Cluster Randomized Trial of Community Case Management of the Severe Pneumonia With Oral Amoxicillin in Children 2-59 Months of Age in Hala and Matiari District, Pakistan

Acute respiratory infection (ARI) is one of the leading causes of morbidity and mortality in children less than five years of age, and is responsible for over 2 million annual deaths in this age group. Of the 10.8 million global child deaths estimated in 2000, 34% were in South Asia and 21% of the total deaths were attributed to pneumonia. Inclusion of all deaths for which acute lower respiratory infections (ALRI) are an associated cause would increase these estimates by two to threefold. The ARI mortality burden is principally constituted by pneumonia. The median incidence of pneumonia in under-five children in developing countries is estimated to be 0.29 episodes (interquartile range 0.21-0.71) per child year. It is estimated that in the developing countries 150.7 million new pneumonia cases occur each year, of which 11-20 million (7-13%) are severe enough to require hospital admission. The region of the world with the highest incidence of pneumonia is South and South East Asia with an estimated 55.2 million episodes occurring in children under five years old. In the developed world, an estimated 14.7 million cases occur each year.

Recent trends indicate that Pakistan has begun to lag behind many regional countries in major indicators such as infant mortality rates (IMR). Currently, Pakistan has an IMR of 81/1000 live births and under-five mortality rate of 103/1000 live births. Annual number of child deaths in Pakistan is estimated at 565,000, giving Pakistan 4th ranking after India, Nigeria and China. Of more than 560,000 under-five deaths reported in Pakistan in 2001, 19% were due to pneumonia.

At the community level WHO guidelines recommend that trained health workers treat non-severe pneumonia with an oral antibiotic and refer children with severe pneumonia (i.e. lower chest wall indrawing [LCI] present) to a local health facility to be treated by injectable antibiotic (and oxygen, as required). A series of WHO sponsored randomized controlled trials and a subsequent meta-analysis of results demonstrated that these guidelines implemented by community-based health workers (CHWs) resulted in a 24-27% reduction in total child mortality and a 36-42% reduction in pneumonia mortality in these research settings.Pandey et al. have shown 28% reduction in total under-five mortality using locally trained community health workers to detect and treat pneumonia.

It has been previously shown that oral amoxicillin is an effective treatment for (WHO-defined) severe pneumonia in children. More recently a multi-centre randomized controlled trial (RCT) conducted in eight countries has shown that oral amoxicillin is as effective as injectable penicillin for the treatment of severe pneumonia in a hospital setting. For non-severe pneumonia two large multicentre RCTs in Pakistan and India have shown that three-days' treatment with oral amoxicillin therapy was equivalent to five-days' treatment. Non-adherence was the most important risk factor for treatment failure in these studies and was also significantly related to longer duration of therapy. In addition, it has been shown in studies from India and Bangladesh/Indonesia that the three-days' antibiotic therapy resulted in lower prevalence of resistant organisms 15 days after initiation of therapy, when compared with a five-days' therapy.

The non-severe pneumonia and severe pneumonia studies mentioned above were all hospital based clinical efficacy studies (several conducted by members of this project team) so that close monitoring and follow-up could be assured. There is now a need to demonstrate the effectiveness of these management strategies for severe pneumonia in the community when implemented by CHWs. If the findings of the hospital-based RCTs can be replicated in community settings then this may have a very significant impact on global policy in community-based management of ARI in young children. Children with very severe pneumonia or very severe disease (such as those who have danger signs) will continue to be referred for hospital treatment following current WHO IMCI guidelines. The use of oral antibiotic for treating severe pneumonia at the community level has many potential benefits. This case management strategy, if shown to be effective, could: