Frequency, kinetics and determinants of viable SARS-CoV-2 in bioaerosols from ambulatory COVID-19 patients infected with the Beta, Delta or Omicron variants.

Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols <10µm and <5µm, respectively, for up to 9 days after symptom onset. Aerosol culturability is significantly associated with lower neutralizing antibody titers, and suppression of transcriptomic pathways related to innate immunity and the humoral response. A nasopharyngeal Ct <17 rules-in ~40% of aerosol culture-positives and identifies those who are probably highly infectious. A parsimonious three transcript blood-based biosignature is highly predictive of infectious aerosol generation (PPV > 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols <5µm at ~6 days after symptom onset). These data, which comprehensively confirm variant-specific culturable SARS-CoV-2 in aerosol, inform the targeting of transmission-related interventions and public health containment strategies emphasizing improved ventilation.

Parental access to hospitalised children during infectious disease pandemics such as COVID-19.

The COVID-19 pandemic has resulted in many hospitals severely limiting or denying parents access to their hospitalised children. This article provides guidance for hospital managers, healthcare staff, district-level managers and provincial managers on parental access to hospitalised children during a pandemic such as COVID-19. It: (i) summarises legal and ethical issues around parental visitation rights; (ii) highlights four guiding principles; (iii) provides 10 practical recommendations to facilitate safe parental access to hospitalised children; (iv) highlights additional considerations if the mother is COVID-19-positive; and (v) provides considerations for fathers. In summary, it is a child's right to have access to his or her parents during hospitalisation, and parents should have access to their hospitalised children; during an infectious disease pandemic such as COVID-19, there is a responsibility to ensure that parental visitation is implemented in a reasonable and safe manner. Separation should only occur in exceptional circumstances, e.g. if adequate in-hospital facilities do not exist to jointly accommodate the parent/caregiver and the newborn/infant/child. Both parents should be allowed access to hospitalised children, under strict infection prevention and control (IPC) measures and with implementation of non-pharmaceutical interventions (NPIs), including handwashing/sanitisation, face masks and physical distancing. Newborns/infants and their parents/caregivers have a reasonably high likelihood of having similar COVID-19 status, and should be managed as a dyad rather than as individuals. Every hospital should provide lodger/boarder facilities for mothers who are COVID-19-positive, COVID-19-negative or persons under investigation (PUI), separately, with stringent IPC measures and NPIs. If facilities are limited, breastfeeding mothers should be prioritised, in the following order: (i) COVID-19-negative; (ii) COVID-19 PUI; and (iii) COVID-19-positive. Breastfeeding, or breastmilk feeding, should be promoted, supported and protected, and skin-to-skin care of newborns with the mother/caregiver (with IPC measures) should be discussed and practised as far as possible. Surgical masks should be provided to all parents/caregivers and replaced daily throughout the hospital stay. Parents should be referred to social services and local community resources to ensure that multidisciplinary support is provided. Hospitals should develop individual-level policies and share these with staff and parents. Additionally, hospitals should ideally track the effect of parental visitation rights on hospital-based COVID-19 outbreaks, the mental health of hospitalised children, and their rate of recovery.

Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics.

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID­19, including hospitalisations and deaths. The  Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID­19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Quality and turnaround times of viral load monitoring under prevention of mother-to-child transmission of HIV Option B+ in six South African districts with a high antenatal HIV burden.

BACKGROUND: Barriers to monitoring maternal HIV viral load (VL) and achieving 90% viral suppression during pregnancy and breastfeeding still need to be understood in South Africa (SA). OBJECTIVES: To measure quality of VL care and turnaround times (TATs) for returning VL results to women enrolled in the prevention of mother-to-child transmission of HIV (PMTCT) programme in primary healthcare facilities. METHODS: Data were obtained from a 2018 cross-sectional evaluation of the PMTCT Option B+ programme in six SA districts with high antenatal and infant HIV prevalence. Quality of VL care was measured as the proportion of clients reporting that results were explained to them. TATs for VL results were calculated using dates abstracted from four to five randomly selected facility-based client records to report overall facility 'short TAT' (≥80% of records with TAT ≤7 days). Logistical regression and logit-based risk difference statistics were used. RESULTS: Achieving overall short TAT was uncommon. Only 50% of facilities in one rural district, zero in one urban metro district and 9 - 38% in other districts had short TAT. The significant difference between districts was influenced by the duration of keeping results in facilities after receipt from the laboratory. Expected quality of VL care received ranged between 66% and 85%. Client-related factors significantly associated with low quality of care, observed in two urban districts and one rural district, included lower education, recent initiation of antiretroviral treatment and experiencing barriers to clinic visits. Experiencing clinic visit barriers was also negatively associated with short TATs. CONCLUSIONS: We demonstrate above-average quality of care and delayed return of results to PMTCT clients. Context-specific interventions are needed to shorten TATs.

