Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment

Background

Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS₃), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border.

Methods and Findings

3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS₃. The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00–2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS₃ efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07–1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0–98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2–5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend).

Conclusion

Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage.     

Oral artesunate prevents Plasmodium berghei Anka infection in mice

Artesunate, a semi-synthetic derivative of a naturally occurring anti-malarial artemisinin was compared with chloroquine in C57BL/6 mice infected with Plasmodium berghei Anka (PbA). A 7-day oral administration of artesunate prevented parasitaemia at 10 mg/kg/day. However, recrudescence of parasitaemia and cerebral malaria occurred upon cessation of treatment followed by death within 28 days. However, a 14-day course of artesunate (100 mg/kg/day) prevented completely the development of parasitaemia and cerebral malaria with a survival of more than 60-days as did 10 mg/kg/day chloroquine. These data demonstrate that oral artesunate inhibits PbA and prevents cerebral malaria, but needs to be administered at high dose and for prolonged time to eradicate PbA infection in mice.     

Rhinitis Symptoms and Asthma among Parents of Preschool Children in Relation to the Home Environment in Chongqing,China

Risk factors for rhinitis and asthma in the home environment were studied by a questionnaire survey. Parents of 4530 1–8 year old children (one parent per child) from randomly selected kindergartens in Chongqing, China participated. 70.4% were females; 47.1% had rhinitis symptoms in the last three months (current rhinitis, CR); 1.6% reported a history of allergic asthma (AA); 2.7% reported a history of allergic rhinitis (AR); 16.4% were current smokers; 50.8% males and 2.4% females were current smokers. Stuffy odor, unpleasant odor, tobacco smoke odor and dry air were associated with CR (adjustment for gender, current smoking and other perceptions of odor or humidity). Associations between home environment and CR, AR, and AA were studied by multiple logistic regression analyses, adjusting for gender, current smoking and other significant home factors. Living near a main road or highway was a risk factor for both CR (OR(95%CI): 1.31(1.13,1.52)) and AR (OR(95%CI): 2.44(1.48,4.03)). Other risk factors for CR included living in rural areas (OR(95%CI): 1.43(1.10,1.85)), new furniture (OR(95%CI): 1.28(1.11,1.49)), water damage (OR(95%CI): 1.68(1.29,2.18)), cockroaches (OR(95%CI): 1.46(1.23,1.73)), and keeping pets (OR(95%CI): 1.24(1.04,1.49)). Other risk factors for AR included redecoration (OR(95%CI): 2.14(1.34,3.41)), mold spots (OR(95%CI): 2.23(1.06,4.68)), window pane condensation (OR(95%CI): 2.04(1.28,3.26)). Water damage was the only home factor associated with AA (2.56(1.34,4.86)). Frequently put bedding to sunshine was protective for CR (OR(95%CI): 0.79(0.68,0.92); cleaning every day was protective for AR (OR(95%CI): 0.40(0.22,0.71)). In conclusion, parents'' CR and AR were related to a number of factors of the home environment.     

Assessment of the efficacy of antimalarial drugs recommended by the National Malaria Control Programme in Madagascar: Up-dated baseline data from randomized and multi-site clinical trials

Background

In order to improve the monitoring of the antimalarial drug resistance in Madagascar, a new national network based on eight sentinel sites was set up. In 2006/2007, a multi-site randomized clinical trial was designed to assess the therapeutic efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP), amodiaquine (AQ) and artesunate plus amodiaquine combination (ASAQ), the antimalarial therapies recommended by the National Malaria Control Programme (NMCP).

Methods

Children between six months and 15 years of age, with uncomplicated falciparum malaria, were enrolled. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping. Risks of clinical and parasitological treatment failure after adjustment by genotyping were estimated using Kaplan-Meier survival analysis. Secondary outcomes included fever clearance, parasite clearance, change in haemoglobin levels between Day 0 and the last day of follow-up, and the incidence of adverse events.

Results

A total of 1,347 of 1,434 patients (93.9%) completed treatment and follow-up to day 28. All treatment regimens, except for the chloroquine (CQ) treatment group, resulted in clinical cure rates above 97.6% by day-14 and 96.7% by day-28 (adjusted by genotyping). Parasite and fever clearance was more rapid with artesunate plus amodiaquine, but the extent of haematological recovery on day-28 did not differ significantly between the four groups. No severe side-effects were observed during the follow-up period.

Conclusion

These findings (i) constitute an up-dated baseline data on the efficacy of antimalarial drugs recommended by the NMCP, (ii) show that antimalarial drug resistance remains low in Madagascar, except for CQ, compared to the bordering countries in the Indian Ocean region such as the Comoros Archipelago and (iii) support the current policy of ASAQ as the first-line treatment in uncomplicated falciparum malaria.

     

The decline of malaria in Finland – the impact of the vector and social variables

Background

Resistance to anti-malarial drugs hampers control efforts and increases the risk of morbidity and mortality from malaria. The efficacy of standard therapies for uncomplicated Plasmodium falciparum and Plasmodium vivax malaria was assessed in Chumkiri, Kampot Province, Cambodia.

Methods

One hundred fifty-one subjects with uncomplicated falciparum malaria received directly observed therapy with 12 mg/kg artesunate (over three days) and 25 mg/kg mefloquine, up to a maximum dose of 600 mg artesunate/1,000 mg mefloquine. One hundred nine subjects with uncomplicated vivax malaria received a total of 25 mg/kg chloroquine, up to a maximum dose of 1,500 mg, over three days. Subjects were followed for 42 days or until recurrent parasitaemia was observed. For P. falciparum infected subjects, PCR genotyping of msp1, msp2, and glurp was used to distinguish treatment failures from new infections. Treatment failure rates at days 28 and 42 were analyzed using both per protocol and Kaplan-Meier survival analysis. Real Time PCR was used to measure the copy number of the pfmdr1 gene and standard 48-hour isotopic hypoxanthine incorporation assays were used to measure IC₅₀ for anti-malarial drugs.

Results

Among P. falciparum infected subjects, 47.0% were still parasitemic on day 2 and 11.3% on day 3. The PCR corrected treatment failure rates determined by survival analysis at 28 and 42 days were 13.1% and 18.8%, respectively. Treatment failure was associated with increased pfmdr1 copy number, higher initial parasitaemia, higher mefloquine IC₅₀, and longer time to parasite clearance. One P. falciparum isolate, from a treatment failure, had markedly elevated IC₅₀ for both mefloquine (130 nM) and artesunate (6.7 nM). Among P. vivax infected subjects, 42.1% suffered recurrent P. vivax parasitaemia. None acquired new P. falciparum infection.

Conclusion

The results suggest that artesunate-mefloquine combination therapy is beginning to fail in southern Cambodia and that resistance is not confined to the provinces at the Thai-Cambodian border. It is unclear whether the treatment failures are due solely to mefloquine resistance or to artesunate resistance as well. The findings of delayed clearance times and elevated artesunate IC₅₀ suggest that artesunate resistance may be emerging on a background of mefloquine resistance.     

Prevalence and Associated Factors of Myopia in High-School Students in Beijing

Purpose

To evaluate prevalence and associated factors for myopia in high school students in Beijing.

Methods

Grade 10 and 11 high school students were randomly selected from nine randomly selected districts of Beijing. The students underwent non-cylcoplegic auto-refractometry and an interview.

Results

Out of 4798 eligible students, 4677 (93.4%) students (mean age:16.9±0.7years;range:16–18 years) participated. Mean refractive error of right eyes and left eyes was −2.78±2.29 diopters and −2.59±2.50 diopters, respectively. Prevalence of myopia (defined as ≤ −1.00 diopters in the worse eye) was 80.7% (95% Confidence Interval (CI): 79.6–81.8%). Out of 3773 students with myopia, 1525 (40.4%) wore glasses daily. In multiple logistic regression analysis, a higher prevalence of myopia was associated with female sex (odds ratio (OR) = 1.31;95%CI:1.11–1.55), Han ethnicity (OR = 1.64;95%CI:1.28–2.11), attending key schools (OR = 1.48;95%CI:1.24,1.77), higher family income (OR = 1.37;95%CI:1.09–1.71), longer time spent for near work (OR = 1.43;95%CI:1.06–1.93), shorter near work distance (OR = 1.87;95%CI:1.55–2.26), lower frequency of active rest during studying (OR = 1.40;95%CI:1.16–1.70), and parental myopia (OR = 2.28;95%CI:1.80–2.87). The interaction between distance from near work and time spent for near work was statistically (P = 0.03) significant. In multiple logistic regression analysis, higher prevalence of high myopia (≤-6.0 diopters) was associated with studying in key schools (OR = 1.38;95%CI:1.05,1.81), lower frequency of active rest during studying (OR = 1.40;95%CI:1.09,1.79), and a higher number of myopic parents (OR = 2.66;95%CI:2.08,3.40).

