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We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

Objectives: This paper describes the development of a physical activity questionnaire (PAQ) designed for Chinese adolescents and their mothers in urban and rural settings, and reports on results of the PAQ, pedometry, and hand grip dynamometry from the Chinese Children and Families Cohort Study pilot investigation (CFCS). Methods: As part of a pilot investigation to evaluate the feasibility to follow-up and obtain detailed nutrition, dietary, physical activity, and ultraviolet radiation (UVR) data from CFCS participants, data were collected in 2013 for 93 adolescent/mother pairs from a rural (n = 41) and an urban site (n = 52) in two provinces. Respondents were asked to wear a pedometer for seven days (Omron HJ-151), use a Takei Digital Grip Strength Dynamometer on (each hand, three trials, two separate days), and complete a 39 item, eight domain PAQ covering the past year. Self-reported physical activity (PA) was linked to metabolic equivalent of task (MET) scores in kcal/kg/hr and used to calculate METs for different domains of PA and intensity categories. Results: Compliance was high (95%) in this measurement protocol administered by health staff during a series of data collection efforts at home and local clinics or health centers. Step counts were highly variable, averaging between 5000 and 10000 per day with somewhat higher step counts in rural adolescent boys. Maximum grip strength (Kgs) was greater in children (Mean = 36.5, SE = 0.8) than mothers (Mean = 28.8, SE = 0.8) and similar in the urban (Mean = 29.6, SE = 0.6) compared to the rural (Mean = 29.6, SE = 0.5) communities overall. Grip strength, step counts, and measures of time spent in different activities or activity intensities were uncorrelated. Conclusion: Device and question-based measurement of PA and strength were readily accepted in these Chinese urban and rural populations. The PAQ on physical activity in the past year produced some plausible population averages, but individual responses suggested recall challenges. If data about specific activities are required, future studies should explore use of standardized survey questions concerning such fewer specific activities or instruments examining shorter time periods such as one, three, or seven day recalls.

Mongolia has the highest incidence of hepatocellular carcinoma (HCC) in the world, but its causative factors and underlying tumor biology remain unknown. Here, we describe molecular characteristics of HCC from 76 Mongolian patients by whole-exome and transcriptome sequencing. We present a comprehensive analysis of mutational signatures, driver genes, and molecular subtypes of Mongolian HCC compared to 373 HCC patients of different races and ethnicities and diverse etiologies. Mongolian HCC consists of prognostic molecular subtypes similar to those found in patients from other areas of Asia, Europe, and North America, as well as other unique subtypes, suggesting the presence of distinct etiologies linked to Mongolian patients. In addition to common driver mutations (TP53, CTNNB1) frequently found in pan-cancer analysis, Mongolian HCC exhibits unique drivers (most notably GTF2IRD2B, PNRC2, and SPTA1), the latter of which is associated with hepatitis D viral infection. These results suggest the existence of new molecular mechanisms at play in Mongolian hepatocarcinogenesis., Mongolia has the highest incidence of—and mortality from—hepatocellular carcinoma (HCC) in the world. Here, the authors examine the genomic and transcriptomic landscape of Mongolian HCC, uncover novel driver mutations, and suggest distinct disease etiologies.

This article reports the study design, methodological issues and early results of a pilot study testing methods for collecting nutrition, physical activity, and ultraviolet (UV) radiation exposure data in a groundbreaking study in China. Epidemiological studies suggest that exposures across the entire life course, including in utero, early childhood, and adolescence, may be important in the etiology of adult cancers and other chronic diseases. The Chinese Children and Families Cohort Study intends to follow-up subjects from the 1993 to 1995 Community Intervention Program of folic acid supplementation for the prevention of neural tube defects. This cohort is unique in that only folic acid exposure during pregnancy varies between groups as other supplements were not available, and there were nutrient deficiencies in the populations. Prior to launching a large-scale follow-up effort, a pilot study was conducted to assess the feasibility of recontacting original study participants to collect extensive diet, physical activity, and UV radiation exposure data in this population. The pilot study included 92 mothers and 184 adolescent children aged 14 to 17 years from 1 urban and 1 rural Community Intervention Program site. Subjects completed a Food Frequency Questionnaire, a 3-day food record, a physical activity questionnaire, a 3-day sun exposure diary together with 3 days of personal UV dosimetry, and 7 days of pedometry measurements and provided blood, saliva, and toenail samples. Grip strength and body composition measurements were taken, and ambient solar UV radiation was monitored in both study sites. While most of the assessments were successful, future studies would likely require different dietary intake instruments. The purpose of this report is to describe the study design and methodological issues emerging from this pilot work relevant for the follow-up of this large birth cohort.

Purpose: Cancer registration is an integral part of national disease surveillance, and actions must be taken to maintain operation of such essential systems, even during concurrent public health emergencies. This abstract summaries the impact of the COVID-19 pandemic on operations of population-based cancer registries (PBCRs) in the Caribbean. Methods: In May 2020, the International Agency for Research on Cancer (IARC) issued a worldwide survey to members of the International Association of Cancer Registries (IACR) to assess the impact of the COVID-19 pandemic on PBCRs. In November, the IARC Caribbean Hub renewed this call for responses from IACR members plus additional Caribbean PBCRs. The experience of ten of thirteen registries contacted is presented. Results: Survey responses were received from PBCRs in the Bahamas, Barbados, Bermuda, Cuba, Dominican Republic, Guyana, Jamaica, Martinique, Puerto Rico, and Trinidad and Tobago. Five (50%) registries reported that the COVID-19 pandemic negatively affected operations. These same registries reported a reduction in data collection capacity ranging from 28% to 100%. Reasons for data collection disruptions included an inability to fully access physical data sources and a reduced capacity or inability to receive cancer notifications and files. Where data collection was impacted, all registries expected missing cancer cases to be registered later in the next 12-15 months. Remote working was one strategy implemented by unaffected registries. One (10%) registry reported an impact on registry financing, and two (20.0%) reported that staffing was affected. Conclusions: Half of responding Caribbean registries reported having been negatively affected by the COVID-19 pandemic, particularly regarding data collection. Improved access to physical data sources for registration activities could mitigate continuing operational challenges in the current pandemic. Accelerating the development of electronic records and direct source abstraction via remote electronic access could support continuous operation of cancer registries amidst future emergencies or operational disruptions. Citation Format: Sarah Quesnel-Crooks, Rachel Hanisch, Isabelle Soerjomataram, Brenda Edwards, Arica White, Betsy Kohler, Ann Chao, Les Mery, Glennis Andall-Brereton. Impact of the COVID-19 Pandemic on Cancer Registry Operations in the Caribbean [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 31.

