Expanding access to maternal, newborn and primary healthcare services through private-community-government partnership clinic models in rural Kenya: the Ubuntu-Afya kiosk model.

BACKGROUND: Fifteen counties contribute 98.7% of the maternal and newborn morbidity and mortality in Kenya. The dismal maternal and newborn (MNH) outcomes in these settings are mostly attributable to limited access to skilled MNH services. Public health services are stretched and limited in reach, and many social programmes are not sustainably designed. We implemented a network of 16 self-sustaining community medical centres (Ubuntu-Afya Kiosks) in Homa Bay County, to facilitate access to MNH and other primary health services. We investigated the effect of these centres on MNH access indicators over a 2-year period of initial implementation. METHODS: We conducted a baseline and end-line survey in June 2016 and May 2018 respectively, in 10 community health units (CHU) served by Ubuntu-Afya Kiosks. We targeted women of child bearing age, ensuring equal sample across the 10 CHUs. The surveys were powered to detect a 10% increase in the proportion of women who deliver under a skilled birth attendant from a perceived baseline of 55%. Background characteristics of the respondents were compared using Fisher's exact test for the categorical data. STATA 'svy' commands were used to calculate confidence intervals for the proportions taking into account the clustering within CHU. RESULTS: The coverage of antenatal care during previous pregnancy was 99% at end-line compared to 81% at baseline. Seventy one percent of mothers attended at least four antenatal care visits, compared to 64% at baseline. The proportion of women who delivered under a skilled birth attendant during previous pregnancy was higher at end-line (90%) compared to baseline (85%). There was an increase in the proportion of women who had their newborns examined within 2 day of delivery from 74 to 92% at end-line. A considerable proportion of the respondents visited private clinics at end-line (31%) compared to 3% at baseline. CONCLUSIONS: Ubuntu-Afya Kiosks were associated with enhanced access to MNH care, with significant improvements observed in newborn examination within 2 days after delivery. More women sought care from private clinics at end-line compared to baseline, indicating potential for private sector in supporting health service delivery gaps in under-served settings.

Correlates of isoniazid preventive therapy failure in child household contacts with infectious tuberculosis in high burden settings in Nairobi, Kenya - a cohort study.

BACKGROUND: Sub-Saharan Africa continues to document high pediatric tuberculosis (TB) burden, especially among the urban poor. One recommended preventive strategy involves tracking and isoniazid preventive therapy (IPT) for children under 5 years in close contact with infectious TB. However, sub-optimal effectiveness has been documented in diverse settings. We conducted a study to elucidate correlates to IPT strategy failure in children below 5 years in high burden settings. METHODS: A prospective longitudinal cohort study was done in informal settlings in Nairobi, where children under 5 years in household contact with recently diagnosed smear positive TB adults were enrolled. Consent was sought. Structured questionnaires administered sought information on index case treatment, socio-demographics and TB knowledge. Contacts underwent baseline clinical screening exclude TB and/or pre-existing chronic conditions. Contacts were then put on daily isoniazid for 6 months and monitored for new TB disease, compliance and side effects. Follow-up continued for another 6 months. RESULTS: At baseline, 428 contacts were screened, and 14(3.2%) had evidence of TB disease, hence excluded. Of 414 contacts put on IPT, 368 (88.8%) completed the 1 year follow-up. Operational challenges were reported by 258(70%) households, while 82(22%) reported side effects. Good compliance was documented in 89% (CI:80.2-96.2). By endpoint, 6(1.6%) contacts developed evidence of new TB disease and required definitive anti-tuberculosis therapy. The main factor associated with IPT failure was under-nutrition of contacts (p = 0.023). CONCLUSION: Under-nutrition was associated with IPT failure for child contacts below 5 years in high burden, resource limited settings. IPT effectiveness could be optimized through nutrition support of contacts.

Abnormal intra-aural pressure waves associated with death in African children with acute nontraumatic coma.

