Sensitivity and Uncertainty Analysis for Two-stream Capture-Recapture Methods in Disease Surveillance.

Capture-recapture methods are widely applied in estimating the number ( ) of prevalent or cumulatively incident cases in disease surveillance. Here, we focus the bulk of our attention on the common case in which there are 2 data streams. We propose a sensitivity and uncertainty analysis framework grounded in multinomial distribution-based maximum likelihood, hinging on a key dependence parameter that is typically nonidentifiable but is epidemiologically interpretable. Focusing on the epidemiologically meaningful parameter unlocks appealing data visualizations for sensitivity analysis and provides an intuitively accessible framework for uncertainty analysis designed to leverage the practicing epidemiologist's understanding of the implementation of the surveillance streams as the basis for assumptions driving estimation of . By illustrating the proposed sensitivity analysis using publicly available HIV surveillance data, we emphasize both the need to admit the lack of information in the observed data and the appeal of incorporating expert opinion about the key dependence parameter. The proposed uncertainty analysis is a simulation-based approach designed to more realistically acknowledge variability in the estimated associated with uncertainty in an expert's opinion about the nonidentifiable parameter, together with the statistical uncertainty. We demonstrate how such an approach can also facilitate an appealing general interval estimation procedure to accompany capture-recapture methods. Simulation studies illustrate the reliable performance of the proposed approach for quantifying uncertainties in estimating in various contexts. Finally, we demonstrate how the recommended paradigm has the potential to be directly extended for application to data from >2 surveillance streams.

A censored quantile regression approach for relative survival analysis: Relative survival quantile regression.

We propose a censored quantile regression model for the analysis of relative survival data. We create a hybrid data set consisting of the study observations and counterpart randomly sampled pseudopopulation observations imputed from population life tables that adjust for expected mortality. We then fit a censored quantile regression model to the hybrid data incorporating demographic variables (e.g., age, biologic sex, calendar time) corresponding to the population life tables of demographically-similar individuals, a population versus study covariate, and its interactions with the variables of interest. These latter variables can be interpreted as relative survival parameters that depict the differences in failure quantiles between the study participants and their population counterparts.

Drug-Inducible Gene Therapy Effectively Reduces Spontaneous Seizures in Kindled Rats but Creates Off-Target Side Effects in Inhibitory Neurons.

Over a third of patients with temporal lobe epilepsy (TLE) are not effectively treated with current anti-seizure drugs, spurring the development of gene therapies. The injection of adeno-associated viral vectors (AAV) into the brain has been shown to be a safe and viable approach. However, to date, AAV expression of therapeutic genes has not been regulated. Moreover, a common property of antiepileptic drugs is a narrow therapeutic window between seizure control and side effects. Therefore, a long-term goal is to develop drug-inducible gene therapies that can be regulated by clinically relevant drugs. In this study, a first-generation doxycycline-regulated gene therapy that delivered an engineered version of the leak potassium channel Kcnk2 (TREK-M) was injected into the hippocampus of male rats. Rats were electrically stimulated until kindled. EEG was monitored 24/7. Electrical kindling revealed an important side effect, as even low expression of TREK M in the absence of doxycycline was sufficient to cause rats to develop spontaneous recurring seizures. Treating the epileptic rats with doxycycline successfully reduced spontaneous seizures. Localization studies of infected neurons suggest seizures were caused by expression in GABAergic inhibitory neurons. In contrast, doxycycline increased the expression of TREK-M in excitatory neurons, thereby reducing seizures through net inhibition of firing. These studies demonstrate that drug-inducible gene therapies are effective in reducing spontaneous seizures and highlight the importance of testing for side effects with pro-epileptic stressors such as electrical kindling. These studies also show the importance of evaluating the location and spread of AAV-based gene therapies in preclinical studies.

Neocortical injury-induced status epilepticus.

