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Diarrhea accounts for an estimated 18% of childhood deaths worldwide.1 Zinc treatment given for 10–14 days during and after the diarrheal episode is associated with reductions in severity and duration, all-cause less than 5-year mortality, and incidence of diarrheal cases in the months after zinc treatment.2–4 World Health Organization (WHO) and the United Nations Children’s Fund (UNICEF) now recommend a 10- to 14-day course of zinc treatment in addition to oral rehydration salts (ORS) for the treatment of acute childhood diarrhea.5
Administration of medications for childhood illness is generally less than adequate.6–8 Concerns have been raised regarding the 10- to 14-day course of zinc treatment, which is longer than most treatment regimens. Adherence with zinc treatment of diarrhea has not been previously reported for Africa. This report characterizes administration of zinc treatment in the home in a small-scale pilot study examining operational issues associated with introduction of this new treatment.
As part of the pilot phase of a multi-center study examining the operational impacts of zinc introduction in Pakistan, India, and Mali health centers and drug kits managed by community health workers (CHWs) provided zinc to children presenting with diarrhea in two health zones in Bougouni District, southern Mali.9 The project trained health center staff and CHWs in 1) diarrhea case management with zinc and ORS, 2) counseling of parents on child feeding and diarrhea prevention and treatment, and 3) recording routine data in notebooks. The recommended 14-day course of zinc treatment is one 20-mg dispersible tablet per day for children of age 6 months or older and 10 mg/d (one half a tablet) for children less than 6 months. Labels attached to the 14-count blister packages provided pictorial and written instructions in Bambara, the local language, on zinc administration. A key message was "give the child with diarrhea one tablet a day for 14 days, even if the diarrhea stops." Pictorial and written instructions for children less than 6 months instructed parents to cut the tablet in half and administer 
tablet to the child each day; the age-specific, labeled, blister packets are shown in Figure 1
. The cost of zinc to patients was 100 francs cfa (~0.19 USD) for the full blister package and 50 francs cfa (~0.09 USD) for of the blister package (for children less than 6 months of age).
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To document reactions to the new treatment and patterns of drug administration, we conducted semi-structured qualitative interviews with 37 caretakers of young children: 28 that had used zinc treatment and 9 that had not, as well as 18 CHWs and 2 health facility nurses.
The minimum dose of zinc treatment was defined as 10 or more days of the same dose of treatment, which is the minimum recommended by the WHO.10 Analysis was carried out in SPSS 11.011 and Stata Version 7.12
The study received ethical approval from Johns Hopkins University Bloomberg School of Public Health Committee for Human Research and the University of Bamako Faculty of Medicine, Pharmacy, and Dentistry Internal Review Board. Consent in each participating village was obtained from village leaders, and parents were asked for consent before interviews.
A total of 123 children who received zinc, 21 at health centers and 102 from CHWs, were followed-up in their homes. Almost one half the children (47%) were 12–23 months of age, with younger children more frequently visiting the health facility (Table 1). Two children died between the day 3 and 14 visits. Verbal autopsy interviews, which investigated the causes of death and the actions taken before the child’s deaths, were conducted with caretakers and identified no connection with zinc administration. Parents reported that their children had diarrhea for an average of 3.2 days (95% confidence interval = 2.6, 3.8) before presenting for care to the health center or CHW. The majority of caretakers reported that their children had symptoms in addition to diarrhea, most commonly fever and vomiting. Table 1 presents characteristics of the illness episodes reported by parents.
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). More than 90% of caretakers reported that CHWs and health center staff sufficiently explained the quantity of zinc needed, duration of treatment, and alternatives for administering the tablets (directly, by or dissolving them in water or breast milk). Fewer than 25% of caretakers reported that they received information about danger signs requiring referral to a health center. Health facility staff and CHWs showed adequate knowledge of treatment and counseling guidelines in semi-structured interviews.
