Well-resourced Countries Research Articles

Accuracy of after-hour ‘red dot’ trauma radiograph triage by radiographers in a South African regional hospital

The global demand for diagnostic imaging exceeds the supply of radiologists and is of particular significance in poorly resourced healthcare environments where many radiographs are unreported. Delayed or absent reporting may negatively impact patient management. In well-resourced countries there is recognition that extending the role of radiographers to radiological reporting tasks helps meet service demands. Aim. To determine the accuracy of acute fracture detection by South African radiographers working in an after-hour setting. We performed a retrospective study of radiographers at a Western Cape Regional Hospital over 2 months in 2011. The sensitivity and specificity of radiographers' fracture detection were compared with that of a consultant radiologist. Differences were evaluated using the McNemar chi-squared test, with p<0.05 regarded as significant. A total of 369 radiographs were analysed. The overall accuracy of reporting by radiographers was 93.7%, with 74.4% sensitivity for fracture detection. Experienced radiographers performed better than inexperienced radiographers; adult fractures were more consistently identified than paediatric fractures, and appendicular fractures were better visualised than axial fractures. In all instances there was a significant difference between fracture detection by radiographers and the radiologist. Experienced radiographers evaluating appendicular fractures in adults achieved the highest sensitivity (89.9%), which was not significantly different from that of a consultant radiologist (p=0.88). The performance of experienced radiographers in our study is comparable with that of experienced radiographers internationally, who have no specific training in trauma radiograph reporting. However, additional training is required if role extension is to be considered.

Why South Africa's proposed advertising ban matters

Why South Africa's proposed advertising ban matters

Computational models can predict response to HIV therapy without a genotype and may reduce treatment failure in different resource-limited settings

Genotypic HIV drug-resistance testing is typically 60%-65% predictive of response to combination antiretroviral therapy (ART) and is valuable for guiding treatment changes. Genotyping is unavailable in many resource-limited settings (RLSs). We aimed to develop models that can predict response to ART without a genotype and evaluated their potential as a treatment support tool in RLSs. Random forest models were trained to predict the probability of response to ART (≤400 copies HIV RNA/mL) using the following data from 14 891 treatment change episodes (TCEs) after virological failure, from well-resourced countries: viral load and CD4 count prior to treatment change, treatment history, drugs in the new regimen, time to follow-up and follow-up viral load. Models were assessed by cross-validation during development, with an independent set of 800 cases from well-resourced countries, plus 231 cases from Southern Africa, 206 from India and 375 from Romania. The area under the receiver operating characteristic curve (AUC) was the main outcome measure. The models achieved an AUC of 0.74-0.81 during cross-validation and 0.76-0.77 with the 800 test TCEs. They achieved AUCs of 0.58-0.65 (Southern Africa), 0.63 (India) and 0.70 (Romania). Models were more accurate for data from the well-resourced countries than for cases from Southern Africa and India (P < 0.001), but not Romania. The models identified alternative, available drug regimens predicted to result in virological response for 94% of virological failures in Southern Africa, 99% of those in India and 93% of those in Romania. We developed computational models that predict virological response to ART without a genotype with comparable accuracy to genotyping with rule-based interpretation. These models have the potential to help optimize antiretroviral therapy for patients in RLSs where genotyping is not generally available.

What’s New in the Recognition and Management of Septic Shock in Children: Dos and Don'ts

While there has been a reduction in the number of children dying of septic shock in the richer countries of the world, septic shock remains an important cause of both mortality and morbidity for children across the world. Major reduction in the incidence of septic shock will depend on the implementation of public health measures, including immunization. Improvements in outcome of pediatric septic shock have been closely linked to early recognition (although this may be challenging in many situations); early antibiotic administration; early and appropriate fluid administration and subsequent escalation of critical care. A particular challenge has been the development and implementation of systems to ensure that these elements of management are reliably and efficiently implemented in children (even in well-resourced countries). Recent studies have highlighted the complexity of caring for patients with acute severe sepsis and septic shock in countries with fewer resources, and there is an urgent need for further studies to elucidate the implications of these studies for the management of children with septic shock, particularly in settings where additional critical care support such as inotropic or ventilator support may not be readily available.

