Village-Randomized Clinical Trial of Home Distribution of Zinc for Treatment of Childhood Diarrhea in Rural Western Kenya

<div><p>Background</p><p>Zinc treatment shortens diarrhea episodes and can prevent future episodes. In rural Africa, most children with diarrhea are not brought to health facilities. In a village-randomized trial in rural Kenya, we assessed if zinc treatment might have a community-level preventive effect on diarrhea incidence if available at home versus only at health facilities.</p><p>Methods</p><p>We randomized 16 Kenyan villages (1,903 eligible children) to receive a 10-day course of zinc and two oral rehydration solution (ORS) sachets every two months at home and 17 villages (2,241 eligible children) to receive ORS at home, but zinc at the health–facility only. Children’s caretakers were educated in zinc/ORS use by village workers, both unblinded to intervention arm. We evaluated whether incidence of diarrhea and acute lower respiratory illness (ALRI) reported at biweekly home visits and presenting to clinic were lower in zinc villages, using poisson regression adjusting for baseline disease rates, distance to clinic, and children’s age.</p><p>Results</p><p>There were no differences between village groups in diarrhea incidence either reported at the home or presenting to clinic. In zinc villages (1,440 children analyzed), 61.2% of diarrheal episodes were treated with zinc, compared to 5.4% in comparison villages (1,584 children analyzed, p<0.0001). There were no differences in ORS use between zinc (59.6%) and comparison villages (58.8%). Among children with fever or cough without diarrhea, zinc use was low (<0.5%). There was a lower incidence of reported ALRI in zinc villages (adjusted RR 0.68, 95% CI 0.46–0.99), but not presenting at clinic.</p><p>Conclusions</p><p>In this study, home zinc use to treat diarrhea did not decrease disease rates in the community. However, with proper training, availability of zinc at home could lead to more episodes of pediatric diarrhea being treated with zinc in parts of rural Africa where healthcare utilization is low.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00530829?term=NCT00530829&rank=1" target="_blank">NCT00530829</a></p></div

Baseline characteristics for participants in home zinc and comparison villages, western Kenya, February 2008–March 2009.

<p>*p value controls for cluster design by village.</p>†<p>Poorer household is defined as the lowest two quintiles using multiple component analysis.</p

Effect of home zinc on rate of sick visits to Lwak clinic, hospitalization, and mortality, western Kenya, from February 2008–March 2009, controlling for baseline rates of morbidity in home zinc and comparison villages.

<p>Intention-to-treat analysis includes all enrolled children. Rates are given as episodes per person-year.</p><p>*Pre-intervention period was October 2006 to November 2007.</p>†<p>While pre-intervention includes all children in the village of appropriate age, the intervention period only includes those enrolled in the home zinc study.</p>‡<p>Rate ratio is comparing rates between home zinc and comparison groups during the intervention period, adjusted for pre-intervention rates of same syndrome in the child’s village, distance of child’s compound to Lwak Hospital and child’s age.</p>¶<p>For primary outcome, intracluster correlation (ICC) = 0.027.</p

Trial profile.

<p>Village randomization and number of children enrolled at the initial enrollment in December 2007 and during the ongoing enrollment during the study period from February 2008–March 2009. Children and person-time contribution given for the analysis of clinic-based surveillance and household morbidity surveillance – see methods. PBIDS = Population-based Infectious Disease Surveillance.</p

Case definitions for major infectious disease syndromes from clinic and household morbidity surveillance (HMS) in Asembo, western Kenya.

<p>*Elevated respiratory rate for age based on WHO Integrated Management of Childhood Illness algorithm <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094436#pone.0094436-Winch1" target="_blank">[14]</a>; <2 months, ≥60 breaths/minute; 2–11 months, ≥50 breaths/minute; 12–59 months, ≥40 breaths/minute.</p>†<p>IMCI danger signs are maternal report of convulsions, inability to drink or breastfeed, or vomiting everything, or on exam lethargy or unconsciousness <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094436#pone.0094436-WHO1" target="_blank">[22]</a>.</p>‡<p>IMCI signs/symptoms of dehydration are the following: sunken eyes, slow skin pinch, restless/irritable behavior, drinking eagerly or not at all <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094436#pone.0094436-WHO1" target="_blank">[22]</a>.</p

Effect of home zinc on rates of reported morbidity at the household morbidity surveillance (HMS), western Kenya, from February 2008–March 2009, controlling for baseline rates of morbidity in home zinc and comparison villages.

<p>Rates are given as episodes per person-year.</p><p>*Pre-intervention period was October 2006 to November 2007.</p>†<p>While pre-intervention includes all children in the village of appropriate age, the intervention period only includes those enrolled in the home zinc study.</p>‡<p>Rate ratio is comparing rates between home zinc and comparison groups during the intervention period, adjusted for pre-intervention rates of the same syndrome in the child’s village, distance of village to Lwak and child’s age.</p

Effect of intervention on drug use and healthcare use for various disease syndromes during the intervention period from household morbidity surveillance (HMS), western Kenya, February 2008–March 2009.

<p>*p-value calculation includes a random effect variable for village, and adjusts for pre-intervention rates of seeking care outside the home by village - F-test in SAS PROC GLIMMIX.</p>†<p>% given in table is the % of biweekly household visits with illness that resulted in medication use or care-seeking outside the home. Denominator for sought care was slightly lower than for medication use due to some missing data for that variable.</p>¶<p>For primary outcome, intracluster correlation (ICC) = 0.030.</p