HIV-uninfected Children Research Articles

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.

Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.

Maternal HIV disclosure to young HIV-uninfected children: an evaluation of a family-centred intervention in South Africa.

Sub-Saharan Africa has large populations of HIV-infected parents who need support to raise their HIV-uninfected children. This research evaluates the 'Amagugu Intervention' aimed at supporting mothers to disclose their own HIV diagnosis to their HIV-uninfected children. Uncontrolled pre and post-intervention evaluation. Africa Centre for Health and Population Studies, South Africa. Two hundred and eighty-one HIV-infected women and their HIV-uninfected children aged 6-10 years. This lay counsellor-led intervention included six sessions conducted with mothers at home, providing printed materials and child-friendly activities to support disclosure of their diagnosis. The primary outcome was disclosure to the child (full, partial, none). The secondary outcomes included maternal mental health (General Health Questionnaire) and child mental health (Child Behaviour Checklist). One hundred and seventy-one (60%) women 'fully' disclosed and 110 (40%) women 'partially' disclosed their HIV status to their child. Women who perceived their health to be excellent were less likely to 'fully' disclose compared to those considering their health to be poorer [adjusted odds ratio 0.50 (0.26-0.98), P = 0.042]. [corrected]. Compared to those not in a current partnership, those with a current partner were almost three times more likely to 'fully' disclose [adjusted odds ratio 2.92 (1.33-6.40), P = 0.008]. Mothers reported that most children reacted calmly to 'full' (79%) or 'partial' disclosure (83%). Compared to 'partial' disclosure, 'full' disclosure was associated with more children asking questions about maternal death (18 versus 8%). This intervention is acceptable in resource-limited settings and shows promise. Further research using a controlled design is needed to test this intervention.

Effectiveness of 7-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in HIV-infected and -uninfected children in south africa: a matched case-control study.

South Africa introduced 7-valent pneumococcal conjugate vaccine (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We estimated the effectiveness of ≥2 PCV7 doses against invasive pneumococcal disease (IPD) in human immunodeficiency virus (HIV)-infected and -uninfected children. IPD (pneumococcus identified from a normally sterile site) cases were identified through national laboratory-based surveillance. Specimens were serotyped by Quellung or polymerase chain reaction. Four controls, matched for age, HIV status, and hospital were sought for each case. Using conditional logistic regression, we calculated vaccine effectiveness (VE) as 1 minus the adjusted odds ratio for vaccination. From March 2010 through November 2012, we enrolled 187 HIV-uninfected (48 [26%] vaccine serotype) and 109 HIV-infected (43 [39%] vaccine serotype) cases and 752 HIV-uninfected and 347 HIV-infected controls aged ≥16 weeks. Effectiveness of ≥2 PCV7 doses against vaccine-serotype IPD was 74% (95% confidence interval [CI], 25%-91%) among HIV-uninfected and -12% (95% CI, -449% to 77%) among HIV-infected children. Effectiveness of ≥3 doses against vaccine-serotype IPD was 90% (95% CI, 14%-99%) among HIV-uninfected and 57% (95% CI, -371% to 96%) among HIV-infected children. Among HIV-exposed but -uninfected children, effectiveness of ≥2 doses was 92% (95% CI, 47%-99%) against vaccine-serotype IPD. Effectiveness of ≥2 doses against all-serotype multidrug-resistant IPD was 96% (95% CI, 62%-100%) among HIV-uninfected children. A 2 + 1 PCV7 schedule was effective in preventing vaccine-serotype IPD in HIV-uninfected and HIV-exposed, uninfected children. This finding supports the World Health Organization recommendation for this schedule as an alternative to a 3-dose primary series among HIV-uninfected individuals.

