The convergence of non-communicable disease (NCD) and infectious disease (ID) in low- and middle-income countries (LMICs) presents new challenges and new opportunities to enact responsive changes in policy and research. Most LMICs have significant dual disease burdens of NCDs such as cardiovascular disease, diabetes and cancer, and IDs including tuberculosis, HIV/AIDS and parasitic diseases. A combined strategy is needed in surveillance and disease control; yet, experts, institutions and policies that support prevention and control of these two overarching disease categories have limited interaction and alignment. NCDs and IDs share common features, such as long-term care needs and overlapping high-risk populations, and there are also notable direct interactions, such as the association between certain IDs and cancers, as well as evidence of increased susceptibility to IDs in individuals with NCDs. Enhanced simultaneous surveillance of NCD and ID comorbidity in LMIC populations would generate the empirical data needed to better understand the dual burden, and to target coordinated care. Where IDs and NCDs are endemic, focusing on vulnerable populations by strengthening social protections and improving access to health services is crucial, as is the re-alignment of efforts to combine NCD and ID screening, treatment programmes, and the assessment of their impact. Integrating public health activities for ID and NCD should extend beyond health care services to prevention, which is widely seen as crucial to successful NCD and ID control campaigns alike. The convergence of NCD and ID in LMICs has the potential to overstretch already strained health systems. With some LMICs now focused on major health system reforms, a unique opportunity is available to address NCD and ID challenges with newfound urgency and novel approaches.
Chronic disease; infectious disease; development transition
The distribution of allergens may vary with different geographic areas, suggesting the importance of local epidemiological data to support evidence-based prevention and management of allergic diseases. We investigated the distribution of common allergens in allergic patients in Guangzhou, southern China.
7,047 patients with allergic symptoms were examined for serum sIgE to 15 common allergens in this region, based on the protocol of reversed enzyme allergosorbent test.
4,869 (69.09%) of the subjects tested positive for sIgE to at least one of the 15 common allergens. There was no statistical difference in the overall rate of positive sIgE detection between males (3128/4523, 69.16%) and females (1741/2524, 68.98%). Der pteronyssinus and Der farinae were the most common aeroallergens, while eggs and cow’s milk the most common food allergens, responsible for higher positive rates of sIgE responses. A good correlation in positive sIgE response was found between Der pteronyssinus and Der farinae. By age-group analysis, we noted several peaks of sensitization to certain allergens: Der pteronyssinus, Der farinae, and Blomiatropicalis at age between 9 and 12; Blattellagermanica and mosquito at age between 15 and 18, cow’s milk before age 3; eggs and flour at age between 3 and 6; crabs and shrimps at age between 12 and 15. Along with older age, there was an ascending tendency in the overall positive rate of sIgE response to house dust mites among subjects who tested positive for sIgE to eggs or cow’s milk.
Der pteronyssinus, Der farinae, cow’s milk, and eggs are major allergens in Guangzhou. Sensitization to eggs and cow’s milk is more common at younger age, and then gives place to the increasing prevalence of sensitization to Der pteronyssinus and Der farinae at older age. Such a sequence of events may be a result of allergy march. Knowledge on the prevalence of allergen sensitization in different age groups would help early diagnosis and intervention of allergic diseases in this large geographical region.
Allergy; Distribution; Prevalence; Specific immunoglobulin E
The purpose of this study was to establish an animal model of chronic pulmonary hypertension with a single-dose intraperitoneal injection of monocrotaline (MCT) in young Tibet minipigs, so as to enable both invasive and noninvasive measurements and hence facilitate future studies.
Twenty-four minipigs (8-week-old) were randomized to receive single-dose injection of 12.0 mg/kg MCT (MCT group, n = 12) or placebo (control group, n = 12 each). On day 42, all animals were evaluated for pulmonary hypertension with conventional transthoracic echocardiography, right heart catheterization (RHC), and pathological changes. Findings of these studies were compared between the two groups.
At echocardiography, the MCT group showed significantly higher pulmonary arterial mean pressure (PAMP) compared with the controls (P<0.001). The pulmonary valve curve showed v-shaped signals with reduction of a-waves in minipigs treated with MCT. In addition, the MCT group had longer pulmonary artery pre-ejection phases, and shorter acceleration time and ejection time. RHC revealed higher mean pulmonary arterial pressure (mPAP) in the MCT group than in the control group (P<0.01). A significant and positive correlation between the mPAP values and the PAMP values (R = 0.974, P<0.0001), and a negative correlation between the mPAP and ejection time (R = 0.680, P<0.0001) was noted. Pathology demonstrated evidence of pulmonary vascular remodeling and higer index of right ventricular hypertrophy in MCT-treated minipigs.
