Review of Opsoclonus-Myoclonus Ataxia Syndrome in Pediatric Patients.

Opsoclonus-myoclonus ataxia syndrome (OMAS), also known as Kinsbourne syndrome, is a rare disorder that presents with myoclonus, ataxia, abnormal eye movements, irritability, and sleep disruptions, often in young children. We report a case of an infant barely 6 months old, with no significant past medical history, who presented to the emergency department with tremors, jerking motions of the head and arms, and rapid eye movements. After an extensive workup, she was found to have a neuroblastoma, which was subsequently surgically removed via thoracotomy. Despite an initial improvement in symptoms post-resection, the patient's symptoms recurred. She was subsequently treated with dexamethasone, intravenous immunoglobulin (IVIG), and rituximab. After treatment, the patient was noted to have mild global developmental delays but was otherwise well. This case report highlights the rare occurrence of OMAS in an infant barely 6 months old at diagnosis. Using the PubMed database, a systematic review was conducted to highlight the clinical presentation, diagnosis, and management of OMAS.

Molecular characterization of Streptococcus pneumoniae causing disease among children in Nigeria during the introduction of PCV10 (GSK).

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (n=189) and Abuja (n=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, n=35), 6B (16 %, n=31), 1 (9 %, n=17), 5 (9 %, n=17) and 6A (9 %, n=17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.

Level of utilization and provider-related barriers to the use of hydroxyurea in the treatment of sickle cell disease patients in Jos, North-Central Nigeria.

BACKGROUND: Hydroxyurea is underutilized by sickle cell health-care providers in Nigeria despite available evidence of its effectiveness in reducing the manifestations and complications of sickle cell disease (SCD). OBJECTIVES: To assess the level of utilization and provider-related barriers to the use of hydroxyurea in SCD therapy in Jos, Nigeria. METHODS: A cross-sectional study conducted among 132 medical doctors providing care for SCD patients. Data on sociodemographics, utilization and barriers to hydroxyurea use were obtained. The barriers were fed cumulatively into the logistic regression model as predictors of utilization. RESULTS: Of the 132 care providers, 88 (67%) had been in medical practice for ≥6years. The level of utilization of hydroxyurea was 24.2%. The significant barriers that predicted the non-utilization of hydroxyurea included lack of expertise (OR=5.1; 95% CI=2.65-9.05), lack of clinical guidelines (OR=3.84; 95% CI=2.37-14.33), fear of side-effects (OR=0.50; 95% CI=0.22-0.68) and doubt about its effectiveness (OR=0.30; 95% CI=0.20-0.90). CONCLUSION: The level of utilization of hydroxyurea in the treatment of SCD among the care providers is sub-optimal with the lack of expertise in its use identified as the most prominent barrier. There is an urgent need for the training of sickle cell care-providers and the development of clinical guidelines on hydroxyurea use.

A Prospective Cohort Study of the Clinical Predictors of Bacteremia in Under-Five Children With Acute Undifferentiated Fever Attending a Secondary Health Facility in Northwestern Nigeria.

BACKGROUND: Children with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use. METHODS: We prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted a multivariable logistic regression model to identify factors predictive of bacteremia among the cohort. RESULT: The prevalence of bacteremia was 17.1%, and Salmonella Typhi was the most frequently (40.9%) isolated pathogen. The majority (78.6%) of the study participants were managed as outpatients. The participants who required admission were four times more likely to have bacteremia when compared to those managed as outpatients (AOR 4.08, 95% CI 1.19 to 14.00). There is a four times likelihood of bacteremia (AOR 4.75, 95% CI 1.48 to 15.29) with a fever duration of beyond 7 days. Similarly, participants who were admitted with lethargy were six times more likely to have bacteremia (AOR 6.20, 95% CI 1.15 to 33.44). Other significant predictors were tachypnea and lymphopenia. CONCLUSION: Among under-five children with acute undifferentiated fever, longer duration of fever, lethargy, inpatient care, tachypnea, and lymphopenia were the significant predictors of bacteremia.

