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Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for N. meningitidis, S. pneumoniae, and H. influenzae used in routine meningitis surveillance. A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and Plasmodium. Overall, Escherichia coli was the most prevalent (4.8%), followed by S. pneumoniae (3.5%) and Plasmodium (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and Plasmodium detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.

Background Endemic Burkitt lymphoma (eBL) is an aggressive B-cell lymphoma, which is a common childhood cancer in areas with intense transmission of Plasmodium falciparum parasites. Early and accurate diagnosis is a prerequisite for successful therapy, but it optimally involves advanced laboratory investigations. These are technologically demanding, expensive, and often difficult to implement in settings where eBL is prevalent. Diagnosis is thus generally based on clinical assessment and morphological examination of tumour biopsies or fine-needle aspirates (FNAs). Methods The purpose of the present study was to assess the accuracy of eBL diagnosis at two tertiary hospitals in Ghana. To that end, we studied FNAs from 29 eBL patients and 21 non-eBL lymphoma patients originally diagnosed in 2018. In addition, we examined 111 archival formalin-fixed and paraffin-embedded (FFPE) biopsies from Ghanaian patients originally diagnosed as eBL (N = 55) or non-eBL (N = 56) between 2010 and 2017. Availability-based subsets of samples were subjected to haematoxylin-eosin or Giemsa staining, C-MYC immunohistochemistry, and fluorescence in situ hybridisation (FISH) analysis of c-myc rearrangements. Results We found a good correlation between original diagnosis and subsequent retrospective assessment, particularly for FNA samples. However, evidence of intact c-myc genes and normal C-MYC expression in samples from some patients originally diagnosed as eBL indicates that morphological assessment alone can lead to eBL over-diagnosis in our study area. In addition, several FFPE samples could not be assessed retrospectively, due to poor sample quality. Therefore, the simpler FNA method of obtaining tumour material is preferable, particularly when careful processing of biopsy specimens cannot be guaranteed. Conclusion We conclude that the accuracy of eBL diagnostic tools available in Ghana is generally adequate, but could be improved by implementation of additional pathology laboratory investigations. Improved attention to adequate preservation of archival samples is recommended.

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S . pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.

Background Global surveillance for vaccine preventable invasive bacterial diseases has been set up by the World Health Organization to provide disease burden data to support decisions on introducing pneumococcal conjugate vaccine (PCV). We present data from 2010 to 2016 collected at the 2 sentinel sites in Ghana. Methods Data were collected from children, The number of children

Background: There is limited information on the safety or efficacy of currently recommended antimalarial drugs in patients with sickle cell disease (SCD), a population predisposed to worse outcomes if affected by acute malaria. Artesunate-amodiaquine (ASAQ) is the first-line treatment for uncomplicated malaria (UM) in many malaria-endemic countries and is also used for treatment of UM in SCD patients. There is, however, no information to date, on the pharmacokinetics (PK) of amodiaquine or artesunate or the metabolites of these drugs in SCD patients. Objectives: This study sought to determine the PK of desethylamodiaquine (DEAQ), the main active metabolite of amodiaquine, among paediatric SCD patients with UM treated with artesunate-amodiaquine (ASAQ). Methods: Plasma concentration-time data (median DEAQ levels) of SCD children (n = 16) was initially compared with those of concurrently recruited non-SCD paediatric patients with acute UM (n = 13). A population PK modelling approach was then used to analyze plasma DEAQ concentrations obtained between 64 and 169 hours after oral administration of ASAQ in paediatric SCD patients with acute UM (n = 16). To improve PK modeling, DEAQ concentration-time data (n = 21) from SCD was merged with DEAQ concentration-time data (n = 169) of a historical paediatric population treated with ASAQ (n = 103) from the same study setting. Results: The median DEAQ concentrations on days 3 and 7 were comparatively lower in the SCD patients compared to the non-SCD patients. A two-compartment model best described the plasma DEAQ concentration-time data of the merged data (current SCD data and historical data). The estimated population clearance of DEAQ was higher in the SCD patients (67 L/h, 21% relative standard error (RSE) compared with the non-SCD population (15.5 L/h, 32% RSE). The central volume of distribution was larger in the SCD patients compared with the non-SCD patients (4400 L, 43% RSE vs. 368 L, 34% RSE). Conclusions: The data shows a tendency towards lower DEAQ concentration in SCD patients and the exploratory population PK estimates suggest altered DEAQ disposition in SCD patients with acute UM. These findings, which if confirmed, may reflect pathophysiological changes associated with SCD on DEAQ disposition, have implications for therapeutic response to amodiaquine in SCD patients. The limited number of recruited SCD patients and sparse sampling approach however, limits extrapolation of the data, and calls for further studies in a larger population. Key words: Clearance, Desethylamodiaquine, Sickle cell disease

We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020–50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.

Background High global neonatal deaths have triggered efforts to improve facility-based care. However, the outcomes achievable at different levels of care are unclear. This study compared morbidity and mortality patterns of newborns admitted to a regional and a district hospital in Ghana to determine outcome, risk and modifiable factors associated with mortality. Objective This study compared morbidity and mortality patterns of newborns admitted to a regional and a district hospital in Ghana to determine outcome, risk and modifiable factors associated with mortality. Methods A cross-sectional study involving a records-review over one year at the Upper West Regional Hospital, and three years at St Joseph's District Hospital, Jirapa was carried out. Age, sex, gestational age, weight, duration of admission, diagnosis, among others were examined. The data were analysed and statistical inference made. Results Altogether, 2004 newborns were examined, comprising 1,241(62%) from St Joseph's District Hospital and 763(38%) from Upper West Regional Hospital. The proportion of neonatal deaths was similar, 8.94% (St Joseph's District Hospital) and 8.91% (Upper West Regional Hospital). Prematurity, neonatal sepsis, birth asphyxia, low birth weight, neonatal jaundice and pneumonia contributed the most to mortality and suspected infections including malaria accounted for almost half (45.5%). Mortality was significantly associated with duration of stay of 48 hours, being premature, and being younger than 3 days. Conclusion Majority of the mortality among the neonates admitted was due to preventable causes. Better stabilization and further studies on the epidemiology of sepsis, prematurity, low birth weight, including the contribution of malaria to these and outcome of transferred neonates are needed.

BackgroundDespite increasing global attention to non-communicable diseases (NCDs) and their incorporation into universal health coverage (UHC), the factors that determine whether and how NCDs are prioritized in national health agendas and integrated into health systems remain poorly understood. Childhood cancer is a leading non-communicable cause of death in children aged 0-14 years worldwide. We investigated the political, social, and economic factors that influence health system priority-setting on childhood cancer care in a range of low- and middle-income countries (LMIC).Methods and findingsBased on in-depth qualitative case studies, we analyzed the determinants of priority-setting for childhood cancer care in El Salvador, Guatemala, Ghana, India, and the Philippines using a conceptual framework that considers four principal influences on political prioritization: political contexts, actor power, ideas, and issue characteristics. Data for the analysis derived from in-depth interviews (n = 68) with key informants involved in or impacted by childhood cancer policies and programs in participating countries, supplemented by published academic literature and available policy documents. Political priority for childhood cancer varies widely across the countries studied and is most influenced by political context and actor power dynamics. Ghana has placed relatively little national priority on childhood cancer, largely due to competing priorities and a lack of cohesion among stakeholders. In both El Salvador and Guatemala, actor power has played a central role in generating national priority for childhood cancer, where well-organized and -resourced civil society organizations have disrupted legacies of fragmented governance and financing to create priority for childhood cancer care. In India, the role of a uniquely empowered private actor was instrumental in creating political priority and establishing sustained channels of financing for childhood cancer care. In the Philippines, the childhood cancer community has capitalized on a window of opportunity to expand access and reduce disparities in childhood cancer care through the political prioritization of UHC and NCDs in current health system reforms.ConclusionsThe importance of key health system actors in determining the relative political priority for childhood cancer in the countries studied points to actor power as a critical enabler of prioritization in other LMIC. Responsiveness to political contexts-in particular, rhetorical and policy priority placed on NCDs and UHC-will be crucial to efforts to place childhood cancer firmly on national health agendas. National governments must be convinced of the potential for foundational health system strengthening through attention to childhood cancer care, and the presence and capability of networked actors primed to amplify public sector investments and catalyze change on the ground.

