Mukhtiar Zaman

Effectiveness of Antiviral Treatment in Human Influenza A(H5N1) Infections: Analysis of a Global Patient Registry

BACKGROUND Influenza A(H5N1) continues to cause infections and possesses pandemic potential. METHODS Data sources were primarily clinical records, published case series, and governmental agency reports. Cox proportional hazards regression was used to estimate the effect of treatment on survival, with adjustment using propensity scores (a composite measure of baseline variables predicting use of treatment). RESULTS In total, 308 cases were identified from 12 countries: 41 from Azerbaijan, Hong Kong SAR, Nigeria, Pakistan, and Turkey (from clinical records); 175 from Egypt and Indonesia (from various sources); and 92 from Bangladesh, Cambodia, China, Thailand, and Vietnam (from various publications). Overall crude survival was 43.5%; 60% of patients who received ≥1 dose of oseltamivir alone (OS(+)) survived versus 24% of patients who had no evidence of anti-influenza antiviral treatment (OS(-)) (P <.001). Survival rates of OS(+) groups were significantly higher than those of OS(-) groups; benefit persisted with oseltamivir treatment initiation <or=6-8 days after symptom onset. Multivariate modeling showed 49% mortality reduction from oseltamivir treatment. CONCLUSIONS H5N1 causes high mortality, especially when untreated. Oseltamivir significantly reduces mortality when started up to 6-8 days after symptom onset and appears to benefit all age groups. Prompt diagnosis and early therapeutic intervention should be considered for H5N1 disease.

H5N1 Avian Influenza in Children

BACKGROUND Avian influenza continues to pose a threat to humans and maintains the potential for greater transmissibility. Understanding the clinical presentation and prognosis in children will help guide effective diagnosis and treatment. METHODS A global patient registry was created to enable systematic collection of clinical, exposure, treatment, and outcomes data on confirmed cases of H5N1. Bivariate and multivariate statistical tools were used to describe clinical presentation and evaluate factors prognostic of survival. RESULTS Data were available from 13 countries on 193 children <18 years who were confirmed as having been infected with H5N1; 35.2% of cases were from Egypt. The case fatality rate (CFR) for children was 48.7%, with Egypt having a very low pediatric CFR. Overall, children aged ≤5 years had the lowest CFR and were brought to hospitals more quickly and treated sooner than older children. Children who presented for medical care with a complaint of rhinorrhea had a 76% reduction in the likelihood of death compared with those who presented without rhinorrhea, even after statistical adjustment for age, having been infected in Egypt, and oseltamivir treatment (P = .02). Delayed initiation of treatment with oseltamivir increases the likelihood of death, with an overall 75% increase in the adjusted odds ratio for death for each day of delay. CONCLUSIONS The presence of rhinorrhea appears to indicate a better prognosis for children with H5N1, with most patients surviving regardless of age, country, or treatment. For individuals treated with oseltamivir, early initiation of treatment substantially enhances the chance of survival.

Human Infection with Avian Influenza Virus, Pakistan, 2007

Human infection with avian influenza (H5N1) virus raises concern for the possibility of a pandemic. We report 20 cases, which ranged from asymptomatic to fatal, in Pakistan in 2007. These cases indicate human-to-human-to-human transmission of this virus, and the number of cases may be higher than realized.

Strengthening Observational Evidence for Antiviral Effectiveness in Influenza A (H5N1)

To the Editor—We recently reported findings from the largest ever patient registry of confirmed influenza A (H5N1) cases [1]. Using data collected from medical records, data made available by ministries of health and other clinical data sources, and data from published case reports, the registry deployed a structured data collection system to assemble data from 308 cases in 12 countries. The source documents for the registry contained varying types of information. The amount of missing data depends on both the record source, because not all data elements of interest were available from every source, and the reporter, because published case studies were selective in their reporting, and individual physicians had different styles and completeness of medical record annotations. The study showed a strong reduction in the risk of mortality for treatment with oseltamivir. In the editorial that accompanied this first report of findings from the global registry of human H5N1 cases, Couch and Davis [2] commented on the challenges of controlling for uneven data and bias-free comparisons when using observational data. While affirming the overall conclusion that treatment with oseltamivir significantly reduces mortality when commenced even as late as 6–8 days after symptom onset, they questioned the methods used for handling missing data. For one key analysis, we used Cox proportional hazards regression to estimate the hazard ratio for survival associated with oseltamivir treatment, and used a propensity score predicting probability of oseltamivir treatment for statistical adjustment in the Cox model. In the Cox model, we used mean imputation to estimate time from first presentation for medical care to death for 54 cases that were missing this information. For the propensity score, if time from symptom onset to first presentation for medical care was missing, it was dropped from the modeling step, but propensity scores were still generated for the 18 cases missing this date. A second key analysis examined survival by timing of oselta-mivir initiation and used a complete case method, which resulted in exclusion of 61 cases missing dates of symptom onset, oseltamivir treatment start, presentation for medical care, and/or death. To evaluate the sensitivity of our overall study conclusions to the data imputation method, we used multiple imputation of missing data and replicated the Cox proportional hazards model on 20 im-puted data sets. The overall estimate of benefit was essentially unchanged, showing roughly a 50% decrease in the risk of death from treatment with oseltamivir. The confidence …

