Secular trends in pediatric antiretroviral treatment programs in rural and urban Zambia: a retrospective cohort study.

Background: Since 2003 pediatric antiretroviral treatment (ART) programs have scaled-up in sub-Saharan Africa and should be evaluated to assess progress and identify areas for improvement. We evaluated secular trends in the characteristics and treatment outcomes of children in three pediatric ART clinics in urban and rural areas in Zambia.

Methods: Routinely collected data were analyzed from three ART programs in rural (Macha and Mukinge) and urban (Lusaka) Zambia between program implementation and July 2008.

Differences in presentation, treatment initiation, and response among children infected with human immunodeficiency virus in urban and rural Zambia.

Background: Access to pediatric antiretroviral therapy (ART) in rural areas remains limited due to the unique challenges faced by providers and patients. Few rural ART programs have been evaluated to determine whether these challenges affect care and treatment response.

Methods: Routinely collected data from 3 pediatric ART programs in rural and urban Zambia were obtained from medical records.

Barriers to the care of HIV-infected children in rural Zambia: a cross-sectional analysis.

Background: Successful antiretroviral treatment programs in rural sub-Saharan Africa may face different challenges than programs in urban areas. The objective of this study was to identify patient characteristics, barriers to care, and treatment responses of HIV-infected children seeking care in rural Zambia.

Methods: Cross-sectional analysis of HIV-infected children seeking care at Macha Hospital in rural southern Zambia.

HIV-1 infection in Zambian children impairs the development and avidity maturation of measles virus-specific immunoglobulin G after vaccination and infection.

Background: Endemic transmission of measles continues in many countries that have a high human immunodeficiency virus (HIV) burden. The effects that HIV infection has on immune responses to measles and to measles vaccine can impact measles elimination efforts. Assays to measure antibody include the enzyme immunoassay (EIA), which measures immunoglobulin G (IgG) to all measles virus (MV) proteins, and the plaque reduction neutralization (PRN) assay, which measures antibody to the hemagglutinin and correlates with protection.

Population immunity to measles virus and the effect of HIV-1 infection after a mass measles vaccination campaign in Lusaka, Zambia: a cross-sectional survey.

Background: Measles control efforts are hindered by challenges in sustaining high vaccination coverage, waning immunity in HIV-1-infected children, and clustering of susceptible individuals. Our aim was to assess population immunity to measles virus after a mass vaccination campaign in a region with high HIV prevalence.

Methods: 3 years after a measles supplemental immunisation activity (SIA), we undertook a cross-sectional survey in Lusaka, Zambia.

Feasibility of satellite image-based sampling for a health survey among urban townships of Lusaka, Zambia.

Objectives: To describe our experience using satellite image-based sampling to conduct a health survey of children in an urban area of Lusaka, Zambia, as an approach to sampling when the population is poorly characterized by existing census data or maps.

Methods: Using a publicly available Quickbird image of several townships, we created digital records of structures within the residential urban study area using ArcGIS 9.2.

Suppression of human immunodeficiency virus type 1 viral load during acute measles.

Acute measles virus infection can result in a transient decrease in plasma human immunodeficiency virus type 1 (HIV-1) RNA loads. We report the kinetics of plasma HIV-1 RNA loads in 2 Zambian children with confirmed and probable measles, and show that the decline in viral load is of similar magnitude to the first-phase decay rate after initiation of antiretroviral therapy.

Survival from 9 months of age among HIV-infected and uninfected Zambian children prior to the availability of antiretroviral therapy.

Background: Few prospective studies have measured survival rates among human immunodeficiency virus (HIV)-infected children in sub-Saharan Africa prior to the availability of antiretroviral therapy.

Methods: In the context of an observational study of the immunogenicity of measles vaccine in Zambia, we prospectively followed up children from approximately 9 months of age and assessed survival rates, risk factors for mortality, and circumstances at the time of death according to HIV-infection or HIV-exposure status.

Results: There were 56 deaths among 492 study children during follow-up to 3 years of age.

Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa.

Assessment of antiretroviral treatment programmes for HIV-infected children in sub-Saharan Africa is important to enable the development of effective care and improve treatment outcomes. We review the effectiveness of paediatric antiretroviral treatment programmes in sub-Saharan Africa and discuss the implications of these findings for the care and treatment of HIV-infected children in this region. Available reports indicate that programmes in sub-Saharan Africa achieve treatment outcomes similar to those in North America and Europe.

Haemophilus influenzae type b conjugate vaccine use and effectiveness.

Haemophilus influenzae type b (Hib) is an important cause of invasive bacterial disease in children, including meningitis and pneumonia. The introduction of Hib conjugate vaccines into routine vaccination schedules has contributed to a substantial reduction in the burden of Hib-related disease in many developed countries. However, introduction of Hib conjugate vaccines in developing countries has progressed more slowly.

Measles virus inhibits human immunodeficiency virus type 1 reverse transcription and replication by blocking cell-cycle progression of CD4+ T lymphocytes.

Acute measles virus (MV) infection results in a decrease in plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in co-infected children. An in vitro peripheral blood mononuclear cell (PBMC) culture system was used to assess the mechanisms by which MV blocks HIV-1 replication. MV inhibited proliferation of CD4(+) T lymphocytes, the target cell for HIV-1 replication.

Predicted impact of the HIV-1 epidemic on measles in developing countries: results from a dynamic age-structured model.

