Papers by Mathews Mulenga
The American Journal of Tropical Medicine and Hygiene, 2006
Whether administration of folic acid to children with malaria anemia is helpful is controversial.... more Whether administration of folic acid to children with malaria anemia is helpful is controversial. Therefore, we conducted a randomised, placebo-controlled trial of 14 days of treatment with folic acid (1 mg/d) in Zambian children with malaria anemia treated with either sulfadoxine/pyrimethamine (SP) or atovaquone/proguanil (AP). Among children who received SP, the prevalence of parasitemia was higher in children treated with folic acid than among those given placebo at days 3, 7, and 14 after the start of treatment, and the difference at day 3 was statistically significant (P ס 0.013). Folic acid treatment had no effect on parasitemia in children treated with AP. Administration of folic acid led to a small increase in packed cell volume over that seen in the placebo group at days 14 and 28 after the start of treatment.
The American Journal of Tropical Medicine and Hygiene, 2015
Malaria risk maps may be used to guide policy decisions on whether vector control interventions s... more Malaria risk maps may be used to guide policy decisions on whether vector control interventions should be targeted and, if so, where. Active surveillance for malaria was conducted through household surveys in Nchelenge District, Zambia from April 2012 through December 2014. Households were enumerated based on satellite imagery and randomly selected for study enrollment. At each visit, participants were administered a questionnaire and a malaria rapid diagnostic test (RDT). Logistic regression models were used to construct spatial prediction risk maps and maps of risk uncertainty. A total of 461 households were visited, comprising 1,725 participants, of whom 48% were RDT positive. Several environmental features were associated with increased household malaria risk in a multivariable logistic regression model adjusting for seasonal variation. The model was validated using both internal and external evaluation measures to generate and assess root mean square error, as well as sensitivity and specificity for predicted risk. The final, validated model was used to predict and map malaria risk including a measure of risk uncertainty. Malaria risk in a high, perennial transmission setting is widespread but heterogeneous at a local scale, with seasonal variation. Targeting malaria control interventions may not be appropriate in this epidemiological setting.
The Journal of Nutrition, 2010
A survey indicated that high-dose vitamin A (HD-VA) supplements had no apparent effect on vitamin... more A survey indicated that high-dose vitamin A (HD-VA) supplements had no apparent effect on vitamin A (VA) status, assessed by serum retinol concentrations, of Zambian children , 5 y of age. To explore possible reasons for the lack of response, we quantified absorption, retention, and urinary elimination of either a single HD-VA supplement (209.8 mmol; 60 mg) or a smaller dose of stable isotope (SI)-labeled VA (17.5 mmol; 5 mg), which was used to estimate VA pool size, in 3-to 4-y-old Zambian boys (n = 4 for each VA dose). A tracer dose of [ 14 C 2 ]-labeled VA (0.925 kBq; 25 nCi) was coadministered with the HD-VA supplement or SI-labeled VA, and 24-h stool and urine samples were collected for 3 and 7 consecutive days, respectively, and 24-h urine samples at 4 later time points. Accelerator MS was used to quantify 14 C in
Science, 2011
Insect midgut-dwelling bacteria generate reactive oxygen species that inhibit malaria parasite de... more Insect midgut-dwelling bacteria generate reactive oxygen species that inhibit malaria parasite development.
