PubMed Health⌕ Search

Biomedical subjects

Heather J Zar

Publications and source records attributed to Heather J Zar.

At least 19 recordsLinked to original sources
PubMed2026

Hypoxaemia and mortality in children with lower respiratory infection in low-income and middle-income countries: systematic review and meta-analysis.

BACKGROUND: Hypoxaemic lower respiratory infections (LRIs) are a leading cause of childhood mortality, with the highest burden in low-income and middle-income countries (LMICs). Hypoxaemia-low peripheral capillary oxyhaemoglobin saturation (SpO2)-is a marker of severity, and WHO recommends hospitalisation and oxygen administration for patients with SpO2 <90%. We aimed to update estimates from a 2015 systematic review and meta-analysis examining the association between hypoxaemia and mortality among children with LRIs in LMICs by incorporating studies published over the subsequent decade and evaluating mortality risk across multiple SpO2 thresholds. METHODS: We conducted a systematic review with meta-analysis by searching PubMed, Embase, LILACS, Global Index Medicus, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2015, and June 18, 2025, with combined terms related to pneumonia, children, mortality, and LMICs. We also included selected earlier studies through citation checking. Eligible studies reported associations between hypoxaemia and mortality in children younger than 5 years with LRIs in LMICs. We excluded case reports and case series with fewer than five deaths, studies focused exclusively on the neonatal period, and those limited to children with specific comorbidities or to postoperative patients, for consistency with the original review. Two reviewers independently screened studies, extracted data, and assessed quality. Eligible studies were combined with those from the original review and analysed using random-effects models to estimate odds ratios (ORs) by hypoxaemia threshold subgroup. The protocol was registered on PROSPERO (CRD42023433946). FINDINGS: We identified 7734 records; 26 new studies met inclusion criteria and were combined with 18 from the original review. The 44 studies were published between 1993 and 2024 and were primarily from Africa (25 [57%] of 44) or Asia (19 [43%]); some studies spanned multiple locations. Data from 33 studies including 155&#x2009;633 participants were included in the primary meta-analysis. Hypoxaemia of any threshold was associated with higher odds of LRI mortality (OR 4&#xb7;36 [95% CI 3&#xb7;52-5&#xb7;39]) compared with no hypoxaemia. For SpO2 <90% versus 90-100%, OR for death was 4&#xb7;75 (95% CI 3&#xb7;42-6&#xb7;58). For SpO2 90-94% versus 95-100%, mortality risk was more than twice as high (OR 2&#xb7;27 [95% CI 1&#xb7;22-4&#xb7;25]). Heterogeneity was substantial (I2 64-85% across analyses), and eight (24%) of 33 studies in the primary meta-analysis had a high overall risk of bias; however, a sensitivity analysis restricted to studies with low or moderate risk of bias yielded similar results. INTERPRETATION: SpO2 <90% strongly predicts mortality in children with LRIs in LMICs. Children with SpO2 90-94% also have elevated risk, suggesting that paediatric LRI and pneumonia treatment algorithms should consider management at this hypoxaemia threshold. FUNDING: None.

Journal Article↗
PubMed2006

Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial.

OBJECTIVES: To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV. DESIGN: Two centre prospective double blind placebo controlled trial. PARTICIPANTS: Children aged > or =8 weeks with HIV. INTERVENTIONS: Isoniazid or placebo given with co-trimoxazole either daily or three times a week. SETTING: Two tertiary healthcare centres in South Africa. MAIN OUTCOME MEASURES: Mortality, incidence of tuberculosis, and adverse events. RESULTS: Data on 263 children (median age 24.7 months) were available when the data safety monitoring board recommended discontinuing the placebo arm; 132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartile range 2.0-9.7) months. Mortality was lower in the isoniazid group than in the placebo group (11 (8%) v 21 (16%), hazard ratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) by intention to treat analysis. The benefit applied across Centers for Disease Control clinical categories and in all ages. The reduction in mortality was similar in children on three times a week or daily isoniazid. The incidence of tuberculosis was lower in the isoniazid group (5 cases, 3.8%) than in the placebo group (13 cases, 9.9%) (hazard ratio 0.28, 0.10 to 0.78, P=0.005). All cases of tuberculosis confirmed by culture were in children in the placebo group. CONCLUSIONS: Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV. Prophylaxis may offer an effective public health intervention to reduce mortality in such children in settings with a high prevalence of tuberculosis. TRIAL REGISTRATION: Clinical Trials NCT00330304.