Short Intensified Treatment in Children with Drug-susceptible Tuberculous Meningitis

The World Health Organization recommends 12-month treatment (2RHZE/10RH) for children with tuberculous meningitis (TBM). Studies evaluating length of antituberculous treatment for TBM report similar completion and relapse rates comparing 6-month treatment with 12-month treatment. A prospective evaluation to determine whether short-course intensified treatment (6 RHZEth for HIV-infected and 9RHZEth for HIV-infected) is sufficient and safe in children with drug-susceptible TBM. Of 184 children with TBM, median age 58 months and 90 (49%) male, 98 children (53%) presented at stage II TBM, 64 (35%) at stage III TBM and only 22 (12%) at stage I TBM. Ninety (49%) children were treated at home after the first month of therapy; all others received their full treatment in hospital. The HIV prevalence was 14% (22/155 children tested). Anti-TB drug-induced hepatotoxicity occurred in 5% (8 of 143 children tested), all tested negative for viral hepatitis; in all 8 cases, the original regimen was restarted without recurrence. After treatment completion, 147 (80%) children had a good outcome, 7 (3.8%) died. There was no difference in outcome between HIV-infected and HIV-uninfected children who completed treatment (P = 0.986) nor between TBM-hydrocephalic children who were medically treated or shunted (P = 0.166). Short intensified treatment is safe and effective in both HIV-infected and HIV-uninfected children with drug-susceptible TBM.

Mortality Associated With Seasonal and Pandemic Influenza and Respiratory Syncytial Virus Among Children &lt;5 Years of Age in a High HIV Prevalence Setting—South Africa, 1998–2009

There are few published data describing the mortality burden associated with influenza and respiratory syncytial virus (RSV) infection in children in low- and middle-income countries and particularly from Africa and settings with high prevalence of human immunodeficiency virus (HIV). We modeled the excess mortality attributable to influenza (seasonal and pandemic) and RSV infection by applying Poisson regression models to monthly all-respiratory and pneumonia and influenza deaths, using national influenza and RSV laboratory surveillance data as covariates. In addition, we estimated the seasonal influenza- and RSV-associated deaths among HIV-infected and -uninfected children using Poisson regression models that incorporated HIV prevalence and highly active antiretroviral therapy coverage as covariates. In children <5 years of age, the mean annual numbers of seasonal influenza- and RSV-associated all-respiratory deaths were 452 (8 per 100 000 person-years [PY]) and 546 (10 per 100 000 PY), respectively. Infants <1 year of age experienced higher mortality rates compared with children 1-4 years of age for both influenza (22 vs 5 per 100 000 PY) and RSV (35 vs 4 per 100 000 PY). HIV-infected compared with HIV-uninfected children <5 years of age were at increased risk of death associated with influenza (age-adjusted relative risk [aRR], 11.5; 95% confidence interval [CI], 9.6-12.6) and RSV (aRR, 8.1; 95% CI, 6.9-9.3) infection. In 2009, we estimated 549 (11 per 100 000 PY) all-respiratory influenza A(H1N1)pdm09-associated deaths among children aged <5 years. Our findings support increased research efforts to guide and prioritize interventions such as influenza vaccination and HIV prevention in low- and middle-income countries with high HIV prevalence such as South Africa.

Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children

BackgroundAdvances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and –KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI).MethodsMultiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and –uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I–III, adenovirus and influenza A/B.ResultsAt least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and –uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than –uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV–uninfected children).ConclusionsWe established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI.

Update on the Diagnosis and Management of Tuberculous Meningitis in Children

Tuberculous meningitis (TBM), the most devastating manifestation of tuberculosis, is often missed or overlooked because of nonspecific symptoms and difficulties in diagnosis. It continues to be an important cause of neurologic handicap in resource-poor countries. Owing to the suboptimal performance of diagnostic tests of TBM, diagnosis relies on thorough history, clinical examination, and relevant investigations. The development of affordable, accurate diagnostic tests for TBM in resource-poor settings remains a priority. Short intensified treatment is safe and effective in both human immunodeficiency virus (HIV)-infected and HIV-uninfected children. Treatment of tuberculous hydrocephalus depends on the level of the cerebrospinal fluid obstruction. Corticosteroids reduce risk of neurodisability and death in HIV-uninfected children. Thalidomide should be considered in children compromised by tuberculosis abscesses and tuberculous-related optochiasmic arachnoiditis. In resource-poor countries, home-based TBM treatment after initial in-hospital stabilization is feasible in carefully selected patients. Early diagnosis and treatment of TBM is the single most important factor determining outcome.

