Kayla F. Laserson

Worldwide emergence of extensively drug-resistant tuberculosis.

Mycobacterium tuberculosis strains are becoming resistant to not only the most powerful first-line drugs but also many second-line drugs.

HIV Infection and Multidrug-Resistant Tuberculosis—The Perfect Storm

BACKGROUND Multidrug-resistant (MDR) tuberculosis (TB) has emerged as a global epidemic, with ~425,000 new cases estimated to occur annually. The global human immunodeficiency virus (HIV) infection epidemic has caused explosive increases in TB incidence and may be contributing to increases in MDR-TB prevalence. METHODS We reviewed published studies and available surveillance data evaluating links between HIV infection and MDR-TB to quantify convergence of these 2 epidemics, evaluate the consequences, and determine essential steps to address these epidemics. RESULTS Institutional outbreaks of MDR-TB have primarily affected HIV-infected persons. Delayed diagnosis, inadequate initial treatment, and prolonged infectiousness led to extraordinary attack rates and case-fatality rates among HIV-infected persons. Whether this sequence occurs in communities is less clear. MDR-TB appears not to cause infection or disease more readily than drug-susceptible TB in HIV-infected persons. HIV infection may lead to malabsorption of anti-TB drugs and acquired rifamycin resistance. HIV-infected patients with MDR-TB have unacceptably high mortality; both antiretroviral and antimycobacterial treatment are necessary. Simultaneous treatment requires 6-10 different drugs. In HIV-prevalent countries, TB programs struggle with increased caseloads, which increase the risk of acquired MDR-TB. Surveillance data suggest that HIV infection and MDR-TB may converge in several countries. CONCLUSIONS Institutional outbreaks, overwhelmed public health programs, and complex clinical management issues may contribute to the convergence of the MDR-TB and HIV infection epidemics. To forestall disastrous consequences, infection control, rapid case detection, effective treatment, and expanded program capacity are needed urgently.

Clinical outcome of individualised treatment of multidrug-resistant tuberculosis in Latvia: a retrospective cohort study

BACKGROUND Latvia has one of the highest rates of multidrug-resistant tuberculosis (MDRTB). Our aim was to assess treatment outcomes for the first full cohort of MDRTB patients treated under Latvias DOTS-Plus strategy following WHO guidelines. METHODS We retrospectively reviewed all civilian patients who began treatment with individualised treatment regimens for pulmonary MDRTB in Latvia between Jan 1, and Dec 31, 2000. We applied treatment outcome definitions for MDRTB, developed by an international expert consensus group, and assessed treatment effectiveness and risk factors associated with poor outcome. FINDINGS Of the 204 patients assessed, 55 (27%) had been newly diagnosed with MDRTB, and 149 (73%) had earlier been treated with first-line or second-line drugs for this disease. Assessment of treatment outcomes showed that 135 (66%) patients were cured or completed therapy, 14 (7%) died, 26 (13%) defaulted, and treatment failed in 29 (14%). Of the 178 adherent patients, 135 (76%) achieved cure or treatment completion. In a multivariate Cox proportional-hazards model of these patients, independent predictors of poor outcome (death and treatment failure) included having previously received treatment for MDRTB (hazard ratio 5.7, 95% CI 1.9-16.6), the use of five or fewer drugs for 3 months or more (3.2, 1.1-9.6), resistance to ofloxacin (2.6, 1.2-5.4), and body-mass index less than 18.5 at start of treatment (2.3, 1.1-4.9). INTERPRETATION The DOTS-Plus strategy of identifying and treating patients with MDRTB can be effectively implemented on a nationwide scale in a setting of limited resources.