Continuous Support During Childbirth by Maternity Care Assistants: An Exploration of Opinions in the Netherlands

BACKGROUND:The Netherlands maintain a high rate of home births relative to other well-resourced countries. Maternity care assistants (MCAs) play an important role, as part of the maternity care team, assisting the midwife during birth and providing postpartum care to women and babies in their homes. A Cochrane review recently described the advantages of continuous support during childbirth. We were interested in the opinions of MCAs about them having an expanded role to include continuous emotional support during childbirth as well as medical tasks such as checking the condition of the fetus and maternal labor progress through internal examination.METHODS:To explore the opinions of MCAs, four semistructured group discussions took place and 190 questionnaires were sent out to MCAs nationally.RESULTS:In both the group discussions and questionnaires, MCAs displayed positive attitudes toward providing continuous support during childbirth. In general, MCAs were not keen on adding medical tasks. The importance of a clear distribution of responsibilities between midwives and MCAs was reported. Most (60.0%) thought midwives would appreciate MCAs providing continuous support. Furthermore, 40.5% disagreed with dividing the profession into childbirth care and postpartum care teams. Two-thirds mentioned the need for extra training in childbirth assistance.CONCLUSION:In general, MCAs were positive about providing continuous support during childbirth. Most MCAs think that it is unwise to give MCAs additional medical responsibilities. The opinions differ concerning issues of practical organization. MCAs generally thought extra schooling was important to be and feel competent to assist childbirth.

Role of the Placenta in Adverse Perinatal Outcomes among HIV-1 Seropositive Women

Women seropositive for human immunodeficiency virus type 1 (HIV-1) are at an increased risk for a number of adverse perinatal outcomes. Although efforts to reduce mother-to-child transmission of HIV (MTCT) remain a priority in resource-limited countries, HIV testing and treatment have led to steep declines in MTCT in well-resourced countries. Even so, HIV seropositive pregnant women in the United States continue to deliver a disproportionately high number of preterm and low birth weight infants. In this mini-review, we address the role of the placenta in such HIV-related perinatal sequelae. We posit that adverse perinatal outcomes may result from two mutually non-exclusive routes: (1) HIV infection of the placenta proper, potentially leading to impaired maternal-fetal exchange; and (2) infection of the maternal decidual microenvironment, possibly disrupting normal placental implantation and development. Further research into the relationship between HIV-1 infection and placental pathology may lead to the development of novel strategies to improve birth outcomes among HIV-1 seropositive parturients.

Benefits and constraints of intimate partnerships for HIV positive sex workers in Kibera, Kenya.

IntroductionResearch on the intimate partnerships of female sex workers (FSWs) tends to focus on the risks associated with these relationships. This paper takes as its starting point that the situation of FSWs is better understood by including knowledge of the benefits of their intimate partnerships. Specifically, we employ the conceptual framework provided by emergent research examining intimacy as a complex fusion of affective and instrumental dimensions among sex workers. This perspective allows us to frame information about FSWs’ intimate partnerships within a behaviour-structural approach that is helpful for identifying how intimate partnerships can be a source of both benefit as well as increased risk to FSWs.MethodsOur results are based on a mixed-methods study carried out in the summer of 2011 in Kibera, Kenya. We conducted face-to-face interviews (n=30) with a non-probability sample of FSWs stratified by age who self-identified as Human Immune Virus positive (HIV+). We asked about participants’ involvement in current and past intimate partnerships, and whether these relationships had a positive or negative impact on their health and well‒being.ResultsParticipants currently in intimate partnerships had fewer clients and thus lower incomes than those without intimate partnerships. Participants presently with partners were also more likely to receive some financial support from partners, to report lower intimate partner violence, and to narrate higher partner emotional support and greater assistance with medications. These participants were also more likely to have disclosed their sex work and HIV+ statuses to their partners. Intimate partnerships, on the other hand, showed increased risk of economic vulnerability and emotional dependence for FSWs. This became especially problematic for those participants in fragile relationships. Despite these variations, none of the differences between the two groups were statistically significant.ConclusionsIntimacy and transactional relations are bound up with one another and intersect with the structural realities and vulnerabilities; this is the case for sex workers in well-resourced and resourced-constrained countries alike. Rather than treating intimate partnerships as distinct from transactional relationships, FSWs’ relationships should be viewed on a continuum of risk and support.

