There exist significant challenges to the receipt of comprehensive oncologic treatment for children diagnosed with cancer in sub-Saharan Africa. To better define those challenges, we investigated ...treatment outcomes and risk factors for treatment abandonment in a cohort of children diagnosed with cancer at the University Teaching Hospital (UTH), the site of the only pediatric oncology ward in Zambia.
Using an established database, a retrospective cohort study was conducted of children aged 0-15 years admitted to the pediatric oncology ward between July 2008 and June 2010 with suspected cancer. Diagnosis, mode of diagnosis, treatment outcome, and risk factors for abandonment of treatment were abstracted from this database and clinical medical records.
Among 162 children treated at the UTH during the study time period that met inclusion criteria, only 8.0% completed a treatment regimen with most of the patients dying during treatment or abandoning care. In multivariable analysis, shorter distance from home to the UTH was associated with a lower risk of treatment abandonment (Adjusted Odds Ratio aOR = 0.48 (95% confidence interval CI 0.23-0.97). Conversely maternal education less than secondary school was associated with increased risk for abandonment (aOR = 1.65; 95% CI 1.05-2.58).
Despite availability of dedicated pediatric oncology treatment, treatment completion rates are poor, due in part to the logistical challenges faced by families, low educational status, and significant distance from the hospital. Alternative treatment delivery strategies are required to bring effective pediatric oncology care to the patients in need, as their ability to come to and remain at a central tertiary care facility for treatment is limited. We suggest that the extensive system now in place in most of sub-Saharan Africa that sustains life-long antiretroviral therapy for children with human immunodeficiency virus (HIV) infection be adapted for pediatric cancer treatment to improve outcome.
To identify best practices and quality improvement initiatives, we aimed to assess whether the incidence of Periprosthetic Joint Infection (PJI) and treatment strategies differed across patients ...treated in Australian, European and United States (US) hospitals.
Routinely collected administrative data for 41397 patients undergoing a primary total hip or knee arthroplasty between July 2007-December 2010 across 22 hospitals were included. Patients were followed for 2 years looking for PJI occurrence, defined as early (within 4 weeks) and late PJI, and surgical treatment during 2.5 years after PJI diagnosis. Logistic and Poisson regression models were used to test for differences in PJI occurrence and treatment strategies across the three geographical regions, adjusted for age, sex, joint and Elixhauser comorbidity groups.
PJI occurrence varied from 1.4% in European to 1.7% in Australian patients, which were significantly higher than US patients after adjustment for patient characteristics (OR 1.24 1.01-1.52 and 1.40 1.03-1.91 respectively). Early PJIs varied between 0.3% in European to 0.6% in Australian patients, but adjusted rates were similar. Revision following PJI was significantly lower in Australian than in US patients (OR 0.46 0.25-0.86) as were the total number of revisions (RR 0.51 0.36-0.71) and number of surgical procedures (RR 0.60 0.44-0.81) used to treat PJI.
The overall PJI rate was significantly higher in Australian patients, but fewer procedures were needed to treat these PJIs. Future research should reveal whether this reflects PJIs caught earlier or less severe when diagnosed, and whether this is associated with the longer length of stay after primary arthroplasty in Australian hospitals.
Burkitt lymphoma, a childhood cancer common in parts of sub-Saharan Africa, has been associated with Epstein Barr Virus (EBV) and malaria, but its association with human immunodeficiency virus (HIV) ...is not clear.
We conducted a case-control study of Burkitt lymphoma among children (aged < or = 15 years) admitted to the pediatric oncology unit in Blantyre, Malawi between July 2005 and July 2006. Cases were 148 children diagnosed with Burkitt lymphoma and controls were 104 children admitted with non-malignant conditions or cancers other than hematological malignancies and Kaposi sarcoma. Interviews were conducted and serological samples tested for antibodies against HIV, EBV and malaria. Odds ratios for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, and residential district. Cases had a mean age of 7.1 years and 60% were male. Cases were more likely than controls to be HIV positive (Odds ratio (OR)) = 12.4, 95% Confidence Interval (CI) 1.3 to 116.2, p = 0.03). ORs for Burkitt lymphoma increased with increasing antibody titers against EBV (p = 0.001) and malaria (p = 0.01). Among HIV negative participants, cases were thirteen times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 13.2; 95% CI 3.8 to 46.6; p = 0.001). Reported use of mosquito nets was associated with a lower risk of Burkitt lymphoma (OR = 0.2, 95% CI, 0.03 to 0.9, p = 0.04).
