Pathology Commons^™

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.

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 …

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. …

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 …

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 …

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.

Age, Temperature, And Parasitaemia Predict Chloroquine Treatment Failure And Anaemia In Children With Uncomplicated Plasmodium Falciparum Malaria, D.H. Hamer, W.B. Macleod, E. Addo-Yobo, C.P Duggan, B. Estrella, W.W. Fawzi, J.K. Konde-Lule, V. Mwanakasale, Zul Premji, F. Sempertegui, F.P. Ssengooba, K. Yeboah-Antwi, J.L. Simon

Pathology, East Africa

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; …

Effect Of Zinc On The Treatment Of Plasmodium Falciparum Malaria In Children: A Randomized Controlled Trial, F. Sempertegui, B. Estrella, F.R. Toapanta, D.S. Torres, D.E. Calahorrano, K. Yeboah-Antwi, E. Addo-Yobo, P. Arthur, S. Newton, Zul Premji, M. Hubert, C.S. Makwaya, F. Ssengooba, J. Konde-Lule, E. Mukisa, D.H. Hamer, W. Macleod, C. Duggan, W. Fawzi, J. Simon, V. Mwanakasale, M. Mulenga, T. Sukwa, J. Tshiula

Pathology, East Africa

Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria.

Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken.

Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and ≥ 2000 asexual forms of Plasmodium falciparum/μL in a thick blood smear received chloroquine and were randomly assigned to …

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 …

A Point Mutation In Codon 76 Of Pfcrt Of P. Falciparum Is Positively Selected For By Chloroquine Treatment In Tanzania, A.G. Schneider, Zul Premji, I. Felger, T. Smith, S. Abdulla, H.-P. Beck, H. Mshinda

Pathology, East Africa

This study was undertaken to validate the relevance of Chloroquine (CQ) resistance markers pfert76 and pfmdrl86 in an endemic area in Tanzania. After treatment with CQ, recrudescence was distinguished from new infection by msp2 genotyping, and the number of concurrent infection was also determined. The rate of children with recrudescent parasites at day 7 and/or day 14 amounted to a parasitological failure rate of 22.4% using PCR. The mean multiplicity of infection at day 0 was 3.2 (n = 71). The allelic frequencies of the mutated pfert76 and pfmdrl86 were estimated to be 92 and 77%, respectively. Both values exceeded …

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.

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 …

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 …

Current Clinical Efficacy Of Chloroquine For The Treatment Of Plasmodium Falciparum Infections In Urban Dar Es Salaam, United Republic Of Tanzania, Zul Premji, C. Makwaya, J.N. Minjas

Pathology, East Africa

Reported is the use of a 14-day WHO protocol, which takes into account the clinical, parasitological and haematological responses to antimalarial drugs, to determine the efficacy of chloroquine in the treatment of uncomplicated malaria in young children (n = 200) in urban Dar es Salaam. Chloroquine failure was found in 43% of the children. Of these, 12.5% were considered to be early treatment failures and were given a single dose of sulfadoxine-pyrimethamine. Fever subsided in all children treated with sulfadoxine-pyrimethamine and there were no parasitological failures. In addition, children treated with sulfadoxine-pyrimethamine because of early treatment failure with chloroquine had …

Mosques Against Malaria, M.S. Mfaume, P.J. Winch, A.M. Makemba, Zul Premji

Pathology, East Africa

In a community-based malaria control project covering a predominantly Muslim population in the United Republic of Tanzania, difficulty was encountered in motivating people to have their mosquito nets reimpregnated with insecticide at six-monthly intervals. Education on this subject was therefore provided in mosques during Friday noon prayers. People who attended these services considered them an appropriate forum for discussing health concerns and viewed them as a credible source of information.Insecticide-impregnated bednets help to control the spread of the malaria parasite Plasmodium falciparum. The Bagamoyo Bednet Project is a community-based scheme to develop a sustainable system for the distribution and promotion …

Social And Cultural Factors Affecting Rates Of Regular Retreatment Of Mosquito Nets With Insecticide In Bagamoyo District, Tanzania, P.J. Winch, A.M. Makemba, V.R. Makame, M.S. Mfaume, M.C. Lynch, Zul Premji, J.N. Minjas, C.J. Shiff

Pathology, East Africa

Insecticide-treated mosquito nets have an impact on mortality and morbidity in young children under controlled conditions. When integrated into larger control programs, there is the danger that rates of regular retreatment of the nets with insecticide will drop, greatly limiting their effectiveness as a public health intervention. In Bagamoyo District, Tanzania, rates of retreatment dropped significantly when payment for the insecticide was introduced. A series of neighbourhood (hamlet) meetings were held in all study villages to discuss people's concerns about the insecticide and ways to increase rates of retreatment. Although changes were made in the procedure for retreatment, rates of …

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 …

Changes In Malaria Associated Morbidity In Children Using Insecticide Treated Mosquito Nets In The Bagamoyo District Of Coastal Tanzania, Zul Premji, P. Lubega, Y. Hamisi, E. Mchopa, J. Minjus, W. Checkley, C. Shiff

Pathology, East Africa

A community based malaria control intervention using insecticide treated mosquito nets (IMN) has been implemented and tested in 13 villages of the Yombo Division, Bagamoyo District in the Coastal Region, Tanzania, an area holoendemic for P. falciparum malaria. Following extensive sociological research into local perceptions of malaria, the programme was implemented. It was decided by consensus that village mosquito net committees would be the appropriate local level implementers. These were formed and provided with IMN's which were sold to villagers at subsidised cost. The income was invested for use by the committees for sustaining the activity. Use patterns were determined …

Local Anaesthetic Cream For The Alleviation Of Pain During Venepuncture In Tanzanian Schoolchidren, U. Hellgren, C.M. Kihamia, Zul Premji, K. Danielson

Pathology, East Africa

The analgesic effect and the usefulness of EMLA cream 5% in connection with venous blood-sampling was investigated in 42 Tanzanian schoolchildren. Approximately 2.5 g EMLA was applied to the right cubital fossa for a minimum of 120 min. The analgesic effect was pronounced - 93% of the venepunctures were pain-free and no child experienced severe pain. No adverse reactions were observed and the children could continue normal school work during the application time.