A role for a global body for paediatric neurodisability

‘Prevent the preventable, treat the treatable and provide effective care’ is the essence of the United Nations Political Declaration on Non-Communicable Diseases (Resolution A/RES/66/2), in which all member states undertook in 2011 to do more to tackle these conditions.1 Since then, groups representing people with cancer and diabetes have adopted the resolution to lobby for better care globally, but this has not yet happened for people with neurodisability. Instead they have been incorporated by the World Health Organization (WHO) into an even larger group, ‘mental, neurological and substance misuse disorders’, where mental health issues appear to predominate.2 This may not be in the best interest of those with neurodisability, especially children. In the meantime, there is plenty of recognized best practice. In terms of prevention, immunization programmes and prevention of accidents – brain trauma still being the most important cause of death and acquired disability in children – should continue to be the main priorities. In terms of treatment, early recognition and treatment of neonatal jaundice, or hypoglycaemia, cerebral infections, and prolonged status epilepticus at all ages, are all well known examples. However, as is made clear in the UN Resolution, there is a massive amount still to do. Best practice is not always applied even in well-resourced countries. Many children, especially in resource-poor countries, still suffer avoidable neurological damage. In terms of rehabilitation the move from dogma-based to scientifically-based approaches is to be applauded but, for example, the physiotherapy prescribed or available for a child with cerebral palsy still varies considerably in different countries. To address these issues properly and lobby more effectively in all countries a global body representing neurodisability is essential. Existing organizations could form the anchors for such a body. As delivery of health care to children, adolescents, and adults with neurodisability requires sharing of expertise amongst multiple disciplines, all should be represented, as well as patients and their families.3 Ideally it should be linked to the WHO, to use their authority when advising governments what actions are most useful. The WHO and the World Federation of Neurology have already collaborated in this way, but the result is very adult orientated.4 In addition, at present the WHO understandably only wants to advocate interventions with a high level of evidence, but given the lower levels available especially in many childhood conditions this is too narrow. The functions of such a body should include setting health priorities, advising how outcomes can best be assessed, and identifying areas needing research, which will differ between countries. As well as major unanswered questions such as how to reduce the incidence of preterm birth, with all its associated intellectual and physical risks to children, more modest and achievable aims could include ensuring that clear guidelines are agreed for common conditions and that health care personnel are trained to follow them properly – an approach that has been shown to be effective in adult conditions such as cardiac arrest. Other initiatives can be supported such as the recently launched and very user-friendly website, Treatable-ID.org, which has identified 81 potentially treatable metabolic conditions that can cause intellectual disability.5 With the impetus from the UN resolution it is now time to act.

Management of Children With a Wilms Tumor in Malawi, Sub-Saharan Africa

Wilms tumor has a survival rate of 85% to 90% in well-resourced countries. Malawi is a country in Sub-Saharan Africa with very limited resources. We evaluated the outcome of a treatment guideline including preoperative chemotherapy, supportive care, and strategies to enable parents to complete treatment. Between 2006 and 2011, 95 patients were initially diagnosed with a Wilms tumor; 11 were later excluded due to misdiagnosis. In 31% of patients, metastases were detected at presentation. Treatment outcomes in 8 patients with bilateral tumors and 3 patients who were referred after nephrectomy are analyzed separately. Treatment failed in 51% of 73 remaining patients. Reasons for failure were: 1) incomplete treatment (7%); 2) treatment-related deaths (15%); and 3) disease-related deaths (28%) with 11% unresectable tumors or metastases after preoperative chemotherapy and 17% relapse of disease. Projected survival is 46%. Challenges remain to improve survival for children with Wilms tumor in Malawi. Earlier diagnosis would reduce disease-related deaths as numbers of unresectable disease and relapse are high. Effective strategies, including social support, to enable parents to complete treatment need to be continued. Improved supportive care and nutritional support and possibly less intense preoperative chemotherapy are needed to reduce treatment-related deaths.