Case Series and Review of Hematological and Non-Hematological Malignancies in Aging Patients with Sickle Cell Disease in the Hydroxyurea Era.

Survival of adult patients with sickle cell disease has increased progressively since the 1970s. Aging patients with sickle cell disease are at risk of developing comorbidities that are not due to sickle cell disease itself, including malignancies. Many studies tried to assess the incidence of malignancy in patients with sickle cell disease. However, no studies have been done to evaluate cancer incidences in aging sickle cell patients, especially in the hydroxyurea (HU) era. In this review, we assessed the prevalence of malignancies in aging patients with sickle cell disease at our institution with or without HU therapy. Retrospective analysis of hospital records identified patients who had been diagnosed to carry sickle cell disease and malignancies before 2020 using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding. Four hundred and eighty-three sickle cell disease patients were seen in our inpatients/outpatients offices. Among these, 12 sickle cell disease patients had a confirmed diagnosis of malignancy. The patients were classified into three categories based on age groups: four patients who were 60 years and older had multiple myeloma. Solid tumors were found in 5/6 patients, aged 40-60 who had the Hb S (HBB: c.20A>T) (ßS/ßS) genotype with signs of iron overload. Two patients, aged 25 and 35, had hematological malignancies. The number of patients on HU was too small to make any comment on relationship to malignancy or mortality. This study is only one institution's experience, further investigation on a larger scale is needed to look into cancer incidences in this population.

Molecular characterization of invasive Enterobacteriaceae from pediatric patients in Central and Northwestern Nigeria.

BACKGROUND: Bacteremia is a leading cause of mortality in developing countries, however, etiologic evaluation is infrequent and empiric antibiotic use not evidence-based. Here, we evaluated the patterns of ESBL resistance in children enrolled into a surveillance study for community acquired bacteremic syndromes across health facilities in Central and Northwestern Nigeria. METHOD: Blood culture was performed for children aged less than 5 years suspected of having sepsis from Sept 2008-Dec 2016. Blood was incubated using the BACTEC00AE system and Enterobacteriacea identified to the species level using Analytical Profile Index (API20E®). Antibiotic susceptibility profile was determined by the disc diffusion method. Real time PCR was used to characterize genes responsible for ESBL production. RESULT: Of 21,000 children screened from Sept 2008-Dec 2016, 2,625(12.5%) were culture-positive. A total of 413 Enterobacteriaceae available for analysis were screened for ESBL. ESBL production was detected in 160 Enterobacteriaceae, high resistance rates were observed among ESBL-positive isolates for Ceftriaxone (92.3%), Aztreonam (96.8%), Cefpodoxime (96.3%), Cefotaxime (98.8%) and Trimethoprim/sulfamethoxazole (90%), while 87.5%, 90.7%, and 91.9% of the isolates were susceptible to Imipenem, Amikacin and Meropenem respectively. Frequently detected resistance genes were blaTEM-83.8% (134/160), and, blaCTX-M 83.1% (133/160) followed by blaSHVgenes 66.3% (106/160). Co-existence of blaCTX-M, blaTEM and blaSHV was seen in 94/160 (58.8%), blaCTX-M and blaTEM in 118/160 (73.8%), blaTEM and blaSHV in 97/160 (60.6%) and blaCTX-M and blaSHV in 100/160 (62.5%) of isolates tested. CONCLUSION: Our results indicate a high prevalence of bacteremia from ESBL Enterobacteriaceae in this population of children. These are resistant to commonly used antibiotics and careful choice of antibiotic treatment options is critical. Further studies to evaluate transmission dynamics of resistance genes could help in the reduction of ESBL resistance in these settings.

Epidemiology of COVID-19 and Predictors of Outcome in Nigeria: A Single-Center Study.

