Comparative genetic variability in HIV-1 subtype C p24 Gene in early age groups of infants.

It is important to study the molecular properties of vertically transmitted viruses in early infancy to understand disease progression. P24 having an important role in virus assembly and maturation was selected to explore the genotypic characteristics. Blood samples, obtained from 82 HIV-1 positive infants, were categorized into acute (≤ 6 months) and early (> 6-18 months) age groups. Of the 82 samples, 79 gave amplification results for p24, which were then sequenced and analysed. Amino acid heterogeneity analysis showed that substitutions were more frequent. Several substitution mutations were present in some of the sequences of both the age groups in the functional motifs of the gene namely Beta hairpin, CyPA binding loop, residues L136 and L190, linker region and major homology region. In the acute age group, an insertion of Asparagine residue (N5NL6) was observed in the ß hairpin region in one of the sequences. This insertion was accompanied with analogous substitutions of N5Q, Q7L and G8R. In the early age group, a deletion of two residues; VK181-182, was observed at the C-terminal end in one of the sequences. These mutations may impair the structure of the protein leading to defective virus assembly. Protein variation effect analyzer software showed that deleterious mutations were more in the acute than the early age group. Variability analysis revealed that the amino acid heterogeneity was comparatively higher in the acute than the early age group. Variability in the virus was decreasing with the increasing age of the infants indicating that the virus is gradually evolving under positive selection pressure. HLA class 1 binding peptide analysis showed that the epitopes TPQDLNTML and RMYSPVSIL may be helpful in designing epitope based vaccine.

Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014.

Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children.

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.

Monitoring antimalarial drug resistance in India via sentinel sites: outcomes and risk factors for treatment failure, 2009-2010.

OBJECTIVE: To describe India's National Antimalarial Drug Resistance Monitoring System, measure the efficacy of first-line malaria treatments, and determine risk factors for treatment failure. METHODS: In 2009-2010, prospective studies with 28 days of follow-up were conducted at 25 sentinel sites. Patients infected with Plasmodium falciparum were given artesunate plus sulfadoxine-pyrimethamine (AS+SP); those infected with P. vivax were given chloroquine. Polymerase chain reaction was used to distinguish post-treatment reinfection from treatment failure. Isolates of P. falciparum were checked for dhfr and dhps mutations. FINDINGS: Overall, 1664 patients were enrolled. Kaplan-Meier survival analysis showed an efficacy of 98.8% for AS+SP. Most patients with P. falciparum parasitaemia cleared their parasitaemias within 24 hours of treatment initiation, but six, including four with treatment failure, remained parasitaemic after 72 hours. Double mutants in dhfr were found in 68.4% of the genotyped isolates. Triple or quadruple mutants in dhfr and mutations in dhps were rare. A daily dose of artesunate of < 3 mg per kg of body weight, age of less than 5 years, and fever at enrolment were associated with an increased risk of treatment failure. Chloroquine remained 100% efficacious and generally cleared P. vivax parasitaemias within 48 hours. Vomiting (seen in 47 patients) was the most common adverse event. CONCLUSION: India's National Antimalarial Drug Resistance Monitoring System provides wide coverage. The first-line antimalarials used in the country remain safe and efficacious. The treatment of malaria in young children and the relative benefits of age- and weight-based dosing need further exploration.

Estimation of malaria mortality of A District in India during 2010 by using three models.

There is no standard method for estimating annual malaria deaths in India. The degree of under-reporting in routine system is uncertain with a varied picture of 10, 15, 25 and 200 times as found in different studies/models. During October 2010 a community based cross-sectional survey was conducted by National Vector Borne Disease Control Programme (NVBDCP) in 32 villages of West Garo Hills district of Meghalaya. 'Gap filling', 'fever survey' and 'verbal autopsy' models, developed in NVBDCP were used on the data obtained from two surveys done simultaneously: 'fever survey' with 2 weeks recall period and 'death survey' with one year recall period. Inputs from demographic and epidemiological data of the district were also given. During 2010, the district has reported 32 malaria deaths. Degrees of under-reporting found in the study were 6.93, 7.53 and 12 times in three models respectively. The first two models yielded closer estimates. But, verbal autopsy model gave inflated value as the method was unreliable for diagnosing malaria deaths. First two models, if found to be replicable, can be incorporated in NVBDCP activities to evaluate malaria control measures at district level. Verbal autopsy model may be used after concordance study in those districts where Pf malaria cases occur but no death is reported.

