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Community- and health facility-based intervention with zinc as adjuvant therapy for pneumonia to enhance child health and nutrition

Final Report Summary - CHIZAP (Community- and health facility-based intervention with zinc as adjuvant therapy for pneumonia to enhance child health and nutrition)

Pneumonia is one of the most important causes of childhood deaths worldwide. Routine zinc administration to children in developing countries reduces the incidence of pneumonia and diarrhoea. Zinc has to be ingested every day and breast milk is a poor source of zinc. It is accordingly difficult to increase the zinc intake in young infants who are supposed to be exclusively breastfed. Therapeutic oral zinc administration during an ongoing infection might be a feasible alternative to counteract the consequences of poor zinc status.

The benefits of therapeutic oral zinc given to children with diarrhoea are well documented but the therapeutic effect of zinc when given during pneumonia or other severe bacterial illnesses has yet to be demonstrated. Furthermore, short courses of zinc have been shown to reduce childhood morbidity for up to six months and may become an alternative to long-term zinc supplementation.

In this project, they assessed the efficacy of oral zinc given during pneumonia in hospitalised and in non-hospitalised children 2 to 35 months of age and during severe bacterial illness in children less than 4 months of age on the severity of the enrolment episode and on subsequent morbidity and nutritional status for six months.

The principal objective of the proposed project was to set up a double masked randomised placebo controlled clinical trials, and measure whether and to what extent zinc given as adjuvant therapy to standard antibiotic treatment for pneumonia or severe bacterial illness reduces the risk of treatment failure, the duration of the illness and whether this short-term micronutrient intervention enhances nutritional and health status for six months thereafter.

It should be noted that in the beginning of 2006 Nepal went through a period of political unrest with frequent general strikes and bloody clashes between the army led by the king and the rebel Maoists. On 2 January that year, the Maoists decided not to extend a four month ceasefire saying that the government had broken the ceasefire with numerous attacks on Maoist villages. The political instability escalated from this date. In April, several protesters were injured, there were several strikes where the country was closed down and it was impossible to use the roads. There were several days with curfews and the king ordered protesters violating the curfew to be 'shot on sight'. On 27 April, the king promised to restore democracy, which also restored stability. This period of turmoil substantially affected the project, with fewer children in two work packages included and fewer samples in another analysed.

In August 2008, the Data Safety Monitoring Board (DSMB) called for a safety analysis, which was done by a neutral body. The results were shared with the DSMB and the other sponsor, Department of Biotechnology (DBT), Govt. of India. The results were as follows; among the total 680 infants enrolled, 349 infants were randomised to the group receiving the standard treatment for sepsis, and 339 infants to the group who received the same standard treatment for sepsis plus zinc (10 mg per day). In the group without zinc, 17 infants died (risk of death = 5.0 %), while in the group with zinc only 10 infants died (risk of death = 3.0 %).

In conclusion, there was a 40 % reduction in risk of dying (or deaths) in the group that got zinc supplementation. This reduction was not statistically significant but the data suggest that there are potential benefits in adding zinc supplementation to the management of infants with severe sepsis. This analysis was undertaken because the public raised suspicions regarding increased mortality in the study.

The project decided to continue to enrol children beyond the allocated time frame of the project. It was, therefore, decided to extend the study as long as possible to gain enough power to look at mortality as an outcome. This was possible with funds from Meltzer Foundation (Norway) and from DBT. The results were published in international peer-reviewed journal and communicated directly to local and regional health authorities.