An in vitro evaluation of extracts from some medicinal plants in Kenya against herpes simplex virus

The extracts from 21 medicinal plants commonly used in traditional remedies in Kenya were screened for antiviral activity against wild type 7401H strain herpes simplex virus type 1. The plant extracts exhibited antiviral activity against the virus in the plaque and yield reduction assays. The results reveal that twelve plants may contain constituents that could be exploited for the management of HSV infections. Although the extracts used in these experiments contain a complex matrix of a large number of compounds the results indicate that useful compounds can be isolated for further exploitation.     

Epidemiological study of the G serotype distribution of group A rotaviruses in Kenya from 1991 to 1994.

An epidemiological study on the G serotype distribution of group A rotaviruses (GARV) isolated in Kenya was carried out in one urban hospital in Nairobi and in two rural hospitals in Nanyuki and Kitui to clarify the prevalent G serotypes before future introduction of the ready licensed rotavirus vaccine in Kenya. A total of 1,431 stool specimens were collected from children, who were mainly outpatients, aged from 0 to 6 years old with acute gastroenteritis from August 1991 to July 1994. Samples positive for GARV by conventional ELISA were then analyzed by subgrouping and serotyping ELISA and by PAGE. To ascertain the G serotypes of viruses in samples that were unable to be typed by serotyping ELISA, polymerase chain reaction was also attempted. The prevalence of GARV was 28.4% in the urban hospital, 22.5% in Nanyuki, and 13.7% in Kitui. Among rotavirus-positive samples, subgroup II rotaviruses were detected in 63.1%, and subgroup I rotaviruses were 25.9%. Serotype G4 was most prevalent, accounting for 41.6% followed by 23.3% of serotype G1, 17.0% of serotype G2, and serotype G3 was rarely isolated. Seven strains of serotype G8/P1B rotavirus was detected for the first time in Kenya by RT-PCR. Eleven specimens with an unusual composition of subgroup, serotype, and electropherotype were atypical GARV in which the P-serotype was P1A, P1B, or P2. Although uncommon GARV serotype G8/P1B and atypical GARV were detected, the four major GARV serotypes, G1 through G4, should be targeted at this moment for vaccination to control this diarrheal disease in Kenya. Continuous monitoring of the G- and P-serotype distribution of GARV should provide important information about the impact of rotavirus vaccination in Kenya.     

Estimating global and regional morbidity from acute bacterial meningitis in children: assessment of the evidence

Aim

To estimate global morbidity from acute bacterial meningitis in children.

Methods

We conducted a systematic review of the PubMed and Scopus databases to identify both community-based and hospital registry-based studies that could be useful in estimation of the global morbidity from bacterial meningitis in children. We were primarily interested in the availability and quality of the information on incidence rates and case-fatality rates. We assessed the impact of the year of study, study design, study setting, the duration of study, and sample size on reported incidence values, and also any association between incidence and case-fatality rate. We also categorized the studies by 6 World Health Organization regions and analyzed the plausibility of estimates derived from the current evidence using median and inter-quartile range of the available reports in each region.

Results

We found 71 studies that met the inclusion criteria. The only two significant associations between the reported incidence and studied covariates were the negative correlation between the incidence and sample size (P < 0.001) and positive correlation between incidence and case-fatality rate (P < 0.001). The median incidence per 100 000 child-years was highest in the African region – 143.6 (interquartile range [IQR] 115.6-174.6), followed by Western Pacific region with 42.9 (12.4-83.4), the Eastern Mediterranean region with 34.3 (9.9-42.0), South East Asia with 26.8 (21.0-60.3), Europe with 20.8 (16.2-29.7), and American region with 16.6 (10.3-33.7). The median case-fatality rate was also highest in the African region (31.3%). Globally, the median incidence for all 71 studies was 34.0 (16.0-88.0) per 100 000 child-years, with a median case-fatality rate of 14.4% (5.3%-26.2%).