Conclusions

A prevalence of about 80% for myopia and a prevalence of about 10% for high myopia in students aged 16 to 18 years and attending classes of grade 10 and 11 in a Chinese metropolitan region is another example of the high prevalence of moderate and high myopia in metropolitan areas of China. With this young myopic generation getting older, myopia as cause for visual impairment and blindness may further increase in importance. Future studies may address whether active rests during studying with looking into the distance are preventive against myopia development or progression.     

Factors Associated with Myopia in School Children in China: The Beijing Childhood Eye Study

Purpose

To assess factors associated with myopia in school children in rural and urban parts of Greater Beijing.

Methods

The Beijing Pedriatic Eye Study was a population-based cross-sectional study, in which one school of each level (primary, junior high, senior high) was randomly selected from nine randomly selected districts out of 18 districts of Greater Beijing. The children underwent non-cylcoplegic refractometry and their parents an interview.

Results

Of 16,771 eligible students, 15,066 (89.8%) children (7,769 (51.6%) girls) participated, with 8,860 (58.8%) participants living in the rural region. Mean age was 13.2±3.4 years (range:7–18 years). In multivariate analysis, prevalence of myopia (defined as ≤−1.00 diopters) was associated with higher age (Odds ratio(OR):1.37; 95% confidence interval(CI):1.35,1.39), female gender (OR:1.35;95%CI:1.25,1.47), key school type (OR:0.77;95%CI: 0.70,0.85), higher family income (OR:1.04;95%CI:1.01,1.07), parental myopia (OR:1.46;95%CI:1.40,1.53), dim reading illumination (OR:0.93;95%CI: 0.88,0.98), longer daily studying duration (OR:1.10;95%CI:1.06,1.15), shorter duration of watching television (or computer) (OR:0.93;95%CI:0.89,0.97), higher self-reported protein intake (OR:0.94;95%CI:0.90,0.99), feeling well about life and status (OR:0.93;95%CI:0.89,0.98), and feeling tired or dizzy (OR:0.94;95%CI:0.91,0.97). Prevalence of high myopia (defined as ≤−6.00 diopters) was associated with higher age (OR:1.43;95%CI:1.38, 1.48), key school type (OR:0.61;95%CI:0.49,0.74), family income (OR:1.07;95%CI:1.02,1.13), parental myopia (OR:1.65;95%CI:1.54,1.76), dim reading illumination (OR:0.86;95%CI:0.77,0.96), less rest during studying (OR:1.18;95%CI:1.10,1.27), feeling well about life and studying (OR:0.88;95%CI: 0.81,0.96) and feeling dizzy or tired (OR:0.93;95%CI:0.87,0.99). Prevalence of high myopia (defined as ≤−8.00 diopters) was significantly associated with higher age (OR:1.39;95%CI:1.31,1.48;), key school type (OR:0.61;95%CI:0.42,0.88) and parental myopia (OR:1.87;95%CI:1.66,2.12).

Conclusions

Myopia in school children in Greater Beijing was associated with higher age, female gender, school type, parental myopia, higher socioeconomic background, dim reading illumination, longer daily studying duration, less rest during study, shorter duration of watching television (or computer), higher self-reported protein intake, feeling well about life and status, and feeling tired and dizzy.     

Rising Diabetes Prevalence among Urban-Dwelling Black South Africans

Objective

To examine the prevalence of and the association of psychosocial risk factors with diabetes in 25–74-year-old black Africans in Cape Town in 2008/09 and to compare the prevalence with a 1990 study.

Research Design and Methods

A randomly selected cross-sectional sample had oral glucose tolerance tests. The prevalence of diabetes (1998 WHO criteria), other cardiovascular risk factors and psychosocial measures, including sense of coherence (SOC), locus of control and adverse life events, were determined. The comparison of diabetes prevalence between this and a 1990 study used the 1985 WHO diabetes criteria.

