Diagnosing childhood pulmonary tuberculosis using a single sputum specimen on Xpert MTB/RIF at point of care

Background. The GeneXpert MTB/RIF (Cepheid, USA) (Xpert) has proved successful for pulmonary  tuberculosis (TB) diagnosis on decontaminated/concentrated induced sputum specimens from children.  Capacity to perform induction in many settings is limited.Objective. To assess: (i) volumes of ‘routinely obtained’ sputum in a district-level academic hospital; (ii) whether sputum specimens not meeting Xpert-required testing volumes could still be tested; and (iii) performance of Xpert on a single paediatric sputum specimen at point of care (POC).Methods. Two sputa were collected from paediatric TB suspects (≤14 years) at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa. One specimen was weighed at POC; if the volume was  ≥0.1 mL but <0.5 mL, it was increased to 0.5 mL using saline. On-site Xpert testing (G3 cartridge) was performed by a dedicated laboratory technician. The second specimen was referred for TB smear microscopy and culture as per standard of care (SOC).Results. A total of 484 patients presumed to have TB (median age 24 months) were eligible for this  study, performed between June 2011  and May 2012. Xpert could not be used on 4.1% of specimens because of volumes <0.1 mL, and 62.8% required addition of saline prior to Xpert testing. Xpert  generated a 2.2% error and 3.7% invalid rate, compared with the SOC that rejected 2.3% because of insufficient volume and 2.3% that were contaminated. The diagnostic performance compared with culture was 62.5% (95% confidence interval (CI) 24.7 - 91) and 99.1% (95% CI 97.4 - 99.8) sensitivity and specificity, respectively, for Xpert (n=345) and 33.3% (7.9 - 69.9) and 99.5% (98.1 - 99.9) sensitivity and specificity, respectively, for smear microscopy (n=374).Conclusions. Up to 67% of ‘routinely obtained’ sputum specimens from children (≤14 years) are below the required volume for Xpert testing but can be ‘topped up’ with saline. Xpert MTB/RIF performed better than microscopy and generated clinically relevant, timeous results, but sensitivity did not reach the  same levels as culture in children

Essential medicine selection during the COVID-19 pandemic: Enabling access in uncharted territory

The COVID-19 pandemic requires urgent decisions regarding treatment policy in the face of rapidly evolving evidence. In response, the South African Essential Medicines List Committee established a subcommittee to systematically review and appraise emerging evidence, within very short timelines, in order to inform the National Department of Health COVID-19 treatment guidelines. To date, the subcommittee has reviewed 14 potential treatments, and made recommendations based on local context, feasibility, resource requirements and equity. Here we describe the rapid review and evidence-to-decision process, using remdesivir and dexamethasone as examples. Our experience is that conducting rapid reviews is a practical and efficient way to address medicine policy questions under pandemic conditions

Epidemiology and aetiology of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 1)

Background. Pneumonia remains a major cause of morbidity and mortality among South African (SA) children. Improved immunisation regimens, strengthening of HIV programmes, better socioeconomic conditions and new preventive strategies have influenced the epidemiology of pneumonia. Furthermore, sensitive diagnostic tests and better sampling methods in young children improve aetiological diagnosis.Objectives. To summarise current information on childhood community-acquired pneumonia (CAP) epidemiology and aetiology in children as part of the revised South African Thoracic Society guidelines.Methods. The Paediatric Assembly of the South African Thoracic Society and the National Institute for Communicable Diseases expert subgroup on epidemiology and aetiology revised the existing SA guidelines.The subgroup reviewed the published evidence in their area; in the absence of evidence, expert opinion was accepted. Evidence was graded using the British Thoracic Society (BTS) grading system, and the relevant section underwent peer review.Results. Respiratory viruses, particularly respiratory syncytial virus, are the key pathogens associated with hospitalisation for radiologically confirmed pneumonia in HIV-uninfected children. Opportunistic organisms, including Pneumocystis jirovecii, are important pathogens in HIV-infected infants, while non-typable Haemophilus influenzae and Staphylococcus aureus are important in older HIV-infected children. Co-infections with bacteria or other respiratory viruses are common in hospitalised children. Mycobacterium tuberculosis is common in children hospitalised with CAP in SA.Conclusions. Numerous public health measures, including changes in immunisation schedules and expansion of HIV prevention and treatment programmes, have influenced the epidemiology and aetiology of CAP in SA children. These changes have necessitated a revision of the South African Paediatric CAP guidelines, further sections of which will be published as part of a CME series in SAMJ