Africa South of the Sahara↗
PubMed2006

Global paediatric pulmonology: out of Africa.

Respiratory illness is the major cause of mortality and morbidity in African children. The spectrum of disease includes acute and chronic respiratory illness. As a result of the HIV epidemic currently occurring in sub-Saharan Africa, HIV-associated acute and chronic respiratory disease has emerged as a major factor in the epidemiology of childhood respiratory illness. Pneumonia is the leading causes of childhood mortality responsible for approximately 21% of deaths in African children under five years of age each year. The HIV pandemic has increased the incidence, severity and pneumonia mortality in African children. Pulmonary tuberculosis (TB) is an important cause of morbidity and death. Globally, the highest TB incidence rates occur in sub-Saharan African countries; many of these countries are also experiencing a dual HIV epidemic, resulting in an exponential increase in TB cases. The burden of childhood respiratory illness has necessitated novel and improved ways of diagnosis, treatment and prevention, particularly in the context of limited resources. Improved diagnosis, treatment and prevention of pneumonia have been a research focus, particularly in HIV-infected children. African studies have provided information on the epidemiology, aetiology and outcome from pneumonia in HIV-infected and uninfected children. The efficacy of trimethoprim-sulphamethoxazole prophylaxis in reducing mortality and morbidity in HIV-infected African children was shown in the only randomized controlled trial. Two large studies have shown the efficacy of the pneumococcal conjugate vaccine in an African context. Regarding TB, areas of research include diagnostic studies and improved preventative strategies. Promising diagnostic studies for childhood TB include the use of sputum induction, PCR techniques and blood interferon assays. The immune reconstitution inflammatory syndrome (IRIS) has emerged as a new clinical entity in HIV-infected children with TB associated with use of antiretroviral therapy. New preventative strategies for TB include novel vaccines and primary prophylaxis. Available, effective interventions for prevention and treatment of childhood respiratory disease exist; the challenge is to achieve widespread implementation and high coverage rates in African countries. Greater access to newer vaccines and, in HIV-infected children, to anti-retroviral therapy and prophylaxis is necessary to further reduce the burden of childhood respiratory illness in Africa.

Africa↗
PubMed2006

Sensitivity and specificity of nested and real-time PCR for the detection of Pneumocystis jiroveci in clinical specimens.

A polymerase chain reaction (PCR)-based test for Pneumocystis jiroveci (formerly Pneumocystis carinii f. sp. hominis) might be an alternative to histologic diagnoses of P. jiroveci pneumonia (PCP). However, previously developed nested PCR methods tend to have low specificities (high false-positive rates). In this study, nested and quantitative real-time PCR methods for the amplification of the P. jiroveci DHPS (dihydropteroate synthase) gene were evaluated in a variety of stored clinical samples from Spain, South Africa, and Brazil. The sensitivities of both assays were high, ranging from 62.5% to 100% depending on the type of specimen. In a subset of 71 microscopically confirmed PCP cases and 70 negative cases, the sensitivities and specificities were 94% and 81% for nested PCR and 94% and 96% for real-time PCR, respectively. Real-time PCR has a statistically significantly better specificity than nested PCR (P = .015) and is likely to generate fewer false positives.

Bronchoalveolar Lavage Fluid↗
PubMed2006

Clinical indicators of Pneumocystis jiroveci pneumonia (PCP) in South African children infected with the human immunodeficiency virus.

BACKGROUND: Pneumocystis pneumonia (PCP) caused by Pneumocystis jiroveci is common in HIV-infected children, producing substantial morbidity and mortality. Initiation of timely, effective therapy depends on clinical identification of children with PCP. OBJECTIVE: To develop a clinical decision rule to diagnose PCP in HIV-infected children for use where diagnostic resources are limited. METHODS: Analysis of data collected during a prospective incidence study of the etiology, features, and outcome of HIV-infected children hospitalized with pneumonia. RESULTS: Four clinical variables were independently associated with a diagnosis of PCP in multivariate analysis: age < 6 months (OR 15.6; 95% CI 2.4-99.8; p = 0.004), respiratory rate > 59 breaths/min (OR 8.1; 95% CI 1.5-53.2; p = 0.018), arterial percentage hemoglobin oxygen saturation (SaO2) < or = 92% (OR 5.1; 95% CI 1.0-26.1; p = 0.052) and absence of history of vomiting (OR 11.2; 95% CI 1.9-68.0; p = 0.008). The sensitivity and specificity of diagnosing PCP with any two or more of these variables were 1.00 (95% CI 0.74-1.00) and 0.49 (95% CI 0.39-0.59), respectively. Diagnosing PCP with three or more of the indicators had a decreased sensitivity of 0.75 (95% CI 0.43-0.95) and increased specificity of 0.90 (95% CI 0.83-0.95). CONCLUSION: Empirical anti-pneumocystis therapy should be considered in HIV-infected infants presenting with tachypnea, hypoxia and absence of vomiting.