Serum Selenium Levels and Nutritional Status of School Children from an HIV Prevention Programme in Zimbabwe

Nutrition programmes in resource poor settings mainly focus on children under the age of five years and this has resulted in limited information on nutritional and micronutrient status of school children in areas with high burden of HIV infection. This cross-sectional study assessed the prevalence of, and factors associated with stunting, thinness, overweight, underweight and selenium deficiency in school aged children from a high HIV burden peri-urban area in Zimbabwe, a low income country. Seven to 10 year old children from a prevention of mother-to-child transmission of HIV cohort had their serum selenium levels determined by mass spectrometry in a cross-sectional study. Height, weight, mid-upper-arm and head circumferences were measured to determine the prevalence of stunting, thinness, underweight and wasting. WHO growth standards were used to define the children's nutritional status. A total of 318 children including 21 (7%) HIV infected were assessed. The prevalence of stunting, thinness and underweight was 12%, 4% and 8% respectively. The prevalence of Selenium deficiency (serum Selenium <0.89 μmol/L) was 48% and it was found to be high in all the children despite their HIV status. Stunting was associated with HIV infection and orphan hood. There was no difference in height or weight between the HIV uninfected (exposed and unexposed) children who were in comparison both taller and heavier than the HIV infected children. Chronic malnutrition and selenium deficiency were prevalent in this cohort of children. Further studies are recommended to guide the need for selenium supplementation. Setting up health programmes to identify malnutrition in school aged children should be a priority.

Socioeconomic Indices Performance for HIV Diagnostic on Severely Malnourished Children in Burkina Faso

Children living with HIV should be diagnosed as early as possible and linked to antiretroviral treatment. The costs of HIV virological testing, individual and social implications of the disease require critical quality of the medical approach to diagnostic strategy. Socioeconomic data can be used to refine the medical decision. The objective of this analysis was to determine informative capacity of socioeconomic indices in the diagnosis and approach of HIV in severely malnourished children using receiver operating characteristic (ROC) curves. Materials and Methods: This was a test performance analysis conducted from data of severely malnourished children at an inpatient feeding therapeutic center in Ouagadougou. Anthropometric and social indices have been used as tests; their sensitivity, specificity and predictive values have been calculated. ROC curves and areas under curves were obtained. Medical decision aid scheme has been validated from severely malnourished children data. Results: Socioeconomic indices showed high performance to discriminate severely malnourished HIV infected and uninfected children, with high area under ROC curves. The medical decision aid scheme specificity reached 97.6% with predictive values close to 85%. Conclusion: This approach can help for expanding ART for children in low income countries and achieve the maximum ART benefits in child socioeconomic kneed context.

Anaemia and iron deficiency in peri-urban school children born in a National HIV Prevention Programme in Zimbabwe: A cross-sectional study.