A chronic pulmonary hypertension model can be successfully established in young minipigs at six weeks after MCT injection. These minipig models exhibited features of pulmonary arterial hypertension that can be evaluated by both invasive (RHC) and noninvasive (echocardiography) measurements, and may be used as an easy and stable tool for future studies on pulmonary hypertension.
Two new peptides, MCh-1 and MCh-2, along with three known trypsin inhibitors (MCTI-I, MCTI-II and MCTI-III), were isolated from the seeds of the tropical vine Momordica charantia. The sequences of the peptides were determined using mass spectrometry and NMR spectroscopy. Using a strategy involving partial reduction and stepwise alkylation of the peptides, followed by enzymatic digestion and tandem mass spectrometry sequencing, the disulfide connectivity of MCh-1 was elucidated to be CysI-CysIV, CysII-CysV and CysIII-CysVI. The three-dimensional structures of MCh-1 and MCh-2 were determined using NMR spectroscopy and found to contain the inhibitor cystine knot (ICK) motif. The sequences of the novel peptides differ significantly from peptides previously isolated from this plant. Therefore, this study expands the known peptide diversity in M. charantia and the range of sequences that can be accommodated by the ICK motif. Furthermore, we show that a stable two-disulfide intermediate is involved in the oxidative folding of MCh-1. This disulfide intermediate is structurally homologous to the proposed ancestral fold of ICK peptides, and provides a possible pathway for the evolution of this structural motif, which is highly prevalent in nature.
Optical coherence tomography (OCT) is a new imaging technique capable of obtaining high-resolution intravascular images and has been used in interventional cardiology. However, an application of OCT in pulmonary arteries had seldom been documented. In this case, OCT imaging is performed in peripheral pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are aspirated and confirmed by a histological examination. These findings suggest that OCT may be a useful tool to depict peripheral pulmonary artery thrombi.
Optical coherence tomography; Peripheral pulmonary artery thrombi; Pulmonary thromboembolism; CT pulmonary angiography; Intravascular ultrasound
In response to several influenza A(H1N1)pdm09 infections that developed in passengers after they traveled on the same 2 flights from New York, New York, USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of fever and respiratory symptoms and detection of virus by PCR in a passenger or crew member of either flight. Illness developed only in passengers who traveled on the New York to Hong Kong flight. We compared exposures of 9 case-passengers with those of 32 asymptomatic control-passengers. None of the 9 case-passengers, compared with 47% (15/32) of control-passengers, wore a face mask for the entire flight (odds ratio 0, 95% CI 0–0.71). The source case-passenger was not identified. Wearing a face mask was a protective factor against influenza infection. We recommend a more comprehensive intervention study to accurately estimate this effect.
influenza; influenza A virus; influenza A(H1N1)pdm09 virus; viruses; aircraft; trans-pacific passenger aircraft; disease outbreak; face masks; China; Hong Kong; United States; outbreak; air travel; travel
Although seasonal variation in tuberculosis (TB) incidence has been described in many countries, it remains unknown in China.
A time series decomposition analysis (X-12-ARIMA) was performed to examine the seasonal variation in active TB cases nationwide from 2005 through 2012 in China. Seasonal amplitude was calculated for the evaluation of TB seasonal variation.
A total of 7.78 million active TB cases were reported over a period of 8 years. A spring peak (April) was observed with seasonal amplitude of 46.3%, compared with the winter trough (February). Most cases in provinces with subtropical and tropical monsoon climate showed lower amplitudes than those in temperate continental, plateau and mountain climate regions. The magnitude of seasonality varied inversely with annual average temperature, r (95% CI) = -0.71 (-0.79, -0.61). The seasonal amplitudes were 56.7, 60.5, 40.6, 46.4 and 50.9% for patients aged ≤14, 15–24, 25–44, 45–64, and ≥65 years, respectively. Students demonstrated greater seasonal amplitude than peasants, migrant workers and workers (115.3% vs. 43.5, 41.6 and 48.1%). Patients with pulmonary TB had lower amplitude compared to patients with pleural and other extra-pulmonary TB (EPTB) (45.9% vs. 52.0 and 56.3%). Relapse cases with sputum smear positive TB (SS+ TB) had significantly higher seasonal amplitude compared to new cases with sputum smear positive TB (52.2% vs. 41.6%).