BACKGROUND: We explored the relationship between tympanic membrane displacement (TMD) measurements, a tool to monitor intracranial pressure noninvasively, and clinical features and death in children with acute coma in Kilifi, Kenya. METHODS: Between November 2007 and September 2009, we made serial TMD measurements and clinical observations on children with acute coma (Blantyre coma score (BCS) ≤ 2) on the pediatric high dependency unit of Kilifi District Hospital, and on well children presenting to the hospital's outpatient department for routine follow-up. We examined middle ear function using tympanometry and measured cardiac pulse (CPA) and respiratory pulse pressure amplitudes (RPA) using the TMD analyzer. RESULTS: We recruited 75 children (32 (43%) females; median age 3.3 (IQR: 2.0, 4.3) years). Twenty-one (28%) children died. Higher TMD measurements predicted death. Adjusting for diagnosis, every 50 nl rise in both semirecumbent and recumbent CPA was associated with increased odds of death associated with intracranial herniation (OR: 1.61, 95% confidence interval (CI): 1.07, 2.41; P = 0.02 and OR: 1.35, 95% CI: 1.10, 1.66; P ≤ 0.01 respectively). CONCLUSION: Raised TMD pulse pressure measurements are associated with death and may be useful in detecting and monitoring risk of intracranial herniation and intracranial pressure in childhood coma.

Value of Plasmodium falciparum histidine-rich protein 2 level and malaria retinopathy in distinguishing cerebral malaria from other acute encephalopathies in Kenyan children.

BACKGROUND: The diagnosis of cerebral malaria is problematic in malaria-endemic areas because encephalopathy in patients with parasitemia may have another cause. Abnormal retinal findings are thought to increase the specificity of the diagnosis, and the level of histidine-rich protein 2 (HRP2) may reflect the parasite biomass. METHODS: We examined the retina and measured plasma HRP2 levels in children with acute nontraumatic encephalopathy in Kenya. Logistic regression, with HRP2 level as an independent variable and World Health Organization-defined cerebral malaria and/or retinopathy as the outcome, was used to calculate malaria-attributable fractions (MAFs) and retinopathy-attributable fractions (RAFs). RESULTS: Of 270 children, 140 (52%) had peripheral parasitemia, 80 (30%) had malaria retinopathy, and 164 (61%) had an HRP2 level of >0 U/mL. During 2006-2011, the incidence of HRP2 positivity among admitted children declined by 49 cases per 100 000 per year (a 78% reduction). An HRP2 level of >0 U/mL had a MAF of 93% for cerebral malaria, with a MAF of 97% observed for HRP2 levels of ≥ 10 U/mL (the level of the best combined sensitivity and specificity). HRP2 levels of >0 U/mL had a RAF of 77% for features of retinopathy combined, with the highest RAFs for macular whitening (99%), peripheral whitening (98%), and hemorrhages (90%). CONCLUSION: HRP2 has a high attributable fraction for features of malarial retinopathy, supporting its use in the diagnosis of cerebral malaria. HRP2 thresholds improve the specificity of the definition.

The tympanic membrane displacement analyser for monitoring intracranial pressure in children.

PURPOSE: Raised intracranial pressure (ICP) is a potentially treatable cause of morbidity and mortality but tools for monitoring are invasive. We sought to investigate the utility of the tympanic membrane displacement (TMD) analyser for non-invasive measurement of ICP in children. METHODS: We made TMD observations on normal and acutely comatose children presenting to Kilifi District Hospital (KDH) at the rural coast of Kenya and on children on follow-up for idiopathic intracranial hypertension at Evelina Children's Hospital (ECH), in London, UK. RESULTS: We recruited 63 patients (median age 3.3 (inter-quartile range (IQR) 2.0-4.3) years) at KDH and 14 children (median age 10 (IQR 5-11) years) at ECH. We observed significantly higher (more negative) TMD measurements in KDH children presenting with coma compared to normal children seen at the hospital's outpatient department, in both semi-recumbent [mean -61.3 (95 % confidence interval (95 % CI) -93.5 to 29.1) nl versus mean -7.1 (95 % CI -54.0 to 68.3) nl, respectively; P = 0.03] and recumbent postures [mean -61.4 (95 % CI -93.4 to -29.3) nl, n = 59) versus mean -25.9 (95 % CI -71.4 to 123.2) nl, respectively; P = 0.03]. We also observed higher TMD measurements in ECH children with raised ICP measurements, as indicated by lumbar puncture manometry, compared to those with normal ICP, in both semi-recumbent [mean -259.3 (95 % CI -363.8 to -154.8) nl versus mean 26.7 (95 % CI -52.3 to 105.7) nl, respectively; P < 0.01] and recumbent postures [mean -137.5 (95 % CI -260.6 to -14.4) nl versus mean 96.6 (95 % CI 6.5 to 186.6) nl, respectively; P < 0.01]. CONCLUSION: The TMD analyser has a potential utility in monitoring ICP in a variety of clinical circumstances.

