A. C. Dhariwal

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 countrys 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.

Surveillance of Artemisinin Resistance in Plasmodium falciparum in India Using the kelch13 Molecular Marker

ABSTRACT Malaria treatment in Southeast Asia is threatened with the emergence of artemisinin-resistant Plasmodium falciparum. Genome association studies have strongly linked a locus on P. falciparum chromosome 13 to artemisinin resistance, and recently, mutations in the kelch13 propeller region (Pfk-13) were strongly linked to resistance. To date, this information has not been shown in Indian samples. Pfk-13 mutations were assessed in samples from efficacy studies of artemisinin combination treatments in India. Samples were PCR amplified and sequenced from codon 427 to 727. Out of 384 samples, nonsynonymous mutations in the propeller region were found in four patients from the northeastern states, but their presence did not correlate with ACT treatment failures. This is the first report of Pfk-13 point mutations from India. Further phenotyping and genotyping studies are required to assess the status of artemisinin resistance in this region.

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study.

BACKGROUND Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the countrys largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 - 24]) and absence of an evening meal (2·2 [1·2-4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3-18·8], without evening meal; OR 3·6 [1·1-11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. INTERPRETATION Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING US Centers for Disease Control and Prevention.

Epidemiology of Plasmodium vivax Malaria in India.

Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases reported globally. Plasmodium vivax has remained resistant to control measures, particularly in urban areas. Urban malaria is predominantly caused by P. vivax and is subject to outbreaks, often associated with increased mortality, and triggered by bursts of migration and construction. The epidemiology of P. vivax varies substantially within India, including multiple relapse phenotypes with varying latencies between primary infection and relapse. Moreover, the hypnozoite reservoir maintains transmission potential and enables reestablishment of the parasite in areas in which it was thought eradicated. The burden of malaria in India is complex because of the highly variable malaria eco-epidemiological profiles, transmission factors, and the presence of multiple Plasmodium species and Anopheles vectors. This review of P. vivax malaria in India describes epidemiological trends with particular attention to four states: Gujarat, Karnataka, Haryana, and Odisha.

Investments in Research and Surveillance Are Needed to Go Beyond Elimination and Stop Transmission of Leishmania in the Indian Subcontinent.

Nazir, A; Mondal, D; Banjara, MR; Das, P; Sundar, S; Rijal, S; Arana, B; Alvar, J; Argaw, D; Peeling, RW; Kroeger, A; Matlashewski, G (2017) Investments in Research and Surveillance Are Needed to Go Beyond Elimination and Stop Transmission of Leishmania in the Indian Subcontinent. PLoS neglected tropical diseases, 11 (1). e0005190. ISSN 1935-2727 DOI: https://doi.org/10.1371/journal.pntd.0005190

Strengthening infection prevention and control and systematic surveillance of healthcare associated infections in India

Establishing and expanding government led networks to strengthen infection prevention and control and healthcare associated infection surveillance are essential to effectively tackle antimicrobial resistance. Soumya Swaminathan and colleagues discuss the progress in India

Clinical and molecular monitoring of Plasmodium falciparum resistance to antimalarial drug (artesunate+sulphadoxine-pyrimethamine) in two highly malarious district of Madhya Pradesh, Central India from 2012–2014

Abstract The spread of P. falciparum resistant strain has led to a significant resurgence of malaria morbidity and mortality. The current cornerstone in malaria treatment in India is Artemisinin based Combination (Artesunate + Sulphadoxine-Pyrimethamine) Therapy (ACT) for treatment of uncomplicated P. falciparum malaria since 2010. In the present study we assessed the therapeutic efficacy of ACT and molecular monitoring of antimalarial resistance. Therapeutic efficacy was determined by in vivo method using 28 days follow-up. Molecular genotyping of dihydrofolate reductase (dhfr), dihydropteroate synthase (dhps) and kelch13 genes were analyzed. msp-1 and msp-2 genotyping were used to differentiate recrudescence. Therapeutic efficacy of ACT was determined in 237 patients over the three year period. Most of the patients showed adequate clinical and parasitological response (99.6%). Molecular study revealed that 72% parasites were of mutant genotype (27.2% single mutants, 43.5% double mutants and 1.3% triple mutants) for pfdhfr while pfdhps showed 78.2% wild type alleles and 21.8% mutants (18.1% single mutants and 3.7% double mutants). Analysis of total 135 samples revealed mutation in k13 gene along with non-synonymous single mutation at codon M579T (1.5%) and double mutations at codon M579T & N657H in 37%. ACT remains effective for the treatment of uncomplicated P. falciparum malaria in Madhya Pradesh, Central India. However, increasing mutation in pfdhfr (particularly triple mutations) and pfdhps may reduce susceptibility to partner drug SP and mutation in k13 propeller gene, highlighting the need for continuous monitoring of the efficacy of ACT.