Feeding difficulties in children with cerebral palsy: low‐cost caregiver training in Dhaka, Bangladesh

The majority of children with cerebral palsy have feeding difficulties, which, if not managed, result in stressful mealtimes, chronic malnutrition, respiratory disease, reduced quality of life for caregiver and child, and early death. In well-resourced countries, high- and low-cost medical interventions, ranging from gastrostomy tube feeding to caregiver training, are available. In resource-poor countries such as Bangladesh, the former is not viable and the latter is both scarce and its effectiveness not properly evaluated. The aim of this study was to evaluate the effectiveness of a low-cost, low-technology intervention to improve the feeding practices of carers of children with moderate-severe cerebral palsy and feeding difficulties in Bangladesh. An opportunistic sample of 37 caregivers and their children aged 1-11 years were invited to a six-session training programme following an initial feeding assessment with brief advice. During home visits, pre- and post-measures of nutritional status, chest health and feeding-related stress were taken and feeding practices were observed. A control phase was evaluated for 20 of the participant pairs following initial assessment with advice, while awaiting full training. A minimum of four training sessions showed significant improvements in the children's respiratory health (P = 0.005), cooperation during mealtimes (P = 0.003) and overall mood (P < 0.001). Improvements in growth were inconsistent. Dramatic reductions were observed in caregiver stress (P < 0.001). A significant difference in the outcomes following advice only compared with advice plus training was also observed. In situations of poverty, compliance is restricted by lack of education, finances and time. Nonetheless, carers with minimal formal education, living in conditions of extreme poverty were able to change feeding practices after a short, low-cost training intervention, with highly positive consequences. The availability of affordable food supplementation for this population, however, requires urgent attention.

Antiviral Drugs for Treatment of Patients Infected with Pandemic (H1N1) 2009 Virus