Risk factors for seizure recurrence after initial withdrawal of anti-seizure medications in children with epilepsy at Aga Khan University Hospital, Nairobi, Kenya.

Objectives: We sought to determine risk factors associated with seizure recurrence following initial withdrawal of anti-seizure medications (ASM) among children with epilepsy. Methods: This was a retrospective observational study of children aged between 2 and 18 years with a diagnosis of epilepsy who underwent withdrawal of anti-seizure medication following remission of seizures. All eligible medical records between January 2011 and December 2019 were included. Demographic, clinical, imaging and electroencephalography data of all eligible patients were analyzed against seizure remission within 24 months after withdrawal of ASM, using appropriate parametric and non-parametric tests. Results: A total of 49 records of children who underwent withdrawal of ASM out of a total of 613 patients on follow up during the same period were included. The median age at ASM withdrawal was 70 months (IQR 52-112 months) and 14 (28.6%) were female. Thirteen patients (26.5%) had seizure recurrence within 24 months following withdrawal of ASM. Focal onset seizure type was associated with significant risk of seizure recurrence (OR 13.7; 95% CI 0.97, 193.54; P value = 0.011). Age at epilepsy diagnosis, abnormal EEG at initiation of treatment and at the time of de-escalation, abnormal MRI findings, first or second degree relative with epilepsy, history of developmental delay, seizure burden, use of 2 or more ASMs and duration of seizure-freedom before de-escalation of ASM were not associated with increased risk of relapse. Conclusion: Focal onset seizure type is associated with increased with risk of seizure recurrence in this cohort.

Telemedicine for Individuals with epilepsy: Recommendations from the International League Against Epilepsy Telemedicine Task Force.

Worldwide, People with Epilepsy (PWE) are confronted with several barriers to face-to-face consultations. These obstacles hamper appropriate clinical follow-up and also increase the treatment gap for Epilepsy. Telemedicine holds the potential to enhance management as follow-up visits for PWE are focused on more on clinical history and counselling rather than physical examination. Besides consultation, telemedicine can also be used for remote EEG diagnostics and tele-neuropsychology assessments. In this article, the Telemedicine Task Force of the International League Against Epilepsy (ILAE) outlines recommendations regarding optimal practice in utilizing in the management of individuals with epilepsy. We formulated recommendations for minimum technical requirements, preparing for the first tele-consultation and the specificities for follow-up consultations. Special considerations are necessary for specific populations, including paediatric patients, patients who are not conversant with tele-medicine and those with intellectual disability. Telemedicine for individuals with epilepsy should be vigorously promoted with the aim of improving the quality of care and ultimately reduce the wide clinician access related treatment gap across several regions of the globe.

High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria.

Cerebral malaria (CM) in children is associated with a high mortality and long-term neurocognitive sequelae. Both erythropoietin (Epo) and vascular endothelial growth factor (VEGF) have been shown to be neuroprotective. We hypothesized that high plasma and cerebrospinal fluid (CSF) levels of these cytokines would prevent neurological sequelae in children with CM. We measured Epo, VEGF, and tumor necrosis factor in paired samples of plasma and CSF of Kenyan children admitted with CM. Logistic regression models were used to identify risk and protective factors associated with the development of neurological sequelae. Children with CM (n = 124) were categorized into three groups: 76 without sequelae, 32 with sequelae, and 16 who died. Conditional logistic regression analysis matching the 32 patients with CM and neurological sequelae to 64 patients with CM without sequelae stratified for hemoglobin level estimated that plasma Epo (>200 units/liter) was associated with >80% reduction in the risk of developing neurological sequelae [adjusted odds ratio (OR) 0.18; 95% C.I. 0.05-0.93; P = 0.041]. Admission with profound coma (adjusted OR 5.47; 95% C.I. 1.45-20.67; P = 0.012) and convulsions after admission (adjusted OR 16.35; 95% C.I. 2.94-90.79; P = 0.001) were also independently associated with neurological sequelae. High levels of Epo were associated with reduced risk of neurological sequelae in children with CM. The age-dependent Epo response to anemia and the age-dependent protective effect may influence the clinical epidemiology of CM. These data support further study of Epo as an adjuvant therapy in CM.

Magnetic Resonance Imaging Findings in Childhood Epilepsy at a Tertiary Hospital in Kenya.

