Depression of platelet counts in apparently healthy children with asymptomatic malaria infection in a Nigerian metropolitan city

Asymptomatic malaria infection is a common feature of malaria endemic regions in the tropics. In this prospective cross sectional survey, involving 240 children aged 1 to 8 years (Boys = 117, Girls = 123; Ratio 1:1.05), the median platelet count was 115 x 10(9)/L (IQR 97.5-190). Thirty-three out of 240 (13.75%) of the children had thrombocytopenia (platelet count < 100 x 10(9)/L). Malaria parasite was found to exert significant reduction in platelet count. This reduction was more pronounced in children under 5 years and also at higher parasite counts. An inverse relationship was established between parasite density and platelet count (y = -0.017x + 96.2, r = -0.2). Thrombocytopenia is not only a feature of acute malaria infection but also that of asymptomatic malaria infection in the tropics and might be a useful indicator of malaria in children.     

Open randomized study of artesunate-amodiaquine vs. chloroquine-pyrimethamine-sulfadoxine for the treatment of uncomplicated Plasmodium falciparum malaria in Nigerian children

BACKGROUND: Artemisinin-based combination antimalarials are currently considered effective alternatives for the treatment of malaria in Africa, but there are few studies of such combinations in Nigerian children. We assessed the safety, treatment efficacy and effects on gametocyte carriage of the combination of artesunate plus amodiaquine and chloroquine plus pyrimethamine-sulfadoxine in children. METHODS: We evaluated 153 children who were aged 12 years or younger who had uncomplicated Plasmodium falciparum malaria. Patients were randomly assigned a combination of artesunate (4 mg/kg of body weight daily for 3 days) plus amodiaquine (30 mg/kg over 3 days), or chloroquine (25 mg/kg over 3 days) plus pyrimethamine-sulfadoxine (25 mg/kg of the sulfadoxine component at presentation). The primary endpoints were the proportions of children with adequate clinical and parasitological response, late parasitological failure, late clinical failure and early treatment failure. The parasitological cure rates on days 14-28 were also used as the primary endpoints. RESULTS: Both regimens were well tolerated; no child was withdrawn because of drug intolerance. All children treated with artesunate plus amodiaquine had adequate clinical and parasitological response (ACPR), while all but five children treated with chloroquine plus pyrimethamine-sulfadoxine had similar response. Fever clearance times were similar in the two treatment groups. However, the proportion of patients whose parasitaemia cleared by day 2 was significantly higher (100 vs. 50%, P = 0.00001) and parasite clearance was significantly faster (1.7 +/- 0.4 vs. 2.5 +/- 0.8 days, P = 0.0001) in children treated with artesunate plus amodiaquine. The cure rates on days 21 (100%vs. 94%, P = 0.03) and 28 (100%vs. 90%, P = 0.003) were also significantly higher in children treated with artesunate plus amodiaquine than in those treated with chloroquine plus pyrimethamine-sulfadoxine. Overall, a significantly higher proportion of children treated with chloroquine plus pyrimethamine-sulfadoxine carried gametocytes at least once during follow-up compared with those treated with artesunate plus amodiaquine [5 of 50 (10%) vs. 1 of 103 (0.97%), P = 0.01]. CONCLUSION: The combination of artesunate plus amodiaquine is therapeutically superior to a combination of chloroquine plus pyrimethamine-sulfadoxine, and significantly reduced gametocyte carriage following treatment.     

Platelet count, mean platelet volume, platelet distribution width, and plateletcrit do not correlate with optical platelet aggegation responses in healthy volunteers

Background Recent advances in technology have made it possible to record various platelet indices. There have been many reports about platelet indices and platelet disorders. The aim of this study is to investigate whether anatomical indices have a correlation with functional aggregation responses using optical method in healthy adults and to evaluate the predictive significance of platelet indices over platelet aggregation responses.Methods This study was carried on 31 adults whose ages ranging between 20 and 42. Platelet parameters, including platelet count, mean platelet volume, platelet distribution width and plateletcrit were determined in platelet rich plasma using Abbott Cell-Dyn 4.000. Platelet aggregation was induced by adenosine diphosphate, collagen and epinephrine. Optical aggregation was performed using a turbidometric method.Results We have observed no correlation between any of platelet indices measured and platelet aggregation responses.Conclusions As a result, we found no correlation between platelet aggregation responses obtained with optical method and platelet indices proposed as indicators of certain pathologic conditions, and it does not seem possible to use platelet indices as a direct indicator of platelet activation. In conditions where platelet functions should have been assessed, platelet indices alone are inappropriate and further evaluation is necessary with different methods.     