AIDS-Related Opportunistic Infections↗
PubMed2006

Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children.

BACKGROUND: Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5-10 microg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. OBJECTIVE: To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIV-infected children. METHODS: A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. RESULTS: Median (25th-75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5-1.5) microg/ml, 1.94 (1.4-2.2) microg/ml and 7.68 (6.1-7.8) microg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4-8.8) microg/ml and 9.25 (8.2-10.3) microg/ml respectively. CONCLUSION: Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children.

AIDS-Related Opportunistic Infections↗
PubMed2006

Childhood pneumonia--progress and challenges.

UNLABELLED: Remarkable progress has been made in the development of antimicrobial therapy, effective vaccines and pneumonia management guidelines in the past 50 years. However, pneumonia is currently the leading cause of death in children younger than 5 years in developing countries, accounting for approximately 20% of childhood deaths. This article reviews changes in the epidemiology, management and prevention of childhood pneumonia in developing countries, specifically in Africa and South Africa, and addresses future challenges. MAIN FINDINGS: The HIV epidemic has sharply increased the incidence, severity of, and mortality due to, childhood pneumonia. Bacterial infection remains a major cause of pneumonia mortality. Additional pathogens such as Pneumocystis jirovecii and Gram-negative bacteria are found in HIV-infected children, associated with a high mortality. Mycobacterium tuberculosis is an important cause of acute pneumonia in both HIV-infected and uninfected children. Use of case management guidelines can substantially reduce neonatal, infant and under-5 mortality and pneumonia-specific mortality. General preventive interventions including micronutrient supplementation with zinc and vitamin A, and immunisations can substantially reduce the burden of childhood pneumonia. Despite a lower efficacy in HIV-infected children, vaccination protects against disease in a significant proportion of children. In South Africa, new advances over the past 50 years have included greater access to primary health care for children, the use of Integrated Management of Childhood Illness guidelines in primary care, development of guidelines for diagnosis and management of childhood pneumonia and adoption of an expanded immunisation programme that includes coverage for Haemophilus influenzae type b. The pneumococcal conjugate vaccine recently licensed in South Africa also has the potential to significantly reduce the burden of childhood pneumonia. Recent roll-out of the national antiretroviral programme can reduce the incidence and severity of HIV-associated pneumonia through the prevention of HIV infection, use of cotrimoxazole prophylaxis and treatment with antiretrovirals. CONCLUSION: Available, effective interventions for prevention and treatment of childhood pneumonia exist; the challenge is to achieve widespread implementation and high coverage rates in developing countries. Greater access to newer vaccines and to antiretroviral therapy and co-trimoxazole prophylaxis in HIV-infected children is necessary to further reduce the burden of childhood pneumonia and the discrepancies in global child lung health.

Child↗
PubMed2005

Neonatal chlamydial infections: prevention and treatment.

Neonatal chlamydial infection, which manifests principally as ophthalmia neonatorum (ON) or pneumonia, is a significant cause of neonatal morbidity. Widespread use of silver nitrate drops resulted in a dramatic decline in the incidence of gonococcal ophthalmia but had much less impact on the incidence of neonatal chlamydial infection. Chlamydia trachomatis has become the most common infectious cause of ON in developed countries.A number of prophylactic antibiotic or antiseptic agents have been used to prevent ON. Prophylaxis with 1% silver nitrate ophthalmic drops, 0.5% erythromycin ophthalmic ointment, or 1% tetracycline ointment has comparable efficacy for the prevention of chlamydial ophthalmia but does not offer protection against nasopharyngeal colonization or the development of pneumonia. Erythromycin or tetracycline topically have been used as prophylactic agents because of their allegedly superior activity for the prevention of ON and because they produced less chemical conjunctivitis compared with silver nitrate. However, the relative efficacy of these agents for chlamydial infection and the emergence of beta-lactamase-producing Neisseria gonorrheae has raised questions regarding their effectiveness when applied topically for prophylaxis of ON. Compared with these agents, a 2.5% povidone-iodine ophthalmic solution has been found to have greater efficacy for the prevention of ON generally, and chlamydial ophthalmia specifically. In countries where the incidence of ON is very low, an alternative strategy is to institute prenatal screening and treatment of infected mothers, forgo routine neonatal prophylaxis, and follow-up infants after birth for the possible development of infection. For the treatment of chlamydial ophthalmia or pneumonia, oral erythromycin for 2 weeks is recommended; additional topical therapy is unnecessary. However, in approximately 20-30% of infants, therapy will not eradicate the organism and the infant may require a repeat oral course of antibiotics. The few published studies on the use of the new oral macrolide antibiotics, such as azithromycin, roxithromycin, or clarithromycin for chlamydial infections in neonates suggest that these agents may be effective; however, more data on their tolerability and efficacy in this patient group are warranted.