Background: Neuroimaging is important for determining etiology and guiding care in early childhood epilepsy. However, access to appropriate imaging in sub-Saharan Africa is modest, and as a consequence, etiological descriptions of childhood epilepsy in the region have been limited. We sought to describe MRI findings in children with epilepsy presenting to a tertiary hospital in Nairobi, Kenya, over a 6-year period of routine care. Materials and Methods: We undertook a retrospective review of MRI findings of children aged between 0 and 18 years with a diagnosis of epilepsy presenting to the pediatric neurology department of Aga Khan University Hospital in Nairobi, Kenya, between January 2014 and July 2020. Over this period, the hospital had 1.5T MRI machines (GE1.5T Signa Excite and GE 1.5T Signa Explorer) and a 3T MRI machine (Philips 3T Ingenia). MRI images were independently reviewed by two study radiologists, and the findings were summarized and categorized into a study database. Related clinical and electroencephalographic (EEG) details were extracted from patient records. Categorical data analysis methods were applied to investigate for relationships between clinically relevant neuroimaging findings and key clinical and EEG observations. Results: Over the study period, 288 children with a confirmed diagnosis of epilepsy had an MRI. They were of median age of 6 [interquartile range (IQR) 2-11] years. Ninety-five (33%) children had abnormal findings on imaging. The most common findings were encephalomalacia related to chronic infarcts (n = 18: 6.3%), cerebral atrophy (n = 11: 3.8%), disorders of neuronal migration (n = 11: 3.8%), periventricular leukomalacia (n = 9: 3.1%), and hippocampal sclerosis (n = 8: 2.8%). Findings related to infectious etiology were only observed in four children. Clinical comorbidity and inter-ictal epileptiform activity on EEG were independently associated with abnormal findings on imaging. Conclusion: Up to a third of the children who underwent an MRI had a positive yield for abnormal findings. Imaging findings related to infectious etiologies were little observed in our cohort, in contradistinction to etiology studies in similar settings. At the time of the study, comorbidity and inter-ictal epileptiform activity on EEG were associated with abnormal findings on imaging and should be considered in informing prioritization for imaging in childhood epilepsy in this setting.

Maturity assessment of Kenya's health information system interoperability readiness.

BACKGROUND: The use of digital technology in healthcare promises to improve quality of care and reduce costs over time. This promise will be difficult to attain without interoperability: facilitating seamless health information exchange between the deployed digital health information systems (HIS). OBJECTIVE: To determine the maturity readiness of the interoperability capacity of Kenya's HIS. METHODS: We used the HIS Interoperability Maturity Toolkit, developed by MEASURE Evaluation and the Health Data Collaborative's Digital Health and Interoperability Working Group. The assessment was undertaken by eHealth stakeholder representatives primarily from the Ministry of Health's Digital Health Technical Working Group. The toolkit focused on three major domains: leadership and governance, human resources and technology. RESULTS: Most domains are at the lowest two levels of maturity: nascent or emerging. At the nascent level, HIS activities happen by chance or represent isolated, ad hoc efforts. An emerging maturity level characterises a system with defined HIS processes and structures. However, such processes are not systematically documented and lack ongoing monitoring mechanisms. CONCLUSION: None of the domains had a maturity level greater than level 2 (emerging). The subdomains of governance structures for HIS, defined national enterprise architecture for HIS, defined technical standards for data exchange, nationwide communication network infrastructure, and capacity for operations and maintenance of hardware attained higher maturity levels. These findings are similar to those from interoperability maturity assessments done in Ghana and Uganda.

Neonatal seizures in a rural Kenyan District Hospital: aetiology, incidence and outcome of hospitalization.

