progress to Sustainable Development Goals, and gauge responses to epidemic and pandemic disease. The combination of electronic health information systems with new methods for data quality monitoring can facilitate quality assessments and help target quality improvement. Since 2015, Tanzania has been upgrading its Civil Registration and Vital Statistics system including efforts to improve the availability and quality of mortality data. METHODS: We used a computer application (ANACONDA v4.01) to assess the quality of medical certification of cause of death (MCCD) and ICD-10 coding for the underlying cause of death for 155,461 deaths from health facilities from 2014 to 2018. From 2018 to 2019, we continued quality analysis for 2690 deaths in one large administrative region 9 months before, and 9 months following MCCD quality improvement interventions. Interventions addressed governance, training, process, and practice. We assessed changes in the levels, distributions, and nature of unusable and insufficiently specified codes, and how these influenced estimates of the leading causes of death. RESULTS: 9.7% of expected annual deaths in Tanzania obtained a medically certified cause of death. Of these, 52% of MCCD ICD-10 codes were usable for health policy and planning, with no significant improvement over 5 years. Of certified deaths, 25% had unusable codes, 17% had insufficiently specified codes, and 6% were undetermined causes. Comparing the before and after intervention periods in one Region, codes usable for public health policy purposes improved from 48 to 65% within 1 year and the resulting distortions in the top twenty cause-specific mortality fractions due to unusable causes reduced from 27.4 to 13.5%. CONCLUSION: Data from less than 5% of annual deaths in Tanzania are usable for informing policy. For deaths with medical certification, errors were prevalent in almost half. This constrains capacity to monitor the 15 SDG indicators that require cause-specific mortality. Sustainable quality assurance mechanisms and interventions can result in rapid improvements in the quality of medically certified causes of death. ANACONDA provides an effective means for evaluation of such changes and helps target interventions to remaining weaknesses

Diagnostic Accuracy of Molecular Amplification Tests for Human African Trypanosomiasis—Systematic Review

A range of molecular amplification techniques has been developed for the diagnosis of HAT, with polymerase chain reaction (PCR) at the forefront. As laboratory strengthening in endemic areas increases, it is expected that the applicability of molecular tests will increase. However, careful evaluation of these tests against the current reference standard, microscopy, must precede implementation. Therefore, we have investigated the published diagnostic accuracy of molecular amplification tests for HAT compared to microscopy for both initial diagnosis as well as for disease staging

Evaluation of a single screen and treat strategy to detect asymptomatic malaria among pregnant women from selected health facilities in Lindi region, Tanzania

Background In areas of high transmission, malaria in pregnancy (MiP) primarily causes asymptomatic infections; these infections nonetheless increase the risk of adverse maternal and fetal outcomes. In 2014, Tanzania initiated a single screening and treatment (SST) strategy for all pregnant women at their first antenatal care (ANC) visit using malaria rapid diagnostic tests (RDT) for surveillance purposes. However, there is paucity of data on the effectiveness of SST in the prevention of MiP. The objective of this study was to estimate the number of asymptomatic infections among pregnant women detected by SST, which would have been missed in the absence of the policy. Methods Data from pregnant women attending their first ANC visits between October 2017 and June 2018, including gestational age, history of fever, and RDT results, were abstracted from ANC registers in eight health centres in two randomly selected districts, Kilwa and Lindi, in Lindi Region. The proportion of symptomatic (with history of fever in the past 48 h) and asymptomatic pregnant women with positive RDTs were calculated and stratified by trimester (first, second and third). The study areas were categorized as low transmission with prevalence < 10% or moderate/high with ≥ 10%. Results Over the study period, 1,845 women attended their first ANC visits; 22.1% were in the first trimester (< 12 weeks gestation age). Overall 15.0% of the women had positive RDTs, and there was a trend towards higher malaria prevalence in the first (15.9%) and second (15.2%) trimesters, compared to the third (7.1%), although the differences were not statistically significant (p = 0.07). In total, 6.9% of women reported fever within the past 48 h and, of these, 96.1% were RDT positive. For every 100 pregnant women in the moderate/high and low transmission areas, SST identified 60 and 26 pregnant women, respectively, with asymptomatic infections that would have otherwise been missed. Among the 15.9% of women detected in the first trimester, 50.7% were asymptomatic. Conclusion In areas of moderate/high transmission, many infected women were asymptomatic, and would have been missed in the absence of SST. The benefits on maternal and fetal birth outcomes of identifying these infections depend heavily on the protection afforded by treatment, which is likely to be greatest for women presenting in the first trimester when intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) is contraindicated, and in areas with high SP resistance, such as most parts of Tanzania. An evaluation of the impact and cost-effectiveness of SST across different transmission strata is warranted