Acute Falciparum Malaria Research Articles

Therapeutic Efficacy of Artesunate–Amodiaquine Combinations and the Plasma and Saliva Concentrations of Desethylamodiaquine in Children With Acute Uncomplicated Plasmodium falciparum Malaria

The treatment efficacy of artesunate-amodiaquine (AQ) coformulated or copackaged, and the plasma and saliva concentrations of desethylamodiaquine (DEAQ), the active metabolite of AQ, were evaluated in 120 and 7 children, respectively, with uncomplicated Plasmodium falciparum malaria treated with oral daily doses of the 2 formulations for 3 days. All children recovered clinically. Fever clearance (1.1 ± 0.2 vs 1.0 ± 0 days) and parasite clearance times (21.1 ± 10.2 vs 19.0 ± 7.0 hours) in artesunate-AQ coformulated and artesunate-AQ copackaged treated children, respectively, were similar. All children remained aparasitemic for at least 28 days. Blood and saliva samples were collected over 35 days and DEAQ in plasma and saliva was determined by high-performance liquid chromatography. DEAQ was detectable in plasma and saliva within 40 minutes of oral administration of artesunate-AQ. DEAQ concentrations 7 days after the start of therapy were 247.8 and 125.1 ng/mL in plasma and saliva, respectively. The concentration-time curves of plasma and saliva in declining phases were approximately parallel giving a similar half-life of 169.1 ± 16.4 and 142.8 ± 6.5 hours in plasma and saliva, respectively. Clearance from plasma and saliva was also similar (335.6 and 443.4 mL·h·kg, respectively). Area under concentration-time curves (AUC0-35d) for plasma and saliva were 94,744.9 and 74,004.2 ng·mL·h, respectively. In general, Saliva-plasma concentration ratio was 0.25-0.4. DEAQ concentrations in saliva may be useful for monitoring therapy and for the evaluation of the disposition of AQ in children with falciparum malaria treated with AQ-based combination.

Clinical Efficacy of Artemether-Lumefantrine in Congolese Children with Acute Uncomplicated Falciparum Malaria in Brazzaville

The Republic of the Congo adopted artemisinin-based combination therapies (ACTs) in 2006: artesunate-amodiaquine and artemether-lumefantrine as the first-line and second-line drugs, respectively. The baseline efficacy of artemether-lumefantrine was evaluated between March and July 2006 in Brazzaville, the capital city of Congo. Seventy-seven children aged between 6 months and 10 years were enrolled in a nonrandomized study. The children were treated under supervision with 6 doses of artemether-lumefantrine and followed up for 28 days in accordance with the 2003 World Health Organization guideline. Pretreatment (i.e., day 0) and recrudescent Plasmodium falciparum isolates between day 14 and day 28 were compared by the polymerase chain reaction to distinguish between true recrudescence and reinfection. The overall cure rate on day 28 was 96.9% after PCR correction. Reported adverse effects included pruritus and dizziness. Artemether-lumefantrine was highly efficacious in Brazzaville.

Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial

BackgroundPrompt treatment of malaria attacks with arteminisin-based combination therapy (ACT) is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM) with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL) for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal.MethodsThe study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i) PCR corrected adequate clinical and parasitological response (ACPR) at day 28, (ii) ACPR at days 42 and 63, (iii) parasites and fever clearance time, (iv) incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation.ResultsOverall, 310 patients were randomized to receive either AM (n = 157) or AL (n = 153). PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83). Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1). At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32). The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm.ConclusionArtesunate-mefloquine (25 mg/Kg mefloquine) is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients.

Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common

In areas of low malaria transmission, it is currently recommended that a single dose of primaquine (0.75 mg base/kg; 45 mg adult dose) be added to artemisinin combination treatment (ACT) in acute falciparum malaria to block malaria transmission. Review of studies of transmission-blocking activity based on the infectivity of patients or volunteers to anopheline mosquitoes, and of haemolytic toxicity in glucose 6-dehydrogenase (G6PD) deficient subjects, suggests that a lower primaquine dose (0.25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated.