Purpose No published study to date has examined total cost and cost-effectiveness of maintaining a pediatric oncology treatment center in an African setting, thus limiting childhood cancer advocacy and policy efforts. Methods Within the Korle Bu Teaching Hospital in Accra, Ghana, costing data were gathered for all inputs related to operating a pediatric cancer unit. Cost and volume data for relevant clinical services (eg, laboratory, pathology, medications) were obtained retrospectively or prospectively. Salaries were determined and multiplied by proportion of time dedicated toward pediatric patients with cancer. Costs associated with inpatient bed use, outpatient clinic use, administrative fees, and overhead were estimated. Costs were summed for a total annual operating cost. Cost-effectiveness was calculated based on annual patients with newly diagnosed disease, survival rates, and life expectancy. Results The Korle Bu Teaching Hospital pediatric cancer unit treats on average 170 new diagnoses annually. Total operating cost was $1.7 million/y. Personnel salaries and operating room costs were the most expensive inputs, contributing 45% and 21% of total costs. Together, medications, imaging, radiation, and pathology services accounted for 7%. The cost per disability-adjusted life-year averted was $1,034, less than the Ghanaian per capita income, and thus considered very cost effective as per WHO-CHOICE methodology. Conclusion To our knowledge, this study is the first to examine institution-level costs and cost-effectiveness of a childhood cancer program in an African setting, demonstrating that operating such a program in this setting is very cost effective. These results will inform national childhood cancer strategies in Africa and other low- and middle-income country settings.

Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and heightfor- age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and - 0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.

BACKGROUND There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modeling analysis in children ages 1-5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups, and regions. METHODS ART-naive children of ages 12-59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation. RESULTS About one quarter of the 5,826 included children was from West Africa (24.6%).The median (first; third quartile) CD4% at the first visit was 16% (11%; 23%), the median weight-for-age z-scores and height-for-age z-scores were -1.5 (-2.7; -0.6) and -2.5 (-3.5; -1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count

Background: The interplay between Epstein-Barr virus infection, malaria, and endemic Burkitt’s Lymphoma is not well understood. Reports show diminished EBV-specific Th1 responses in children living in malaria endemic areas and deficiency of EBNA1-specific IFN-γ T cell responses in children with endemic Burkitt’s Lymphoma (eBL). This study, therefore, examined some factors involved in the loss of EBNA-1-specific T cell responses in eBL. Methods: T-cell subset frequencies, activation, and IFN-γ- or IL-4-specific responses were analyzed by flow-cytometry. Plasma cytokine levels were measured by ELISA. Results: CD4+ and CD8+ cells in age- and sex-matched healthy controls (n = 3) expressed more IFN-γ in response to all immunostimulants than in pediatric endemic BL (eBL) patients (n = 4). In healthy controls, IFN-γ expression was higher than IL-4 expression, whereas in eBL patients the expression of IL-4 by CD4+ cells to EBNA-1 was slightly higher than IFN-γ. Moreover, the blood levels of TNF-α was significantly lower (p = 0.004) while IL-10 was significantly higher (p = 0.038), in eBL patients (n = 21) compared to controls (n = 16). Additionally, the frequency of CD4+CD25hi+ T cells was higher in both age-matched acute uncomplicated malaria (n = 26) and eBL (n = 14) patients compared to healthy controls (n = 19, p = 0.000 and p = 0.027, respectively). Conclusion: The data suggest that reduced Th1 response in eBL might be due to increased levels of IL-10 and T reg cells.

SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons.OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries.DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n = 14), East Africa (n = 8), West Africa (n = 7), Central Africa (n = 5), Latin America (n = 7) and the Asia-Pacific (n = 6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs.RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11 (23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages.CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.

Introduction: There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods: Standardized collection of data from HIV-infected children (positive PCR B18 months or positive serology )18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Cote d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age B16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb B7g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results: As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was2.7; and 1772 (60.4%) had a first-line ZDV- containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p50.01): the prevalence of severe anaemia was 3.0% (n38) in the ZDV group versus 10.2% (n89) in those without (p B0. 01). Over the first-line follow-up, 58.9% of the children had )1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p50.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score 53 was a strong predictor associated with a 5.59 times risk of severe anaemia (p B0.01). Conclusions: Severe anaemia is frequent at baseline and guides the first-line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care.

Mitochondrial damage is implicated in highly active antiretroviral therapy (HAART) toxicity. HIV infection also causes mitochondrial toxicity (MT). Differentiating between the two is critical for HIV management. Our objective was to test the utility of the Mitochondrial Disease Criteria (MDC) and the Enquête Périnatale Française (EPF) to screen for possible HAART related MT in HIV-infected children in Ghana. The EPF and MDC are compilations of clinical symptoms, or criteria, of MT: a (+) score indicates possible MT. We applied these criteria retrospectively to 403 charts of HIV-infected children. Of those studied, 331/403 received HAART. Comparing HAART exposed and HAART naïve children, the difference in EPF score, but not MDC, approached significance (P = 0.1). Young age at HIV diagnosis or at HAART initiation was associated with (+) EPF (P ≤ 0.01). Adherence to HAART trended toward an association with (+) EPF (P = 0.09). Exposure to nevirapine, abacavir, or didanosine increased risk of (+) EPF (OR = 3.55 (CI = 1.99-6.33), 4.76 (2.39-9.43), 4.93 (1.29-18.87)). Neither EPF nor MDC identified a significant difference between HAART exposed or naïve children regarding possible MT. However, as indicators of HAART exposure are associated with (+) EPF, it may be a candidate for prospective study of possible HAART related MT in resource-poor settings.

