Strategies & recent development of transmission-blocking vaccines against Plasmodium falciparum.

Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines.

Emergence of dengue in tribal villages of Mandla district, Madhya Pradesh, India.

Background & objectives: Dengue (DEN) is a rapidly spreading arboviral disease transmitted by Aedes mosquitoes. Although it is endemic in India, dengue virus (DENV) infection has not been reported from tribal areas of Madhya Pradesh. Investigations were conducted to establish the aetiology of sudden upsurge of cases with febrile illness in June 2013 from tribal villages of Mandla district of Madhya Pradesh, India. Methods: The rapid response team of the National Institute for Research in Tribal Health, Jabalpur, conducted clinical investigations and field surveys to collect the samples from suspected cases. Samples were tested using molecular and serological tools. Collected mosquitoes were identified and tested for the presence of virus using semi nested reverse transcriptase-polymerase chain reaction (nRT-PCR). The sequences were analysed to identify serotype and genotype of the virus. Results: of the 648 samples collected from 18 villages of Mandla, 321 (49.53%) were found to be positive for dengue. The nRT-PCR and sequencing confirmed the aetiology as dengue virus type 2. Eighteen per cent of patients needed hospitalization and five deaths were attributed to dengue. The virus was also detected from Aedes aegypti mosquito, which was incriminated as a vector. Phylogenetic analysis revealed that the dengue virus 2 detected belonged to cosmopolitan genotype of the virus. Interpretation & conclusions: Dengue virus serotype 2 was detected as the aetiological agent in the outbreak in tribal villages of Mandla district of Madhya Pradesh. Conducive man-made environment favouring mosquitogenic conditions and seeding of virus could be the probable reasons for this outbreak. Urgent attention is needed to control this new threat to tribal population, which is already overburdened with other vector borne diseases.

Establishing communication mechanism for malaria prevention in Baiga tribal villages in Baiga chak area of Dindori district, Madhya Pradesh.

Background & objectives: Malaria is a serious public health concern in several parts of India, particularly in tribal areas of Madhya Pradesh (MP). Dindori district inhabitated by Baiga tribe, contributes about 15 per cent to the total malaria burden in MP. The tribal and other local inhabitants believe in magico-religious treatment of malaria and use modern health facilities only as second line of treatment. The present study was planned in the villages of one of the particularly vulnerable tribal group of MP, the Baigas. The objective of the study was to generate awareness and utilization of health services for malaria by establishing a communication strategy using local students and unemployed youths as agents of change. Methods: The study was undertaken in 47 villages and the need based IEC (information, education and communication) intervention was evaluated within four months of initiation by adopting before and after with control design. For both baseline and resurvey the households covered each time were 2350. Results: The baseline data generated revealed that around 53 per cent of the people in the study villages were aware of malaria. Among the non Baigas, 59 per cent were aware of malaria, while among the Baigas it was 49 per cent. IEC intervention could raise the level of awareness to malaria significantly with a net intervention effect of 23 per cent. The IEC intervention also improved the utilization of modern health services significantly. Interpretation & conclusions: The IEC strategy designed by using local children and youths was effective as the malaria was on decline in the study area. The same strategy with necessary modifications may be replicated in other areas pandemic for malaria.

Socio-economic & household risk factors of malaria in tribal areas of Madhya Pradesh, central India.

Background & objectives: Malaria is a major public health problem in many states of the country, particularly, in Madhya Pradesh where both Plasmodium vivax and P. falciparum are endemic. Although many studies have been conducted to investigate risk factors for malaria, but only a few have examined household and socio-economic risk factors. The present study was, therefore, undertaken to explore the relationship of different socio-demographic, socio-economic and behavioural risk factors with malaria prevalence in tribal areas of Madhya Pradesh, India. Methods: This study was undertaken in all 62 villages of Bargi Primary Health Centre from May 2005 to June 2008. These villages comprised 7117 households with an average family size of five members. fortnightly fever surveys were conducted in all villages to assess prevalence of malaria infection in the community. The distinct univariate and multivariate logistic regression models were fitted on the data set. Results: The important socio-demographic risk factors like age of household head, social group, occupation and family size; socio-economic factors like type of walls of house, place of drinking water source, irrigated land, cash crop; and behavioural variables like place of sleeping, use of bed nets, etc. were found significantly associated with malaria in univariate analyses. in multivariate analyses only social groups, family size, type of walls of house, and place of sleeping had strong significant association with prevalence of malaria. Interpretation & conclusions: The study shows that in tribal areas where people are living in poor quality of houses with no proper use of preventive measures, malaria is firmly established. We conclude that community based interventions which bring improvement in standard of living, access to healthcare facilities and health awareness, will have a significant impact on malaria prevention in these areas.

