The Natural History of Trachoma Infection and Disease in a Gambian Cohort with Frequent Follow-Up

Background

The natural history of ocular Chlamydia trachomatis infections in endemic communities has not been well characterised and is an important determinant of the effectiveness of different mass treatment strategies to prevent blindness due to trachoma.

Methodology/Principal Findings

A multistate hidden Markov model was fitted to data on infection and active disease from 256 untreated villagers in The Gambia who were examined every 2 weeks over a 6-month period. Parameters defining the natural history of trachoma were estimated, and associations between these parameters, demographic and baseline immune measurements examined. The median incubation period following infection was estimated at 17 days (95% confidence interval: 11–28). Disease persisted for longer than infection (median 21 (15–32) weeks) versus 17 (12–24) weeks), with an estimated median duration of post-infection inflammation of 5 (3–8) weeks. The duration of active disease showed a significant decline with age even after accounting for lower rates of re-infection and disease at older ages (p = 0.004). Measurements of levels of baseline IgA to epitopes in the major outer membrane protein of Chlamydia trachomatis were not significantly correlated with protection or more rapid clearance of infection.

Conclusions

The average duration of infection with Chlamydia trachomatis especially at younger ages is long. This contributes to the persistence and gradual return of trachoma after community-wide treatment with antibiotics.     

Natural History of Cutaneous Human Papillomavirus (HPV) Infection in Men: The HIM Study

Accumulating evidence suggests that cutaneous human papillomavirus (HPV) infection is associated with non-melanoma skin cancer (NMSC). Little is known about the natural history of cutaneous HPV. A sub-cohort of 209 men with no NMSC history, initially enrolled in the HPV infection in men (HIM) study, were followed for a median of 12.6 months. Epidemiological data were collected through self-administered questionnaires. Cutaneous HPV DNA was measured in normal skin swabs (SS) and eyebrow hairs (EB) for 25 and 16 HPV types in genera β and γ, respectively. Any β HPV infection was more prevalent in SS (67.3%) compared to EB (56.5%, p = 0.04). Incidence in SS was higher than 20 per 1,000 person-months for HPV types 4, 5, 23, 38 and 76. Median duration of persistence of β and γ HPV infection was 8.6 and 6.1 months in EB, respectively, and 11.3 months and 6.3 months, in SS, respectively. Older age (>44 years vs. 18-30 years) was significantly associated with prevalent (SS OR = 3.0, 95% CI = 1.2–7.0) and persistent β HPV infection (EB OR = 6.1, 95% CI = 2.6–14.1). History of blistering sunburn was associated with prevalent (OR = 2.8, 95% CI = 1.3–5.8) and persistent (OR = 2.3, 95% CI = 1.2–4.6) β HPV infection in SS. Cutaneous HPV is highly prevalent in men, with age and blistering sunburn being significant risk factors for cutaneous β HPV infection.     

Hepatitis B Virus Infection in HIV-Positive Individuals in the UK Collaborative HIV Cohort (UK CHIC) Study

Background

Hepatitis B virus (HBV) infection is an increasingly important cause of morbidity and mortality in HIV-infected adults. This study aimed to determine the prevalence and incidence of HBV in the UK CHIC Study, a multicentre observational cohort.

Methods and Findings

12 HIV treatment centres were included. Of 37,331 patients, 27,450 had at least one test (HBsAg, anti-HBs or anti-HBc) result post-1996 available. 16,043 were white, 8,130 black and 3,277 other ethnicity. Route of exposure was homosexual sex 15,223 males, heterosexual sex 3,258 males and 5,384 females, injecting drug use 862 and other 2,723. The main outcome measures used were the cumulative prevalence and the incidence of HBV coinfection. HBV susceptible patients were followed up until HBsAg and/or anti-HBc seroconversion incident infection, evidence of vaccination or last visit. Poisson regression was used to determine associated factors. 25,973 had at least one HBsAg test result. Participants with HBsAg results were typically MSM (57%) and white (59%) (similar to the cohort as a whole). The cumulative prevalence of detectable HBsAg was 6.9% (6.6 to 7.2%). Among the 3,379 initially HBV-susceptible patients, the incidence of HBV infection was 1.7 (1.5 to 1.9)/100 person-years. Factors associated with incident infection were older age and IDU. The main limitation of the study was that 30% of participants did not have any HBsAg results available. However baseline characteristics of those with results did not differ from those of the whole cohort. Efforts are on-going to improve data collection.

