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.
Falciparum and endemic Burkitt lymphoma (eBL) are co-endemic in Africa, but the malaria experience in eBL patients is unknown. A lower prevalence of falciparum has been reported in eBL patients, but ...those results are anecdotally attributed to pre-enrollment anti-malaria treatment.
We studied 677 eBL patients and 2920 community controls aged 0-15 years enrolled in six regions in Uganda, Tanzania, and Kenya during 2010-2016. Falciparum was diagnosed using thick blood film microscopy (TFM) and antigen-capture rapid diagnostic tests (RDTs). Guardians of the children answered a 40-item structured questionnaire about their child's pre-enrollment lifetime malaria history and treatment, demographics, socioeconomics, animal exposures, fevers, and hospitalizations. We utilized exploratory factor analysis to reduce the 40 questionnaire variables into six factors, including Inpatient malaria and Outpatient malaria factors that were surrogates of pre-enrollment anti-malaria treatment. The six factors accounted for 83-90% of the variance in the questionnaire data. We calculated odds ratios and 95% confidence intervals (OR 95% CI) of association of eBL with falciparum positivity, defined as positive both on TFM or RDTs, or only RDTs (indicative of recent infection) or TFM (indicative of current falciparum infection) versus no infection, using multivariable logistic regression, controlling for group of age (0-2, 3-5, 6-8, 9-11 and 12-15 years), sex, and study site and the afore-mentioned pre-enrollment factors.
The prevalence of falciparum infection was 25.6% in the eBL cases and 45.7% in community controls (aOR = 0.43, 95% CI: 0.40, 0.47; P < 0.0001). The results were similar for recent falciparum infection (6.9% versus 13.5%, aOR = 0.44, 95% CI: 0.38, 0.50; P < 0.0001) and current falciparum infection (18.7% versus 32.1%, aOR = 0.47, 95% CI: 0.43, 0.51; P < 0.0001). These aORs for any, recent and current falciparum infection did not change when we adjusted for pre-enrollment factors (aORs = 0.46, =0.44, and = 0.51, respectively) were significantly lower in stratified analysis for any infection in children < 5 years (aOR = 0.46; 95% CI: 0.29, 0.75) or ≥ 10 years (aOR = 0.47; 95% CI: 0.32, 0.71).
Our study results reduce support for pre-enrollment antimalaria treatment as a sole explanation for the observed lower falciparum prevalence in eBL cases and open a space to consider alternative immunology-based hypotheses.
The introduction of combination antiretroviral therapy (cART) has led to a significant reduction in Kaposi sarcoma (KS) incidence among people with HIV (PWH). However, it is unclear if incidence has ...declined similarly across key demographic and HIV transmission groups and the annual number of incident and prevalent KS cases remains unquantified.
Using population-based registry linkage data, we evaluated temporal trends in KS incidence using adjusted Poisson regression. Incidence and prevalence estimates were applied to CDC HIV surveillance data, to obtain the number of incident (2008-2015) and prevalent (2015) cases in the United States.
Among PWH, KS rates were elevated 521-fold 95% confidence intervals (CI), 498-536 compared with the general population and declined from 109 per 100,000 person-years in 2000 to 47 per 100,000 person-years in 2015, at an annual percentage change of -6%. Rates declined substantially (
< 0.005) across all demographic and HIV transmission groups. Of the 5,306 new cases estimated between 2008 and 2015, 89% occurred among men who have sex with men. At the end of 2015, 1,904 PWH (0.20%) had been diagnosed with KS in the previous 5 years.
A consistent gradual decline in KS incidence has occurred among PWH in the United States during the current cART era. This decrease is uniform across key demographic and HIV transmission groups, though rates remain elevated relative to the general population.
Continued efforts to control HIV through early cART initiation and retention in care need to be maintained and possibly expanded to sustain declines.
HIV-infected people have increased cancer risk. Lymphoma survivors have an increased risk of certain second primary cancers in the general population, but second cancer risk among HIV-infected people ...is poorly understood. Herein, we characterized the risk of cancers following lymphoid malignancies among HIV-infected people.
Population-based linkage of HIV and cancer registries.
We used data from the US HIV/AIDS Cancer Match Study (1996-2015) and evaluated the risk of first nonlymphoid malignancy in Cox regression models, with first lymphoid malignancy diagnosis as a time-dependent variable.
