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William J Moss

Publications and source records attributed to William J Moss.

At least 19 recordsLinked to original sources

Do vaccinated cases transmit measles? A systematic review and meta-analysis.

INTRODUCTION: We reviewed evidence on whether vaccinated individuals can transmit measles and conducted a meta-analysis to understand transmission characteristics. METHODS: We searched and extracted data from peer-reviewed and gray literature and included studies reporting measles transmission events from vaccinated individuals. We meta-analyzed the data to calculate the median number of transmissions from vaccinated cases by measles burden, number of doses, and time since first and last dose. RESULTS: We identified 11,911 peer-reviewed and 22 gray literature records and included 33 articles in our review. Seventy individuals who had received 1 or more doses of measles-containing vaccine transmitted measles virus, resulting in 237 secondary cases. Vaccinated transmitters in eliminated areas were older (median age of 19 years (IQR: 3, 21)) than those in non-eliminated areas (median age 16 years; IQR 13, 18) (p = 0.12). Additionally, 91% (30/33) of studies provided data on subsequent transmission generations, leading to 812 measles cases traced back to vaccinated individuals, with a median of 4 (IQR: 1, 10) cases per vaccinated transmitter. CONCLUSION: Measles transmissions from vaccinated cases, although relatively uncommon, must be considered in public health investigations, as such transmissions can contribute to outbreaks.

Adolescent↗

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. This review discusses the pathogenesis of measles and the likelihood of the worldwide elimination of this disease.

Animals↗

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. HIV-1 genotypes derived from samples stored as dried blood spots were compared to those derived from paired liquid plasma samples in American young adults infected with HIV-1 subtype B. The method reproducibly amplified patient-specific sequences and detected drug resistance mutations from all of the dried blood spots or excess frozen RNA extracts with detectable viremia over a broad range of viral loads (193-3 million HIV-1 RNA copies/mL) in both HIV-1 subtypes B and C infection. This method captured the genetic variation typical of HIV-1 infection, including mutations at usual sites of drug resistance, polymorphisms, and mixtures. This sensitive and reproducible genotypic assay is feasible for detection of antiretroviral resistance in resource-constrained settings.

Adolescent↗

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. Much of the literature details the burden of disease and the causes of morbidity and mortality; few interventional studies have been published. Surveys of international relief organizations showed that most use World Health Organization (WHO), United Nations Children's Fund (UNICEF), and ministry of health guidelines designed for use in stable situations. Organizations were least likely to have formal guidelines on the management of asphyxia, prematurity, and infection in neonates; diagnosis and management of children with human immunodeficiency virus (HIV) infection; active case-finding and treatment of tuberculosis; paediatric trauma; and the diagnosis and management of mental-health problems in children. Guidelines often are not adapted to the different types of health-care workers who provide care in complex emergencies. Evidence-based, locally adapted guidelines for the care of children in complex emergencies should be adopted by ministries of health, supported by WHO and UNICEF, and disseminated to international relief organizations to ensure appropriate, effective, and uniform care.

Adolescent↗

HIV-1 infection as a risk factor for incomplete childhood immunization in Zambia.

Immunizations are of particular importance for human immunodeficiency virus type 1(HIV-1)-infected children as they are at increased risk of severe disease and death from several vaccine-preventable diseases. Outside the United States, however, research on the impact of the HIV-1 epidemic on childhood immunization coverage is sparse. We conducted a nested case-control study in hospitalized children with measles to assess whether HIV-1 infection was a risk factor for incomplete immunization with diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV). Of 473 children, whose immunization status was determined from the immunization record or maternal recall, 23% were incompletely immunized and 19% were HIV-1 infected. After adjusting for age, sex, and measles vaccination status, HIV-1 infection was significantly associated with incomplete immunization with DTP and OPV (adjusted OR 1.9; 95% CI 1.1, 3.3). In a subset of children for whom information on maternal education was available, less than 7 years of school education was a risk factor for incomplete immunization (adjusted OR 3.7; 95% CI 1.8. 7.5). Children from homes with more than three children were twice as likely to be incompletely immunized as those from homes with one to three children. Our findings suggest that HIV-1-infected children are at increased risk of vaccine-preventable diseases not only because of impaired immune responses but because of lower rates of vaccine coverage.

Child, Preschool↗

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. The microarray included 71 pairs of oligonucleotide probes (oligoprobes) immobilized on glass slides. Each pair consisted of a genotype-specific oligoprobe, which matched the sequence of only one target genotype, and a control oligoprobe, which contained mismatches at the nucleotide positions unique to this genotype. A pattern recognition algorithm based on cluster analysis of the ratios of hybridization signals from specific and control oligoprobes was used to identify the specific MV genotype. Following the initial validation, the method was used for rapid genotyping of two panels of coded samples. The results of this study showed good sensitivity (90.7%), specificity (100%), and genotype agreement (91.8%) for the new method compared to the results of genotyping conducted using phylogenetic analysis of viral sequences of the C terminus of the N gene. In addition, the microarray demonstrated the ability to identify potential new genotypes of MV based on the similarity of their hybridization patterns with those of known MV genotypes.