Results

There were 1099 participants, 392 men and 707 women (response rate 86%). The age-standardised (SEGI) prevalence of diabetes was 13.1% (95% confidence interval (CI) 11.0–15.1), impaired glucose tolerance (IGT) 11.2% (9.2–13.1) and impaired fasting glycaemia 1.2% (0.6–1.9). Diabetes prevalence peaked in 65–74-year-olds (38.6%). Among diabetic participants, 57.9% were known and 38.6% treated. Using 1985 WHO criteria, age-standardised diabetes prevalence was higher by 53% in 2008/09 (12.2% (10.2–14.2)) compared to 1990 (8.0% (5.8–10.3)) and IGT by 67% (2008/09: 11.7% (9.8–13.7); 1990: 7.0% (4.9–9.1)). In women, older age (OR: 1.05, 95%CI: 1.03–1.08, p<0.001), diabetes family history (OR: 3.13, 95%CI: 1.92–5.12, p<0.001), higher BMI (OR: 1.44, 95%CI: 1.20–1.82, p = 0.001), better quality housing (OR: 2.08, 95%CI: 1.01–3.04, p = 0.047) and a lower SOC score (≤40) was positively associated with diabetes (OR: 2.57, 95%CI: 1.37–4.80, p = 0.003). Diabetes was not associated with the other psychosocial measures in women or with any psychosocial measure in men. Only older age (OR: 1.05, 95%CI: 1.02–1.08, p = 0.002) and higher BMI (OR: 1.10, 95%CI: 1.04–1.18, p = 0.003) were significantly associated with diabetes in men.

Conclusions

The current high prevalence of diabetes in urban-dwelling South Africans, and the likelihood of further rises given the high rates of IGT and obesity, is concerning. Multi-facetted diabetes prevention strategies are essential to address this burden.     

Prevalence and Associated Factors for Pterygium in Rural Agrarian Central India. The Central India Eye and Medical Study

Purpose

To evaluate the prevalence of pterygia and associated factors in a rural population in a mostly undeveloped agrarian region.

Methods

The Central India Eye and Medical Study is a population-based study performed in a rural region of Central India. The study comprised 4711 subjects (aged 30+ years). A detailed ophthalmic and medical examination was performed. A pterygium was diagnosed during the slit lamp examination and confirmed on corneal photographs. It was defined as a fleshy fibrovascular growth, crossing the limbus and typically seen on the nasal, and sometimes temporal, conjunctiva.

Results

A pterygium was detected in 798 eyes (prevalence rate: 8.47±0.29%) of 608 (12.91±0.49%) subjects. Bilateral pterygia were present in 190 subjects (4.0% of study population). Pterygia prevalence increased from 6.7±0.8% in the age group 30-39 years, to 13.5±1.2% in the age group 50-59 years, to 25.3±2.1% in the age group 70-79 years. Prevalence of pterygia was associated with older age (P<0.001; regression coefficient B: 0.02; odds ratio (OR): 1.02; 95%CI: 1.01, 1.03), male gender (P<0.001;B:-0.73;OR: .48;95%CI:0.39,0.61), lower level of education (P<0.001;B:-0.30;OR:0.74;95%CI:0.69,0.80), lower body height (P=0.001;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.26;95%CI:1.18,1.34). If the education level was dropped, the number of hours spent with vigorous activity outdoors (P=0.001;B:0.001;OR:1.001;95%CI:1.000,1.0001) was significantly associated with the prevalence of pterygia, in addition to older age (P<0.001;B:0.03;OR:1.03;95%CI:1.03,1.04), male gender (P<0.001;B:-0.49;OR:0.62;95%CI:0.49,0.77), lower body height (P=0.005;B:-0.02;OR:0.98;95%CI:0.97,0.99), and higher cylindrical refractive error (P<0.001;B:0.23;OR:1.25;95%CI:1.18,1.34).

Conclusions

Pterygium prevalence in rural Central India is about 13% among adult Indians aged 30+ years. Older age, male gender, lower educational level, lower body height and more time spent outdoors with vigorous work were associated factors. Since the living conditions in the study location were mostly untouched by modern developments, the results may show the prevalence and associations of pterygia without major medical or technologic influences.     

Pimecrolimus Cream 1% in the Management of Atopic Dermatitis in Pediatric Patients: A Meta-Analysis

Objective

To evaluate the efficacy and safety of pimecrolimus cream 1% in the treatment of AD in the pediatric population.

Methods

PubMed, EMBASE, Web of Science and Cochrane library databases were searched till July 2013. The randomized and nonrandomized blinded studies of pimecrolimus cream 1% applied twice daily with Jaded score ≥3 in pediatric patients with AD were included. The efficacy outcomes included investigator global assessment (IGA), eczema area and severity index (EASI) scores, pruritus and care giver''s assessments and flares free period. Adverse events were reviewed to assess the safety.