Transmission dynamics & epidemiology of malaria in two tribal districts in Madhya Pradesh, India.

Background and objectives: Epidemiology and transmission of malaria vary within the tribal areas with the variation in topography, forest cover and type of forest. For the control of disease, understanding of the dynamics of transmission in the varied ecological situation is essential. This study was carried out in the two distinct tribal areas- Baiga Chak (thick forested area) of Dindori district and Bichhia block (forest fringe area) of Mandla district, Madhya Prasdesh, India, to understand the epidemiology and transmission dynamics of malaria. Methods: Mosquitoes were collected using hand catch and whole night collections to determine the proportion of vectors, their density and seasonality. Vector incrimination was done by sporozoite ELISA and feeding preferences of vector by gel diffusion method. Active fever surveys were carried out fortnightly to determine the age specific malaria parasite rates among the inhabitants of two areas. Results: Density of Anopheles culicifacies was significantly higher in Bichhia while the density of An. fluviatilis was higher in Baiga Chak. An. culicifacies was incriminated from both the areas while An. fluviatilis was incriminated from Baiga Chak only. Malaria slide positivity rate (SPR) was significantly higher (OR=3.7 95%CI, 3.1-4.4) in Baiga Chak (28.2%) than Bichhia (9.6%). Interpretation & conclusions: The features of malaria transmission in tribal areas differed from those reported in rural or semirural population. Site-specific and region-specific studies are required to develop appropriate intervention measures to control malaria.

Malaria situation in India with special reference to tribal areas.

Background & objectives: In India, malaria is a major public health problem in states having predominantly tribal population. The objective of this analysis was to find out the incidence of malaria in various states/districts having varied proportions of tribal population using National Vector Borne Disease Control Programme (NVBDCP) data. Methods: States and districts were classified into three categories based on proportions of Scheduled Tribes (ST) population as <10, 10-29.9 and 30 per cent + ST population. Five year average (2008-2012) of all important malaria indicators collected by NVBDCP was taken to normalize the effect of annual fluctuations in malaria incidence. Results: State level analysis revealed that ten states/UTs with 30 per cent or more tribal population comprising only three per cent of total population, contributed 14 per cent of total malaria, 21 per cent Plasmodium falciparum and 29 per cent of deaths due to malaria. Similarly, district level analysis showed that districts with 30 per cent or more tribal population comprising about eight per cent country’s population contributed to 46 per cent of total malaria cases, 70 per cent P. falciparum and 47 per cent malarial deaths in the country. Interpretation & conclusions: our analysis showed that the neglect of the ethnic communities in tribal areas would be detrimental to the overall reduction of morbidity and mortality due to malaria. The fight against the increasing burden of malaria in tribal belt requires adoption of multiple approaches and socio-economic development of the tribal communities.

Co-circulation of dengue virus serotypes with chikungunya virus in Madhya Pradesh, central India.

Background: Dengue and chikungunya present with very similar signs and symptoms in the initial stage of illness and so it is difficult to distinguish them clinically. Both are transmitted by Aedes aegypti and Aedes albopictus mosquitoes. This study was conducted with the aim to explore the co-circulation of dengue and chikungunya viruses in central India. Materials and methods: Samples from suspected dengue cases were subjected to dengue immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) and dengue-negative samples were tested with chikungunya-specific IgM ELISA. The samples collected in acute phase of illness were tested by nested reverse transcription polymerase chain reaction (nRT-PCR). Chikungunya virus (CHIKV) sequences were analysed to determine their genotype. Results: Of 138 samples screened for dengue, 21 (15.2%) were positive, and of 119 samples screened for chikungunya, 13 (10.9%) were positive. Dengue viruses 1 and 4 were found co-circulating with chikungunya virus in Jabalpur, central India. The chikungunya virus detected belonged to the East Central South African genotype. Conclusion: Accurate and timely diagnosis would help in patient management and use of resources. It is advocated to simultaneously test samples for these two diseases in endemic areas. This will also aid in understanding the epidemiology of chikungunya.

Vector-borne diseases in central India, with reference to malaria, filaria, dengue and chikungunya.