Conclusions

The prevalence of HBV in UK CHIC is in line with estimates from other studies and low by international standards. Incident infection continued to occur even after entry to the cohort, emphasising the need to ensure early vaccination.     

Natural History of Anal Dysplasia in an HIV-Infected Clinical Care Cohort: Estimates Using Multi-State Markov Modeling

Objectives

(1) To model the natural history of anal neoplasia in HIV-infected patients using a 3-state Markov model of anal cancer pathogenesis, adjusting for cytology misclassification; and (2) to estimate the effects of selected time-varying covariates on transition probabilities.

Design

A retrospective cytology-based inception screening cohort of HIV-infected adults was analyzed using a 3-state Markov model of clinical pathogenesis of anal neoplasia.

Methods

Longitudinally ascertained cytology categories were adjusted for misclassification using estimates of cytology accuracy derived from the study cohort. Time-varying covariate effects were estimated as hazard ratios.

Results

(1) There was a moderate to high probability of regression of the high grade squamous intraepithelial lesion (HSIL) state (27–62%) at 2 years after initial cytology screening; (2) the probability of developing invasive anal cancer (IAC) during the first 2 years after a baseline HSIL cytology is low (1.9–2.8%); (3) infrared coagulation (IRC) ablation of HSIL lesions is associated with a 2.2–4.2 fold increased probability of regression to <HSIL; and (4) antiretroviral therapy, suppressed HIV plasma viral load, and CD4 ≥350/mm³ are each associated with reduced probability of progression from <HSIL to HSIL.

Conclusions

The finding of moderate to high rates of regression of the HSIL state accompanied by low rates of progression to IAC should inform both screening and precursor treatment guideline development. There appears to be a consistent and robust beneficial effect of antiretroviral therapy, suppressed viral load, and higher CD4 on the transition from the <HSIL state to the HSIL state.     

Natural History of Progression of HPV Infection to Cervical Lesion or Clearance: Analysis of the Control Arm of the Large,Randomised PATRICIA Study

Background

The control arm of PATRICIA (PApillomaTRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants.

Methods and Findings

Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 womenwith 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear.

Conclusions

Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.     

Clinical Manifestations and the Natural History of HIV Infection in Adults

The clinical expression of infection with the human immunodeficiency virus (HIV) appears increasingly complex. It includes manifestations due to opportunistic diseases, as well as illness directly caused by HIV itself. Neurologic disease may include involvement of the brain, spinal cord and peripheral nerves and is probably directly caused by HIV, as is lymphocytic interstitial pneumonia. The etiology of the chronic diarrhea and a papular pruritic skin eruption associated with HIV infection is unclear. Between 2% and 8% of HIV-infected persons progress to the acquired immunodeficiency syndrome (AIDS) per year, with no apparent decrease in the rate of disease progression over time. A chronically activated state secondary to chronic microbial antigenic exposure may increase both the susceptibility to HIV infection and development of disease. Increased HIV gene expression, followed by persistent antigenemia, appear to be triggering factors in clinical deterioration. The role, if any, of environmental and/or genetic cofactors remains unclear.     

Natural History of Perceived Food Hypersensitivity and IgE Sensitisation to Food Allergens in a Cohort of Adults

Background

No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults.

Objective

To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity.

Methods

Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20–45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation.

Results

Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (p<0.001) and IgE sensitisation to peanut decreased in particular by 67% (p = 0.003). The prevalence of timothy grass IgE sensitisation decreased by 15% (p = 0.003) while cat, mite and birch IgE sensitisation did not decrease significantly. Female sex, rhinitis, eczema and presence of IgE sensitisation to aeroallergens were independently associated with new onset food hypersensitivity.

Conclusion

The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens.     

Adherence to Chemoprophylaxis and Plasmodium falciparum Anti-Circumsporozoite Seroconversion in a Prospective Cohort Study of Dutch Short-Term Travelers

Background

We conducted a prospective study in a cohort of short-term travelers assessing the incidence rate of anti-circumsporozoite seroconversion, adherence to chemoprophylaxis, symptoms of malaria during travel, and malaria treatment abroad.

Methods

Adults were recruited from the travel clinic of the Public Health Service Amsterdam. They kept a structured daily travel diary and donated blood samples before and after travel. Blood samples were serologically tested for the presence of Plasmodium falciparum anti-circumsporozoite antibodies.

Results

Overall, the incidence rate (IR) of anti-circumsporozoite seroconversion was 0.8 per 100 person-months. Of 945 travelers, 620 (66%) visited high-endemic areas and were advised about both chemoprophylaxis and preventive measures against mosquito bites. Most subjects (520/620 = 84%) took at least 75% of recommended prophylaxis during travel. Travel to Africa, use of mefloquine, travel duration of 14–29 days in endemic areas, and concurrent use of DEET (N,N-diethyl-meta-toluamide) were associated with good adherence practices. Four travelers without fever seroconverted, becoming anti-circumsporozoite antibody-positive. All four had been adherent to chemoprophylaxis; two visited Africa, one Suriname, one India. Ten subjects with fever were tested for malaria while abroad and of these, three received treatment. All three were adherent to chemoprophylaxis and tested negative for anti-circumsporozoite antibodies.

Conclusion

Travel to Africa, using mefloquine, travel duration of 14–29 days in endemic areas, and use of DEET were associated with good adherence to chemoprophylaxis. The combination of chemoprophylaxis and other preventive measures were sufficient to protect seroconverting travelers from clinical malaria. Travelers who were treated for malaria abroad did not seroconvert.     

Pregnancy Outcomes after a Mass Vaccination Campaign with an Oral Cholera Vaccine in Guinea: A Retrospective Cohort Study

Introduction

Since 2010, WHO has recommended oral cholera vaccines as an additional strategy for cholera control. During a cholera episode, pregnant women are at high risk of complications, and the risk of fetal death has been reported to be 2–36%. Due to a lack of safety data, pregnant women have been excluded from most cholera vaccination campaigns. In 2012, reactive campaigns using the bivalent killed whole-cell oral cholera vaccine (BivWC), included all people living in the targeted areas aged ≥1 year regardless of pregnancy status, were implemented in Guinea. We aimed to determine whether there was a difference in pregnancy outcomes between vaccinated and non-vaccinated pregnant women.

Methods and Findings

From 11 November to 4 December 2013, we conducted a retrospective cohort study in Boffa prefecture among women who were pregnant in 2012 during or after the vaccination campaign. The primary outcome was pregnancy loss, as reported by the mother, and fetal malformations, after clinical examination. Primary exposure was the intake of the BivWC vaccine (Shanchol) during pregnancy, as determined by a vaccination card or oral history. We compared the risk of pregnancy loss between vaccinated and non-vaccinated women through binomial regression analysis. A total of 2,494 pregnancies were included in the analysis. The crude incidence of pregnancy loss was 3.7% (95%CI 2.7–4.8) for fetuses exposed to BivWC vaccine and 2.6% (0.7–4.5) for non-exposed fetuses. The incidence of malformation was 0.6% (0.1–1.0) and 1.2% (0.0–2.5) in BivWC-exposed and non-exposed fetuses, respectively. In both crude and adjusted analyses, fetal exposure to BivWC was not significantly associated with pregnancy loss (adjusted risk ratio (aRR = 1.09 [95%CI: 0.5–2.25], p = 0.818) or malformations (aRR = 0.50 [95%CI: 0.13–1.91], p = 0.314).

Conclusions

In this large retrospective cohort study, we found no association between fetal exposure to BivWC and risk of pregnancy loss or malformation. Despite the weaknesses of a retrospective design, we can conclude that if a risk exists, it is very low. Additional prospective studies are warranted to add to the evidence base on OCV use during pregnancy. Pregnant women are particularly vulnerable during cholera episodes and should be included in vaccination campaigns when the risk of cholera is high, such as during outbreaks.     

