Respiratory Infection (ARI)
Integrated Management of Childhood Illness (IMCI)
| Through its collaborating partners,
CHR identifies the challenges for child health in developing
countries and countries in transition, and designs the most
effective approach to overcome them. These challenges range
from infectious diseases to malnutrition to improper disease
management by health workers. Since its induction in 1996, CHR
has conducted extensive applied research in six targeted areas
to promote child health and reduce childhood mortality and morbidity:
Acute Respiratory Infection (ARI)
ARI remains one of the leading causes of morbidity and mortality
in children under the age of five in developing countries. Even
with significant progress in addressing the burden of disease
due to ARI, pneumonia claims approximately 2 million lives annually
of children under the age of five.
The CHR partners seek to increase recognition, prevention, and
treatment of ARI by:
Improving health care provider's recognition and treatment
approaches through refinement of the treatment strategies
for the three categories of pneumonia: non-severe (simple)
pneumonia, severe pneumonia, and very severe pneumonia;
Reducing the spread of antibiotic resistant pathogens and
adverse drug reactions by:
o Assessing the necessity of antibiotic therapy for non-severe
pneumonia (e.g. NARIMA Study);
o Determining the etiology of very severe pneumonia, documenting
antimicrobial resistance patterns, and identifying best treatment
practices, (e.g SPEAR Study);
Demonstrating that oral therapy may be safely substituted
for parenteral therapy in the treatment of children with severe
pneumonia (e.g. APPIS Study);
Developing improved diagnostics to identify co-morbidity
and recognition of pneumococcal infections (meningitis, pneumonia,
bacteremia, and otitis media), and malaria;
Adapting treatment strategies in areas with endemic malaria
and HIV/AIDS; and
Evaluating and introducing promising vaccines, e.g. pneumococcal,
HiB, and RSV.
Selected CHR Achievements
A 7-valent pneumococcal conjugate vaccine demonstrated
an estimated efficacy of 77% among all children who received
at least one dose of the vaccine prior to 24 months.
Showed that improved nutrition in developing countries
(including breastfeeding and reduction of low-birth weight)
would greatly reduce pneumonia mortality.
After the introduction of Haemophilus influenzae type b
(Hib) conjugate vaccine into The Gambia, the annual incidence
of Hib meningitis has fallen from more than 200 per 100,000
before vaccination to 21 per 100,000 in less than 1 year.
Showed that ARI could be prevented in the developing world
through improved nutrition and increased breastfeeding.
A 45% reduction in pneumonia incidence with zinc supplementation
Determined that cotrimoxazole is effective for non-severe
pneumonia, but amoxycillin is better for severe cases.
95% efficacy of Haemophilus influenzae type-b (Hib) conjugate
vaccine in The Gambia.
Improved case management of ARI and reduced antibiotic
use by 26% and case fatality rate by 27% in Pakistan.
Showed that maternal immunization against Streptococcus
pneumoniae elevated infant serum antibody levels 2 to 3 fold
higher than control infants.
An estimated 2.2 million diarrheal deaths occur annually in
developing countries in children under five. Thousands of
deaths could be averted through interventions such as Oral
Rehydration Therapy, appropriate drug therapy, optimal breastfeeding
practices, improved nutrition, increased access to clean water
and sanitation facilities and improved personal and domestic
CHR seeks to improve diagnosis and assessment and increase
prevention, and treatment by:
Advancing the understanding of causes and risk factors
of diarrheal diseases;
Developing new revised guidelines for management of diarrhea;
Evaluating new and alternate drug treatments and rehydration
Contributing to the prevention of diarrhea through evaluation
of new vaccines (e.g. rotavirus and shigella) and improved
nutrition and micronutrient status.
Selected CHR Achievements
Developed a standardized approach for ORS rehydration for
treatment of children with severe malnutrition and diarrhea
that resulted in fewer episodes of hypoglycemia, less need
for intravenous fluids, and a 47% reduction in mortality.
These findings were incorporated into new WHO guidelines.
Determined that El Nino increased hospital admissions due
to diarrhea over 200% during the last season.
Showed that approximately 40% of all hospitalized diarrhea
cases are due to rotavirus in urban and rural Bangladesh.
In addition, reanalysis of the efficacy of the past rotavirus
vaccine trials in Peru and Brazil has demonstrated that a
safe vaccine would have a significant public health impact.
Characterized newly emergent pathogen Vibrio cholerae O139
and designed rapid diagnostic tests.
Characterized a new toxigenic clone of Vibrio cholerae
O1 El Tor.
Designed a surveillance system to detect Vibrio cholerae
O1 by sampling potable water and sewage in Peru.
Designed an algorithm, using locally-available foods, that
is up to 89% effective in treating persistent diarrhea (1996),
and is now incorporated into the IMCI guidelines in over 79
countries around the world.
