Effect of dose reduction of supplemental zinc for childhood diarrhoea: study protocol for a double-masked, randomised controlled trial in India and Tanzania.

BACKGROUND: Diarrhoea-associated mortality and morbidity are highest in infants and young children in low-income and middle-income countries (LMICs). Zinc supplementation during acute diarrhoea has been shown to reduce the duration of illness and the risk of persistent diarrhoea. However, vomiting with zinc supplementation is a common side effect that may interfere with compliance and programmatic scale-up, and may be related to the dose prescribed. METHODS/DESIGN: The Zinc Therapeutic Dose Trial (ZTDT) is a two-centre (Tanzania and India), three-arm randomised, double-blind controlled non-inferiority trial. Children 6-59 months of age with acute diarrhoea are eligible to participate. Enrolled children (1500 per arm; 4500 total) will be randomly allocated to receive 5, 10 or 20 mg of zinc sulfate daily for 14 days and will be followed up for 60 days after enrolment. All children will receive WHO/Unicef Integrated Management of Childhood Illness standard of care (oral or intravenous rehydration and zinc as indicated and feeding advice). The primary efficacy outcomes of the trial are the percentage of subjects with diarrhoea duration >5 days, the mean total number of loose or watery stools after enrolment and the proportion of children vomiting within 30 min of zinc administration. DISCUSSION: The ZTDT trial will determine the optimal dose of therapeutic zinc supplements for treatment of acute diarrhoea in children aged 6-59 months in two LMICs. The results of the trial are likely to be generalisable to childhood acute diarrhoea in similar resource-limited settings and may influence global policy about zinc supplementation dosage during acute diarrhoea. TRIAL REGISTRATION NUMBER: NCT03078842. TRIAL STATUS: Enrolment began in January 2017 and follow-up is estimated to be completed by April 2019. As of 1 February 2019, 742 children are still contributing data to the ZTDT study.

Effectiveness of 4% chlorhexidine umbilical cord care on neonatal mortality in Southern Province, Zambia (ZamCAT): a cluster-randomised controlled trial.

BACKGROUND: Chlorhexidine umbilical cord washes reduce neonatal mortality in south Asian populations with high neonatal mortality rates and predominantly home-based deliveries. No data exist for sub-Saharan African populations with lower neonatal mortality rates or mostly facility-based deliveries. We compared the effect of chlorhexidine with dry cord care on neonatal mortality rates in Zambia. METHODS: We undertook a cluster-randomised controlled trial in Southern Province, Zambia, with 90 health facility-based clusters. We enrolled women who were in their second or third trimester of pregnancy, aged at least 15 years, and who would remain in the catchment area for follow-up of 28 days post-partum. Newborn babies received clean dry cord care (control) or topical application of 10 mL of a 4% chlorhexidine solution once per day until 3 days after cord drop (intervention), according to cluster assignment. We used stratified, restricted randomisation to divide clusters into urban or two rural groups (located <40 km or ≥40 km to referral facility), and randomly assigned clusters (1:1) to use intervention (n=45) or control treatment (n=45). Sites, participants, and field monitors were aware of their study assignment. The primary outcomes were all-cause neonatal mortality within 28 days post-partum and all-cause neonatal mortality within 28 days post-partum among babies who survived the first 24 h of life. Analysis was by intention to treat. Neonatal mortality rate was compared with generalised estimating equations. This study is registered at ClinicalTrials.gov (NCT01241318). FINDINGS: From Feb 15, 2011, to Jan 30, 2013, we screened 42 356 pregnant women and enrolled 39 679 women (mean 436·2 per cluster [SD 65·3]), who had 37 856 livebirths and 723 stillbirths; 63·8% of deliveries were facility-based. Of livebirths, 18 450 (99·7%) newborn babies in the chlorhexidine group and 19 308 (99·8%) newborn babies in the dry cord care group were followed up to day 28 or death. 16 660 (90·0%) infants in the chlorhexidine group had chlorhexidine applied within 24 h of birth. We found no significant difference in neonatal mortality rate between the chlorhexidine group (15·2 deaths per 1000 livebirths) and the dry cord care group (13·6 deaths per 1000 livebirths; risk ratio [RR] 1·12, 95% CI 0·88-1·44). Eliminating day 0 deaths yielded similar findings (RR 1·12, 95% CI 0·86-1·47). INTERPRETATION: Despite substantial reductions previously reported in south Asia, chlorhexidine cord applications did not significantly reduce neonatal mortality rates in Zambia. Chlorhexidine cord applications do not seem to provide clear benefits for newborn babies in settings with predominantly facility-based deliveries and lower (<30 deaths per 1000 livebirths) neonatal mortality rates. FUNDING: Bill & Melinda Gates Foundation.