Pharmacokinetic Disposition of Sulfadoxine in Children with Acute Uncomplicated Falciparum Malaria Treated with Sulfadoxine–Pyrimethamine in South West Nigeria

Sulfadoxine (SDX)-pyrimethamine is currently recommended as a partner drug with artesunate in the chemotherapy of malaria. However, information on pharmacokinetic disposition of SDX-pyrimethamine in children is limited. Efforts in this study were thus devoted to evaluation of pharmacokinetic disposition of SDX using high-pressure liquid chromatographic techniques and effects of pharmacokinetic variability on treatment outcome in Nigerian children with falciparum malaria. The blood concentration profile of SDX was similar in patients whose infection responded to treatment and those who failed treatment; mean SDX concentration values were similar for day 3 (179 vs 157 μg/mL, P = 0.734), day 7 (84 vs 51 μg/mL, P = 0.365), and day 14 (50 vs 14 μg/mL, P = 0.151). Extent of exposure (area under the curve) to SDX was also similar in the patients (1196 vs 1013 μg d/mL, P = 0.561). Pearson's correlation, showed significant correlation between area under the curve and D3 or D7 concentration of SDX (P = 0.001, r = 0.702 or P = 0.001, r = 0.835, respectively). Age-stratified analysis showed that SDX concentrations were significantly higher in older children (older than 5 years); the mean maximum concentration (125 vs 295 μg/mL, P = 0.001), extent of exposure (812 vs 1562 μg d/mL, P = 0.001), day 3 concentration (98 vs 250 μg/mL, P = 0.001), and day 7 concentration (54 vs 128 μg/mL, P = 0.007) were higher. The study revealed no differences in posttreatment blood SDX concentrations in patients who responded to treatment and those who failed to respond to treatment. Furthermore, there was an age-related pharmacokinetic variability of SDX in the group of children studied with potential impact on treatment outcome.

Review of pyronaridine anti-malarial properties and product characteristics

Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic Disease and has been used in China for over 30 years for the treatment of malaria. Pyronaridine has high potency against Plasmodium falciparum, including chloroquine-resistant strains. Studies in various animal models have shown pyronaridine to be effective against strains resistant to other anti-malarials, including chloroquine. Resistance to pyronaridine appears to emerge slowly and is further retarded when pyronaridine is used in combination with other anti-malarials, in particular, artesunate. Pyronaridine toxicity is generally less than that of chloroquine, though evidence of embryotoxicity in rodents suggests use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and children with acute uncomplicated falciparum and vivax malaria in artemisinin-combination therapy. Clinical data for mono or combined pyronaridine therapy show excellent anti-malarial effects against P. falciparum and studies of combination therapy also show promise against Plasmodium vivax. Pyronaridine has been developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate for the treatment of acute uncomplicated P. falciparum malaria and blood stage P. vivax malaria with the name of Pyramax® and has received Positive Opinion by European Medicines Agency under the Article 58 procedure.

Hepcidin demonstrates a biphasic association with anemia in acute Plasmodium falciparum malaria

Hepcidin levels are high and iron absorption is limited in acute malaria. The mechanism(s) that regulate hepcidin secretion remain undefined. We have measured hepcidin concentration and cytokines in 100 Kenyan children with acute falciparum malaria and different degrees of anemia. Hepcidin was increased on admission and fell significantly one week and one month after treatment. The association of hepcidin with hemoglobin was not linear and hepcidin was very low in severe malarial anemia. Parasite density, IL-10 and IL-6 were significantly associated with hepcidin concentration. Hepcidin response to acute malaria supports the notion of iron sequestration during acute malaria infection and suggests that iron administration during acute malaria is futile. These data suggest iron supplementation policies should take into account the high hepcidin levels and probable poor utilization of iron for up to one week after treatment for the majority of patients with acute malaria.

Clinical study on efficacy and safety of piperamisinin (dihydroartemisinin-piperaquine) in uncomplicated falciparum malaria