Anti-Bacterial Agents↗
PubMed2004

Pneumonia in HIV-infected and HIV-uninfected children in developing countries: epidemiology, clinical features, and management.

PURPOSE OF REVIEW: Pneumonia is a leading cause of illness and death in children younger than 5 years in developing countries, accounting for approximately 20% of childhood deaths. The HIV epidemic has sharply increased the incidence, severity, and mortality of childhood pneumonia in the developing world, particularly in sub-Saharan Africa. This article reviews recent findings on the epidemiology, clinical features, and management of HIV-infected and -uninfected children with pneumonia in developing countries. RECENT FINDINGS: Bacterial infection remains a major cause of pneumonia mortality; in HIV-infected children, a broader spectrum of pathogens including gram-negative infections and Pneumocystis jiroveci occurs. Mycobacterium tuberculosis is an important cause of acute pneumonia among children from high tuberculosis prevalence areas. Use of case management guidelines substantially reduces neonatal, infant, and under-5 mortality and pneumonia-specific mortality in developing countries. New advances in therapy include the use of short-course antibiotics and high-dose amoxicillin twice daily for ambulatory treatment of HIV-negative children with pneumonia. New preventive interventions include the development of conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae, but these are not widely affordable nor available in developing countries. Despite a lower efficacy in HIV-infected children, these vaccines still protect against disease in a significant proportion of children. Available preventive interventions including micronutrient supplementation with zinc and vitamin A, and immunization as contained in the WHO Expanded Program of Immunization can substantially reduce the burden of childhood pneumonia. SUMMARY: Urgent measures to implement existing available, effective interventions for prevention and treatment of childhood pneumonia and achieve high coverage rates in developing countries are needed.

AIDS-Related Opportunistic Infections↗
PubMed2003

The impact of HIV infection and trimethoprim-sulphamethoxazole prophylaxis on bacterial isolates from children with community-acquired pneumonia in South Africa.

The aim of this study was to compare the type and antimicrobial resistance patterns of bacteria cultured from blood or respiratory tract secretions by HIV status and the use of trimethoprim-sulphamethoxazole (TMP-SMX) prophylaxis in children hospitalized with community-acquired pneumonia. During a 1-year prospective study in Cape Town, South Africa, 250 children [median aged 6 (3-16) months] hospitalized with pneumonia were enrolled; 151 (60.4 per cent) were HIV-infected. The incidence of bacteremia [35 of 244 cultures (14.3 per cent)] did not differ by HIV status. Bacteria were cultured in 17 of 32 (53 per cent) bronchoalveolar lavage specimens (BAL), 128 of 210 (61 per cent) induced sputa and 166 of 231 (71 per cent) nasopharyngeal specimens (NPAs). The type and number of bacteria in respiratory secretions did not differ by HIV status, except for a higher rate of Staphylococcus aureus in sputum or BAL [22 of 146 (15 per cent) vs. 3 of 96 (3 per cent), p = 0.003] and NPAs [41 of 135 (30 per cent) vs. 9 of 96 (9 per cent), p < 0.001] of HIV-positive children. The use of TMP-SMX prophylaxis in HIV-infected children was associated with an increased nasopharyngeal carriage of S. aureus [22 of 51 (43 per cent) vs. 17 of 79 (22 per cent), p = 0.009]. The rising prevalence of HIV infection and the use of TMP-SMX prophylaxis may alter the spectrum of colonizing and pathogenic bacteria in children in developing countries.

AIDS-Related Opportunistic Infections↗
PubMed2002

A 500-ml plastic bottle: an effective spacer for children with asthma.