Engagement of the community, traditional leaders, and public health system in the design and implementation of a large community-based, cluster-randomized trial of umbilical cord care in Zambia.

Conducting research in areas with diverse cultures requires attention to community sensitization and involvement. The process of community engagement is described for a large community-based, cluster-randomized, controlled trial comparing daily 4% chlorhexidine umbilical cord wash to dry cord care for neonatal mortality prevention in Southern Province, Zambia. Study preparations required baseline formative ethnographic research, substantial community sensitization, and engagement with three levels of stakeholders, each necessitating different strategies. Cluster-specific birth notification systems developed with traditional leadership and community members using community-selected data collectors resulted in a post-natal home visit within 48 hours of birth in 96% of births. Of 39,679 pregnant women enrolled (93% of the target of 42,570), only 3.7% were lost to follow-up or withdrew antenatally; 0.2% live-born neonates were lost by day 28 of follow-up. Conducting this trial in close collaboration with traditional, administrative, political, and community stakeholders facilitated excellent study participation, despite structural and sociocultural challenges.

Household dynamics and socioeconomic conditions in the context of incident adolescent orphaning in KwaZulu-Natal, South Africa.

We compared demographics, socioeconomic status, and food insecurity between households with and without recent orphans in a region of high HIV/AIDS mortality in South Africa. We recruited a cohort of 197 recent orphans and 528 non-orphans ages 9-15 and their households using stratified cluster sampling. Households were classified into three groups: orphan-only (N=50); non-orphan-only (N=377); and mixed (N=210). Between September 2004 and May 2007, households were interviewed three times regarding demographics, income and assets, and food insecurity. Baseline bivariate associations were assessed using chi-square- and t-tests. Longitudinal bivariate associations and multivariate models were tested using generalized estimating equations. At baseline, mixed households generally exhibited greater characteristics of vulnerability than orphan and non-orphan households. They were larger, had older, less educated household heads, and reported a much smaller annual per capita income. Orphan households were more likely to report a death in the previous year, and less likely to have an adult employed. These differences persisted over the study. Even non-orphan households exhibited characteristics of vulnerability, with 14% reporting a death one year before baseline, 45% of whom were prime-age adults. At baseline, a much smaller proportion of orphan households reported receiving the child support grant than the other household types, but notably, there were no differences among households in receipt of the grant by Round 3. Household food insecurity was highly prevalent: more than one in five orphan-only and mixed households reported being food insecure in the previous month. These findings suggest that the effects of HIV/AIDS only exacerbate existing high levels of poverty in the district, as virtually all households are vulnerable regardless of orphan status. Community-level programs must help families address a spectrum of needs, including food security, caregiving, and financial support, as well as better target social welfare grants and make them more accessible to vulnerable households.

Antiretroviral therapy, labor productivity, and sex: a longitudinal cohort study of tea pluckers in Kenya.

