Digital Commons Network^™

Artemisinin Partial Resistance Mutations In Zanzibar And Tanzania Suggest Regional Spread And African Origins, 2023, Sean V. Connelly, Julia G. Muller, Mohamed Ali, Billy E. Ngasala, Wahida Hassan, Bakari Mohamed, Kyaw L. Thwai, Jacob M. Sadler, Jacob Marglous, Abebe A. Fola, Abdallah Zacharia, Shija J. Shija, Safia Mohammed, Dominick C. Msolo, Hamza Said, Editruda E. Peter, Melic Odas, Isaack J. Rutha, Mwanaidi Nwange, Karamoko Naire, Shazia Ruybal-Pesántez, Robert Verity, Rebecca Crudale, Varun Goel, Barbara B. Choloi, Anders Björkman, Jeffrey A. Bailey, Jessica T. Lin, Jonathan J. Juliano

Faculty Publications

Artemisinin partial resistance, driven by Plasmodium falciparum K13 mutations, threatens malaria control. Zanzibar is vulnerable to artemisinin partial resistance spread but lacks recent molecular surveillance. We sequenced samples in Zanzibar and mainland Tanzania collected from 2022 to 2024. K13 mutations were found in 2 of 1440 participants (P441L, A675V) in Zanzibar and 6 of 3762 (R561H, P441L) in mainland Tanzania. Based on whole genome sequencing data, K13 mutations appear to be of African origin with regional spread. Frequent parasite importation appears to maintain partner drug mutation frequencies similar to the mainland, where artemether-lumefantrine selects for mutations favoring artesunate-amodiaquine sensitivity. Ongoing …

Understanding The Epidemiology Of Malaria In Zanzibar Through Molecular And Serological Analysis Of Samples Collected During Reactive Case Detection, Vanrun Goel, Wahida Hassan, Caroline Murphy, Barbara B. Choloi, Mohamed Ali, Shija J. Shija, Jeffrey A. Bailey, Anders Björkman, Billey E. Ngasala, Eric Rogier, Jonathan J. Juliano, Jessica T. Lin

Faculty Publications

Background

The Zanzibar archipelago has been a pre-elimination region for malaria thanks to rigorous control interventions, but recent surges in malaria cases have been observed. The contribution of non-falciparum species to the current malaria situation is unknown.

Method

This study investigates the epidemiology of falciparum and non-falciparum malaria species in Zanzibar. Leveraging plasma extracted from dried blood spots (DBS) collected during reactive case detection (RCD) activities across Unguja island from May 2022 to January 2023, we measured immunoglobulin G (IgG) responses to Plasmodium MSP1-19kD antigens using a multiplex bead-based immunoassay. Additionally, active infections were detected using species-specific real-time PCR.

Results …

Modelling The Combined Use Of Long-Lasting Insecticidal Nets And Insecticides Zooprophylaxis Against The Resilience Of Anopheles Arabiensis For Effective Malaria Control, Watson Levens

Tanzania Journal of Science

Malaria is a significant public health concern, especially in tropical regions. It remains endemic in many areas where malaria mosquitoes are prevalent. This study investigates the viability of insecticide zooprophylaxis (IZ) in conjunction with Long Lasting Insecticidal Nets (LLINs) as a strategic approach to combat malaria transmission, particularly in regions dominated by zoophagic vectors. Through the presentation and analysis of a mathematical model that integrates IZ and LLINs for the control of Anopheles arabiensis (An. arabiensis), the research underscores IZ's role in reducing zoophagic vector populations and enhancing malaria control efforts. Notably, the study reveals that achieving comprehensive coverage of …

Dispelling The Malaria-Typhoid Co-Infection Myth In Nigeria. A Literature Review, Olawale Akinola