To determine the prevalence of anaemia, iron deficiency and iron deficiency anaemia in school children who were born in a national HIV prevention programme. This was a community based cross-sectional study. A resource poor peri-urban setting with high prevalence of HIV infection. School aged children six to 10 years old who were born in a national mother-to-child HIV prevention programme. Haemoglobin (Hb), serum Ferritin (F) and serum Transferrin receptor (sTfR) levels. Three hundred and eighteen children were recruited including 21 HIV positive. The prevalence of anaemia (Hb < 11.5 grams per litre), iron deficiency (F<15 micrograms per litre) and iron deficiency anaemia (Hb < 11.5 g/L and either F < 15 μg/L or sTfR > 8.3 μg/L) were 15%, 4% and 2% respectively. When a higher cut-off for ferritin of 30 micrograms per litre was applied to adjust for high infection disease burden, iron deficiency prevalence increased to 32% and iron deficiency anaemia increased to 5%. Anaemia was 4.9 (C.I 1.9-12.4) times more likely to occur in HIV infected children compared to the HIV uninfected children. Maternal HIV status at birth was not related to presence of anaemia in the school children. Anaemia was of mild public health significance in this cohort of children. Iron deficiency anaemia contributed less than a quarter of the cases of anaemia. HIV infection was an important determinant for presence of anaemia. Therefore continued efforts to eliminate paediatric HIV infection as a way of reducing anaemia in children are essential.

Tuberculosis and HIV co-infection in children.

HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes.Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV.ConclusionData on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings.

Humoral Immune Responses to Pneumocystis jirovecii Antigens in HIV-Infected and Uninfected Young Children with Pneumocystis Pneumonia

BackgroundHumoral immune responses in human immunodeficiency virus (HIV)-infected and uninfected children with Pneumocystis pneumonia (PcP) are poorly understood. MethodsConsecutive children hospitalized with acute pneumonia, tachypnea, and hypoxia in South Africa were investigated for PcP, which was diagnosed by real-time polymerase chain reaction on lower respiratory tract specimens. Serum antibody responses to recombinant fragments of the carboxyl terminus of Pneumocystis jirovecii major surface glycoprotein (MsgC) were analyzed. Results149 children were enrolled of whom 96 (64%) were HIV-infected. PcP occurred in 69 (72%) of HIV-infected and 14 (26%) of HIV-uninfected children. HIV-infected children with PcP had significantly decreased IgG antibodies to MsgC compared to HIV-infected patients without PcP, but had similar IgM antibodies. In contrast, HIV-uninfected children with PcP showed no change in IgG antibodies to MsgC, but had significantly increased IgM antibodies compared to HIV-uninfected children without PCP. Age was an independent predictor of high IgG antibodies, whereas PcP was a predictor of low IgG antibodies and high IgM antibodies. IgG and IgM antibody levels to the most closely related MsgC fragments were predictors of survival from PcP. ConclusionsYoung HIV-infected children with PcP have significantly impaired humoral immune responses to MsgC, whereas HIV-uninfected children with PcP can develop active humoral immune responses. The children also exhibit a complex relationship between specific host factors and antibody levels to MsgC fragments that may be related to survival from PcP.

Epidemiology of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Tract Infection Hospitalizations Among HIV-Infected and HIV-Uninfected South African Children, 2010-2011

There are limited data on respiratory syncytial virus (RSV) infection among children in settings with a high prevalence of human immunodeficiency virus (HIV). We studied the epidemiology of RSV-associated acute lower respiratory tract infection (ALRTI) hospitalizations among HIV-infected and HIV-uninfected children in South Africa. Children aged <5 years admitted to sentinel surveillance hospitals with physician-diagnosed neonatal sepsis or ALRTI were enrolled. Nasopharyngeal aspirates were tested by multiplex real-time polymerase chain reaction assays for RSV and other viruses. Associations between possible risk factors and severe outcomes for RSV infection among HIV-infected and uninfected children were examined. The relative risk of hospitalization in HIV-infected and HIV-uninfected children was calculated in 1 site with population denominators. Of 4489 participants, 4293 (96%) were tested for RSV, of whom 1157 (27%) tested positive. With adjustment for age, HIV-infected children had a 3-5-fold increased risk of hospitalization with RSV-associated ALRTI (2010 relative risk, 5.6; [95% confidence interval (CI), 4.5-6.4]; 2011 relative risk, 3.1 [95% CI, 2.6-3.6]). On multivariable analysis, HIV-infected children with RSV-associated ALRTI had higher odds of death (adjusted odds ratio. 31.1; 95% CI, 5.4-179.8) and hospitalization for >5 days (adjusted odds ratio, 4.0; 95% CI, 1.5-10.6) than HIV-uninfected children. HIV-infected children have a higher risk of hospitalization with RSV-associated ALRTI and a poorer outcome than HIV-uninfected children. These children should be targeted for interventions aimed at preventing severe RSV disease.