To the Editor: The emergence of influenza A pandemic (H1N1) 2009 virus in North America and associated illness and death suggest that humanity faces a dangerous threat. Viruses isolated from a sample of patients with confirmed cases in early phases of the outbreak demonstrated resistance to amantadine and rimantadine. At present, circulating viruses appear to be largely susceptible to the neuraminidase inhibitors oseltamivir and zanamivir, although oseltamivir resistance has been observed in recent cases in Europe, Asia, and North America (1). More recently, pandemic (H1N1) 2009 virus resistance to oseltamivir emerged during treatment of 2 immunosuppressed patients in the United States. Such cases demonstrate that oseltamivir resistance can emerge in infected persons treated with oseltamivir. To date, all isolates tested have been susceptible to zanamivir. Vaccines are being deployed in some well-resourced countries but are generally not available to the public. It appears that little if any protection is offered from previous seasonal influenza vaccines. In the spring of 1918, epidemiologic observations indicated the likely emergence and spread of another influenza virus (H1N1) that caused few deaths. However, later that year, transmission resurged and was associated in 2 waves with increased illness and deaths. We cannot predict whether the 2009 pathogen will follow a similar temporal pattern and evolve toward increased virulence. Even if vaccine development and delivery could be achieved within 6 months, an aggressive schedule, large supplies of vaccine against pandemic (H1N1) 2009 may not be available until late 2009. Antiviral drugs are used to treat patients with strongly suspected or confirmed influenza. However, until a vaccine is available, specific protection by pharmaceutical products is limited to antiviral drugs. Nonpharmaceutical interventions are also available for prevention. Some governments and organizations are taking steps that would enable mass administration of these drugs (2). This administration may prove problematic. A recent study showed that schoolchildren may incompletely adhere to oseltamivir prophylaxis instructions (3). If other groups are given oseltamivir prophylaxis, they cannot necessarily be expected to follow administration guidelines; compliance with taking the recommended number of doses at appropriate times is difficult to enforce. Moreover, even when compliance is high, oseltamivir prophylaxis may fail (4). The first viable oseltamivir-resistant human influenza viruses (H1N1) emerged and became prevalent in the United States and Europe in the 2007–08 influenza season, and prevalence of such viruses has continued in 2009. The potential for overuse of antiviral drugs, especially oseltamivir, to select for existing antiviral drug-resistant strains is unknown. Ecologic studies suggest a lack of association between prevalence of oseltamivir use and prevalence of oseltamivir resistance (5). However, examination of seasonal influenza virus isolates obtained before introduction of oseltamivir showed an absence of resistance (6), leading some to conclude that antiviral monotherapy leads to selection pressure for resistance (7). Regardless of origin of resistance, recent seasonal influenza viruses (H1N1) of the A/Brisbane/57/2007 lineage from around the world display such resistance. A similar resistance pattern could occur with pandemic (H1N1) 2009 virus. Regardless of the mutational mechanism for antiviral drug resistance, mass use of antiviral drugs could potentially lead to selection pressure for drug-resistant viruses (7). Experience with seasonal influenza demonstrated the fitness of some oseltamivir-resistant strains (8). Moreover, modeling studies suggest that antiviral-resistant strains may spread rapidly and markedly affect pandemic outcomes (9). What are we to do? Until a vaccine is available, combination antiviral therapy and rapid diagnostic testing may be needed (7). Given the recently described low sensitivity of currently available rapid tests, applying such assays to all patients is problematic (10). If rapid testing has a role, it should be used in testing persons at highest risk for developing influenza complications. However, early empiric therapy based on clinical manifestations and knowledge of circulating strains is likely more appropriate than reliance on tests with low sensitivity. Updated guidelines recently issued by the World Health Organization (www.who.int/csr/resources/publications/swineflu/h1n1_guidelines_pharmaceutical_mngt.pdf) and the Centers for Disease Control and Prevention (www.cdc.gov/h1n1flu/recommendations.htm) for prophylaxis should be followed to keep resistance in check and save the lives of patients. A widely administered protective vaccine is needed to prevent transmission and infection and preserve the efficacy of antiviral agents. Indiscriminant administration of these agents could support proliferation of antiviral resistance in pandemic (H1N1) 2009 virus or an evolved variant. Appropriate use of antiviral chemotherapy is complex. Identifying the groups at high risk for serious illness for drug therapy and appropriate antiviral therapy in situations of co-circulation of seasonal and pandemic (H1N1) viruses with various susceptibility patterns needs elucidation. Without clear evidence-based guidance, a global public health disaster could occur if pandemic (H1N1) 2009 reemerges later this year with higher virulence or widespread antiviral drug resistance.

An audit of PMTCT services at a regional hospital in South Africa

SA Fam Pract 2009;51(6):492-495 Prevention of mother-to-child transmission (PMTCT) is a major intervention world-wide in the fight against the HIV pandemic, and has resulted in markedly reduced rates of mother-to-child transmission rates in well-resourced countries. However, it seems that barriers to implementation of the programme exist at all levels of health care at all facilities providing maternal care. Aim: To conduct a clinical audit of the PMTCT programme at a regional hospital in Pietermaritzburg, KwaZulu-Natal, South Africa. Methods: Data was collected from an analysis of antenatal and medical records of women who attended antenatal care and delivered at the regional hospital between January and December 2007. Only pregnant women who attended antenatal care at this regional hospital and delivered in its facilities were selected for the study. Patients eligible for review were identified using the labour ward delivery log book. Results: Of the 499 records analysed, 479 women (96%) were offered testing, of which 473 accepted. Of those tested, 227 (48%) were HIV positive. Only 15 (6.1%) of the 246 who tested negative were re-tested. CD4 counts were done for only 159 (70%) of the 227 HIV-positive women. More importantly, only 134 (84.3%) received their results. Of the 227 HIV-positive women, only 131 (57.7%) were given 200 mg nevirapine at ≥ 28 weeks gestation (to take home and swallow once they had strong labour pains); 185 (81.5%) took nevirapine before delivery (i.e. the total number of both those that took NVP 2hrs) 143 (77.3%) took nevirapine > 2 hours before delivery and 84 (37%) took nevirapine < 2 hours before delivery. Of the babies, 208 (91.6%) were given nevirapine within 72 hours. Discussion: This audit shows that progress has been made in the implementation of PMTCT of HIV at this regional hospital by the high uptake of HIV testing; however, barriers to full implementation are caused by the lack of integration of testing, counselling and obtaining CD4 count results.

