Infectious etiology modifies the treatment effect of zinc in severe pneumonia

Coles, Christian; Bose, Anuradha; Moses, Prabhakar D.; Mathew, Leni Grace; Agarwal, Indira; Mammen, Thomas; Santosham, Mathuram

doi:10.1093/ajcn/86.2.397

Cited by 31 publications

(40 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies on the effect of zinc supplementation on pneumonia have not reported the prevalence of HIV in the patients studied [10,20]. None the less, the prevalence of HIV in children in our study was high.…”

Section: Discussioncontrasting

confidence: 79%

See 1 more Smart Citation

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

Srinivasan

Ndeezi

Mboijana

et al. 2012

BMC Med

View full text Add to dashboard Cite

BackgroundPneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda.MethodsIn this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups.ResultsTime to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); P-value for homogeneity of risk differences = 0.006.ConclusionZinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapynaïve HIV infected children in our environment.Clinical trials registration number...

show abstract

Section: Discussioncontrasting

confidence: 79%

“…We did not find a similar study with which to compare our results. In a related study, Cole and Bose [20] used a CRP of > 40 mg/L as a proxy for bacterial pneumonia. They found that zinc therapy for children with severe pneumonia was associated with prolonged hospitalization.…”

Section: Discussionmentioning

confidence: 99%

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

Srinivasan

Ndeezi

Mboijana

et al. 2012

BMC Med

View full text Add to dashboard Cite

show abstract

“…A total of thirteen studies remained after screening titles/abstracts. Among the thirteen studies, four were excluded, of which one (23) was an advanced abstract of an included study, two (24,25) focused on children with severe acute lower respiratory tract infection (LRTI) but not severe pneumonia and one (26) used the same data from the included trial. Finally, nine RCT (9)(10)(11)(12)(13)(14)(15)(16)(17) were included.…”

mentioning

confidence: 99%

Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials

et al. 2016

View full text Add to dashboard Cite

The effect of Zn, as an adjunct to antibiotics, on the treatment of severe pneumonia in young children is still under debate; therefore, we performed a meta-analysis to evaluate the therapeutic role of Zn for severe pneumonia in children younger than 5 years. PubMed, Cochrane library and Embase databases were systematically searched from inception until October 2015 for randomised-controlled trials (RCT) that assessed the effect of Zn as an adjunct to antibiotics for severe pneumonia. Random-effects model was used for calculating the pooled estimates, and intention-to-treat principle was also applied. Nine RCT involving 2926 children were included. Overall, the pooled results showed that adjunct treatment with Zn failed to reduce the time to recovery from severe pneumonia (hazard ratios (HR) = 1·04; 95 % CI 0·90, 1·19; I 2 = 39 %; P = 0·58), hospital length of stay (HR = 1·04; 95 % CI 0·83, 1·33; I 2 = 57 %; P = 0·74), treatment failure (relative risk (RR) = 0·95; 95 % CI 0·79, 1·14; I 2 = 20 %; P = 0·58) or change of antibiotics (RR = 1·07; 95 % CI 0·79, 1·45; I 2 = 44 %; P = 0·67). In addition, continuous outcomes were consistent while meta-analysed with standard mean difference, and all outcomes remained stable in intention-to-treat analysis. No significant differences were observed in the two groups between death rate, adverse events or recovery times of severe pneumonia indicators. Our results suggested that adjunct treatment with Zn failed to benefit young children in the treatment of severe pneumonia. Considering the clinical heterogeneity, baseline characteristics of children, definition of severe pneumonia and Zn supplement way should be taken into consideration in future research. This study was registered at PRESPERO as CRD42015019798.Key words: Children: Meta-analyses: Severe pneumonia: ZincPneumonia is a leading disease and cause of death in children under 5 years in developing countries (1) . It is reported that 14·9 % of 6·3 million deaths of children <5 years old were caused by pneumonia worldwide (2) . With advances in medicine, economy and society, pneumonia with diarrhoea and measles was responsible for half of the reduction in mortality of children under 5 years from 2000 to 2013 (2) . Although great progress was achieved, only a few countries could reach the goal of Millennium Development Goal 4 to reduce under 5 child mortality by two-thirds between 1990 and 2015, and pneumonia is still the leading cause of child mortality (3) . Therefore, intensive effort should be made in the research of pneumonia.Under-nutrition has been reported to be strongly associated with impaired immune response, (4) and it has been proven to be responsible for greater severity of pneumonia, prolonged course of disease and increased mortality of pneumonia (5) .Zn, as an important micro-element, has an essential role in cellular growth and immune defence, and its deficiency is associated with significant increased susceptibility to various infection pathogens (6)(7)(8) . In a randomised-controlled trial (RCT...

show abstract

“…A similar study in India (2007) on 299 children aged 2–23 months and hospitalized due to severe pneumonia showed that, compared to the comparison group, disease symptoms were improved faster and the duration of hospitalization decreased significantly in the zinc-receiving patients [17]. …”

Section: Discussionmentioning

confidence: 99%

The Effect of Adjuvant Zinc Therapy on Recovery from Pneumonia in Hospitalized Children: A Double-Blind Randomized Controlled Trial

et al. 2014

View full text Add to dashboard Cite

Objectives. Pneumonia is one of the common mortality causes in young children. Some studies have shown beneficial effect of zinc supplements on treatment of pneumonia. The present study aimed to investigate the effects of short courses of zinc administration on recovery from this disease in hospitalized children. Methods. In a parallel Double-Blind Randomized Controlled Trial at Ayatollah Golpaygani Hospital in Qom, 120 children aged 3–60 months with pneumonia were randomly assigned 1 : 1 to receive zinc or placebo (5 mL every 12 hours) along with the common antibiotic treatments until discharge. Primary outcome was recovery from pneumonia which included the incidence and resolving clinical symptoms and duration of hospitalization. Results. The difference between two groups in all clinical symptoms at admittance and the variables affecting the disease such as age and sex were not statistically significant (P < 0.05) at baseline. Compared to the placebo group, the treatment group showed a statistically significant decrease in duration of clinical symptoms (P = 0.044) and hospitalization (P = 0.004). Conclusions. Supplemental administration of zinc can expedite the healing process and results in faster resolution of clinical symptoms in children with pneumonia. In general, zinc administration, along with common antibiotic treatments, is recommended in this group of children. It can also reduce the drug resistance caused by multiple antibiotic therapies. This trial is approved by Medical Ethic Committee of Islamic Azad University in Iran (ID Number: 8579622-Q). This study is also registered in AEARCTR (The American Economic Association's Registry for Randomized Controlled Trials). This trial is registered with RCT ID: AEARCTR-0000187.

show abstract

Infectious etiology modifies the treatment effect of zinc in severe pneumonia

Cited by 31 publications

References 44 publications

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials

The Effect of Adjuvant Zinc Therapy on Recovery from Pneumonia in Hospitalized Children: A Double-Blind Randomized Controlled Trial

Contact Info

Product

Resources

About