Profile: The KEMRI/CDC Health and Demographic Surveillance System—Western Kenya

The KEMRI/Centers for Disease Control and Prevention (CDC) Health and Demographic Surveillance System (HDSS) is located in Rarieda, Siaya and Gem Districts (Siaya County), lying northeast of Lake Victoria in Nyanza Province, western Kenya. The KEMRI/CDC HDSS, with approximately 220 000 inhabitants, has been the foundation for a variety of studies, including evaluations of insecticide-treated bed nets, burden of diarrhoeal disease and tuberculosis, malaria parasitaemia and anaemia, treatment strategies and immunological correlates of malaria infection, and numerous HIV, tuberculosis, malaria and diarrhoeal disease treatment and vaccine efficacy and effectiveness trials for more than a decade. Current studies include operations research to measure the uptake and effectiveness of the programmatic implementation of integrated malaria control strategies, HIV services, newly introduced vaccines and clinical trials. The HDSS provides general demographic and health information (such as population age structure and density, fertility rates, birth and death rates, in- and out-migrations, patterns of health care access and utilization and the local economics of health care) as well as disease- or intervention-specific information. The HDSS also collects verbal autopsy information on all deaths. Studies take advantage of the sampling frame inherent in the HDSS, whether at individual, household/compound or neighbourhood level.

Operational research in low-income countries: what, why, and how?

Operational research is increasingly being discussed at institutional meetings, donor forums, and scientific conferences, but limited published information exists on its role from a disease-control and programme perspective. We suggest a definition of operational research, clarify its relevance to infectious-disease control programmes, and describe some of the enabling factors and challenges for its integration into programme settings. Particularly in areas where the disease burden is high and resources and time are limited, investment in operational research and promotion of a culture of inquiry are needed so that health care can become more efficient. Thus, research capacity needs to be developed, specific resources allocated, and different stakeholders (academic institutions, national programme managers, and non-governmental organisations) brought together in promoting operational research.

A reversal in reductions of child mortality in Western Kenya, 2003-2009

We report and explore changes in child mortality in a rural area of Kenya during 2003-2009, when major public health interventions were scaled-up. Mortality ratios and rates were calculated by using the Kenya Medical Research Institute/Centers for Disease Control and Prevention Demographic Surveillance System. Inpatient and outpatient morbidity and mortality, and verbal autopsy data were analyzed. Mortality ratios for children less than five years of age decreased from 241 to 137 deaths/1,000 live-births in 2003 and 2007 respectively. In 2008, they increased to 212 deaths/1,000 live-births. Mortality remained elevated during the first 8 months of 2009 compared with 2006 and 2007. Malaria and/or anemia accounted for the greatest increases in child mortality. Stock-outs of essential antimalarial drugs during a time of increased malaria transmission and disruption of services during civil unrest may have contributed to increased mortality in 2008-2009. To maintain gains in child survival, implementation of good policies and effective interventions must be complemented by reliable supply and access to clinical services and essential drugs.

Rotavirus disease burden and impact and cost-effectiveness of a rotavirus vaccination program in kenya.

BACKGROUND The projected impact and cost-effectiveness of rotavirus vaccination are important for supporting rotavirus vaccine introduction in Africa, where limited health intervention funds are available. METHODS Hospital records, health utilization surveys, verbal autopsy data, and surveillance data on diarrheal disease were used to determine rotavirus-specific rates of hospitalization, clinic visits, and deaths due to diarrhea among children <5 years of age in Nyanza Province, Kenya. Rates were extrapolated nationally with use of province-specific data on diarrheal illness. Direct medical costs were estimated using record review and World Health Organization estimates. Household costs were collected through parental interviews. The impact of vaccination on health burden and on the cost-effectiveness per disability-adjusted life-year and lives saved were calculated. RESULTS Annually in Kenya, rotavirus infection causes 19% of hospitalizations and 16% of clinic visits for diarrhea among children <5 years of age and causes 4471 deaths, 8781 hospitalizations, and 1,443,883 clinic visits. Nationally, rotavirus disease costs the health care system

Impact of Antiretroviral Therapy on the Incidence of Tuberculosis: The Brazilian Experience, 1995–2001

10.8 million annually. Routine vaccination with a 2-dose rotavirus vaccination series would avert 2467 deaths (55%), 5724 hospitalizations (65%), and 852,589 clinic visits (59%) and would save 58 disability-adjusted life-years per 1000 children annually. At

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

3 per series, a program would cost

Home-based HIV testing and counseling in rural and urban Kenyan communities.

2.1 million in medical costs annually; the break-even price is