ICU-Onset Clostridium difficile Infection in a University Hospital in China: A Prospective Cohort Study

A prospective study was conducted to investigate the incidence, clinical profiles and outcome of ICU-onset CDI in a 50-bed medical ICU at a university hospital in China. Stools were collected from patients who developed ICU-onset diarrhea and was screened for tcdA (toxin A gene) and tcdB (toxin B gene) by PCR. CDI cases were compared with the ICU-onset non-CDI diarrhea cases for demographics, comorbidities, potential risk factors, major laboratory findings and outcomes. Stool samples from CDI cases were subjected to C. difficile culture and C. difficile isolates were screened for tcdA, tcdB and the binary toxin genes (cdtA and cdtB) using multiplex PCR. Strain typing of toxigenic C. difficile isolates was performed using multilocus sequence typing. There were 1,277 patients in the ICU during the study period and 124 (9.7%) developed ICU-onset diarrhea, of which 31 patients had CDI. The incidence of ICU-onset CDI was 25.2 cases per 10,000 ICU days. ICU-onset CDI cases had similar features with ICU-onset non-CDI diarrhea cases including the use of proton pump inhibitors and antibacterial agents. The crude mortality rate of ICU-onset CDI was 22.6%, but the attributable mortality rate of ICU-onset CDI was only 3.2% here. Toxigenic C. difficile isolates were recovered from 28 out of the 31 patients with CDI. cdtA and cdtB were found in two strains. Seventeen STs including 11 new STs were identified. All of the 11 new STs were single-locus variants of known STs and the 17 STs identified here could be clustered into 3 clades. The incidence of ICU-onset CDI here is similar to those in Europe and North America, suggesting that CDI is likely to be a common problem in China. Toxigenic C. difficile here belonged to a variety of STs, which may represent a significant clonal expansion rather than the true clonal diversity.     

Lifetime Smoking History and Cause-Specific Mortality in a Cohort Study with 43 Years of Follow-Up

BackgroundIn general, smoking increases the risk of mortality. However, it is less clear how the relative risk varies by cause of death. The exact impact of changes in smoking habits throughout life on different mortality risks is less studied.MethodsWe studied the impact of baseline and lifetime smoking habits, and duration of smoking on the risk of all-cause mortality, mortality of cardiovascular diseases (CVD), chronic obstructive pulmonary disease (COPD), any cancer and of the four most common types of cancer (lung, colorectal, prostate, and breast cancer) in a cohort study (Vlagtwedde-Vlaardingen 1965–1990, with a follow-up on mortality status until 2009, n = 8,645). We used Cox regression models adjusted for age, BMI, sex, and place of residence. Since previous studies suggested a potential effect modification of sex, we additionally stratified by sex and tested for interactions. In addition, to determine which cause of death carried the highest risk we performed competing-risk analyses on mortality due to CVD, cancer, COPD and other causes.ResultsCurrent smoking (light, moderate, and heavy cigarette smoking) and lifetime persistent smoking were associated with an increased risk of all-cause, CVD, COPD, any cancer, and lung cancer mortality. Higher numbers of pack years at baseline were associated with an increased risk of all-cause, CVD, COPD, any cancer, lung, colorectal, and prostate cancer mortality. Males who were lifetime persistent pipe/cigar smokers had a higher risk of lung cancer [HR (95% CI) = 7.72 (1.72–34.75)] as well as all-cause and any cancer mortality. A longer duration of smoking was associated with a higher risk of COPD, any and lung cancer [HR (95% CI) = 1.06 (1.00–1.12), 1.03 (1.00–1.06) and 1.10 (1.03–1.17) respectively], but not with other mortality causes. The competing risk analyses showed that ex- and current smokers had a higher risk of cancer, CVD, and COPD mortality compared to all other mortality causes. In addition, heavy smokers had a higher risk for COPD mortality compared to cancer, and CVD mortality.ConclusionOur study indicates that lifetime numbers of cigarettes smoked and the duration of smoking have different impacts for different causes of mortality. Moreover, our findings emphasize the importance of smoking-related competing risks when studying the smoking-related cancer mortality in a general population and that smoking cessation immediately effectively reduces the risk of all-cause and any cancer mortality.     

Epidemiology of Anal HPV Infection in High-Risk Men Attending a Sexually Transmitted Infection Clinic in Puerto Rico

Purpose

Recent studies in Puerto Rico have reported an increasing incidence of anal cancer in Puerto Rican men. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among men attending an STI clinic in Puerto Rico.