BACKGROUND: Acute seizures are common among children admitted to hospitals in resource poor countries. However, there is little data on the burden, causes and outcome of neonatal seizures in sub-Saharan Africa. We determined the minimum incidence, aetiology and immediate outcome of seizures among neonates admitted to a rural district hospital in Kenya. METHODS: From 1st January 2003 to 31st December 2007, we assessed for seizures all neonates (age 0-28 days) admitted to the Kilifi District Hospital, who were resident in a defined, regularly enumerated study area. The population denominator, the number of live births in the community on 1 July 2005 (the study midpoint) was modelled from the census data. RESULTS: Seizures were reported in 142/1572 (9.0%) of neonatal admissions. The incidence was 39.5 [95% confidence interval (CI) 26.4-56.7] per 1000 live-births and incidence increased with birth weight. The main diagnoses in neonates with seizures were sepsis in 85 (60%), neonatal encephalopathy in 30 (21%) and meningitis in 21 (15%), but only neonatal encephalopathy and bacterial meningitis were independently associated with seizures. Neonates with seizures had a longer hospitalization [median period 7 days - interquartile range (IQR) 4 to10] -compared to 5 days [IQR 3 to 8] for those without seizures, P = 0.02). Overall, there was no difference in inpatient case fatality between neonates with and without seizures but, when this outcome was stratified by birth weight, it was significantly higher in neonates >or= 2.5 kg compared to low birth weight neonates [odds ratio 1.59 (95%CI 1.02 to 2.46), P = 0.037]. Up to 13% of the surviving newborn with seizures had neurological abnormalities at discharge. CONCLUSION: There is a high incidence of neonatal seizures in this area of Kenya and the most important causes are neonatal encephalopathy and meningitis. The high incidence of neonatal seizures may be a reflection of the quality of the perinatal and postnatal care available to the neonates.

The role for osmotic agents in children with acute encephalopathies: a systematic review.

BACKGROUND: Raised intracranial pressure (ICP) is known to complicate both traumatic and non-traumatic encephalopathies. It impairs cerebral perfusion and may cause death due to global ischaemia and intracranial herniation. Osmotic agents are widely used to control ICP. In children, guidelines for their use are mainly guided by adult studies. We conducted this review to determine the current evidence of the effectiveness of osmotic agents and their effect on resolution of coma and outcome in children with acute encephalopathy. METHODS: We searched several databases for published and unpublished studies in English and French languages, between January 1966 and March 2009. We considered studies on the use of osmotic agents in children aged between 0 and 16 years with acute encephalopathies. We examined reduction in intracranial pressure, time to resolution of coma, and occurrence of neurological sequelae and death. RESULTS: We identified four randomized controlled trials, three prospective studies, two retrospective studies and one case report. Hypertonic saline (HS) achieved greater reduction in intracranial pressure (ICP) compared to mannitol and other fluids; normal saline or ringer's lactate. This effect was sustained for longer when it was given as continuous infusion. Boluses of glycerol and mannitol achieved transient reduction in ICP. Oral glycerol was associated with lower mortality and neurological sequelae when compared to placebo in children with acute bacterial meningitis. HS was associated with lower mortality when compared to mannitol in children with non-traumatic encephalopathies. CONCLUSION: HS appears to achieve a greater reduction in ICP than other osmotic agents. Oral glycerol seems to improve outcome among children with acute bacterial meningitis. A sustained reduction in ICP is desirable and could be achieved by modifying the modes and rates of administration of these osmotic agents, but these factors need further investigation.

HIV infection, malnutrition, and invasive bacterial infection among children with severe malaria.

BACKGROUND: Human immunodeficiency virus (HIV) infection, malnutrition, and invasive bacterial infection (IBI) are reported among children with severe malaria. However, it is unclear whether their cooccurrence with falciparum parasitization and severe disease happens by chance or by association among children in areas where malaria is endemic. METHODS: We examined 3068 consecutive children admitted to a Kenyan district hospital with clinical features of severe malaria and 592 control subjects from the community. We performed multivariable regression analysis, with each case weighted for its probability of being due to falciparum malaria, using estimates of the fraction of severe disease attributable to malaria at different parasite densities derived from cross-sectional parasitological surveys of healthy children from the same community. RESULTS: HIV infection was present in 133 (12%) of 1071 consecutive parasitemic admitted children (95% confidence interval [CI], 11%-15%). Parasite densities were higher in HIV-infected children. The odds ratio for admission associated with HIV infection for admission with true severe falciparum malaria was 9.6 (95% CI, 4.9-19); however, this effect was restricted to children aged 1 year. Malnutrition was present in 507 (25%) of 2048 consecutive parasitemic admitted children (95% CI, 23%-27%). The odd ratio associated with malnutrition for admission with true severe falciparum malaria was 4.0 (95% CI, 2.9-5.5). IBI was detected in 127 (6%) of 2048 consecutive parasitemic admitted children (95% CI, 5.2%-7.3%). All 3 comorbidities were associated with increased case fatality. CONCLUSIONS: HIV, malnutrition and IBI are biologically associated with severe disease due to falciparum malaria rather than being simply alternative diagnoses in co-incidentally parasitized children in an endemic area.