OBJECTIVE: To characterize neocortical onset status epilepticus (SE) in the C57BL/6J mouse. METHODS: We induced SE by administering homocysteine 16-18 hours after cobalt (Co) implantation. SE was monitored by video and electroencephalography (EEG). We evaluated brain structure with magnetic resonance imaging (MRI). Neurodegeneration was evaluated 72 hours after SE using Fluoro-Jade C staining. RESULTS: Cobalt triggered seizures in a dose-dependent manner (median effective dose, ED50  = 0.78 mg) and the latency to peak seizure frequency shortened with increased dose. Animals developed SE after homocysteine administration. SE began with early intermittent focal seizures, consisting of frontal onset rhythmic spike-wave discharges manifested as focal dystonia with clonus. These focal seizures then evolved into generalized continuous convulsive activity. Behavioral manifestations of SE included tonic stiffening, bilateral limb clonus, and bilateral tonic-clonic movements, which were accompanied by generalized rhythmic spike-wave discharges on EEG. After prolonged seizures, animals became comatose with intermittent bilateral myoclonic seizures or jerks. During this period, EEG showed seizures interspersed with generalized periodic discharges on a suppressed background. MRI obtained when animals were in a coma revealed edema, midline shift in frontal lobe around the Co implantation site, and ventricular effacement. Fluoro-Jade C staining revealed neurodegeneration in the cortex, amygdala, and thalamus. SIGNIFICANCE: We have developed a mouse model of severe, refractory cortical-onset SE, consisting of convulsions merging into a coma, EEG patterns of cortical seizures, and injury, with evidence of widespread neocortical edema and damage. This model replicates many features of acute seizures and SE resulting from traumatic brain injury, subarachnoid, and lobar hemorrhage.

Anaemia in HIV-infected pregnant women receiving triple antiretroviral combination therapy for prevention of mother-to-child transmission: a secondary analysis of the Kisumu breastfeeding study (KiBS).

OBJECTIVE: The prevalence of anaemia during pregnancy is estimated to be 35-75% in sub-Saharan Africa and is associated with an increased risk of maternal mortality. We evaluated the frequency and factors associated with anaemia in HIV-infected women undergoing antiretroviral (ARV) therapy for prevention of mother-to-child transmission (PMTCT) enrolled in The Kisumu Breastfeeding Study 2003-2009. METHODS: Maternal haematological parameters were monitored from 32 to 34 weeks of gestation to 2 years post-delivery among 522 enrolled women. Clinical and laboratory assessments for causes of anaemia were performed, and appropriate management was initiated. Anaemia was graded using the National Institutes of Health Division of AIDS 1994 Adult Toxicity Tables. Data were analysed using SAS software, v 9.2. The Wilcoxon two-sample rank test was used to compare groups. A logistic regression model was fitted to describe the trend in anaemia over time. RESULTS: At enrolment, the prevalence of any grade anaemia (Hb < 9.4 g/dl) was 61.8%, but fell during ARV therapy, reaching a nadir (7.4%) by 6 months post-partum. A total of 41 women (8%) developed severe anaemia (Hb < 7 g/dl) during follow-up; 2 (4.9%) were hospitalised for blood transfusion, whereas 3 (7.3%) were transfused while hospitalised (for delivery). The greatest proportion of severe anaemia events occurred around delivery (48.8%; n = 20). Anaemia (Hb ≥ 7 and < 9.4 g/dl) at enrolment was associated with severe anaemia at delivery (OR 5.87; 95% CI: 4.48, 7.68, P < 0.01). Few cases of severe anaemia coincided with clinical malaria (24.4%; n = 10) and helminth (7.3%; n = 3) infections. CONCLUSION: Resolution of anaemia among most participants during study follow-up was likely related to receipt of ARV therapy. Efforts should be geared towards addressing common causes of anaemia in HIV-infected pregnant women, prioritising initiation of ARV therapy and management of peripartum blood loss.

Power and sample size calculations for interval-censored survival analysis.

We propose a method for calculating power and sample size for studies involving interval-censored failure time data that only involves standard software required for fitting the appropriate parametric survival model. We use the framework of a longitudinal study where patients are assessed periodically for a response and the only resultant information available to the investigators is the failure window: the time between the last negative and first positive test results. The survival model is fit to an expanded data set using easily computed weights. We illustrate with a Weibull survival model and a two-group comparison. The investigator can specify a group difference in terms of a hazards ratio. Our simulation results demonstrate the merits of these proposed power calculations. We also explore how the number of assessments (visits), and thus the corresponding lengths of the failure intervals, affect study power. The proposed method can be easily extended to more complex study designs and a variety of survival and censoring distributions.

Increased Rates of Respiratory and Diarrheal Illnesses in HIV-Negative Persons Living With HIV-Infected Individuals in a Densely Populated Urban Slum in Kenya.