Background: Dihydroartemisinin and piperaquine phosphate co-formulated tablets manufactured from Pharmaceutical Companies of Republic of China namely Artekin and Artepip had been studied in Clinical Research Unit (Malaria) No. (1) DSGH (1000-Beds) Mingalardon in 2006-2008 for the treatment of uncomplicated falciparum malaria and it was found to be safe and effective. Piperamisinin, a combined tablet, containing 50mg dihydroartemisinin and 350 mg piperaquine phosphate, is first produced from Myanmar Pharmaceutical Factory (MPF) of Ministry of Industry in 2009. Methods: An hospital based clinical study following 28 days WHO standard therapeutic efficacy test was conducted at 1000 Bedded Hospital in Mingalardon, Yangon Division, 300 Bedded Hospital in Myitkyinar, Kachin State and 100 Bedded Hospital in Lashio, Shan State on a total of 23 patients with acute uncomplicated falciparum malaria between March to October 2010, to study the effectiveness, tolerability and safety of piperamisinin. The patients who met the inclusion criteria were given Piperamisinin combined tablets with the dosage of 3 tablet at 0-Hr, 24-Hr & 48-Hr. The patients were thoroughly assessed and monitored clinically including ECG, parasitologically, haematologically, and biochemically (Blood sugar, urea & serum creatinine) for side effects during the 28 days of confinement at the respective hospitals. Results: The participants were 29.52 years old on average and ranged from 14 to 57 years of age. Initial parasitaemia was 1983.16 ± 2685.45 per μL whereas initial temperature was 37.8 ± 0.88 °C. Fever clearance time (FCT) and parasite clearance time (PCT) were 14.63 ± 10.72 hours 27.18 ± 11.44 hours respectively. Neither early treatment failure nor late treatment failure was observed. Adequate clinical and parasitological response (ACPR) was 100 percents.There were no serious clinical or laboratory side effects observed in the study. Conclusion: In general, Domestically manufactured Piperamisinin combined tablet is safe and effective for the treatment of uncomplicated falciparum malaria patients in three different states and divsion of Myanmar.

Therapeutic Efficacy of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Northern Ethiopia

Introduction. Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. This has posed major challenges to malaria control in sub-Saharan Africa. Objective. The aim of the study was to evaluate the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in North Ethiopia. Methods. This prospective study was undertaken during August–November 2009 on 71 malaria patients that fulfilled the inclusion criteria set by the WHO. Patients were followed up for 28 days. Thick and thin blood films were prepared by Giemsa stain for microscopy to determine parasite density. A standard six-dose regimen of artemether-lumefantrine was administered over three days and was followed up with clinical and parasitological evaluations over 28 days. Results. The cure rate (ACPR) was found to be high (97.2%) in this study. The parasite and fever clearance time was also rapid. Artemether-lumefantrine for the treatment of acute uncomplicated Plasmodium falciparum malaria in the study area showed 97.2% cure rate and only 2.8% failure rate. Conclusion. The result showed that the drug could continue as first line for the treatment of uncomplicated Plasmodium falciparum malaria in the study area. The efficacy of artemether-lumefantrine needs to be carefully monitored periodically in sentinel sites representing different areas of the country.

Human African trypanosomiasis in travellers to Kenya

In this issue, two cases are described of human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense. They occurred recently in European tourists returning from Masai Mara area, Kenya, to Germany and Belgium, respectively [1,2]. These are, to our knowledge, the first two HAT cases described in travellers to Kenya in the last 12 years, while several cases were reported mainly from Tanzania (Serengeti and Tarangire game parks), Zambia, Zimbabwe and Malawi [3]. HAT, also known as sleeping sickness, is caused by a flagellated trypanosome protozoan, which is transmitted by Glossina (tsetse) flies. T. b. gambiense – found in western and central Africa – is transmitted mainly by G. palpalis, which prefers areas of vegetation near rivers and cultivated fields; T. b. rhodesiense – found in eastern and southern Africa – is transmitted predominantly by G. morsitans, which feeds on wild animals in savannah areas, far from human settlements [4]. While humans are the only substantial reservoir of T. b. gambiense, T. b. rhodesiense HAT is a zoonosis and humans occasionally visiting affected areas (usually for hunting or tourism) are accidental hosts. T. b. gambiense HAT is usually characterised by a chronic course of illness, lasting months to years, whereas T. b. rhodesiense HAT causes a more acute and aggressive course, clinically resembling acute septicaemia or severe falciparum malaria, with death occurring within days, weeks or months of the untreated disease. HAT of both forms is characterised by two distinct phases: the early or haemo-lymphatic stage and the late or meningoencephalitic stage, with trypanosome invasion of the central nervous system of patients surviving the early stage [5].