Media scanning and verification system as a supplemental tool to disease outbreak detection & reporting at National Centre for Disease Control, Delhi.

Media scanning for unusual health events can efficiently supplement conventional communicable disease surveillance systems for early detection and response to outbreaks. There is a need to rapidly process and appropriately disseminate the media reports on unusual health events for timely action. Hence to address this need in India a Media Scanning & Verification Cell (MSVC) was established in July 2008 at the National Centre for Disease Control, Delhi. MSVC is supervised by Epidemiologists working in Central Surveillance Unit of IDSP. This unique system monitors Global and National Media sources such as National and Regional print media, news on internet, news wires and websites, news channels and news shared by partners like Global Public Health Intelligence Network (GPHIN), Canada, WHO and other International and national agencies. The information is shared to the districts affected and District Surveillance Officer (DSO) and his team is expected to investigate and revert through the internet about the correctness and action taken. A mean number of 4 Media Alert reports are generated each day. A total of 1685 alerts were reported in a period between July 2008 to December 2011. Of these 1241 (73.7%) were verified as real events and 183 (10.9%) were considered outbreaks by local health officials. Most events were captured through internet (57%) followed by the print media (24%). The most common disease events identified were food-borne and diarrhea (29.1%), dengue (10.68%), influenza & respiratory disease (8.1%) and malaria (7.4%). The sensitivity of MSVC to detect outbreaks was 14.8% with more than half of outbreaks detected before they were identified by the conventional surveillance system. It has proven to be a highly effective supplemental tool to official surveillance system in the detection of early warning signals and hence timely detection and management of public health threats in India.

Impact of mass drug administration on elimination of lymphatic filariasis in Surat city, India.

Lymphatic filariasis (LF) is one of the major public health problems in some of the endemic districts in India including Surat city of Gujarat province. Historical data reveals that in 1960s, Surat city had infection rate of about 23% and infectivity rate of 1.6%. Since then, Surat city has been reporting the cases of Lymphoedema and hydrocele. Filaria Control Unit was established under National Filaria Control Programme to detect and provide treatment to the cases. Based on the reports of NFCP, Surat City has been considered as LF endemic. During 2004, the country launched campaign of Elimination of Lymphatic Filariasis through Mass Drug Administration (MDA) with annual single dose of 6 mg/kg body weight of DEC tablets in all LF endemic districts including Surat city. Four rounds of MDA (2004-2007) had shown 41% reduction in mf rate, with drastic reduction in infection rate of 88% and 100% in infectivity rate. Serious adverse effect (SAE) after 4th round of MDA was insignificant (< 0.5%) during 2007. An assessment by surveying 5058 people in different parts of Surat city revealed the drug distribution coverage of more than 95% but actual drug compliance between 70-90%. Analysis of the data revealed that though the overall Microfilaria rate has been reduced due to MDA, higher Microfilaria rate was noticed in North zone of city where the migrant populations influx is higher. The observation and analysis of the data in Surat city towards elimination of Lymphatic filariasis has been discussed in this paper.

An algorithmic approach to identifying the aetiology of acute encephalitis syndrome in India: results of a 4-year enhanced surveillance study.