Impact of the Antiretroviral Treatment Program on the Burden of Hospitalization for Culture-confirmed Tuberculosis in South African Children

The HIV epidemic increased the burden of tuberculosis (TB) in sub-Saharan Africa. We evaluated the impact that scaling-up of the public-funded antiretroviral treatment (ART) program had on incidence of hospitalization for culture-confirmed and overall-TB in HIV-infected and HIV-uninfected children from 2005 to 2009. The study was undertaken in Soweto, South Africa, where ART coverage of HIV-infected children increased from 43% in 2005 to 84% by 2009. Trends in incidence of hospitalization for clinically diagnosed and culture-confirmed TB in children 3 months to <15 years of age, identified through laboratory and electronic databases, were analyzed by comparing crude incidence and regression analysis. The incidence (per 100,000) of culture-confirmed TB declined by 63.1% from 2005 (69.8) compared with 2009 (25.8; P < 0.0001). This included a 70.6% reduction between 2005 and 2009 among HIV-infected children (incidence: 1566.3 versus 460.7, respectively; P < 0.0001) and 41.3% decrease in HIV-uninfected children (18.7 versus 11.0, respectively; P = 0.0003). The month-by-month rate of decline of culture-confirmed TB was 2.3% in HIV-infected and 1.1% in HIV-uninfected children over the study period. The residual burden of TB remained 42-fold greater in HIV-infected children, 78% of whom were severely immune compromised, compared with HIV-uninfected children by 2009. Increase in ART coverage was associated with significant decline in TB hospitalizations in HIV-infected children. This reduction may also in part have been due to reduced Mycobacterium tuberculosis transmission resulting from increased ART access among HIV-infected adults, which may have contributed to the reduction of culture-confirmed TB in HIV-uninfected children.

Association of Streptococcus pneumoniae common protein antigen (CPA) antibodies and pneumococcal nasopharyngeal colonization in HIV-infected and HIV-uninfected African children

Due to the high cost and limited serotype coverage of pneumococcal conjugate vaccines (PCV), pneumococcal common protein antigens (CPAs) are being investigated as potential vaccine candidates. CPAs are likely to be immunogenic in infants and could confer serotype-independent protection. There are limited data on natural antibody kinetics against CPAs in African populations. We aimed to determine the prevalence of naturally acquired antibody titres to 15 CPAs and explore their association to concurrent pneumococcal nasopharyngeal colonization in children aged 4–7 years with and without underlying HIV-infection and/or previous PCV-vaccination. A 15-plex Luminex assay was established to measure serum IgG titres against “cell-wall associated or surface-exposed” proteins (PspA, PspC, LytB, IgA1-proteinase, SP0082, PdB and PcsB), “membrane-associated” proteins (PsaA, SP0609, SP0749, PpmA, SlrA, StkP and SP2194) as well as the hypothetical protein, SP2027. Archived serum samples from HIV-uninfected (n=212) and HIV-infected (n=74) children were analyzed. Concurrent pneumococcal nasopharyngeal colonization was determined with standard microbiological methods. HIV-uninfected children had significantly higher antibody titres against PspA, PspC, PdB, SP0082, LytB, IgA1 proteinase and PcsB compared to HIV-infected children. In contrast, antibody titres against membrane associated proteins (PsaA, SP2027, PpmA and SlrA) were significantly lower in HIV-uninfected compared to HIV-infected children. Higher antibody titres against PdB, and PcsB were associated with the absence of pneumococcal colonization. There was no association between anti-CPA titres and PCV vaccination. In conclusion PdB and PcsB antigens are potential vaccine-candidates which may protect against pneumococcal colonization and consequently pneumococcal disease.