OBJECTIVE: To estimate the impact of antiretroviral therapy (ART) on labor productivity and income using detailed employment data from two large tea plantations in western Kenya for HIV-infected tea pluckers who initiated ART. DESIGN: Longitudinal study using primary data on key employment outcomes for a group of HIV-infected workers receiving antiretroviral therapy (ART) and workers in the general workforce. METHODS: We used nearest-neighbor matching methods to estimate the impacts of HIV/AIDS and ART among 237 HIV-positive pluckers on ART (index group) over a 4-year period (2 years pre-ART and post-ART) on 4 monthly employment outcomes - days plucking tea, total kilograms (kgs) harvested, total days working, and total labor income. Outcomes for the index group were compared with those for a matched reference group from the general workforce. RESULTS: We observed a rapid deterioration in all four outcomes for HIV-infected individuals in the period before ART initiation and then a rapid improvement after treatment initiation. By 18-24 months after treatment initiation, the index group harvested 8% (men) and 19% (women) less tea than reference individuals. The index group earned 6% (men) and 9% (women) less income from labor than reference individuals. Women's income would have dropped further if they had not been able to offset their decline in tea plucking by spending more time on nonplucking assignments. CONCLUSION: HIV-infected workers experienced long-term income reductions before and after initiating ART. The implications of such long-term impacts in low-income countries have not been adequately addressed.

Longitudinal evaluation of the psychosocial wellbeing of recent orphans compared with non-orphans in a school-attending cohort in KwaZulu-Natal, South Africa.

To assess differences in psychosocial wellbeing between recent orphans and non-orphans, we followed a cohort of 157 school-going orphans and 480 non-orphans ages 9-15 in a context of high HIV/AIDS mortality in South Africa from 2004 to 2007. Several findings were contrary to published evidence to date, as we found no difference between orphans and non-orphans in anxiety/depression symptoms, oppositional behavior, self-esteem, or resilience. Female gender, self-reported poor health, and food insecurity were the most important predictors of children's psychosocial wellbeing. Notably, girls had greater odds of reporting anxiety/depression symptoms than boys, and scored lower on self-esteem and resilience scales. Food insecurity predicted greater anxiety/depression symptoms and lower resilience. Perceived social support was a protective factor, as it was associated with lower odds of anxiety/depression symptoms, lower oppositional scores, and greater self-esteem and resilience. Our findings suggest a need to identify and strengthen psychosocial supports for girls, and for all children in contexts of AIDS-affected and economic adversity.

Effect of training traditional birth attendants on neonatal mortality (Lufwanyama Neonatal Survival Project): randomised controlled study.

OBJECTIVE: To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare. DESIGN: Prospective, cluster randomised and controlled effectiveness study. SETTING: Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers' homes, in rural village settings. PARTICIPANTS: 127 traditional birth attendants and mothers and their newborns (3559 infants delivered regardless of vital status) from Lufwanyama district. INTERVENTIONS: Using an unblinded design, birth attendants were cluster randomised to intervention or control groups. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. Control birth attendants continued their existing standard of care (basic obstetric skills and use of clean delivery kits). MAIN OUTCOME MEASURES: The primary outcome was the proportion of liveborn infants who died by day 28 after birth, with rate ratios statistically adjusted for clustering. Secondary outcomes were mortality at different time points; and comparison of causes of death based on verbal autopsy data. RESULTS: Among 3497 deliveries with reliable information, mortality at day 28 after birth was 45% lower among liveborn infants delivered by intervention birth attendants than control birth attendants (rate ratio 0.55, 95% confidence interval 0.33 to 0.90). The greatest reductions in mortality were in the first 24 hours after birth: 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants (0.40, 0.19 to 0.83). Deaths due to birth asphyxia were reduced by 63% among infants delivered by intervention birth attendants (0.37, 0.17 to 0.81) and by 81% within the first two days after birth (0.19, 0.07 to 0.52). Stillbirths and deaths from serious infection occurred at similar rates in both groups. CONCLUSIONS: Training traditional birth attendants to manage common perinatal conditions significantly reduced neonatal mortality in a rural African setting. This approach has high potential to be applied to similar settings with dispersed rural populations. Trial registration Clinicaltrials.gov NCT00518856.

Children of female sex workers and drug users: a review of vulnerability, resilience and family-centred models of care.