Our findings support prior evidence that EBV and malaria act jointly in the pathogenesis of Burkitt lymphoma, suggesting that malaria prevention may decrease the risk of Burkitt lymphoma. HIV may also play a role in the etiology of this childhood tumor.
Objectives
Human T‐lymphotropic virus (HTLV)‐1 causes T‐cell leukaemia and myelopathy. Together with HTLV‐2, it is endemic in some African nations. Seroprevalence data from Malawi are scarce, with no ...reports on associated disease incidence. HTLV seroprevalence and type were tested in 418 healthy mothers from Malawi. In addition, we tested the sera of 534 children to investigate mother‐to‐child transmission. To provide context, we conducted a systematic review and meta‐analysis of HTLV seroprevalence in African women and children.
Methods
Stored samples from a previous childhood cancer and BBV study were analysed. ELISA was used for HTLV screening followed by immunoblot for confirmation and typing. Standard methods were used for the systematic review.
Results
HTLV seroprevalence was 2.6% (11/418) in mothers and 2.2% (12/534) in children. Three mothers carried HTLV‐1 alone, seven had HTLV‐2 and one was dually infected. Three children carried HTLV‐1 alone, seven had HTLV‐2 and two were dually infected. Only two corresponding mothers of the 12 HTLV‐positive children were HTLV positive. The systematic review included 66 studies of women and 13 of children conducted in 25 African countries. Seroprevalence of HTLV‐1 varied from 0 to 17% and of HTLV‐2 from 0 to 4%.
Conclusions
In contrast to findings from other studies in Africa, the seroprevalence of HTLV‐2 was higher than that of HTLV‐1 in Malawi and one of the highest for the African region. The lack of mother–child concordance suggests alternative sources of infection among children. Our data and analyses contribute to HTLV prevalence mapping in Africa.
Objectifs
Le virus T‐lymphotropique humain (HTLV) ‐1 provoque la leucémie des lymphocytes T et la myélopathie. Ensemble avec HTLV‐2, il est endémique dans certains pays africains. Les données de séroprévalence du Malawi sont rares, avec aucun report sur l'incidence de la maladie associée. La séroprévalence et le type de HTLV ont été testés chez 418 mères en bonne santé du Malawi. En outre, nous avons testé les sérums de 534 enfants pour investiguer sur la transmission mère‐enfant. Afin de fournir un contexte, nous avons effectué une revue systématique et une méta‐analyse de la séroprévalence du HTLV chez les femmes et les enfants africains.
Méthodes
Des échantillons stockés provenant de cancer de l'enfance et de l’étude BBV ont été analysés. Le test ELISA a été utilisé pour le dépistage du HTLV suivi par l'immunoblot pour la confirmation et le typage. Des méthodes standard ont été utilisées pour l'analyse systématique.
Résultats
La séroprévalence du HTLV était de 2,6% (11/418) chez les mères et de 2,2% (12/534) chez les enfants. Trois mères portaient HTLV‐1 seul, sept avaient HTLV‐2 et une était doublement infectée. Trois enfants portaient HTLV‐1 seul, sept avaient HTLV‐2 et deux étaient doublement infectés. Seules deux mères correspondantes chez les 12 HTLV enfants séropositifs étaient positives pour HTLV. L'analyse systématique a inclus 66 études sur des femmes et 13 sur des enfants, menées dans 25 pays africains. La séroprévalence du HTLV‐1 variait de 0 à 17% et celle de HTLV‐2 de 0 à 4%.
Conclusions
Contrairement aux résultats d'autres études en Afrique, la séroprévalence du HTLV‐2 était plus élevée que celle du HTLV‐1 au Malawi et une des plus élevées de la région africaine. Le manque de concordance mère‐enfant suggère d'autres sources de l'infection chez les enfants. Nos données et les analyses contribuent à la cartographie de la prévalence du HTLV en Afrique.