Ready-to-use therapeutic food for home-based treatment of severe acute malnutrition in children from six months to five years of age.

Malnourished children have a higher risk of death and illness. Treating severe acute malnourished children in hospitals is not always desirable or practical in rural settings, and home treatment may be better. Home treatment can be food prepared by the carer, such as flour porridge, or commercially manufactured food such as ready-to-use therapeutic food (RUTF). RUTF is made according to a standard, energy-rich composition defined by the World Health Organization (WHO). The benefits of RUTF include a low moisture content, long shelf life without needing refrigeration and that it requires no preparation. To assess the effects of home-based RUTF on recovery, relapse and mortality in children with severe acute malnutrition. We searched the following electronic databases up to April 2013: Cochrane Central Register of Clinical Trials (CENTRAL), MEDLINE, MEDLINE In-process, EMBASE, CINAHL, Science Citation Index, African Index Medicus, LILACS, ZETOC and three trials registers. We also contacted researchers and clinicians in the field and handsearched bibliographies of included studies and relevant reviews. We included randomised and quasi-randomised controlled trials where children between six months and five years of age with severe acute malnutrition were treated at home with RUTF compared to a standard diet, or different regimens and formulations of RUTFs compared to each other. We assessed recovery, relapse and mortality as primary outcomes, and anthropometrical changes, time to recovery and adverse outcomes as secondary outcomes. Two review authors independently assessed trial eligibility using prespecified criteria, and three review authors independently extracted data and assessed trial risk of bias. We included four trials (three having a high risk of bias), all conducted in Malawi with the same contact author. One small trial included children infected with human immunodeficiency virus (HIV). We found the risk of bias to be high for the three quasi-randomised trials while the fourth trial had a low to moderate risk of bias. Because of the sparse data for HIV, we reported below the main results for all children together. RUTF meeting total daily requirements versus standard dietWhen comparing RUTF with standard diet (flour porridge), we found three quasi-randomised cluster trials (n = 599). RUTF may improve recovery slightly (risk ratio (RR) 1.32; 95% confidence interval (CI) 1.16 to 1.50; low quality evidence), but we do not know whether RUTF improves relapse, mortality or weight gain (very low quality evidence). RUTF supplement versus RUTF meeting total daily requirementsWhen comparing RUTF supplement with RUTF that meets total daily nutritional requirements, we found two quasi-randomised cluster trials (n = 210). For recovery, relapse, mortality and weight gain the quality of evidence was very low; therefore, the effects of RUTF are unknown. RUTF containing less milk powder versus standard RUTFWhen comparing a cheaper RUTF containing less milk powder (10%) versus standard RUTF (25% milk powder), we found one trial that randomised 1874 children. For recovery, there was probably little or no difference between the groups (RR 0.97; 95% CI 0.93 to 1.01; moderate quality evidence). RUTF containing less milk powder may lead to slightly more children relapsing (RR 1.33; 95% CI 1.03 to 1.72; low quality evidence) and to less weight gain (mean difference (MD) -0.5 g/kg/day; 95% CI -0.75 to -0.25; low-quality evidence) than standard RUTF. We do not know whether the cheaper RUTF improved mortality (very low quality evidence). Given the limited evidence base currently available, it is not possible to reach definitive conclusions regarding differences in clinical outcomes in children with severe acute malnutrition who were given home-based ready-to-use therapeutic food (RUTF) compared to the standard diet, or who were treated with RUTF in different daily amounts or formulations. For this reason, either RUTF or flour porridge can be used to treat children at home depending on availability, affordability and practicality. Well-designed, adequately powered pragmatic randomised controlled trials of HIV-uninfected and HIV-infected children with severe acute malnutrition are needed.

Intestinal parasitic infections in children presenting with diarrhoea in outpatient and inpatient settings in an informal settlement of Nairobi, Kenya.

