William J. Moss

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. However, progress in several areas is required to improve the care of HIV-infected children in sub-Saharan Africa. The findings emphasise the need for low-cost diagnostic tests that allow for earlier identification of HIV infection in infants living in sub-Saharan Africa, improved access to antiretroviral treatment programmes, including expansion of care into rural areas, and the integration of antiretroviral treatment programmes with other health-care services, such as nutritional support.

Immunization of children at risk of infection with human immunodeficiency virus

This paper reviews the English language literature on the safety, immunogenicity and effectiveness in children infected with the human immunodeficiency virus (HIV) of vaccines currently recommended by WHO for use in national immunization programmes. Immunization is generally safe and beneficial for children infected with HIV, although HIV-induced immune suppression reduces the benefit compared with that obtained in HIV-uninfected children. However, serious complications can occur following immunization of severely immunocompromised children with bacillus Calmette-Gu rin (BCG) vaccine. The risk of serious complications attributable to yellow fever vaccine in HIV-infected persons has not been determined. WHO guidelines for immunizing children with HIV infection and infants born to HIV-infected women differ only slightly from the general guidelines. BCG and yellow fever vaccines should be withheld from symptomatic HIV-infected children. Only one serious complication (fatal pneumonia) has been attributed to measles vaccine administered to a severely immunocompromised adult. Although two HIV-infected infants have developed vaccine-associated paralytic poliomyelitis, several million infected children have been vaccinated and the evidence does not suggest that there is an increased risk. The benefits of measles and poliovirus vaccines far outweigh the potential risks in HIV-infected children. The policy of administering routine vaccines to all children, regardless of possible HIV exposure, has been very effective in obtaining high immunization coverage and control of preventable diseases. Any changes in this policy would have to be carefully examined for a potential negative impact on disease control programmes in many countries.

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 1960s, 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.

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 Greys 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.

Research Priorities for the Reduction of Perinatal and Neonatal Morbidity and Mortality in Developing Country Communities

Although post-neonatal and child mortality rates have declined dramatically in many developing countries in recent decades, neonatal mortality rates have remained relatively unchanged. Neonatal mortality now accounts for approximately two-thirds of the 8 million deaths in children less than 1 year of age, and nearly four-tenths of all deaths in children less than 5 years of age. Worldwide, 98% of all neonatal deaths occur in developing countries, mostly at home, and largely attributable to infections, birth asphyxia and injuries, and consequences of prematurity, low birth weight and congenital anomalies. We review principal determinants of neonatal morbidity and mortality during the antenatal, intrapartum and postpartum periods, and propose priority community-based research activities to develop, test and adapt inexpensive, practical and sustainable interventions during these periods to reduce perinatal and neonatal morbidity and mortality in developing countries.

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. We review the worldwide use and effectiveness of Hib conjugate vaccines. At present, 119 countries have programmes for routine Hib immunisation. WHO estimates that in the developed world 92% of the eligible population is vaccinated against Hib; however, average coverage is 42% in developing countries and only 8% in the poorest countries. Africa and southeast Asia have the lowest rates of Hib vaccine introduction. Vaccine costs and debate about the burden of disease are obstacles to the global use of Hib conjugate vaccine. Even with new funding support, there are many ongoing challenges and vaccine use remains suboptimal, particularly in developing countries.

A method of active case detection to target reservoirs of asymptomatic malaria and gametocyte carriers in a rural area in Southern Province, Zambia

BackgroundAsymptomatic reservoirs of malaria parasites are common yet are difficult to detect, posing a problem for malaria control. If control programmes focus on mosquito control and treatment of symptomatic individuals only, malaria can quickly resurge if interventions are scaled back. Foci of parasite populations must be identified and treated. Therefore, an active case detection system that facilitates detection of asymptomatic parasitaemia and gametocyte carriers was developed and tested in the Macha region in southern Zambia.MethodsEach week, nurses at participating rural health centres (RHC) communicated the number of rapid diagnostic test (RDT) positive malaria cases to a central research team. During the dry season when malaria transmission was lowest, the research team followed up each positive case reported by the RHC by a visit to the homestead. The coordinates of the location were obtained by GPS and all consenting residents completed a questionnaire and were screened for malaria using thick blood film, RDT, nested-PCR, and RT-PCR for asexual and sexual stage parasites. Persons who tested positive by RDT were treated with artemether/lumefantrine (Coartem®). Data were compared with a community-based study of randomly selected households to assess the prevalence of asymptomatic parasitaemia in the same localities in September 2009.ResultsIn total, 186 and 141 participants residing in 23 case and 24 control homesteads, respectively, were screened. In the case homesteads for which a control population was available (10 of the 23), household members of clinically diagnosed cases had a 8.0% prevalence of malaria using PCR compared to 0.7% PCR positive individuals in the control group (p = 0.006). The case and control groups had a gametocyte prevalence of 2.3% and 0%, respectively but the difference was not significant (p = 0.145).ConclusionsThis pilot project showed that active case detection is feasible and can identify reservoirs of asymptomatic infection. A larger sample size, data over multiple low transmission seasons, and in areas with different transmission dynamics are needed to further validate this approach.

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.

Implications of the Human Immunodeficiency Virus Epidemic for Control and Eradication of Measles

Human immunodeficiency virus (HIV)-infected persons may be important, unrecognized transmitters of measles virus, thwarting eradication efforts. We reviewed the published English-language literature on measles and measles immunization in HIV-infected persons to investigate the clinical features of measles, the responses to measles immunization, and the safety of measles vaccine in HIV-infected persons and, conversely, the effect of measles and measles immunization on HIV infection. HIV-infected persons with measles are likely to have uncharacteristic clinical findings and severe illness, with high rates of pneumonitis and death. Primary and secondary failure of measles vaccine in HIV-infected children may permit transmission of measles virus in spite of high rates of immunization coverage. A factor that complicates measles-control efforts in areas of high prevalence of HIV is the potential for fatal infection with measles vaccine virus. Further research on the impact of the HIV epidemic on measles and measles immunization is necessary to guide strategies for the eradication of measles.

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.