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Adherence to the full 14-day regimen was high, and dosing was generally appropriate (Table 2
). About two thirds of children received the dose of zinc exactly as recommended for 14 days. In addition, 89% of children followed received at least 10 days of zinc treatment. Those cases who only received the minimum dose rather than the recommended quantity either stopped administering zinc on day 12 or 13 or skipped 1–2 days during the 2-week period. One child under 6 months was prescribed and received a full tablet (20 mg) per day instead of the recommended one half of a tablet (10 mg). Children that did not receive the minimum treatment either had their treatment stopped after a few days or were children over 6 months who received only one half of a tablet per day. The rate of correct prescription and levels of administration of the zinc treatment did not differ greatly by source of prescription (Figure 2).
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"Before I gave the zinc to my child, he could not go 2 weeks without having diarrhea. Every time I gave him the medications, the diarrhea would stop for a few days and then start again. But with the zinc it was different, the child took the zinc and he is relieved....he plays a lot as you can see, he eats, and breast feeds without stopping."
In summary, most children received the minimum recommended dose of zinc, despite the long duration of the dosing schedule, acceptance of the new treatment was high, and few side effects were noted. Blister packs likely facilitated correct prescription and administration, as has been seen in previous studies,9,13–20 although no conclusions can be drawn from our study design. It is possible that the levels of correct prescription, counseling, and administration we observed are higher than those expected a typical program context. Although this study aimed to characterize administration under routine program conditions, zinc was a newly introduced treatment under conditions of closer-than-usual observation. Interviewers visiting households for follow-up could also have increased the level of compliance, especially if families were expecting a visit on the 14th day and suspected the interviewer would examine the blister package.
Most children received at least 10 days of treatment in our study. This is very promising for the expected public health impact of the introduction of zinc treatment of childhood diarrhea. Significant benefits from zinc treatment of diarrhea have been reported in Bangladesh even when children receive a mean of 7 days of treatment.2 However, many fewer children were administered zinc for 14 days (all the tablets in the blister package). It is likely that, similar to our observations, caretakers might give fewer than the 10 tablets contained in the commercially available blister package, resulting in fewer children receiving the minimum recommended dose. The 10-day treatment regimen should be introduced with approaches to ensure high levels of compliance, such as inclusion of locally appropriate dosing instructions and communication of clear counseling messages by health workers; levels of correct administration should also be evaluated for this dosing regimen.
This study did not examine factors affecting administration of zinc such as who purchases the zinc, counseling received from the health care provider, educational level of the parents, concomitant symptoms and medications, and side effects such as vomiting. The next phase of research will examine these aspects in more depth.
Received July 19, 2005. Accepted for publication November 19, 2005.
* Address correspondence to Peter J. Winch, Department of International Health, Social and Behavioral Interventions Program, Johns Hopkins Bloomberg School of Public Health, Room E5030, 615 North Wolfe Street, Baltimore, MD 21205-2103. E-mail: pwinch{at}jhsph.edu 
Authors’ addresses: Peter J. Winch, Kate Gilroy, and Robert Black, Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD USA 21205-2103. Seydou Doumbia, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, BP 1895, Bamako, Mali. Amy E. Patterson, Department of Behavioral Science and Health Education, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA, 30322. Zana Daou and Seyon Coulibaly, Save the Children/USA, Sahel Field Office, BP 3105, Bamako, Mali. Eric Swedberg, Save the Children/USA, 54 Wilton Road, Westport, Connecticut USA 06880. Olivier Fontaine, World Health Organization, Division of Child and Adolescent Health and Development, 20 Avenue Appia, Geneva, Switzerland.
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  P. J. Winch, S. Doumbia, M. Kante, A. Diarra Male, E. Swedberg, K. E. Gilroy, A. A. Ellis, G. Cisse, and B. Sidibe Differential Community Response to Introduction of Zinc for Childhood Diarrhea and Combination Therapy for Malaria in Southern Mali J. Nutr., March 1, 2008; 138(3): 642 - 645. [Abstract] [Full Text] [PDF]
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