In 1995, WHO identified that 56% of global child deaths were
attributed to malnutrition, and that most of this mortality
was the result of infectious complications of mild to moderate,
rather than severe malnutrition. Recent nutrition research
has demonstrated that: micronutrients sustain and improve
child health; malnutrition is a major risk factor for disease
and death; and low birth weight impacts adult health and the
health of subsequent generations.
CHR seeks to improve nutrition in children by:
Conducting research on the use of zinc and other micronutrients
to treat and prevent disease;
Fostering innovations in successful breastfeeding counseling;
Research and consensus building within the scientific and
programmatic community to reduce low birth weight;
Increasing the quality of complementary feeding practices
in at-risk populations; and
Promoting the use of a child's nutritional status in the
re-estimation of the Global Burden of Disease.
Selected CHR Achievements
Daily zinc supplementation in small for gestational age
babies documented a 66% reduction in mortality.
Demonstrated that oral zinc supplementation in children
under 5 reported a 24% reduced probability of continuing diarrhea
and a 42% reduced probability of treatment failure or death
in children with persistent-diarrhea.
The use of zinc to prevent infectious diseases showed that
zinc had a significant preventive effect on incidence and
prevalence of diarrhea and pneumonia.
Established the safety of vitamin A when administered with
Established that a single, large postpartum dose of vitamin
A raised breastmilk retinol levels in women, and reduced duration
of ARI and febrile illness in their infants.
Among young mothers with infants hospitalized for diarrhea,
exclusive breastfeeding levels were increased significantly
to 75% through the use of community lactation counselors.
Infectious diseases account for 63% of deaths in children
ages 0-4 years. Unfortunately, ARI, DD, TB, malaria, and other
diseases have been shown to develop some degree of resistance
to commonly used antimicrobial drugs. As a result, the decreasing
effectiveness of these drugs has contributed to persistent
infections, higher morbidity and mortality, prolonged hospitalization
and increased health expenditures. The emergence of drug resistance
and new infectious agents presents a serious challenge to
global public health.
CHR-funded research has assisted USAID in accomplishing its
goals by conducting research in and building capacity to:
Combat AMR by addressing its major causes and consequences,
establishing a global strategy and action plan, contributing
to the understanding of mechanisms of antimicrobial resistance,
developing methods to detect resistance, responding to data
on antimicrobial resistance and drug-use, and preventing and
slowing the spread of antimicrobial resistance;
Support the work of the USAID Zambia mission strategy in
Respond to a congressional earmark to provide regional
and national training to improve tuberculosis control programs
committed to the WHO DOTS strategy, with special attention
to issues concerning high-risk and marginalized populations;
foster development of local and national TB control program
capacities to utilize operations research as a program tool;
and implement and evaluate new and innovative approaches to
community-based interventions for TB control; and
Conduct research to develop delivery strategies and identify
impediments to the successful completion of the global strategy
to eradicate polio.
Selected CHR Achievements
Demonstrated that steroid therapy did not improve outcome
in bacterial meningitis allowing WHO to make a clear recommendation
against the use of steroids in this disease.
Developed emergency response system for a dengue outbreak
at the request of the Bangladesh government and mission. This
approach has been adopted by WHO for use globally.
Developed an innovative and field-appropriate education
process involving immediate feedback and small group discussions,
followed by self-assessment meetings. These efforts have reduced
the number of children inappropriately treated with antibiotics
for simple ARI from 70% to 23%.
An ongoing effort to strengthen tuberculosis control and
establish effective DOTS campaigns in rural areas of Rio de
Janeiro, Brazil. This work has demonstrated that 82% completion
of all doses is achievable and that patient cure rates in
a country with a 40% default rate of DOTS interventions can
be improved. The program has already moved treatment success
rates from 60% to 84% in its first year of existence.
Trained key officials in Russia's Kemerovo region in the
control of MDR-TB and assisted in the development of an action
Field testing of an innovative, rapid, and inexpensive
technique for diagnosing TB in an urban slum of Lima, Peru
that has some of the world's highest prevalence of TB and
morbidity and mortality for HIV/MDR-TB.
In Cambodia, the CHR project has developed and implemented
a cross-training effort for the country's HIV and TB care
programs. This has been accomplished by adding a TB component
to an existing HIV-care program that provides home care to
about 700 symptomatic patients in the greater Phnom Penh area.
Implementation of a DOTS program in Indonesian hospitals
and then linking them to the national TB program.
