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Biomedical subjects

Umberto D'Alessandro

Publications and source records attributed to Umberto D'Alessandro.

At least 19 recordsLinked to original sources
PubMed2006

CD4 T-cell count and HIV-1 infection in adults with uncomplicated malaria.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗
PubMed2006

HIV-1 immune suppression and antimalarial treatment outcome in Zambian adults with uncomplicated malaria.

BACKGROUND: Human immunodeficiency virus (HIV)-1 infected adults with low CD4 cell count have a higher risk of malaria infection and clinical malaria. We assessed the influence that HIV-1 immune suppression has on the efficacy 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% confidence interval {CI}, 0.82-1.53]; P=.45). HIV-1-infected patients with a CD4 cell count <300 cells/microL had an increased risk of recurrent parasitemia, compared with those with a CD4 cell count >or=300 cells/microL (RR, 2.24 [95% CI, 1.20-4.14]; P=.01). After genotyping, the risk of recrudescence was higher in HIV-1-infected patients with a CD4 cell count <300 cells/microL than in the other patients with malaria (RR, 1.67 [95% CI, 1.13-2.47]; P=.02). CONCLUSION: HIV-1-infected patients with malaria with a CD4 cell count <300 cells/microL have a higher risk of experiencing a recrudescent infection, compared with those with a CD4 cell count >or=300 cells/microL or without HIV-1 infection. Trial registered at http://www.clinicaltrials.gov/; reference number NCT00304980.

Adolescent↗
PubMed2006

Safety and efficacy of lumefantrine-artemether (Coartem) for the treatment of uncomplicated Plasmodium falciparum malaria in Zambian adults.

BACKGROUND: In Zambia, unacceptably high resistance to commonly used antimalarial drugs prompted the choice of artemether-lumefantrine (AL) as first line treatment for uncomplicated Plasmodium falciparum malaria. Although the safety and efficacy of AL have been extensively documented, no clinical trials had been carried out in Zambia. METHODS: Nine hundred seventy one adult patients with uncomplicated malaria were randomized to either sulfadoxine-pyrimethamine (SP)(486) or AL (485) and followed up for 45 days. Outcome of treatment was defined according to the standard WHO classification. Recurrent parasitaemia were genotyped to distinguish between recrudescence and new infection. RESULTS: Fever at day 3 was significantly lower (AL: 0.9%; 4/455; SP: 3,5%; 15/433; p = 0.007) and the mean haemoglobin at day 45 significantly higher (AL: 134 g/l; SP 130 g/l; p = 0.02) in the AL group. Almost all clinical symptoms cleared faster with AL. Early treatment failure was significantly higher in the SP (25/464) than in the AL (2/463) (OR: 13.1 95% CI: 3.08-55.50; P < 0.001). The rate of new infections was similar in both groups (18 with SP and 19 with AL). Late clinical failure (OR: 2.55; 95% CI: 1.34-4.84; P = 0.004) and late parasitological failure (OR:3.18; 95% CI: 1.25-8.09; P = 0.02) were significantly higher in the SP group. Total treatment failure was significantly higher in the SP group (96/393; 19.3%) as compared to the AL (22/403; 5.4%) group (OR: 4.15; 95% CI: 2.52-6.83; P < 0.001). CONCLUSION: In Zambia, the new first line regimen AL is far more efficacious than SP in treating uncomplicated P. falciparum malaria in adults. Data on safety and efficacy of AL in pregnant women are urgently needed.

Adult↗
PubMed2006

Pharmacovigilance of antimalarial treatment in Africa: is it possible?