Haptoglobin HP2-2 genotype, alpha-thalassaemia and acute seizures in children living in a malaria-endemic area.

Polymorphisms of the haptoglobin (HP) gene and deletions in alpha-globin gene (alpha-thalassaemia) are common in malaria-endemic Africa. The same region also has high incidence rates for childhood acute seizures. The haptoglobin HP2-2 genotype has been associated with idiopathic generalized epilepsies and altered iron metabolism in children with alpha-thalassaemia can potentially interfere with neurotransmission and increase the risk of seizures. We investigated the hypothesis that the HP2-2 genotype and the common African alpha-globin gene deletions are associated with the increased risk of seizures. 288 children aged 3-156 months admitted with acute seizures to Kilifi District Hospital (Kenya), were matched for ethnicity to an equal number of community controls. The proportion of cases (72/288 [25.0%]) and controls (80/288 [27.8%]) with HP2-2 genotype was similar, p=0.499. The allele frequency of HP2 gene in cases (49.3%) and controls (48.6%) was also similar, p=0.814. Similarly, we found no significant difference between the proportion of cases (177/267 [66.3%]) and controls (186/267 [69.7%]) with deletions in alpha-globin gene (p=0.403). Among cases, HP2-2 polymorphism and deletions in alpha-globin gene were neither associated with changes in the type, number or duration of seizures nor did they affect outcome. We conclude that the HP2-2 polymorphism and deletions in alpha-globin gene are not risk factors for acute seizures in children. Future studies should examine other susceptibility genes.

The incidence, aetiology and outcome of acute seizures in children admitted to a rural Kenyan district hospital.

BACKGROUND: Acute seizures are a common cause of paediatric admissions to hospitals in resource poor countries and a risk factor for neurological and cognitive impairment and epilepsy. We determined the incidence, aetiological factors and the immediate outcome of seizures in a rural malaria endemic area in coastal Kenya. METHODS: We recruited all children with and without seizures, aged 0-13 years and admitted to Kilifi District hospital over 2 years from 1st December 2004 to 30th November 2006. Only incident admissions from a defined area were included. Patients with epilepsy were excluded. The population denominator, the number of children in the community on 30th November 2005 (study midpoint), was modelled from a census data. RESULTS: Seizures were reported in 900/4,921(18.3%) incident admissions and at least 98 had status epilepticus. The incidence of acute seizures in children 0-13 years was 425 (95%CI 386, 466) per 100,000/year and was 879 (95%CI 795, 968) per 100,000/year in children <5 years. This incidence data may however be an underestimate of the true incidence in the community. Over 80% of the seizures were associated with infections. Neonatal infections (28/43 [65.1%]) and falciparum malaria (476/821 [58.0%]) were the main diseases associated with seizures in neonates and in children six months or older respectively. Falciparum malaria was also the main illness (56/98 [57.1%]) associated with status epilepticus. Other illnesses associated with seizures included pyogenic meningitis, respiratory tract infections and gastroenteritis. Twenty-eight children (3.1%) with seizures died and 11 surviving children (1.3%) had gross neurological deficits on discharge. Status epilepticus, focal seizures, coma, metabolic acidosis, bacteraemia, and pyogenic meningitis were independently associated with mortality; while status epilepticus, hypoxic ischaemic encephalopathy and pyogenic meningitis were independently associated with neurological deficits on discharge. CONCLUSION: There is a high incidence of acute seizures in children living in this malaria endemic area of Kenya. The most important causes are diseases that are preventable with available public health programs.

Burden of brain tumors in low- and middle-income countries: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to determine the best available evidence on the burden of brain tumors in low- and middle-income countries (LAMICs). More specifically, the objective is to determine the incidence and prevalence rates for brain tumors in LAMICs.

Treatment of Madura foot: a systematic review.