The Lancet Infectious Diseases, 2012
AOT, RWS, and UD'A shaped the ideas and approaches proposed, and drafted and revised the report. ... more AOT, RWS, and UD'A shaped the ideas and approaches proposed, and drafted and revised the report. CK contributed to writing the report and organised and participated in the meeting in Kigali, Rwanda on efforts to revive the East African Network for Monitoring Antimalarial Treatment. EJ, AN, BO, and JL reviewed the report and were part of the Kigali meeting. MM, WFM, and PJG reviewed the report. CR took part in the original discussions of the ideas proposed, helped to revise the report, and contributed to figure 3. AOT and RWS have been invited speakers at scientific symposia organised by Novartis, Pfizer, Sigma Tau, and Sanofi. AOT has received a research grant from Sanofi and RWS has received research grants from Pfizer and Novartis. RWS and AOT have been cochairpersons of best-practice workshops in regional and national malaria control programmes sponsored by Novartis, for which they received honoraria. UD'A has been an invited speaker at symposia organised by Sigma Tau and Novartis, and has received a research grant from Sigma Tau. BO has been an invited speaker at scientific symposia organised by Novartis, Sanofi, and Pfizer and has received research grants from the same companies.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2006
HIV-1-negative children with malaria have reversible lymphocyte and CD4 count decreases. We asses... more HIV-1-negative children with malaria have reversible lymphocyte and CD4 count decreases. We assessed the impact of malaria parasitemia on the absolute CD4 count in both HIV-1-infected and non-HIV-infected adults. In Ndola, Zambia, at the health-center level, we treated 327 nonpregnant adults for confirmed, uncomplicated, clinical malaria. We assessed HIV-1 status, CD4 count, and HIV-1 viral load (if HIV-1-infected) at enrollment and at 28 and 45 days after treatment. After successful antimalarial treatment, the median CD4 count at day 28 of follow-up increased from 468 to 811 cells/microL in HIV-1-negative and from 297 to 447 cells/microL in HIV-1-positive patients (paired t test, P < 0.001 for both). CD4 count increment was inversely correlated with CD4 count at day 0 in both HIV-1-negative (P < 0.001) and HIV-1-positive patients (P = 0.03). After successful treatment, the proportion of patients with CD4 count <200/microL at day 45 decreased from 9.6% to 0% in HIV-1-negative and from 28.7% to 13.2% in HIV-1-positive malaria patients (P < 0.001 for both). In patients with detectable but mostly asymptomatic parasitemia, CD4 count and, if HIV-1-infected, viral load at day 45 of follow-up were similar to those observed at enrollment. Interpretation of absolute CD4 count might be biased during or just after a clinical malaria episode. Therefore, in malaria-endemic areas, before taking any decision on the management of HIV-1-positive individuals, their malaria status should be assessed.
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2009
Background: Anemia is the most frequent cytopenia in HIVinfected individuals and is often associa... more Background: Anemia is the most frequent cytopenia in HIVinfected individuals and is often associated with malaria. Objective: To assess the impact of HIV-1 on the hematological recovery after a clinical malaria episode. Methods: In Ndola, Zambia, a region with high malaria and HIV prevalence, hemoglobin (Hb) was measured in 634 malaria patients 14 and 45 days after antimalarial treatment. Risk factors for hematological recovery were analyzed in a multivariate linear regression model. Results: At enrollment, HIV-1-infected malaria patients had lower Hb compared with HIV-1 uninfected (122.7 vs 136.0 g/L; P , 0.001). In both groups, mean Hb was significantly lower at day 14 posttreatment than day 0 (P , 0.0001) and significantly higher at day 45 than at day 14 (HIV-1 negative: P = 0.0001; HIV-1 infected: P = 0.005). HIV-1 was a risk factor for a larger Hb decrease until day 14 (P , 0.001) and slower recovery until day 45 (P = 0.048). When considering the whole 45-day follow-up period, mean Hb increased in the HIV-1-negative group (+3.54 g/L; 95% confidence interval: 1.37 to 5.70; P = 0.001) but not in the HIV-1-infected group (20.72 g/L; 95% confidence interval: 23.85 to +2.40; P = 0.64). HIV-1 infection as such (P , 0.0001), not CD4 cell count (P = 0.46), was an independent risk factor for a slower hematological recovery. Conclusions: HIV-1-infected malaria patients had a slower hematological recovery after successful parasite clearance. Malaria preventive measures should be targeted to this high-risk group.
The Journal of …, 2009
... accelerator mass spectrometry EK Aklamati, M. Mulenga, SR Dueker, BA Buchholz, JM Peerson, E.... more ... accelerator mass spectrometry EK Aklamati, M. Mulenga, SR Dueker, BA Buchholz, JM Peerson, E. Kafwembe, KH Brown, MJ Haskell ... By comparison, the total effective dose of a 6-hour airline flight is 3.0 mrem and the dose of a dental X-ray examination is 20 mrem. ...
The Journal of …, 2009
... accelerator mass spectrometry EK Aklamati, M. Mulenga, SR Dueker, BA Buchholz, JM Peerson, E.... more ... accelerator mass spectrometry EK Aklamati, M. Mulenga, SR Dueker, BA Buchholz, JM Peerson, E. Kafwembe, KH Brown, MJ Haskell ... By comparison, the total effective dose of a 6-hour airline flight is 3.0 mrem and the dose of a dental X-ray examination is 20 mrem. ...