BACKGROUND: Prolonged pathogen shedding and increased duration of illness associated with infections in immunosuppressed individuals put close human immunodeficiency virus (HIV)-negative contacts of HIV-infected persons at increased risk of exposure to infectious pathogens. METHODS: We calculated incidence and longitudinal prevalence (number of days per year) of influenzalike illness (ILI), diarrhea, and nonspecific febrile illness during 2008 from a population-based surveillance program in the urban slum of Kibera (Kenya) that included 1830 HIV-negative household contacts of HIV-infected individuals and 13 677 individuals living in exclusively HIV-negative households. RESULTS: For individuals ≥5 years old, incidence was significantly increased for ILI (risk ratio [RR], 1.47; P < .05) and diarrhea (RR, 1.41; P < .05) in HIV-negative household contacts of HIV-infected individuals compared with exclusively HIV-negative households. The risk of illness among HIV-negative persons was directly proportional to the number of HIV-infected persons living in the home for ILI (RR, 1.39; P < .05) and diarrhea (RR, 1.36; P < .01). We found no increased rates of illness in children <5 years old who lived with HIV-infected individuals. CONCLUSIONS: Living with HIV-infected individuals is associated with modestly increased rates of respiratory and diarrheal infections in HIV-negative individuals >5 years old. Targeted interventions are needed, including ensuring that HIV-infected persons are receiving appropriate care and treatment.

Emergence of Community-Acquired, Multidrug-Resistant Invasive Nontyphoidal Salmonella Disease in Rural Western Kenya, 2009-2013.

BACKGROUND: Nontyphoidal Salmonella (NTS), mainly serotypes Typhimurium and Enteritidis, cause invasive infections with high mortality in children in sub-Saharan Africa. Multidrug resistance is common, and resistance to third-generation cephalosporins has emerged. METHODS: We reviewed clinical features, outcomes, and antimicrobial resistance patterns in invasive NTS infections among children aged 6 weeks to 5 years participating in malaria vaccine studies in an area of high malaria and human immunodeficiency virus (HIV) transmission in Siaya, western Kenya. Blood culture was performed in hospitalized children and pediatric outpatients with prolonged fever. RESULTS: From July 2009 to December 2013, 1696 children aged 6 weeks to 17 months were enrolled into vaccine trials and followed for up to 53 months. We obtained 1692 blood cultures from 847 children. Of 134 bacterial pathogens isolated, 102 (76.1%) were Salmonella serogroup B or D. Invasive NTS disease occurred in 94 (5.5%) children, with an incidence of 1870, 4134, and 6510 episodes per 100 000 person-years overall, in infants, and in HIV-infected children, respectively. Malaria infection within the past 2 weeks occurred in 18.8% (3/16) of invasive NTS episodes in HIV-infected and 66.2% (53/80) in HIV-uninfected children. Case fatality rate was 3.1%. Salmonella group B resistant to ceftriaxone emerged in 2009 and 2010 (6.2% [2/32 isolates]), rising to 56.5% (13/23 isolates) in 2012 and 2013. CONCLUSIONS: Incidence of invasive NTS disease was high in this area of high malaria and HIV transmission, especially in HIV-infected children. Rapidly emerging resistance against ceftriaxone requires urgent reevaluation of antibiotic recommendations and primary prevention of exposure to Salmonella.

A Simple Approach for Sample Size Calculation for Comparing Two Concordance Correlation Coefficients Estimated on the Same Subjects.

Some studies are designed to assess the agreement between different raters and/or different instruments in the medical sciences and pharmaceutical research. In practice, the same sample will be used to compare the agreement of two or more assessment methods for simplicity and to take advantage of the positive correlation of the ratings. The concordance correlation coefficient (CCC) is often used as a measure of agreement when the rating is a continuous variable. We present an approach for calculating the sample size required for testing the equality of two CCCs, H0: CCC1 = CCC2 vs. HA: CCC1 ≠ CCC2, where two assessment methods are used on the same sample, with two raters resulting in correlated CCC estimates. Our approach is to simulate one large "exemplary" dataset based on the specification of the joint distribution of the pairwise ratings for the two methods. We then create two new random variables from the simulated data that have the same variance-covariance matrix as the two dependent CCC estimates using the Taylor series linearization method. The method requires minimal computing time and can be easily extended to comparing more than two CCCs, or Kappa statistics.

A potassium leak channel silences hyperactive neurons and ameliorates status epilepticus.