Asymptomatic parasitaemia as a risk factor for symptomatic malaria in a cohort of Ugandan children

OBJECTIVES:To assess the prevalence of asymptomatic parasitaemia, determine its association with symptomatic malaria, and identify independent predictors of asymptomatic parasitaemia in a cohort of children from Kampala, Uganda. METHODS:A total of 316 children aged 6 months to 5 years were recruited from the community. The prevalence of asymptomatic parasitaemia was assessed at enrollment and approximately every 30 days during follow-up. Participants received all of their health care in our clinic, including a standardized approach to the diagnosis and treatment of symptomatic malaria. RESULTS:A total of 283 (90%) subjects completed the full 1-year follow-up and were included in this study, yielding 2557 routine smears. The prevalence of asymptomatic parasitaemia was 17% at enrollment, but 5-8% for the remainder of the study. The risk of developing symptomatic malaria within 30 days was significantly higher in those with a positive routine than in those with a negative one (50%vs. 9%, P < 0.001). Higher parasite densities were associated with increased odds of developing symptomatic malaria within 30 days (P = 0.003). Only 11% of episodes of asymptomatic parasitaemia, involving 6% of subjects, arose and cleared without therapy. In multivariate analysis the only significant risk factor for asymptomatic parasitaemia was whether a child had any episode of symptomatic malaria during the course of the study (OR = 3.0, P = 0.02). CONCLUSION:In our cohort of children from an urban meso-endemic environment, asymptomatic parasitaemia was uncommon and frequently followed by symptomatic malaria. This suggests that presumptive treatment of asymptomatic parasitaemia in such settings would be an efficient means of preventing symptomatic malaria.     

The relation between baseline and 150 min platelet counts in response to selective beta-1-receptor blockade an experimental study on healthy subjects

Summary In 30 healthy volunteers after an oral administration of 50 mg metoprolol basal and 150 min platelet counts were determined. A significant negative correlation (p < 0.01) between the baseline platelet count and the percentage increase at 150 min was shown to be present. It is postulated that this observation reflects interindividual differences between the magnitude of the exchangeable splenic platelet pool.     

Relationships between platelet counts, platelet volumes and reticulated platelets in patients with ITP: evidence for significant platelet count inaccuracies with conventional instrument methods

The platelet count has a primary role in the diagnosis and treatment of idiopathic thrombocytopenic purpura (ITP). This study analysed the accuracy of ITP patient platelet counts determined by Abbott CD-Sapphire (impedance/optical) and Bayer Advia 120 (optical) analyses, compared with a reference immunoplatelet method. Instrument platelet estimates showed broad equivalence in the higher range of observed values, but significant discrepancies against the immunoplatelet count were seen when platelet counts were <10 x 10(9)/l. CD-Sapphire mean platelet volume (MPV) results revealed increased (>12 fl) platelet volumes in eight of eight ITP patients with counts of <20 x 10(9)/l compared with 6/6 and 5/13 patients with platelet counts of 20-50 and >50 x 10(9)/l. In contrast, Bayer Advia MPV values showed no relationship with the platelet count. Increased reticulated platelets were associated with an increasing CD-Sapphire MPV (R(2) = 0.61) and a decreasing platelet count. High (>40%) reticulated platelet values were seen in 9/9 patients with immunoplatelet counts of <20 x 10(9)/l compared with 0/19 patients with platelet counts above 20 x 10(9)/l. There may be a need for caution in the interpretation of platelet counts in ITP patients obtained with conventional instrument methods, and therapeutic decisions should ideally be validated by reference immunoplatelet procedures.     