Uptake of antenatal care in high HIV-prevalence settings: Results from three population-based surveys in South Africa.

BACKGROUND: Despite substantial progress in reducing pregnancy-related preventable morbidity and mortality, these remain unacceptably high in developing countries. In 2016, the World Health Organization (WHO) revised recommendations for antenatal care (ANC) from a 4-visit model to a minimum of 8 ANC contacts to reduce perinatal mortality further and improve women's experience of care. The guidelines also recommend that the first ANC visit (ANC-1) should occur during the first trimester. OBJECTIVES: To describe the uptake of routine ANC and its associated factors in South Africa (SA) prior to the 2016 WHO recommendations, when the country recommended 4 ANC visits, to bring to light potential challenges in achieving the current recommendations. METHODS: Secondary data analyses were performed from 3 facility-based, cross-sectional national surveys, conducted to measure 6-week mother-to-child transmission of HIV and coverage of related interventions in SA. These surveys recruited mother-infant pairs attending selected public primary healthcare facilities for their infants' 6-week immunisation in 2010, 2011 -2012 and 2012 -2013. Quantitative questionnaires were used to gather sociodemographic and antenatal-to-peripartum information from Road to Health cards and maternal recall. The inclusion criteria for this secondary assessment were at least 1 ANC visit, the primary outcome being uptake of ≥4 ANC visits. A multivariable logistic regression model was used to: (i) identify maternal factors associated with ANC visits; and (ii) establish whether receiving selected ANC activities was associated with frequency or timing of ANC-1. RESULTS: Of the 9 470, 9 646 and 8 763 women who attended at least 1 ANC visit, only 47.5% (95% confidence interval (CI) 45.4 -49.6), 55.6% (95% CI 53.2 -58.0) and 56.7% (95% CI 54.3 -59.1) adhered to ≥4 ANC visits, while 36.0% (95% CI 34.5 -37.5), 43.5% (95% CI 42.0 -45.1) and 50.8% (95% CI 49.3 -52.2) attended ANC-1 early (before 20 weeks' gestation) in 2010, 2011 -2012 and 2012 -2013, respectively. Multiparity and lower socioeconomic status were significantly associated with non-adherence to the 4-visit ANC recommendation, while a later survey year, higher education, being married, >19 years old, HIV-positive, planned pregnancy and knowing how HIV is transmitted vertically were strongly related to ≥4 ANC visits. The number of women who received selected ANC activities increased significantly with survey year and ≥4 ANC visits, but was not associated with timing of ANC-1. CONCLUSIONS: Despite increases in the uptake of ≥4 ANC visits and early ANC-1 rates between 2010 and 2013, these practices remain suboptimal. Adhering to ≥4 ANC visits improved coverage of selected ANC activities, implying that strengthening efforts to increase the uptake of ANC from at least 4 to 8, could improve overall outcomes.

The role of serological testing in the SARS-CoV-2 outbreak.

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies.

Child health, infant formula funding and South African health professionals: Eliminating conflict of interest.

Letters by Van Niekerk and Khan on article by Lake et al. (Lake L, Kroon M, Sanders D, et al. Child health, infant formula funding and South African health professionals: Eliminating conflict of interest. S Afr Med J 2019;109(12):902-906. https://doi.org/10.7196/SAMJ.2019.v109i12.14336); and response by Lake et al.

A rapid review of the effectiveness of screening practices at airports, land borders and ports to reduce the transmission of respiratory infectious diseases such as COVID-19.