REVIEW QUESTION/OBJECTIVE: The objective of this review was to determine the best available evidence on the most effective treatment of Madura foot. INTRODUCTION: Madura foot or mycetoma is a chronic granulomatous soft-tissue infection that is endemic to several regions of Africa and Asia. It may be of fungal (eumycetoma) or bacterial (actinomycetoma) origin, warranting therapy with either antifungal or antibacterial medication as well as surgery. Without timely intervention, it often results in lifelong disability. However, it is unclear what regimes are most effective for treatment. INCLUSION CRITERIA: This review considered studies that included individuals of all ages with Madura foot (actinomycetoma or eumycetoma) as confirmed by microbiological or histological studies. Studies that evaluated antibiotic and antifungal regimens (any drug, dosage, frequency, duration) as well as surgical interventions (wound debridement, advanced excision or limb amputation) for Madura foot were included. Outcomes of interest were disease resolution (as determined by complete healing of mycetoma lesion after treatment), recurrence (return of mycetoma lesion after successful treatment) and mortality. Although this review considered both experimental and epidemiological study designs for inclusion, only case series and individual case reports were identified and were therefore included in the review. METHODS: A three-step search strategy, involving an initial search, a second more comprehensive search using identified keywords and a third search involving the reference lists of included articles, was utilized. Ten databases were searched. An additional 13 sources were searched for gray and/or unpublished literature. Included studies were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute. Disagreements were resolved through discussion or with a third reviewer. A data extraction tool was used to extract data on interventions, populations, study designs and outcomes of significance to the review question. Statistical pooling was not possible, therefore a narrative synthesis was performed. RESULTS: Thirty-one studies were included in the review (27 case reports and four case series). A total of 47 patients with Madura foot were analyzed. Twenty-five had eumycetoma, 21 actinomycetoma and one had both. Therapy involved varying dosages of sulfa drugs (co-trimoxazole and dapsone), amikacin and tetracyclines administered for the therapy of actinomycetoma with resolution of disease in all affected patients. The azole derivatives (itraconazole, ketoconazole, voriconazole, fluconazole and miconazole) as well as co-trimoxazole were the most commonly employed drugs for eumycetoma, with resolution of disease in 88% of included patients. Surgery was performed in a total of 21 patients with resolution of disease in all cases. The overall resolution rate following therapy was 95.7%. CONCLUSION: Therapy for Madura foot is informed by case series and case reports which provide low level evidence for practice. Antimicrobials in conjunction with surgery lead to resolution of disease.

Over-diagnosis and co-morbidity of severe malaria in African children: a guide for clinicians.

Severe malaria is clinically similar to other severe febrile illnesses. However, in endemic areas, parasitological confirmation of parasitemia is often unavailable or unreliable. False-positive malaria microscopy is common. The most important consequence of treating only for malaria when no parasitemia exists is failure to address other life-threatening conditions. Invasive bacterial infections are detected in up to one third of children with clinical features of severe malaria but a slide with results negative for malaria. Even among genuinely parasitized children, severe illness is not always due to malaria in endemic areas. We believe that routine use of parenteral antibiotics among children with a slide that indicates malaria and life-threatening disease is warranted because invasive bacterial infections are likely to be under-ascertained and are associated with increased mortality. Published data on co-morbidity with HIV infection and malnutrition are reviewed. A structured approach to assessment and care is essential, and is largely independent of underlying etiology.

Antimalarial drugs and the prevalence of mental and neurological manifestations: A systematic review and meta-analysis.

Background: Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans.  Methods: We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques.  Results: Of the 2,349 records identified in the initial search, 51 human studies met the eligibility criteria. The median pooled prevalence range of mental and neurological manifestations associated with antimalarial drugs ranged from 0.7% (dapsone) to 48.3% (minocycline) across all studies, while it ranged from 0.6% (pyrimethamine) to 42.7% (amodiaquine) during treatment of acute malaria, and 0.7% (primaquine/dapsone) to 55.0% (sulfadoxine) during prophylaxis. Pooled prevalence of mental and neurological manifestations across all studies was associated with an increased number of antimalarial drugs (prevalence ratio= 5.51 (95%CI, 1.05-29.04); P=0.045) in a meta-regression analysis. Headaches (15%) and dizziness (14%) were the most common mental and neurological manifestations across all studies. Of individual antimalarial drugs still on the market, mental and neurological manifestations were most common with the use of sulphadoxine (55%) for prophylaxis studies and amodiaquine (42.7%) for acute malaria studies. Mefloquine affected more domains of mental and neurological manifestations than any other antimalarial drug.  Conclusions: Antimalarial drugs, particularly those used for prophylaxis, may be associated with mental and neurological manifestations, and the number of antimalarial drugs taken determines the association. Mental and neurological manifestations should be assessed following the use of antimalarial drugs.