BACKGROUND: Annual outbreaks of acute encephalitis syndrome pose a major health burden in India. Although Japanese encephalitis virus (JEV) accounts for around 15% of reported cases, the aetiology of most cases remains unknown. We aimed to establish an enhanced surveillance network and to use a standardised diagnostic algorithm to conduct a systematic evaluation of acute encephalitis syndrome in India. METHODS: In this large-scale, systematic surveillance study in India, patients presenting with acute encephalitis syndrome (ie, acute onset of fever with altered mental status, seizure, or both) to any of the 18 participating hospitals across Uttar Pradesh, West Bengal, and Assam were evaluated for JEV (serum and cerebrospinal fluid [CSF] IgM ELISA) per standard of care. In enhanced surveillance, JEV IgM-negative specimens were additionally evaluated for scrub typhus, dengue virus, and West Nile virus by serum IgM ELISA, and for Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, dengue virus, herpes simplex virus, and enterovirus by CSF PCR across five referral laboratories. In 2017, chikungunya and Leptospira serum IgM by ELISA and Zika virus serum and CSF by PCR were also tested. FINDINGS: Of 10 107 patients with acute encephalitis syndrome enrolled in enhanced surveillance between Jan 1, 2014, and Dec 31, 2017, 5734 (57·8%) of 9917 participants with available data were male and 6179 (62·7%) of 9856 were children aged 15 years and younger. Among patients who provided a sample of either CSF or serum in enhanced surveillance, an aetiology was identified in 1921 (33·2%) of 5786 patients enrolled between 2014 and 2016 and in 1484 (34·3%) of 4321 patients enrolled in 2017. The most commonly identified aetiologies were JEV (1023 [17·7%] of 5786 patients), scrub typhus (645 [18·5%] of 3489), and dengue virus (161 [5·2%] of 3124). Among participants who provided both CSF and serum specimens, an aetiology was identified in 1446 (38·3%) of 3774 patients enrolled between 2014 and 2016 and in 936 (40·3%) of 2324 enrolled in 2017, representing a 3·1-times increase in the number of patients with acute encephalitis syndrome with an identified aetiology compared with standard care alone (299 [12·9%]; p<0·0001). INTERPRETATION: Implementation of a systematic diagnostic algorithm in an enhanced surveillance platform resulted in a 3·1-times increase in identification of the aetiology of acute encephalitis syndrome, besides JEV alone, and highlighted the importance of scrub typhus and dengue virus as important infectious aetiologies in India. These findings have prompted revision of the national testing guidelines for this syndrome across India. FUNDING: US Centers for Disease Control and Prevention.

India's need for long-term solutions to COVID-19-like pandemics: A policy paper by Organized Medicine Academic Guild.

The entire world seems to have responded to COVID-19 pandemic in a knee-jerk manner with a short mindset without building on the existing strengths of public health infrastructure. National governments cannot be blamed for this as we are dealing with a crisis that comes once in a lifetime. Realising this, the Organized Medicine Academic Guild (OMAG) an association of major health associations in this country has suggested measures for long-term solutions to COVID-19-like pandemics in the form of a policy paper by OMAG.

Role of information technology (IT) in public health, India (problems & prospects): Role of information communication technology (ICT) in disease surveillance under Integrated Disease Surveillance Project (IDSP).

Information Communication Technology (ICT) has proven to be a strong public health tool. Keeping the future need of country and building National Disease Surveillance System, Integrated Disease Surveillance Project (IDSP) was launched by Hon'ble Union Minister of Health & Family Welfare in November 2004. It is a decentralized, State based surveillance program in the country. It is intended to detect early warning signals of impending outbreaks and help initiate an effective response in a timely manner. One of the major components of the project is the - use of Information Technology for collection, collation, compilation, analysis and dissemination of data besides distance education and video conferencing. A network of 800 sites across India has been established through Satellite, Broadband and High end Video conferencing equipments. The network is managed by a team of data managers and data entry operators at all state surveillance units and district surveillance units respectively. The network was proven to be extremely useful to respond to the current influenza A H1N1 pandemic. It is proposed to extend the network to cover private sector and provide convergence with other National Health Programs.