Epidemiology of congenital malaria in Nigeria: a multi-centre study

Objective To determine the burden of congenital malaria in newborns in Nigeria. Methods In a prospective multi‐centre study, 1875 consecutive mother–baby pairs were enrolled over a continuous 12‐month period. Blood smears were prepared from mothers, neonates, placental aspirates and cord blood within 4 h of delivery. Outcome variables were patent parasitaemia in the mother, placenta, cord and neonate in addition to maternal and neonatal haematocrit. Results Patent parasitaemia was detected in 95 neonates (5.1%). The occurrence varied between study centres, but was found year round in all sites. The mean parasite density among infected neonates was low (48 asexual forms per μl, range 8–200/μl). Maternal and placental parasitaemia were the most important risk factors for patent neonatal parasitaemia (P < 0.0001). Spontaneous clearance of parasitaemia occurred in 62.1% of neonates before day 2. 33.7% were symptomatic within 3 days of birth. Conclusion Congenital malaria is often asymptomatic, clears spontaneously and may not warrant treatment. However, newborns with unexplained fever and refusal to feed in malaria endemic areas should be tested for malaria.     

Relation between dynamic changes of platelet counts and 30-day mortality in severely burned patients

Thrombocytopenia is a common event in severely burned patients and associated with adverse outcome. The underlying relationship between the dynamic changes of platelet counts and mortality has not been well defined. We performed a 6-year retrospective chart of adult patients with a burn index of 50 or greater admitted to two burn centers and collected data on patient demographics, laboratory results, and patient outcomes. The mean daily increase in the platelet count (?PC/?t) from day 3 to day 10 was calculated, and 30-day mortality was determined. For the study, 141 survivors and 65 nonsurvivors were enrolled. The sequential changes in PCs presented a biphasic pattern after admission, with a slump to the nadir during the first 3 days and a subsequent recovery. With respect to 30-day mortality, compared with the AUC of APACHE-Ⅱ score (0.841), no significant difference was noted between ΔPC/ΔT and APACHE-Ⅱ score (p = 0.0648). The ΔPC/ΔT associated with the best discrimination between survivors and nonsurvivors was 20.57 × 10⁹/L due to the cutoff with optimal Youden index (0.453). By multiple logistic regression, ΔPC/ΔT ＜ 20.57 × 10⁹/L was one of the prognostic predictors of 30-day mortality. Furthermore, Kaplan–Meier estimates of hospital survival according to the size of ΔPC/ΔT revealed that a blunted increase with ΔPC/ΔT ＜ 20.57 × 10⁹/L was associated with increased 30-day mortality. A blunted daily increase in PCs, especially ΔPC/ΔT < 20.57 × 10⁹/L, is associated with increased 30-day mortality, which provides prognostic information for mortality risk assessment in severely burned patients.     

Remarkable efficacy of tocilizumab for treating rheumatoid arthritis in patients with high platelet counts

Objectives. To optimize the efficacy of treatment with tocilizumab for rheumatoid arthritis (RA), we comparatively analyzed the outcome of tocilizumab treatment in patients with normal background changes associated closely with IL-6.

Patients and Methods. The study involved 87 patients with RA satisfying the diagnostic criteria of the American College of Rheumatology (ACR) and receiving continuous tocilizumab treatment for 24 weeks or longer. The outcome of tocilizumab treatment in these patients was comparatively analyzed in relation to the baseline platelet count (the high platelet count group and the normal group), pretreatment hemoglobin levels (the low group and the normal platelet count group), and speed of bone destruction (the rapid progression group and slow progression group).

Results. Treatment with tocilizumab significantly improved the 28-joint disease activity score using the erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI), regardless of baseline platelet count, hemoglobin level, or annual speed of bone destruction (ΔTSS). The margins of improvement in DAS28-ESR and CDAI did not differ depending on baseline hemoglobin level or ΔTSS, but the improvement was significantly greater in the high platelet count group than in the normal platelet count group.

Conclusions. These results suggest that in patients with high platelet count, IL-6 is a more important factor involved in RA pathogenesis and that tocilizumab is suitable as a first-line biologic for the treatment of RA patients with high platelet count.     