Artesunate/dihydroartemisinin pharmacokinetics in acute falciparum malaria in pregnancy: absorption, bioavailability, disposition and disease effects

AIMTo determine if reported lower plasma concentrations of artemisinin derivatives for malaria in pregnancy result from reduced oral bioavailability, expanded volume of distribution or increased clearance.METHODSIn a sequentially assigned crossover treatment study, pregnant women with uncomplicated falciparum malaria received i.v. artesunate (i.v. ARS) (4 mg kg−1) on the first day and oral ARS (4 mg kg−1) on the second, or, oral on the first and i.v. on the second, in both groups followed by oral ARS (4 mg kg−1 day−1) for 5 days. Plasma concentrations of ARS and dihyroartemisinin (DHA) were measured by liquid chromatography-mass-spectrometry on days 0, 1, 2 and 6. Controls were the same women restudied when healthy (3 months post partum).RESULTSI.v. ARS administration resulted in similar ARS and DHA pharmacokinetics in pregnant women with malaria (n = 20) and in controls (n = 14). Oral administration resulted in higher total drug exposure in pregnancy [AUC (95% CI) in (ng ml−1 h)/(mg kg−1)] of 55.1 (30.1, 100.0) vs. 26.5 (12.2, 54.3) for ARS, P = 0.002 and 673 (386, 1130) vs. 523 (351, 724) for DHA, P = 0.007. The corresponding median absolute oral bioavailability (F%) was 21.7 (12.6, 75.1) vs. 9.9 (6.0, 36.81) for ARS (P = 0.046) and 77.0 (42.2, 129) vs. 72.7 (42.0, 87.7) for DHA, P = 0.033. Total DHA exposure was lower at day 6 in pregnant women with malaria (P < 0.001) compared with day 0 or 1, but not in the controls (P = 0.084).CONCLUSIONSThis study demonstrates the effects of malaria on oral ARS drug disposition are greater than those of pregnancy. This probably results from a disease related reduction in first pass metabolism. The data are reassuring regarding current dosing recommendations.

How Do We Best Diagnose Malaria in Africa?

How Do We Best Diagnose Malaria in Africa?

Characteristics and Spectrum of Disease Among Ill Returned Travelers from Pre- and Post-Earthquake Haiti: The GeoSentinel Experience

To describe patient characteristics and disease spectrum among foreign visitors to Haiti before and after the 2010 earthquake, we used GeoSentinel Global Surveillance Network data and compared 1 year post-earthquake versus 3 years pre-earthquake. Post-earthquake travelers were younger, predominantly from the United States, more frequently international assistance workers, and more often medically counseled before their trip than pre-earthquake travelers. Work-related stress and upper respiratory tract infections were more frequent post-earthquake; acute diarrhea, dengue, and Plasmodium falciparum malaria were important contributors of morbidity both pre- and post-earthquake. These data highlight the importance of providing destination- and disaster-specific pre-travel counseling and post-travel evaluation and medical management to persons traveling to or returning from a disaster location, and evaluations should include attention to the psychological wellbeing of these travelers. For travel to Haiti, focus should be on mosquito-borne illnesses (dengue and P. falciparum malaria) and travelers' diarrhea.

Usefulness of automated cell counter in detection of malaria in a cancer set up-Our experience

Malaria diagnosis presents a challenge to all laboratories. In malaria-endemic areas, there is a need for rapid, sensitive and cost-effective method to effectively screen all samples, especially when the workload is very high. Various hematology analyzers have been investigated for detection of malaria in the past. Here, we present our experience of malaria detection in a cancer hospital where a large number of complete blood count requests are received either before or during chemotherapy. Fever, being a very common symptom in cancer patients, causes a suspicion of malaria. This study was conducted to assess the usefulness of hematology cell counter, viz. WBC-DIFF and WBC/BASO scatter plots and the flaggings generated in malaria-positive cases. The occurrence of pseudoeosinophilia as reported by previous studies was also assessed. The parasitic index was determined and its correlation with the abnormalities found on the Hematology analyzer was also studied. Blood samples were collected from 80 out-patient department and inpatients with various solid as well as hematological malignancies, who presented with acute febrile illness during September 2010 and January 2012, and for whom complete blood cell analysis and peripheral smear for malaria parasite had been requested. Of the 80 patients who presented with fever and suspicion of malaria, 29 patients were positive for malaria and 10 cases were diagnosed incidentally by the findings on the cell counter and were confirmed by Giemsa-stained blood smears. The sensitivity and specificity of the abnormalities detected in the WBC-Diff channel in detecting malaria is 82% and 100% respectively. Using WBC-BASO channel abnormality for initial diagnosis the sensitivity and specificity is 50% and 92.5% respectively. The sensitivity and specificity with respect to pseudoeosinophilia is 18% and 100% respectively. The most common WBC and PLT flags were leukopenia, atypical lymphocytes, lymphopenia, WBC abnormal scattergram, platelet clumps, thrombocytopenia, platelet abnormal distribution flag. The instrument provides significantly valuable diagnostic parameters in detecting acute Plasmodium vivax malaria; however, it is not very useful for acute falciparum malaria infection. It is suggested that the laboratories using the hematology analyzers should be aware of such specific parameters, even in the absence of a clinical request.