A large multi-center study in India to document the etiology
and antimicrobial resistance of S. pneumoniae and H. influenzae
invasive infections. This study has found up to 85% resistance
to routinely used antimicrobial drugs. Higher levels of drug
resistance were found in urban areas (78% cotrimoxazole resistance)
vs. 39% in rural areas, and identified pneumococcal serotypes
that should optimally be included in vaccine formulation for
Developed Invasive Bacterial Infection Surveillance (IBIS)
to monitor Streptococcus pneumoniae and Hemophilus influenzae
- b prevalence and antibiotic resistance in India. IBIS found:
Significant levels of resistance (up to 85%) to antimicrobial
drugs; higher levels of drug resistance in urban areas (78%
resistance to cotrimoxazole in New Delhi) than in rural areas
(39%), and determined pneumococcal serotypes that must be
included in vaccine formulation for India.
Demonstrated that greater improvements in prescribing practices
resulted when problem oriented, small-group educational approaches
were used in addition to ongoing discussions among clinical
peers that were reinforced by routine supervision and monitoring.
Determined that physician prescribing practices were influenced
by factors other than knowledge of the correct therapeutic
choice. Factors, such as duration of practice, and caregivers'
expectations have an important influence on physician prescribing
practices of antimicrobials.
Showed that compliance in administering cotrimoxazole preparations
was strongly correlated with caregivers' difficulty in administering
The World Health Organization (WHO) estimates that 5 million
neonates die each year. A very large proportion of these neonatal
deaths (3.4 million) take place in the first week of life.
More than 40% of neonatal deaths are caused by infection.
Many cases of neonatal infection never reach treatment facilities,
and the case-fatality rate for those that do ranges from 13%
CHR supports refinement of the IMCI approach for the health
needs of very young infants through:
Applied research on the cause of disease and death in this
Documenting the clinical signs to aid in diagnosis; and
Research on the treatment and prevention strategies to
reduce neonatal mortality.
CHR has also been one of the major advocates for focusing
attention on neonatal health.
Selected CHR Achievements
Field research has found that zinc supplements reduce mortality
by 66% in low birth weight (SGA) infants.
A large multi-center study in The Gambia, Papua New Guinea,
The Philippines and Ethiopia documented that S. pneumoniae
and S. aureus are the most common causes of severe infections
(together comprising more than 40% of infections) in neonates
and young children. This emphasizes the necessity to maintain
adequate stocks of drug formularies to combat these common
neonatal pathogens, and establish an urgent need to deliver
conjugate pneumococcal vaccines to the developing world.
Low birth weight (LBW), not premature birth, was found
to be the most important determinant for subsequent poor growth
in infants and children. Because most study infants experienced
chronic intrauterine undernourishment, catch-up growth was
highly restricted and weight, at 12 months, was highly correlated
with birth weight. Improvement of LBW is likely to lead to
increases in one-year weight and overall infant nutrition
In the process of developing a new diagnostic tool and
treatment approach for Group B Streptococcus and bacterial
vaginosis, which are major causes of perinatal/neonatal deaths.
Validated the verbal autopsy method for determining infant
death in a nationwide study in Bangladesh.
Integrated Management of Childhood Illness
Surveys reveal that many sick children are not properly assessed
and treated by health care providers in developing countries,
and that their parents are poorly advised. At first-level
health facilities in low-income countries, diagnostic supports
such as radiology and laboratory services are minimal or non-existent,
and drugs and equipment are often scarce. Limited supplies
and equipment, combined with an irregular flow of patients,
leave doctors at this level with few opportunities to practice
complicated clinical procedures. Instead, they often rely
on history and signs and symptoms to determine a course of
management that makes the best use of the available resources.
The three components to IMCI are: improving the skills of
health workers; improving the health system, and improving
household and community practices. IMCI is considered to be
among the most cost-effective interventions in both low- and
middle-income countries and most likely to have the greatest
impact on the global burden of disease. As of December 2000,
over 81 countries around the world have adopted IMCI guidelines.
Much of CHR's work supports the refinement and implementation
of IMCI. Through research and field tests, the CHR partners
have developed, refined, and validated the IMCI guidelines.
Implementation of CHR's results through IMCI allows for rapid
dissemination of its findings, and to globally increase the
quality of illness diagnosis, treatment, and prevention. CHR
has 22 completed or ongoing tasks classified specifically
as IMCI activities. However, IMCI related activities are also
included under the categories of acute respiratory infection
and diarrheal disease.
Selected CHR Achievements
Developed a tool to measure the effectiveness of counseling
caregivers in treatment compliance that has been adopted by
the Ugandan Ministry of Health as part of nationwide monitoring
of worker performance.
Developed simple guidelines for emergency triage assessment
and treatment of patients in the developing world.
Validated the basic IMCI outpatient guidelines for treatment
of pneumonia, diarrhea, malnutrition and need for referral
in six countries - these guidelines are the cornerstone of
IMCI which are now widely implemented around the world.
Validated IMCI guidelines were developed for need of referral
in young infants and children with pneumonia in Bangladesh.
Refined the malaria diagnosis guidelines for highly endemic
Developed an IMCI Course for Health Workers.