There is a paucity of information regarding the epidemiology and outcome of COVID-19 from low/middle-income countries, including from Nigeria. This single-center study described the clinical features, laboratory findings, and predictors of in-hospital mortality of COVID-19 patients. Patients admitted between April 10, 2020 and June 10, 2020 were included. Forty-five patients with a mean age of 43 (16) years, predominantly male (87%), presented with fever (38%), cough (29%), or dyspnea (24%). In-hospital mortality was 16%. The independent predictors of mortality were hypoxemia (adjusted odds ratio [aOR]: 2.5; 95% CI: 1.3-5.1) and creatinine > 1.5 mg/dL (aOR: 4.3; 95% CI: 1.9-9.8).

Fatal case of newborn Lassa fever virus infection mimicking late onset neonatal sepsis: a case report from northern Nigeria.

BACKGROUND: Lassa fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa fever infections are rare in scientific literature. We report a fatal case of Lassa fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis. CASE PRESENTATION: The patient is a 26-day-old neonate who was admitted with a day history of fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting the need to evaluate for Lassa fever using reverse transcription polymerase chain reaction (RT-PCR). He died 31 h into admission and RT-PCR result was positive for Lassa fever. CONCLUSIONS: Neonatal Lassa fever infection is highly fatal and can mimic neonatal sepsis. High index of suspicion is needed particularly for atypical presentations of neonatal sepsis in Lassa fever endemic areas.

Blood transfusion services for patients with sickle cell disease in Nigeria.

BACKGROUND: Safe, timely red blood cell transfusion saves lives and chronic transfusion therapy (CTT) prevents or limits morbidities such as stroke, therefore improving quality of life of patients with sickle cell disease (SCD). METHODS: This questionnaire-based study assessed the ability of sickle cell centers in Nigeria to provide safe blood to patients with SCD between March and August 2014. RESULTS: Out of the 73 hospitals contacted, responses were obtained from 31. Twenty four (78%) hospitals were unable to transfuse patients regularly due to blood scarcity. Packed red blood cells were available in 14 (45%), while only one provided leukocyte-depletion. Most centers assessed donor risk and screened for HIV in 30 (97%), hepatitis B in 31(100%) and hepatitis C in 27 (87%) hospitals. Extended phenotyping and alloantibody screening were not available in any center. A quarter of the hospitals could monitor iron overload, but only using serum ferritin. Access to iron chelators was limited and expensive. Seventeen (55%) tertiary hospitals offered CTT by top-up or manual exchange transfusion; previous stroke was the most common indication. CONCLUSION: Current efforts of Nigerian public hospitals to provide safe blood and CTT fall short of best practice. Provision of apheresis machines, improvement of voluntary non-remunerated donor drive, screening for red cell antigens and antibodies, and availability of iron chelators would significantly improve SCD care in Nigeria.

Salmonella Bacteremia Among Children in Central and Northwest Nigeria, 2008-2015.

BACKGROUND: Etiologic agents of childhood bacteremia remain poorly defined in Nigeria. The absence of such data promotes indiscriminate use of antibiotics and delays implementation of appropriate preventive strategies. METHODS: We established diagnostic laboratories for bacteremia surveillance at regional sites in central and northwest Nigeria. Acutely ill children aged <5 years with clinically suspected bacteremia were evaluated at rural and urban clinical facilities in the Federal Capital Territory, central region and in Kano, northwest Nigeria. Blood was cultured using the automated Bactec incubator system. RESULTS: Between September 2008 and April 2015, we screened 10,133 children. Clinically significant bacteremia was detected in 609 of 4051 (15%) in the northwest and 457 of 6082 (7.5%) in the central region. Across both regions, Salmonella species account for 24%-59.8% of bacteremias and are the commonest cause of childhood bacteremia, with a predominance of Salmonella enterica serovar Typhi. The prevalence of resistance to ampicillin, chloramphenicol, and cotrimoxazole was 38.11%, with regional differences in susceptibility to different antibiotics but high prevalence of resistance to readily available oral antibiotics. CONCLUSIONS: Salmonella Typhi is the leading cause of childhood bacteremia in central Nigeria. Expanded surveillance is planned to define the dynamics of transmission. The high prevalence of multidrug-resistant strains calls for improvement in environmental sanitation in the long term and vaccination in the short term.

Ackee Fruit Poisoning in Eight Siblings: Implications for Public Health Awareness.

Ackee apple fruit is a native fruit to Jamaica and some parts of west Africa. Its toxicity known as "Jamaican vomiting sickness" dates back to the nineteenth century. However, there is a dearth of reported published data on toxicity from Nigeria where it is popularly known in the southwest as "ishin." We report a case series of eight previously well Nigerian siblings who presented at various intervals after ingestion of roasted seeds and aril of the ackee fruit.

A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease.

BACKGROUND: Malaria prophylaxis is recommended for persons with sickle cell disease (SCD), but the value of this has been questioned. The aim of this study was to find out whether intermittent preventive treatment (IPT) with a fixed-dose combination of mefloquine-artesunate (MQAS) or sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) was more effective than daily proguanil for malaria prevention in subjects with SCD. METHODS: Patients with SCD were randomized to receive daily treatment with proguanil or IPT with either MQAS or SPAQ once every 2 months at routine clinic visits. Patients were followed up for 14 months. FINDINGS: A total of 270 patients with SCD were studied, with 90 in each group. Adherence to the IPT regimens was excellent, but 57% of patients took <75% of their daily doses of proguanil. IPT was well tolerated; the most common side effects were vomiting and abdominal pain. Protective efficacy against malaria, compared with daily proguanil, was 61% (95% confidence interval, 3%-84%) for MQAS and 36% (40%-70%) for SPAQ. There were fewer outpatient illness episodes in children who received IPT than those who received proguanil. CONCLUSIONS: IPT with MQAS administered to patients with SCD during routine clinic visits was well tolerated and more effective in preventing malaria than daily prophylaxis with proguanil. CLINICAL TRIALS REGISTRATION: NCT01319448 and ISRCTN46158146.

Spread of artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS: Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS: The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS: Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).

Clinical features of severe malaria associated with death: a 13-year observational study in the Gambia.

BACKGROUND: Severe malaria (SM) is a major cause of death in sub-Saharan Africa. Identification of both specific and sensitive clinical features to predict death is needed to improve clinical management. METHODS: A 13-year observational study was conducted from 1997 through 2009 of 2,901 children with SM enrolled at the Royal Victoria Teaching Hospital in The Gambia to identify sensitive and specific predictors of poor outcome in Gambian children with severe malaria between the ages 4 months to 14 years. We have measured the sensitivity and specificity of clinical features that predict death or development of neurological sequelae. FINDINGS: Impaired consciousness (odds ratio {OR} 4.4 [95% confidence interval {CI}, 2.7-7.3]), respiratory distress (OR 2.4 [95%CI, 1.7-3.2]), hypoglycemia (OR 1.7 [95%CI, 1.2-2.3]), jaundice (OR 1.9 [95%CI, 1.2-2.9]) and renal failure (OR 11.1 [95%CI, 3.3-36.5]) were independently associated with death in children with SM. The clinical features that showed the highest sensitivity and specificity to predict death were respiratory distress (area under the curve 0.63 [95%CI, 0.60-0.65]) and impaired consciousness (AUC 0.61[95%CI, 0.59-0.63]), which were comparable to the ability of hyperlactatemia (blood lactate>5 mM) to predict death (AUC 0.64 [95%CI, 0.55-0.72]). A Blantyre coma score (BCS) of 2 or less had a sensitivity of 74% and specificity of 67% to predict death (AUC 0.70 [95% C.I. 0.68-0.72]), and sensitivity and specificity of 74% and 69%, respectively to predict development of neurological sequelae (AUC 0.72 [95% CI, 0.67-0.76]).The specificity of this BCS threshold to identify children at risk of dying improved in children less than 3 years of age (AUC 0.74, [95% C.I 0.71-0.76]). CONCLUSION: The BCS is a quantitative predictor of death. A BCS of 2 or less is the most sensitive and specific clinical feature to predict death or development of neurological sequelae in children with SM.

Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria.