Among 531 460 HIV-infected people included in our study, 6513 first lymphoid and 18 944 first nonlymphoid malignancies were diagnosed. Risk of nonlymphoid cancer following a lymphoid malignancy was increased overall adjusted hazard ratio (aHR) = 2.7; 95% confidence interval (CI) = 2.3--3.2, and specifically for cancers of the oral cavity (aHR = 2.6; 95% CI = 1.2-5.5), colon (2.4; 1.1-5.0), rectum (3.6; 1.9-6.7), anus (3.6; 2.5-5.1), liver (2.0; 1.2-3.5), lung (1.6; 1.1-2.4), vagina/vulva (6.1; 2.3-16.3), and central nervous system (5.0; 1.6-15.6), Kaposi sarcoma (4.6; 3.4-6.2), and myeloid malignancies (9.7; 6.1-15.4). After additional adjustment for prior AIDS diagnosis and time since HIV diagnosis, aHRs were attenuated overall (aHR = 1.7; 95% CI = 1.5-2.0) and remained significant for cancers of the rectum, anus, and vagina/vulva, Kaposi sarcoma, and myeloid malignancies.
HIV-infected people with lymphoid malignancies have an increased risk of subsequent non-lymphoid cancers. As risks remained significant after adjustment for time since HIV diagnosis and prior AIDS diagnosis, it suggests that immunosuppression may explain some, but not all, of these risks.
Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub‐Saharan African countries, however, few epidemiologic studies have been undertaken and none attempted enrolling cases from ...multiple countries. We therefore conducted a population‐based case–control study of eBL in children aged 0–15 years old in six regions in Northern Uganda, Northern Tanzania and Western Kenya, enrolling 862 suspected cases and 2,934 population controls (response rates 98.5–100%), and processing ~40,000 vials of samples using standardized protocols. Risk factor questionnaires were administered, and malaria period prevalence was measured using rapid diagnostic tests (RDTs). A total of 80.9% of the recruited cases were diagnosed as eBL; 61.4% confirmed by histology. Associations with eBL risk were computed using logistic regression models adjusted for relevant confounders. Associations common in at least two countries were emphasized. eBL risk was decreased with higher maternal income and paternal education and elevated with history of inpatient malaria treatment >12 months before enrollment. Reporting malaria‐attributed fever up to 6 months before enrollment and malaria‐RDT positivity at enrollment were associated with decreased eBL risk. Conversely, reporting exposure to mass malaria suppression programs (e.g., indoor residual insecticide) was associated with elevated risk. HIV seropositivity was associated with elevated eBL risk, but the relative impact was small. The study shows that it is feasible to conduct networked, multisite population‐based studies of eBL in Africa. eBL was inversely associated with socioeconomic status, positively associated with inpatient malaria treatment 12 months ago and with living in areas targeted for malaria suppression, which support a role of malaria in eBL.
What's new?
Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub‐Saharan Africa, but there have been few epidemiologic studies. In this multi‐country analysis, the authors used harmonized protocols to investigate infectious, environmental, and other risk factors for eBL. Socioeconomic status and recent malarial fever were associated with reduced eBL risk, while HIV infection, previous malaria, and living in areas targeted for malaria suppression increased eBL risk. These results provide new baseline data regarding eBL epidemiology, indicating that malaria may play a role. They also confirm the feasibility of multi‐site, population‐based enrolment for crucial future eBL studies.
Purpose
Invasive cervical cancer (ICC) rates have tremendously declined in the United States, yet new cases consistently occur in Maryland and throughout the United States. We hypothesized that ...although rates have generally declined, this decline is uneven across counties and over time.
Methods
Space–time cluster detection analysis was conducted to evaluate clusters of ICC incidence at the county level within Maryland between 2003 and 2012.
Results
The most likely cluster was a cluster of low incidence, which included 6 counties in eastern Maryland for the period 2009–2012. A secondary cluster of low rates, comprising 2 metropolitan counties in northern Maryland, was observed for the period 2009–2012. Two of the three clusters of high ICC rates occurred in 2009–2012 in the large metropolitan area of Baltimore City and another cluster in Frederick County, in rural western Maryland. The third cluster of high rates was observed 2005–2008, in western Maryland.
Conclusion
In recent periods, some Maryland counties have experienced anomalously high or low ICC incidence. Clusters of high incidence are not explained by differences in screening rates and may be due to failures in follow-up care for cervical abnormalities that need to be investigated. Clusters of low incidence may represent areas of successful ICC control.
Introduction: There is a high burden of cervical cancer in Cambodia, yet published data on the prevalence of cervical
dysplasia and the risk factors contributing to the development of pre-cancerous ...lesions in Cambodian women is very
limited. In addition, as it is well known that HIV positivity increases cervical cancer risk, it is important to quantify
the prevalence of cervical dysplasia and carcinoma among Cambodian women living with HIV disease. Methods: A
cross-sectional study was conducted with a sample of 499 HIV+ and 501 HIV- Cambodian women at the Sihanouk
Hospital Center of HOPE. Visual inspection with 5% acetic acid was the method of screening. Colposcopy was performed
on all VIA+ patients, and subsequent treatment followed WHO guidelines. Logistic regression models, stratified by
both HIV+ and HIV- groups, were used to assess significant factors associated with having dysplasia. Results: VIA+
results were prevalent in both the HIV+ and HIV- arms of the study. The HIV+ patients were more likely to have a
lower age at coitarche, lower weight, 2 or more lifetime sexual partners, two or greater pregnancies, or be unmarried.