Dartmouth Library Staff Publications

Malaria and typhoid fever are public health concerns in Nigeria, with high prevalence rates. The perception of a widespread co-infection between these diseases may be misleading, due to limitations in diagnostic methods, particularly the Widal test for typhoid fever. This literature review examines the prevalence of malaria-typhoid co-infection in Nigeria and identifies factors contributing to misdiagnosis, including non-specific symptoms, limited diagnostic resources, and the diagnostic accuracy of tests employed. Additionally, the review discusses the implications of misdiagnosis, such as the overuse of broad-spectrum antibiotics leading to a rising incidence of antimicrobial resistance. Strategies to address this issue are explored, emphasizing …

Ethnobotanical Survey On The Knowledge And Use Of Medicinal Plants For Malaria Management Among University Students, Felista W. Mwingira, Deokary J. Matiya, Neema G. Mogha

Tanzania Journal of Science

Malaria remains a public health problem in Tanzania, escalated by the emergence of both parasite and vector resistance. Plant-based traditional medicines have been widely utilized as alternatives to malaria management. However, proper documentation is minimal, especially among the younger generation. This study assessed the knowledge of medicinal plants for malaria management among 532 Dar es Salaam University College of Education students. Overall, twenty-four plant species, most belonging to the family Asteraceae, were identified with Azaradichta indica being the most dominant species. These results reveal a substantial knowledge of medicinal plants for malaria management among university students.

Biological Characterization Of Plasmodium Falciparum Mitochondrial Heat Shock Protein Pfhsp70-3: Possible Involvement In Malaria Pathogenesis, David O. Nyakundi, Aileen Boshoff

Tanzania Journal of Science

Malaria remains a global health burden accounting for many deaths and illnesses in sub-Saharan Africa notwithstanding many decades of research on the disease. P. falciparum, the causative agent of the most fatal form of malaria, expresses a repertoire of heat shock proteins (Hsp) that cushion the parasite against heat shocks as it shuttles between extreme temperatures in human and mosquito vector hosts. By so doing, such proteins promote parasite’s cytoprotection, survival and pathogenesis. Heat shock proteins are named according to their molecular weights and there are six P. falciparum Hsp70 (PfHsp70) found in various cell compartments with mitochondrial putative PfHsp70-3. …

An Age-Structured Model For Transmission Dynamics Of Malaria With Infected Immigrants And Asymptomatic Carriers, Asha S Kalula, Eunice Mureithi, Theresia Marijani, Isambi Mbalawata

Tanzania Journal of Science

Abstract An age-structured (children and adults) model for the transmission dynamics of malaria with asymptomatic carriers and infected immigrants has been analyzed. We first analyze a model without infected immigrants. It shows that the disease-free equilibrium exists and is stable when and unstable for . Also, we compute the sensitivity indices of the basic reproduction number. The basic reproduction number is most sensitive to the mosquito biting rate. Besides, the sensitivity of the basic reproduction number shows that the children's class parameters are more sensitive than those of adults. In the presence of infected immigrants, the model does not admit …

Investigation Of Some Factors Associated With Utilization Of Maternal Health Care Services By Adolescent Mothers In Tanzania, Elia Magwaja, Jacqueline Minja, Majige Selemani Budeba, Rocky R.J. Akarro

Tanzania Journal of Science

This study examined some factors associated with the utilization of maternal health care servicesby adolescent mothers (15-19 years) in Tanzania in order to provide advice accordingly. The studyused cross-sectional study of adolescent mothers aged 15-19 years using Demographic HealthSurvey and Malaria indicator Survey 2015/16 data. The dependent variables were number ofantenatal care visits, the place where an adolescent mother delivered and post-natal checkup(adolescent mother’s health checking after being discharged or after a home delivery). Theindependent variables were birth order, education level of a mother, marital status of a mother,media exposure, wealth index, distance to health facility. Multiple binary logistic regression …

Socio-Demographic Evaluation Of Ownership Levels And Utilization Rates Of Llins Against Malaria Vectors Within Urban Settlements Of Osogbo District, Osun State, Nigeria, Kamilu A. Fasasi, Akinlabi M. Rufai, Damilola H. Familoni, Monsuru A. Adeleke