OBJECTIVE: To develop a constitutively active K(+) leak channel using TREK-1 (TWIK-related potassium channel 1; TREK-M) that is resistant to compensatory down-regulation by second messenger cascades, and to validate the ability of TREK-M to silence hyperactive neurons using cultured hippocampal neurons. To test if adenoassociated viral (AAV) delivery of TREK-M could reduce the duration of status epilepticus and reduce neuronal death induced by lithium-pilocarpine administration. METHODS: Molecular cloning techniques were used to engineer novel vectors to deliver TREK-M via plasmids, lentivirus, and AAV using a cytomegalovirus (CMV)-enhanced GABRA4 promoter. Electrophysiology was used to characterize the activity and regulation of TREK-M in human embryonic kidney (HEK-293) cells, and the ability to reduce spontaneous activity in cultured hippocampal neurons. Adult male rats were injected bilaterally with self-complementary AAV particles composed of serotype 5 capsid into the hippocampus and entorhinal cortex. Lithium-pilocarpine was used to induce status epilepticus. Seizures were monitored using continuous video-electroencephalography (EEG) monitoring. Neuronal death was measured using Fluoro-Jade C staining of paraformaldehyde-fixed brain slices. RESULTS: TREK-M inhibited neuronal firing by hyperpolarizing the resting membrane potential and decreasing input resistance. AAV delivery of TREK-M decreased the duration of status epilepticus by 50%. Concomitantly it reduced neuronal death in areas targeted by the AAV injection. SIGNIFICANCE: These findings demonstrate that TREK-M can silence hyperexcitable neurons in the brain of epileptic rats and treat acute seizures. This study paves the way for an alternative gene therapy treatment of status epilepticus, and provides the rationale for studies of AAV-TREK-M's effect on spontaneous seizures in chronic models of temporal lobe epilepsy.

Applying the RIME Framework to Level Nurse Practitioner Curriculum Competencies.

BACKGROUND: Nurse practitioner (NP) faculty assess student acquisition of knowledge through examinations, simulation, and clinical performance. PROBLEM: Developing appropriately leveled curriculum, assessments, and clinical expectations that accurately capture student maturation presents a challenge. APPROACH: The Reporter, Interpreter, Manager, Educator (RIME) provided the framework for doctor of nursing practice NP curriculum redesign to enhance student performance and content mastery. Faculty used a gap analysis approach, iteratively leveling specialty content, course competencies, examination questions, simulation cases, and clinical expectations using the building blocks of RIME. OUTCOMES: Objective scores on student evaluations for clinical courses exceeded the threshold established, including 83% of simulation encounters. Faculty implemented targeted methods to remediate areas of underperformance. CONCLUSIONS: Structuring the course competencies and preceptor feedback around RIME made it easier to pinpoint specific deficiencies and target remediation. It also helped guide discussions about the minimum acceptable standard for student performance.

Power and sample size calculations for current status survival analysis.

Although sample size calculations have become an important element in the design of research projects, such methods for studies involving current status data are scarce. Here, we propose a method for calculating power and sample size for studies using current status data. This method is based on a Weibull survival model for a two-group comparison. The Weibull model allows the investigator to specify a group difference in terms of a hazards ratio or a failure time ratio. We consider exponential, Weibull and uniformly distributed censoring distributions. We base our power calculations on a parametric approach with the Wald test because it is easy for medical investigators to conceptualize and specify the required input variables. As expected, studies with current status data have substantially less power than studies with the usual right-censored failure time data. Our simulation results demonstrate the merits of these proposed power calculations.

Relative Contribution of Schistosomiasis and Malaria to Anemia in Western Kenya.

Because anemia is one of the markers of morbidity associated with schistosomiasis, it has been proposed as a potential measure to evaluate the impact of control programs. However, anemia is also a common consequence of malaria, and schistosomiasis and malaria are often co-endemic. To estimate the attributable fraction of anemia due to Schistosoma mansoni and Plasmodium falciparum infections, we applied a log-binomial model to four studies measuring these parameters of a combined 5,849 children in western Kenya. In our studies, malaria contributed 23.3%, schistosomiasis contributed 6.6%, and co-infection contributed 27.6% of the anemia. We conclude that in areas where S. mansoni and P. falciparum are co-endemic, the contribution of schistosomiasis to anemia is masked by anemia resulting from malaria, thus limiting anemia as a useful measure for schistosomiasis control programs in these settings.

Weighting condom use data to account for nonignorable cluster size.