Conclusions

Our study showed that there was now sufficient evidence to generate improved and internally consistent estimates of the global burden of acute bacterial meningitis in children. Although some of our region-specific estimates are very uncertain due to scarcity of data from the corresponding regions, the estimates of morbidity and case-fatality from childhood bacterial meningitis derived from this study are consistent with mortality estimates derived from multi-cause mortality studies. Both lines of evidence imply that bacterial meningitis is a cause of 2% of all child deaths.Meningitis is an infectious disease affecting the brain membrane and spinal cord (1). Globally, bacterial meningitis is the most severe type of meningitis, mainly caused by a triad of species Neisseria meningitidis, Streptocccus pneumonia, and Haemophilus influenzae (2). While viral meningitis is usually a self-limiting disease with good prognosis, bacterial meningitis is potentially fatal, requiring urgent medical assistance and management with antibiotics treatment (3). Various estimates of the burden of bacterial meningitis have been proposed to date, but they have mainly focused on mortality (4), long-term sequels (5), or etiology-specific morbidity and mortality (6-8).Interestingly, there have been no comprehensive attempts to estimate the overall global burden of bacterial meningitis in children. This is not surprising, because such attempt would face almost insurmountable methodological challenges. First, there is a problem with case definition of “bacterial meningitis” (9). In low resource settings, where the problem is most common, many children may present with “purulent meningitis,” whose cause is highly likely bacterial, but laboratory capacity may not be sufficient to isolate the causal agent and confirm the diagnosis. This leads to a discrepancy between morbidity burden estimates based on “all purulent meningitis” and “laboratory confirmed meningitis” – the latter always being lower than the former, but to a different extent in different contexts (10). The second large methodological obstacle is the problem of “meningitis belt.” The meningitis belt is the band of countries extending from Senegal to Ethiopia, characterized by semi-arid climate, dry seasons, and dusty winds, with seasonal outbreaks of meningococcal meningitis being recorded since the beginning of the 20th century (11). The problem with these epidemics is that they can last for several years and dramatically change the importance of meningococcus in comparison to the other two bacterial agents (S. pneumoniae and H. influenzae) both regionally and globally (11). This makes it difficult to express the “burden of disease” for any given year, because it will be very different in intra-epidemic and inter-epidemic years. Moreover, the extent of vaccine coverage against N. meningitidis, S. pneumoniae and H. influenzae is changing the burden rapidly and rather dramatically in many places, rendering the scarce evidence from before the period of vaccination rather useless and indicates a need of revision (12). Finally, the emergence of HIV/AIDS pandemic led to a substantial number of infected children, whose resistance to other infections is impaired and they present a specific category of population in which the rates of incidence and case-fatality rates may be very different from those in other children (13).It is apparent that meningitis continues to contribute significantly to global mortality and morbidity, but the impact of the efforts to control it is difficult to estimate given that we do not have comprehensive estimates of global morbidity patterns. Understanding the global morbidity from bacterial meningitis would be useful because it would also help to validate the existing mortality estimates through application of appropriate case-fatality rates. The purpose of the present study is to provide a comprehensive assessment of the evidence that is available for estimating the global morbidity from acute bacterial meningitis in children globally. We will also propose initial, robust estimates of the burden, with suggestions on the possible ways to address the methodological challenges in future studies.     

10种抗精神病药物对多巴胺D2受体占有率的模拟分析

目的 模拟分析10种抗精神病药物氟哌啶醇（haloperidol）、舒必利（sulpiride）、美哌隆（melperone）、氯氮平（clozapine）、喹硫平（quetiapine）、利培酮（risperidone）、齐拉西酮（ziprasidone）、瑞莫必利（remoxipride）、氨磺必利（amisulpride）、雷氯必利（raclopride）口服给药后在人体内对多巴胺D₂受体（DRD₂）占有的时间过程。方法 通过对10种抗精神病药物的口服给药和静脉给药的药动学数据模拟计算获取建模的药动学（PK）参数;通过已发表的文献数据计算获取10种抗精神病药物的结合动力学（BK）参数和细胞内DRD₂受体合成动力学（TK）参数;基于获取的PK、BK、TK参数建立10种抗精神病药物的DRD₂受体占有率数学计算模型（PK-BK-TK模型）。结果 已上市的9种（不包含雷氯必利）抗精神病药物在临床推荐剂量下对DRD₂的最大受体占有率均在65%以上,预测的DRD₂受体占有率曲线与其临床药效持续时间有良好的一致性;雷氯必利的合理给药剂量为2mg。结论 利用PK-BK-TK数学模型能准确预测抗精神病药物口服后在人体内对DRD₂受体的占有过程。该模型可为评估化合物在体内拮抗DRD₂受体的活性与潜在毒性提供一种新的研究思路和方法。     