Inhaled therapy using a metered-dose inhaler (MDI) with attached spacer has been increasingly recognized as the optimal method for delivering asthma medication for acute attacks and chronic prophylaxis. However, in developing countries the cost and availability of commercially produced spacers limit the use of MDI-spacer delivery systems. A 500-ml plastic bottle has been recently adapted to function as a spacer. This article reviews the current data on the efficacy of this bottle-spacer and discusses its advantages and limitations. It is concluded that a modified 500-ml plastic bottle is an effective spacer; modification and use of this device should be incorporated into international guidelines for the management of children with asthma.

Anti-Asthmatic Agents↗
PubMed2002

Serum immunoglobulin E levels in human immunodeficiency virus-infected children with pneumonia.

Elevated serum immunoglobulin E (IgE) levels have been reported in association with human immunodeficiency virus (HIV) infection in adults, but there is little information in children. The aim of the present study was to compare serum IgE levels in HIV-positive and -negative children hospitalized with pneumonia in South Africa and to investigate whether IgE may be useful as a marker of specific infections or prognosis in HIV-infected children. History, examination, blood tests, and induced sputum or bronchoalveolar lavage were carried out. Of 122 children [45% female, median age 8 months (3-20 months)], 81 were infected with HIV. A history of allergy or asthma was present in three children (two of whom were HIV positive). Serum IgE was higher in HIV-infected children [83 (33-147) vs. 29 (6-113) IU/l; p = 0.011] as was immunoglobulin G (IgG) [49 (37-63) vs. 27.5 (23-34) g/l; p < 0.001]. CD4 lymphocytes [600 (330-1,210) vs. 1,900 (1,500-3,030) cells/ micro l], percentage CD4 cells [13.6 (9.4-20.3) vs. 40.1 (31.1-44.9)] and CD4 : CD8 ratio [0.3 (0.2-0.4) vs. 2 (1.4-2.8)] were lower in HIV-positive children (p < 0.001 for all). Bacteremia occurred in 12 (10%) children; other specific pathogens identified included Mycobacterium tuberculosis in eight (7%) and Pneumocystis carinii in nine (7%). There was no correlation with CD4 count, CD4 : CD8 ratio, or the presence of specific pathogens, and IgE level. In-hospital mortality (11%) did not correlate with IgE levels. HIV-infected children with pneumonia have higher serum IgE compared with seronegative patients. In HIV-positive children, IgE levels did not correlate with the degree of immunosuppression or with outcome.

Bacteremia↗
PubMed2002

Nosocomial pneumonia in pediatric patients: practical problems and rational solutions.

Nosocomial pneumonia is a common hospital-acquired infection in children, and is often fatal. Risk factors for nosocomial pneumonia include admission to an intensive care unit, intubation, burns, surgery, and underlying chronic illness. Viruses, predominantly respiratory syncytial virus (RSV), are the most common cause of pediatric nosocomial respiratory tract infections. Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) are the predominant bacterial pathogens, and are associated with a high mortality rate. Staphylococcus aureus and Staphylococcus epidermidis are the most common Gram-positive bacteria causing nosocomial pneumonia; infections with these organisms have a better outcome than those with Gram-negative organisms. An increasing problem is the emergence of multiresistant Gram-positive and Gram-negative nosocomial pathogens. Distinguishing nosocomial pneumonia from other pulmonary processes may be difficult; diagnosis is based on clinical signs, radiological findings, and microbiological results. Recommended empiric therapy should consider factors such as the time of onset of illness, severity of disease, and specific risk factors for nosocomial pneumonia, including use of mechanical ventilation, underlying disease, or recent use of antibacterials. The resident local hospital flora should be considered when selecting therapy for nosocomial pneumonia. Early initiation of appropriate empiric therapy reduces morbidity and mortality. For empiric treatment of bacterial nosocomial pneumonia, an intravenous antibacterial regimen that includes coverage of Gram-negative bacilli and Gram-positive organisms should be used. A carbapenem or ureidopenicillin derivative (piperacillin) plus a beta-lactamase inhibitor should be used where extended spectrum beta-lactamase-producing Enterobacteriaceae are endemic. Therapy should be modified when a specific pathogen and its antimicrobial susceptibility are identified. Effective prevention of nosocomial pneumonia requires infection control measures that affect the environment, personnel, and patients. Of these, hand hygiene, appropriate infection control policies, and judicious use of antibacterials are essential.

Anti-Bacterial Agents↗