Background Delays to cancer diagnosis exist, resulting in worse survival outcomes for many cancers. Interventions targeting delays and barriers to cancer diagnosis and treatment have been investigated, but mostly in high-income countries. We conducted a systematic literature review to identify and characterize the interventions studied across cancers, within low- and middle-income countries (LMICs). Methods This systematic review forms part two of a wider study examining solutions to delays and barriers in cancer early diagnosis in LMICs. A comprehensive literature search was conducted on November 27, 2017, encompassing published studies from the preceding 15 years. We extracted study design, population, and intervention, and reported outcome measures from each study. Results were presented by target of interventions (general vs. health care professionals). A narrative synthesis was used to summarize intervention efficacy. Results Of 10,193 abstracts returned, 25 were included, consisting of studies across World Health Organization geographical regions, examining breast, cervix, childhood, prostate, head and neck, and gastric cancers. Altogether, 11 intervention studies targeted the general population, 12 targeted health care professionals, and 2 targeted both. The majority (17/25) of studies reported interventions focusing on patient and diagnosis-related barriers early in the cancer care pathway. Most studies reported knowledge score as primary outcome measure (17/25); few (6/25) reported on clinically relevant measures such as reducing disease stage at presentation or diagnostic time interval. Effectiveness of interventions was demonstrated for some cancers only. Conclusion More interventions reporting clinically relevant measures and using standardized methods and outcomes are required to improve our ability to effectively improve cancer early diagnosis in LMICs. Implications for Practice Prior to this study, the extent of intervention literature in cancer early diagnosis in low- and middle-income countries had not been characterized. This study aimed to outline and characterize interventions across all cancer types and across all countries. This systematic review demonstrated that interventions have been investigated targeting both the general population and health care professionals. Furthermore, this review demonstrates that the majority of studies report knowledge as an outcome measure, rather than clinically significant measures that improve cancer-related outcomes, such as delay intervals or downstaging of disease. Future interventions should address clinically relevant measures to better assess efficacy of interventions.

Background Few studies in China have examined personal ultraviolet radiation (UVR) exposure using polysulfone dosimetry. Methods In this study, 93 mother and adolescent child pairs (N = 186) from two locations in China, one rural (higher latitude) and one urban (lower latitude), completed 3 days of personal UVR dosimetry and a sun/clothing diary, as part of a larger pilot study. Results The average daily ambient UVR in each location as measured by dosimetry was 20.24 Minimal Erythemal Doses (MED) in the rural location and 20.53 MED in the urban location. Rural mothers had more average daily time outdoors than urban mothers (5.5 h, compared with 1.5 h, in urban mothers) and a much higher daily average personal UVR exposure (4.50 MED, compared with 0.78 MED in urban mothers). Amongst adolescents, rural males had the highest average daily personal UVR exposure, followed by rural females, urban females and urban males (average 2.16, 1.05, 0.81, and 0.48 MED, respectively). Conclusions Although based on small numbers, our findings show the importance of geographic location, age, work/school responsibilities, and sex of the adolescents in determining personal UVR exposure in China. These results suggest that latitude of residence may not be a good proxy for personal UVR exposure in all circumstances.

This review outlines causes of delays in diagnosis and barriers to early diagnosis of cancer in patients in low‐ and middle‐income countries., Background. Advanced stage presentation of patients with is common in low‐ and middle‐income countries (LMICs). A comprehensive analysis of existing delays and barriers in LMICs has not been previously reported. We conducted a systematic literature review to comprehensively outline delays and barriers to identify targets for future interventions and provide recommendations for future research in this field. Materials and Methods. Multiple electronic databases were searched using a standardized search strategy. Eligible articles were of any language, from LMICs, and published between January 1, 2002, and November 27, 2017. Included studies reported cancer care intervals or barriers encountered. Intervals and associated barriers were summarized by cancer type and geographical region. Results. This review included 316 study populations from 57 LMICs: 142 (44.9%) studies addressed time intervals, whereas 214 (67.7%) studies described barriers to cancer diagnosis. The median intervals were similar in the following three stages of early diagnosis: (a) access (1.2 months), (b) diagnostic (0.9 months), and (c) treatment (0.8 months). Studies from low‐income countries had significantly longer access intervals (median, 6.5 months) compared with other country income groups. Patients with breast cancer had longer delay intervals than patients with childhood cancer. No significant variation existed between geographic regions. Low health literacy was reported most frequently in studies describing barriers to cancer diagnosis and was associated with lower education level, no formal employment, lower income, and rural residence. Conclusion. Early diagnosis strategies should address barriers during all three intervals contributing to late presentation in LMICs. Standardization in studying and reporting delay intervals in LMICs is needed to monitor progress and facilitate comparisons across settings. Implications for Practice. This review draws the attention of cancer implementation scientists globally. The findings highlight the significant delays that occur throughout the cancer care continuum in low‐ and middle‐income countries and describe common barriers that cause them. This review will help shape the global research agenda by proposing metrics and implementation studies. By demonstrating the importance of standardized reporting metrics, this report sets forth additional research and evidence needed to inform cancer control policies.

Population–based cancer registries (PBCR) are vital to the assessment of the cancer burden and in monitoring and evaluating national progress in cervical cancer surveillance and control. Yet the level of their development in countries exhibiting the highest cervical cancer incidence rates is suboptimal, and requires considerable investment if they are to document the impact of WHO global initiative to eliminate cervical cancer as a public health problem. As a starting point we propose a comprehensive cancer surveillance framework, positioning PBCR in relation to other health information systems that are required across the cancer control continuum. The key concepts of PBCR are revisited and their role in providing a situation analysis of the scale and profile of the cancer-specific incidence and survival, and their evolution over time is illustrated with specific examples. Linking cervical cancer data to screening and immunization information systems enables the development of a comprehensive set of measures capable of assessing the short- and long-term achievements and impact of the initiative. Such data form the basis of national and global estimates of the cancer burden and permit comparisons across countries, facilitating decision-making or triggering cancer control action. The initiation and sustainable development of PBCR must be an early step in the scale-up of cervical cancer control activities as a means to ensure progress is successfully monitored and appraised., Highlights • Cancer registries play a critical role in the Cervical Cancer Elimination Initiative. • A framework facilitates understanding surveillance and monitoring for cancer control. • Cancer registries provide short and long term indicators for cervical cancer control. • There is great need to develop and sustain cancer registries in many countries.