PURPOSE: We examined the impact of weighting the generalized estimating equation (GEE) by the inverse of the number of sex acts on the magnitude of association for factors predictive of recent condom use. METHODS: Data were analyzed from a cross-sectional survey on condom use reported during vaginal intercourse during the past year among male students attending two Georgia universities. The usual GEE model was fit to the data predicting the binary act-specific response indicating whether a condom was used. A second cluster-weighted GEE model (i.e., weighting the GEE score equation by the inverse of the number of sex acts) was also fit to predict condom use. RESULTS: Study participants who engaged in a greater frequency of sex acts were less likely to report condom use, resulting in nonignorable cluster-size data. The GEE analysis weighted by sex act (usual GEE) and the GEE analysis weighted by study subject (cluster-weighted GEE) produced different estimates of the association between the covariates and condom use in last year. For example, the cluster-weighted GEE analysis resulted in a marginally significant relationship between age and condom use (odds ratio of 0.49 with 95% confidence interval (0.23-1.03) for older versus younger participants) versus a nonsignificant relationship with the usual GEE model (odds ratio of 0.67 with a 95% confidence interval of 0.28-1.60). CONCLUSIONS: The two ways of weighting the GEE score equation, by the sex act or by the respondent, may produce different results and a different interpretation of the parameters in the presence of nonignorable cluster size.

Computer programs for the concordance correlation coefficient.

The CCC macro is presented for computation of the concordance correlation coefficient (CCC), a common measure of reproducibility. The macro has been produced in both SAS and R, and a detailed presentation of the macro input and output for the SAS program is included. The macro provides estimation of three versions of the CCC, as presented by Lin [L.I.-K. Lin, A concordance correlation coefficient to evaluate reproducibility, Biometrics 45 (1989) 255-268], Barnhart et al. [H.X. Barnhart, J.L. Haber, J.L. Song, Overall concordance correlation coefficient for evaluating agreement among multiple observers, Biometrics 58 (2002) 1020-1027], and Williamson et al. [J.M. Williamson, S.B. Crawford, H.M. Lin, Resampling dependent concordance correlation coefficients, J. Biopharm. Stat. 17 (2007) 685-696]. It also provides bootstrap confidence intervals for the CCC, as well as for the difference in CCCs for both independent and dependent samples. The macro is designed for balanced data only. Detailed explanation of the involved computations and macro variable definitions are provided in the text. Two biomedical examples are included to illustrate that the macro can be easily implemented.

Prevalence of Hepatitis B Virus Infection in Kenya, 2007.

Current estimates put the prevalence of hepatitis B virus (HBV) infection in Kenya at 5-8%. We determined the HBV infection prevalence in the human immunodeficiency virus (HIV)-negative Kenyan adult and adolescent population based on samples collected from a national survey. We analyzed data from HIV-negative participants in the 2007 Kenya AIDS Indicator Survey to estimate the HBV infection prevalence. We defined past or present HBV infection as presence of total hepatitis B core antibody (HBcAb), and chronic HBV infection (CHBI) as presence of both total HBcAb and hepatitis B surface antigen (HBsAg). We calculated crude and adjusted odds of HBV infection by demographic characteristics and risk factors using logistic regression analyses. Of 1,091 participants aged 15-64 years, approximately 31.5% (95% confidence interval [CI] = 28.0-35.3%) had exposure to HBV, corresponding to approximately 6.1 million (CI = 5.4-6.8 million) with past or present HBV infection. The estimated prevalence of CHBI was 2.1% (95% CI = 1.4-3.1%), corresponding to approximately 398,000 (CI = 261,000-602,000) with CHBI. CHBI is a major public health problem in Kenya, affecting approximately 400,000 persons. Knowing the HBV infection prevalence at baseline is important for planning and public health policy decision making and for monitoring the impact of viral hepatitis prevention programs.

A longitudinal analysis of the effect of mass drug administration on acute inflammatory episodes and disease progression in lymphedema patients in Leogane, Haiti.

We conducted a longitudinal analysis of 117 lymphedema patients in a filariasis-endemic area of Haiti during 1995-2008. No difference in lymphedema progression between those who received or did not receive mass drug administration (MDA) was found on measures of foot (P = 0.24), ankle (P = 0.87), or leg (P = 0.46) circumference; leg volume displacement (P = 0.09), lymphedema stage (P = 0.93), or frequency of adenolymphangitis (ADL) episodes (P = 0.57). Rates of ADL per year were greater after initiation of MDA among both groups (P < 0.01). Nevertheless, patients who received MDA reported improvement in four areas of lymphedema-related quality of life (P ≤ 0.01). Decreases in foot and ankle circumference and ADL episodes were observed during the 1995-1998 lymphedema management study (P ≤ 0.01). This study represents the first longitudinal, quantitative, leg-specific analysis examining the clinical effect of diethylcarbamazine on lymphedema progression and ADL episodes.