Diagnosis of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 2)

Background. Accurate diagnosis and attribution of the aetiology of pneumonia are important for measuring the burden of disease, implementing appropriate treatment strategies and developing more effective interventions.Objectives. To produce revised guidelines for the diagnosis of pneumonia in South African (SA) children, encompassing clinical, radiological and aetiological methods.Methods. An expert group was established to review diagnostic evidence and make recommendations for a revised SA guideline. Published evidence was reviewed and graded using the British Thoracic Society grading system.Results. Diagnosis of pneumonia should be considered in a child with acute cough, fast breathing or difficulty breathing. Revised World Health Organization guidelines classify such children into: (i) severe pneumonia; (ii) pneumonia (tachypoea or lower chest indrawing); or (iii) no pneumonia. Malnourished or immunocompromised children with lower chest indrawing should be managed as cases of severe pneumonia. Pulse oximetry should be done, with hospital referral for oxygen saturation <92%. A chest X-ray is indicated in severe pneumonia or when tuberculosis (TB) is suspected. Microbiological investigations are recommended in hospitalised patients or in outbreak settings. Improved aetiological methods show the importance of co-infections. Blood cultures have a low sensitivity (<5%), for diagnosing bacterial pneumonia. Highly sensitive, multiplex tests on upper respiratory samples or sputum detect multiple potential pathogens in most children. However, even in symptomatic children, it may be impossible to distinguish colonising from causative organisms, unless identification of the organism is strongly associated with attribution to causality, e.g. respiratory syncytial virus, Mycobacterium tuberculosis, Bordetella pertussis, influenza, para-influenza or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Investigations for TB should be considered in children with severe pneumonia who have been hospitalised, in a case of a known TB contact, if the tuberculin skin test is positive, if a child is malnourished or has lost weight, and in children living with HIV. Induced sputum may provide a higher yield than upper respiratory sampling for B. pertussis, M. tuberculosis and Pneumocystis jirovecii. Conclusions. Advances in clinical, radiological and aetiological methods have improved the diagnosis of childhood pneumonia

Prevention of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 4)

Background. More comprehensive immunisation regimens, strengthening of HIV prevention and management programmes and improved socioeconomic conditions have impacted on the epidemiology of paediatric community-acquired pneumonia (CAP) in South Africa (SA).Objectives. To summarise effective preventive strategies to reduce the burden of childhood CAP.Methods. An expert subgroup reviewed existing SA guidelines and new publications focusing on prevention. Published evidence on pneumonia prevention informed the revisions; in the absence of evidence, expert opinion was used. Evidence was graded using the British Thoracic Society (BTS) grading system.Recommendations. General measures for prevention include minimising exposure to tobacco smoke or air pollution, breastfeeding, optimising nutrition, optimising maternal health from pregnancy onwards, adequate antenatal care and improvement in socioeconomic and living conditions. Prevention of viral transmission, including SARS-CoV-2, can be achieved by hand hygiene, environmental decontamination, use of masks and isolation of infected people. Specific preventive measures include vaccines as contained in the Expanded Programme on Immunisation schedule, isoniazid prophylaxis for tuberculosis, co-trimoxazole prophylaxis for HIV-infected infants and children who are immunosuppressed, and timely diagnosis of HIV, as well as antiretroviral therapy (ART) initiation. HIV-infected children treated with ART from early infancy, and HIV-exposed children, have similar immunogenicity and immune responses to most childhood vaccines as HIV-unexposed infants.Validation. These recommendations are based on available published evidence supplemented by the consensus opinion of SA paediatric experts, and are consistent with those in published international guidelines