The estimated prevalence of VIA detected cervical dysplasia was 11% for the entire study sample, 13.4% in the HIV
positive (HIV+) group and 8.6% in the HIV negative (HIV-) group (OR: 1.65; 95% CI: 1.10, 2.48; p=0.01). For the
HIV+ group, having a history of 4 or more full-term pregnancies (OR: 3.42; 95% CI: 1.01-11.64; p=0.049) was found
to be significantly associated with having an increased risk of developing cervical dysplasia in the multivariate model.
Conclusion: Cervical dysplasia is prevalent in both HIV positive and negative Cambodian women and a VIA based
national screening programs need to be developed and expanded to provide access to affordable and effective treatment
for cervical dysplasia and cancers.
Summary
Platelet counts are decreased in Plasmodium falciparum malaria, which is aetiologically linked with endemic Burkitt lymphoma (eBL). However, the pattern of platelet counts in eBL cases is ...unknown. We studied platelet counts in 582 eBL cases and 2 248 controls enrolled in a case‐control study in Uganda, Tanzania and Kenya (2010–2016). Mean platelet counts in controls or eBL cases with or without malaria‐infection in controls versus eBLcases were compared using Student’s t‐test. Odds ratios (ORs) and two‐sided 95% confidence intervals (95% CIs) were estimated using multiple logistic regression, controlling for age, sex, haemoglobin and white blood cell counts. Platelets were decreased with malaria infection in the controls 263 vs. 339 × 109 platelets/l, P < 0·0001; adjusted OR (aOR) = 3·42, 95% CI: 2·79–4·18 and eBL cases (314 vs. 367 × 109 platelets/l, P‐value = 0·002; aOR = 2·36, 95% CI: 1·49–3·73). Unexpectedly, platelets were elevated in eBL cases versus controls in overall analyses (mean: 353 vs. 307 × 109 platelets/l, P < 0·0001; aOR = 1·41; 95% CI: 1·12–1·77), and when restricted to malaria‐positive (mean 314 vs. 263 × 109 platelets/l, P < 0·0001; OR = 2·26; 95% CI: 1·56–3·27) or malaria‐negative (mean 367 vs. 339 × 109 platelets/l, P < 0·001; OR = 1·46; 95% CI: 1·17–1·83) subjects. Platelets were decreased with malaria infection in controls and eBL cases but elevated with eBL.
Objectives
Northern Tanzania experiences significant malaria‐related morbidity and mortality, but accurate data are scarce. We update the data on patterns of low‐grade Plasmodium falciparum malaria ...infection among children in northern Tanzania.
Methods
Plasmodium falciparum malaria prevalence (pfPR) was assessed in a representative sample of 819 children enrolled in 94 villages in northern Tanzania between October 2015 and August 2016, using a complex survey design. Individual‐ and household‐level risk factors for pfPR were elicited using structured questionnaires. pfPR was assessed using rapid diagnostic tests (RDTs) and thick film microscopy (TFM). Associations with pfPR, based on RDT, were assessed using adjusted odds ratios (aOR) and confidence intervals (CI) from weighted survey logistic regression models.
Results
Plasmodium falciparum malaria prevalence (pfPR) was 39.5% (95% CI: 31.5, 47.5) by RDT and 33.4% (26.0, 40.6) by TFM. pfPR by RDT was inversely associated with higher‐education parents, especially mothers (5–7 years of education: aOR 0.55; 95% CI: 0.31, 0.96, senior secondary education: aOR 0.10; 95% CI: 0.02, 0.55), living in a house near the main road (aOR 0.34; 95% CI: 0.15, 0.76), in a larger household (two rooms: aOR 0.40; 95% CI: 0.21, 0.79, more than two rooms OR 0.35; 95% CI: 0.20, 0.62). Keeping a dog near or inside the house was positively associated with pfPR (aOR 2.01; 95% CI: 1.26, 3.21). pfPR was not associated with bed‐net use or indoor residual spraying.
Conclusions
Nearly 40% of children in northern Tanzania had low‐grade malaria antigenaemia. Higher parental education and household metrics but not mosquito bed‐net use were inversely associated with pfPR.
Objectifs
La Tanzanie connaît une morbidité et une mortalité importantes liées au paludisme, mais les données précises sont rares. Nous mettons à jour les données sur les profils en matière d'infection par le paludisme à Plasmodium falciparum de faible grade chez les enfants dans le nord de la Tanzanie.