Control of Plasmodium falciparum erythrocytic cycle: γδ T cells target the red blood cell–invasive merozoites

AbstractThe control of Plasmodium falciparum erythrocytic parasite density is essential for protection against malaria, because it prevents pathogenesis and progression toward severe disease. P falciparum blood-stage parasite cultures are inhibited by human Vγ9Vδ2 γδ T cells, but the underlying mechanism remains poorly understood. Here, we show that both intraerythrocytic parasites and the extracellular red blood cell–invasive merozoites specifically activate Vγ9Vδ2 T cells in a γδ T cell receptor–dependent manner and trigger their degranulation. In contrast, the γδ T cell–mediated antiparasitic activity only targets the extracellular merozoites. Using perforin-deficient and granulysin-silenced T-cell lines, we demonstrate that granulysin is essential for the in vitro antiplasmodial process, whereas perforin is dispensable. Patients infected with P falciparum exhibited elevated granulysin plasma levels associated with high levels of granulysin-expressing Vδ2+ T cells endowed with parasite-specific degranulation capacity. This indicates in vivo activation of Vγ9Vδ2 T cells along with granulysin triggering and discharge during primary acute falciparum malaria. Altogether, this work identifies Vγ9Vδ2 T cells as unconventional immune effectors targeting the red blood cell–invasive extracellular P falciparum merozoites and opens novel perspectives for immune interventions harnessing the antiparasitic activity of Vγ9Vδ2 T cells to control parasite density in malaria patients.

Assessment of the efficacy of first-line antimalarial drugs after 5 years of deployment by the National Malaria Control Programme in C&amp;ocirc;te d'Ivoire

Correspondence: Andre T Offianan Malariology Department, Institut Pasteur de Cote d’Ivoire, PO Box 490, Abidjan 01, Cote d’Ivoire Tel +225 22 44 84 25 Fax +225 22 48 53 05 Email andre_offianan@yahoo.fr Background: The emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. Artesunate + amodiaquine (ASAQ) and artemetherlumefantrine (AL) are respectively the firstand second-line treatments for uncomplicated falciparum malaria in Cote d’Ivoire. A comparison of the efficacy and safety of these two drug combinations was necessary to make evidence-based drug treatment policies. Methods: In an open-label, non inferiority, randomized, controlled clinical trial, children aged 6–59 months were randomized to receive ASAQ or AL. Both drug regimens were given for 3 days, and follow-up was for 28 days. The primary endpoint was the 28-day cure rates and was defined as proportion of patients with polymerase chain reaction (PCR)-corrected cure rate after 28 days of follow-up. Findings: A total of 251 patients who were attending the Ayame and Dabakala hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive ASAQ (128) and AL (123). The intention-to-treat analysis showed effectiveness rates of 94.5% and 93.5% for ASAQ and AL, respectively on day 28. After adjustment for PCR results, these rates were 96.1% and 96.8%, respectively. On day 28, the per-protocol analysis showed effectiveness rates of 98.4% and 96.6% for ASAQ and AL, respectively. After adjustment by PCR for reinfection, these rates were 100% for each drug, and both regimens were well tolerated. Conclusion: ASAQ and AL remain efficacious treatments of uncomplicated falciparum malaria in Ivorian children 5 years after adoption. The efficacy of ASAQ and AL in Cote d’Ivoire requires, therefore, continuous monitoring and evaluation.

