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Treatment Of Asymptomatic Carriers With Artemether-Lumefantrine: An Opportunity To Reduce The Burden Of Malaria?, B. Ogutu, A.B. Tiono, M. Makanga, Zul Premji, A.D. Gbadoe, D. Ubben, A.C. Marrast, O. Gaye

Pathology, East Africa

Background: Increased investment and commitment to malaria prevention and treatment strategies across Africa has produced impressive reductions in the incidence of this disease. Nevertheless, it is clear that further interventions will be necessary to meet the international target of a reversal in the incidence of malaria by 2015. This article discusses the prospective role of an innovative malaria control strategy - the community-based treatment of asymptomatic carriers of Plasmodium falciparum, with artemisinin-based combination therapy (ACT). The potential of this intervention was considered by key scientists in the field at an Advisory Board meeting held in Basel, in April 2009. …

Population Pharmacokinetics And Pharmacodynamics Of Artemether And Lumefantrine During Combination Treatment In Children With Uncomplicated Falciparum Malaria In Tanzania, S.F. Hietala, A. Martensson, B. Ngasala, S. Dahlstrom, N. Lindegardh, A. Annerberg, Zul Premji, A. Farnert, P. Gil, A. Bjorkman, M. Ashton

Pathology, East Africa

The combination of artemether (ARM) and lumefantrine is currently the first-line treatment of uncomplicated falciparum malaria in mainland Tanzania. While the exposure to lumefantrine has been associated with the probability of adequate clinical and parasitological cure, increasing exposure to artemether and the active metabolite dihydroartemisinin (DHA) has been shown to decrease the parasite clearance time. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of artemether, dihydroartemisinin, and lumefantrine in African children with uncomplicated malaria. In addition to drug concentrations and parasitemias from 50 Tanzanian children with falciparum malaria, peripheral parasite densities from 11 asymptomatic children were …

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 …

In Vivo Selection Of Plasmodium Falciparum Parasites Carrying The Chloroquine-Susceptible Pfcrt K76 Allele After Treatment With Artemether-Lumefantrine In Africa, C. Sisowath, I. Petersen, M.I. Veiga, A. Martensson, Zul Premji, A. Bjorkman, D.A. Fidock, J.P. Gil

Pathology, East Africa

Background: Artemether-lumefantrine (AL) is a major and highly effective artemisinin-based combination therapy that is becoming increasingly important as a new first-line therapy against Plasmodium falciparum malaria. However, recrudescences occurring after AL treatment have been reported. Identification of drug-specific parasite determinants that contribute to treatment failures will provide important tools for the detection and surveillance of AL resistance.

Methods: The findings from a 42-day follow-up efficacy trial in Tanzania that compared AL with sulfadoxinepyrimethamine (SP) were analyzed to identify candidate markers for lumefantrine tolerance/resistance in the chloroquine resistance transporter gene (pfcrt) and multidrug resistance gene 1 (pfmdr1). The findings were corroborated …

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.

Chlorproguanil - Dapsone - Artesunate Versus Artemether - Lumefantrine: A Randomized, Double-Blind Phase Iii Trial In African Children And Adolescents With Uncomplicated Plasmodium Falciparum Malaria, Zul Premji, R.E. Umeh, S. Owusu-Agyei, F. Esamai, E.U. Ezedinachi, S. Oguche, S. Borrmann, A. Sowunmi, S. Duparc, P.L. Kirby, A. Pamba, L. Kellam, R. Guiguemde, B. Greenwood, S.A. Ward, P.A. Winstanley

Pathology, East Africa

Background: Chlorproguanil-dapsone-artesunate (CDA) was developed as an affordable, simple, fixed-dose artemisinin-based combination therapy for use in Africa. This trial was a randomized parallel-group, double-blind, double-dummy study to compare CDA and artemether-lumefantrine (AL) efficacy in uncomplicated Plasmodium falciparum malaria and further define the CDA safety profile, particularly its hematological safety in glucose-6-phosphate dehydrogenase (G6PD) -deficient patients. Methods and Findings: The trial was conducted at medical centers at 11 sites in five African countries between June 2006 and August 2007. 1372 patients (≥1 to <15 years>old, median age 3 years) with acute uncomplicated P. falciparum malaria were randomized (2:1) to receive CDA 2/2.5/4 …

Coartem°: The Journey To The Clinic, Zul Premji

Pathology, East Africa

Artemisinin, from which the artemether component of Coartem° (artemether/lumefantrine, AL) is derived, is obtained from the plant sweet wormwood (Artemisia annua) which has been used for over 2,000 years as a Chinese herbal remedy. Artemisinin was first identified by Chinese researchers as the active anti-malarial constituent of A. annua and its derivatives were found to be the most potent of all anti-malarial drugs. Artemether acts rapidly, reducing the infecting parasite biomass by approximately 10,000-fold per asexual life cycle. Lumefantrine, the other active constituent of AL, acts over a longer period to eliminate the residual 100-100,000 parasites that remain after artemether …

Willingness And Ability To Pay For Artemisinin-Based Combination Therapy In Rural Tanzania, E.C. Saulo, B.C. Forsberg, Zul Premji, S.M. Montgomery, A. Bjorkman

Pathology, East Africa

Background: The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.

