Mwaka Monze

Declining HIV prevalence and risk behaviours in Zambia: evidence from surveillance and population-based surveys.

ObjectiveTo examine trends in HIV prevalence and behaviours in Zambia during the 1990s. MethodsThe core Zambian system for epidemiological surveillance and research has two major components: (i) HIV sentinel surveillance at selected antenatal clinics (ANC) in all provinces; and (ii) population-based HIV surveys in selected sentinel populations (1996 and 1999). The former was refined in 1994 to improve the monitoring of prevalence trends, whereas the latter was designed to validate ANC-based data, to study change in prevalence and behaviour concomitantly and to assess demographic impacts. ResultsThe ANC-based data showed a dominant trend of significant declines in HIV prevalence in the 15–19 years age-group, and for urban sites also in age-group 20–24 years and overall when rates were adjusted for over-representation of women with low education. In the general population prevalence declined significantly in urban women aged 15–29 years whereas it showed a tendency to decline among rural women aged 15–24 years. Prominent decline in prevalence was associated with higher education, stable or rising prevalence with low education. There was evidence in urban populations of increased condom use, decline in multiple sexual partners and, among younger women, delayed age at first birth. ConclusionsThe results suggested a dominant declining trend in HIV prevalence that corresponds to declines in incidence since the early 1990s attributable to behavioural changes. Efforts to sustain the ongoing process of change in the well-educated segments of the population should not be undervalued, but the modest change in behaviour identified among the most deprived groups represents the major preventive challenge.

Prolonged Measles Virus Shedding in Human Immunodeficiency Virus—Infected Children, Detected by Reverse Transcriptase—Polymerase Chain Reaction

A reverse transcriptase-polymerase chain reaction assay was used to detect measles virus RNA in peripheral blood mononuclear cells, urine, and nasopharyngeal specimens from Zambian children during hospitalization and approximately 1-2 months after discharge. Of 47 children, 29 (61.7%) had prolonged measles virus shedding, as defined by detection of measles virus RNA in > or =1 specimen obtained 30-61 days after rash onset. Ten (90.9%) of 11 human immunodeficiency virus (HIV)-infected children had prolonged measles virus shedding, compared with 19 (52.8%) of 36 HIV-uninfected children (P=.02). Prolonged measles virus shedding did not correlate with levels of measles virus-specific antibody. HIV-infected children with measles may have a prolonged infectious period that potentially enhances measles virus transmission and hinders measles control.

Suppression of Human Immunodeficiency Virus Replication during Acute Measles

To determine the effect of measles virus coinfection on plasma human immunodeficiency virus (HIV) RNA levels, a prospective study of hospitalized children with measles was conducted between January 1998 and October 2000 in Lusaka, Zambia. Plasma HIV RNA levels were measured during acute measles and 1 month after hospital discharge. The median plasma HIV RNA level in 33 children with measles who were followed longitudinally was 5339 copies/mL at study entry, 60,121 copies/mL at hospital discharge, and 387,148 copies/mL at 1-month follow-up. The median plasma HIV RNA level in children without acute illness was 228,454 copies/mL. Plasma levels of immune activation markers were elevated during the period of reduced plasma HIV RNA. Plasma levels of several potential HIV suppressive factors also were elevated during acute measles. HIV replication is transiently suppressed during acute measles at a time of intense immune activation.

Differential Regulation of Interleukin (IL)–4, IL-5, and IL-10 during Measles in Zambian Children

To determine the effect of measles virus infection on cytokine production in children from sub-Saharan Africa, temporal changes in cytokine production in vivo were analyzed and the T cell sources of type 1 and type 2 cytokines were identified in Zambian children with measles. The immune response during measles involved early type 1 responses, with production of interferon-gamma by CD8(+) T cells and of interleukin (IL)-2 by CD4(+) T cells. Subsequently, more-prolonged increases were observed in the type 2 cytokines IL-4 and IL-13, both produced by CD4(+) T cells. IL-5 was regulated differently from IL-4 and IL-13: levels were low compared with levels in control children and were reflected in lower eosinophil counts during measles. Immunoglobulin E was lower in children with measles, despite high levels of IL-4 and IL-13. Plasma levels of IL-10 were elevated for weeks, potentially contributing to impaired cellular immunity and depressed hypersensitivity responses following measles.

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. Within 6 months of vaccination, 88% of 50 HIV-1-infected children developed antibody levels of >or=120 mIU/mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P=.3). By 27 months after vaccination, however, only half of the 18 HIV-1-infected children who survived and returned for follow-up maintained measles antibody levels >or=120 mIU/mL, compared with 89% of 71 uninfected children (P=.001) and in contrast with 92% of 12 HIV-1-infected children revaccinated during a supplemental measles immunization activity. CONCLUSIONS Although HIV-1-infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence.

Prospective Study of Measles in Hospitalized, Human Immunodeficiency Virus (HIV)—Infected and HIV—Uninfected Children in Zambia

Measles in persons coinfected with human immunodeficiency virus (HIV) has been reported to be unusual in its presentation and frequently fatal. To determine the effect of HIV coinfection on the clinical features and outcome of measles, a prospective study of hospitalized children with measles was conducted between January 1998 and October 2000 in Lusaka, Zambia. One-sixth (17%) of 546 children hospitalized with laboratory-confirmed measles were coinfected with HIV. One-third of the HIV-infected children hospitalized with confirmed measles were <9 months old, compared with 23% of HIV-uninfected children (P=.03). Few differences in clinical manifestations, complications, or mortality were found between HIV-infected and HIV-uninfected children with measles. HIV-infected children constitute a significant proportion of children hospitalized with measles in countries with high HIV prevalence and are more likely to be younger than the age for routine measles immunization.