Methods

We conducted a cross-sectional study among 205 men 18 years and older. A comprehensive survey was administered that included a demographic and a behavioral assessment. Separate logistic regression models were performed to determine factors associated with any, high-risk (HR), and multiple anal HPV infection.

Results

The mean age of the study sample was 38.0±13.5 years. The most common HR types were 58, 51 and 31. Overall, HR anal HPV infection was found in 53.5% of the participants. Multiple HPV types in the anal canal were found in 47.6% of the sample. A third (29.8%) of participants reported being men who had sex with men (MSM). MSM had a significantly higher prevalence of any, HR and multiple HPV infection (p-value<0.05). Separate multivariate logistic regression analyses showed that being MSM was associated with any (OR = 4.5; [95%CI: 1.9–10.7]), HR (OR = 3.4; [95%CI: 1.1–10.3) and multiple anal HPV infection (OR = 3.6; [95%CI: 1.5–9.1). HIV was marginally associated with multiple anal HPV infection in multivariate analysis (OR = 3.3; 95%CI = 1.0–11.0).

Conclusions

Anal HPV is common among sexually active men attending this STI clinic, with higher likelihood of anal HPV infection among MSM.     

HPV16 Seropositivity and Subsequent HPV16 Infection Risk in a Naturally Infected Population: Comparison of Serological Assays

Background

Several serological assays have been developed to detect antibodies elicited against infections with oncogenic human papillomavirus (HPV) type 16. The association between antibody levels measured by various assays and subsequent HPV infection risk may differ. We compared HPV16-specific antibody levels previously measured by a virus-like particle (VLP)-based direct enzyme-linked immunoassay (ELISA) with levels measured by additional assays and evaluated the protection against HPV16 infection conferred at different levels of the assays.

Methodology/Principal Findings

Replicate enrollment serum aliquots from 388 unvaccinated women in the control arm of the Costa Rica HPV vaccine trial were measured for HPV16 seropositivity using three serological assays: a VLP-based direct ELISA; a VLP-based competitive Luminex immunoassay (cLIA); and a secreted alkaline phosphatase protein neutralization assay (SEAP-NA). We assessed the association of assay seropositivity and risk of subsequent HPV16 infection over four years of follow-up by calculating sampling-adjusted odds ratios (OR) and HPV16 seropositivity based on standard cutoff from the cLIA was significantly associated with protection from subsequent HPV16 infection (OR = 0.48, CI = 0.27–0.86, compared with seronegatives). Compared with seronegatives, the highest seropositive tertile antibody levels from the direct ELISA (OR = 0.53, CI = 0.28–0.90) as well as the SEAP-NA (OR = 0.20, CI = 0.06, 0.64) were also significantly associated with protection from HPV16 infection.

Conclusions/Significance

Enrollment HPV16 seropositivity by any of the three serological assays evaluated was associated with protection from subsequent infection, although cutoffs for immune protection were different. We defined the assays and seropositivity levels after natural infection that better measure and translate to protective immunity.     

Discovery of Metabolic Biomarkers for Duchenne Muscular Dystrophy within a Natural History Study

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown compounds at m/z of 357 and 312 while decreased metabolites included creatinine, androgen derivatives and other unknown yet to be identified compounds. Furthermore, the creatine to creatinine ratio is significantly associated with disease progression in DMD patients. This ratio sharply increased with age in DMD patients while it decreased with age in healthy controls. Overall, this study yielded promising metabolic signatures that could prove useful to monitor DMD disease progression and response to therapies in the future.     

乌兰布和沙漠天然白刺适应性群团抽样技术的研究

以乌兰布和沙漠地区天然白刺为具体研究对象,对不同抽样方法获取的数据进行了分析.研究结果表明,当适应性标准大于等于占位单元平均数时,适应性群团抽样比简单随机抽样更有效,并且可以保证估计精度;初始抽样比例越大,总体均值估计值和抽样相对效率越稳定.在该研究区域采用二阶适应性群团抽样,可以达到估计精度,但与简单随机抽样和适应性群团抽样相比效率偏低.     