Pharmacovigilance, defined as "the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug related problem", is increasingly being recognized in Africa. Many African countries have simultaneously adopted artemisinin derivative based combination therapy (ACT) as first-line treatment for uncomplicated malaria, offering an opportunity to assess the safety of these drugs when used widely. While ACTs appear to be safe and well-tolerated, there is little experience with these medicines in Africa, outside clinical trials. Pharmacovigilance for ACTs and other combination treatments in Africa is essential. Malaria transmission intensity is high and antimalarial medicines are used frequently. Presumptive treatment of fever with antimalarials is common, often in the absence of a confirmed diagnosis, using drugs obtained without a prescription. Informal use of antimalarial drugs may increase the risk of incorrect dosing, inappropriate treatment, and drug interactions, which may impact negatively on drug safety. Furthermore, the administration of antimalarial treatments in patients with a concomitant illness, including HIV/AIDs, tuberculosis and malnutrition, is a concern. African countries are being encouraged to establish pharmacovigilance systems as ACTs are rolled out. However, pharmacovigilance is difficult, even in countries with a well-developed health care system. The rationale for pharmacovigilance of antimalarial drugs is discussed here, outlining the practical challenges and proposing approaches that could be adopted in Africa.

Adverse Drug Reaction Reporting Systems↗
PubMed2006

Safety and efficacy of dihydroartemisinin/piperaquine (Artekin) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children.

In Rwanda, amodiaquine+sulfadoxine/pyrimethamine (AQ+SP) is the current first-line treatment for malaria, introduced in 2001 as an interim strategy before the future deployment of an artemisinin-based combination treatment (ACT). Dihydroartemisinin/piperaquine (DHA-PQP) is a new co-formulated and well tolerated ACT increasingly used in Southeast Asia where it has proved to be highly effective against Plasmodium falciparum malaria. We tested the efficacy, safety and tolerability of DHA-PQP in children with uncomplicated P. falciparum malaria. A randomised, open trial was carried out in 2003-2004. Seven hundred and sixty-two children aged 12-59 months with uncomplicated P. falciparum malaria were randomly allocated to one of the following treatments: amodiaquine+artesunate; AQ+SP; or DHA-PQP. Patients were followed-up until Day 28 after treatment. Adverse events and clinical and parasitological outcomes were recorded. Children treated with DHA-PQP or AQ+AS had a significantly higher cure rate compared with those treated with amodiaquine+sulfadoxine/pyrimethamine (95.2% and 92.0% vs. 84.7%, respectively). Parasite clearance was significantly faster in children treated with DHA-PQP and AQ+AS compared with those treated with amodiaquine+sulfadoxine/pyrimethamine. The frequency of adverse events was significantly lower in patients treated with DHA-PQP than in those treated with combinations containing amodiaquine. A 3-day treatment with DHA-PQP proved to be efficacious with a good safety and tolerability profile and could be a good candidate for the next first-line treatment.

Antimalarials↗
PubMed2006

Tolerability of amodiaquine and sulphadoxine-pyrimethamine, alone or in combination for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan adults.

OBJECTIVE: To assess the tolerability and efficacy of amodiaquine (AQ)+sulphadoxine-pyrimethamine (SP), the first-line malaria treatment in Rwanda. METHOD: Randomized, double-blind trial in 2003 in Kigali town. A total of 351 adult patients with uncomplicated Plasmodium falciparum malaria were randomly allocated to one of the following treatments: AQ+SP, AQ or SP. We followed patients until day 14 after treatment and recorded adverse events (AEs) and clinical and parasitological outcomes. RESULTS: One hundred and eighteen patients reported at least one AE: 40% in the AQ, 39% in the AQ+SP and 21% in the SP groups. The AE was classified as possibly related to the antimalarial treatment for 86 patients. The Risk Ratio for at least one AE after treatment was significantly and about fourfold higher in patients receiving AQ or AQ+SP than in patients receiving SP. Pruritus and fatigue were significantly more frequent in patients treated with AQ or AQ+SP than in those receiving SP. Severe AEs, such as fatigue, nausea, dizziness and vomiting, were observed in four patients treated with AQ, in 10 treated with AQ+SP and in one patient treated with SP. CONCLUSION: Amodiaquine+SP is not well tolerated and a substantial proportion of patients experienced pruritus and fatigue, thus decreasing their compliance and compromising the first line treatment implementation at national level. This renders AQ-containing regimens sub-optimal; better-tolerated treatments should be identified.

