Cancer Registration in India - Current Scenario and Future Perspectives

Cancer registration, an important component of cancer surveillance, is essential to a uni ed, scienti c and public health approach to cancer prevention and control. India has one of the highest cancer incidence and mortality rates in the world. A good surveillance system in the form of cancer registries is important for planning and evaluating cancer-control activities. Cancer registration in India was initiated in 1964 and expanded since 1982, through initiation of the National Cancer Registry Program (NCRP) by the Indian Council of Medical Research. NCRP currently has twenty-six population based registries and seven hospital based registries. Yet, Indian cancer registries, mostly in urban areas, cover less than 15% of the population. Other potential concerns about some Indian registries include accuracy and detail of information on cancer diagnosis, and timeliness in updating the registry databases. It is also important that necessary data collection related quality assurance measures be undertaken rigorously by the registries to ensure reliable and valid information availability. This paper reviews the current status of cancer registration in India and discusses some of the important pitfalls and issues related to cancer registration. Cancer registration in India should be complemented with a nationwide effort to foster systematic investigations of cancer patterns and trends by states, regions and sub populations and allow a continuous cycle of measurement, communication and action.     

The rationale for integrated childhood meningoencephalitis surveillance: a case study from Cambodia

Problem

Recent progress in vaccine availability and affordability has raised prospects for reducing death and disability from neurological infections in children. In many Asian countries, however, the epidemiology and public health burden of neurological diseases such as Japanese encephalitis and bacterial meningitis are poorly understood.

Approach

A sentinel surveillance system for Japanese encephalitis was developed and embedded within the routine meningoencephalitis syndromic surveillance system in Cambodia in 2006. The sentinel surveillance system was designed so surveillance and laboratory testing for other etiologies of neurological infection could be incorporated.

Local setting

The Communicable Disease Control department of the Ministry of Health in Cambodia worked with partners to establish the sentinel surveillance system.

Relevant changes

The sentinel surveillance system has provided important information on the disease burden of Japanese encephalitis in Cambodia and is now providing a platform for expansion to incorporate laboratory testing for other vaccine-preventable neurological infections in children.

Lessons learned

Sentinel surveillance systems, when linked to syndromic reporting systems, can characterize the epidemiology of meningoencephalitis and identify the proportion of hospital-based neurological infection in children that is vaccine preventable. Integrated systems enable consistency in data collection, analysis and information dissemination, and they enhance the capacity of public health managers to provide more credible and integrated information to policy-makers. This will assist decision-making about the potential role of immunization in reducing the incidence of childhood neurological infections.     

Display of neutralizing epitopes of Canine parvovirus and a T-cell epitope of the fusion protein of Canine distemper virus on chimeric tymovirus-like particles and its use as a vaccine candidate both against Canine parvo and Canine distemper

Expression of Physalis mottle tymovirus coat protein in Escherichia coli was earlier shown to self-assemble into empty capsids that were nearly identical to the capsids formed in vivo. Amino acid substitutions were made at the N-terminus of wild-type Physalis mottle virus coat protein with neutralizing epitopes of Canine parvovirus containing the antigenic sites 1–2, 4 and 6–7 and T-cell epitope of the fusion protein of Canine distemper virus in various combinations to yield PhMV1, PhMV2, PhMV3, PhMV4 and PhMV5. These constructs were cloned and expressed in E. coli. The chimeric proteins self-assembled into chimeric tymovirus-like particles (TVLPs) as determined by electron microscopy. The TVLPs were purified by ultracentrifugation and injected into guinea pigs and dogs to determine their immunogenicity. Initial immunogenicity studies in guinea pigs indicated that PhMV3 gave a higher response in comparison to the other TVLPs for both CPV and CDV and hence all further experiments in dogs were done with PhMV3. HI was done against different isolates obtained from various parts of the country. Protective titres indicated the broad spectrum of the vaccine. In conclusion the study indicated that the above chimeric VLP based vaccine could be used in dogs to generate a protective immune response against diseases caused by both Canine parvo and Canine distemper virus.     

Evaluation of Japanese encephalitis virus DNA vaccine candidates in rhesus monkeys [Macaca mulatta