Patterns of platelet response in idiopathic TTP/HUS: frequency of declining platelet counts with plasma exchange and the recognition and significance of a pseudo refractory state

For thrombotic thrombocytopenic purpura (TTP), daily plasma exchange (TPE) is typically discontinued when the platelet count normalizes (>150 x 10(9)/L). We observed a decline in platelet count during TPE and in patients who appeared pseudo-refractory because of a platelet count plateau (100-150 10(9)/L range). In the present study, we evaluated platelet count trends in TTP patients. Retrospective review of TTP patients from 01/1999 to 12/2004 was completed. Patients were categorized based on platelet count trends: Group I, counts rose then decreased to levels <100 x 10(9)/L; Group II, counts declined following TPE initiation; Group III, counts rose continuously; Group IV, counts decreased after the count was >100 x 10(9)/L. Additionally, we identified pseudo-refractory patients caused by a platelet count plateau (>100 x 10(9)/L but <150 x 10(9)/L). We identified 60 TTP patients. Within Group I (17 patients/17 series/19.1% of total), the mean decrease in platelet count was 67.3% +/- 22.1% following initial rise. Within Group II (24 patients/25 series/28.1% of total), the mean decrease was 28% +/- 5.3% following presentation. Group III included 31 patients/39 series (43.8% of the total). Within Group IV (seven patients/eight series/9.0% of total), the mean decrease was 17.4% +/- 12.6% following a sustained rise >100 x 10(9)/L. With a declining platelet count and daily TPE, it is generally sufficient to stay the course and the decline will reverse. Our limited experience with pseudo-refractory patients supports discontinuing TPE when counts plateau between 100 and 150 x 10(9)/L when a therapy goal is a platelet count of 150 x 10(9)/L. Recognition of this pseudo-refractory state can minimize the risks of prolonged TPE and the risks of adjunct interventions.     

Serum ferritin and other haematological measurements in apparently healthy adults with malaria parasitaemia in Lagos, Nigeria

We studied 300 apparently healthy residents of Lagos aged 16-57 years. Their mean ferritin levels were 99.6 +/- 50.5 microg/l (men aged 20-57) and 66.5 +/- 44 microg/l (women aged 20-53) in aparasitaemic individuals. In parasitaemic subjects, mean ferritin levels were 133.1 +/- 48.3 microg/l (men aged 20-56) and 114.8 +/- 51.1 microg/l (women aged 16-50). Mean haematocrit values for aparasitaemic males were 45.7 +/- 5.6% and 37.9 +/- 5% for females, while mean haemoglobin levels were 153.2 +/- 1.5 microg/l and 124 +/- 3 microg/l, respectively. The mean values for MCV (mean corpuscular volume), MCH (mean corpuscular haemoglobin), MCHC (mean corpuscular haemoglobin concentration) were 101.7 +/- 8fl, 30.6 +/- 2.2 pg, 335 +/- 0.4 g/l and 99.8 +/- 10.1fl, 29.1 +/- 6.5 pg, 335 +/- 6 g/l. Serum iron levels were 34.2 +/- 5 micromol/l and 29.5 +/- 77 micromol/l. All haematological parameters measured were similar in both malaria parasitaemia positive and negative subjects, except ferritin level which was significantly higher in parasitaemic individuals (P < 0.05). Ferritin concentration and malaria density (r = 0.76 in males, r = 0.74 in females, P < 0.05) were positively correlated. Ferritin levels of subjects infected with Plasmodium falciparum were significantly higher than of those infected with P. malariae (P < 0.05). Hence ferritin estimation without examination for malaria parasitaemia in a malaria-endemic region such as Nigeria is not reliable. Asymptomatic malaria parasitaemia increases the ferritin level. Considering the mean ferritin level we found in normal subjects on a balanced diet, routine iron supplementation may not be necessary in the treatment of malaria-induced anaemia in Nigeria.     