Sustained high incidence of injuries from burns in a densely populated urban slum in Kenya: an emerging public health priority.

INTRODUCTION: Ninety-five percent of burn deaths occur in low- and middle-income countries (LMICs); however, longitudinal household-level studies have not been done in urban slum settings, where overcrowding and unsafe cook stoves may increase likelihood of injury. METHODS: Using a prospective, population-based disease surveillance system in the urban slum of Kibera in Kenya, we examined the incidence of household-level burns of all severities from 2006-2011. RESULTS: Of approximately 28,500 enrolled individuals (6000 households), we identified 3072 burns. The overall incidence was 27.9/1000 person-years-of-observation. Children <5 years old sustained burns at 3.8-fold greater rate compared to (p<0.001) those ≥5 years old. Females ≥5 years old sustained burns at a rate that was 1.35-fold (p<0.001) greater than males within the same age distribution. Hospitalizations were uncommon (0.65% of all burns). CONCLUSIONS: The incidence of burns, 10-fold greater than in most published reports from Africa and Asia, suggests that such injuries may contribute more significantly than previously thought to morbidity in LMICs, and may be increased by urbanization. As migration from rural areas into urban slums rapidly increases in many African countries, characterizing and addressing the rising burden of burns is likely to become a public health priority.

Viral shedding in patients infected with pandemic influenza A (H1N1) virus in Kenya, 2009.

BACKGROUND: Understanding shedding patterns of 2009 pandemic influenza A (H1N1) (pH1N1) can inform recommendations about infection control measures. We evaluated the duration of pH1N1 virus shedding in patients in Nairobi, Kenya. METHODS: Nasopharyngeal (NP) and oropharyngeal (OP) specimens were collected from consenting laboratory-confirmed pH1N1 cases every 2 days during October 14-November 25, 2009, and tested at the Centers for Diseases Control and Prevention-Kenya by real time reverse transcriptase polymerase chain reaction (rRT-PCR). A subset of rRT-PCR-positive samples was cultured. RESULTS: Of 285 NP/OP specimens from patients with acute respiratory illness, 140 (49%) tested positive for pH1N1 by rRT-PCR; 106 (76%) patients consented and were enrolled. The median age was 6 years (Range: 4 months-41 years); only two patients, both asthmatic, received oseltamivir. The median duration of pH1N1 detection after illness onset was 8 days (95% CI: 7-10 days) for rRT-PCR and 3 days (Range: 0-13 days) for viral isolation. Viable pH1N1 virus was isolated from 132/162 (81%) of rRT-PCR-positive specimens, which included 118/125 (94%) rRT-PCR-positive specimens collected on day 0-7 after symptoms onset. Viral RNA was detectable in 18 (17%) and virus isolated in 7/18 (39%) of specimens collected from patients after all their symptoms had resolved. CONCLUSIONS: In this cohort, pH1N1 was detected by rRT-PCR for a median of 8 days. There was a strong correlation between rRT-PCR results and virus isolation in the first week of illness. In some patients, pH1N1 virus was detectable after all their symptoms had resolved.

A reversal in reductions of child mortality in western Kenya, 2003-2009.

We report and explore changes in child mortality in a rural area of Kenya during 2003-2009, when major public health interventions were scaled-up. Mortality ratios and rates were calculated by using the Kenya Medical Research Institute/Centers for Disease Control and Prevention Demographic Surveillance System. Inpatient and outpatient morbidity and mortality, and verbal autopsy data were analyzed. Mortality ratios for children less than five years of age decreased from 241 to 137 deaths/1,000 live-births in 2003 and 2007 respectively. In 2008, they increased to 212 deaths/1,000 live-births. Mortality remained elevated during the first 8 months of 2009 compared with 2006 and 2007. Malaria and/or anemia accounted for the greatest increases in child mortality. Stock-outs of essential antimalarial drugs during a time of increased malaria transmission and disruption of services during civil unrest may have contributed to increased mortality in 2008-2009. To maintain gains in child survival, implementation of good policies and effective interventions must be complemented by reliable supply and access to clinical services and essential drugs.