On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the Study of Lung Cancer, and the agenda was designed with significant input from staff at the U.S. National Cancer Institute and National Institute of Environmental Health Sciences. A multidisciplinary group of participants presented updates reflecting a range of disciplinary perspectives, including mineralogy, geology, epidemiology, toxicology, biochemistry, molecular biology, genetics, public health, and clinical oncology. The group identified knowledge gaps that are barriers to preventing and treating malignant mesothelioma (MM) and the required next steps to address barriers. This manuscript reports the group's efforts and focus on strategies to limit risk to the population and reduce the incidence of MM. Four main topics were explored: genetic risk, environmental exposure, biomarkers, and clinical interventions. Genetics plays a critical role in MM when the disease occurs in carriers of germline BRCA1 associated protein 1 mutations. Moreover, it appears likely that, in addition to BRCA1 associated protein 1, other yet unknown genetic variants may also influence the individual risk for development of MM, especially after exposure to asbestos and related mineral fibers. MM is an almost entirely preventable malignancy as it is most often caused by exposure to commercial asbestos or mineral fibers with asbestos-like health effects, such as erionite. In the past in North America and in Europe, the most prominent source of exposure was related to occupation. Present regulations have reduced occupational exposure in these countries; however, some people continue to be exposed to previously installed asbestos in older construction and other settings. Moreover, an increasing number of people are being exposed in rural areas that contain noncommercial asbestos, erionite, and other mineral fibers in soil or rock (termed naturally occurring asbestos [NOA]) and are being developed. Public health authorities, scientists, residents, and other affected groups must work together in the areas where exposure to asbestos, including NOA, has been documented in the environment to mitigate or reduce this exposure. Although a blood biomarker validated to be effective for use in screening and identifying MM at an early stage in asbestos/NOA-exposed populations is not currently available, novel biomarkers presented at the meeting, such as high mobility group box 1 and fibulin-3, are promising. There was general agreement that current treatment for MM, which is based on surgery and standard chemotherapy, has a modest effect on the overall survival (OS), which remains dismal. Additionally, although much needed novel therapeutic approaches for MM are being developed and explored in clinical trials, there is a critical need to invest in prevention research, in which there is a great opportunity to reduce the incidence and mortality from MM. © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Mongolia has the highest incidence of-and mortality from- hepatocellular carcinoma (HCC) in the world, which is between three and seven times higher than that observed in other high-incidence populations, such as South Korea, Thailand, and China. In Mongolia, where cancer is the second most common cause of death accounting for nearly a fifth of deaths, HCC is the most prevalent cancer type at about 40% of all cancers. Despite the daunting proportion of this longstanding health crisis, the molecular landscape of Mongolian HCC has not been studied yet. Filling this gap, we aim to identify robust molecular subclasses and driver features informative of the etiology and progression of the disease. Here, we describe molecular characteristics of 76 Mongolian HCC patients by whole-exome and whole-transcriptome sequencing. We present a comprehensive comparison of mutational signatures, driver genes and molecular subtypes of Mongolian HCC versus 373 HCC patients of different ethnicities and diverse etiologies. Mongolian HCC consists of several similar prognostic molecular subtypes in patients from other areas of Asia, Europe and North America as well as several unique types, suggesting potentially the presence of unique etiologies linked to Mongolian patients. Consistently, Mongolian HCC exhibits several common driver mutations (TP53, CTNNB1) frequently found in pan-cancer analyses but also a unique driver (SPTA1) that may be linked to hepatitis D viral infection. Furthermore, unique hotspot missense mutations were identified in driver genes GTF2IRD2B and PNRC2. These results indicate the existence of novel molecular mechanisms at play in Mongolian hepatocarcinogenesis. Citation Format: Julián Candia, Enkhjargal Bayarsaikhan, Mayank Tandon, Anuradha Budhu, Marshonna Forgues, Justin Lack, Ann Chao, Jigjidsuren Chinburen, Xin W. Wang. The genomic landscape of Mongolian hepatocellular carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5855.

ObjectiveTo determine the feasibility of long-term prospective follow-up and ascertainment of cancer in offspring and mothers from the 1993–1995 Chinese Community Intervention Program that provided folic acid supplements before and during early pregnancy to reduce neural tube defects.DesignFeasibility pilot study for a prospective cohort study.SettingFamilies residing during 2012–2013 in one rural and one urban county from 21 counties in 3 provinces in China included in the Community Intervention Program campaign.ParticipantsThe feasibility study targeted 560 families, including 280 from the rural and 280 from the urban county included in the large original study; about half of mothers in each group had taken and half had not taken folic acid supplements.InterventionThe planned new study is observational.Primary and secondary outcome measuresPrimary: incidence of paediatric cancers in offspring; secondary: other chronic diseases in offspring and chronic diseases in mothersResultsOnly 3.4% of pilot study families could not be found, 3.9% had moved out of the study area and 8.8% refused to participate. Interviews were completed by 82% of mothers, 79% of fathers and 83% of offspring in the 560 families. Almost all mothers and offspring who were interviewed also participated in anthropometric measurements. We found notable urban–rural differences in sociodemographic and lifestyle characteristics of the parents, but fewer differences among the offspring. In eight catchment area hospitals, we identified a broad range of paediatric cancers diagnosed during 1994–2013, although paediatric brain tumours, lymphomas and rarer cancers were likely under-represented.ConclusionsOverall, 20 years after the original Community Intervention Program, the pilot study achieved high levels of follow-up and family member interview participation, and identified substantial numbers of paediatric malignancies during 1994–2013 in catchment area hospitals. Next steps and strategies for overcoming limitations are described.

The incidence and mortality rate of colorectal cancer (CRC) have increased dramatically over the past 3 decades in China due to changes in lifestyle factors. Early detection and treatment guidelines for asymptomatic cases have shown to improve CRC control in developed countries. In response to these challenges, the Shanghai Municipal Government launched a community-based CRC screening program in 2012.Free initial screening, inclusive of immunochemical fecal occult blood and risk assessment (questionnaire), was provided by community health centers in Shanghai. Participants with positive results were referred to a specialist for a colonoscopy.In 2013, 828,302 Shanghai residents were registered; 97.7% (809,528) of the registrants completed initial screening. Among 180,094 initial screening-positive participants, 71,733 underwent colonoscopy. The proportion of compliance to colonoscopy was 39.8%; the proportion decreased with age and educational level. A total of 6,668 adenomas were detected, and 1,630 CRC cases were diagnosed. The CRC detection rate of the program was 201.35/100,000; among the detected CRCs, 51.6% were in stage 0-I.The screening program achieved great progress, especially on initial screening completion and CRC early stage rate, although particular intervention is still needed to improve the compliance of colonoscopy.Due to socioeconomic transitions and lifestyle changes, colorectal cancer is now becoming one of the most common cancers in developing countries, as it is in developed countries. While most developed countries have now initiated national colorectal cancer screening programs based on recommended country-specific colorectal cancer screening guidelines, colonoscopy has become the most commonly used screening method. This is a challenge in developing countries due to limited resources. Based on the analysis of the Shanghai colorectal cancer screening program, with immunological fecal occult blood test and risk assessment as initial screening, followed by a diagnostic testing of colonoscopy for individuals with positive results, this article provides the basis and suggestion for similar program in other regions of China and other developing countries.