BackgroundThe distribution of and factors associated with intestinal parasitic infections are poorly defined in high risk vulnerable populations such as urban slums in tropical sub-Saharan Africa.MethodsIn a cross sectional study, children aged 5 years and below who presented with diarrhoea were recruited from selected outpatient clinics in Mukuru informal settlement, and from Mbagathi District hospital, Nairobi, over a period of two years (2010–2011). Stool samples were examined for the presence of parasites using direct, formal-ether concentration method and the Modified Ziehl Neelsen staining technique.ResultsOverall, 541/2112 (25.6%) were positive for at least one intestinal parasite, with the common parasites being; Entamoeba histolytica, 225 (36.7%),Cryptosporidium spp. 187, (30.5%), Giardia lamblia, 98 (16%).The prevalence of intestinal parasites infection was higher among children from outpatient clinics 432/1577(27.4%) than among those admitted in hospital 109/535 (20.1%) p < 0.001. Infections with E. histolytica, and G. lamblia were higher among outpatients than inpatients (13.8% vs 1.3% p < 0.001 and 5.8% vs 1.3% p < 0.049) respectively, while infection with Cryptosporidium spp. was higher among inpatients than outpatients (15.3% vs 6.7%) respectively p < 0.001. Other parasites isolated among outpatients included Isospora belli, 19 (1.2%), Ascaris lumbricoides, 26 (1.6%), and Hymenolepis nana 12 (0.8%), with the remainder detected in less than ten samples each. HIV-infected participants were more likely to be infected with any parasite than uninfected participants, Adjusted Odds Ratio (AOR), 2.04, 95% CI, 1.55-2.67, p < 0.001), and with Cryptosporidium spp. (AOR, 2.96, 95% CI 2.07-4.21, p < 0.001).The inpatients were less likely to be infected with E. histolytica than outpatients (AOR, 0.11, 95% CI, 0.51- 0.24, p < 0.001), but more likely for inpatients to be infected with Cryptosporidium spp. than outpatients (AOR, 1.91, 95% CI, 1.33-2.73, p < 0.001). Mixed parasitic infections were seen in 65 (12.0%) of the 541 infected stool samples.ConclusionIntestinal parasitic infections are common in urban informal settlements’ environment. Routine examinations of stool samples and treatment could benefit both the HIV infected and uninfected children in outpatient and inpatient settings.

Epidemiology of invasive pneumococcal disease in the pre-conjugate vaccine era: South Africa, 2003–2008

IntroductionDynamics of pneumococcal disease incidence and serotype distribution prior to introduction of pneumococcal conjugate vaccines (PCV) will assist in understanding effects of the vaccine over time and will be important in choosing the optimal PCV formulation. MethodsWe conducted active, laboratory-based, national surveillance for invasive pneumococcal disease (IPD) through the Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) from 2003 through 2008. Over 130 laboratories report to this system. Pneumococci were serotyped using Quellung and isolates screened for resistance by disk diffusion; minimum inhibitory concentrations were determined on potentially resistant isolates. We used univariate and multivariable multinomial regression models to assess differences between serotypes. ResultsGERMS-SA identified 8674 cases among children <5 years. Overall, 58% (3849/6668), 65% (4314/6668), and 85% (5669/6668) of cases and 61% (455/751), 64% (482/751), 82% (616/751) of deaths were due to serotypes included in 7-valent PCV, 10-valent PCV and 13-valent PCV, respectively. Serotypes 6A and 19A accounted for 16% (527/3252) of penicillin non-susceptible disease. In 2008, reported incidence of IPD was 6-fold higher in children <1 compared to children 1–4 years of age: 87 per 100,000 population and 14/100,000, respectively. The relative risk of IPD was 21-fold (95% CI, 19–24) and 34-fold (29–41) greater in HIV-infected compared to HIV-uninfected children in the <1 year and 1–4-year-old age groups respectively. On multivariable analysis serotypes 6B (relative risk ratio (RRR) 0.7; confidence interval (CI) 0.5–0.9), 18C (RRR 0.3; CI 0.1–0.5), 1 (RRR 0.2; CI 0.1–0.4) and 8 (RRR 0.2; CI 0.1–0.4) were significantly less common in HIV-infected individuals than serotype 14. ConclusionsAll vaccine formulations have the potential to prevent most cases and deaths from IPD in children in South Africa. Vaccines with protection against 19A would be advantageous in South Africa.