Results

Out of 81 studies, 7 were selected that enrolled 2,170 pediatric patients. The pooled analysis reported that pimecrolimus was no better to vehicle reducing eczema at day-8, day-26 and six weeks (OR 4.95, 95% CI 2.79–8.80), (OR 9.69, 95% CI 4.12–22.83) and (OR 3.83. 95% CI 1.94–7.56), respectively in children. Similarly, pimecrolimus did not show beneficial effects when analyzed for mild or absent pruritus at day 4 (OR 8.29, 95% CI 3.88–17.72 favoring vehicle), day 43 (OR 1.81 95% CI 1.13–2.89 favoring vehicle) and 1 week (OR 2.29, 95%CI 1.45 to 3.60 favoring vehicle) as compared with vehicle. One study comparing pimecrolimus with tacrolimus found no significant difference in achieving mild or absent pruritus (OR 0.94, 95% CI 0.44–1.99). More patients showed an improvement in overall disease in vehicle group at day 8 (OR 3.30, 95% CI 2.03–5.35), day 29 (OR 14.14, 95% CI 6.87–29.13) and day 43 (OR 4.11, 95% CI 2.59–6.52) as compared with pimecrolimus 1% group, as assessed by caregivers. No significant difference was seen between the total AEs in both groups (pimecrolimus vs vehicle/tacrolimus) (OR 1.19, 95% CI 0.85, 1.65)

Conclusion

The results of the present meta-analysis showed that pimecrolimus cream 1% was not significantly better to vehicle for AD in pediatrics population.     

The Burden and Determinants of Non Communicable Diseases Risk Factors in Nepal: Findings from a Nationwide STEPS Survey

Background

World Health Organization (WHO) estimates for deaths attributed to Non Communicable Diseases (NCDs) in Nepal have risen from 51% in 2010 to 60% in 2014. This study assessed the distribution and determinants of NCD risk factors among the Nepalese adult population.

Methods and Findings

A nationally representative cross-sectional survey was conducted from Jan to June 2013 on the prevalence of NCD risk factors using the WHO NCD STEPS instrument. A multistage cluster sampling method was used to randomly select the 4,200 respondents. The adjusted prevalence ratio (APR) was used to assess the determinants of NCD risk factors using a Poisson regression model. The prevalence of current smoking (last 30 days) was 19% (95%CI:16.6-20.6), and harmful alcohol consumption (≥60 g of pure alcohol for men and ≥40 g of pure alcohol for women on an average day) was 2% (95%CI:1.4-2.9). Almost all (99%, 95%CI:98.3-99.3) of the respondents consumed less than five servings of fruits and vegetables combined on an average day and 3% (95%CI:2.7-4.3) had low physical activity. Around 21% (95%CI:19.3-23.7) were overweight or obese (BMI≥25). The prevalence of raised blood pressure (SBP≥140 mm of Hg or DBP≥90 mm of Hg) and raised blood glucose (fasting blood glucose ≥126 mg/dl), including those on medication were 26% (95%CI:23.6-28.0) and 4% (95%CI:2.9-4.5) respectively. Almost one quarter of respondents, 23% (95%CI:20.5-24.9), had raised total cholesterol (total cholesterol ≥190 mg/dl or under current medication for raised cholesterol). he study revealed a lower prevalence of smoking among women than men (APR:0.30; 95%CI:0.25-0.36), and in those who had higher education levels compared to those with no formal education (APR:0.39; 95%CI:0.26-0.58). Harmful alcohol use was also lower in women than men (APR:0.26; 95%CI:0.14-0.48), and in Terai residents compared to hill residents (APR:0.16; 95%CI:0.07-0.36). Physical inactivity was lower among women than men (APR:0.55; 95%CI:0.38-0.80), however women were significantly more overweight and obese (APR:1.19; 95%CI:1.02-1.39). Being overweight or obese was significantly less prevalent in mountain residents than in hill residents (APR:0.41; 95%CI:0.21-0.80), and in rural compared to urban residents (APR:1.39; 95%CI:1.15-1.67). Lower prevalence of raised blood pressure was observed among women than men (APR:0.69; 95%CI: 0.60-0.80). Higher prevalence of raised blood glucose was observed among urban residents compared to rural residents (APR:2.05; 95%CI:1.29-3.25). A higher prevalence of raised total cholesterol was observed among the respondents having higher education levels compared to those respondents having no formal education (APR:1.76; 95%CI:1.35-2.28).

Conclusion

The prevalence of low fruit and vegetable consumption, overweight and obesity, raised blood pressure and raised total cholesterol is markedly high among the Nepalese population, with variation by demographic and ecological factors and urbanization. Prevention, treatment and control of NCDs and their risk factors in Nepal is an emerging public health problem in the country, and targeted interventions with a multi-sectoral approach need to be urgently implemented.     