BACKGROUND: Injection drug users and female sex workers are two of the populations most at risk for becoming infected with HIV in countries with concentrated epidemics. Many of the adults who fall into these categories are also parents, but little is known about the vulnerabilities faced by their children, their children's sources of resilience, or programmes providing services to these often fragile families. This review synthesizes evidence from disparate sources describing the vulnerabilities and resilience of the children of female sex workers and drug users, and documents some models of care that have been put in place to assist them. REVIEW: A large literature assessing the vulnerability and resilience of children of drug users and alcoholics in developed countries was found. Research on the situation of the children of sex workers is extremely limited. Children of drug users and sex workers can face unique risks, stigma and discrimination, but both child vulnerability and resilience are associated in the drug use literature with the physical and mental health of parents and family context. Family-centred interventions have been implemented in low- and middle-income contexts, but they tend to be small, piecemeal and struggling to meet demand; they are poorly documented, and most have not been formally evaluated. We present preliminary descriptive data from an organization working with pregnant and new mothers who are drug users in Ukraine and from an organization providing services to sex workers and their families in Zambia. CONCLUSIONS: Because parents' drug use or sex work is often illegal and hidden, identifying their children can be difficult and may increase children's vulnerability and marginalization. Researchers and service providers, therefore, need to proceed with caution when attempting to reach these populations, but documentation and evaluation of current programmes should be prioritized.

Improvements in physical wellbeing over the first two years on antiretroviral therapy in western Kenya.

Improvements in physical wellbeing during the first six months on antiretroviral therapy (ART) are well known, but little is known regarding long-term follow-up. We conducted a prospective cohort study among 222 HIV-positive adult tea plantation workers in western Kenya to assess wellbeing over their first two years on ART. Study subjects completed a standardized questionnaire during repeat ART clinic visits. A 30-day recall period was used to elicit the number of days when subjects experienced poor health and the number of days that pain made it difficult to complete usual activities at home and work. A seven-day recall period was used to assess the severity of bodily pain, nausea, fatigue, and rash. Prevalence of most symptoms declined over time. A median of seven days poor health during the first month on ART declined to three days in the 24th month (p=0.043). For pain making usual activities difficult, a median of seven days during the first month on ART fell to zero by 12 months (p< or =0.0001) but increased to three days by two years. Any bodily pain (range 59-83%) and fatigue (range 51-84%) over the past seven days were common through two years. However, pain and fatigue often over the past seven days declined over two years (from 24-10% (p=0.067) and 41-15% (p=0.002)). Skin rash was rare at all times, though higher at two years (8.6%) than any other time. Initial improvements in physical wellbeing were sustained over two years, however, increased pain and skin rash at year two may indicate problems as treatment programs mature. These improvements in physical wellbeing will be important in sustaining the long-term success of HIV treatment programs.

Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial.

BACKGROUND: WHO case management guidelines for severe pneumonia involve referral to hospital for treatment with parenteral antibiotics. If equally as effective as parenteral treatment, home-based oral antibiotic treatment could reduce referral, admission, and treatment costs. Our aim was to determine whether home treatment with high-dose oral amoxicillin and inpatient treatment with parenteral ampicillin were equivalent for the treatment of severe pneumonia in children. METHODS: This randomised, open-label equivalency trial was done at seven study sites in Pakistan. 2037 children aged 3-59 months with severe pneumonia were randomly allocated to either initial hospitalisation and parenteral ampicillin (100 mg/kg per day in four doses) for 48 h, followed by 3 days of oral amoxicillin (80-90 mg/kg per day; n=1012) or to home-based treatment for 5 days with oral amoxicillin (80-90 mg/kg per day in two doses; n=1025). Follow-up assessments were done at 1, 3, 6, and 14 days after enrollment. The primary outcome was treatment failure (clinical deterioration) by day 6. Analyses were done per protocol and by intention to treat. This trial is registered, ISRCTN95821329. FINDINGS: In the per-protocol population, 36 individuals were excluded from the hospitalised group and 37 from the ambulatory group, mainly because of protocol violations or loss to follow-up. There were 87 (8.6%) treatment failures in the hospitalised group and 77 (7.5%) in the ambulatory group (risk difference 1.1%; 95% CI -1.3 to 3.5) by day 6. Five (0.2%) children died within 14 days of enrollment, one in the ambulatory group and four in the hospitalised group. In each case, treatment failure was declared before death and the antibiotic had been changed. None of the deaths were considered to be associated with treatment allocation; there were no serious adverse events reported in the trial. INTERPRETATION: Home treatment with high-dose oral amoxicillin is equivalent to currently recommended hospitalisation and parenteral ampicillin for treatment of severe pneumonia without underlying complications, suggesting that WHO recommendations for treatment of severe pneumonia need to be revised.