Genotype↗

Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial.

BACKGROUND: Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence. METHODS: We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol. FINDINGS: The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001). INTERPRETATION: Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea. RELEVANCE TO PRACTICE: Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.

CD4 Lymphocyte Count↗

Improved measles surveillance in Cameroon reveals two major dynamic patterns of incidence.

OBJECTIVE: To characterize the province-specific incidence patterns of measles in Cameroon and determine if an increase in measles incidence during the period January 2000-June 2001 is consistent with coincident epidemics in several regions with different inter-epidemic periods. METHOD: Periodic behavior of the monthly measles incidence time-series from each province of Cameroon was analyzed using time-series analysis and cluster techniques. Cumulative incidence in each province of Cameroon over a five-year period was associated with birth rates, and vaccination coverage. RESULTS: Distinct patterns of measles incidence were found in two different areas of Cameroon. The three northern-most provinces experience major epidemics every year. Seven southern provinces show evidence of experiencing major epidemics every third year. In January 2000, Cameroon experienced coincident peaks in these two cycles and thus an increase in measles incidence countrywide over the previous year. Higher cumulative province-specific incidence rates were associated with higher birth rates and lower routine vaccination coverage rates. CONCLUSION: Within one country, two dramatically different dynamic patterns of measles incidence were observed. Long-term surveillance data is crucial to the evaluation of measles immunization campaigns. The availability of a five-year record of measles incidence in Cameroon reveals an interesting dynamic pattern of measles incidence that accounts for the increase in countrywide incidence in 2000-2001.

Cameroon↗

Influence of HIV infection on changes in circulating leukocyte counts during measles in Zambian children.

Measles remains an important problem in Africa, where human immunodeficiency virus type 1 (HIV-1) infection is prevalent. To identify the consequences of coinfection, Zambian children hospitalized with measles were studied at entry, discharge, and 1 month after discharge. All children had low lymphocyte and eosinophil counts at entry and high leukocyte and monocyte counts during recovery. The death of cultured lymphocytes was more prolonged for HIV-positive children. CD38 and Fas were increased on CD4+ and CD8+ lymphocytes, and CD28 was decreased on CD8+ lymphocytes in all children. Abnormalities in CD4+ and CD8+ lymphocyte percentages and CD28 expression associated with HIV infection were preserved during measles. Therefore, the patterns of changes in leukocyte counts were similar, with little evidence that measles exacerbated HIV-associated lymphocyte abnormalities.

Adolescent↗

The association of Blastocystis hominis and Endolimax nana with diarrheal stools in Zambian school-age children.

To determine the prevalence of endoparasites and their association with diarrhea, a survey was conducted in the Southern Province of Zambia that used conventional and molecular techniques applied to stool and urine samples from school-age children (n = 93). Almost half of the stools (49.5%) were diarrhetic. The overall prevalence of Endolimax nana, Schistosoma haematobium, Blastocystis hominis, Giardia lamblia, Cryptosporidium parvum, Encephalitozoon intestinalis, and Strongyloides stercoralis was 64.3, 59.1, 53.8, 19.4, 8.6, 8.6, and 1.1%, respectively. Only the associations between infection with B. hominis and E. nana with diarrhea were statistically significant. Although B. hominis and E. nana are considered to be nonpathogenic organisms, this study demonstrated that they can be associated with diarrhea in children when they occur at high prevalence and intensity. This survey supports the recent evidence that B. hominis and E. nana infections are associated with deficient sanitation and low hygiene standards and can contribute to diarrhea in children in developing countries.

Adolescent↗

Evaluating the impact of the HIV pandemic on measles control and elimination.

OBJECTIVE: To estimate the impact of the HIV pandemic on vaccine-acquired population immunity to measles virus because high levels of population immunity are required to eliminate transmission of measles virus in large geographical areas, and HIV infection can reduce the efficacy of measles vaccination. METHODS: A literature review was conducted to estimate key parameters relating to the potential impact of HIV infection on the epidemiology of measles in sub-Saharan Africa; parameters included the prevalence of HIV, child mortality, perinatal HIV transmission rates and protective immune responses to measles vaccination. These parameter estimates were incorporated into a simple model, applicable to regions that have a high prevalence of HIV, to estimate the potential impact of HIV infection on population immunity against measles. FINDINGS: The model suggests that the HIV pandemic should not introduce an insurmountable barrier to measles control and elimination, in part because higher rates of primary and secondary vaccine failure among HIV-infected children are counteracted by their high mortality rate. The HIV pandemic could result in a 2-3% increase in the proportion of the birth cohort susceptible to measles, and more frequent supplemental immunization activities (SIAs) may be necessary to control or eliminate measles. In the model the optimal interval between SIAs was most influenced by the coverage rate for routine measles vaccination. The absence of a second opportunity for vaccination resulted in the greatest increase in the number of susceptible children. CONCLUSION: These results help explain the initial success of measles elimination efforts in southern Africa, where measles control has been achieved in a setting of high HIV prevalence.

Adolescent↗

Inhibition of HIV-1 replication in human lymphoid tissues ex vivo by measles virus.