Adult↗
PubMed2006

Short report: molecular markers associated with Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in the Democratic Republic of Congo.

Sulfadoxine-pyrimethamine (SP) is the first line antimalarial treatment in the Democratic Republic of Congo. Using polymerase chain reaction, we assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulfadoxine, respectively. Four hundred seventy-four patients were sampled in Kilwa (N = 138), Kisangani (N = 112), Boende (N = 106), and Basankusu (N = 118). The proportion of triple mutations dhfr varied between sites but was always > 50%. The proportion of dhps double mutations was < 20%, with some sites as low as 0.9%. A quintuple mutation was present in 12.8% (16/125) samples in Kilwa; 11.9% (13/109) in Kisangani, 2.9% (3/102) in Boende, and 0.9% (1/112) in Basankusu. These results suggest high resistance to pyrimethamine alone or combined with sulfadoxine. Adding artesunate to SP does not seem a valid alternative to the current monotherapy.

Animals↗
PubMed2006

Variation in malaria transmission intensity in seven sites throughout Uganda.

Knowledge of the baseline malaria transmission in a given environment is important to guide malaria control interventions. However, in Uganda, recent information on malaria transmission intensity is lacking. Therefore, a 1-year entomological study was conducted in seven ecologically different sites throughout the country to assess spatial and temporal patterns in malaria transmission intensity. Anopheles gambiae sensu stricto was the main vector in five of the seven study sites, and An. funestus was the most important vector in the two other sites. In a peri-urban village, An. arabiensis contributed substantially to malaria transmission. Clear differences in annual entomological inoculation rates (AEIR) were observed between the study sites, ranging from 4 infective bites per person per year in the southwestern part of the country to >1,500 infective bites per person per year in a swampy area near the Nile River. Between villages with parasite prevalences of >or= 80% in children between 1 and 9 years old, a 4-fold difference in AEIR was observed. Based on the observed behavior of the vectors, insecticide-treated bed nets will be highly effective in controlling malaria. However, in the high transmission areas, additional measures will be needed to reduce the malaria burden to acceptable levels.

Animals↗
PubMed2005

In-vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda.

Plasmodium falciparum in-vitro susceptibility to chloroquine (CQ), monodesethylamodiaquine, quinine and dihydroartemisinin was investigated in Rwandan patients with a parasitaemia of at least >or=4000/microl. The study was carried out in November-December 2003. Dihydroartemisinin was the most potent (GM IC(50)=2.6nmol/l, 95% CI 2.2-3.2) among the drugs tested. Resistance to chloroquine was 45% (33/74) and that to monodesethylamodiaquine 7% (5/74). All the tested isolates were susceptible to quinine. The mean IC(50) of monodesethylamodiaquine, quinine and dihydroartemisinin was significantly higher for chloroquine-resistant than for chloroquine-sensitive strains (P<0.05). The IC(50) of each drug was significantly and positively correlated to that of the other three drugs (P<0.005), and this correlation was higher between CQ and monodesethylamodiaquine (r=0.8). In-vitro CQ resistance is linked to that of the other drugs tested. Most worrying is the positive correlation between the IC(50) of dihydroartemisinin and the other drugs, more particularly with CQ, suggesting an increased tolerance of the parasites to all drugs.

Adolescent↗
PubMed2005

Efficacy of chloroquine, sulfadoxine-pyrimethamine and amodiaquine for treatment of uncomplicated Plasmodium falciparum malaria among children under five in Bongor and Koumra, Chad.

We report two 28-day in-vivo antimalarial efficacy studies carried out in the urban centres of Bongor and Koumra, southern Chad. We assess chloroquine (CQ), sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) to treat Plasmodium falciparum uncomplicated malaria. Methods and outcome classification complied with latest WHO guidelines. Out of the 301 and 318 children aged 6-59 months included in Bongor and Koumra, respectively, 246 (81.7%) and 257 (80.8%) were eligible for analysis. In Bongor and Koumra, the 28-day PCR-adjusted failure rates for CQ were 23.7% (95% CI 14.7-34.8%) and 32.9% (95% CI 22.1-45.1%), respectively, and those for SP were 16.3% (95% CI 9.4-25.5%) and 4.3% (95% CI 1.2-10.5%). AQ failure rates were 6.4% (95% CI 2.1-14.3%) and 2.2% (95% CI 0.3-7.6%). The current use of CQ in Bongor and Koumra is questionable, and a more efficacious treatment is needed. Considering the reduced efficacy of SP in Bongor, AQ seems to be the best option for the time being. Following WHO recommendations that prioritize the use of artemisinin-based combinations, artesunate plus amodiaquine could be a potential first-line treatment. Nevertheless, the efficacy of this combination should be evaluated and the change carefully prepared, implemented and monitored.

Amodiaquine↗
PubMed2005

Malaria transmission intensity and the rate of spread of chloroquine resistant Plasmodium falciparum: Why have theoretical models generated conflicting results?

The rate at which falciparum resistant malaria spreads in different transmission settings is still a controversial subject. We have assessed the spread of mutant Plasmodium falciparum parasites in six Ugandan populations with varying prevalence of chloroquine resistance (CQR), malaria transmission intensity, multiplicity of parasite clones and prevalence of CQ use. For each population, we have determined the wild and mutant allele frequency at codons 76 and 86 of the pfcrt and pfmdr1 genes, respectively. The highest frequency (median = 16.3%, range: 0.0-70.4%) of infections with two pure mutants (no wild genotype in either gene), adjusted for clone multiplicity, was observed at the extremes of malaria transmission intensity. The wild/mutant (W/M) allele ratio (an index for tracking the progression of CQR) was less than one in all sites (median = 0.51, range: 0.09-0.98) for the pfcrt-76 gene, while it was greater than one in two of six sites (median = 0.75, range: 0.4-1.6) for the pfmdr1-86 gene, suggesting that the pfcrt-76 mutants were the predominant parasites at all sites. Furthermore, the pfmdr1-86 W/M allele ratio was consistently higher than that of the pfcrt-76. The spread of mutations linked to CQR in P. falciparum commences with the pfcrt-76 gene mutations, followed later by the pfmdr1-86 gene mutations that modulate higher CQR. Such spread occurs faster at the extremes of the transmission spectrum and could explain why mathematical models have previously generated conflicting results with respect to malaria transmission intensity and spread of CQR.

Alleles↗
PubMed2005

Malaria and urbanization in sub-Saharan Africa.

There are already 40 cities in Africa with over 1 million inhabitants and the United Nations Environmental Programme estimates that by 2025 over 800 million people will live in urban areas. Recognizing that malaria control can improve the health of the vulnerable and remove a major obstacle to their economic development, the Malaria Knowledge Programme of the Liverpool School of Tropical Medicine and the Systemwide Initiative on Malaria and Agriculture convened a multi-sectoral technical consultation on urban malaria in Pretoria, South Africa from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies for the assessment and control of urban malaria. This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria.

Africa South of the Sahara↗
PubMed2005

Antimalarial efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, and the combinations of amodiaquine + artesunate and sulfadoxine-pyrimethamine + artesunate in Huambo and Bie provinces, central Angola.