Tanzania Journal of Science

Globally, malaria is one of the major endemic diseases of public health importance caused by Plasmodium spp. and transmitted by Anopheles mosquitoes. Efforts to eradicate malaria disease are on the decline despite appreciable progress recorded in the past. This warranted holistic review of malaria interventions which include among others, the assessment of Long Lasting Insecticidal Treated Nets (LLINs). Adopted questionnaires from Roll Back Malaria (RBM), World Health Organization (WHO) and United Nations Children’s Fund (UNICEF) were administered to evaluate ownership levels and utilization rates of LLINs against malaria vectors in urban settlements of Osogbo district, Osun state, Nigeria. Out of …

Current Epidemiological Assessment Of Plasmodium Falciparum And Helminth Co-Infections In Children After A Decade Of Implementation Of Control Programs In Morogoro Region, Tanzania, Christopher Kisiringyo, Winifrida Kidima

Tanzania Journal of Science

A school based cross-sectional study was conducted from July to November 2018 to assess the burden of asymptomatic Plasmodium falciparum, Schistosoma and soil transmitted helminth (STH) infections in Mvomero. A total of 374 children (age range =  5–16 years, mean age = 11.3 years) were recruited from five primary schools. Prevalence of asymptomatic P. falciparum infections were 29.9%, S. haematobium 49.7%, hookworm 20.3%, Ascaris lumbricoides 12.6%, Taenia saginata 0.5% and S. mansoni 0.3%. Malaria parasite density increased with increasing children age (r = 0.99). Only 6.5% (12/186) of S. haematobium infected children were presented with heavy infections, whereas all STH-positive …

Breath Biomarkers And An Expanded Role For Isoprenoids In Plasmodium Falciparum, Chad Louis Schaber

Arts & Sciences Graduate Student Theses and Dissertations

Malaria remains one of the deadliest infectious diseases worldwide, and efforts to combat it require novel insights into diagnostics, vector transmission, and drug inhibitor targets. Previous studies suggest that malaria infection causes hosts to preferentially attract the transmission vector, the Anopheles mosquito, but the mechanism and wider implication of these findings were not known. By analyzing the headspace above malaria parasite cultures, we identified several molecules that might engender mosquito attraction. We demonstrated that several of these molecules activate mosquito odorant receptors, including the known plant-emitted mosquito attractant _-pinene. During patient studies involving two independent pediatric clinical populations from Malawi, …

The Malaria Testing And Treatment Landscape In Mainland Tanzania, 2016., Kathryn A. O'Connell, Vamsi Vasireddy, Megan Littrell, Andria Rusk, Actwatch Group, Daniel Michael, Sigsbert Patila Mkunde

Collected Faculty Scholarship

BACKGROUND: Understanding the key characteristics of malaria testing and treatment is essential to the control of a disease that continues to pose a major risk of morbidity and mortality in mainland Tanzania, with evidence of a resurgence of the disease in recent years. The introduction of artemisinin combination therapy (ACT) as the first-line treatment for malaria, alongside policies to promote rational case management following testing, highlights the need for evidence of anti-malarial and testing markets in the country. The results of the most recent mainland Tanzania ACTwatch outlet survey are presented here, including data on the availability, market share and …

Impact Of Community-Based Interventions For The Prevention And Control Of Malaria On Intervention Coverage And Health Outcomes For The Prevention And Control Of Malaria, Rehana A. Salam, Jai K. Das, Zohra S. Lassi, Zulfiqar A. Bhutta

Department of Paediatrics and Child Health

In this paper, we aim to evaluate the effectiveness of community-based interventions (CBIs) for the prevention and management of malaria. We conducted a systematic review and identified 42 studies for inclusion. Twenty-five of the included studies evaluated the impact of the community-based distribution of insecticide-treated nets (ITNs), indoor residual spraying (IRS), or impregnated bed sheets; 14 studies evaluated intermittent preventive therapy (IPT) delivered in community settings; two studies focused on community-based education for malaria prevention; and one study evaluated environmental management through drain cleaning. Our analysis suggests that, overall, the community-based delivery of interventions to prevent and control malaria resulted …