中国不同地区狂犬病病毒种群分布的差异

目的 明确我国不同地区流行的狂犬病病毒种群类别及其流行特征。方法 汇总GenBank数据库所有中国狂犬病流行株的N、G和全基因组序列以及国家狂犬病实验室新测定毒株序列,分别构建N基因和G基因种系发生树,明确每个毒株的种群归属。统计各地区流行株的种群类别及不同种群的毒株数量。结果 全国共流行6个毒株群（ChinaⅠ~Ⅵ）,云南和湖南是我国大陆种群最丰富省份,均有多达4个群流行;河南、福建等6省份均有3个毒株群流行;上海、江西等8省份皆流行2个病毒种群;北京、天津等14省份目前只监测到1个毒株群流行。优势毒株群ChinaⅠ已蔓延至我国东北部和西部地区,共计覆盖25个省份;China Ⅲ群近年在内蒙古、新疆地区的野生动物中流行且溢出至家畜中;China Ⅳ是青海、西藏地区的流行种群,同时流行于内蒙古、黑龙江地区的野生动物中。结论 我国不同地区狂犬病病毒种群类别和数量差异明显。     

Hepatitis B in the family

During a 3-year period (1992–1995), 239 index cases of hepatitis B virus (HBV) infection and 459 members of their households from the Osijek-Baranja county were examined. The aim of the study was to determine the spread of HBV infection in the families with a member verified as a virus carrier, and to identify the family members with the highest risk of infection according to kinship degrees. The retrospective and prospective methods were used in the study. The probable route of infection was assessed by the use of an epidemiologic questionnaire, and the serologic status of the study subjects concerning infection with HBV was determined by enzyme immunoassays (HBsAg, anti-HBs, anti-HBe and anti-HBc). The first member of a family identified as a virus carrier was considered an index case. HBV infection was demonstrated in 334 (47.85%) out of a total of 698 subjects. Only 21 (6.28%) of the 334 subjects with verified HBV infection developed the clinical picture of acute hepatitis B. The ratio of clinically manifest vs inapparent infection was 1:16. Serologic traces of infection were detected in 95 of the 459 family members of the index cases, yielding a mean rate of the infection among the virus carrier family members of 20.70%.     

Poliomyelitis: epidemiology and prophylaxis. 4. Serological and virological surveys conducted after a mass vaccination campaign for the control of a threatening poliomyelitis epidemic.

In 1973, a type 1 poliomyelitis epidemic in Kenya was curtailed at an early stage by two mass distributions of trivalent oral vaccine. It was considered useful to know the immunity status of the child population that had resulted from the vaccine distributions and that had presumably contributed to its control. We also wished to know to what extent wild and vaccine virus strains were in circulation after the mass vaccination campaign. Anal swabs and blood were collected from a sample of the children in four areas where the efficiency of vaccine distribution had varied, and the results of virus isolation attempts and antibody tests are reported. Three poliovirus strains were isolated. It was surprising that, in general, the herd immunity after two vaccination rounds did not substantially differ from that found in Kenya on other occasions. Possible reasons for these results are discussed.     

Leprosy epidemics during history increased protective allele frequency of PARK2/PACRG genes in the population of the Mljet Island, Croatia

Introduction

Two regulatory polymorphisms (rs1040079 and rs9356058) shared by PARK2 and PACRG genes were identified as major risk variants for leprosy susceptibility. The aim of this study was to investigate if allele frequencies of these polymorphisms in the isolated population of the island of Mljet, which served as a quarantine for leprosy patients during past centuries, were different to allele frequencies in two control populations with no history of leprosy.

Subjects and methods

This study included 88 unrelated Caucasian individuals from the island of Mljet while two control groups included 93 individuals from the island of Rab and 160 individuals from the region of Split. Genotyping for rs1040079 and rs9356058 was performed by “real-time” PCR analysis. We also compared the allele frequency of the rs9356058 polymorphism from the population of Mljet with allele frequencies derived from the existing genome wide association scans in two additional island populations, Vis (924 subjects) and Korcula (909 subjects).