Vaccine Poliovirus Shedding and Immune Response to Oral Polio Vaccine in HIV-Infected and -Uninfected Zimbabwean Infants

With prolonged replication, attenuated polioviruses used in oral polio vaccine (OPV) can mutate into vaccine-derived poliovirus (VDPV) and cause poliomyelitis outbreaks. Individuals with primary humoral immunodeficiencies can become chronically infected with vaccine poliovirus, allowing it to mutate into immunodeficiency-associated VDPV (iVDPV). It is unclear if children perinatally infected with the human immunodeficiency virus (HIV), who have humoral as well as cellular immunodeficiencies, might be sources of iVDPV. We conducted a prospective study collecting stool and blood samples at multiple time points from Zimbabwean infants receiving OPV according to the national schedule. Nucleic acid extracted from stool was analyzed by real-time polymerase chain reaction for OPV serotypes. We analyzed 825 stool samples: 285 samples from 92 HIV-infected children and 540 from 251 HIV-uninfected children. Poliovirus shedding was similar after 0-2 OPV doses but significantly higher in the HIV-infected versus uninfected children after ≥ 3 OPV doses, particularly within 42 days of an OPV dose, independent of seroconversion status. HIV infection was not associated with prolonged or persistent poliovirus shedding. HIV infection was associated with significantly lower polio seroconversion rates. HIV infection is associated with decreased mucosal and humoral immune responses to OPV but not the prolonged viral shedding required to form iVDPV.

Acquisition of Streptococcus pneumoniae in Pneumococcal Conjugate Vaccine-naïve South African Children and Their Mothers

Pneumococcal nasopharyngeal colonization is a prerequisite to developing pneumococcal disease. We investigated the dynamics of pneumococcal colonization in perinatal HIV-unexposed and HIV-exposed children and their mothers and risk factors associated with new serotypes acquisition. Two hundred forty-three mother-child pairs (120 HIV-infected, 123 HIV-uninfected mothers) were studied at 4.4, 7.2, 9.4, 12.3 and 16.0 months of the child's age. Demographic data, nasopharyngeal swabs, as well as oropharyngeal swabs, from mothers were collected for pneumococcal conventional culture and serotyping by the Quellung method. The rate of new serotype acquisition during the 16 months did not differ between HIV-exposed (49.1%) and HIV-unexposed (52.0%) children, or between HIV-infected (18.9%) and HIV-uninfected (19.5%) mothers. Serotypes included in the 7-valent pneumococcal conjugate vaccine (PCV7) were acquired more often by HIV-infected (10.0%) compared with HIV-uninfected mothers (6.4%; P = 0.03). On multivariate analysis, day-care attendance (adjusted odds ratio [AOR], = 1.80, P = 0.02) and maternal pneumococcal colonization (AOR = 1.54, P = 0.01) were positively associated with pneumococcal acquisition in the child, whereas breast-feeding had a protective effect on PCV7-serotype acquisition in HIV-uninfected children. New acquisition of PCV7 and PCV13 serotypes in the mother was positively associated with colonization in the child (AOR = 2.01, P = 0.006 and AOR = 2.04, P = 0.002, respectively). There is an association of acquisition of PCV7 and PCV13 serotypes between young children and their mothers. The higher prevalence of PCV7 serotype in HIV-infected mothers suggests that they may be a reservoir for transmission of these serotypes, which could delay indirect effects of PCV in settings with a high HIV burden.