Usefulness Of Plasmodium Falciparum-Specific Rapid Diagnostic Tests For Assessment Of Parasite Clearance And Detection Of Recurrent Infections After Artemisinin-Based Combination Therapy, B. Aydin-Schmidt, M. Mubi, U. Morris, M. Petzold, B.E. Ngasala, Zul Premji, A. Bjorkman, A. Martensson

Pathology, East Africa

Background: Rapid diagnostic test (RDT) is an important tool for parasite-based malaria diagnosis. High specificity of RDTs to distinguish an active Plasmodium falciparum infection from residual antigens from a previous infection is crucial in endemic areas where residents are repeatedly exposed to malaria. The efficiency of two RDTs based on histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens were studied and compared with two microscopy techniques (Giemsa and acridine orange-stained blood smears) and real-time polymerase chain reaction (PCR) for assessment of initial clearance and detection of recurrent P. falciparum infections after artemisinin-based combination therapy (ACT) in a moderately high …

Malaria Diagnosis And Treatment Practices Following Introduction Of Rapid Diagnostic Tests In Kibaha District, Coast Region, Tanzania, M. Mubi, D. Kakoko, B. Ngasala, Zul Premji, S. Peterson, A. Bjorkman, A. Martensson

Pathology, East Africa

Background: The success of the universal parasite-based malaria testing policy for fever patients attending primary health care (PHC) facilities in Tanzania will depend highly on health workers' perceptions and practices. The aim of this study was, therefore, to assess the present use of malaria diagnostics (rapid diagnostic tests (RDTs) and microscopy), prescription behaviour and factors affecting adherence to test results at PHC facilities in Kibaha District, Coast Region, Tanzania.

Methods: Exit interviews were conducted with fever patients at PHC facilities and information on diagnostic test performed and treatment prescribed were recorded. Interviews with prescribers to assess their understanding, perceptions and …

Temporal Trends Of Molecular Markers Associated With Artemether- Lumefantrine Tolerance/Resistance In Bagamoyo District, Tanzania, M. Malmberg, B. Ngasala, P.E. Ferreira, E. Larsson, I. Jovel, A. Hjalmarsson, M. Petzold, Zul Premji, J.P. Gil, A. Bjorkman, A. Martensson

Pathology, East Africa

Background: Development and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy (ACT) constitutes a major threat to recent global malaria control achievements. Surveillance of molecular markers could act as an early warning system of ACT-resistance before clinical treatment failures are apparent. The aim of this study was to analyse temporal trends of established genotypes associated with artemether-lumefantrine tolerance/resistance before and after its deployment as first-line treatment for uncomplicated malaria in Tanzania 2006.

Methods: Single nucleotide polymorphisms in the P. falciparum multidrug resistance gene 1 (pfmdr1) N86Y, Y184F, D1246Y and P. falciparum chloroquine transporter gene (pfcrt) K76T were analysed from …

Simplified Models Of Vector Control Impact Upon Malaria Transmission By Zoophagic Mosquitoes, Samson S. Kiware, Nakul Chitnis, Sarah J. Moore, Gregor J. Devine, Silas Majambere, Stephen Merrill, Gerry F. Killeen

Mathematics, Statistics and Computer Science Faculty Research and Publications

Background

High coverage of personal protection measures that kill mosquitoes dramatically reduce malaria transmission where vector populations depend upon human blood. However, most primary malaria vectors outside of sub-Saharan Africa can be classified as “very zoophagic,” meaning they feed occasionally (

Methods and Findings

We extended a published malaria transmission model to examine the relationship between transmission, control, and the baseline proportion of bloodmeals obtained from humans (human blood index). The lower limit of the human blood index enables derivation of simplified models for zoophagic vectors that (1) Rely on only three field-measurable parameters. (2) Predict immediate and delayed (with …

Plasmodium Falciparum Population Dynamics During The Early Phase Of Anti-Malarial Drug Treatment In Tanzanian Children With Acute Uncomplicated Malaria, A.M. Carlsson, B.E. Ngasala, S. Dahlstrom, C. Membi, I.M. Veiga, L. Rombo, S. Abdulla, Zul Premji, J.P. Gil, A. Bjorkman, A. Martensson

Pathology, East Africa

Background: This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa.