Background The aim of the study was to characterize the histological and epidemiological features of lung cancer in Chinese women. Methods Demographic and histological information on female lung cancer cases identified during 1 January 2000 through 31 December 2012 from the Cancer Hospital of the Chinese Academy of Medical Sciences were collected. The International Classification of Diseases for Oncology system was used to classify the histological subtypes. Relative frequencies (RF) were estimated for major histological subtypes and compared by the years of diagnosis and birth, and among residential areas. Statistical differences were tested for RFs in the time periods with a trend test and with Pearson Chi square tests for distribution. Results Of 7070 female Chinese lung cancer cases, the major histological subtypes were adenocarcinoma (ADC) 65.79%; squamous cell carcinoma (SCC) 10.21%; small cell cancer 8.12%; large cell carcinoma, 2.79%; and adeno-squamous carcinoma (ASC), 2.19%. ADC increased, with RFs from 46.72% in the cases identified in 2000–2002 to 76.49% in 2011–2012 (Z = 16.998, P < 0.0001); SCC decreased from 15.69% to 5.97% (Z = −8.750, P < 0.0001). Compared to the cases identified in 2000–2006, the age-adjusted RFs of ADC in 2007–2012 consistently increased in all study areas. Conclusion The significant increase of ADC of the lung in Chinese women suggests that a persistently strong exposure to potential carcinogens in the Chinese population should be further and fully investigated.

BACKGROUND Questions remain about the effectiveness, dose, and timing of folic acid in preventing orofacial clefts. Case-control studies report conflicting results. There have been no cohort studies of orofacial clefts and the use of folic acid without other vitamins. METHODS In a prospective cohort of 240,244 women enrolled between 1993 and 1995 in 1 northern and 2 southern provinces in China, we examined the risk of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP) in relation to maternal use of 400 μg of folic acid without other vitamins. RESULTS Daily use of 400 μg of folic acid without other vitamins, started before the last menstrual period (LMP), was associated with reduced risk of CL/P with adjusted rate ratio (aRR) of 0.69 (95% confidence interval = 0.55-0.87). The greatest reduction in risk was observed in the north among daily users who began taking folic acid pills before LMP (aRR = 0.21 [0.10-0.44]); in the south there was marginal reduction in risk (aRR = 0.81 [0.63-1.05]). No evidence of reduced CL/P risk was observed among women who started folic acid pills on or after their LMP. No persuasive evidence for reduction in CP risk was seen with folic acid pill use at any time. CONCLUSION Daily maternal consumption of 400 μg of folic acid without other vitamins, started before mother's LMP, was associated with a reduced risk of CL/P in babies born in a high-prevalence region of China.

Background More insight is needed regarding risk factors for prevalent and incident HIV-1 infection among male farm workers in Sub-Saharan Africa to control the HIV-1 epidemic. Methods Male farm workers were recruited from a sugar estate in Zambia to participate in a prospective cohort study. Questionnaire data were collected via interview, and testing was conducted for HIV-1, herpes simplex virus type 2 (HSV-2), and syphilis infection at baseline and follow-up between May 2006 and September 2007. Results Among 1062 workers enrolled, HIV-1 prevalence at baseline was 20.7%. Testing HSV-2 seropositive (adjusted odds ratio (AOR) 5.4, 95% CI 3.6 to 8.1), self-reported genital ulcers in the past year (AOR 2.8, 95% CI 1.9 to 4.2), and being widowed (AOR 3.7, 95% CI 2.0 to 6.9) were significantly associated with prevalent HIV-1 infection. The HIV-1 incidence among 731 initially negative participants with at least one follow-up visit was 4.1 per 1000 person-months (95% CI 2.6 to 5.7); seroconversion was independently associated with prevalent HSV-2 infection (adjusted hazard ratio (AHR) 2.4, 95% CI 1.0 to 5.8) and incident HSV-2 infection (AHR 18.0, 95% CI 4.2 to 76.3). HIV-1 prevalence and incidence rates were similar among migrant and non-migrant workers. Conclusions HIV-1 prevalence and incidence were high, and HSV-2 infection was a risk factor for HIV-1 acquisition. There is an urgent need to expand HIV-1 prevention programmes tailored to farm workers and their communities.

The epidemic of human immunodeficiency virus in Zambia has led to a dramatic rise in the incidence of human herpesvirus-8 (HHV-8)-associated Kaposi's sarcoma in both adults and children. However, there is a paucity of knowledge about the routes of HHV-8 transmission to young children. The Zambia Children's KS-HHV8 Study, a large, prospective cohort study in Lusaka, Zambia, was launched in 2004 to investigate the role of household members as a source of HHV-8 infection in young children and social behaviors that may modify the risk of HHV-8 acquisition. This cohort is distinct from other epidemiologic studies designed to investigate HHV-8 incidence and transmission because it recruited and followed complete households in the urban central African context. Between July 2004 and March 2007, 1,600 households were screened; 368 households comprising 464 children and 1,335 caregivers and household members were enrolled. Follow-up of this population continued for 48 months postrecruitment, affording a unique opportunity to study horizontal transmission of HHV-8 and understand the routes and sources of transmission to young children in Zambia. The authors describe the study rationale, design, execution, and characteristics of this cohort, which provides critical data on the epidemiology and transmission of HHV-8 to young children in Zambia.

Three new coordination polymers with angular bis(1-tetrazol)diphenyl ligands as bridges, {[Ag(L1)2](NO3) ⋅ 2H2O}∞ [L1 = 4,4'-bis(1-tetrazolyl)diphenyl methane], 1, [Ag(L2)2(NO3)]∞ [L2 = 4,4'-bis(1-tetrazolyl)diphenyl sulfone], 2, and [CuBr(L3)0.5]∞ [L3 = 4,4'-bis(1-tetrazolyl)diphenyl ether], 3, are reported, which show unique 2D structural types. Complex 1 forms 1D double-stranded helical chains where the cavities are threaded by linear hydrogen bondings formed by the co-crystallized water molecules and nitrate anions and complex 2 shows 2D grids involving M4L4 64-membered metallocycles composed of helical chains, while complex 3 exhibits a 2D pleated net comprising 1D channels linked by the double-chain CuBr ribbons.