Methods: Structured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave- it" …

Impact Of Training In Clinical And Microscopy Diagnosis Of Childhood Malaria On Antimalarial Drug Prescription And Health Outcome At Primary Health Care Level In Tanzania: A Randomized Controlled Trial, B. Ngasala, M. Mubi, M. Warsame, M.G. Petzold, A.Y. Massele, L.L. Gustafsson, G. Tomson, Zul Premji, A. Bjorkman

Pathology, East Africa

Background: Prescribing antimalarial medicines based on parasite confirmed diagnosis of malaria is critical to rational drug use and optimal outcome of febrile illness. The impact of microscopy-based versus clinical-based diagnosis of childhood malaria was assessed at primary health care (PHC) facilities using a cluster randomized controlled training intervention trial.

Methods: Sixteen PHC facilities in rural Tanzania were randomly allocated to training of health staff in clinical algorithm plus microscopy (Arm-I, n = 5) or clinical algorithm only (Arm-II, n = 5) or no training (Arm-III, n = 6). Febrile under-five children presenting at these facilities were assessed, treated and scheduled …

Causes, Magnitude And Management Of Burns In Under-Fives In District Hospitals In Dar Es Salaam, Tanzania., M. Justin-Temu, G. Rimoy, Zul Premji, G. Matemu

Pathology, East Africa

Objectives: To determine the causes, magnitude and management of burns in children under five years of age who were admitted in the district hospitals of Dar es Salaam City, Tanzania.

Methods: In this study, a total of 204 under fives were enrolled. Questionnaires were used to elicit if the parent/caretaker had the knowledge of the cause of the burns, what was done immediately after burn injury, first aid given immediately after burn, source of the knowledge of first aid and when the child was taken to the hospital. Also the questionnaire was cited with data on the management of burns …

The Content Of African Diets Is Adequate To Achieve Optimal Efficacy With Fixed-Dose Artemether-Lumefantrine: A Review Of The Evidence, Zul Premji, S. Abdulla, B. Ogutu, A. Ndong, C.O. Falade, I. Sagara, N. Mulure, O. Nwaiwu, G. Kokwaro

Pathology, East Africa

A fixed-dose combination of artemether-lumefantrine (AL, Coartem®) has shown high efficacy, good tolerability and cost-effectiveness in adults and children with uncomplicated malaria caused by Plasmodium falciparum. Lumefantrine bioavailability is enhanced by food, particularly fat. As the fat content of sub-Saharan African meals is approximately a third that of Western countries, it raises the question of whether fat consumption by African patients is sufficient for good efficacy. Data from healthy volunteers have indicated that drinking 36 mL soya milk (containing only 1.2 g of fat) results in 90% of the lumefantrine absorption obtained with 500 mL milk (16 g fat). African …

Influence Of Consecutive-Day Blood Sampling On Polymerase Chain Reaction-Adjusted Parasitological Cure Rates In An Antimalarial-Drug Trial Conducted In Tanzania, Andreas Martensson, Johan Ursing, M. Isabel Veiga, Lisa Wiklund, Christopher Membi, Scott M. Montgomery, Zul Premji, Anna Farnert, Andres Bjorkman, Billy Ngasala

Pathology, East Africa

We assessed the influence that consecutive-day blood sampling, compared with single-day blood sampling, had on polymerase chain reaction (PCR)-adjusted parasitological cure after stepwise genotyping of merozoite surface proteins 2 (msp2) and 1 (msp1) in 106 children in Tanzania who had uncomplicated falciparum malaria treated with either sulfadoxine-pyrimethamine or artemether- lumefantrine; 78 of these children developed recurrent parasitemia during the 42-day follow-up period. Initial msp2 genotyping identified 27 and 33 recrudescences by use of single- and consecutive-day sampling, respectively; in subsequent msp1 genotyping, 17 and 21 of these episodes, respectively, were still classified as recrudescences; these results indicate a similar sensitivity …

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 The Six-Dose Regimen Of Artemether-Lumefantrine In Pediatrics With Uncomplicated Plasmodium Falciparum Malaria: A Pooled Analysis Of Individual Patient Data, M. Makanga, Zul Premji, C. Falade, J. Karbwang, E.A. Mueller, K. Andriano, P. Hunt, P.I. De Palacios

Pathology, East Africa

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene.

