Roadmap for the international collaborative epidemiologic monitoring of safety and effectiveness of new high priority vaccines

With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC's are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety.     

The economic burden of maternal mortality on households: evidence from three sub-counties in rural western Kenya

This study explores the consequences of a maternal death to households in rural Western Kenya focusing particularly on the immediate financial and economic impacts. Between September 2011 and March 2013 all households in the study area with a maternal death were surveyed. Data were collected on the demographic characteristics of the deceased woman; household socio-economic status; a history of the pregnancy and health care access and utilization; and disruption to household functioning due to the maternal death. These data were supplemented by in-depth and focus group discussions. The health service utilization costs associated with maternal deaths were significantly higher, due to more frequent service utilization as well as due to the higher cost of each visit suggesting more involved treatments and interventions were sought with these women. The already high costs incurred by cases during pregnancy were further increased during delivery and postpartum mainly a result of higher facility-based fees and expenses. Households who experienced a maternal death spent about one-third of their annual per capita consumption expenditure on healthcare access and use as opposed to at most 12% among households who had a health pregnancy and delivery. Funeral costs were often higher than the healthcare costs and altogether forced households to dis-save, liquidate assets and borrow money. What is more, the surviving members of the households had significant redistribution of labor and responsibilities to make up for the lost contributions of the deceased women. Kenya is in the process of instituting free maternity services in all public facilities. Effectively implemented, this policy can lift a major economic burden experienced by a very large number of household who seek maternal health services which can be catastrophic in complicated cases that result in maternal death. There needs to be further emphasis on insurance schemes that can support households through catastrophic health spending.     

Kyasanur Forest Disease Outbreak and Vaccination Strategy,Shimoga District,India, 2013–2014

We investigated a Kyasanur Forest disease outbreak in Karnataka, India during December 2013–April 2014. Surveillance and retrospective study indicated low vaccine coverage, low vaccine effectiveness, and spread of disease to areas beyond those selected for vaccination and to age groups not targeted for vaccination. To control disease, vaccination strategies need to be reviewed.     

Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana.

OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana. DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection. METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results. Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed. A positive test was defined as > or = 10 mm induration. Skin test results were compared with results obtained from a population survey of children of similar age from the same community. RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005). Of the infected children, 22 (78.6%) were contacts of a close female relative. The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001). In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006). CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M. tuberculosis during the era of HIV. However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS.     

Population-based chest X-ray screening for pulmonary tuberculosis in people living with HIV/AIDS, An Giang, Vietnam.

SETTING: Human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS) program, An Giang Province, Vietnam. OBJECTIVE: To evaluate the coverage and yield of a chest radiography (CXR) screening program for tuberculosis (TB) among people living with HIV/AIDS (PLHA), risk factors for a TB CXR, inter-rater reliability of CXR readings and direct costs. DESIGN: Retrospective review of routine public health program records and CXRs. RESULTS: An increasing proportion of PLHAs received a screening CXR each year of the program (range 21% in 2001 to 61% in 2004, P<0.001). Of 876 screening CXRs performed, 191 (22%) were classified as suspicious for active TB ('TB CXR'). Compared to PLHAs with a CXR not suspicious for active TB, PLHAs with a TB CXR were more likely to be aged between 24 and 64 years, male and previously treated for TB (P<0.01 for each comparison). Agreement between the expert and local program CXR readings was 81% (kappa 0.50). Direct costs were approximately US$40 per TB suspect identified. Among TB suspects, <10% were followed up with sputum smear examination and enrolled for treatment. CONCLUSION: In An Giang Province, a large proportion of PLHAs are screened for TB annually, and one in five persons screened is classified as a TB suspect based on CXR. Annual CXRs may be a high-yield, inexpensive method for TB screening in PLHAs, but the follow-up of TB suspects to confirm diagnosis and initiate treatment is crucial.     

Improved tuberculosis case detection through public-private partnership and laboratory-based surveillance, Kannur District, Kerala, India, 2001-2002.

BACKGROUND: Efforts to intensify global tuberculosis (TB) control are limited by difficulties in coordinating with private doctors. More than half of Indian TB patients may initially consult a private provider, but many are neither diagnosed accurately nor treated effectively. We established and evaluated a public-private partnership based on surveillance of TB detected in private laboratories and use of standardised directly observed treatment regimens. METHODS: In one district, the governmental TB control programme offered training in microscopy to all large private sector laboratories, and educated private physicians on the importance of microscopy for TB diagnosis. We reviewed records from participating private laboratories and all publicly diagnosed patients. RESULTS: Of 2328 pulmonary TB patients registered from July 2001 to December 2002, 404 (17%) were detected in the private sector. The annual new AFB-positive case notification rate increased by 21%, from 27.8/100,000 in 2000 to 33.5/100,000 in 2002. Surveillance at private laboratories found an additional 260 nonregistered AFB-positive patients. CONCLUSIONS: This public-private partnership substantially increased TB case detection and established a sustainable framework for private sector involvement in TB control. In the setting of a strong public sector programme, the combination of active surveillance of private laboratories along with physician sensitisation is a promising approach to improve TB case detection.     

TST reversion in a BCG-revaccinated population of nursing and medical students, S?o Paulo, Brazil, 1997-2000.

SETTING: A major university in S?o Paulo, Brazil, where vaccination against tuberculosis (TB) with bacille Calmette-Guerin (BCG) was routinely offered to first-year medical and nursing students. OBJECTIVES: To estimate the probability of negative tuberculin skin test (TST) results over a 4-year period following BCG revaccination, and to evaluate the effect of factors associated with reversion. DESIGN: Students were enrolled in 1997, initially given a two-step TST, and were retested annually or biannually for the duration of the study. Data on TB exposures and potential risk factors for TST negativity and reversion were collected through annual surveys. A linear mixture survival model was used to estimate the probability of negative TST results over time. RESULTS: Of 159 students, an estimated 20% had a negative TST result despite revaccination, and a further 31% reverted to negative over 4 years of follow-up. No cofactors significantly affected the probability of reversion. CONCLUSION: Overall, in the absence of reported exposure to Mycobacterium tuberculosis, 51% of students revaccinated upon entering nursing or medical school would have a negative TST result by the time they begin their internships. In this recently vaccinated population, reversion was common, suggesting that annual TST screening may remain a useful tool.     

Seasonality of tuberculosis in India: is it real and what does it tell us?

India has a third of the world's tuberculosis cases. Large-scale expansion of a national programme in 1998 has allowed for population-based analyses of data from tuberculosis registries. We assessed seasonal trends using quarterly reports from districts with stable tuberculosis control programmes (population 115 million). In northern India, tuberculosis diagnoses peaked between April and June, and reached a nadir between October and December, whereas no seasonality was reported in the south. Overall, rates of new smear-positive tuberculosis cases were 57 per 100000 population in peak seasons versus 46 per 100000 in trough seasons. General health-seeking behaviour artifact was ruled out. Seasonality was highest in paediatric cases, suggesting variation in recent transmission.