TB is a seasonal disease in China. The peak and trough of TB transmission actually are in winter and in autumn respectively after factors of delay are removed. Higher amplitudes of TB seasonality are more likely to happen in temperate continental, plateau and mountain climate regions and regions with lower annual average temperature, and young person, students, patients with EPTB and relapse cases with SS+ TB are more likely to be affected by TB seasonality.
A prolonged measles epidemic occurred in Wenzhou City, China after a nationwide measles mass immunization campaign (MMIC) in 2010. We conducted an investigation to identify factors contributing to this epidemic and to provide evidence-based recommendations for measles elimination strategies in China.
Measles was diagnosed using the national standard case-definitions. We estimated the population vaccination coverage based on the proportion of measles patients that had been vaccinated. In a case–control investigation, all measles patients who received treatment in The Second Affiliated Hospital of Wenzhou Medical College (Hospital S) during November 1 to December 31, 2010 served as cases; controls were randomly selected among all other patients who received treatment in Hospital S during the same time period, frequency matched by month of hospital visit. We reviewed medical records of case- and control-patients to compare their exposure history at Hospital S and to its intravenous rehydration room (IV room) during the incubation period (7–21 days before their illness onset).
The attack rate of measles in Wenzhou City was 3.3/100,000 during September 1, 2010 to January 11, 2011. Children aged 8-11 m had the highest attack rate (171/100,000) of all age groups. In children not age-eligible for the MMIC but should have been routinely vaccinated after the MMIC, the vaccination rate was only 52%. In the case–control investigation, 60% (25/42) of case-patients compared with 21% (35/168) of control-patients had visited Hospital S (adjusted ORM-H = 5.5, 95% CI = 2.7–11). Among unvaccinated children who had received treatment in Hospital S, 84% (21/25) of case-patients compared 38% (11/29) of control-patients had visited the IV room (adjusted ORM-H = 9.2, 95% CI = 1.5–59).
Relaxed routine measles vaccination among children after the MMIC was the main factor responsible for this epidemic. Exposure in the IV room at Hospital S facilitated the epidemic. To reach the goal of measles elimination, the Chinese public health authorities should make greater efforts to improve timely routine measles vaccination, and to reduce nosocomial transmission.
On 12 May 2012, over 200 college students with acute diarrhoea were reported to the Guizhou Center for Disease Control and Prevention. We conducted an investigation to identify the agent and mode of transmission and to recommend control measures.
A suspected case was a person at the college with onset of ≥ two of the following symptoms: diarrhoea (more than three loose stools in 24 hours), abdominal pain, vomiting or fever (> 37.5C) between 6 and 15 May 2012. A confirmed case also had a positive Aeromonas hydrophila culture from a stool sample. A retrospective-cohort study of 902 students compared attack rates (AR) by dining place, meals and food history. We reviewed the implicated premise, its processes and preparation of implicated food.
We identified 349 suspected cases (AR = 14%) and isolated Aeromonas hydrophila from three stools of 15 cases. Students who ate in cafeteria A were more likely to be ill compared to those eating in other places (relative risk [RR]: 3.1, 95% confidence interval [CI]: 2.0–4.8). The cohort study implicated cold cucumber (RR: 2.6, 95% CI: 2.0–3.3) and houttuynia dishes (RR: 1.8, 95% CI: 1.4–2.3). Environmental investigation showed that vegetables were washed in polluted water from a tank close to the sewage ditch, then left at 30 °C for two hours before serving. The Escherichia coli count of the tank was well above the standard for drinking-water.
This outbreak of Aeromonas hydrophila was most probably caused by salad ingredients washed in contaminated tank water. We recommended enhancing training of foodhandlers, ensuring tanks and sewerage systems comply with appropriate standards and adequate monitoring of drinking-water sources.
The evaluation of the carotid artery wall is essential for the diagnosis of cardiovascular pathologies or for the assessment of a patient’s cardiovascular risk. This paper presents a completely user-independent algorithm, which automatically extracts the far double line (lumen–intima and media–adventitia) in the carotid artery using an Edge Flow technique based on directional probability maps using the attributes of intensity and texture. Specifically, the algorithm traces the boundaries between the lumen and intima layer (line one) and between the media and adventitia layer (line two). The Carotid Automated Ultrasound Double Line Extraction System based on Edge-Flow (CAUDLES-EF) is characterized and validated by comparing the output of the algorithm with the manual tracing boundaries carried out by three experts. We also benchmark our new technique with the two other completely automatic techniques (CALEXia and CULEXsa) we previously published. Our multi-institutional database consisted of 300 longitudinal B-mode carotid images with normal and pathologic arteries. We compared our current new method with previous methods, and showed the mean and standard deviation for the three methods: CALEXia, CULEXsa, and CAUDLES-EF as 0.134 ± 0.088, 0.074 ± 0.092, and 0.043 ± 0.097 mm, respectively. Our IMT was slightly underestimated with respect to the ground truth IMT, but showed a uniform behavior over the entire database. Regarding the Figure of Merit (FoM), CALEXia and CULEXsa showed the values of 84.7% and 91.5%, respectively, while our new approach, CAUDLES-EF, performed the best at 94.8%, showing a good improvement compared to previous methods.