Relationship Between Antipyretic Effects And Cytokine Levels In Uncomplicated Falciparum Malaria During Different Treatment Regimes, Elisabeth Hugosson, Scott M. Montgomery, Zul Premji, Marita Troye-Blomberg, Anders Bjorkman

Pathology, East Africa

We have previously shown that both chloroquine and paracetamol (acetaminophen) have antipyretic activity during treatment of acute uncomplicated Plasmodium falciparum malaria in children 1-4 years old. Here, we studied if this effect was accompanied by changes in plasma cytokine levels. The 104 children were treated with either chloroquine or sulfadoxine/pyrimethamine (SP) alone, SP + chloroquine or SP + paracetamol for 4 days. Cytokine levels were determined days 0, 2 and 3, body temperature every sixth hour until 72 h and parasitemia once daily for 4 days. At admission, body temperature correlated with levels of IL-10, IFN-γ and IL-6, and parasitemia …

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.

Habitat Characterization And Spatial Distribution Of Anopheles Sp. Mosquito Larvae In Dar Es Salaam (Tanzania) During An Extended Dry Period, M.A. Sattler, D. Mtasiwa, M. Kiama, Zul Premji, M. Tanner, G.F. Killeen, C. Lengeler

Pathology, East Africa

Introduction: By 2030, more than 50% of the African population will live in urban areas. Controlling malaria reduces the disease burden and further improves economic development. As a complement to treated nets and prompt access to treatment, measures targeted against the larval stage of Anopheles sp. mosquitoes are a promising strategy for urban areas. However, a precise knowledge of the geographic location and potentially of ecological characteristics of breeding sites is of major importance for such interventions.

Methods: In total 151 km2 of central Dar es Salaam, the biggest city of Tanzania, were systematically searched for open mosquito breeding sites. …

The Pervasive Triad Of Food Security, Gender Inequity And Women's Health: Exploratory Research From Sub-Saharan Africa, A.A. Hyder, S. Maman, J.E. Nyoni, S.A. Khasiani, N. Teoh, Zul Premji, S. Sohani

Pathology, East Africa

Objectives: This study was designed to explore the interactions between food securing activities, health and gender equity from the perspective of rural east African women. The specific objectives were to document the critical interaction among these three issues - food security, gender inequity, women's health within the context of sub-Saharan Africa; to describe the nature of this triad from the perspective of women farmers in Africa; and to propose a framework for linking available interventions to the vicious nature of this triad.

Setting: In-depth interviews and focus group discussions were conducted with rural women farmers in Kwale District, Kenya and …

Therapeutic Efficacy Of Sulfadoxine-Pyrimethamine And Prevalence Of Resistance Markers In Tanzania Prior To Revision Of Malaria Treatment Policy: Plasmodium Falciparum Dihydrofolate Reductase And Dihydropteroate Synthase Mutations In Monitoring In Vivo Resistance, K. Mugittu, M. Ndejembi, A. Malisa, M. Lemnge, Zul Premji, A. Mwita, W. Nkya, J. Kataraihya, S. Abdulla, H.-P. Beck, H. Mshinda

Pathology, East Africa

Prior to the 2001 malarial treatment policy change in Tanzania, we conducted trials to assess the efficacy of sulfadoxine-pyrimethamine (SP) and the usefulness of molecular markers in monitoring resistance. A total of 383 uncomplicated Plasmodium falciparum malaria patients (between 6 and 59 months old) were treated with SP and their responses were assessed. Mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes in admission day blood samples were analyzed. Results indicated that 85.6% of the patients showed an adequate clinical response, 9.7% an early treatment failure, and 4.7% a late treatment failure. The quintuple mutant genotype …

Rare, Highly Pyrimethamine-Resistant Alleles Of The Plasmodium Falciparum Dihydrofolate Reductase Gene From 5 African Sites, S.J. Bates, P.A. Winstanley, W.M. Watkins, A. Alloueche, J. Bwika, T.C. Happi, P.G. Kremsner, J.G. Kublin, Zul Premji, C.H. Sibley