Methods: A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 …

Factors Influencing Adherence To Referral Advice Following Pre-Referral Treatment With Artesunate Suppositories In Children In Rural Tanzania, Daudi Simba, Marian Warsame, Omari Kimbute, Deodatus Kakoko, Max Petzold, Goran Tomson, Zul Premji, Melba Gomes

Pathology, East Africa

Objective: WHO recommends artemisinin suppository formulations as pre-referral treatment for children who are unable to take oral medication and cannot rapidly reach a facility for parenteral treatment. We investigated factors influencing caretakers’ adherence to referral advice following pre-referral treatment of their children with rectal artesunate suppositories.

Methods: The study was nested within an intervention study that involved pre-referral treatment of all children who came to a community dispenser for treatment because they were unable to take oral medications because of repeated vomiting, lethargy, convulsions or altered consciousness. All patients who did not comply with referral advice were stratified by actions …

Efficacy And Safety Of Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine For Malaria In African Infants: A Pooled Analysis Of Six Randomised, Placebo-Controlled Trials, J.J. Aponte, D. Schellenberg, A. Egan, A. Breckenridge, I. Carneiro, J. Critchley, I. Danquah, A. Dodoo, R. Kobbe, B. Lell, J. May, Zul Premji, S. Sanz, E. Sevene, R. Soulaymani-Becheikh, P. Winstanley, S. Adjei, S. Anemana, D. Chandramohan, S. Issifou, F. Mockenhaupt F., S. Owusu-Agyei, B. Greenwood, M.P. Grobusch, P.G. Kremsner, E. Macete, H. Mshinda, R.D. Newman, L. Slutsker, M. Tanner, P. Alonso, C. Menendez

Pathology, East Africa

Background: Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa. Methods: We pooled data from six double-blind, randomised, placebo-controlled trials (undertaken one each in Tanzania, Mozambique, and Gabon, and three in Ghana) that assessed the efficacy of IPTi with sulfadoxine-pyrimethamine. In all trials, IPTi or placebo was given to infants at the time of routine vaccinations delivered by WHO's Expanded Program on Immunization. Data from the trials for incidence of clinical malaria, risk of anaemia (packed-cell volume <25% or haemoglobin <80 g/L), and incidence of hospital admissions and adverse events in infants up to 12 months of age were reanalysed by use of standard outcome definitions and time periods. Analysis was by modified intention to treat, including all infants who received at least one dose of IPTi or placebo. Findings: The six trials provided data for 7930 infants (IPTi, n=3958; placebo, n=3972). IPTi had a protective efficacy of 30·3% (95% CI 19·8-39·4, p<0·0001) against clinical malaria, 21·3% (8·2-32·5, p=0·002) against the risk of anaemia, 38·1% (12·5-56·2, p=0·007) against hospital admissions associated with malaria parasitaemia, and 22·9% (10·0-34·0, p=0·001) against all-cause hospital admissions. There were 56 deaths in the IPTi group compared with 53 in the placebo group (rate ratio 1·05, 95% CI 0·72-1·54, p=0·79). One death, judged as possibly related to IPTi because it occurred 19 days after a treatment dose, was subsequently attributed to probable sepsis. Four of 676 non-fatal hospital admissions in the IPTi group were deemed related to study treatment compared with five of 860 in the placebo group. None of three serious dermatological adverse events in the IPTi group were judged related to study treatment compared with one of 13 in the placebo group. Interpretation: IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings, suggesting that this intervention is a useful contribution to malaria control. Funding: Bill & Melinda Gates Foundation. © 2009 Elsevier Ltd. All rights reserved.