Objetivos
El virus linfotrópico humano de células T (HTLV)‐1 causa leucemia de las células T y mielopatía. Junto con HTLV‐2 es endémico en algunas naciones africanas. Los datos de seroprevalencia para Malawi son escasos, sin informes sobre la incidencia de la patología asociada. Se evaluó la seroprevalencia y el tipo de HTLV en 418 madres sanas de Malawi. Adicionalmente evaluamos el suero de 534 niños para investigar la transmisión madre‐hijo. Para ponerlo en contexto, realizamos una revisión sistemática y metaanálisis de seroprevalencia de HTLV en mujeres y niños africanos.
Métodos
Se analizaron muestras de un estudio previo de cáncer infantil y estudio BBV. Se utilizó la prueba de ELISA para el cribado de HTLV seguido por un inmunoblot para realizar la confirmación y el tipado. Se utilizaron metodologías estándar para la revisión sistemática.
Resultados
La seroprevalencia de HTLV era del 2.6% (11/418) en madres y 2.2% (12/534) en niños. Tres madres tenían el HTLV‐1 solamente, siete tenían HTLV‐2 y una estaba infectada con ambos. Tres niños estaban infectados con HTLV‐1 solamente, siete tenían HTLV‐2 y dos estaban infectados con ambos. Solo dos madres de los 12 niños HTLV positivos eran HTLV positivas. La revisión sistemática incluyó 66 estudios de mujeres y 13 de niños realizados en 25 países africanos. La seroprevalencia de HTLV‐1 variaba entre 0‐17% y de HTLV‐2 entre 0‐4%.
Conclusiones
En contraste con los hallazgos de otros estudios en África, en Malawi la seroprevalencia de HTLV‐2 era mayor que la de HTLV‐1, y una de las más altas para regiones africanas. La falta de concordancia en la transmisión madre‐hijo sugiere la existencia de fuentes alternativas de infección entre niños. Nuestros datos y análisis contribuyen a mapear la prevalencia de HTLV en África.
Endemic Burkitt lymphoma (eBL) has been linked to Plasmodium falciparum (Pf) malaria infection, but the contribution of infection with multiple Pf genotypes is uncertain. We studied 303 eBL (cases) ...and 274 non eBL-related cancers (controls) in Malawi using a sensitive and specific molecular-barcode array of 24 independently segregating Pf single nucleotide polymorphisms. Cases had a higher Pf malaria prevalence than controls (64.7% versus 45.3%; odds ratio OR 2.1, 95% confidence interval (CI): 1.5 to 3.1). Cases and controls were similar in terms of Pf density (4.9 versus 4.5 log copies, p = 0.28) and having ≥3 non-clonal calls (OR 2.7, 95% CI: 0.7-9.9, P = 0.14). However, cases were more likely to have a higher Pf genetic diversity score (153.9 versus 133.1, p = 0.036), which measures a combination of clonal and non-clonal calls, than controls. Further work is needed to evaluate the possible role of Pf genetic diversity in the pathogenesis of endemic BL.
Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to
(
) malaria infection, one of the most common and deadly childhood infections in Africa; however, the ...role of
genetic diversity is unclear. A potential role of
genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of
infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher
genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in
serine repeat antigen-5 (
), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all
polymerase chain reaction (PCR)-positive, in Malawi.
We performed
PCR and sequencing (~3.3 kb over exons II-IV) to determine single or mixed
SERA5 infection status. The patterns of
PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed
infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured
genetic diversity.
PCR was positive in 108 eBL cases and 70 controls. Mixed
SERA5 infection was detected in 41.7% of eBL cases versus 24.3% of controls; the odds ratio (OR) was 2.18, and the 95% confidence interval (CI) was 1.12-4.26, which remained significant in adjusted results (adjusted odds ratio aOR of 2.40, 95% CI of 1.11-5.17). A total of 29 nucleotide variations and 96 haplotypes were identified, but these were unrelated to eBL.
Our results increase the evidence supporting the hypothesis that infection with mixed
infection is increased with eBL and suggest that measuring
genetic diversity may provide new insights into the role of
infection in eBL.