Results

We found a significant increase in the frequency of rs9356058 allele C in the population of Mljet when compared to both control groups. We also observed a significant increase in the frequency of rs1040079 allele A in the population of Mljet when compared with the population of Rab, however this increase was not significant when compared with the population of Split. Allele frequencies of both examined polymorphisms did not differ between the two control populations. Protective haplotype rs9356058-rs1040079 CA was also more frequent in the population of Mljet compared with the Rab and Split populations. In addition, an increase of frequency of rs9356058 allele C was also observed in the population of Mljet when compared with the frequency in the Korcula population.

Conclusion

The results of our study show the association of polymorphisms rs9356058 and rs1040079 in gene PARK2/PACRG with leprosy. The results of our study indicate that exposure to leprosy and mortality in the population caused by leprosy on Mljet resulted in the selection of rs9356058 “protective” C allele in the PARK2 gene, while this was not observed in the two control groups. This is the first study to assess the genetic susceptibility to leprosy in a European population.     

Reversal of cardiomyopathy in patients with congestive heart failure secondary to tachycardia

Objectives

Tachycardia-induced cardiomyopathy (TCM) is a reversible cause of heart failure. Little is known of the characteristics of tachycardia associated with the development of left ventricular (LV) dysfunction and the reversal of cardiomyopathy after cure of tachycardia. This study aimed to examine the reversal of cardiomyopathy in patients undergoing ablation with congestive heart failure secondary to tachycardia.

Methods

A total of 625 patients underwent radiofrequency ablation for tachycardiarrhymias between January 2009 and July 2011. Echocardiography analysis was performed to identify patients with depressed LV function, defined as a left ventricular ejection fraction <50 %. Patients with preexisting structural heart disease (n?=?10) were excluded. NT-pro-B-type natriuretic peptide (NT-proBNP) assessment was performed before ablation in patients considered to have TCM (n?=?17). Repeated echocardiography study and NT-proBNP assessment were measured after a mean follow-up of 3 months. Levels of NT-proBNP before and after ablation were compared. Reversal of cardiomyopathy was also assessed.

Results

The incidence of TCM was 2.7 % (12 males; age, 35.8?±?17.1 years). Successful ablation was performed in 16 of 17 patients (94.1 %). There was a significant improvement in left ventricular ejection fraction (36.7?±?7.5 vs. 59.4?±?9.7 %; P?<?0.001). The mean left ventricular end-diastolic diameter before treatment was 59.5?±?8.3 mm (range, 43 to 70), compared with 51.9?±?7.4 mm (range, 40 to 67) (P?=?0.009) after 3 months follow-up. The levels of NT-proBNP decreased after ablation procedure, from 4,092.6?±?3,916.6 to 478.9?±?881.9 pg/ml (P?<?0.001). After successful ablation, ventricular function normalized in 15 of 17 (88.2 %) patients at a mean of 3 months.

Conclusions

Restoration of LV function and reversal of LV remodeling can be achieved with successful elimination of tachycardia in the majority of patients. NT-proBNP level elevates in subjects with TCM and decreases sharply after ablation.     

Investigation of the effectiveness of measles vaccination in children in Kenya

Laboratory studies were performed on 128 children clinically diagnosed as measles when seen at the Infectious Diseases Hospital, Kenyatta National Hospital (IDH), Nairobi (86 cases) and the Rural Health Training Centre, Maragua, Central Province (42 cases) between 9 July and 31 August 1984. A concurrent measles infection was confirmed in 95% of the children seen at IDH and in 85% of those seen at Maragua, with similar proportions of confirmations in children who had, and who had not, received measles vaccine. No differences in the number of sero-conversions nor in the absolute levels of acute or convalescent HI antibody titres could be detected between vaccinated and unvaccinated children. Analysis of the cases seen at Maragua indicates that about two thirds of the children who had received vaccine were protected. A pilot study of vaccinating children at 8 months and again at 12-13 months is suggested in an attempt to eradicate measles.