Vivien Tsu

Estimated global incidence of Japanese encephalitis: a systematic review.

OBJECTIVE To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. METHODS Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. FINDINGS A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE-endemic countries were identified. Approximately 67,900 JE cases typically occur annually (overall incidence: 1.8 per 100,000), of which only about 10% are reported to the World Health Organization. Approximately 33,900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51,000 (75%) occur in children aged 0-14 years (incidence: 5.4 per 100,000). Approximately 55,000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12,900 (19%) occur in areas with minimal or no JE vaccination programmes. CONCLUSION Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates.

Breast Cancer in Limited-Resource Countries: Health Care Systems and Public Policy

Abstract:   As the largest cancer killer of women around the globe, breast cancer adversely impacts countries at all levels of economic development. Despite major advances in the early detection, diagnosis, and treatment of breast cancer, health care ministries face multitiered challenges to create and support health care programs that can improve breast cancer outcomes. In addition to the financial and organizational problems inherent in any health care system, breast health programs are hindered by a lack of recognition of cancer as a public health priority, trained health care personnel shortages and migration, public and health care provider educational deficits, and social barriers that impede patient entry into early detection and cancer treatment programs. No perfect health care system exists, even in the wealthiest countries. Based on inevitable economic and practical constraints, all health care systems are compelled to make trade‐offs among four factors: access to care, scope of service, quality of care, and cost containment. Given these trade‐offs, guidelines can define stratified approaches by which economically realistic incremental improvements can be sequentially implemented within the context of resource constraints to improve breast health care. Disease‐specific “vertical” programs warrant “horizontal” integration with existing health care systems in limited‐resource countries. The Breast Health Global Initiative (BHGI) Health Care Systems and Public Policy Panel defined a stratified framework outlining recommended breast health care interventions for each of four incremental levels of resources (basic, limited, enhanced, and maximal). Reallocation of existing resources and integration of a breast health care program with existing programs and infrastructure can potentially improve outcomes in a cost‐sensitive manner. This adaptable framework can be used as a tool by policymakers for program planning and research design to make best use of available resources to improve breast health care in a given limited‐resource setting.

Cervical screening by visual inspection, HPV testing, liquid‐based and conventional cytology in Amazonian Peru

Cervical cancer is an important public health problem in many developing countries, where cytology screening has been ineffective. We compared four tests to identify the most appropriate for screening in countries with limited resources. Nineteen midwives screened 5,435 women with visual inspection (VIA) and collected cervical samples for HPV testing, liquid‐based cytology (LBC) and conventional cytology (CC). If VIA was positive, a doctor performed magnified VIA. CC was read locally, LBC was read in Lima and HPV testing was done in London. Women with a positive screening test were offered colposcopy or cryotherapy (with biopsy). Inadequacy rates were 5% and 11% for LBC and CC respectively, and less than 0.1% for VIA and HPV. One thousand eight hundred eighty‐one women (84% of 2,236) accepted colposcopy/cryotherapy: 79 had carcinoma in situ or cancer (CIS+), 27 had severe‐ and 42 moderate‐dysplasia on histology. We estimated a further 6.5 cases of CIS+ in women without a biopsy. Sensitivity for CIS+ (specificity for less than moderate dysplasia) was 41.2% (76.7%) for VIA, 95.8% (89.3%) for HPV, 80.3% (83.7%) for LBC, and 42.5% (98.7%) for CC. Sensitivities for moderate dysplasia or worse were better for VIA (54.9%) and less favourable for HPV and cytology. In this setting, VIA and CC missed the majority of high‐grade disease. Overall, HPV testing performed best. VIA gives immediate results, but will require investment in regular training and supervision. Further work is needed to determine whether screened‐positive women should all be treated or triaged with a more specific test.

Oxytocin in prefilled Uniject injection devices for managing third-stage labor in Indonesia.