Efficacy of a Six-Month versus a 36-Month Regimen for Prevention of Tuberculosis in HIV-Infected Persons in India: A Randomized Clinical Trial

Background

The optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown.

Methods

An open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared.

Findings

Tuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100py (95%CI- 1.4–3.5) and 1.6/100py (95% CI-0.8–3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8–3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6–4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant.

Interpretation

Both regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients.The trial is registered at ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00351702","term_id":"NCT00351702"}}NCT00351702.     

Determinants of Acceptance and Subsequent Uptake of the HPV Vaccine in a Cohort in Eldoret,Kenya

The development of Human Papillomavirus (HPV) vaccines provides new opportunities in the fight against cervical cancer. Many acceptability studies have revealed high interest in these vaccines, but acceptance is only a precursor of behavior, and many factors, at personal, community and provider level, may inhibit the translation of willingness to vaccinate into actual uptake. Through a longitudinal study in Eldoret, Kenya, HPV vaccine acceptability was measured before a vaccination program (n = 287) and vaccine uptake, as reported by mothers, once the program was finished (n = 256). In between baseline and follow-up, a pilot HPV vaccination program was implemented via the GARDASIL Access Program, in which parents could have their daughter vaccinated for free at the referral hospital. The program was promoted at schools: Health staff informed teachers who were then asked to inform students and parents. Even though baseline acceptance was very high (88.1%), only 31.1% of the women reported at follow-up that their daughter had been vaccinated. The vaccine was declined by 17.7%, while another 51.2% had wanted the vaccination but were obstructed by practical barriers. Being well-informed about the program and baseline awareness of cervical cancer were independently associated with vaccine uptake, while baseline acceptance was correlated in bivariate analysis. Side effects were of great concern, even among those whose daughter was vaccinated. Possible partner disapproval lowered acceptance at baseline, and women indeed reported at follow-up that they had encountered his opposition. In Kenya, women prove to be very willing to have their daughter vaccinated against cervical cancer. However, in this study, uptake was more determined by program awareness than by HPV vaccine acceptance. School-based vaccination might improve coverage since it reduces operational problems for parents. In addition, future HPV vaccination campaigns should address concerns about side effects, targeting men and women, given both their involvement in HPV vaccination decision-making.     

HPV和HCMV在慢性宫颈炎病人中的分布及相关性研究

本文采用DNA-DNA分子杂交技术对病理组织学确诊的87例慢性宫颈炎患者和25例健康宫颈的宫颈活检组织DNA进行了HPV 6、11、16、18型DNA及HCMV HindⅢE片段检测。结果表明,对照宫颈检出率全部为0,慢性宫颈炎检出率HPV 6为16％,HPVll为12.6％,HPV16为11.5％,HPVl8为5％,总的HPV DNA相关序列为29.0％,HCMV为12.64％。经显著性检验,HPV DNA相关序列检出率在慢性宫颈炎与对照组间具显著性差异,HPV DNA相关序列阳性者患慢性宫颈炎的危险性为HPV DNA相关序列阴性者20.81的倍。本实验结果还表明HCMV阳性患者中72.7％的病人同时有HPV感染,提示HCMV感染与HPV感染有关。     

鸭肝炎病毒感染和垂直传播的研究

用α-~(32)P-dATP-DHBV DNA探针做斑点杂交试验、检测了不同鸭种血清中携带DHBV情况。其中北京鸭与樱桃谷鸭的杂交种鸭杂交阳性率为5.1％;而不同鸭龄不同饲养条件的高邮麻鸭血清阳性率32.7—58.8％,经EM检测均在血清中找到病毒颗粒。将DHBV DNA不同的亲代配对所组成的四个组分群饲养,观察产卵后再孵化出的雏鸭DHBVDNA阳性率。第一组(♀-(?)-)为0％,第二组(♀ (?) )为100％,第三组(♀-(?) )28％,第四组(♀ (?)-)100％。然而亲代雌雄鸭均为DHBV DNA阴性的雌鸭所产卵在孵化到第9天时,经尿囊腔注射1×10~9病毒颗粒/m110μl的血清,孵出雏鸭时DHBV DNA阳性率达83.3％。