Carotid artery; Ultrasound; Multiresolution; Edge flow; Localization; Intima–media thickness; Hausdorff distance; Polyline distance; Segmentation; Automated measurement; Carotid imaging; Intima-media thickness measurement; Edge-flow operator
On 23 May 2012, a university in Jiangxi, China reported a gastroenteritis outbreak. We investigated the outbreak to identify the agent, source and mode of transmission and to recommend control measures.
A case was defined as any person from the university with onset of diarrhoea (≥ 3 times/24h) from 1 to 31 May 2012. Active case finding was conducted by reviewing university hospital and drug-store records and interviewing students, workers and teachers. We then conducted a case-control study in which we compared food, water and environmental exposure history. Water samples were collected and tested.
We identified 417 cases – an attack rate (AR) of 4.7% (417/8781) for the university. There were 416 student cases (AR = 5.7%) distributed across all 11 colleges, five of which were more heavily affected (AR range = 5.9–14%). In the case-control study, cases had higher odds of having drunk bottled water (odds ratio [OR] = 4.1; 95% confidence interval [CI] = 1.7–9.9), and there was a dose–response relationship (χ2trend = 4.6, P < 0.05). Drinking boiled bottled water was inversely associated with being a case (OR = 0.22, 95% CI = 0.07–0.71). Eating in any of the three university canteens or drinking-water from the city water supply was not associated with being a case. Pathogenic Escherichia coli was isolated from two unopened bottled water specimens and from four student cases.
This gastroenteritis outbreak was most likely caused by contaminated bottled water. The company in question has been shut down and no further cases have been reported. Increased regulation of bottled water plants and better coordination between different investigators for future outbreaks is recommended.
Clusters of sudden unexplained death (SUD) in Yunnan Province, China, have been linked to eating Trogia venenata mushrooms. We evaluated the toxic effect of this mushroom on mice.
We prepared extracts of fresh T. venenata and Laccaria vinaceoavellanea mushrooms collected from the environs of a village that had SUD. We randomly allocated mice into treatment groups and administered mushroom extracts at doses ranging from 500 to 3500 mg/kg and water (control) via a gavage needle. We observed mice for mortality for 7 days after a 3500 mg/kg dose and for 24 hours after doses from 500 to 3000 mg/kg. We determined biochemical markers from serum two hours after a 2000 mg/kg dose.
Ten mice fed T. venenata extract (3500 mg/kg) died by five hours whereas all control mice (L. vinaceoavellanea extract and water) survived the seven-day observation period. All mice died by five hours after exposure to single doses of T. venenata extract ranging from 1500 to 3000 mg/kg, while the four mice exposed to a 500 mg/kg dose all survived. Mice fed 2000 mg/kg of T. venenata extract developed profound hypoglycemia (median = 0.66 mmol/L) two hours after exposure.
Hypoglycemia and death within hours of exposure, a pattern unique among mushroom toxicity, characterize T. venenata poisoning.
Since the late 1970's, time-space clusters of sudden unexplained death (SUD) in northwest Yunnan, China have alarmed the public and health authorities. From 2006–2009, we initiated enhanced surveillance for SUD to identify a cause, and we warned villagers to avoid eating unfamiliar mushrooms.
We established surveillance for SUD, defined as follows: sudden onset of serious, unexplained physical impairment followed by death in <24 hours. A mild case was onset of any illness in a member of the family or close socially related group of a SUD victim within 1 week of a SUD. We interviewed witnesses of SUD and mild case-persons to identify exposures to potentially toxic substances. We tested blood from mild cases, villagers, and for standard biochemical, enzyme, and electrolyte markers of disease.
We identified 33 SUD, a 73% decline from 2002–2005, distributed among 21 villages of 11 counties. We found a previously undescribed mushroom, Trogia venenata, was eaten by 5 of 7 families with SUD clusters compared to 0 of 31 other control-families from the same villages. In T. venenata–exposed persons SUD was characterized by sudden loss of consciousness during normal activities. This mushroom grew nearby 75% of 61 villages that had time-space SUD clusters from 1975 to 2009 compared to 17% of 18 villages with only single SUD (p<0.001, Fisher's exact test).