We assessed the use and acceptability of an injection device (Uniject™) prefilled with oxytocin, as part of active management of third‐stage labor (AMTL) by Indonesian midwives attending home births. We interviewed 140 village midwives (bidan di desa) and 2220 mothers whose deliveries they attended during the intervention period. We completed baseline and post‐intervention assessments to determine their experiences and views of oxytocin Uniject™ use. Delivery logs and supervisory reports were reviewed. The assessment was done in three rural districts and one municipality in Lombok. Injection practices and oxytocin availability did not change dramatically, although dose accuracy, use of sterile injection equipment, and proper disposal improved when the Uniject™ device was used. Midwives had little difficulty using the Uniject™ device properly; they overwhelmingly preferred it to standard needles and syringes. Postpartum hemorrhage rates did not change substantially. Oxytocin via Uniject™ holds promise for safer, more convenient use of oxytocin by trained midwives attending home deliveries, thereby potentially reducing the incidence of postpartum hemorrhage.

Postpartum haemorrhage in Zimbabwe: a risk factor analysis

Objectives To identify risk factors associated with postpartum haemorrhage (PPH) in order to improve the effectiveness of antenatal screening.

Immunogenicity and Reactogenicity of Alternative Schedules of HPV Vaccine in Vietnam: A Cluster Randomized Noninferiority Trial

CONTEXT Human papillomavirus (HPV) vaccine programs may decrease the morbidity and mortality due to cervical cancer seen among women in low-resource countries. However, the 3-dose schedule over a 6-month period is a potential barrier to vaccine introduction in such settings. OBJECTIVE To determine the immunogenicity and reactogenicity of different dosing schedules of quadrivalent HPV vaccine in adolescent girls in Vietnam. DESIGN, SETTING, AND PARTICIPANTS Open-label, cluster randomized, noninferiority study (conducted between October 2007 and January 2010) assessing 4 schedules of an HPV vaccine delivered in 21 schools to 903 adolescent girls (aged 11-13 years at enrollment) living in northwestern Vietnam. INTERVENTION Intramuscular injection of 3 doses of quadrivalent HPV vaccine delivered on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months). MAIN OUTCOME MEASURES Serum anti-HPV geometric mean titers (GMT) measured 1 month after the third dose of the HPV vaccine was administered; GMT was determined by type-specific competitive immunoassay. Noninferiority of each alternative vaccination dosing schedule was achieved if the lower bound of the multiplicity-adjusted confidence interval (CI) of the type-specific GMT ratio for HPV-16 and HPV-18 was greater than 0.5 (primary outcome). Safety outcomes were immediate reactions, local reactions, fever within 7 days after each dose, and serious adverse events up to 30 days following the last dose. RESULTS In the intention-to-treat analysis, 809 girls who received at least 1 HPV vaccine dose had valid serum measurements 1 month after the third dose. After the third dose, the GMTs for those in the standard schedule group who received doses at 0, 2, and 6 months were 5808.0 (95% CI, 4961.4-6799.0) for HPV-16 and 1729.9 (95% CI, 1504.0-1989.7) for HPV-18; 5368.5 (95% CI, 4632.4-6221.5) and 1502.3 (95% CI, 1302.1-1733.2), respectively, for those whose received doses at 0, 3, and 9 months; 5716.4 (95% CI, 4876.7-6700.6) and 1581.5 (95% CI, 1363.4-1834.6), respectively, for those who received doses at 0, 6, and 12 months; and 3692.5 (95% CI, 3145.3-4334.9) and 1335.7 (95% CI, 1191.6-1497.3), respectively, for those who received doses at 0, 12, and 24 months. Noninferiority criteria were met for the alternative schedule groups that received doses at 0, 3, and 9 months (HPV-16 GMT ratio: 0.92 [95% CI, 0.71-1.20]; HPV-18 GMT ratio: 0.87 [95% CI, 0.68-1.11]) and at 0, 6, and 12 months (HPV-16 GMT ratio: 0.98 [95% CI, 0.75-1.29]; HPV-18 GMT ratio: 0.91 [95% CI, 0.71-1.17]). Prespecified noninferiority criteria were not met for the alternative schedule group that received doses at 0, 12, and 24 months (HPV-16 GMT ratio: 0.64 [95% CI, 0.48-0.84]; HPV-18 GMT ratio: 0.77 [95% CI, 0.62-0.96]). Pain at the injection site was the most common adverse event. CONCLUSIONS Among adolescent girls in Vietnam, administration of the HPV vaccine on standard and alternative schedules was immunogenic and well tolerated. The use of 2 alternative dosing schedules (at 0, 3, and 9 months and at 0, 6, and 12 months) compared with a standard schedule (at 0, 2, and 6 months) did not result in inferior antibody concentrations. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00524745.