The implementation of disease-specific research or service programs may have an ancillary beneficial or harmful impact on routine clinical services. We reviewed the records of 5801 first visits to 22 antenatal clinics from 1997 to 2004 in Lusaka Zambia and examined documented syphilis rapid plasma reagin (RPR) screening and syphilis treatment before and after implementation of research and/or service programs in prevention of mother-to-child (PMTCT) HIV transmission. Compared with before PMTCT program implementation the prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for documented RPR screening were 0.9 (0.7 to 1.1) after implementation of research 0.7 (0.6 to 0.8) after service and 2.5 (2.1 to 3.0) after research and service programs. Documented RPR screening was improved after implementation of PMTCT research and service were operating simultaneously and not with research or service alone. Health policy makers and researchers should plan explicitly for how the targeted HIV programs service and/or research can have a broader primary care impact. (authors)

This chapter is addressed primarily to potential funders of health research at the national, provincial, and state levels. Health research in general, and cancer research in particular, is not a luxury reserved for high-income countries (HICs); it is a necessity for all countries across the income spectrum. The extent and depth of that research may vary by a country’s financial situation, and the topics may vary by a country’s specific burden of cancers and associated risk factors. Nevertheless, a comprehensive health research plan is foundational to the ability to allocate resources efficiently and effectively, develop human capacity and infrastructure, and identify the appropriate technologies and medicines for health and health services delivery. In short, robust research is essential to building evidence-based cancer prevention and control programs.In recognition of the foundational nature of research, ministers and representatives of ministries of health, science and technology, agriculture, education, foreign affairs, and international cooperation from 53 countries convened in 2008 in Mali at the Bamako Global Ministerial Forum on Research in Health. Of the 53 participating countries, 38 were low- and middle-income countries (LMICs), according to World Bank criteria. The group issued its Call to Action, which articulates the rationale for supporting research to inform public policy, and sent the Call to Action to the World Health Organization (WHO 2008). The Call to Action recommends that national governments allocate at least 2 percent of the budgets of ministries of health to research and that international development agencies invest at least 5 percent of development assistance funds earmarked for the health sector in research. Box 15.1 highlights many of the principles applicable to cancer research.Subsequent white papers and policy statements have made clear the importance of research on noncommunicable diseases and cancer to guide public policy and public investment (See Annotated Select Bibliography).

Cancer surveillance is a fundamental component of national or sub-national cancer control planning and research. Cancer incidence and mortality data allow countries to monitor change in cancer incidence, mortality, and survival over time, by geographic region, and by demographic characteristics. Such data provide important clues to form hypotheses for cancer etiologic research, including research to examine environmental contributions to cancer. Strengthening cancer surveillance systems is urgently needed to conduct high quality research in environmental pollution and cancer in many countries. The United States National Cancer Institute Center for Global Health organized the first symposium on Environmental Contributions to Cancer during the 16th International Conference of Pacific Basin Consortium (PBC) for Environment and Health. PBC provided an important forum for dialog to establish partnerships and collaborations among researchers of environmental pollution and cancer.

Previous epidemiologic studies have suggested that intake of red meat may be associated with increased risk of prostate cancer. Few studies, however, have examined these associations by race. We examined intake of red meat, processed meat, and poultry in relation to incident prostate cancer among Black and White men in the Cancer Prevention Study II Nutrition Cohort. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle in 1992 to 1993. After excluding men with a history of cancer and incomplete dietary information, 692 Black and 64,856 White men were included in the cohort. During follow-up through August 31, 2001, we documented 85 and 5,028 cases of incident prostate cancer among Black and White men, respectively. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI). No measure of meat consumption was associated with risk of prostate cancer among White men. Among Black men, total red meat intake (processed plus unprocessed red meat) was associated with higher risk of prostate cancer (RR, 2.0; 95% CI, 1.0-4.2 for highest versus lowest quartile; Ptrend = 0.05); this increase in risk was mainly due to risk associated with consumption of cooked processed meats (sausages, bacon, and hot dogs; RR, 2.7; 95% CI, 1.3-5.3 for highest versus lowest quartile; Ptrend = 0.008). This study suggests that high consumption of cooked processed meats may contribute to prostate cancer risk among Black men in the United States.(Cancer Epidemiol Biomarkers Prev 2006;15(2):211–6)

Physical activity has consistently been associated with lower risk of colon cancer, but information is limited on the amount, type, and timing of activities. The relationship between physical activity and rectal cancer is unclear. We examined characteristics of recreational physical activity in relation to colon and rectal cancer in the Cancer Prevention Study II Nutrition Cohort of 70,403 men and 80,771 women (median age, 63 years); 940 colon and 390 rectal cancers were identified from enrollment in 1992 to 1993 through August 1999. The multivariate-adjusted rate ratios (95% confidence intervals) associated with any recreational physical activity compared with none were 0.87 (0.71-1.06) for colon cancer and 0.70 (0.53-0.93) for rectal cancer. Colon cancer risk decreased significantly with increasing total hours (P for trend without reference group = 0.007) and metabolic equivalent hours (P for trend = 0.006) per week of activities. No clear decrease in rectal cancer risk was seen with increasing hours per week of physical activity. Rate ratios (95% confidence intervals) were 0.72 (0.52-0.98) for

Objectives. We examined the prevalence of endoscopy (sigmoidoscopy or colonoscopy) by indication and by demographic and lifestyle factors. Methods. We analyzed cross-sectional data collected in 1997 from participants aged 50 years and older in the Cancer Prevention Study (CPS) II Nutrition Cohort. Results. Fifty-eight percent of men and 51% of women reported ever having undergone endoscopy; only 42% of men and 31% of women reported endoscopy for screening rather than for disease diagnosis or follow-up. Prevalence varied by demographic and lifestyle factors. Conclusions. Efforts to increase colorectal cancer screening need to target women, all persons aged 50–64 years, and those with colorectal cancer risk factors. Future studies should distinguish endoscopy for screening from procedures for disease diagnosis and follow-up to avoid overestimating screening compliance.

Objective: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. Methods: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1992–93. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models. Results: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.67–1.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.49–0.96 for ≥500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.51–0.98, p trend = 0.02). Dairy product intake was not related to overall risk. Conclusions: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men.

Linxian, China, is a region with high incidence of esophageal cancer and a history of poor nutritional status. Nutrition Intervention Trials were conducted in this area from 1985 through 1991 and found a reduction in total cancer mortality in the group receiving supplementation of beta-carotene/selenium/alpha-tocopherol. The positive results of those trials have, in part, been ascribed to the poor nutritional status of this population. To investigate more recent food patterns, nutrient intakes, and seasonal variations in the diet, dietary surveys were conducted among the residents of Linxian in 1996. Food consumption data were collected among 104 households in spring and 106 households in autumn using a method of food inventory changes. Intake of nutrients was estimated and compared to the Chinese Recommended Dietary Allowance (RDA). In both seasons, the five most common food groups consumed were cereals, fresh vegetables, yams, seasonings, and eggs. Low nutrient intakes were found for selenium (79% RDA and 66% RDA), zinc (72% RDA and 62% RDA), vitamin B2 (64% RDA and 52% RDA), and calcium (53% RDA and 39% RDA) in both spring and autumn. A large seasonal variation was seen in the consumption of leafy vegetables, root vegetables and eggs, all of which might have contributed to the lower intake of vitamin A (25% RDA), vitamin C (75% RDA), protein (76% RDA), and vitamin E (78% RDA) in autumn. These indicate that the nutrient intake in Linxian is inadequate for a number of vitamins and minerals including those shown to be associated with esophageal cancer.

Introduction. Cervical cancer is one of the most commonly diagnosed cancers among women in China. The World Health Organization (WHO) recommends routine screening for cervical cancer, and the WHO Global Monitoring Framework suggests that every nation monitors cervical cancer screening. However, little information is available on cervical cancer screening behavior among women in China. Methods. We used data from the 2010 China Chronic Disease and Risk Factor Surveillance System that included 51,989 women aged 18 years and older. We report the proportion of women who reported ever having had a Papanicolaou (Pap) test, stratified by sociodemographic characteristics and geographic region. Multivariable logistic regression modeling was performed to adjust for potential confounders. Results. Overall, 21% of 51,989 women reported having ever had a Pap test. The highest proportion was reported among women aged 30–39 years (30.1%, 95% confidence interval, 26.8%–33.4%). In all geographic regions, women in rural areas were consistently less likely than women in urban areas to report having had a Pap test. Among women who reported ever having a Pap test, 82% reported having the most recent test in the past 3 years. Factors associated with reporting ever having a test were being aged 30–49 years, higher education, being married, and having urban health insurance. Conclusion. Our results indicate that screening programs need to be strengthened along with a more intense focus on specific demographic groups. National cervical cancer screening guidelines and comprehensive implementation strategies are needed to make screening services available and accessible to all women. Implications for Practice: This study is the largest nationwide and population-based assessment of self-reported history of Pap test for cervical cancer screening in China. This article describes cervical cancer screening behavior among women and examines key demographic and geographic factors. Only one fifth of Chinese women reported having ever had a Pap test for cervical cancer screening. The results highlight the urgent need to develop national cervical cancer screening guidelines and strategies that make screening services widely available, accessible, and acceptable to all women, especially to those who reside in rural areas and those with no health insurance.

Objective: Multivitamins contain several nutrients, including folic acid, which are hypothesized to reduce colon cancer risk. Previous epidemiologic studies have suggested that effects of multivitamins containing substantial amounts of folic acid (introduced in 1973) may not be evident until 15 or more years since first use. Methods: We examined the association between daily multivitamin use and colon cancer mortality among 806,397 US men and women in the Cancer Prevention Study II cohort who completed a questionnaire at enrollment in 1982 and were followed for mortality through 1998. Results: After multivariate adjustment, multivitamin use at enrollment showed little association with colon cancer mortality. After 15 years since first use of a multivitamin potentially containing folic acid, we observed slightly decreased risk of colon cancer mortality (rate ratio (RR) = 0.89, 95% confidence interval (CI) 0.80–0.99). Consistent with previous reports, this association was stronger among participants consuming two or more alcoholic drinks per day (RR = 0.71, 95% CI 0.56–0.91). Conclusion: Our results are consistent with a modest reduction in colon cancer mortality associated with use of folic acid-containing multivitamins among moderate to heavy alcohol users.

Background: Recent studies suggest that long-term cigarette smoking is associated with an increased risk of colorectal cancer. Whether the association is causal or due to confounding remains unclear. Methods: We examined cigarette smoking in relation to colorectal cancer mortality, evaluating smoking duration and recency and controlling for potential confounders in the Cancer Prevention Study II. This prospective nationwide mortality study of 1 184 657 adults (age ≥30 years) was begun by the American Cancer Society in 1982. After exclusions, our analytic cohort included 312 332 men and 469 019 women, among whom 4432 colon or rectal cancer deaths occurred between 1982 and 1996 among individuals who were cancer free in 1982. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazards models. All statistical tests were two-sided. Results: Multivariate-adjusted colorectal cancer mortality rates were highest among current smokers, were intermediate among former smokers, and were lowest in lifelong nonsmokers. The multivariate-adjusted RR (95% CI) for current compared with never smokers was 1.32 (1.16– 1.49) among men and 1.41 (1.26–1.58) among women. Increased risk was evident after 20 or more years of smoking for men and women combined as compared with never smokers. Risk among current and former smokers increased with duration of smoking and average number of cigarettes smoked per day; risk in former smokers decreased significantly with years since quitting. If the multivariate-adjusted RR estimates in this study do, in fact, reflect causality, then approximately 12% of colorectal cancer deaths among both men and women in the general U.S. population in 1997 were attributable to smoking. Conclusions: Long-term cigarette smoking is associated with increased risk of colorectal cancer mortality in both men and women. Clear reduction in risk is observed with early smoking cessation. [J Natl Cancer Inst 2000;92:1888–96]

Objectives: This study evaluates time trends in colon and rectal cancer incidence and mortality among the three major race/ethnic groups (Hispanics, American Indians, and non-Hispanic Whites) in New Mexico (United States). Methods: We used data from the New Mexico Tumor Registry (NMTR) and computed average annual age-standardized incidence and mortality rates. Colon cancer incidence rates were further examined by anatomical subsite. Estimated annual percent change (EAPC) in incidence and mortality over time were computed using Poisson regression. Results: Invasive colorectal cancer incidence rates increased from 1969-89 in all three race/ethnic groups, but decreased among non-Hispanic Whites in 1990-94, while rates continued to increase among minority populations, especially among minority men. Over the 26-year period, EAPC in colon cancer incidence among men was 3.6 percent for Hispanics, 4.7 percent for American Indians, and 0.7 percent for non-Hispanic Whites. Right-sided colon cancers were more common among American Indian women, and among all women aged 65 years and older. Mortality rates decreased steadily among non-Hispanic Whites over the study period, especially among women. Conclusions: Studies are needed to identify important modifiable risk factors and to develop strategies to increase the use of colorectal cancer screening-procedures among the minority populations.