The contribution of α+–thalassaemia to anaemia in a Nigerian population exposed to intense malaria transmission

The proportion to which alpha-thalassaemia contributes to anaemia in Africa is not well recognized. In an area of intense malaria transmission in South-West Nigeria, haematological parameters of alpha-thalassaemia were examined in 494 children and 119 adults. The -alpha3.7 type of alpha+-thalassaemia was observed at a gene frequency of 0.27. Nine and 36.5% of individuals were homozygous and heterozygous, respectively. P.falciparum-infection was present in 78% of children and in 39% of adults. The alpha-globin genotypes did not correlate with the prevalence of P. falciparum-infection. alpha+-thalassaemic individuals had significantly lower mean values of haemoglobin, mean corpuscular volume, and mean corpuscular haemoglobin than non-thalassaemic subjects. Anaemia was seen in 54. 7% of children with a normal alpha-globin genotype, in 69.9% of heterozygous (odds ratio: 1.99, 95% confidence interval: 1.32-3.00, P = 0.001), and in 88.4% of homozygous alpha+-thalassaemic children (odds ratio: 7.72, 95% confidence interval: 2.85-20.90, P = 0.0001). The findings show that alpha+-thalassaemia contributes essentially to mild anaemia, microcytosis, and hypochromia in Nigeria.     

3种检测方法在中缅边境疟疾无症状感染者筛查中的比较

目的比较3种不同检测方法对疟疾无症状感染者的检出能力,并了解中缅边境地区的疟疾无症状感染水平。方法2014年7月在中缅边境地区云南省盈江县选择那邦镇、支那乡和缅甸拉咱安置点等3个调查点,采集调查对象血样,制作厚薄血膜和滤纸血标本,分别采用显微镜观察、荧光定量PCR和超敏PCR检测疟原虫感染情况。结果共采集387份血样,显微镜观察检出6例无症状感染者(间日疟5例、恶性疟1例),感染检出率为1.6%;荧光定量PCR检出13例无症状感染者(间日疟12例、恶性疟1例),感染检出率为3.4%;超敏PCR检出38例无症状感染者(间日疟29例、恶性疟9例),感染检出率为9.8%。以显微镜观察为疟原虫感染诊断的金标准,荧光定量PCR检测无症状感染者的灵敏度为100%,特异性为98.2%;超敏PCR检测无症状感染者的灵敏度为100%,特异性91.6%。超敏PCR结果显示,那邦镇的无症状感染检出率最高,为17.1%(22/129),其次为缅甸拉咱难民安置点,为10.0%(11/110),支那乡最低,为3.4%(5/148),3个调查点的感染检出率差异有统计学意义(P<0.05)。检出虫种以间日疟原虫为主,占76.3%,恶性疟原虫占23.7%;女性无症状感染检出率为10.7%(23/215),高于男性的8.7%(15/172),两者差异无统计学意义(P>0.05)。不同年龄组以15~29岁的无症状感染检出率最高,为17.5%(10/57),各年龄组间差异无统计学意义(P>0.05)。结论超敏PCR对疟疾无症状感染者的检出率高于荧光定量PCR和显微镜观察。中缅边境地区人群中存在一定比例的疟疾无症状感染者。     

老年急性感染性疾病血小板四项参数检测的临床意义

目的探讨老年人血小板参数在急性感染性疾病中的临床意义。方法利用库尔特ＪＴ－ＩＲ血球计数仪对１１３名老年急性感染疾病患者的血小板四项参数血小板计数（ＰＬＴ）、血小板压积（ＰＣＴ）、平均血小板体积（ＭＰＶ）、血小板分布宽度（ＰＤＷ）进行测定。结果老年急性感染疾病患者４个组别（急性病毒性肝炎组、败血症组、急性肺炎组、急性腹膜炎组）均显示ＰＬＴ、ＰＣＴ减小，而ＭＰＶ、ＰＤＷ增高。与健康老年组相比差别显著（Ｐ＜０．０５）。结论这对老年人感染疾病的早期诊断有较大的诊断价值     

肝炎肝硬化脾肿大患者脾切除术前后血小板计数变化

目的分析肝炎肝硬化脾大患者行脾切除术前后血小板变化情况及其影响因素。方法收集2003年1月至2008年12月在西安交通大学医学院第二附属医院住院的70例肝炎肝硬化脾亢患者,回顾性分析行脾切除术前后血小板、肝功能、骨髓涂片等结果。结果按Child-Pugh分级的A、B、C三组肝硬化患者中,切脾后血小板回升到正常的比例分别是97.6%（40/41）、79.2%（19/24）和60%（3/5）;肝功能分级与术后的血小板数量恢复相关,肝功能损害越轻,血小板恢复越理想（P〈0.05）;血小板恢复高低与术前骨髓增生情况没有明显的相关性。结论脾切除术是治疗肝炎肝硬化脾亢血小板减少症的主要有效方法,术前肝功能整体评价可以帮助预测切脾后血小板的恢复状况。     