Making the case for cervical cancer prevention: what about equity?

Abstract Cervical cancer is a major cause of suffering and premature death among women in the developing world, yet it is largely prevented in most higher-income countries. From an equity perspective, cervical cancer is unequally distributed globally in ways that are unnecessary, avoidable and unjust. Although cost-effectiveness analyses demonstrate that prevention measures are justified in low-resource countries, affordability and lack of prioritisation have contributed to a lack of progress. This paper describes the inequities in cervical cancer disease burden, barriers in access to and utilisation of services, and the underlying conditions of poverty and low socio-economic status that put women in a disadvantaged position. These social disadvantages are aggravated by the disease itself, with serious consequences for women, their families and communities. Remedies are available in the form of new prevention and treatment approaches, including vaccines against human papillomavirus (HPV), rapid HPV testing, visual inspection of the cervix with acetic acid (VIA) and cryotherapy. These technologies could help to overcome the social, economic, and political disadvantages that contribute to disparities in cervical cancer incidence and mortality through an optimal combination of vaccination, screening and treatment. In the long run, however, increasing women’s access to care will also require societies to address structural barriers related to health systems and poverty. Résumé Le cancer du col de l’utérus est une cause majeure de souffrance et de décès prématuré dans le monde en développement. Pourtant, il est surtout prévenu dans les pays riches. Cette forme de cancer est répartie inégalement dans le monde pour des motifs évitables et injustes. Même si les analyses de rentabilité montrent que les mesures de prévention sont justifiées dans les pays à faible revenu, les coûts et une priorité insuffisante ont contribué à un manque de progrès. Cet article décrit les inégalités de la charge de morbidité du cancer du col de l’utérus, les obstacles à l’accès et à l’utilisation des services, ainsi que la pauvreté et le médiocre statut socio-économique qui placent les femmes dans une position défavorisée. Ces handicaps sociaux sont aggravés par la maladie elle-même, qui a de graves conséquences pour les femmes, leur famille et leur communauté. Les solutions sont disponibles avec de nouvelles méthodes de prévention et de traitement, notamment les vaccins contre le papillomavirus humain (PVH), les tests rapides du PVH, l’inspection visuelle après application d’acide acétique (VIA) et la cryothérapie. Ces techniques pourraient surmonter les handicaps sociaux, économiques et politiques qui contribuent aux disparités dans l’incidence de la maladie et sa mortalité par une association optimale de vaccination, dépistage et traitement. Néanmoins, à long terme, élargir l’accès des femmes aux soins exigera aussi des sociétés qu’elles lèvent les obstacles structurels liés aux systèmes de santé et à la pauvreté. Resumen El cáncer cervical es una causa principal de sufrimiento y muerte prematura entre las mujeres de los países en desarrollo; sin embargo, en países con ingresos más elevados, se evita en gran medida. Desde un punto de vista de equidad, el cáncer cervical es distribuido de manera desigual mundialmente, en formas que son innecesarias, evitables e injustas. Aunque los análisis de costo-eficacia demuestran que las medidas de prevención se justifican en países con escasos recursos, se han logrado pocos avances debido a la falta de asequibilidad y priorización. En este artículo se describen las injusticias en el impacto de la enfermedad del cáncer cervical, las barreras en el acceso a los servicios y la utilización de estos, y las condiciones subyacentes de pobreza y baja condición socioeconómica, que no favorecen a las mujeres. Estas desventajas sociales son agravadas por la enfermedad en sí, con graves consecuencias para las mujeres, sus familias y sus comunidades. Existen remedios en la forma de nuevas modalidades de prevención y tratamiento, como vacunas contra el virus del papiloma humano (VPH), pruebas rápidas de VPH, inspección visual del cérvix con ácido acético (IVAA) y crioterapia. Estas tecnologías podrían ayudar a superar las desventajas sociales, económicas y políticas que contribuyen a las disparidades en la incidencia del cáncer cervical y la mortalidad a causa de éste, mediante una combinación óptima de vacunación, tamizaje y tratamiento. No obstante, a la larga no sólo será necesario ampliar el acceso de las mujeres a la atención médica sino también vencer las barreras estructurales relacionadas con los sistemas de salud y la pobreza.