We have previously described DNA vaccine candidates against Japanese encephalitis virus (JEV) that were immunogenic in mice. Present study was conducted to evaluate their immunogenicity in rhesus monkeys (Macaca mulatta) and compare it with the commercial mouse brain-derived, formalin-inactivated vaccine. Groups of four monkeys were immunized with either pMEa (expressing the anchored form of the envelope protein along with the pre-membrane protein of JEV) or pMEs (expressing the secretory form of the envelope protein along with pre-membrane protein of JEV) by intra-muscular (IM, using needle) or intra-dermal (ID, using gene gun) routes. Following primary immunization with 1mg plasmid DNA given IM, or 5 microg plasmid DNA given ID, the monkeys were boosted after 1 and 2 months with 0.5mg DNA given IM or 5 microg DNA given ID, and observed for a period of 6 months. After the second booster, most of the monkeys sero-converted and developed JEV neutralizing antibodies, albeit of low titer. Importantly however, following a sham challenge with the mouse brain-derived inactivated JEV vaccine given 6 months after immunization, the neutralizing antibody titers rose rapidly indicating a vigorous anamnestic response. Based on the JEV neutralizing antibody response following the vaccination and the extent of anamnestic response generated in the immunized monkeys, plasmid pMEa was superior to pMEs. This study indicates that the JEV candidate DNA vaccine is capable of generating protective levels of JEV neutralizing antibodies in rhesus monkeys and prime the immune system effectively against a subsequent exposure to JEV.     

Association of obesity with diabetic retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS Report no. 8)

The aim of the study was to report the prevalence of obesity indices in individuals with diabetes and find out their association with diabetic retinopathy in the urban Indian population. Subjects (n = 1,414) were recruited from Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetics Study (SN-DREAMS-I), a cross-sectional study between 2003 and 2006. Anthropometric measurements were carried out, and all patients’ fundi were photographed using 45° four-field stereoscopic digital photography. The diagnosis of diabetic retinopathy was based on the modified Klein classification. Generalized obesity and abdominal obesity were defined using WHO Asia Pacific guidelines with the BMI (body mass index) cutoff as ≥23 kg/m², WC (waist circumference) cutoffs as ≥90 cm in men and ≥80 cm in women and WHO guidelines using WHR (waist-to-hip ratio) cutoffs as ≥0.90 for men and ≥0.85 for women. Prevalence of obesity defined by BMI and WC was more in women compared to men, and that defined by WHR was more in men compared to women (P < 0.001). The prevalence of isolated generalized obesity, isolated abdominal obesity and combined obesity were 5.4, 10.1 and 58% in men and 4.5, 10.8 and 74.4% in women, respectively. The prevalence of any diabetic retinopathy and sight-threatening diabetic retinopathy was more in the isolated abdominal obesity group (26.35 and 6.08%, respectively) than in other subgroups. On logistic regression analysis, isolated abdominal obesity (OR 2.02, 95% CI: 1.06–3.86) and increased WHR in women (OR 1.48 95% CI: 1.10–2.38) were associated with diabetic retinopathy; BMI ≥ 23 (OR 0.66, 95% CI: 0.48–0.90) and combined obesity (OR 0.72, 95% CI: 0.53–0.99) had a protective role for any diabetic retinopathy in the overall group. In the urban south Indian population, isolated abdominal obesity and higher WHR in women were associated with diabetic retinopathy, but not with the severity of diabetic retinopathy.     

Effects of insulin-like growth factor-1 (IGF-1) receptor signaling on rates of apoptosis in retina of dopamine beta hydroxylase (Dbh−/−) knockout mice

We have investigated whether insulin-like growth factor-1 (IGF-1) receptor signaling alters rates of apoptosis in dopamine beta-hydroxylase (Dbh^?/?) knockout mice. Retinal lysates from Dbh^?/? and their heterozygote littermates (Dbh^+/?) were used to examine the role of norepinephrine in the regulation of IGF-1 receptor signaling and apoptosis in the retina. Western blot analysis was done for protein levels of total and phosphorylated IGF-1 receptor, insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), and Akt. A caspase 3 ELISA and dopamine ELISA were done on retinal lysates. To verify which regions of the retina were undergoing apoptosis, TUNEL labeling was performed. No changes in dopamine were noted between the KO and heterozygote mice. IGF-1 receptor phosphorylation was significantly decreased in Dbh^?/? mice as compared to their heterozygote littermates (P < 0.05 vs. heterozygous mice). IRS-1 protein phosphorylation was significantly decreased in KO mice (P < 0.05 vs. heterozygous mice), while no significant changes were noted in IRS-2 protein phosphorylation. Akt protein phosphorylation was also reduced in the KO mice, likely leading to increased cleaved caspase 3 levels. The increase in apoptosis in the Dbh^?/? mice occurred predominantly in the inner retina. Our results suggest that IGF-1 receptor signaling is reduced in the retina of mice with dysfunctional adrenergic receptor signaling. The data also indicate that IGF-1 receptor signaling occurs primarily through IRS-1, rather than IRS-2. The reduction in Akt phosphorylation, likely through reduced IGF-1 receptor signaling, could explain the increase in cleaved caspase 3, leading to apoptosis. These results suggest that alterations in adrenergic receptor signaling modulate IGF-1 receptor signaling, which can regulate apoptosis in the retina.