Organ Trafficking: Global Solutions for a Global Problem

The organ trafficking market is on the rise worldwide. Numerous unfortunate stories of networks of brokers, physicians, and hospitals engaged in illegal trade have been featured in high-profile media. The profitable enterprises facilitating these unregulated services exploit the poor in underresourced countries and offer substandard medical care with unacceptable outcomes to the rich recipients. Despite efforts to boost altruistic organ donation and resolutions to curb transplant tourism, their implementation has been compromised. At the same time, the worldwide escalation in the number of patients with kidney failure coupled with a shortage in the supply of organs continues to fuel this trade. Thus, measures to enhance the donor pool in well-resourced countries to meet their own needs will act as a strong deterrent to the proliferation of transplant tourism in impoverished nations. Regulated schemes that include reimbursement for removing potential disincentives to organ donation and ensure the long-term safety of donors and their families are likely to increase living donations. Such socially responsible programs should be tested in both developed and developing countries for their own populations. It also is vital that developing countries establish a regulated, standardized, and ethical system of organ procurement; create awareness in physicians and the public; upgrade facilities and standardize medical care; and enforce legislation for transplantation. The World Health Organization, National Kidney Foundation, and international transplant and nephrology societies can have an instrumental role in facilitating initiatives in these critical areas. There should be clearly defined codes of conduct for health care facilities and professionals' roles in unregulated paid organ donations and transplants. Ultimately, physicians and transplant surgeons have the responsibility to ensure to the best of their ability that the organs they transplant were obtained upholding the highest standards of ethics.

Surviving sepsis in low-income and middle-income countries: new directions for care and research

Sepsis is a disorder characterised by systemic inflammation secondary to infection. Despite recent progress in the understanding and treatment of sepsis, no data or recommendations exist that detail effective approaches to sepsis care in resource-limited low-income and middle-income countries (LMICs). Although few data exist on the burden of sepsis in LMICs, the prevalence of HIV and other comorbid conditions in some LMICs suggest that sepsis is a substantial contributor to mortality in these regions. In well-resourced countries, sepsis management relies on protocols and complex invasive technologies not widely available in most LMICs. However, the key concepts and components of sepsis management are potentially translatable to resource-limited environments. Health personnel in LMICs should be educated in the recognition of sepsis and the importance of early and appropriate antibiotic use. Simple and low-cost standardised laboratory testing should be emphasised to allow accurate diagnosis, prognosis, and monitoring of treatment response. Evidence-based interventions and treatment algorithms tailored to LMIC ecology and resources should thus be developed and validated.

An overview of training curricula for diabetes peer educators

Global community members who experience similar health problems gravitate to each other for information and support. Peers may be more approachable and can relate to the particular living circumstances one experiences. In well-resourced countries, people have opportunities for learning diabetes self-management; however, empathy may be more helpful when practical barriers arise. Little is published in medical literature about how to foster diabetes peer support and what is published is often limited to English language. Among those programs available, commonalities are readily seen. There is significant evidence that well-informed people cope better with adapting their lifestyle to medical regimens. Professionally delivered diabetes education has been well defined, but there may be additional benefit from learning from those who are living the experience everyday regarding how to navigate health care systems, handle finances, deal with natural emotions or family relations. Diabetes is epidemic and worldwide. There will never be sufficient traditional health care services to meet all future patients needs. While we persist in training health care professionals to deliver better diabetes care, we can explore how to mobilize willing volunteers to provide additional ongoing support to people with diabetes, where they live and work. While the characteristics of a peer educator have been defined slightly differently by several programs, there is agreement across programs that they need to be able to communicate clearly, they need to be willing to learn, they need to have confidence and they need to be flexible and dependable.