BACKGROUND: Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. METHODS: Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania. RESULTS: There was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration. CONCLUSIONS: These findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection.

Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement.

BACKGROUND: In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2) is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. METHODS AND FINDINGS: Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo) aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH)-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054). In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209), acidosis (p<0.0001), and severe anaemia (p<0.0001). Admission geometric mean (95%CI) plasma PfHRP2 was 1,611 (1,350-1,922) ng/mL in fatal cases (n = 381) versus 1,046 (991-1,104) ng/mL in survivors (n = 3,445, p<0.0001), without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10) plasma PfHRP2 and risk of death. Mortality increased 20% per log(10) increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009). A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR) for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018) in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82). A limitation of the study is that some conclusions are drawn from a mechanistic model, which is inherently dependent on certain assumptions. However, a sensitivity analysis of the model indicated that the results were robust to a plausible range of parameter estimates. Further studies are needed to validate our findings. CONCLUSIONS: Plasma PfHRP2 has prognostic significance in African children with severe falciparum malaria and provides a tool to stratify the risk of "true" severe malaria-attributable disease as opposed to other severe illnesses in parasitaemic African children.

Predicting the clinical outcome of severe falciparum malaria in african children: findings from a large randomized trial.

BACKGROUND: Data from the largest randomized, controlled trial for the treatment of children hospitalized with severe malaria were used to identify such predictors of a poor outcome from severe malaria. METHODS: African children (<15 years) with severe malaria participated in a randomized comparison of parenteral artesunate and parenteral quinine in 9 African countries. Detailed clinical assessment was performed on admission. Parasite densities were assessed in a reference laboratory. Predictors of death were examined using a multivariate logistic regression model. RESULTS: Twenty indicators of disease severity were assessed, out of which 5 (base deficit, impaired consciousness, convulsions, elevated blood urea, and underlying chronic illness) were associated independently with death. Tachypnea, respiratory distress, deep breathing, shock, prostration, low pH, hyperparasitemia, severe anemia, and jaundice were statistically significant indicators of death in the univariate analysis but not in the multivariate model. Age, glucose levels, axillary temperature, parasite density, heart rate, blood pressure, and blackwater fever were not related to death in univariate models. CONCLUSIONS: Acidosis, cerebral involvement, renal impairment, and chronic illness are key independent predictors for a poor outcome in African children with severe malaria. Mortality is markedly increased in cerebral malaria combined with acidosis. Clinical Trial Registration. ISRCTN50258054.

Cost-effectiveness of parenteral artesunate for treating children with severe malaria in sub-Saharan Africa.

OBJECTIVE: To explore the cost-effectiveness of parenteral artesunate for the treatment of severe malaria in children and its potential impact on hospital budgets. METHODS: The costs of inpatient care of children with severe malaria were assessed in four of the 11 sites included in the African Quinine Artesunate Malaria Treatment trial, conducted with over 5400 children. The drugs, laboratory tests and intravenous fluids provided to 2300 patients from admission to discharge were recorded, as was the length of inpatient stay, to calculate the cost of inpatient care. The data were matched with pooled clinical outcomes and entered into a decision model to calculate the cost per disability-adjusted life year (DALY) averted and the cost per death averted. FINDINGS: The mean cost of treating severe malaria patients was similar in the two study groups: 63.5 United States dollars (US$) (95% confidence interval, CI: 61.7-65.2) in the quinine arm and US$ 66.5 (95% CI: 63.7-69.2) in the artesunate arm. Children treated with artesunate had 22.5% lower mortality than those treated with quinine and the same rate of neurological sequelae: (artesunate arm: 2.3 DALYs per patient; quinine arm: 3.0 DALYs per patient). Compared with quinine as a baseline, artesunate showed an incremental cost per DALY averted and an incremental cost per death averted of US$ 3.8 and US$ 123, respectively. CONCLUSION: Artesunate is a highly cost-effective and affordable alternative to quinine for treating children with severe malaria. The budgetary implications of adopting artesunate for routine use in hospital-based care are negligible.