Pathology, East Africa

In eastern and southern Africa, there has been a rapid increase in the prevalence of alleles with mutations in the Plasmodium falciparum dihydrofolate reductase gene (dhfr) associated with increased risk of clinical failure of sulfadoxine-pyrimethamine (S/P). Molecular methods for surveillance of these mutations are now widespread, but the usual analysis detects only the most prevalent allele in a polyclonal sample. We used a yeast-expression system to identify rare, highly pyrimethamine-resistant alleles of dhfr in isolates from 5 African countries-Kenya, Tanzania, Malawi, Gabon, and Nigeria. Only the isolates from Nigeria yielded significant numbers of novel resistant alleles, and only 1 of …

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 …

Antipyretic, Parasitologic, And Immunologic Effects Of Combining Sulfadoxine/Pyrimethamine With Chloroquine Or Paracetamol For Treating Uncomplicated Plasmodium Falciparum Malaria, E. Hugosson, D. Tarimo, M. Troye-Blomberg, S.M. Montgomery, Zul Premji, A. Bjorkman

Pathology, East Africa

Sulfadoxine/pyrimethamine (SP) is increasingly used against malaria in sub-Saharan Africa because of chloroquine resistance. However, chloroquine may have a beneficial antipyretic effect. We therefore compared the combination of SP plus chloroquine, chloroquine alone, SP alone, and SP plus paracetamol in the treatment of uncomplicated Plasmodium falciparum malaria in 175 Tanzanian children (1-4 years old) in a randomized trial. Outcome variables were axillary temperatures every six hours, daily parasitemias, and serum levels of IgG antibodies to P. falciparum. Lower mean temperatures (6-48 hours) were achieved with SP plus chloroquine or paracetamol than with SP alone (P < 0.001) or chloroquine alone (P < 0.05). All three SP-treated groups showed high and similar parasite reduction (0-48 hours), whereas treatment with chloroquine alone was much less effective. Levels of IgG antibodies to P. falciparum increased significantly (P < 0.001) and similarly in the four treatment groups between days 0, 2. and 3. Thus, the addition of chloroquine or paracetamol to SP improved the clinical outcome, but did not affect the parasitologic response or antibody production.

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 …

Hemoglobin Concentration In Children In A Malaria Holoendemic Area Is Determined By Cumulated Plasmodium Falciparum Parasite Densities, H. Ekvall, Zul Premji, S. Bennett, A. Bjorkman

Pathology, East Africa

In malaria holoendemic areas children are anemic, but the exact influence of falciparum malaria on hemoglobin (Hb) concentration remains largely unsettled. Prospective data were therefore collected in children < 24 months of age during five months in a Tanzanian village. Children with mean asymptomatic parasitemia ≥ 400/μl had lower median Hb levels during the study than those with mean density < 400/μl. The difference was 9.7 g/L (95% confidence interval [CI] 2.8-17). In children with one or more clinical malaria episodes, the median Hb was 8.3 g/L (95% CI 0.9-16) lower than those without episode. If early treatment failure was recorded, the immediate effect on Hb was particularly important with a mean drop of 17 g/L. Interestingly, at study-end the Hb concentration represented a function of the area under the parasitemia curve (AUPC) during the previous five months, adjusting for age. In conclusion, stepwise deterioration in median Hb levels was found by asymptomatic parasitemia, clinical malaria episode, and most significantly, treatment failure.

Micronutrient And Iron Supplementation And Effective Anti-Malarial Treatment Synergistically Improve Childhood Anaemia, H. Ekvall, Zul Premji, A. Bjorkman

Pathology, East Africa

The control of childhood anaemia in malaria holoendemic areas is a major public health challenge for which an optimal strategy remains to be determined. Malaria prevention may compromise the development of partial immunity. Regular micronutrient supplementation has been suggested as an alternative but its effectiveness remains unsettled. We therefore conducted a randomised placebo-controlled intervention trial with 207 Tanzanian children aged 5 months to 3 years on the efficacy of supervised supplementation of low-dose micronutrients including iron (Poly Vi-Sol with iron) three times per week, with an average attendance of ≥ 90%. The mean haemoglobin (Hb) level increased by 8 g/l …

Acute Adenolymphangitis Due To Bancroftian Filariasis In Rufiji District, South East Tanzania, D.B. Gasarasi, Zul Premji, P.G.M. Mujinja, R. Mpembeni

Pathology, East Africa

A longitudinal prospective surveillance for acute adenolymphagitis (ADL) was carried out in three villages in Rufiji district. A sample population of 3000 individuals aged 10 years and above was monitored fortnightly for a period of 12 months. The annual incidence of ADL was found to be 33 per 1000 population and was significantly higher in males than females (52.7/1000 and 18.7/1000 respectively). ADL episodes were more frequent in the age group of 40 years and above. Individuals with chronic manifestations seemed to be more vulnerable to ADL attacks with 62.2% of the total episodes occurring in this group. Furthermore, individuals …