The conduct of public health surveillance and epidemiologic investigations would be enhanced by a cost-effective method for the collection of population-based cancer risk-factor data. We assessed the feasibility of ascertaining such data from hospital medical records during routine abstraction of information from a cancer registry. We examined the medical records of a representative sample of prostate and lung cancer cases diagnosed during 1992 and 1993 from the New Mexico (United States) Tumor Registry (NMTR) database. Registry personnel abstracted ancillary information from the medical records of 575 prostate and 273 lung cancer cases. Of medical records from 848 cases, 90 percent documented a history of tobacco use, 77 percent contained any family medical history, and 48 percent documented occupational information sufficient to allow coding into standard occupational groups. Availability of occupation and industry varied by patient ethnicity, age at diagnosis, marital status, and type of hospital, indicating the potential for bias in studies using occupational information from medical records. Our findings suggest that risk factor information abstracted from medical records may provide valuable information for public health surveillance, but is generally too incomplete to serve as a single source of exposure information for etiologic studies. Family histories in medical records may be sufficient for population-based ascertainment of affected relative pairs for genetic epidemiology studies for some cancer types.

To characterize the histological and epidemiological features of male lung cancer patients in China.The demographic and histological information about male lung cancer patients identified from 2000-01-01 to 2012-12-31, was collected from the Cancer Hospital of the Chinese Academy of Medical Sciences. Relative frequencies (RF) were estimated for major histological subtypes and compared according to the years of diagnosis and birth.The RF of adenocarcinoma (ADC) increased from 21.96% to 43.36% and the RF of squamous cell carcinoma (SCC) decreased from 39.11% to 32.23% from 2000 to 2012 in the 15 427 male lung cancer patients included in this study (Z=17.909, P0.0001; Z=-6.117, P0.0001). The RF of ADC increased from 28.72% in 2000-2004, 36.88% in 2005-2008 to 48.61% in 2009-2012 in patients born after 1960. The age-adjusted RF of ADC in 2007-2012 increased consistently in all the investigated areas.The increased RF of ADC in male lung cancer patients highlights the need for further investigation of the etiologic factors of these tumors. Smoke-free policies rather than modifying tobacco products should be enforced.

Although group A meningococcal disease is a major cause of child morbidity and mortality in sub-Saharan Africa, little is known about vitamin A status and T-cell subpopulations in affected children. A prospective study of vitamin A levels and T-cell subpopulations was conducted in 41 children hospitalized for meningococcal meningitis in Butare, Rwanda, during an epidemic from September through November, 1992. The mean age of cases was 3.6 +/- 2.7 years (range 0.5-16 years). The case-fatality rate was 20 per cent; 73 per cent of the children had serum vitamin A levels consistent with subclinical deficiency (< 0.7 mumol/l), and 27 per cent had levels consistent with severe deficiency (< 0.35 mumol/l). Mean CD4 per cent was higher and CD8 per cent was lower among children with meningitis compared with known reference populations. These results suggest that meningococcal disease is characterized by T-cell subpopulation alterations and vitamin A deficiency.

The authors evaluated the diagnostic utility and prognostic value of immune-complex-dissociated (ICD) HIV-1 p24 antigen detection in a prospective cohort study of perinatally acquired HIV-1 infection in Butare Rwanda. HIV-1 p24 antigen was measured after acid dissociation in plasma samples collected at 6 weeks and 3 months of age from 36 HIV-1 infected and 80 uninfected children born to HIV-1 infected women. Among children with persistent HIV-1 antibody after 12 months of age 26.7% of samples tested ICD HIV-1 p24 antigen positive. Among children who died between 3 and 12 months of age but were classified as HIV-1 infected 17.6% tested p24 antigen positive at 6 weeks of age and 33.3% at 3 months of age. Female infants were more likely to test p24 antigen positive than male infants (p = 0.046). The specificity of the assay was 96.8%. Cumulative probabilities of child survival to 36 months of age were computed by HIV-1 status of the child and early p24 antigenemia. The mean survival time was 7 months for HIV-1 infected children with a high (> 50 pg/ml) p24 antigen concentration vs 20 months for children with p24 antigen concentrations between 10 and 50 pg/ml (p = 0.02). Cumulative probabilities of survival to 36 months of age were 0% among HIV-1 infected children with at least one positive p24 antigen test 44% among confirmed HIV-1 infected children who were p24 antigen-negative at both 6 weeks and 3 months of age and 95% among seroconverting children (p < 0.001). These results suggest a lower sensitivity of the ICD HIV-1 p24 antigen assay among Rwandan children compared with previous reports from developed countries. However a positive p24 antigen test was strongly predictive of rapid progression to AIDS and early death. (authors)

To investigate the risk of occupationally acquired HIV infection among traditional birth attendants (TBA) in Rwanda, Africa.A serosurvey was conducted among 219 TBA practicing in a rural but densely populated area in southern Rwanda. Each TBA was interviewed about sociodemographic information, work-related habits and practices, and presence of nonoccupational risk factors for HIV infection. The frequency of skin exposure to HIV-infected blood was estimated for each TBA from HIV seroprevalence data collected previously from pregnant women stratified by the geographic zones in which the TBA practiced.Four TBA (1.8%) tested HIV-1-antibody-positive; all four had reported nonoccupational risk factors for HIV infection. We estimated that the 215 HIV-negative TBA had 2234 potentially infectious blood-skin contacts out of a total of approximately 35,000 deliveries assisted in the past 5 years. However, we found no evidence of HIV infection caused by occupational blood contact (none out of 2234; upper limit of the 95% confidence interval because of one potentially infectious blood-skin contact = 0.2%).Although these findings may not be universal to all TBA in Africa, the risk of occupationally acquired HIV infection among TBA appears small. The high frequency of blood-skin contact among TBA in Rwanda highlights the need to include infection control precautions in the training of TBA.Samples of blood from 219 traditional birth attendants (TBA) practicing in a rural, densely populated area in southern Rwanda were tested for the presence of antibody against HIV-1 in an investigation of the risk for acquiring HIV infection occupationally. The TBAs were interviewed for sociodemographic data, on work-related habits and practices, and about nonoccupational risk factors for HIV infection. The researchers also estimated the frequency of skin exposure to HIV-infected blood for each TBA from HIV seroprevalence data collected previously from pregnant women stratified by the geographic zones in which each TBA practiced. Four TBAs tested seropositive for HIV-1 antibody; all had reported nonoccupational risk factors for infection. It was also estimated that the 215 HIV-negative TBAs had 2234 potentially infectious blood-skin contacts out of a total of approximately 35,000 deliveries assisted over the previous past five years. No evidence was therefore found of HIV infection caused by occupational blood contact and the risk of occupationally acquired HIV infection among TBAs seems small. The high frequency of blood-skin contact among TBAs in Rwanda, however, highlights the need to include infection control precautions in the training of TBAs.