BACKGROUND: Travel screening for infectious diseases is often implemented to delay or prevent the entry of infected persons to a country/area. OBJECTIVES: To evaluate the effectiveness of different point-of-entry screening strategies in achieving a reduction in imported COVID-19 transmission. METHODS: A rapid evidence review was conducted, systematically searching PubMed and Google Scholar and grey literature on 27 March 2020. RESULTS: We screened 1 194 records. Nine potential full-text articles were assessed for eligibility and included. Three articles investigated the effectiveness of entry-based thermal and body temperature scanning. Entry-based infrared thermal or body temperature scanning for COVID-19 was unlikely to be effective. Two systematic reviews found no additional benefit of travel restrictions/screening. In a COVID-19 modelling study, airport screening was not effective, with exit and entry thermal scanning identifying half and missing almost half of infected travellers. Two other modelling studies found that entry-based travel screening would achieve only modest delays in community transmission, while international travel quarantine could reduce case importations by 80%. CONCLUSIONS: There is insufficient evidence to support entry and exit screening at points of entry, as these strategies detect just over half of the infected cases, missing almost half at entry points. The benefits of airport screening therefore need to be context specific and weighed against the resources and cost of implementation, the contribution of imported cases to total cases, and the benefits of identifying 50% of cases in the South African context with the country's high HIV and tuberculosis prevalence and limited resources to deal with a pandemic of this nature.

A rapid review of the effectiveness of screening practices at airports, land borders and ports to reduce the transmission of respiratory infectious diseases such as COVID-19

Background. Travel screening for infectious diseases is often implemented to delay or prevent the entry of infected persons to a country/area.Objectives. To evaluate the effectiveness of different point-of-entry screening strategies in achieving a reduction in imported COVID-19 transmission.Methods. A rapid evidence review was conducted, systematically searching PubMed and Google Scholar and grey literature on 27 March 2020.Results. We screened 1 194 records. Nine potential full-text articles were assessed for eligibility and included. Three articles investigated the effectiveness of entry-based thermal and body temperature scanning. Entry-based infrared thermal or body temperature scanning for COVID-19 was unlikely to be effective. Two systematic reviews found no additional benefit of travel restrictions/screening. In a COVID-19 modelling study, airport screening was not effective, with exit and entry thermal scanning identifying half and missing almost half of infected travellers. Two other modelling studies found that entry-based travel screening would achieve only modest delays in community transmission, while international travel quarantine could reduce case importations by 80%.Conclusions. There is insufficient evidence to support entry and exit screening at points of entry, as these strategies detect just over half of the infected cases, missing almost half at entry points. The benefits of airport screening therefore need to be context specific and weighed against the resources and cost of implementation, the contribution of imported cases to total cases, and the benefits of identifying 50% of cases in the South African context with the country's high HIV and tuberculosis prevalence and limited resources to deal with a pandemic of this nature

The role of serological testing in the SARS-CoV-2 outbreak

Antibody tests for the novel coronavirus, SARS-CoV2, have been developed both as rapid diagnostic assays and for high-throughput formal serology platforms. Although these tests may be a useful adjunct to a diagnostic strategy, they have a number of limitations. Because of the antibody and viral dynamics of the coronavirus, their sensitivity can be variable, especially at early time points after symptom onset. Additional data are required on the performance of the tests in the South African population, especially with regard to development and persistence of antibody responses and whether antibodies are protective against reinfection. These tests may, however, be useful in guiding the public health response, providing data for research (including seroprevalence surveys and vaccine initiatives) and development of therapeutic strategies

Child health, infant formula funding and South African health professionals: Eliminating conflict of interest.

Despite clear evidence of the benefits of exclusive and continued breastfeeding for children, women and society, far too few children in South Africa (SA) are breastfed. One of the major impediments to improving this situation is the continued and aggressive marketing of breastmilk substitutes (BMSs) and infiltration of the BMS industry into contexts with exposure to health professionals. In this article we, as academics, practitioners and child health advocates, describe contraventions of the regulations that protect breastfeeding in SA and argue that bold, proactive leadership to eliminate conflict of interest in respect of the BMS industry is urgently required, together with far greater investments in proven interventions to promote and support breastfeeding.

Moving towards universal health coverage: Strengthening the evidence ecosystem for the South African health system.

Health policy and systems research (HPSR) guides health system reforms and is essential for South Africa (SA)'s progress towards universal coverage of high-quality healthcare. For HPSR evidence to inform and strengthen health systems, it needs to flow efficiently between evidence producers, evidence synthesisers, evidence processers and disseminators and evidence implementors in an evidence ecosystem. A substantial body of evidence for health systems strengthening is generated in SA, and this informs national and international health system guidelines and guidance. In this manuscript, in celebration of the 50th anniversary of the SA Medical Research Council, we apply an evidence ecosystem lens to the SA health system, and discuss its current functioning in support of the achievement of a high-quality health system that is able to achieve universal health coverage. We use three case studies to describe successes, challenges and gaps in the functioning of the evidence ecosystem. The first case study focuses on using evidence to strengthen health-system governance and support for community health worker programmes. The second case focuses on managing the growing epidemic of drug-resistant tuberculosis, while the third case focuses on social protection, the child support grant and its impact on health. SA scientists are part of global initiatives to strengthen the health-systems evidence ecosystem, specifically through pioneering methods to synthesise evidence and produce evidence-informed guidelines to facilitate evidence use in health-system decision-making. SA institutes of health policy analysis facilitate involvement of evidence producers and synthesisers in the national health system policy-making process. A future priority is to further strengthen national initiatives to translate evidence into policy and practice and to sustain capacity for continuous technical support to health-systems policy development and implementation.

The impact of health programmes to prevent vertical transmission of HIV. Advances, emerging health challenges and research priorities for children exposed to or living with HIV: Perspectives from South Africa.

Over the past three decades, tremendous global progress in preventing and treating paediatric HIV infection has been achieved. This paper highlights the emerging health challenges of HIV-exposed uninfected (HEU) children and the ageing population of children living with HIV (CLHIV), summarises programmatic opportunities for care, and highlights currently conducted research and remaining research priorities in high HIV-prevalence settings such as South Africa. Emerging health challenges amongst HEU children and CLHIV include preterm delivery, suboptimal growth, neurodevelopmental delay, mental health challenges, infectious disease morbidity and mortality, and acute and chronic respiratory illnesses including tuberculosis, pneumonia, bronchiectasis and lymphocytic interstitial pneumonitis. CLHIV and HEU children require three different categories of care: (i) optimal routine child health services applicable to all children; (ii) routine care currently provided to all HEU children and CLHIV, such as HIV testing or viral load monitoring, respectively, and (iii) additional care for CLHIV and HEU children who may have growth, neurodevelopmental, behavioural, cognitive or other deficits such as chronic lung disease, and require varying degrees of specialised care. However, the translation thereof into practice has been hampered by various systemic challenges, including shortages of trained healthcare staff, suboptimal use of the patient-held child's Road to Health book for screening and referral purposes, inadequate numbers and distribution of therapeutic staff, and shortages of assistive/diagnostic devices, where required. Additionally, in low-middle-income high HIV-prevalence settings, there is a lack of evidence-based solutions/models of care to optimise health amongst HEU and CLHIV. Current research priorities include understanding the mechanisms of preterm birth in women living with HIV to optimise preventive interventions; establishing pregnancy pharmacovigilance systems to understand the short-, medium- and long-term impact of in utero ART and HIV exposure; understanding the role of preconception maternal ART on HEU child infectious morbidity and long-term growth and neurodevelopmental trajectories in HEU children and CLHIV, understanding mental health outcomes and support required in HEU children and CLHIV through childhood and adolescence; monitoring HEU child morbidity and mortality compared with HIV-unexposed children; monitoring outcomes of CLHIV who initiated ART very early in life, sometimes with suboptimal ART regimens owing to medication formulation and registration issues; and testing sustainable models of care for HEU children and CLHIV including later reproductive care and support.

Neonatal, infant and child health in South Africa: Reflecting on the past towards a better future.

Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living with HIV, expanded immunisation policies, strengthening breastfeeding practices, and health policies to contain tobacco and sugar use. The Sustainable Development Goals (2016 - 2030) have shifted the focus from keeping children alive, as expressed in the Millennium Development Goals (1990 - 2015), to achieving optimal health through the 'Survive, thrive and transform' global agenda. This paper focuses on important remaining causes of childhood mortality and morbidity in SA, specifically respiratory illness, environmental pollution, tuberculosis, malnutrition and vaccine-preventable conditions. The monitoring of maternal and child health (MCH) outcomes is crucial, and has improved in SA through both the District Health Information and Civil Registration and Vital Statistics systems, although gaps remain. Intermittent surveys and research augment the routinely collected data. However, availability and use of local data to inform quality and effectiveness of care is critical, and this requires ownership at the collection point to facilitate local redress. Potential game changers to improve MCH outcomes include mobile health and community-based interventions. In SA, improved MCH remains a crucial factor for human capital development. There is a pressing need to focus beyond childhood mortality and to ensure that each child thrives.

Leveraging the Road to Health booklet as a unique patient identifier to monitor the prevention of mother-to-child transmission programme.

BACKGROUND: Currently there is no unique patient identification system in the South African public health sector. Therefore, routine laboratory data cannot effectively be de-duplicated, thereby hampering surveillance of laboratory-diagnosed diseases such as mother-to-child transmission of HIV. OBJECTIVES: To determine the uptake of Road to Health booklet (RTHB) identifiers at HIV polymerase chain reaction (PCR) birth test and describe their performance in linking follow-up test results in the early infant diagnosis programme. METHODS: Between May 2016 and May 2017, Tshwane District Clinical Services implemented a unique patient identifier pilot project in which a sticker-page of unique, readable, barcoded patient identifiers was incorporated in the patient-retained immunisation record (the RTHB) before distribution. Uptake of RTHB identifiers at birth was calculated as the proportion of HIV PCR tests in infants aged <6 days registered with an RTHB identifier over the total number of registered HIV PCR tests. Descriptive analysis of demographic details was performed among infants with two registered HIV PCR tests linked by the RTHB identifier, and performance of the National Health Laboratory Service Corporate Data Warehouse (NHLS CDW)-linking algorithm in matching RTHB-linked results was calculated using a 2 × 2 table. RESULTS: A total of 5 309 HIV PCR birth tests registered with an RTHB identifier were extracted from the NHLS CDW over the 13-month period of the pilot project. The number of registered RTHB identifiers increased from 24 (2% of birth PCR tests) in May 2016, peaking at 728 (56% of birth PCR tests) in May 2017. Among infants with a registered RTHB identifier at birth, 635 (12%) had a subsequent linked HIV PCR test, as indicated by the same RTHB number registered for a later specimen. Demographic details at the time of birth and subsequent PCR test were compared, demonstrating that <4% of infants had exact matches for name, surname, date of birth and sex; 74% of birth tests had variations such as 'born to' or 'baby of ' in place of a first name; surnames matched exactly in 61% of cases; 18% (n=116) of infants had both tests performed at the same facility, of which only 27% (n=31) had the same patient folder number on both test results. CONCLUSIONS: Leveraging RTHBs as unique patient identifiers, even if used temporarily until linkage to other future national unique identifiers, promises to be an effective scalable approach to laboratory-based surveillance, facilitating healthcare provider access to all test results from birth.

Elimination of mother-to-child transmission of HIV in South Africa: rapid scale-up using quality improvement.

BACKGROUND: South Africa (SA) is committed to achieving the goal of eliminating mother-to-child transmission (MTCT) of HIV by 2015. To achieve this, universal coverage of quality antenatal, labour, delivery and postnatal services for all women has to be attained. Over the past decade, the prevention of mother-to-child transmission (PMTCT) programme has been scaled up to reach all healthcare facilities in the country. However, challenges persist in achieving 100% coverage and access to the programme. OBJECTIVES: We describe the process undertaken by the National Department of Health (NDoH), in collaboration with partners, to develop, implement and monitor a data-driven intervention to improve facility, district, provincial and national PMTCT-related performance. METHODS: Between 2011 and 2013, the NDoH developed and implemented an intervention using data-driven participatory processes to understand facility-level bottlenecks to optimise PMTCT implementation and to scale up priority PMTCT actions nationally. RESULTS: There was remarkable improvement across all key indicators in the PMTCT cascade over the 3 years 2011-2013. Simple monitoring tools such as a visual dashboard and data for action reports were successfully used to improve the performance of the PMTCT programme across SA. MTCT has shown a significant downward trend. CONCLUSIONS: It is feasible to implement district-level, data-driven quality improvement processes at a national scale to improve the performance of the PMTCT programme at the local level.

Survival of infants in the context of prevention of mother to child HIV transmission in South Africa.

AIM: We sought to study the survival of newborn children according to HIV status of the mother, that of the child and the timing of infection. METHODS: This is a prospective cohort study of 883 mothers (665 HIV-positive and 218 HIV-negative) and their infants. Data were collected using semi-structured questionnaires during home visits between the antenatal period and 36 weeks post-delivery. Infant HIV status was determined at 3, 24 and 36 weeks by HIV DNA PCR. RESULTS: The majority (81.3%) of infected infants who died were infected by 3 weeks of age. Of the HIV-exposed infants who died, 19 (28.4%) died before 6 weeks and 38 (56.7%) died by 12 weeks. The hazard ratio (HR) of mortality at 36 weeks of age in HIV-infected infants compared with exposed but negative infants was 8.9 (95% CI: 6.7-11.8). There was no significant difference in 36 week survival rates between HIV-non-exposed and HIV-exposed but negative infants (HR: 0.7; 95% CI: 0.3-1.5). The infant being HIV-positive at age 3 weeks (HR: 32 95% CI: 14.0-73.1) and rural site (HR: 4.4 95% CI: 1.2-23.4) were the two independent risk factors for infant death amongst HIV-exposed infants. CONCLUSION: The prognosis for infants with early HIV infection was very poor in this cohort. A greater focus on prevention of early infection, earlier screening for HIV infection and access to antiretrovirals for eligible infants is recommended.

Free formula milk for infants of HIV-infected women: blessing or curse?

There is vigorous controversy around whether HIV-infected women in developing countries should choose formula or breastfeeding for their infants. Formula eliminates HIV transmission but incurs risk of increased mortality, whereas breastfeeding has multiple benefits but entails risk of HIV transmission. International guidelines are available but need to be strengthened. This commentary summarizes data on the scale and rate of mother-to-child transmission (MTCT) of HIV through breastfeeding, and the hazards and benefits of breast- and formula-feeding. The case against providing free or subsidized formula to HIV-infected mothers is based on the following: it exacerbates disadvantages of formula feeding; compromises free choice; targets beneficiaries erroneously; creates a false perception of endorsement by health workers; compromises breastfeeding; results in disclosure of HIV status; ignores hidden costs of preparation of formula; increases mixed breastfeeding, which is an unsatisfactory method for all women; requires organization and management of programmes that are complicated and costly; and finally increases the 'spill-over' effect into the normal breastfeeding population. Recommendations to minimize these drawbacks include use of affordable antiretrovirals to reduce MTCT; investments in high-quality, widely available HIV counselling; support for choice of feeding; and exclusive breastfeeding for those who choose to breastfeed.

A functional screen for regulators of the c-Abl protein tyrosine kinase.

c-Abl protein tyrosine kinase activity is tightly regulated in vertebrate cells. Several mutations can activate Abl and convert it into an oncogene. In man, chromosomal translocations result in fusion proteins associated with chronic myelogenous leukemias and some acute lymphocytic leukemias. In viral forms of abl, gag sequences are fused to Abl portions resulting in a deletion of N-terminal sequences. To study c-Abl activity in a cellular environment likely to lack specific regulators, we have expressed human c-Abl in Schizosaccharomyces pombe in an inducible fashion. c-Abl causes growth arrest followed by death of the cells. Mutations in the SH2 domain or in the autophosphorylation site dramatically reduce the ability of Abl to confer the growth arrest phenotype and to phosphorylate endogenous proteins, suggesting a fundamental role of these structures in the activity of the enzyme. An SH3 domain deletion mutant of Abl is as active as c-Abl in yeast indicating that there is no intrinsic regulation of c-Abl occurring via the SH3 domain and suggesting that the inhibitory effect of the SH3 domain observed in cells of vertebrate origin is mediated by a factor that is absent in fission yeast. We have used this assay to functionally screen a human cDNA library for molecules able to counteract the lethal effect of c-Abl expression. We are currently in the process of characterising the isolated clones. We hope to identify among them the molecule(s) responsible for regulating c-Abl activity in human cells.