Exploring and optimising maternal and infant nutrition in North West Pakistan

OBJECTIVES the aim of this study was to explore and contextualise meanings, beliefs and practices surrounding maternal and infant nutrition in North West Pakistan and to use the findings to inform the development of a nutritional improvement programme adapted to local needs. DESIGN the Context-Mechanism-Outcome framework was used to gather contextual data, formulate questions and conduct focus groups to inform the design of a culturally appropriate nutritional health programme with the overall goal of improving practices related to maternal and infant nutrition. Two focus groups were conducted with the team of local lady health workers (n=16), one prior to implementing a nutritional improvement programme and one 6 months after implementation. SETTINGS the study was conducted in communities surrounding and served by the Emergency Satellite Hospital (ESH) in Nahaqi in Khyber Pakhtunkhawa (KP) (formally known as the Northwest Frontier Province), Pakistan. FINDINGS poverty and specific cultural practices impeded the achievement of optimum maternal and infant nutrition. A nutrition support programme was implemented; it involved cookery demonstration kitchens and free food supplements, coupled with nutrition and health-care information-giving for pregnant and lactating women. Focus group discussions revealed that women had positive perceptions of the impact of the nutritional health improvement programme, feeling that knowledge and practices were enhanced. However, structural and cultural factors continued to have a powerful influence on their practices. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE this study highlights that despite structural, cultural and practical barriers, a culturally sensitive health improvement programme has the potential to enhance maternal and infant nutritional practices. However, we should not underestimate the powerful influence of poverty and culturally embedded norms upon womens decisions and practices.

Development and implementation of a nutrition intervention programme in North West Pakistan: a realist framework

Maternal and infant malnutrition is prevalent in rural regions of NW Pakistan. This article reports on the use of a combination of a realist Context-Mechanism-Outcome framework and participatory appraisal methods to facilitate the development of a locally sensitive and responsive nutritional intervention programme. Data were gathered through a series of focus group (FG) discussions with local lady health workers, as well as pregnant and breastfeeding women attending an Emergency Field Hospital in North West Pakistan between May 2008 and March 2009. A nutrition intervention programme was implemented that involved cookery demonstration kitchens and free food supplements, coupled with nutrition and healthcare information and advice for pregnant and breastfeeding women. Subsequent FG discussions revealed that the programme had a positive impact on knowledge gained by women in the community and generated an openness to receiving and spreading knowledge. The framework, which rested on the use of a double feedback loop, involving local women, lady health workers, local researchers and UK-based researchers, has enabled not only the establishment of the programme, but has also given the local team the tools to apply for, and gain, further funding for the development of nutrition support services. The development of such methodological tools, which empower local researchers and service providers (wherever located) to operationalize local knowledge and assess interventions, is particularly relevant in international financially-constrained contexts.

Developing health service delivery in a poor and marginalised community in North West Pakistan

Objectives: To improve maternal health and reduce child mortality through developing health service delivery in a poor and marginalised community in North West Pakistan. Methods: This was a multifaceted intervention to extend and strengthen the range and quality of services provided at an existing health centre, in a rural community in Peshawar District, Khyber Pakhtunkhwa Province. The intervention was developed with community involvement and had four main components: service development, staff capacity development, community engagement and the introduction of a micro-credit scheme. The evaluation assessed the efficiency and effectiveness of project implementation, including a survey of maternal and child health indicators. Results: Between 2014 and 2017, a range of new health services were developed at the health centre. Local volunteers were trained to promote health awareness in the community and refer pregnant women to the health centre. The survey indicated health improvements, such as increased vaccination rates for women and children, and a dramatic reduction in unskilled deliveries. Conclusions: Community engagement was essential to achieve much needed maternal and child health improvements in this poor and marginalised community. Sustainability was achieved by training local volunteers as community health workers.