Eff ectiveness of the 13-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in South African children: a case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was designed to include disease-causing serotypes that are important in low-income and middle-income countries. Vaccine eff ectiveness estimates are scarce in these settings. South Africa replaced PCV7 with PCV13 in 2011 using a 2 + 1 schedule. We aimed to assess the eff ectiveness of two or more doses of PCV13 against invasive pneumococcal disease in children with HIV infection and in those not infected with HIV. Methods Cases of invasive pneumococcal disease in children aged 5 years or younger were identifi ed through national laboratory-based surveillance. Isolates were serotyped with the Quellung reaction or PCR. We sought in-hospital controls for every case, matched for age, HIV status, and study site. We aimed to enrol four controls for every case not infected with HIV and six controls for every case with HIV infection (case-control sets). With conditional logistic regression, we calculated vaccine eff ectiveness as a percentage, with the equation 1 – [adjusted odds ratio for vaccination] × 100. We included data from an earlier investigation of PCV7 to assess vaccine eff ectiveness in children exposed to but not infected with HIV and in malnourished children not infected with HIV. Findings Between January, 2012, and December, 2014, we enrolled children aged 16 weeks or older to our study: 240 were cases not infected with HIV, 75 were cases with HIV infection, 1118 were controls not infected with HIV, and 283 were controls with HIV infection. The eff ectiveness of two or more doses of PCV13 against PCV13-serotype invasive pneumococcal disease was 85% (95% CI 37 to 96) among 11 case-control sets of children not infected with HIV and 91% (–35 to 100) among three case-control sets of children with HIV infection. PCV13 eff ectiveness among 26 case-control sets of children not infected with HIV was 52% (95% CI –12 to 79) against all-serotype invasive pneumococcal disease and 94% (44 to 100) for serotype 19A. Vaccine eff ectiveness against PCV7-serotype invasive pneumococcal disease was 87% (95% CI 38 to 97) in children exposed to HIV but uninfected and 90% (53 to 98) in malnourished children not infected with HIV. Interpretation Our results indicate that PCV13 in a 2 + 1 schedule is eff ective for preventing vaccine-type pneumococcal infections in young children not infected with HIV, including those who are malnourished or who have been exposed to HIV. Although the point estimate for PCV13 vaccine eff ectiveness in children infected with HIV was high, it did not reach signifi cance, possibly because of the small sample size. These fi ndings support recommendations for widespread use of pneumococcal conjugate vaccine in low-income and middle-income countries

A review of the use of blood and blood products in HIV-infected patients

Despite numerous publications on the appropriate use of blood and blood products, few specifically consider the role of transfusion in the management of HIV. This review is a synthesis of conditions encountered in the management of HIV-infected patients where the transfusion of blood or blood products may be indicated. A consistent message emerging from the review is that the principles of transfusion medicine do not differ between HIV-negative and -positive patients. The aim of the review is to provide clinicians witha practical and succinct overview of the haematological abnormalities and clinical circumstances most commonly encountered in the HIV setting, while focusing on the rational and appropriate use of blood and blood products forHIV patients. Important ethical considerations in dealing with both the collection and transfusion blood and blood products in the HIV era have also been addressed

Epidemiology and aetiology of community-acquired pneumonia in children : South African Thoracic Society guidelines (part 1)

BACKGROUND. Pneumonia remains a major cause of morbidity and mortality among South African (SA) children. Improved immunisation regimens, strengthening of HIV programmes, better socioeconomic conditions and new preventive strategies have influenced the epidemiology of pneumonia. Furthermore, sensitive diagnostic tests and better sampling methods in young children improve aetiological diagnosis. OBJECTIVES. To summarise current information on childhood community-acquired pneumonia (CAP) epidemiology and aetiology in children as part of the revised South African Thoracic Society guidelines. METHODS. The Paediatric Assembly of the South African Thoracic Society and the National Institute for Communicable Diseases expert subgroup on epidemiology and aetiology revised the existing SA guidelines.The subgroup reviewed the published evidence in their area; in the absence of evidence, expert opinion was accepted. Evidence was graded using the British Thoracic Society (BTS) grading system, and the relevant section underwent peer review. RESULTS. Respiratory viruses, particularly respiratory syncytial virus, are the key pathogens associated with hospitalisation for radiologically confirmed pneumonia in HIV-uninfected children. Opportunistic organisms, including Pneumocystis jirovecii, are important pathogens in HIV-infected infants, while non-typable Haemophilus influenzae and Staphylococcus aureus are important in older HIV-infected children. Co-infections with bacteria or other respiratory viruses are common in hospitalised children. Mycobacterium tuberculosis is common in children hospitalised with CAP in SA. CONCLUSIONS. Numerous public health measures, including changes in immunisation schedules and expansion of HIV prevention and treatment programmes, have influenced the epidemiology and aetiology of CAP in SA children. These changes have necessitated a revision of the South African Paediatric CAP guidelines, further sections of which will be published as part of a CME series in SAMJ.The SA Medical Research Councilhttp://www.samj.org.zaam2021Paediatrics and Child Healt