Early effects of antiretroviral therapy on work performance: preliminary results from a cohort study of Kenyan agricultural workers.

OBJECTIVE: This paper estimates the impact of antiretroviral therapy (ART) on days harvesting tea per month for tea-estate workers in Kenya. Such information is needed to assess the potential economic benefits of providing treatment to working adults. METHODS: Data for this analysis come from company payroll records for 59 HIV-infected workers and a comparison group of all workers assigned to the same work teams (reference group, n = 1992) for a period covering 2 years before and 1 year after initiating ART. Mean difference tests were used to obtain overall trends in days harvesting tea by month. A difference in difference approach was used to estimate the impact of HIV/AIDS on days working in the pre-ART period. Information on likely trends in the absence of the therapy was used to estimate the positive impacts on days harvesting tea over the initial 12 months on ART. RESULTS: No significant difference existed in days plucking tea each month until the ninth month before initiating ART, when workers worked -2.79 fewer days than references (15% less). This difference grew to 5.09 fewer days (27% less) in the final month before initiating ART. After 12 months on ART, we conservatively estimate that workers worked at least twice as many days in the month than they would have in the absence of ART. CONCLUSIONS: Treatment had a large, positive impact on the ability of workers to undertake their primary work activity, harvesting tea, in the first year on ART.

From chloroquine to artemether-lumefantrine: the process of drug policy change in Zambia.

BACKGROUND: Following the recognition that morbidity and mortality due to malaria had dramatically increased in the last three decades, in 2002 the government of Zambia reviewed its efforts to prevent and treat malaria. Convincing evidence of the failing efficacy of chloroquine resulted in the initiation of a process that eventually led to the development and implementation of a new national drug policy based on artemisinin-based combination therapy (ACT). METHODS: All published and unpublished documented evidence dealing with the antimalarial drug policy change was reviewed. These data were supplemented by the authors' observations of the policy change process. The information has been structured to capture the timing of events, the challenges encountered, and the resolutions reached in order to achieve implementation of the new treatment policy. RESULTS: A decision was made to change national drug policy to artemether-lumefantrine (AL) in the first quarter of 2002, with a formal announcement made in October 2002. During this period, efforts were undertaken to identify funding for the procurement of AL and to develop new malaria treatment guidelines, training materials, and plans for implementation of the policy. In order to avoid a delay in implementation, the policy change decision required a formal adoption within existing legislation. Starting with donated drug, a phased deployment of AL began in January 2003 with initial use in seven districts followed by scaling up to 28 districts in the second half of 2003 and then to all 72 districts countrywide in early 2004. CONCLUSION: Drug policy changes are not without difficulties and demand a sustained international financing strategy for them to succeed. The Zambian experience demonstrates the need for a harmonized national consensus among many stakeholders and a political commitment to ensure that new policies are translated into practice quickly. To guarantee effective policies requires more effort and recognition that this becomes a health system and not a drug issue. This case study attempts to document the successful experience of change to ACT in Zambia and provides a realistic overview of some of the painful experiences and important lessons learnt.

Exploring the Cinderella myth: intrahousehold differences in child wellbeing between orphans and non-orphans in Amajuba District, South Africa.