Using Decision Analysis To Improve Malaria Control Policy Making, Jonathan B. Wiener, Randall A. Kramer, Katherine L. Dickinson, Richard M. Anderson, Vance G. Fowler, Marie Lynn Miranda, Clifford M. Mutero, Kathryn A. Saterson

Faculty Scholarship

Malaria and other vector-borne diseases represent a significant and growing burden in many tropical countries. Successfully addressing these threats will require policies that expand access to and use of existing control methods, such as insecticide-treated bed nets (ITNs) and artemesinin combination therapies (ACTs) for malaria, while weighing the costs and benefits of alternative approaches over time. This paper argues that decision analysis provides a valuable framework for formulating such policies and combating the emergence and re-emergence of malaria and other diseases. We outline five challenges that policy makers and practitioners face in the struggle against malaria, and demonstrate how decision …

Variant Merozoite Protein Expression Is Associated With Erythrocyte Invasion Phenotypes In Plasmodium Falciparum Isolates From Tanzania, A.K. Bei, C.D. Membi, J.C. Rayner, M. Mubi, B. Ngasala, A.A. Sultan, Zul Premji, M.T. Duraisingh

Pathology, East Africa

[No abstract available]

Efficacy And Safety Of Artemether-Lumefantrine (Coartem®) Tablets (Six-Dose Regimen) In African Infants And Children With Acute, Uncomplicated Falciparum Malaria, C. Falade, M. Makanga, Zul Premji, C.E. Ortmann, M. Stockmeyer, P. Ibarra De Palacios

Pathology, East Africa

Approximately one million children die from malaria each year. A recently approved artemisinin-based tablet, Coartem (co-artemether), comprising artemether 120 mg plus lumefantrine 20 mg, given in four doses, provides effective antimalarial treatment for children in many sub-Saharan countries. However, this regimen is considered insufficient for non-immune infants and in areas where multidrug-resistant Plasmodium falciparum predominates. This open-label study assessed the efficacy and safety of co-artemether administered to 310 African children weighing 5-25 kg, with acute, uncomplicated falciparum malaria. Six doses of co-artemether were given over 3 days, with follow-up at 7, 14 and 28 days. Treatment rapidly cleared parasitemia and …

Plasma Zinc Concentrations Are Depressed During The Acute Phase Response In Children With Falciparum Malaria, C. Duggan, W.B. Macleod, N.F. Krebs, J.L. Westcott, W.W. Fawzi, Zul Premji, V. Mwanakasale, J.L. Simon, K. Yeboah-Antwi, D.H. Hamer

Pathology, East Africa

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 μmol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response. © 2005 American Society for Nutritional Sciences.

Averting A Malaria Disaster In Africa - Where Does The Buck Stop?, C.J.M. Whitty, R. Allan, V. Wiseman, S. Ochola, M.V. Nakyanzi-Mugisha, B. Vonhm, M. Mwita, C. Miaka, A. Oloo, Zul Premji, C. Burgess, T.K. Mutabingwa

Pathology, East Africa

The serious threat posed by the spread of drug-resistant malaria in Africa has been widely acknowledged. Chloroquine resistance is now almost universal, and resistance to the successor drug, sulfadoxine-pyrimethamine (SP), is growing rapidly. Combination therapy has been suggested as being an available and potentially lasting solution to this impending crisis. However, the current cost of combination therapy, and especially that of artemisinin combination therapy (ACT), is potentially a serious drawback, even if a significant part of its cost is passed on to the end-user. If the question of cost is not successfully addressed this could lead to adverse results from …

Higher Il-10 Levels Are Associated With Less Effective Clearance Of Plasmodium Falciparum Parasites, E. Hugosson, S.M. Montgomery, Zul Premji, M. Troye-Blomberg, A. Bjorkman