With the advent of highly active antiretroviral therapy (HAART) HIV-infected children are surviving into adulthood. Despite emerging evidence of the benefits of disclosure, when and how to disclose the diagnosis of HIV to children remain a clinical dilemma. We investigated the prevalence and determinants of HIV disclosure in a cross-sectional study of 71 caregiver-child dyads from the Pediatric HIV/AIDS Care Program at Korle-Bu Teaching Hospital (Accra, Ghana). The children were between 8 and 14 years of age (median age, 10.39 years). The prevalence of disclosure was 21%. In the unadjusted analyses, the age of child, the level of education of child, deceased biologic father, administration of own HIV medications, and longer duration on HIV medication were significantly associated with disclosure. The low prevalence of disclosure underscores the need for a systematic and a staged approach in disclosing HIV status to infected children in resource limited countries.

Background The IeDEA West Africa Pediatric Working Group (pWADA) was established in January 2007 to study the care and treatment of HIV-infected children in this region. We describe here the characteristics at antiretroviral treatment (ART) initiation and study the 12-month mortality and loss-to-program of HIV-infected children followed in ART programs in West Africa. Methods Standardized data from HIV-infected children followed-up in ART programs were included. Nine clinical centers from six countries contributed to the dataset (Benin, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal). Inclusion criteria were the followings: age 0-15 years and initiated triple antiretroviral drug regimens. Baseline time was the date of ART initiation. WHO criteria was used to define severe immunosuppression based on CD4 count by age or CD4 percent < 15%. We estimated the 12-month Kaplan-Meier probabilities of mortality and loss-to-program (death or loss to follow-up > 6 months) after ART initiation and factors associated with these two outcomes. Results Between June 2000 and December 2007, 2170 children were included. Characteristics at ART initiation were the following: median age of 5 years (Interquartile range (IQR: 2-9) and median CD4 percentage of 13% (IQR: 7-19). The most frequent drug regimen consisted of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitors (62%). During the first 12 months, 169 (7.8%) children died and 461(21.2%) were lost-to-program. Overall, in HIV-infected children on ART, the 12-month probability of death was 8.3% (95% Confidence Interval (CI): 7.2-9.6%), and of loss-to-program was 23.1% (95% CI: 21.3-25.0%). Both mortality and loss-to program were associated with advanced clinical stage, CD4 percentage < 15% at ART initiation and year (> 2005) of ART initiation. Conclusion Innovative and sustainable approaches are needed to better document causes of death and increase retention in HIV pediatric clinics in West Africa.

Background. CD4+ T-lymphocyte monitoring is not routinely available in most resource-limited settings. We investigated predictors of time to CD4+ T-lymphocyte recovery in HIV-infected children on highly active antiretroviral (HAART) at Korle-Bu Teaching Hospital, Ghana.Methods. Time to CD4+ T-lymphocyte recovery was defined as achieving percent CD4+ T-lymphocytes of 25%. We used Cox proportional hazard models for identifying significant predictor variables.Results. Of the 233 children with complete CD4+ T-lymphocyte data, the mean age at HAART initiation was 5.5 (SD=3.1) years. The median recovery time was 60 weeks (95% CL: 55–65). Evidence at baseline of severe suppression in CD4+ T-lymphocyte count adjusted for age, age at HAART initiation, gender, and having parents alive were statistically significant in predicting time to CD4+ T-lymphocyte recovery.Conclusions. A targeted approach based on predictors of CD4+ T-lymphocyte recovery can be a viable and cost-effective way of monitoring HAART in HIV-infected children in resource-limited settings.

Two cases of melanotic neuroectodermal tumour of infancy (MNTI), otherwise known as melanotic progonoma, both arising from the maxilla are presented here. The two infants both presented within three months of each other and though clinically Burkitt's lymphoma was stated as a possible diagnosis, the correct diagnosis was made on biopsy specimens. Radical surgery consisting of wide resection of the tumour with margins of healthy tissue via hemi-maxillectomy was performed in each case as an initial method of treatment. At follow up four months later, both infants appeared clinically well. One infant was then lost to follow up thereafter but the other was reviewed three years later, and apart from slight facial asymmetry, there was no evidence of tumour recurrence.

Background HIV-infected children in sub-Saharan Africa may be at a high risk of staying on a failing first-line regimen and developing drug-resistance HIV variants due to lack of routine viral load monitoring. We investigated whether cumulative viral load, measured as viremia copy-years (VCY) could predict morbidity in a setting where viral load is not routinely monitored. Methods This was a single-center prospective observational longitudinal study of HIV-infected children initiating antiretroviral therapy (ART) at the Pediatric HIV/AIDS Care program at Korle-Bu Teaching Hospital in Accra, Ghana. The main outcome was morbidity measured as frequency of hospitalizations, opportunistic infections, and outpatient sick visits. The main explanatory variable was viral load measured as VCY. Results The study included 140 children who initiated ART between September 2009 and May 2013 and had at least 2 viral load measurements. There were 184 hospitalizations, with pneumonia being the most common cause (22.8 %). A total of 102 opportunistic infections was documented, with tuberculosis being the most common opportunistic infection (68 %). A total of 823 outpatient sick visits was documented, with upper respiratory infections (14.2 %) being the most common cause. Forty-four percent of our study participants had >4 log10 VCY. Children in this sub-cohort had a higher frequency of sick visits compared with those with 4 log10 VCY had been identified as treatment failure using WHO clinical and immunological treatment failure criteria. Conclusions High level of cumulative viral load may translate to virological failure and subsequent increased all-cause morbidity. Our finding of potential utility of VCY in pediatrics warrants further investigations. VCY may be a good alternate to routine viral load measurement as its determination may be less frequent and could be personalized to save cost.

Background Antiretroviral therapy (ART) scale-up in resource-limited countries, with limited capacity for CD4 and HIV viral load monitoring, presents a unique challenge. We determined the effectiveness of first-line ART in a real world pediatric HIV clinic and explored associations between readily obtainable patient data and the trajectories of change in CD4 count and HIV viral load. Methods We performed a longitudinal study of a cohort of HIV-infected children initiating ART at the Korle-Bu Teaching Hospital Pediatric HIV clinic in Accra, Ghana, aged 0-13 years from 2009-2012. CD4 and viral load testing were done every 4 to 6 months and genotypic resistance testing was performed for children failing therapy. A mixed linear modeling approach, combining fixed and random subject effects, was employed for data analysis. Results Ninety HIV-infected children aged 0 to 13 years initiating ART were enrolled. The effectiveness of first-line regimen among study participants was 83.3%, based on WHO criteria for virologic failure. Fifteen of the 90 (16.7%) children met the criteria for virologic treatment failure after at least 24 weeks on ART. Sixty-seven percent virologic failures harbored viruses with ≥ 1 drug resistant mutations (DRMs); M184V/K103N was the predominant resistance pathway. Age at initiation of therapy, child’s gender, having a parent as a primary care giver, severity of illness, and type of regimen were associated with treatment outcomes. Conclusions First-line ART regimens were effective and well tolerated. We identified predictors of the trajectories of change in CD4 and viral load to inform targeted laboratory monitoring of ART among HIV-infected children in resource-limited countries.

Background Sickle cell disease (SCD) is a genetic disorder common in malaria endemic areas. In endemic areas, malaria is a major cause of morbidity and mortality among SCD patients. This suggests the need for prompt initiation of efficacious anti-malarial therapy in SCD patients with acute malaria. However, there is no information to date, on the efficacy or safety of artemisinin combination therapy when used for malaria treatment in SCD patients. Methods Children with SCD and acute uncomplicated malaria (n = 60) were randomized to treatment with artesunate-amodiaquine (AA), or artemether-lumefantrine (AL). A comparison group of non-SCD children (HbAA genotype; n = 59) with uncomplicated malaria were also randomized to treatment with AA or AL. Recruited children were followed up and selected investigations were done on days 1, 2, 3, 7, 14, 28, 35, and 42. Selected clinical and laboratory parameters of the SCD patients were also compared with a group of malaria-negative SCD children (n = 82) in steady state. Results The parasite densities on admission were significantly lower in the SCD group, compared with the non-SCD group (p = 0.0006). The parasite reduction ratio (PRR) was lower, clearance was slower (p