Functional and Phenotypic Changes in Circulating Lymphocytes from Hospitalized Zambian Children with Measles

ABSTRACT Measles is associated with immunosuppression and increased susceptibility to secondary infections and is a particular problem in developing countries. Lymphocyte changes accompanying immune activation and regulation of the immune response may contribute to immunosuppression. To evaluate lymphocyte changes during measles, children (n = 274) hospitalized with measles in Lusaka, Zambia, were evaluated at entry, discharge, and 1-month follow-up and compared to healthy Zambian children (n = 98). Lymphopenia was present on hospital admission and reflected decreased CD4 and CD8 T cells but resolved quickly. Lymphopenia was most marked in girls, in those with temperatures of >38.5°C, and in malnourished children. CD4/CD8 ratios were decreased at all time points and were lower in boys than in girls at discharge and follow-up. Spontaneous death occurred in cultured lymphocytes, and the proportions of freshly isolated cells undergoing apoptosis, based on annexin V and propidium iodide staining, were increased. Surface Fas was increased on both CD4 and CD8 T cells compared to controls, and expression was greater on CD4 T cells and was inversely correlated with lymphocyte viability in culture at study entry. Mitogen stimulation of lymphocytes improved viability, but inhibitors of Fas, tumor necrosis factor (TNF)-related apoptosis-inducing ligand, and TNF did not. Plasma levels of β2 microglobulin and soluble Fas, Fas ligand, CD8, CD4, and TNF receptor were increased, and soluble CD8 was higher in boys than in girls. The multiple effects of measles on lymphocytes from Zambian children include decreased numbers in circulation, increased activation, and increased susceptibility to cell death, with substantive differences in the magnitude of these changes between boys and girls.

Predominant Human Herpesvirus 6 Variant A Infant Infections in an HIV-1 Endemic Region of Sub-Saharan Africa

Human herpesvirus 6, HHV‐6, commonly infects children, causing febrile illness and can cause more severe pathology, especially in an immune compromised setting. There are virulence distinctions between variants HHV‐6A and B, with evidence for increased severity and neurotropism for HHV‐6A. While HHV‐6B is the predominant infant infection in USA, Europe and Japan, HHV‐6A appears rare. Here HHV‐6 prevalence, loads and variant genotypes, in asymptomatic compared to symptomatic infants were investigated from an African region with endemic HIV‐1/AIDS. DNA was extracted from blood or sera from asymptomatic infants at 6 and 18 months age in a population‐based micronutrient study, and from symptomatic infants hospitalised for febrile disease. DNA was screened by qualitative and quantitative real‐time PCR, then genotyped by sequencing at variable loci, U46 (gN) and U47 (gO). HIV‐1 serostatus of infants and mothers were also determined. HHV‐6 DNA prevalence rose from 15% to 22% (80/371) by 18 months. At 6 months, infants born to HIV‐1 positive mothers had lower HHV‐6 prevalence (11%, 6/53), but higher HCMV prevalence (25%, 17/67). HHV‐6 positive febrile hospitalized infants had higher HIV‐1, 57% (4/7), compared to asymptomatic infants, 3% (2/74). HHV‐6A was detected exclusively in 86% (48/56) of asymptomatic HHV‐6 positive samples genotyped. Co‐infections with both strain variants were linked with higher viral loads and found in 13% (7/56) asymptomatic infants and 43% (3/7) HIV‐1 positive febrile infants. Overall, the results show HHV‐6A as the predominant variant significantly associated with viremic infant‐infections in this African population, distinct from other global cohorts, suggesting emergent infections elsewhere. J. Med. Virol. 81:779–789, 2009.

Human Cytomegalovirus Infant Infection Adversely Affects Growth and Development in Maternally HIV-Exposed and Unexposed Infants in Zambia

Maternally human immunodeficiency virus (HIV)-exposed but seronegative Zambian infants had reduced length and psychomotor development associated with human cytomegalovirus infection. Slower growth was also associated with human cytomegalovirus in HIV-unexposed infants. We conclude that human cytomegalovirus impacts negatively on child health in HIV-endemic regions of sub-Saharan Africa.

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. Antibody avidity may affect neutralizing capacity. METHODS HIV-infected and HIV-uninfected Zambian children were studied after measles vaccination (n=44) or MV infection (n=57). Laboratory or wild-type MV strains were used to infect Vero or Vero/signaling lymphocyte-activation molecule (SLAM) cells in PRN assays. IgG to MV was measured by EIA, and avidity was determined by ammonium thiocyanate dissociation. RESULTS HIV infection impaired EIA IgG responses after vaccination and measles but not PRN responses measured using laboratory-adapted MV. Avidity was lower among HIV-infected children 3 months after vaccination and 1 and 3 months after measles. Neutralization of wild-type MV infection of Vero/SLAM cells correlated with IgG avidity. CONCLUSION Lower antibody quality and quantity in HIV-infected children after measles vaccination raise challenges for assuring the long-term protection of these children. Antibody quality in children receiving antiretroviral therapy requires assessment.