A prospective cohort study of 318 human immunodeficiency virus 1 (HIV-1)-infected and 309 seronegative pregnant women was carried out in Butare, Rwanda. Birth weight was significantly lower among singleton infants born alive to HIV-1-infected mothers compared with those born alive to seronegative mothers (2706 g vs. 2825 g; P = 0.002). Crown-to-heel length, head circumference, chest circumference and placental weight were also reduced. Maternal HIV-1 infection was significantly associated with intrauterine growth retardation but not with preterm birth. Differences in the body mass index and weight/head ratio suggest that the adverse impact on live born infants may have been most severe towards the end of pregnancy, resulting in a lean infant with a relatively large head. The higher frequency of intrauterine growth retardation could not be explained by potential confounding factors such as maternal cigarette smoking, history of sexually transmitted diseases or sociodemographic characteristics. The neonatal physical examination did not reveal any differences in clinical signs or symptoms within 48 hours of birth except for the presence of conjunctivitis which was more common among infants of HIV-1-infected mothers. The perinatal and neonatal mortality rates were not significantly affected by maternal HIV-1 status.

We conducted a nested case-control study of placental malaria (PM) and mother-to-child transmission (MTCT) of human immunodeficiency virus-1 (HIV-1) within a prospective cohort of 627 mother-infant pairs followed from October 1989 until April 1994 in rural Rwanda. Sixty stored placentas were examined for PM and other placental pathology, comparing 20 HIV-infected mother-infant (perinatal transmitter) pairs, 20 HIV-uninfected pairs, and 20 HIV-infected mothers who did not transmit to their infant perinatally. Of 60 placentas examined, 45% showed evidence of PM. Placental malaria was associated with increased risk of MTCT of HIV-1 (adjusted odds ratio [aOR] = 6.3; 95% confidence interval [CI] = 1.4–29.1), especially among primigravidae (aOR = 12.0; 95% CI = 1.0–150; P < 0.05). Before antiretroviral therapy or prophylaxis, PM was associated with early infant HIV infection among rural Rwandan women living in a hyper-endemic malaria region. Primigravidae, among whom malaria tends to be most severe, may be at higher risk.

We mailed a health survey to the 18,408 residents of a California retirement community and compared the 11,550 respondents on a number of characteristics by time of response. Early respondents were more likely to be the "worried well," that is, healthy individuals who see their doctor regularly, receive disease detection screening, and follow healthful life-style practices. Late respondents tended to answer questions regarding their mental function and emotional status more negatively. Early and late respondents did not differ in the rates of death or hospitalization during the first 5 years of the study; nonrespondents had a higher incidence of hospitalization than respondents in year 1 and higher death rates in the first 3 years, but not thereafter.

As part of a prospective study begun in 1981, we evaluated 8,600 postmenopausal women and 5,049 men residing in a southern California retirement community for risk factors for hip fracture. Incidence rates were twice as high in women as in men, but in both sexes the rates nearly doubled every 5 years between 70 and 90 years. Active exercise was strongly and negatively associated with hip fracture risk in both sexes; the age-adjusted relative risk was 0.6 and 0.5 for females and males, respectively, for 1 or more hours of exercise per day compared with less than 1/2 hour of exercise. A high body mass index (upper tertile of weight divided by height squared) was associated with a strong reduction in hip fracture risk for females (RR = 0.5). Current cigarette smokers had a significantly increased risk (RR = 1.8 and RR = 2.2 for females and males, respectively) compared with never-smokers, but the risk for past smokers was not different from that of lifetime nonsmokers. Other factors related to reduced hip fracture risk in women were high parity, late age at menarche, and long menstrual cycle length. These age-adjusted relative risk estimates did not change materially in multivariate analysis when adjusted simultaneously for age, active exercise, body mass, smoking, and, for women, age at menarche and number of children. Among estrogen users, the lowest risk of hip fracture was observed for recent users (RR = 0.8), while users who had stopped estrogen use 15 or more years ago had a relative risk of 1.1, suggesting that the protective effect of estrogen dissipates after many years since cessation of estrogen therapy.

Kaposi's sarcoma occurs at high incidence among Zambian adults and children, but there is a paucity of data on human herpesvirus 8 (HHV-8) incidence and routes of infection, especially in children. Between 1998 and 2004, the authors conducted a prospective study of viral transmission in a cohort of 684 children in Lusaka, Zambia, to estimate the annual incidence of HHV-8 from birth through 48 months of age. Maternal and pediatric human immunodeficiency virus type 1 (HIV-1) infection status was also determined. The results, based on 1,532 child-years of follow-up, showed that HHV-8 seroconversion occurs early in life. The incidence rate of HHV-8 seroconversion was 13.8 infections per 100 child-years by 48 months of age. HIV-1-infected children were at substantially higher risk for HHV-8 seroconversion (adjusted hazard ratio = 4.60, 95% confidence interval: 2.93, 7.22). Maternal HIV-1 and HHV-8 infection status were not independently associated with risk of HHV-8 seroconversion in the child. HHV-8 antibody titers in children followed at all consecutive time points revealed sero-reversion of HHV-8 antibodies, with undetectable titers in some children at one or more time points after seroconversion. These results demonstrate that cross-sectional serologic screening probably underestimates true HHV-8 seroprevalence in young Zambian children because of fluctuations in detectable antibody titers.

Understanding whether hormonal contraception increases the risk of incident HIV-1 infection among women is a critical public health issue. Hormonal contraception a novelty just four decades ago has become the norm in many countries because of its high efficacy and ease of use. Over 120 million women worldwide use hormonal contraception and its use especially depo-medroxyprogesterone acetate (DMPA) is increasing rapidly in many resource-limited settings. Effective contraception has a key role to play in reducing maternal and infant mortality (by spacing pregnancies) and in allowing women a measure of control over when and how often they become pregnant. At the same time the HIV/AIDS epidemic has reached crisis proportions in a number of sub-Saharan countries and calls for a rapid expansion of both prevention and treatment in resource-limited settings particularly among women of childbearing age. Despite the magnitude of the HIV/AIDS epidemic the level of condom use among married or cohabiting couples in countries classified by UNAIDS as experiencing a generalized HIV epidemic remains very low. Most women who do use contraception rely on oral contraceptives (OC) or injectable DMPA. (excerpt)