Emergence of Drug Resistance in HIV Type 1–Infected Patients after Receipt of First‐Line Highly Active Antiretroviral Therapy: A Systematic Review of Clinical Trials

Resistance to antiretroviral combination therapy is associated with increased mortality. Understanding the relative risks of emerging resistance to first-line therapy is of importance for both resource-rich and resource-poor settings. We undertook an overview of clinical trials of adults receiving first-line highly active antiretroviral therapy (HAART), which consisted of dual nucleoside reverse-transcriptase inhibitors (NRTIs) combined with a third agent (either a nonnucleoside reverse-transcriptase inhibitor [NNRTI] or a ritonavir-boosted protease inhibitor [bPI]). The primary outcome measures were incidences of mutations conferring resistance to key drugs (NRTIs, NNRTIs, or bPIs) per trial at week 48. For meta-analysis, inverse-variance weighting was used to create estimates of overall incidences per group, with exact 95% confidence intervals (95% CIs). The study included 20 clinical trials that comprised 30 treatment arms and 7970 patients. Virologic failure at 48 weeks occurred in 4.9% (95% CI, 3.9%-6.1%) of NNRTI recipients, compared with 5.3% (95% CI, 4.4%-6.4%; P= .50) of bPI recipients. Of failures that were successfully genotyped, the M184V mutation in the HIV reverse transcriptase (lamivudine resistance) occurred in 35.3% (95% CI, 29.3%-41.6%) of patients who started NNRTI-based HAART, compared with 21.0% (95% CI, 14.4%-28.8%; P< .001) for those who received a bPI. For the K65R mutation in the HIV reverse transcriptase (multinucleoside resistance), incidences were 5.3% (95% CI, 2.4%-9.9%) and 0.0% (95% CI, 0.0%-3.6%; P= .01), respectively, in patients treated with non-zidovudine-containing regimens. Resistance to the third agent (an NNRTI or PI) occurred in 53% (95% CI, 46%-60%) and 0.9% (95% CI, 0.0%-6.2%; P< .001) of such patients, respectively. Initial therapy with bPI-based regimens resulted in less resistance within and across drug classes. This finding is of particular significance for the developing world, where rates of resistance to NRTIs and NNRTIs at 48 weeks are much higher than has been seen in both cohorts and clinical trials in well-resourced countries.

Vertically acquired paediatric HIV infection: the challenges of providing comprehensive packages of care in resource‐limited settings

The successes achieved in paediatric disease management in well-resourced countries in recent years highlight the vast divide between the care options, and ultimately survival, between developed and developing areas of the world. Using an extensive literature review, we quantify recent achievements in terms of improved survival and quality of life, and examine current evidence of the effects of treatment on the survival and morbidity of HIV-infected children in developing countries. When provided with the same care as their counterparts in developed countries, children in developing countries show similar improvements in survival and general health, with 1-year survival rates exceeding 90% in many African settings. Despite the challenges of providing comprehensive packages of care in resource-limited settings, there is an urgent need to scale up prevention and treatment of HIV infections in children, focussing on strengthening Prevention of Mother-to-Child Transmission programmes in order to reduce the numbers of infants who are infected in addition to reducing morbidity and mortality among their mothers.

Asthma in Latin America: where the asthma causative/protective hypotheses fail

protection have been the subject of challenges and changes during the last years. Probably the most important are related with the findings of large, well-standardized epidemiological studies undertaken at global scale which have included children from several countries in different stages of development and with diverse ethnic and cultural backgrounds1-3. These studies have provided information on largely ignored aspects related to asthma prevalence in low-resourced countries, and have shown that findings, conclusions and hypotheses based on studies from well-resourced countries are not globally applicable. Furthermore, they are widely insufficient to explain the peculiarities of the distribution pattern of asthma symptoms’ prevalence in the world. The consistent lack of representation of low-resourced and culturally diverse populations in past epidemiologic studies on asthma in children has subtracted global validity to their results and has been probably an important impediment for advancing in the determination of the etiopathogenic bases of the disease. The inadequacy and partiality of this developed-countries’ approach, has been recently shown by worldwide large and inclusive studies which indicate that several “truths” regarding asthma-related epidemiologic issues are not consistent and are probably applicable only to the minority of asthmatic children. The International Study of Asthma and Allergies in Childhood (ISAAC), the largest epidemiological study ever performed at global-scale, has consistently demonstrated a remarkable variability of current asthma symptoms in the different countries and regions of the world, high prevalence in developing countries, lack of universal application of hypotheses on causation (low proportion of asthma attributable to atopy), and protection (high prevalence of asthma in children living in developing localities and low hygienic standards), and an erratic relationship between air pollution (smog) and prevalence of asthma symptoms (low asthma prevalence in centres with heavy air pollution). In Latin America, a developing region where there was no regional comparative information of childhood asthma until the advent of ISAAC (13 years ago), it has been consistently found that several of its centres were among those with the highest prevalence of asthma symptoms in the world2,4,5. The high prevalence of asthma in developing countries has been simplistically explained as that in such localities there is a different type of asthma, mainly determined by infections or viral respiratory diseases and where allergy or atopy plays a very minor role. The concept that asthma is non-atopic in developing countries, and atopic in developed ones, has commanded the notions on asthma causality, at least from a first world perspective for a long time. This would be supported by the theory that the lack of stimulation of the immune system by agents and fac-