Dengue Scourge in Delhi – What the Stakeholders Think, a Search for Perspective

Background and Objective: Amongst all the states and union territories in India, New Delhi shares the highest burden of the disease. Dengue infection is influenced by several socioeconomic factors, which involve roles, and responsibilities of various stakeholders of the society. In this study, we attempt to explore the awareness, knowledge and perception about dengue amongst relevant stakeholders. Methodology: A sample of 30 stakeholders having different roles in management of dengue was taken all over from Delhi. In-depth, face-to-face, qualitative interviews were taken using an interview tool customized as per roles and responsibilities of the stakeholders. Result: The study identified four key themes in management of dengue in Delhi. These themes were studied in depth and various challenges in dengue management were explored.

Visceral leishmaniasis cyclical trends in Bihar, India – implications for the elimination programme.

Background: Visceral leishmaniasis (VL) is a vector-borne disease of public health importance in India, with the highest burden of disease in the states of Bihar, Jharkhand, West Bengal and Uttar Pradesh. The disease is currently targeted for elimination (annual incidence to less than one per 10,000 population) using indoor residual spraying, active case detection and treatment. Historically the disease trend in India has been regarded as cyclical with case resurgence characteristically occurring every 15 years. Understanding this pattern is essential if the VL elimination gains are to be sustained. To better understand the cyclical trends, annual climatic indicators including rainfall, temperature and humidity over time were compared with annual VL case incidence data. Methods: Annual climate data (rainfall, average and maximum temperature and specific humidity) from 1956-2004 were used to identify potential factors influencing VL incidence. Months relevant to the VL life-cycle were identified and defined (Monsoon, Sand-fly Peak, Pre-Sand-fly Peak and Annual) for analysis. The Kruskall-Wallis test was used to determine significant difference between categorical rainfall and VL incidence, whilst univariate negative binomial regression models were used to determine predictors of disease incidence. Results: The negative binomial regression model showed statistically significant associations (p <0.05) for VL incidence and maximum temperature, and average temperature, when considering annual and pre-sand fly peak time periods. No other associations between humidity, rainfall or temperature and VL incidence were detected (all values p >0.05). Conclusion: The VL programme in Bihar has made significant progress in adopting best practices for improved treatment and vector control, with the aim to achieve VL elimination. However, open access granular programme data for indoor residual spray activities and case detection is required to fully understand the role of climate in disease transmission and potential resurgence.

Lychee-associated acute hypoglycaemic encephalopathy outbreaks in Muzaffarpur, India – Author's reply

www.thelancet.com/lancetgh Vol 5 September 2017 e861 to hypoglycin A and MCPG toxicity in cases but not controls, provided the conclusive data to confirm the lychee– hypoglycin A–MCPG hypothesis. During prospective surveillance, we used a highly sensitive case definition to ensure that all potential cases were captured. This is not unusual in investigations of unexplained, severe illnesses, and also helped to ensure patients received appropriate and prompt clinical management. If there had been misclassification between cases and controls, as Das and John suggest, the significant associations identified between lychee consumption, absence of evening meal, and illness would have, at worst, been biased toward the null. Both case-patients and controls were residents of villages in the Muzaffarpur district—ie, the same community. Controls were identified among children who were admitted to the same hospitals where case-patients were admitted. The presence of lychee orchards and agricultural fields, and the availability of lychees were ubiquitous in the Muzaffarpur villages where both case-patients and controls lived. It was with these data, and after a multisectoral meeting of stakeholders from district-level, state-level, and national-level agencies in February, 2015, that the Director General of Health Services, Government of India, issued official recommendations to the Government of Bihar to encourage parents and carers in the affected Muzaffarpur area to minimise children’s lychee consumption and ensure they eat an evening meal, and to re-emphasise the need for clinicians to rapidly test for, and correct, hypoglycaemia among children with suspected illness. After this, the NCDC and, more broadly, the Ministry of Health and Family Welfare, and the Ministry of Women and Child Development have continued to support the Government of Bihar’s response to the Muzaffarpur outbreaks in 2015 and 2016, and Lychee-associated acute hypoglycaemic encephalopathy outbreaks in Muzaffarpur, India