Effect of Acute Plasmodium falciparum Malaria on Reactivation and Shedding of the Eight Human Herpes Viruses

Human herpes viruses (HHVs) are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8). We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0) and 14 days later (after treatment), or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria.

Hematologic Parameters in Pediatric Uncomplicated Plasmodium falciparum Malaria in Sub-Saharan Africa

Hematologic changes in acute and convalescent uncomplicated Plasmodium falciparum malaria have not been well studied, particularly in young children in Africa. Hematologic data were obtained for 3,044 children less than five years of age in seven randomized controlled trials at 14 sites. Using paired analysis between day 28 and baseline in patients without parasitologic failure as a proxy for malaria-induced effects, we found a statistically significant but clinically modest increase in leukocyte counts (5%) resulting from a larger increase in neutrophils (43%) than the decrease in lymphocytes counts (-16%); levels of hemoglobin and platelets decreased (-13% and -49%, respectively). Multivariate random effects analysis showed trends during follow-up (increased levels of hemoglobin, platelets and lymphocytes, and decreased levels of leukocytes and neutrophils) and identified explanatory variables. The risk of neutropenia increased with follow-up time independent of treatment outcome, and was lower with age, higher baseline parasitemia, and artemisinin combination treatment. These analyses provides information on hematologic variations caused by malaria.

Plasmodium falciparum gametocyte carriage, sex ratios and asexual parasite rates in Nigerian children before and after a treatment protocol policy change instituting the use of artemisinin-based combination therapies

The effects of artemisinin-based combination therapies (ACTs) on transmission of Plasmodium falciparum were evaluated after a policy change instituting the use of ACTs in an endemic area. P. falciparum gametocyte carriage, sex ratios and inbreeding rates were examined in 2,585 children at presentation with acute falciparum malaria during a 10-year period from 2001-2010. Asexual parasite rates were also evaluated from 2003-2010 in 10,615 children before and after the policy change. Gametocyte carriage declined significantly from 12.4% in 2001 to 3.6% in 2010 (χ2 for trend = 44.3, p < 0.0001), but sex ratios and inbreeding rates remained unchanged. Additionally, overall parasite rates remained unchanged before and after the policy change (47.2% vs. 45.4%), but these rates declined significantly from 2003-2010 (χ2 for trend 35.4, p < 0.0001). Chloroquine (CQ) and artemether-lumefantrine (AL) were used as prototype drugs before and after the policy change, respectively. AL significantly shortened the duration of male gametocyte carriage in individual patients after treatment began compared with CQ (log rank statistic = 7.92, p = 0.005). ACTs reduced the rate of gametocyte carriage in children with acute falciparum infections at presentation and shortened the duration of male gametocyte carriage after treatment. However, parasite population sex ratios, inbreeding rates and overall parasite rate were unaffected.

Clinical efficacy of a tea-bag formulation of &lt;i&gt;Cryptolepis sanguinolenta&lt;/i&gt; root in the treatment of acute uncomplicated falciparum malaria

To evaluate the clinical efficacy and safety of a tea bag formulation of the root of C. sanguinolenta This is a prospective descriptive open trial. Patients were recruited from Korle-Bu, Mamprobi and Dansoman Polyclinics. Forty-four subjects with uncomplicated malaria were recruited for the study. Patients presented with clinical symptoms of malaria. Laboratory investigations conducted included malaria parasite counts, haematological indices and biochemical tests which were obtained before, during and after a 5-day treatment period, up to Day 28 posttreatment. All patients in the study were symptomatic with significant parasitaemia. Patients were given one teabag three times a day, that is, morning, noon and night, for five days of treatment. Fifty percent of the patients were cleared of their P. falciparum parasitaemia by 72 hours, and all by Day 7. Presenting symptoms of fever, chills, nausea and vomiting cleared rapidly, all by Day 3, but resolution of haematological and biochemical abnormalities associated with malaria was generally slow, a feature seen in malaria post-treatment. The overall cure rate was 93.5% due to two cases of recrudescence on Days 21 and 28. The laboratory findings did not suggest any toxicity. On the basis of fever clearance and disappearance of parasitaemia by Day 7, the formulation has been shown to be non-toxic and highly effective in the treatment of acute uncomplicated malaria.