A study on dengue outbreak during 2009 in Bhopal and Indore districts of Madhya Pradesh, India.

An outbreak of mysterious virus disease reported from Bhopal, Indore and adjoining districts of Madhya Pradesh (MP) state during 2009. The outbreak started in Bhopal in early September and then from Indore in last week of September. Subsequently cases were also reported from adjoining districts. On basis of Epidemiological, Clinical, Entomological and Laboratory findings dengue outbreak was declared in the area. A total of 620 IgM Elisa positive cases were reported from Bhopal and Indore district and adjoining areas. The outbreak involved 8 districts in the state. The control measures were undertaken in the area and the outbreak of dengue subsided in December 2009.

Status of lymphatic filariasis in Lucknow District, Uttar Pradesh.

Lucknow district was endemic for lymphatic filariasis (LF). During March 2008, LF survey was carried out in 14 randomly selected villages (six Primary Health Centres) and 4 Mohallas of Lucknow city. Out of 3,654 night blood smears (NBS) collected and examined, 209 were found positive for Wuchereria bancrofti (micrifilaria rate: 5.7%). Microfilaria (mf) carriers were detected from all surveyed villages and Mohallas. The age of these positive persons ranged from 6-70 years. In all areas, prevalence of microfilaraemia generally increased with age up to 21-30 years. Males (6.7%) were more affected than females (3.9%). All mf carriers were residents of Lucknow district. Overall disease rate was 4.7%. In all, 175 individuals had disease manifestations of LF. Out of 108 males, 81 had hydrocele(75%). Disease rate was similar in males (4.7%) and females (4.8%). The mean mf density was 9.5 per 20 cmm blood, but no significant difference between males (9.4) and females (9.9). Vector density ranged from 150 to 810 per ten-man-hours. Infectivity and infection rates were 0.14%. The present survey indicates that filariasis is one of the major public health problems in surveyed areas.

Communicable disease outbreak detection by using supplementary tools to conventional surveillance methods under Integrated Disease Surveillance Project (IDSP), India.

Communicable disease control relies on effective response systems and effective response systems rely on effective disease surveillance. Surveillance is first step towards prevention. In addition to conventional routine indicator based surveillance system, countries must develop additional tools in terms of supplementary surveillance system for providing information on early detection of outbreaks in India so that a timely and an appropriate action can be taken. Presently Integrated Disease Surveillance Project (IDSP) at National Centre for Disease Control, Delhi, India is carrying out country wide surveillance. IDSP has developed four supplementary event reporting tools to strengthen and increase the sensitivity of its routine weekly indicator based surveillance system. These event based reporting tools are Early Warning Signals/Outbreak reporting, Media Surveillance, Toll free number (1075) and Community Based Surveillance. These supplementary tools have proven to be efficient and effective in timely detection of many public health threats.

Study on the eco-epidemiology of Chikungunya in U.T of Lakshadweep.

An unusual increase in the incidence of viral fever was noticed in Androth and Kalpeni Island, U.T of Lakshadweep during November 2006. The Eco-epidemiology of the disease was studied in detail. The study indicated that Aedes albopictus is the predominant species (98.74%) and it exhibited a wide spectrum of breeding preferences with a clear-cut predilection for rat-damaged coconuts (RDCs). All the entomological indices were very high in both the Islands with a marked increase in Kalpeni Island. The clinical presentation of the cases was typical of chikungunya and the laboratory study confirmed this. Based on the investigation, control and preventive measures were planned, advised and implemented. The details regarding the bio-ecology of vectors, clinical presentation, laboratory investigations and effectiveness of control measures are discussed.

Persistent diarrhoea in a 5-month-old baby carrying Vibrio cholerae nonO1/nonO139 producing Haitian cholera toxin.