Background: Vector-borne diseases (VBDs) caused by parasites and viruses are a major cause of morbidity and mortality in Madhya Pradesh (MP), central India. These diseases are malaria, lymphatic filariasis, dengue and chikungunya. Epidemiological information is lacking on different VBDs that are commonly prevalent in rural-tribal areas of MP, except on malaria. Methods: The studies were carried out at the request of Government of Madhya Pradesh, in three locations where many VBDs are endemic. Data on malaria/filaria prevalence were collected by repeatedly undertaking cross-sectional parasitological surveys in the same areas for 3 years. For dengue and chikungunya, suspected cases were referred to the research centre. Results: Monitoring of results revealed that all the diseases are commonly prevalent in the region, and show year-to-year variation. Malaria slide positivity (the number of malaria parasitaemic cases, divided by the total number of blood smears made) was 18.7% (190/1018), 16.4% (372/2266) and 20.4% (104/509) respectively in the years 2011, 2012 and 2013. There was a strong age pattern in both Plasmodium vivax and P. falciparum. The slide vivax rate was highest among infants, at 5% (odds ratio [OR] = 3.8; 95% confidence interval [CI] = 1.5 to 9.4; P<0.05) and the highest slide falciparum rate was 20% in children aged 1–4 years (OR = 2.0; 95% CI 1.5 to 2.7; P<0.0001). This age-related pattern was not seen in other VBDs. The microfilaria rate was 7.5%, 7.6% and 7.8% in the years 2010, 2012 and 2013, respectively. Overall, microfilaria rates were higher in males (8.7%) as compared to females 6.4% (OR = 1.5; 95% CI = 1.1 to 2.0; P < 0.01). The prevalence of dengue was 48% (dengue viruses 1 and 4 – DENV-1 and DENV-4), 59% (DENV-1) and 34% (DENV-3) respectively, in the years 2011, 2012 and 2013 among referred samples, while for chikungunya very few samples were found to be positive. Conclusion: Despite recent advances in potential vaccines and new therapeutic schemes, the control of VBDs remains difficult. Therefore, interruption of transmission still relies on vector-control measures. A coordinated, consistent, integrated vector-management approach is needed to control malaria, filaria, dengue and chikungunya.

Detection of dengue virus 4 from central India.

Background & objectives: Dengue is an important arboviral disease. All four dengue virus serotypes are reported to be circulating in India. It is also known that different serotypes, genotypes and clades of genotype determine outbreak severity. Dengue affected children are known to have serious disease outcome. We carried out this study to give reliable diagnosis of dengue infection in children and to detect circulating serotype in central India. Methods: Samples collected from paediatric patients suspected to have dengue fever were subjected to IgM and IgG ELISA to determine dengue virus infection. Samples collected within 0-5 days of onset of illness and positive by IgM ELISA were tested by nested reverse transcription polymerase chain reaction (nRT-PCR). The PCR products were sequenced and analyzed. Results: Of the 89 samples tested, 18 and 7 were positive for dengue IgM and IgG, respectively. Dengue activity was observed in both Jabalpur city and adjoining rural settings. One sample found positive by nRT-PCR was further sequenced to confirm dengue virus 4 as aetiological agent. Interpretation & conclusions: Our findings demonstrated dengue virus infection in children and adolescent in central India. Because of continuous changing epidemiology, it is important to monitor dengue virus activity at both serological and molecular level in this part of the country for better patient care and management.

Retrospective study of chikungunya outbreak in urban areas of India.

Background & objectives: A retrospective study on chikungunya outbreak in India in five States viz. Delhi, Madhya Pradesh, Orissa, Maharashtra and Kerala was conducted in 2007-2008 to know the distribution and determinants of chikungunya fever outbreak in India. Methods: On the basis of high and low incidence of chikungunya fever, two districts from each State and two wards from the selected district were taken for random selection of 1000 households from 10 districts and 5 States. Semi-structured questionnaires were administered to individuals, patients, qualified health professionals and to stakeholders for collecting information. Results: The educational background and occupation of the respondents showed variations across the study States. Only in high incidence ward of Maharashtra, water storage period for 3-6 days and emptying, drying of water containers on weekly basis was noted. The study through knowledge, attitude, belief, practice (KABP) obtained individual's perception of chikungunya fever, its prevention and control. Patients’ expenditure on treatment was mainly recorded less than Rs 500 across study States. Health facility survey obtained an overview of the capacity of local health facilities. Stakeholders’ perception regarding chikungunya fever was also noted. Interpretation & Conclusions: The study revealed differences in awareness of chikungunya, cause of the disease, vector responsible, mode of transmission, biting time and elimination of breeding of mosquitoes statistically significant among high and low incidence wards of all the States. Expenditure on treatment was independent of economically active status and loss of man-days across all the States. Education and occupation did not have any relation with emptying/drying of water containers in high incidence wards. Strengthening of surveillance, information, education and communication (IEC) activities along with case management facilities may be provided by the State health department for prevention of chikungunya outbreaks in future. Stakeholders should be more involved in outbreak management and future planning.