Méthodes
La prévalence du paludisme à P. falciparum (pfPR) a été évaluée sur un échantillon représentatif de 819 enfants inscrits dans 94 villages dans le nord de la Tanzanie entre octobre 2015 et août 2016, à l'aide d'un plan d'enquête complexe. Des facteurs de risque de pfPR au niveau individuel et au niveau du ménage ont été déterminés à l'aide de questionnaires structurés. La pfPR a été évaluée à l'aide de tests de diagnostic rapides (TDR) et de microscopie à film épais (TFM). Les associations avec la pfPR, sur la base des TDR, ont été évaluées à l'aide des rapports de cotes ajustés (aOR) et des intervalles de confiance (IC) de modèles de régression logistique de surveillances pondérées.
Résultats
La pfPR était de 39,5% (IC95%: 31,5–47,5) avec les TDR et de 33,4% (26,0–40,6) avec la TFM. La pfPR par les TDR était inversement associée aux parents avec un niveau d’éducation plus élevé, en particulier les mères (5‐7 ans d’études: aOR: 0,55; IC95%: 0,31–0,96, enseignement secondaire supérieur: aOR: 0,10; IC95%: 0,02–0,55), vivre dans une maison proche de la route principale (aOR: 0,34; IC95%: 0,15–0,76), dans un ménage plus grand (2 chambres: aOR: 0,40; IC95%: 0,21–0,79, plus de 2 pièces aOR: 0,35; IC95%: 0,20–0,62). Garder un chien près ou à l'intérieur de la maison était positivement associé à la pfPR (aOR: 2,01; IC95%: 1,26–3,21). La pfPR n’était pas associée à l'utilisation de moustiquaire ou à la pulvérisation de résidus à l'intérieur.
Conclusions
Près de 40% des enfants dans nord de la Tanzanie présentaient une antigénémie paludéenne de faible grade. Un niveau d’éducation parentale plus élevé et les indicateurs du ménage, mais pas l'utilisation de moustiquaires, étaient inversement associés à la pfPR.
Background: In spite of the general decline in cervical cancer incidence and the highly preventable nature of this cancer, new cases and deaths are recorded annually in Maryland and in other parts of ...the United States. Using the cancer care continuum and the Human Papillomavirus (HPV) carcinogenesis process as guiding frameworks, this research evaluated the prevention and control of invasive cervical cancer (ICC) among the subgroups at highest risk for disease. Methods: In Aim 1 using registry data we evaluated space-time variation in ICC incidence over a 10-year period at the county level within the state of Maryland. For Aim 2 we longitudinally assessed utilization and determinants of Pap testing among women living with HIV (WLWH) seen at Johns Hopkins Hospital over a 10-year period. Finally, in Aim 3 using data from HIV positive and high-risk HIV negative women enrolled in the Women’s Interagency Health Study (WIHS) cohort, we examined the determinants and risk conferred by prevalent type-specific cervical HPV infections on the acquisition of oral HPV infections. Results: Aim 1- The overall average annual crude and adjusted state ICC rate between 2003-2012 for Maryland was 7.3 per 100,000. Upon adjusting for contextual differences including median income, age and Pap testing rates at the county level, the average annual adjusted ICC incidence rate in Maryland for this period was 9.2 per 100,000. Within this period, 2003-2012, we identified some clusters with significantly different ICC incidence rates than rates observed in the rest of the state. These included both clusters of significantly lower and higher than expected incidence rates (p-value ≤0.05). Two of the 3 significant clusters of higher than expected ICC incidence rates identified occurred in a more recent time period, 2009-2012. The third significant cluster of high rates was observed in an earlier period, 2005-2008. Aim 2- Our findings showed that although most WLWH (79%) in clinical care receive Pap testing, some women (21%) are not screened and others (5%) consistently receive Pap testing at intervals longer than recommended. WLWH with a decreased likelihood of screening included older women, injection drug users, white women and those who had lived for a longer time with HIV. Aim 3- Factors associated with an increased risk of incident oral HPV infection included a recent history of sexual activity with either a male (adjusted hazard (aHR)=2.47, 95%CI: 1.02-6.01) or female partner (aHR=2.79, 95%CI: 1.14, 6.79) as well as a recent history of performing oral sex (aHR=1.75, 95%CI: 1.16, 2.62). No association was observed with type-specific cervical HPV infection, age, alcohol or condom use during oral sex. Conclusions: Although ICC rates have declined over time, there are still some counties experiencing an anomalously high ICC incidence rate. The recent clusters of high ICC incidence rates identified need to be prioritized and investigated further, while the clusters of low incidence rates identified may represent areas of successful prevention and control within the state of Maryland. The determinants of Pap testing identified in Aim 2 present potential targets in an urban HIV care setting for closer monitoring and directed interventions to improve Pap test adherence among WLWH. Findings for Aim3 suggest that having a prevalent cervical HPV infection does not increase the risk of an incident type-specific oral HPV infection; however, sexual activity remains a significant risk factor for acquiring oral HPV infections.
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