Cholera toxin (CT) is the principal virulence factor of Vibrio cholerae for fatal cholera diarrhoea. Serogroups O1 and O139 harbour CT and are known to be epidemic strains. The remaining serogroups (nonO1/nonO139) are non-toxigenic and may be associated with mild disease. O1 serogroup emerged with a variant of CT known as Haitian cholera toxin (HCT). The HCT strains are hypervirulent and have been associated with severe cholera outbreaks in India, Western Africa and Haiti. Here, we report the presence of HCT (ctxB7) in a nonO1/nonO139 isolate causing persistent diarrhoea.

A rare case of trypanosomiasis in a two month old infant in Mumbai, India.

Human Trypanosomiasis is a rare occurrence in India. In the cases reported so far the disease causative species have been the species infective to animals viz., Trypanosoma lewisi and Trypanosoma evansi. These animal species usually non pathogenic in humans can acquire the desired virulence and emerge as human pathogens causing serious disease, in the right combination of environmental, host related and organism related factors. We report here a case of trypanosomiasis caused by the rodent parasite T. lewisi in a two months old infant in urban Mumbai. Under the fastly changing environmental scenario there is an urgent need to be prepared for the emerging zoonoses. Any unusual disease occurrence in a given geographical area acquires a special significance in this context and should be reported to assess its public health importance and be prepared to deal with the consequent challenges posed, if any.

Evaluation of Og4C3 antigen ELISA as a tool for detection of bancroftian filariasis under lymphatic filariasis elimination programme.

Diagnosis of Lymphatic Filariasis by microscopic examination of thick blood films (TBF) collected between 8.30 pm to 12 midnight, though highly specific is operationally problematic. We evaluated the TropBio Og4C3 serum ELISA as a tool for detection of W. bancrofti microfilaria carriers using Dried Blood Spots (DBS). The study was carried out in two parts (i) to test the sensitivity and specificity of the ELISA test for detection of circulating filarial antigen (CFA) in microfilaria (Mf) carriers vis-à-vis the conventional thick blood film (TBF) microscopy and its persistence in different categories of individuals during the course of disease viz., Endemic normals (n=51), microfilaria (Mf) carriers (n=27), acute cases (n=27), chronic cases (n=50) and a control group of non-endemic normals (n=48) using sera samples and ii) to study the utility of finger prick Dried Blood Spots (DBS) collected on filter paper for detection of Mf carriers and its comparison with another antigen detection assay, the Immunochromatographic test (ICT). Considering the non-endemic normals and microfilaria carriers, the ELISA test was found to have 100% sensitivity and 94.12% specificity for detection of Mf carriers in sera samples. The CFA was absent in majority of the subjects tested under other categories with a positivity of 7.8% among endemic normals, 11.12% among acute cases, 7.84% among chronic cases and 6.25% among nonendemic normals. Comparison of finger prick DBS and sera samples by ELISA vis-à-vis the ICT, carried out on Mf carriers (n=91) and endemic normals (n=97), showed a positivity of 88 (96.7%) in DBS as against 86 (94.5%) in sera samples and 88 (96.7%) by ICT, amongst Mf carriers, with a statistically significant correlation in antigen units between sera and DBS samples (r = 0.959, p = 0.000) amongst the microfilaria carriers. Out of 97 endemic normals, 19 (19.6%) sera and 17 (17.5%) DBS samples tested positive by ELISA while as 12(12.4%) tested positive by ICT, again with a statistically significant correlation between the antigen units in sera and DBS samples (r = 0.942, p = 0.000). DBS prepared from 25 microl of blood were found to be as sensitive as 50 microl for antigen detection. Antigen positivity detected from DBS collected during day and night from known microfilaria carriers (n=27) showed a statistically insignificant difference (p = 0.125) and a significant correlation in antigen units (r = 0.820 and p = 0.013). In view of the comparable results of ELISA, ICT and TBF microscopy, it is concluded that the TropBio Og4C3 ELISA using finger prick DBS can be used as an alternate to TBF microscopy for detection of bancroftian Filariasis under the LFE programme.