Background: Although measles incidence has been reduced to low levels in many countries, the potential exists for HIV-1 infection to enhance measles virus (MV) transmission and hinder measles control and elimination efforts.

Methods: HIV-1 infection was incorporated into an age-structured, deterministic compartmental model of MV transmission. Parameter estimates were obtained from published studies.

HIV type 1 infection is a risk factor for mortality in hospitalized Zambian children with measles.

Background: Measles remains a significant cause of vaccine-preventable mortality in sub-Saharan Africa, yet few studies have investigated risk factors for measles mortality in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence.

Methods: Between January 1998 and July 2003, children with clinically diagnosed measles who were hospitalized at the University Teaching Hospital in Lusaka, Zambia, were enrolled in an observational study. Demographic and clinical information was recorded at enrollment and at discharge or death.

The influence of HIV-1 exposure and infection on levels of passively acquired antibodies to measles virus in Zambian infants.

Background: The age at which passively acquired antibodies are lost is critical to determining the optimal age for measles vaccination. Little is known about the influence of human immunodeficiency virus type 1 (HIV-1) infection on levels of prevaccination antibodies to measles virus.

Methods: Antibodies to measles virus were measured by plaque reduction neutralization assay in HIV-1-infected, HIV-seropositive but uninfected, and HIV-seronegative Zambian infants aged 6 weeks to 9 months.

Measles vaccines.

Measles is caused by infection with measles virus (MV), a negative strand RNA virus in the Morbillivirus genus of the Paramyxoviridae family. Measles is a highly infectious disease of humans spread by the respiratory route and characterized by fever and rash. Important complications include secondary infections associated with MV-induced immune suppression and the neurological disease post-infectious encephalomyelitis.

Slow clearance of measles virus RNA after acute infection.

Background: Measles virus (MV) RNA was detected 1 month after hospitalization with measles in more than half of Zambian children but the duration of detectable RNA was not determined.

Objectives: To characterize the time course of MV clearance and identify factors associated with presence of viral RNA at late times after clinical recovery from infection.

Study Design: Blood, urine and nasopharyngeal specimens from 49 Zambian children with laboratory-confirmed measles were collected a median of 100 days (range 65-118) after rash onset.

Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: an observational study.

Background: Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination.

Methods: We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka, Zambia.

Results: From May 2000 to November 2002, 696 children aged 2-8 months were enrolled.

Gene expression changes in peripheral blood mononuclear cells during measles virus infection.

Measles virus continues to cause morbidity and mortality despite the existence of a safe and efficacious vaccine. Measles is associated with induction of both a long-lived protective immune response and immunosuppression. To gain insight into immunological changes during measles virus infection, we examined gene expression in blood mononuclear cells from children with acute measles and children in the convalescent phase compared to uninfected control children.

Hemagglutinin protein is a primary target of the measles virus-specific HLA-A2-restricted CD8+ T cell response during measles and after vaccination.

To characterize the measles virus (MV)-specific T cell responses important for evaluation of measles vaccines, human leukocyte antigen (HLA)-A2-positive and -negative adults immunized with measles-mumps-rubella vaccine were studied. Both groups developed increases in antibody and in interferon (IFN)- gamma -producing cells in response to pooled hemagglutinin (H) and fusion peptides. HLA-A2-binding peptides were predicted for all MV-encoded proteins and confirmed by T2 cell stabilization.

Measles still has a devastating impact in unvaccinated populations.

Although global mortality from measles is falling, a study in found that children in Nigeria, Niger, and Chad face unacceptably high mortality from measles, a largely preventable disease.

Global measles elimination.

Measles remains a leading vaccine-preventable cause of child mortality worldwide, particularly in sub-Saharan Africa where almost half of the estimated 454,000 measles deaths in 2004 occurred. However, great progress in measles control has been made in resource-poor countries through accelerated measles-control efforts. The global elimination of measles has been debated since measles vaccines were first licensed in the 1960's, and this debate is likely to be renewed if polio virus is eradicated.

Genotyping of measles virus in clinical specimens on the basis of oligonucleotide microarray hybridization patterns.

An oligonucleotide microarray hybridization method for identification of most known measles virus (MV) genotypes was developed. Like the conventional genotyping method, the microarray relied on detecting sequence differences in the 450-nucleotide region coding for the COOH-terminal 150 amino acids of the nucleoprotein (N). This region was amplified using PCR primers binding to all known MV genotypes.

A sensitive genotyping assay for detection of drug resistance mutations in reverse transcriptase of HIV-1 subtypes B and C in samples stored as dried blood spots or frozen RNA extracts.

Exposure to antiretroviral drugs in resource-constrained settings is likely to result in the emergence of drug-resistant HIV-1 variants, limiting treatment options. Genotypic drug resistance testing assists clinical management and outcomes assessment, but a sensitive and reproducible genotypic assay feasible for resource-constrained settings is needed. A sensitive, reproducible genotyping assay to detect HIV-1 drug resistance mutations in reverse transcriptase and protease was developed and validated using blood stored as dried blood spots or as frozen RNA extracts from Zambian children infected with subtype C.

Child health in complex emergencies.

Coordinated and effective interventions are critical for relief efforts to be successful in addressing the health needs of children in situations of armed conflict, population displacement, and/or food insecurity. We reviewed published literature and surveyed international relief organizations engaged in child health activities in complex emergencies. Our aim was to identify research needs and improve guidelines for the care of children.