Epstein-Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of
in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both ...infections in the development of eBL by investigating the IgG and IgM profiles against several EBV and
antigens. Serum samples collected in a childhood study in Malawi (2005-2006) from 442 HIV-seronegative children (271 eBL cases and 171 controls) between 1.4 and 15 years old were tested by quantitative suspension array technology against a newly developed multiplex panel combining 4 EBV antigens Z Epstein-Barr replication activator protein (ZEBRA), early antigen-diffuse component (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 subunit (VCA-p18) and 15
antigens selected for their immunogenicity, role in malaria pathogenesis, and presence in different parasite stages. Principal component analyses, multivariate logistic models, and elastic-net regressions were used. As expected, elevated levels of EBV IgG (especially against the lytic antigens ZEBRA, EA-D, and VCA-p18) were strongly associated with eBL high vs low tertile odds ratio (OR) = 8.67, 95% confidence interval (CI) = 4.81-15.64. Higher IgG responses to the merozoite surface protein 3 were observed in children with eBL compared with controls (OR = 1.29, 95% CI = 1.02-1.64), showing an additive interaction with EBV IgGs (OR = 10.6, 95% CI = 5.1-22.2,
= 0.05). Using elastic-net regression models, eBL serological profile was further characterized by lower IgM levels against
preerythrocytic-stage antigen CelTOS and EBV lytic antigen VCA-p18 compared with controls. In a secondary analysis, abdominal Burkitt lymphoma had lower IgM to EBV and higher IgG to EA-D levels than cases with head involvement. Overall, this exploratory study confirmed the strong role of EBV in eBL and identified differential IgG and IgM patterns to erythrocytic vs preerythrocytic
antigens that suggest a more persistent/chronic malaria exposure and a weaker IgM immune response in children with eBL compared with controls. Future studies should continue exploring how the malaria infection status and the immune response to
interact with EBV infection in the development of eBL.
The impact of infection with HIV on the risk of cancer in children is uncertain, particularly for those living in sub-Saharan Africa. In an ongoing study in a paediatric oncology centre in Malawi, ...children (aged </= 15 years) with known or suspected cancers are being recruited and tested for HIV and their mothers or carers interviewed. This study reports findings for children recruited between 2005 and 2008.
Only children with a cancer diagnosis were included. Odds ratios (OR) for being HIV positive were estimated for each cancer type (with adjustment for age (<5 years, >/= 5 years) and sex) using children with other cancers and non-malignant conditions as a comparison group (excluding the known HIV-associated cancers, Kaposi sarcoma and lymphomas, as well as children with other haematological malignancies or with confirmed non-cancer diagnoses).
Of the 586 children recruited, 541 (92%) met the inclusion criteria and 525 (97%) were tested for HIV. Overall HIV seroprevalence was 10%. Infection with HIV was associated with Kaposi sarcoma (29 cases; OR = 93.5, 95% CI 26.9 to 324.4) and with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4, 95% CI 1.1 to 17.9) but not with Burkitt lymphoma (269 cases; OR = 2.2, 95% CI 0.8 to 6.4).
In this study, only Kaposi sarcoma and non-Burkitt, non-Hodgkin lymphoma were associated with HIV infection. The endemic form of Burkitt lymphoma, which is relatively frequent in Malawi, was not significantly associated with HIV. While the relatively small numbers of children with other cancers, together with possible limitations of diagnostic testing may limit our conclusions, the findings may suggest differences in the pathogenesis of HIV-related malignancies in different parts of the world.
To institute and evaluate the benefits of an enhanced recovery after surgery (ERAS) program across three hospitals in Victoria.
We used a before-and-after quality improvement study design consisting ...of three phases: pre-ERAS program data collection from March to September 2012; ERAS training and implementation during September 2012; and change performance measurement following ERAS implementation from October 2012 to May 2013.
The primary end point was duration of hospital stay after knee or hip arthroplasty. Secondary end points were adherence to the ERAS bundle, and process and patient recovery characteristics.
We enrolled 412 patients to the pre-ERAS (existing-practice) phase and compared them with 297 patients in the ERAS phase. For ERAS patients, compared with existing-practice patients, hospital stay was reduced (geometric mean, 5.3 SD, 1.6 v 4.9 SD, 1.6 days; P < 0.001) and there was a significant improvement in the proportion of patients ready for discharge on Day 3 after surgery (41% v 59%; P < 0.001). The most common reason for delayed discharge was patients waiting for review or access to rehabilitation services. There were markedly improved indicators of processes and outcomes of care, including improved patient education, reduced fasting times, less blood loss, better analgesia, earlier ambulation and improved overall quality of recovery.
We found that an ERAS program could be successfully implemented in elective joint arthroplasty, leading to a shorter duration of hospital stay. We recommend this orthopaedic ERAS pathway.
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