Long-Term Outcome after Bone Marrow Transplantation for Adult Thalassemia.

Advances in management of thalassemia have increased the proportion of patients living into adulthood. However, disease and treatment related complications in these patients progress over time causing severe morbidity and shortened life expectancy even in well-resourced countries with universal access to good medical treatment. Adult thalassemics constitute a high risk group of patients for transplantation due to both advanced age and acquired multiple organ damage. We present here long-term outcome after BMT for adult thalassemia and a new approach to transplant adult patients. Between November 1988 and September 1996, 107 consecutive patients (median age 22 years; range 17–35) received BMT from HLA-identical related donors following BU14/16 CY120/160 regimen. There were 18 class 2 and 89 class 3 patients. The probability of overall survival, event-free survival, mortality and rejection were 66%, 62%, 37% and 4% respectively. Interestingly, unlike class 3 younger patients (age <17 years) adult patients treated with the same treatment regimens had a low probability of rejection suggesting that donor-host tolerance might be induced even among extensively transfused patients. The incidence of grade 2–4 acute GVHD was 24.5%, and moderate or severe chronic GVHD was 5.6%. The presence of chronic active hepatitis at the time of transplant was the only factor associated with poor survival (RR 2.5; p=0.05). Sixty eight patients survive with a median follow-up of 12 years (range 8.3–16.2), and 66 of them are free of thalassemia. Current myeloablative BMT in adult patients is characterised by higher transplant related mortality due to the advanced stage of disease. Therefore, new approach to SCT that might reduce transplant related morbidity and mortality in adults is warranted. In 1997 we devised a new treatment protocol (Protocol 26) for adult thalassemics aimed at reducing the bone marrow and gradually increasing immunosuppression before transplant to avoid peritransplant drug toxicity. Patients were given hydroxiurea 30 mg/kg/day, azathioprine 3 mg/kg/day from day -45 through day -11, and fludarabine 20 mg/m2/day from day -17 through day -13 along with hypertransfusion and continuous chelation. On day -9 they started a reduced dose intensity conditioning regimen with BU14 CY90. Fifteen higher risk patients (median age 21 years; range 17–31) with class 3 thalassemia (n=14) or sickle cell anemia (n=1) were given BMT from HLA-identical siblings after preparation with this new protocol. Overall, treatment was well tolerated with no increase in toxicity. The probability of thalassemia-free survival and transplant related mortality were 67% and 27% respectively. Our new approach to transplant adult patients with a reduced dose intensity conditioning regimen showed some improvement in thalassemia-free survival but transplant related mortality in these high risk patients still remains elevated.

Human immunodeficiency virus infection and pediatric bacterial meningitis in developing countries

Over a million children are infected by the human immunodeficiency virus (HIV); most of whom live in the developing world. Bacterial meningitis is a serious infection of childhood that is 10 times more common in resource-constrained settings than well-resourced countries, and the outcome is worse. This paper reviews the relationship of bacterial meningitis to HIV infection and also the effect of HIV status on antibiotic sensitivity to common causes of childhood meningitis. The combined effects on outcome and long-term sequelae of meningitis are discussed and illustrated with results from Malawi and Southern Africa.