Integration of Human Papillomavirus Vaccination and Cervical Cancer Screening in Latin America and the Caribbean

Despite substantial efforts to control cervical cancer by screening, most Latin American and Caribbean countries continue to experience incidence rates of this disease that are much higher than those of other Western countries. The implementation of universal human papillomavirus (HPV) vaccination for young adolescent women is the best prospect for changing this situation. Even though there are financial challenges to overcome to implement such a policy, there is broad political support in the region for adopting universal HPV vaccination. The costs of implementing this policy could be largely alleviated by changing cervical cancer control practices that rely on inefficient use of resources presently allocated to cytology screening. In view of the strong evidence base concerning cervical cancer prevention technologies in the region and the expected impact of vaccination on the performance of cytology, we propose a reformulation of cervical cancer screening policies to be based on HPV testing using validated methods followed by cytologic triage. This approach would serve as the central component of a system that plays the dual role of providing screening and surveillance as integrated and complementary activities sharing centralized resources and coordination.

New and underused technologies to reduce maternal mortality

In July 2003 maternal health specialists from around the world gathered in Bellagio Italy to develop a list of proven and promising technologies appropriate for low resource settings to reduce maternal mortality. We defined technologies as equipment consumable supplies including medicines and techniques. While technology especially in health care often provokes thoughts of complex costly interventions the technologies identified at the Bellagio meeting are mostly simple and inexpensive. What is lacking are resources human and financial to scale-up and put proven technologies into widespread use and to assess and document the effectiveness of promising new interventions. There is an urgent need to accelerate the appropriate use of technologies and to reduce the inequitable burden of pregnancy-related mortality borne by women in poor countries. The 2003 Lancet series on child survival highlighted the interventions needed to ensure the health of children worldwide. We would add that saving the life of the mother is one of the best ways to prevent the death of a child. The half million women who die from pregnancy-related and childbirth-related causes every year leave behind at least 1 million motherless children who are all at increased mortality risk. (excerpt)

Postpartum hemorrhage in developing countries: is the public health community using the right tools?

Objectives: To identify new and underutilized technologies that may assist in reducing maternal mortality due to obstetric hemorrhage. Methods: Review of published and unpublished literature, including systematic reviews of randomized trials and individual clinical studies. Results: Hemorrhage, primarily postpartum, accounts for approximately 25% of maternal deaths globally. Uterotonic drugs offer great promise for both prevention and management of postpartum hemorrhage (PPH). Other technologies—such as anti‐shock garments, umbilical vein injection of oxytocin, and simple anemia detection methods—represent potential new opportunities to reduce PPH‐related mortality. Conclusions: Clinical and operational research is needed to answer remaining questions about misoprostol, the anti‐shock garment, and umbilical vein injection of oxytocin for retained placenta. Efforts are needed to ensure the availability of technologies with proven value, such as oxytocin in Uniject™ prefilled injection devices. Equally important, technologies and techniques with proven efficacy—such as active management of third‐stage labor and aortic compression—must be translated into general use by disseminating the evidence for them, incorporating them into national guidelines and training curricula, and ensuring the availability of supportive supplies and equipment.