Antimicrobial Agents and Chemotherapy, 2008
The Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme is the target of pyrimethamine,... more The Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme is the target of pyrimethamine, a component of the antimalarial pyrimethamine-sulfadoxine. Resistance to this drug is associated primarily with mutations in the Pf dhfr gene. The I164L mutant allele is of particular interest, because strains possessing this mutation are highly resistant to pyrimethamine and to chlorproguanil, a component of chlorproguanil-dapsone. A recent study from Malawi reported this mutation at a prevalence of 4.7% in parasites from human immunodeficiency virus-positive pregnant women by using a real-time PCR method. These observations have huge implications for the use of pyrimethamine-sulfadoxine, chlorproguanil-dapsone, and future antifolate-artemisinin combinations in Africa. It was imperative that this finding be rigorously tested. We identified a number of critical limitations in the original genotyping strategy. Using a refined and validated real-time PCR strategy, we report here that this...
Antimicrobial Agents and Chemotherapy, 2009
Annals of Tropical Paediatrics, 2005
Many cases of severe malarial anaemia are clinically stable, but some can deteriorate rapidly. In... more Many cases of severe malarial anaemia are clinically stable, but some can deteriorate rapidly. In a crosssectional survey of 255 children with clinically stable malarial anaemia, 72 had severe anaemia (PCV (15%) and 183 were moderately anaemic (PCV ,15-21%). Being female, or febrile, or a referral and having low parasitaemia or hepatomegaly were the risk factors for severe anaemia.
Acta Tropica, 2012
The burden of malaria has decreased dramatically within the past several years in parts of sub-Sa... more The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, following the scale-up of interventions supported by the Roll Back Malaria Partnership, the President's Malaria Initiative and other partners. It is important to appreciate that the reductions in malaria have not been uniform between and within countries, with some areas experiencing resurgence instead. Furthermore, while interventions have greatly reduced the burden of malaria in many countries, it is also recognized that the malaria decline pre-dated widespread intervention efforts, at least in some cases where data are available. This raises more questions as what other factors may have been contributing to the reduction in malaria transmission and to what extent. The International Center of Excellence for Malaria Research (ICEMR) in Southern Africa aims to better understand the underlying malaria epidemiology, vector ecology and parasite genomics using three contrasting settings of malaria transmission in Zambia and Zimbabwe: an area of successful malaria control, an area of resurgent malaria and an area where interventions have not been effective. The Southern Africa ICEMR will capitalize on the opportunity to investigate the complexities of malaria transmission while adapting to intervention and establish the evidence-base to guide effective and sustainable malaria intervention strategies. Key
The Journal of Infectious Diseases, 2006
Background. Human immunodeficienc virus (HIV)-1 infected adults with low CD4 cell count have a hi... more Background. Human immunodeficienc virus (HIV)-1 infected adults with low CD4 cell count have a higher risk of malaria infection and clinical malaria. We assessed the influenc that HIV-1 immune suppression has on the efficac of antimalarial treatment in adults with uncomplicated malaria Methods. This clinical trial included 971 Zambian adults with uncomplicated malaria. Patients were tested for HIV-1, and, if positive, a CD4 cell count was assessed. The primary outcome was recurrent parasitemia corrected by molecular genotyping within 45 days after treatment. Results. HIV-1 infection was detected in 33% (320/971) of adult patients with malaria. Treatment failure was not associated with HIV-1 infection (relative risk [RR], 1.12 [95% confidenc interval {CI}, 0.82-1.53];). P p .45 HIV-1-infected patients with a CD4 cell count !300 cells/mL had an increased risk of recurrent parasitemia, compared with those with a CD4 cell count у300 cells/mL (RR, 2.24 [95% CI, 1.20-4.14];). After ge-P p .01 notyping, the risk of recrudescence was higher in HIV-1-infected patients with a CD4 cell count !300 cells/mL than in the other patients with malaria (RR, 1.67 [95% CI, 1.13-2.47];). P p .02 Conclusion. HIV-1-infected patients with malaria with a CD4 cell count !300 cells/mL have a higher risk of experiencing a recrudescent infection, compared with those with a CD4 cell count у300 cells/mL or without HIV-1 infection. Trial registered at http://www.clinicaltrials.gov/; reference number NCT00304980.
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Papers by Mathews Mulenga