Human immunodeficiency virus (HIV) type 1 replication and disease progression are enhanced by various pathogens in coinfected individuals. However, acute infection with measles virus (MV) has been found to suppress HIV-1 replication in coinfected children. We investigated the mechanisms of this phenomenon using human lymphoid tissues coinfected ex vivo with HIV-1 and MV. MV inhibited both CXCR4-tropic (X4) and CCR5-tropic (R5) HIV-1, but the inhibitory effect was particularly profound for R5 virus, which transmits infection and dominates the early stages of HIV-1 disease. MV inhibits the replication of R5 HIV-1 in coinfected tissues by up-regulation of the CC chemokine RANTES, a well-known inhibitor of R5 HIV-1 infection, and this up-regulation is augmented in tissues coinfected with R5 HIV-1. Deciphering the molecular mechanisms by which MV and other pathogens alter local cytokine/chemokine networks and cause tissue microenvironments to become detrimental to HIV-1 may significantly contribute to the development of effective anti-HIV therapies.

Chemokine CCL4↗

Emerging diseases: measles.

High vaccination coverage rates and the administration of a second dose of measles vaccine have resulted in a significant decline in the incidence of measles and neurologic diseases due to measles in many countries. However, intermittent outbreaks of measles still occur even in countries with excellent vaccination coverage, suggesting the existence of high rates of measles virus introduction from endemic regions and/or waning of vaccine-induced immunity. Strategies to sustain high levels of global immunity to measles virus by increasing vaccine coverage with routine and supplementary vaccination campaigns must be supported.

Communicable Diseases, Emerging↗

In vitro suppression of human immunodeficiency virus type 1 replication by measles virus.

During the acute phase of measles, human immunodeficiency virus type 1 (HIV-1)-infected children have a transient, but dramatic, decrease in plasma HIV-1 RNA levels (W. J. Moss, J. J. Ryon, M. Monze, F. Cutts, T. C. Quinn, and D. E. Griffin, J. Infect. Dis. 185:1035-1042, 2002). To determine the mechanism(s) by which coinfection with measles virus (MV) decreases HIV-1 replication, we established an in vitro culture system that reproduces this effect. The addition of MV to CCR5- or CXCR4-tropic HIV-1-infected human peripheral blood mononuclear cells (PBMCs) decreased HIV-1 p24 antigen production in a dose-dependent manner. This decrease occurred with the addition of MV before or after HIV-1. The inhibition of HIV-1 p24 antigen production was decreased when UV-inactivated MV or virus-free supernatant fluid from MV-infected PBMCs was used. Inhibition was not due to increased production of chemokines known to block coreceptor usage by HIV-1, a decrease in the percentage of CD4+ T cells, or a decrease in chemokine receptor expression by CD4+ T cells. Viability of PBMCs was decreased only 10 to 20% by MV coinfection; however, lymphocyte proliferation was decreased by 60 to 90% and correlated with decreased production of p24 antigen. These studies showed that an in vitro system of coinfected PBMCs could be used to dissect the mechanism(s) by which MV suppresses HIV-1 replication in coinfected children and suggest that inhibition of lymphocyte proliferation by MV may play a role in the suppression of HIV-1 p24 antigen production.

CD4 Antigens↗

Estimating the force of measles virus infection from hospitalised cases in Lusaka, Zambia.

Estimates of the force of infection (the rate at which susceptible individuals acquire infection) are essential for modelling the transmission dynamics of infectious diseases and can be a useful tool in evaluating mass vaccination strategies. Few estimates exist of the force of infection of measles virus in sub-Saharan Africa. A mathematical model was applied to age-specific recorded hospital admissions between September 1996 and September 1999 to estimate the force of measles virus infection in Lusaka, Zambia. The average force of infection was estimated to be 20% per year (95% confidence intervals (CI) 16.5, 23.5) which was insensitive to varying assumptions about vaccine coverage. The force of infection varied from year to year (P < 0.001) reflecting the cyclic pattern of measles incidence. The estimated probability of a case being hospitalised decreased with age, consistent with less severe disease in older children. Estimates of the force of infection using routinely available data were consistent with those based upon serological surveys in other sub-Saharan African countries.

Adolescent↗

Measles: immune suppression and immune responses.

Measles is a highly contagious viral disease that remains the leading vaccine-preventable cause of child mortality worldwide. Deaths from measles are due largely to an increased susceptibility to secondary bacterial and viral infections, attributed to a prolonged state of immune suppression. Several abnormalities of the immune system have been described, including changes in lymphocyte number and function, shifts in cytokine responses, immunomodulatory effects of interleukin-10, down regulation of interleukin-12, impaired antigen presentation, and altered interferon alpha/beta signaling pathways. Although the current vaccine is very effective, knowledge of the molecular basis of the immune responses to measles virus could contribute to the development of a safer, more immunogenic measles vaccine. However, the safety of new measles vaccines must be carefully investigated, as two measles vaccines have resulted in unintended immunologic consequences: atypical measles following administration of the formalin-inactivated measles vaccine and increased mortality in girls following administration of high-titer measles vaccines.

Humans↗