Interleukin 2 gene polymorphisms are associated with non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy worldwide. Interleukin-2 (IL-2) plays a key role in the proliferation of T cells and natural killer cells. It has been reported that polymorphisms in the IL-2 gene are associated with various cancers. The aim of this study was to examine the effect of polymorphisms in the IL-2 gene on the development of NHL in the Chinese population. IL-2-330T/G and +114T/G polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 438 NHL cases and 482 age-matched healthy controls. Data were analyzed using the Chi-square test. Results showed that individuals with -330TG genotype or -330GG genotype had significantly increased susceptibility to NHL (Odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.05-1.85, p = 0.020 and OR = 2.04, 95%CI: 1.28-3.24, p = 0.002). Meanwhile, the +114T/G polymorphism did not show any correlation with NHL. When analyzing the haplotypes of these two polymorphisms, the prevalence of -330G/+114T haplotype was significantly higher in NHL cases than in controls (OR = 1.45, 95%CI: 1.12-1.88, p = 0.005). These data indicate that IL-2 gene polymorphisms may be new risk factors for NHL.     

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.     

Sub-clinical mastitis and associated risk factors on lactating cows in the Savannah Region of Nigeria

ABSTRACT: BACKGROUND: Sub-clinical mastitis limits milk production and represents an important barrier to profitable livestock economics worldwide. Milk production from cows in Nigeria is not at optimum levels in view of many factors including sub-clinical mastitis. RESULTS: The overall herd-level prevalence rate for SCM was 85.33% (256/300 heads of cows) while the quarter-level prevalence rate of SCM was 43.25% (519/1,200 quarters). The prevalence of SCM was 50.67%, 43.67%, 39.67% and 39.13% for the left fore-quarter, right hind-quarter, left hind-quarter and right fore-quarter, respectively. The Rahaji breed had the highest prevalence of SCM with 65.91% (29/44), Sokoto while the White Fulani breed had the least with 32.39% (57/176). A total of 32.33% (97/300) had only one mammary quarter affected, 30.33% (91/300) had two quarters affected, 16.00% (48/300) had three quarters affected while 6.67% (20/300) had all the four quarters affected. A total of 53.00% had SCM in multiple quarters (159/300). The risk of SCM decreased significantly among young lactating cows compared to older animals (OR = 0.283; P < 0.001; 95%CI = 0.155; 0.516). The Rahaji breed had significantly higher risk compared with the White Fulani breed (OR = 8.205; P = 0.013; 95%CI = 1.557; 43.226). Improved sanitation (washing hands before milking) will decrease the risk of SCM (OR = 0.173; P = 0.003; 95%CI = 0.054; 0.554). CONCLUSION: SCM is prevalent among lactating cows in the Nigerian Savannah; and this is associated with both animal characteristics (age, breed and individual milk quarters) and milking practices (hand washing).Good knowledge of the environment and careful management of the identified risk factors with improved sanitation should assist farm managers and veterinarians in implementing preventative programmes to reduce the incidence of SCM.     

Association of the − 1082G/A polymorphism in the interleukin-10 gene with systemic lupus erythematosus: A meta-analysis

A great many studies have investigated the − 1082G/A polymorphism (rs1800896) in the interleukin-10 gene (IL10) with SLE susceptibility, but the results are inconsistent and inconclusive. The aim of this meta-analysis was in order to more precisely estimate the relationship. The databases of Pubmed and Web of Science updated to Oct, 2012 were retrieved. Odds ratio (OR) and corresponding 95% confidence interval (95%CI.) as effect size were calculated by fixed-effect model. Analysis for allele contrast of stratification by ethnicity in either Asian or Caucasian, as well as in overall population indicated no significant association (Overall: OR 1.096, 95%CI. 0.995–1.207; Asian: OR 1.204, 95%CI.: 0.944–1.535; Caucasian: OR 1.075, 95%CI.: 0.961–1.202). Analysis for recessive model showed no association in overall populations and in Caucasian (Overall: OR 1.135, 95%CI.: 0.945–1.362; Caucasian: OR 1.069, 95%CI.: 0.882–1.296), but significant association in Asian (OR: 2.848; 95%CI.: 1.194–6.791). Analysis for dominant model indicated that the variant G allele carriers (GG + GA) may have increased the risk of SLE when compared with the homozygote AA in overall populations and in Caucasian (Overall: OR 1.203, 95%CI.: 1.029–1.407; Caucasian: OR 1.233, 95%CI.: 1.014–1.499), but not in Asian (OR: 1.154; 95%CI.: 0.856–1.557). Significant association was found by using homozygote contrast model in overall populations and Asian (Overall: OR 1.303, 95%CI.: 1.031–1.648; Asian: OR 3.206, 95%CI.: 1.241–8.284), while no association was found in Caucasian (OR: 1.209; 95%CI.: 0.940–1.556). The results provided evidence for the association between the IL10 − 1082G/A polymorphism and the risk of SLE. To confirm these findings, more case–control studies with subtle study design based on adequately sized populations are required.     

