Anti-malarial prescription practices among children admitted to six public hospitals in Uganda from 2011 to 2013.

BACKGROUND: In 2011, Uganda's Ministry of Health switched policy from presumptive treatment of malaria to recommending parasitological diagnosis prior to treatment, resulting in an expansion of diagnostic services at all levels of public health facilities including hospitals. Despite this change, anti-malarial drugs are often prescribed even when test results are negative. Presented is data on anti-malarial prescription practices among hospitalized children who underwent diagnostic testing after adoption of new treatment guidelines. METHODS: Anti-malarial prescription practices were collected as part of an inpatient malaria surveillance program generating high quality data among children admitted for any reason at government hospitals in six districts. A standardized medical record form was used to collect detailed patient information including presenting symptoms and signs, laboratory test results, admission and final diagnoses, treatments administered, and final outcome upon discharge. RESULTS: Between July 2011 and December 2013, 58,095 children were admitted to the six hospitals (hospital range 3294-20,426).A total of 56,282 (96.9 %) patients were tested for malaria, of which 26,072 (46.3 %) tested positive (hospital range 5.9-57.3 %). Among those testing positive, only 84 (0.3 %) were first tested after admission and 295 of 30,389 (1.0 %) patients who tested negative at admission later tested positive. Of 30,210 children with only negative test results, 11,977 (39.6 %) were prescribed an anti-malarial (hospital range 14.5-53.6 %). The proportion of children with a negative test result who were prescribed an anti-malarial fluctuated over time and did not show a significant trend at any site with the exception of one hospital where a steady decline was observed. Among those with only negative test results, children 6-12 months of age (aOR 3.78; p < 0.001) and those greater than 12 months of age (aOR 4.89; p < 0.001) were more likely to be prescribed an anti-malarial compared to children less than 6 months of age. Children with findings suggestive of severe malaria were also more likely to be prescribed an anti-malarial after a negative test result (aOR 1.98; p < 0.001). CONCLUSIONS: Despite high testing rates for malaria at all sites, prescription of anti-malarials to patients with negative test results remained high, with the exception of one site where a steady decline occurred

Predictors of anti-convulsant treatment failure in children presenting with malaria and prolonged seizures in Kampala, Uganda

BACKGROUND: In endemic areas, falciparum malaria remains the leading cause of seizures in children presenting to emergency departments. In addition, seizures in malaria have been shown to increase morbidity and mortality in these patients. The management of seizures in malaria is sometimes complicated by the refractory nature of these seizures to readily available anti-convulsants. The objective of this study was to determine predictors of anti-convulsant treatment failure and seizure recurrence after initial control among children with malaria. METHODS: In a previous study, the efficacy and safety of buccal midazolam was compared to that of rectal diazepam in the treatment of prolonged seizures in children aged three months to 12 years in Kampala, Uganda. For this study, predictive models were used to determine risk factors for anti-convulsant treatment failure and seizure recurrence among the 221 of these children with malaria. RESULTS: Using predictive models, focal seizures (OR 3.21; 95% CI 1.42-7.25, p = 0.005), cerebral malaria (OR 2.43; 95% CI 1.20-4.91, p = 0.01) and a blood sugar >or=200 mg/dl at presentation (OR 2.84; 95% CI 1.11-7.20, p = 0.02) were independent predictors of treatment failure (seizure persistence beyond 10 minutes or recurrence within one hour of treatment). Predictors of seizure recurrence included: 1) cerebral malaria (HR 3.32; 95% CI 1.94-5.66, p < 0.001), 2) presenting with multiple seizures (HR 2.45; 95% CI 1.42-4.23, p = 0.001), 3) focal seizures (HR 2.86; 95% CI 1.49-5.49, p = 0.002), 4) recent use of diazepam (HR 2.43; 95% CI 1.19-4.95, p = 0.01) and 5) initial control of the seizure with diazepam (HR 1.96; 95% CI 1.16-3.33, p = 0.01). CONCLUSION: Specific predictors, including cerebral malaria, can identify patients with malaria at risk of anti-convulsant treatment failure and seizure recurrence

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Validity of Verbal Autopsy Procedures for Determining Malaria Deaths in Different Epidemiological Settings in Uganda

BACKGROUND: Verbal autopsy (VA) procedures can be used to estimate cause of death in settings with inadequate vital registries. However, the sensitivity of VA for determining malaria-specific mortality may be low, and may vary with transmission intensity. We assessed the diagnostic accuracy of VA procedures as compared to hospital medical records for determining cause of death in children under five in three different malaria transmission settings in Uganda, including Tororo (high), Kampala (medium), and Kisoro (low). METHODS AND FINDINGS: Caretakers of children who died in participating hospitals were interviewed using a standardized World Health Organization questionnaire. Medical records from the child's hospitalization were also reviewed. Causes of death based on the VA questionnaires and the medical records were assigned independently by physician reviewers and then compared. A total of 719 cases were included in the final analysis, 67 in Tororo, 600 in Kampala, and 52 in Kisoro. Malaria was classified as the underlying or contributory cause of death by review of medical records in 33 deaths in Tororo, 60 in Kampala, and 0 in Kisoro. The sensitivity of VA procedures for determining malaria deaths in Tororo was 61% (95% CI 44-78%) and 50% in Kampala (95% CI 37-63%). Specificity for determining malaria deaths in Tororo and Kampala was high (>88%), but positive predictive value varied widely, from 83% in Tororo to 34% in Kampala (difference 49%, 95% CI 31-67, p<0.001). The difference between the cause-specific mortality fraction for malaria as determined by VA procedures and medical records was -11% in Tororo, +5% in Kampala, and +14% in Kisoro. CONCLUSIONS: Our results suggest that these VA methods have an acceptable level of diagnostic accuracy for determining malaria deaths at the population level in high and medium transmission areas, but not in low transmission areas

Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

BACKGROUND: New antimalarial regimens, including artemisinin-based combination therapies (ACTs), have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. CASE DESCRIPTION: Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. DISCUSSION AND EVALUATION: Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. CONCLUSION: Although the World Health Organization has supported the development of pharmacovigilance systems in African countries deploying ACTs, additional guidance on adverse events monitoring in antimalarial clinical trials is needed, similar to the standardized recommendations available for assessment of drug efficacy

Malaria infection and severe disease risks in Africa

The relationship between community prevalence of Plasmodium falciparum and the burden of severe, life-threatening disease remains poorly defined. To examine the three most common severe malaria phenotypes from catchment populations across East Africa, we assembled a dataset of 6506 hospital admissions for malaria in children aged 3 months to 9 years from 2006 to 2020. Admissions were paired with data from community parasite infection surveys. A Bayesian procedure was used to calibrate uncertainties in exposure (parasite prevalence) and outcomes (severe malaria phenotypes). Each 25% increase in prevalence conferred a doubling of severe malaria admission rates. Severe malaria remains a burden predominantly among young children (3 to 59 months) across a wide range of community prevalence typical of East Africa. This study offers a quantitative framework for linking malaria parasite prevalence and severe disease outcomes in children

Increasing malaria hospital admissions in Uganda between 1999 and 2009

<p>Abstract</p> <p>Background</p> <p>Some areas of Africa are witnessing a malaria transition, in part due to escalated international donor support and intervention coverage. Areas where declining malaria rates have been observed are largely characterized by relatively low baseline transmission intensity and rapid scaling of interventions. Less well described are changing patterns of malaria burden in areas of high parasite transmission and slower increases in control and treatment access.</p> <p>Methods</p> <p>Uganda is a country predominantly characterized by intense, perennial malaria transmission. Monthly pediatric admission data from five Ugandan hospitals and their catchments have been assembled retrospectively across 11 years from January 1999 to December 2009. Malaria admission rates adjusted for changes in population density within defined catchment areas were computed across three time periods that correspond to periods where intervention coverage data exist and different treatment and prevention policies were operational. Time series models were developed adjusting for variations in rainfall and hospital use to examine changes in malaria hospitalization over 132 months. The temporal changes in factors that might explain changes in disease incidence were qualitatively examined sequentially for each hospital setting and compared between hospital settings</p> <p>Results</p> <p>In four out of five sites there was a significant increase in malaria admission rates. Results from time series models indicate a significant month-to-month increase in the mean malaria admission rates at four hospitals (trend <it>P </it>< 0.001). At all hospitals malaria admissions had increased from 1999 by 47% to 350%. Observed changes in intervention coverage within the catchments of each hospital showed a change in insecticide-treated net coverage from <1% in 2000 to 33% by 2009 but accompanied by increases in access to nationally recommended drugs at only two of the five hospital areas studied.</p> <p>Conclusions</p> <p>The declining malaria disease burden in some parts of Africa is not a universal phenomena across the continent. Despite moderate increases in the coverage of measures to reduce infection and disease without significant coincidental increasing access to effective medicines to treat disease may not lead to severe disease burden reductions in high transmission areas of Africa. More data is needed from a wider range of malaria settings to provide an honest tracking progress of the impact of scaled intervention coverage in Africa.</p

Malaria hospitalisation in East Africa: age, phenotype and transmission intensity.

BACKGROUND: Understanding the age patterns of disease is necessary to target interventions to maximise cost-effective impact. New malaria chemoprevention and vaccine initiatives target young children attending routine immunisation services. Here we explore the relationships between age and severity of malaria hospitalisation versus malaria transmission intensity. METHODS: Clinical data from 21 surveillance hospitals in East Africa were reviewed. Malaria admissions aged 1 month to 14 years from discrete administrative areas since 2006 were identified. Each site-time period was matched to a model estimated community-based age-corrected parasite prevalence to provide predictions of prevalence in childhood (PfPR2-10). Admission with all-cause malaria, severe malaria anaemia (SMA), respiratory distress (RD) and cerebral malaria (CM) were analysed as means and predicted probabilities from Bayesian generalised mixed models. RESULTS: 52,684 malaria admissions aged 1 month to 14 years were described at 21 hospitals from 49 site-time locations where PfPR2-10 varied from < 1 to 48.7%. Twelve site-time periods were described as low transmission (PfPR2-10 < 5%), five low-moderate transmission (PfPR2-10 5-9%), 20 moderate transmission (PfPR2-10 10-29%) and 12 high transmission (PfPR2-10 ≥ 30%). The majority of malaria admissions were below 5 years of age (69-85%) and rare among children aged 10-14 years (0.7-5.4%) across all transmission settings. The mean age of all-cause malaria hospitalisation was 49.5 months (95% CI 45.1, 55.4) under low transmission compared with 34.1 months (95% CI 30.4, 38.3) at high transmission, with similar trends for each severe malaria phenotype. CM presented among older children at a mean of 48.7 months compared with 39.0 months and 33.7 months for SMA and RD, respectively. In moderate and high transmission settings, 34% and 42% of the children were aged between 2 and 23 months and so within the age range targeted by chemoprevention or vaccines. CONCLUSIONS: Targeting chemoprevention or vaccination programmes to areas where community-based parasite prevalence is ≥10% is likely to match the age ranges covered by interventions (e.g. intermittent presumptive treatment in infancy to children aged 2-23 months and current vaccine age eligibility and duration of efficacy) and the age ranges of highest disease burden