Open randomized study of pyrimethamine-sulphadoxine vs. pyrimethamine-sulphadoxine plus probenecid for the treatment of uncomplicated Plasmodium falciparum malaria in children

BACKGROUND: Increasing drug resistance in Plasmodium falciparum has necessitated renewed search for cheap, effective alternatives to commonly available antimalarials, chloroquine and pyrimethamine-sulphadoxine, for the treatment of malaria in Africa. Probenecid, an inhibitor of organic anion transporters and multiresistance-associated proteins, can chemosensitize P. falciparum to pyrimethamine and sulphadoxine in vitro, but the clinical significance is unclear. We assessed the safety, treatment efficacy, and effects on gametocyte carriage of adding probenecid to pyrimethamine-sulphadoxine. METHODS: We evaluated 151 children aged 12 years or younger who had uncomplicated P. falciparum malaria. Patients were randomly assigned pyrimethamine-sulphadoxine (25 mg/kg of the sulphadoxine component) or pyrimethamine-sulphadoxine as above plus probenecid 20-25 mg/kg of bodyweight in two divided doses daily for 3 days. The primary endpoints were parasitological cure rates on days 14 and 28. RESULTS: Both regimens were well tolerated; no child was withdrawn because of drug intolerance. Fever (1.9 +/- 1.1 vs. 2.4 +/- 1.2 days, P = 0.02) and parasite clearance (2.3 +/- 0.9 vs. 2.7 +/- 1.1 days, P = 0.04) were significantly shorter, and the parasitological cure rate on day 14 (96.2%vs. 83.5%, P = 0.02) but not day 28 (79.4%vs. 72.6%, P = 0.4), was significantly higher in children treated with pyrimethamine-sulphadoxine-probenecid than in those treated with pyrimethamine-sulphadoxine. Gametocyte carriage was similar with both treatment regimens. CONCLUSIONS: The combination of pyrimethamine-sulphadoxine, and probenecid, at a relatively moderate dose, improved treatment efficacy but had no effect on gametocyte carriage. The pyrimethamine-sulphadoxine-probenecid combination merits further evaluation as a potential treatment for use in Nigeria.     

Severe anaemia in Zambian children with Plasmodium falciparum malaria

BACKGROUND: Severe anaemia and cerebral malaria are highly prevalent complications of Plasmodium falciparum malaria among African children. The mechanisms of severe malarial anaemia, and the relative importance of this condition in comparison to cerebral malaria, are not known for many regions of Africa. METHODS We reviewed the records of 6200 children up to 6 years of age admitted to one rural Zambian hospital between 1994 and 1996. Severe malarial anaemia was defined as an haemoglobin concentration < 5.0 g/dl in a patient with asexual forms of P. falciparum in the peripheral blood. Cerebral malaria was defined as impaired consciousness (Blantyre coma score < 5) not attributable to any other cause in a patient with a positive malaria smear. RESULTS Severe malarial anaemia was found in 590 children (9.5% of paediatric admissions) and strictly defined cerebral malaria occurred in 286 children (4.6% of paediatric admissions); 98 of these patients had the combination of both complications. Severe malarial anaemia correlated strongly with the degree of parasitaemia, with malnutrition as indicated by low weight for age, with absence of fever and with presentation late in the malaria season. In comparison, patients with cerebral malaria were more often febrile and presented earlier in the malaria season. The case fatality rate of severe malarial anaemia (0.088) was about half that of cerebral malaria (0.189), but because severe malarial anaemia was more common, these two forms of complicated malaria were implicated in similar numbers of in-hospital paediatric deaths. CONCLUSION Severe anaemia is a more common complication of P. falciparum malaria in hospitalized Zambian children than cerebral malaria and is associated with a similar number of deaths. Malnutrition and changes in immune response patterns due to prolonged exposure to P. falciparum may contribute to the development of this complication.