We studied three antimalarial treatments in Caala and Kuito, Angola, in 2002 and 2003. We tested chloroquine (CQ), amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) in Caala, and AQ, SP and the combinations AQ+artesunate (AQ+AS) and SP+artesunate (SP+AS) in Kuito. A total of 619 children (240 in Caala, 379 in Kuito) with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days, with PCR genotyping to distinguish recrudescence from reinfection. PCR-corrected failure proportions at day 28 were very high in the CQ group (83.5%, 95% CI 74.1-90.5), high in the SP groups (Caala: 25.3%, 95% CI 16.7-35.8; Kuito: 38.8%, 95% CI 28.4-50.0), around 20% in the AQ groups (Caala: 17.3%, 95% CI 10.0-27.2; Kuito: 21.6%, 95% CI 14.3-30.6) and very low in the artemisinin-based combination groups (1.2%, 95% CI 0.0-6.4 for each combination AQ+AS and SP+AS). These results show that CQ and SP are no longer efficacious in Caala and Kuito and that the moderate efficacy of AQ is likely to be compromised in the short term if used as monotherapy. We recommend the use of AQ with AS, though this combination might not have a long useful therapeutic life because of AQ resistance.

Amodiaquine↗
PubMed2005

Malaria infection among pregnant women attending antenatal clinics in six Rwandan districts.

OBJECTIVES: The aim of the study was to assess the knowledge, attitude and practices of pregnant women towards malaria and their association with malaria morbidity. METHODS: Cross-sectional malaria survey of 1432 pregnant women attending six health centres, each of them situated in a specific health district in Rwanda from September to October 2002. RESULTS: The overall prevalence of malaria infection was 13.6% and all infections but two were caused by Plasmodium falciparum. The six health districts were significantly different in terms of malaria prevalence, which varied between 11.5% and 15.4% in four and was <5% in the other two districts. The prevalence of anaemia and splenomegaly mirrored that of malaria infection. In three districts, the prevalence of infection was significantly higher in primigravidae than in secundigravidae and multigravidae (P = 0.01), while in two others it did not vary with parity. Bed net use was low - only 13.1% of the women had at least one bed net at home and 8.3% of them slept under it - and significantly different between districts. Most women knew that malaria might have serious consequences for their pregnancy and that insecticide-treated bed nets are useful for malaria prevention. However, the bed net market price [1525 Rwandan Francs (RFr), approximately 1.6] was much higher than that considered as affordable and acceptable (389 RFr, approximately 0.3). CONCLUSION: Malaria in pregnancy is a major problem in Rwanda, even in the districts of low transmission. Bed net use among pregnant women is low. The option of providing free insecticide-treated bed nets to pregnant women should be explored and possibly implemented; it could rapidly increase bed net use and earlier attendance to antenatal clinics with clear benefits for the women's health.

Adult↗
PubMed2005

Usefulness of the Plasmodium falciparum chloroquine resistance transporter T76 genotype failure index for the estimation of in vivo chloroquine resistance in Burkina Faso.

The prevalence of chloroquine (CQ) treatment failure and the genotype failure index was determined in four sentinel sites in Burkina Faso. In three sites, the genotype failure index varied between 1.7 and 3, a result confirming the relationship between the Plasmodium falciparum CQ resistance transporter (Pfcrt) T76 mutation and CQ resistance. In the remaining site, the genotype failure index was unusually low, 1.1, which was significantly different than that in the other sites (P < 0.00001). These findings are discussed. Often but not always, the prevalence of CQ resistance can be correctly estimated by the Pfcrt T76 genotype failure index.

Animals↗
PubMed2005

Plasmodium falciparum genotyping by microsatellites as a method to distinguish between recrudescent and new infections.

In vivo tests for susceptibility to antimalarial drugs require molecular methods to distinguish recrudescence from new infection. The most commonly used DNA markers (merozoite surface proteins [MSPs]) are under immune selective pressure, which might lead to misclassification. We evaluated immunologically neutral microsatellite markers in blood samples collected during a drug efficacy trial in Rwanda. Fifty percent of the infections classified as recrudescent by MSP were classified as new by microsatellite markers. Reciprocally, 23.3% of infections classified as recrudescent by microsatellite markers were identified as new by MSP. In drug efficacy studies, microsatellite markers should complement MSP genotyping to distinguish a recrudescence from a new infection.

Animals↗