Simple flow cytometric detection of haemozoin containing leukocytes and erythrocytes for research on diagnosis, immunology and drug sensitivity testing

Background

Plasmodium falciparum malaria remains endemic in sub-Saharan Africa including Ghana. The epidemiology of malaria in special areas, such as mining areas needs to be monitored and controlled. Newmont Ghana Gold Limited is conducting mining activities in the Brong Ahafo Region of Ghana that may have an impact on the diseases such as malaria in the mining area.

Methods

Prior to the start of mining activities, a cross-sectional survey was conducted in 2006/2007 to determine malaria epidemiology, including malaria parasitaemia and anaemia among children < 5 years and monthly malaria transmission in a mining area of Ghana.

Results

A total of 1,671 households with a child less than five years were selected. About 50% of the household heads were males. The prevalence of any malaria parasitaemia was 22.8% (95% CI 20.8 - 24.9). Plasmodium falciparum represented 98.1% (95% CI 96.2 - 99.2) of parasitaemia. The geometric mean P. falciparum asexual parasite count was 1,602 (95% CI 1,140 - 2,252) and 1,195 (95% CI 985 - 1,449) among children < 24 months and ≥ 24 months respectively. Health insurance membership (OR 0.60, 95% CI 0.45 - 0.80, p = 0.001) and the least poor (OR 0.57, 95% CI 0.37 - 0.90, p = 0.001) were protected against malaria parasitaemia. The prevalence of anaemia was high among children < 24 months compared to children ≥ 24 months (44.1% (95% CI 40.0 - 48.3) and 23.8% (95% CI 21.2 - 26.5) respectively. About 69% (95% CI 66.3 - 70.9) of households own at least one ITN. The highest EIRs were record in May 2007 (669 ib/p/m) and June 2007 (826 ib/p/m). The EIR of Anopheles gambiae were generally higher than Anopheles funestus.

Conclusion

The baseline malaria epidemiology suggests a high malaria transmission in the mining area prior to the start of mining activities. Efforts at controlling malaria in this mining area have been intensified but could be enhanced with increased resources and partnerships between the government and the private sector.     

Association between methylene tetrahydrofolate reductase and glutathione S-transferase M1 gene polymorphisms and chronic myeloid leukemia in a Brazilian population

Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.     

MTHFR C677T and A1298C polymorphisms and cervical carcinoma susceptibility: meta-analyses based on 4421 individuals

MTHFR polymorphisms have been implicated as risk factors for several cancers. Studies have conducted on the associations of MTHFR polymorphisms with cervical carcinoma risk and have generated inconclusive results. The aim of the present study was to increase power demonstrating the possible relations. Meta-analyses examining the association between MTHFR C677T and A1298C polymorphisms and cervical carcinoma risk were performed. Separate analyses on ethnicity and source of controls were also implemented. Eligible studies were identified for the period up to Dec 2011. Eleven case-control studies containing 1859 cases and 2562 controls regarding MTHFR C677T polymorphisms were selected, of which four studies containing 461 cases and 832 controls described A1298C polymorphisms. For the overall data, no associations of MTHFR C677T polymorphisms with cervical carcinoma were observed (TT vs CC: OR = 1.07; 95 %CI = 0.73-1.58; dominant model: OR = 0.89; 95 %CI = 0.66-1.18; recessive model: OR = 1.13; 95 %CI = 0.84-1.52). In the subgroup analysis by ethnicity, MTHFR 677T allele was associated with decreased cervical cancer susceptibility among Caucasians (TT vs CC: OR = 0.65; 95 %CI = 0.45-0.93; dominant model: OR = 0.70; 95 %CI = 0.58-0.86) but not Asians. As for A1298C polymorphism, no marked associations of A1298C genetic variation with cervical cancer risk were observed (CC vs AA: OR = 1.01; 95 %CI = 0.60-1.73; dominant model: OR = 1.17; 95 %CI = 0.91-1.49; recessive model: OR = 0.99; 95 %CI = 0.60-1.63). Collectively, the results of the present study suggest that MTHFR 677T allele might play a preventive role for cervical carcinoma among Caucasians. A1298C polymorphisms might exert little effect on cervical cancerigenesis.     

Association between polymorphisms in the promoter region of miR‐17‐92 cluster and systemic lupus erythematosus in a Chinese population

The aim of this study was to investigate the association of genetic polymorphisms in the promoter region of miR‐17‐92 with systemic lupus erythematosus (SLE). The gene polymorphism was analysed using SNaPshot in 312 SLE patients and 396 controls. Relative expression of miR‐17‐92 was measured by quantitative real‐time PCR. Association was found between rs9515692 and a decreased risk of SLE (CT vs CC: OR = 0.65, 95%CI, 0.46‐0.92, P = .014; CT+TT vs CC: OR = 0.64, 95%CI, 0.46‐0.90, P = .009; T vs C: OR = 0.69, 95%CI, 0.52‐0.92, P = .010, respectively). Haplotype analysis showed that C‐G‐G, C‐A‐A haplotypes were associated with an increased SLE risk (OR=4.46, 95%CI, 2.17‐9.17, P < 0.001; OR=2.33, 95%CI, 1.44‐3.76, P < 0.001, respectively). T allele and CT+TT genotypes in rs9515692 were associated with decreased risk of anti‐dsDNA in SLE (CT+TT vs CC: OR = 0.42, 95%CI = 0.24‐0.72, P = .002; T vs A: OR = 0.49, 95%CI = 0.31‐0.79, P = .003). Moreover, rs9515692 CT+TT genotypes had a higher level of miR‐17 as compared to CC genotype (P = .017). These findings suggest that the rs9515692 CT+TT genotypes were a protective factor for the susceptibility of SLE, probably by increasing the expression of miR‐17.     

Malaria prevalence among pregnant women in two districts with differing endemicity in Chhattisgarh, India

ABSTRACT: BACKGROUND: In India, malaria is not uniformly distributed. Chhattisgarh is a highly malarious state where both Plasmodium falciparum and Plasmodium vivax are prevalent with a preponderance of P. falciparum. Malaria in pregnancy (MIP), especially when caused by P. falciparum, poses substantial risk to the mother and foetus by increasing the risk of foetal death, prematurity, low birth weight (LBW), and maternal anaemia. These risks vary between areas with stable and unstable transmission. The specific objectives of this study were to determine the prevalence of malaria, its association with maternal and birth outcomes, and use of antimalarial preventive measures for development of evidence based interventions to reduce the burden of MIP. METHODS: A cross-sectional study of pregnant women presenting to antenatal clinics (ANC) or delivery units (DU), or hospitalized for non-obstetric illness was conducted over 12 months in high (Bastar) and low (Rajnandgaon) transmission districts in Chhattisgarh state. Intensity of transmission was defined on the basis of slide positivity rates with a high proportion due to P. falciparum. In each district, a rural and an urban health facility was selected. RESULTS: Prevalence of peripheral parasitaemia was low: 1.3% (35/2696) among women at ANCs and 1.9% at DUs (19/1025). Peripheral parasitaemia was significantly more common in Bastar (2.8%) than in Rajnandgaon (0.1%) (p < 0.0001). On multivariate analysis of ANC participants, residence in Bastar district (stable malaria transmission) was strongly associated with peripheral parasitaemia (adjusted OR [aOR] 43.4; 95% CI, 5.6-335.2). Additional covariates associated with parasitaemia were moderate anaemia (aOR 3.7; 95% CI 1.8-7.7), fever within the past week (aOR 3.2; 95% CI 1.2-8.6), and lack of formal education (aOR 4.6; 95% CI 2.0-10.7). Similarly, analysis of DU participants revealed that moderate anaemia (aOR 2.5; 95% CI 1.1-5.4) and fever within the past week (aOR 5.8; 95% CI 2.4-13.9) were strongly associated with peripheral and/or placental parasitaemia. Malaria-related admissions were more frequent among pregnant women in Bastar, the district with greater malaria prevalence (51% vs. 11%, p < 0.0001). CONCLUSIONS: Given the overall low prevalence of malaria, a strategy of enhanced anti-vector measures coupled with intermittent screening and targeted treatment during pregnancy should be considered for preventing malaria-associated morbidity in central India.