Immunobiology of mild micronutrient deficiencies

Nutrition is a critical determinant of the outcome of host microbe interactions through a modulation of the immune response. Besides macronutrient malnutrition, deficiencies of several macronutrients also influence immune homeostasis and thus affect infection-related morbidity and mortality. Deficiencies of micronutrients like vitamin A, iron and zinc are widely prevalent among populations living in developing countries. Besides their severe deficiencies, subclinical deficiencies are known to impair biological functions in the host, immune function being one of them. The effects of these micronutrients on various immune mechanisms are briefly reviewed in this article.     

Horizontal and vertical transmission of dengue virus type 2 in highly and lowly susceptible strains of Aedes aegypti mosquitoes.

Isofemale lines of Aedes aegypti mosquitoes highly and lowly susceptible to dengue type 2 (DEN-2) virus (DEN(h) and DEN(l), respectively) were established by oral feeding and individual rearing. The susceptibility at F13 generation was found to be 61% and 25% for the DEN(h) and DEN(l) line, respectively. The virus-infected mosquito females were allowed to probe on bovine albumin phosphate saline pH 7.2 (BAPS) through membrane feeders. The presence of virus in the probed BAPS was determined either by ELISA or by intrathoracic (i.t.) inoculation of mosquitoes or by both methods. The rate of oral transmission of virus was found to be 2 times higher in the DEN(h) isofemale line than in the DEN(l) one. Similarly, vertical transmission rate of the virus was found to be 7 times higher in the DEN(h) line. When batches of eggs obtained from infected female mosquitoes were allowed to hatch after two months the vertical transmission rate of the virus was very high. It is possible that, at room temperature, the virus gets an opportunity to multiply and increase its copy number in the quiescent embryos. The progeny obtained from the infected mosquitoes was found to be capable of transmitting the virus horizontally when allowed to probe on BAPS through the membrane feeder. This is the first report demonstrating horizontal transmission of DEN-2 virus by mosquitoes infected through vertical transmission. The higher vertical transmission rate of the virus in the progeny obtained from the eggs dessicated for a longer time and the horizontal transmission of the virus from the progeny is of very high epidemiological significance.     

BCG vaccination in malnourished child population.

The efficacy of BCG vaccination is still a subject of controversy. In the present study the protective role of BCG vaccination, the influence of nutritional status and justification for revaccination in children were investigated. Of the 504 preschool children suffering from tuberculosis who were registered for the study, 345 children did not receive BCG vaccine while the others had it during early infancy. Vaccinated children showed a significantly greater tendency to localise the tubercular lesions while most of the unvaccinated children suffered from progressive forms of the infection. Vaccination had similar effects even when there was associated malnutrition. Age did not seem to influence the severity of the disease in unvaccinated children while older children (greater than 3 yrs) had a greater tendency to localise the lesion in the vaccinated group. These data do not support the proposal of administering a booster dose of BCG to children who were vaccinated during early infancy.     

Micronutrient Malnutrition, Infection, and Immunity: An Overview

Micronutrient deficiencies and infectious diseases often coexist and exhibit complex interactions leading to the vicious cycle of malnutrition and infections among underprivileged populations of the developing countries, particularly in preschool children. Several micronutrients such as vitamin A, beta-carotene, folic acid, vitamin B_12, vitamin C, riboflavin, iron, zinc, and selenium, have immunomodulating functions and thus influence the susceptibility of a host to infectious diseases and the course and outcome of such diseases. Certain of these micronutrients also possess antioxidant functions that not only regulate immune homeostasis of the host, but also alter the genome of the microbes, particularly in viruses, resulting in grave consequences like resurgence of old infectious diseases or the emergence of new infections. These micronutrient infection and immune function interactions and their clinical and public health relevance in developing countries are briefly reviewed in this article.     

Interleukin-1 in malnutrition.

The effect of malnutrition on the in vitro production of interleukin-1 by lipopolysaccharide stimulated circulating monocytes has been investigated in children suffering from kwashiorkor and marasmus. The interleukin-1 activity was significantly lower in children with severe malnutrition. Furthermore, macrophages from children with kwashiorkor produced factors that suppressed mouse thymocyte proliferation. These observations show a significant impairment of macrophage function and provide a mechanism for the suppression of cellular immunity in malnutrition.     

Prevalence of West Nile virus infection in India

During the course of the virological investigation of cases of suspected viral fevers carried out at the National Institute of Virology (NIV), Pune, India, evidence of recent infection with West Nile (WN) virus was detected in 88 cases. Fever, general aches, headache, nausea and vomiting were the principal clinical features in 92% (81/88) of the cases; there were seven cases of encephalitis, in which WN virus-specific IgM class antibodies were detected in CSF samples. These cases of encephalitis were from Japanese encephalitis (JE) nonendemic areas, like Maharashtra and Rajasthan, as well as from JE endemic areas, like Goa and Orissa. Interestingly, neutralizing antibodies predominantly to WN virus were detected in CSF samples by the 50% cytopathic effect inhibition method; the titers ranged from 5 to 375. Cases of WN virus infection associated with both encephalitis and classic features have been reported for the first time in recent years in India. Reports of unique urban West Nile virus encephalitis epidemics in New York, Romania, and Algeria in recent years have signaled the emergence of neurological infection due to West Nile virus as a novel public health threat. This study is important because it records evidence of WN virus infection in India.     

Effect of measles on the nutritional status of preschool children

A total of 1426 children admitted to the hospital for measles were studied. Of these, 84 were followed up for a period of 6 months after they were discharged from the hospital. It was observed that about 23% of the cases developed secondary infection during the acute stage of measles. Diarrhoea and respiratory infection were the common complications. Some children developed corneal lesions during the acute stage. Serum vitamin A levels were significantly low in these children and they showed a good clinical response to vitamin A therapy. During the follow-up period the children suffered from frequent episodes of infections for nearly 6 months after the attack of measles and the weight gain was significantly lower compared to normal children. These observations suggest that measles plays a significant role in precipitation of malnutrition and blindness due to vitamin A deficiency in preschool children.     

Malnutrition and childhood tuberculosis

Cell-mediated immune status (CMI) of sixty-five children suffering from various clinical forms of tuberculosis and thirty age- and sex-matched healthy children aged between 1 and 5 years was investigated to understand the role of malnutrition in tuberculosis. A significant association between severe malnutrition and severe forms of infection was observed. Data on CMI showed immunosuppressive effect of tuberculosis per se in all children. Well nourished children had similar CMI status irrespective of the severity of the disease while malnourished children with severe forms of disease showed lowest CMI response. These data suggest not only the synergistic interactions of malnutrition and tuberculosis, but the contributory role of malnutrition in causing more severe immuno suppression. The results point out the importance of better nutritional status of the child in preventing the severe forms of the disease.