Pathology, East Africa

The implications of high levels of the immune regulatory cytokine IL-10 in Plasmodium falciparum malaria are unclear. IL-10 may down-regulate pro-inflammatory responses and also exacerbate disease by inhibiting anti-parasitic immune functions. To study possible inhibiting effects on parasite clearance, IL-10 plasma levels were determined in 104 Tanzanian children, 1 to 4 years old, with acute uncomplicated P. falciparum malaria, and analysed for association with parasite densities during 3 days of anti-malarial treatment. Higher baseline IL-10 plasma levels were associated with statistically significantly higher parasite densities after 24, 48 and 72 h of treatment. These associations could not be explained by …

Acridine Orange For Malaria Diagnosis: Its Diagnostic Performance, Its Promotion And Implementation In Tanzania, And The Implications For Malaria Control, J. Keiser, J. Utzinger, Zul Premji, Y. Yamagata, B.H. Singer

Pathology, East Africa

One hundred years ago, Giemsa's stain was employed for the first time for malaria diagnosis. Giemsa staining continues to be the method of choice in most malarious countries, although, in the recent past, several alternatives have been developed that exhibit some advantages. Considerable progress has been made with fluorescent dyes, particularly with Acridine Orange (AO). The literature on the discovery, development and validation of the AO method for malaria diagnosis is reviewed here. Compared with conventional Giemsa staining, AO shows a good diagnostic performance, with sensitivities of 81.3%-100% and specificities of 86.4%-100%. However, sensitivities decrease with lower parasite densities, and …

An Analysis Of Anemia And Child Mortality, B.J. Brabin, Zul Premji, F. Verhoeff

Pathology, East Africa

The relationship of anemia as a risk factor for child mortality was analyzed by using cross-sectional, longitudinal and case-control studies, and randomized trials. Five methods of estimation were adopted: 1) the proportion of child deaths attributable to anemia; 2) the proportion of anemic children who die in hospital studies; 3) the population-attributable risk of child mortality due to anemia; 4) survival analyses of mortality in anemic children; and 5) cause-specific anemia-related child mortality. Most of the data available were hospital based. For children aged 0-5 y the percentage of deaths due to anemia was comparable for reports from highly malarious …

Acute Haemolysis In Childhood Falciparum Malaria, H. Ekvall, P. Arese, F. Turrini, K. Ayi, F. Mannu, Zul Premji, A. Bjorkman

Pathology, East Africa

Acute haemolysis associated with clinical episodes of high-level Plasmodium falciparum parasitaemia was studied in 20 children from an holoendemic area (coastal Tanzania). The change in blood haemoglobin (Hb) concentration ranged from -46 to +5 g/L during the 72-h observation period and was linearly related to maximum parasitaemia. Balance studies between loss of blood Hb, increase in plasma Hb and appearance of Hb in the urine indicated that extravascular clearance of red cells was the predominant mode of erythrocyte clearance. Most subjects, however, showed minor signs of intravascular haemolysis. The plasma Hb was ≪1% of blood Hb and haemoglobinuria was detected …

Treatment Practices For Degedege, A Locally Recognized Febrile Illness, And Implications For Strategies To Decrease Mortality From Severe Malaria In Bagamoyo District, Tanzania, A.M. Makemba, P.J. Winch, V.M. Makame, G.L. Mehl, Zul Premji, J.N. Minjas, C.J. Shiff

Pathology, East Africa

Malaria remains one of the chief causes of mortality among young children in sub-Saharan Africa. Verbal autopsies for cases of childhood mortality in Bagamoyo District, Tanzania demonstrated that degedege, a locally defined illness of children characterized by fever and convulsions, is frequently treated by traditional healers. To investigate this further, an ethnographic study was carried out in one village that included in-depth interviews with 14 traditional healers and 3 focus groups with parents. Parents and traditional healers were unanimous in their conviction that degedege requires traditional treatments, at least initially, and that these treatments are effective. While traditional healers do …