Description of the condition
Measles is an important cause of childhood morbidity and mortality in high-income and low-income countries. It is an acute viral infection characterised by high fever and maculopapular rash (Maldonado 2003). According to the World Health Organization (WHO), 53,5000 children died of measles in 2000, accounting for 5% of all under-five mortalities (UNICEF 2011). Between 2000 and 2010, there was a 74% reduction in measles deaths globally as a result of improved vaccine coverage efforts (Simons 2012). However, recently large outbreaks have occurred in some countries such as Bulgaria in 2009 to 2010 and France in 2011, as a result of sub-optimal immunisation levels (Carrillo-Santisteve 2012). In low-income countries, such as Sierra Leone (between 2009 and 2010) and South Africa (between 2003 and 2005; 2009 and 2011), there were outbreaks of measles probably as a result of HIV infection and poor vaccine coverage (Sartorius 2013). Amongst young children in low-income countries, case-fatality rates for measles still hover at around 5% to 6% (Wolfson 2009). Acute lower respiratory infection is a common complication of measles, associated with mortality. Other important complications of measles include otitis media, laryngotracheobronchitis (croup), diarrhoea, encephalitis and cortical damage leading to blindness (Perry 2004).
Worldwide, the prevalence of zinc deficiency is estimated to be more than 20% (Wuehler 2005), and in many low-income countries it is extremely prevalent amongst children (World Bank 2012). The majority of zinc excretion takes place through the gastrointestinal tract, therefore children exposed to gastrointestinal pathogens on a regular basis and who have a poor diet, low in animal products and high in phytate, are most at risk of zinc deficiency (Lazzerini 2012). Zinc deficiency results in dysfunction of both humoral and cell-mediated immunity and increases the susceptibility to infectious diseases such as diarrhoea and respiratory infection (Tuerk 2009). Respiratory tract infections such as acute lower respiratory tract infections (ALRIs) are a common complication of measles infection (Aggarwal 2007; Roth 2008; Shakur 2009).
Description of the intervention
Zinc is one of the most important trace elements in the human body. It is a component of over 1000 transcription factors and is required in more than 300 zinc-containing enzymes (Haase 2009; Stefanidou 2006). Zinc supplementation may reduce the duration of acute and persistent diarrhoea in children over six months of age (Lazzerini 2012), as well as the frequency of diarrhoeal and respiratory illnesses in children (Aggarwal 2007). Zinc supplements can be given in the form of either zinc sulphate, zinc gluconate, zinc acetate or zinc chloride. The recommended daily dose is 10 mg to 20 mg of zinc for children with diarrhoea (WHO/UNICEF 2004).
How the intervention might work
The importance of zinc in the maintenance of normal immune functions has been demonstrated by several studies (Bach 1989; Prasad 1998; Prasad 2000; Prasad 2009; Stefanidou 2006; Tapiero 2003). Zinc is said to be crucial for effective innate and acquired immunity and insufficient zinc status could be the most common cause of secondary immunodeficiency in humans (Tapiero 2003). Zinc deficiency impairs phagocytosis of macrophages and neutrophils, oxidative burst activity and complement natural killer (NK) cell activity (Prasad 2000). Zinc is also involved in T-cell differentiation and enhancement of T-cell and NK cell actions through its role in thymulin activity (Bach 1989). In the absence of zinc, lymphocyte proliferation is depressed, as well as delayed-type hypersensitivity skin responses and T-cell dependent antigen-antibody responses (Prasad 1998). Zinc has also been shown to have anti-inflammatory as well as antioxidant properties (Prasad 2009; Stefanidou 2006). Supplements will increase the availability of zinc for these immunologic processes and may improve measles morbidity and mortality. In children, zinc supplementation is reported to reduce morbidity, mortality and recovery time from acute infectious diseases (Cuevas 2005). Sazawal 2007 showed that zinc supplements given to children aged between 1 and 48 months resulted in reduced mortality from acute infections including measles. Zinc supplementation has also been shown to reduce respiratory morbidity significantly in preschool children (Sazawal 1998), and may reduce the incidence of ALRIs by improving measles morbidity.
Why it is important to do this review
Several published reviews have shown that zinc supplementation is associated with reduced incidence and prevalence of pneumonia in children (Aggarwal 2007; Bhutta 1999; Lassi 2010). Other Cochrane Reviews evaluating zinc supplementation in children have looked at otitis media, diarrhoea and common cold (Gulani 2012; Lazzerini 2012; Singh 2013). This review aims to identify, critically appraise and synthesise data from studies evaluating the effects of zinc supplementation in children with measles.