Epidemiologic data has implicated T. venenata as a probable cause of clusters of SUD in northwestern Yunnan Province. Warnings to villagers about eating this mushroom should continue.
Increased intima-media thickness (IMT) is an early marker of atherosclerotic disease and several prospective studies have demonstrated that IMT is a strong predictor of cerebrovascular complications. In this paper we propose a novel method to assess IMT, called “intima media thickness variability” (IMTV) and evaluate its relationship with the development of cerebrovascular events.
Material and Methods
The study was approved by the local IRB. Twenty consecutive patients underwent ultrasound analysis of the carotid arteries (mean age 68 years; age range 59-81 years). The IMT and IMTV of the 40 carotid vessels was assessed. Bland–Altman statistics were employed to measure the inter-observer variability, and ROC analysis was used to assess the association with cerebrovascular events.
In all cases the ROC area under the curve was higher for IMTV than IMT. There was a statistical significant association between IMTV and cerebrovascular events (P=0.018), but no relationship between IMT and events. The results for inter-observer variability showed a systematic error between 0.04 and 0.08 mm. In the Person Rho correlation analysis in no case a statistical association between IMT and symptoms was detected whereas in 2 cases (observer 1 and observer 2), a statistically significant association between IMTV and symptoms was found.
Data of this preliminary study suggest that IMTV may represent a powerful method to assess carotid atherosclerotic disease with a significant association to cerebrovascular events.
Increased intima-media thickness; intima media thickness variability; carotid atherosclerotic disease; cerebrovascular events
Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer’s dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer’s Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer’s dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were ‘amyloid positive’ (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were ‘amyloid negative’ (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan–Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P < 0.001) while Aβ load did not (P = 0.44). In contrast, when all 218 subjects with mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter-quartile difference of 2.6 for both); however, the risk profile was linear throughout the range of hippocampal atrophy values but reached a ceiling at higher values of brain Aβ load. Our results are consistent with a model of Alzheimer’s disease in which Aβ deposition initiates the pathological cascade but is not the direct cause of cognitive impairment as evidenced by the fact that Aβ load severity is decoupled from risk of progression at high levels. In contrast, hippocampal atrophy indicates how far along the neurodegenerative path one is, and hence how close to progressing to dementia. Possible explanations for our finding that many subjects with mild cognitive impairment have intermediate levels of Aβ load include: (i) individual subjects may reach an Aβ load plateau at varying absolute levels; (ii) some subjects may be more biologically susceptible to Aβ than others; and (iii) subjects with mild cognitive impairment with intermediate levels of Aβ may represent individuals with Alzheimer’s disease co-existent with other pathologies.
mild cognitive impairment; amyloid imaging; magnetic resonance imaging; cerebrospinal fluid; Alzheimer’s disease biomarkers
This outbreak was caused by droplet transmission.
During June 2–8, 2009, an outbreak of influenza A pandemic (H1N1) 2009 occurred among 31 members of a tour group in China. To identify the mode of transmission and risk factors, we conducted a retrospective cohort investigation. The index case-patient was a female tourist from the United States. Secondary cases developed in 9 (30%) tour group members who had talked with the index case-patient and in 1 airline passenger (not a tour group member) who had sat within 2 rows of her. None of the 14 tour group members who had not talked with the index case-patient became ill. This outbreak was apparently caused by droplet transmission during coughing or talking. That airborne transmission was not a factor is supported by lack of secondary cases among fellow bus and air travelers. Our findings highlight the need to prevent transmission by droplets and fomites during a pandemic.
influenza; H1N1; outbreak; pandemic; transmission; droplet; viruses; expedited; China; research
To identify mutations within the TGFBI gene in a Chinese family with lattice corneal dystrophy type I (LCD I).
Genomic DNA of three affected, four unaffected family members and 50 normal individuals was extracted from peripheral leukocytes. All exons of TGFBI were amplified by polymerase chain reaction (PCR) methods and direct sequencing was carried out for mutation analysis.
A missense mutation (1565T→A) in exon12 of TGFBI led to an amino acid substitution I522N in the TGFB-induced protein in all affected family members, but the mutation was not detected in normal subjects of the family and control individuals.
We conclude that the novel mutation I522N causes lattice corneal dystrophy type I in the studied family. This is the first report of the I522N mutation within TGFBI in LCD I worldwide.