OBJECTIVE: To determine whether differences in wellbeing (defined by a variety of education and health outcomes) exist between recent school-aged orphans and non-orphans who live in the same household in a context of high HIV/AIDS mortality in KwaZulu Natal, South Africa. DESIGN: The data come from the first 2 years (2004-2006) of an ongoing 3-year longitudinal cohort study in a district in KwaZulu-Natal, the Amajuba Child Health and Well-being Research Project. Using stratified cluster sampling based on school and age, we constructed a cohort of 197 recent orphans and 528 non-orphans aged 9-16 years and their households and caregivers. Household heads, caregivers, and children were interviewed regarding five domains of child wellbeing: demographic, economic, educational, health/nutrition/lifestyle, and psychosocial status. METHODS: The analytical sample consists of 174 children (87 orphans and 87 comparable non-orphans who live together) at baseline and 124 children in round 2. We estimated a linear regression model using household fixed effects for continuous outcomes (grade adjusted for age, annual expenditure on schooling and body mass index) and a logit model using household fixed effects for categorical variables (malnutrition) to compare co-resident orphans and non-orphans. RESULTS: We found no statistically significant differences in most education, health and labour outcomes between orphans and the non-orphans with whom they live. Paternal orphans are more likely to be behind in school, and recent mobility has a positive effect on schooling outcomes.

Improved diagnostic testing and malaria treatment practices in Zambia.

CONTEXT: Improving the accuracy of malaria diagnosis with rapid antigen-detection diagnostic tests (RDTs) has been proposed as an approach for reducing overtreatment of malaria in the current era of widespread implementation of artemisinin-based combination therapy in sub-Saharan Africa. OBJECTIVE: To assess the association between use of microscopy and RDT and the prescription of antimalarials. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, cluster sample survey, carried out between March and May 2006, of all outpatients treated during 1 working day at government and mission health facilities in 4 sentinel districts in Zambia. MAIN OUTCOME MEASURE: Proportions of patients undergoing malaria diagnostic procedures and receiving antimalarial treatment. RESULTS: Seventeen percent of the 104 health facilities surveyed had functional microscopy, 63% had RDTs available, and 73% had 1 or more diagnostics available. Of patients with fever (suspected malaria), 27.8% (95% confidence interval [CI], 13.1%-42.5%) treated in health facilities with malaria diagnostics were tested and 44.6% had positive test results. Of patients with negative blood smear results, 58.4% (95% CI, 36.7%-80.2%) were prescribed an antimalaria drug, as were 35.5% (95% CI, 16.0%-55.0%) of those with a negative RDT result. Of patients with fever who did not have diagnostic tests done, 65.9% were also prescribed antimalarials. In facilities with artemether-lumefantrine in stock, this antimalarial was prescribed to a large proportion of febrile patients with a positive diagnostic test result (blood smear, 75.0% [95% CI, 51.7%-98.3%]; RDT, 70.4% [95% CI, 39.3%-100.0%]), but also to some of those with a negative diagnostic test result (blood smear, 30.4% [95% CI, 8.0%-52. 9%]; RDT, 26.7% [95% CI, 5.7%-47.7%]). CONCLUSIONS: Despite efforts to expand the provision of malaria diagnostics in Zambia, they continue to be underused and patients with negative test results frequently receive antimalarials. Provision of new tools to reduce inappropriate use of new expensive antimalarial treatments must be accompanied by a major change in clinical treatment of patients presenting with fever but lacking evidence of malaria infection.

Health promotion in older adults: evidence-based smoking cessation programs for use in primary care settings.

Tobacco dependency is a growing problem among older adults. Given the addictive nature of tobacco use, smokers need a multifactorial treatment program to help stop smoking. Health care professionals can play a pivotal role in the promotion of a smoking cessation treatment program to people of all ages, including the elderly. This paper presents important evidence that smoking cessation services for the elderly are effective, and describes how primary care physicians can support elderly people quit smoking.

No room for complacency about adherence to antiretroviral therapy in sub-Saharan Africa.

Medication adherence is essential to successful treatment of HIV/AIDS. Maintaining high adherence will likely prove a major challenge in Africa -- just as it has in developed nations. Despite early reports suggesting that adherence would not pose a major barrier to treatment success, more recent research shows that adherence rates in Africa are quite variable and often poor. Given the large number of patients whose disease will progress if adherence is suboptimal, research is urgently needed to determine patient-level behavioral barriers to adherence and the most effective and appropriate methods for assessing adherence in African cohorts.

Plasma zinc concentrations are depressed during the acute phase response in children with falciparum malaria.

Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 micromol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response.