Impact of climate change and natural disasters on fungal infections.

The effects of climate change and natural disasters on fungal pathogens and the risks for fungal diseases remain incompletely understood. In this literature review, we examined how fungi are adapting to an increase in the Earth's temperature and are becoming more thermotolerant, which is enhancing fungal fitness and virulence. Climate change is creating conditions conducive to the emergence of new fungal pathogens and is priming fungi to adapt to previously inhospitable environments, such as polluted habitats and urban areas, leading to the geographical spread of some fungi to traditionally non-endemic areas. Climate change is also contributing to increases in the frequency and severity of natural disasters, which can trigger outbreaks of fungal diseases and increase the spread of fungal pathogens. The populations mostly affected are the socially vulnerable. More awareness, research, funding, and policies on the part of key stakeholders are needed to mitigate the effects of climate change and disaster-related fungal diseases.

Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects.

INTRODUCTION: The unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk-benefit messaging when a safety signal is identified. DISCUSSION: The Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll-out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high-quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified. CONCLUSIONS: The response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk-benefit trade-offs in a variety of contexts; guidance to transform this risk-benefit balance into effective and agreed-upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise.

Do Quality Improvement Initiatives Improve Outcomes for Patients in Antiretroviral Programs in Low- and Middle-Income Countries? A Systematic Review.

BACKGROUND: There have been a range of quality improvement (QI) and quality assurance initiatives in low- and middle-income countries to improve antiretroviral therapy (ART) treatment outcomes for people living with HIV. To date, these initiatives have not been systematically assessed and little is known about how effective, cost-effective, or sustainable these strategies are in improving clinical outcomes. METHODS: We conducted a systematic review adhering to PRISMA guidelines (PROSPERO ID: CRD42017071848), searching PubMed, MEDLINE, Embase, Web of Science, and the Cochrane database of controlled trials for articles reporting on the effectiveness of QI and quality assurance initiatives in HIV programs in low- and middle-income countries in relation to ART uptake, retention in care, adherence, viral load suppression, mortality, and other outcomes including cost-effectiveness and long-term sustainability. RESULTS: One thousand eight hundred sixty articles were found, of which 29 were included. QI approaches were categorized as follows: (1) health system approaches using QI methods; (2) QI learning networks including collaboratives; (3) standard-based methods that use QI tools to improve performance gaps; and (4) campaigns using QI methods. The greatest improvements were seen in ART uptake [median increase of 14.0%; interquartile range (IQR) -9.0 to 29.3], adherence [median increase of 22.0% (IQR -7.0 to 25.0)], and viral load suppression [median increase 26.0% (IQR -8.0 to 26.0)]. CONCLUSIONS: QI interventions can be effective in improving clinical outcomes; however, there was significant variability, making it challenging to identify which aspects of interventions lead to clinical improvements. Standardizing reporting and assessment of QI initiatives is needed, supported by national quality policies and directorates, and robust research.

The growing burden of noncommunicable disease among persons living with HIV in Zimbabwe.

OBJECTIVES: We aim to characterize the future noncommunicable disease (NCD) burden in Zimbabwe to identify future health system priorities. METHODS: We developed an individual-based multidisease model for Zimbabwe, simulating births, deaths, infection with HIV and progression and key NCD [asthma, chronic kidney disease (CKD), depression, diabetes, hypertension, stroke, breast, cervical, colorectal, liver, oesophageal, prostate and all other cancers]. The model was parameterized using national and regional surveillance and epidemiological data. Demographic and NCD burden projections were generated for 2015 to 2035. RESULTS: The model predicts that mean age of PLHIV will increase from 31 to 45 years between 2015 and 2035 (compared with 20-26 in uninfected individuals). Consequently, the proportion suffering from at least one key NCD in 2035 will increase by 26% in PLHIV and 6% in uninfected. Adult PLHIV will be twice as likely to suffer from at least one key NCD in 2035 compared with uninfected adults; with 15.2% of all key NCDs diagnosed in adult PLHIV, whereas contributing only 5% of the Zimbabwean population. The most prevalent NCDs will be hypertension, CKD, depression and cancers. This demographic and disease shift in PLHIV is mainly because of reductions in incidence and the success of ART scale-up leading to longer life expectancy, and to a lesser extent, the cumulative exposure to HIV and ART. CONCLUSION: NCD services will need to be expanded in Zimbabwe. They will need to be integrated into HIV care programmes, although the growing NCD burden amongst uninfected individuals presenting opportunities for additional services developed within HIV care to benefit HIV-negative persons.

Choice of antiretroviral drugs for continued treatment scale-up in a public health approach: what more do we need to know?

INTRODUCTION: There have been several important developments in antiretroviral treatment in the past two years. Randomized clinical trials have been conducted to evaluate a lower dose of efavirenz (400 mg once daily). Integrase inhibitors such as dolutegravir have been approved for first-line treatment. A new formulation of tenofovir (alafenamide) has been developed and has shown equivalent efficacy to tenofovir in randomized trials. Two-drug combination treatments have been evaluated in treatment-naïve and -experienced patients. The novel pharmacokinetic booster cobicistat has been compared to ritonavir in terms of pharmacokinetics, efficacy and safety. The objective of this commentary is to assess recent developments in antiretroviral drug treatment to determine whether new treatments should be included in new international guidelines. DISCUSSION: The use of first-line treatment with tenofovir and efavirenz at the standard 600 mg once-daily dose should remain the first-choice standard of care treatment. Evidence supporting a switch to efavirenz 400 mg once daily or integrase inhibitors is sufficient to consider these drugs as alternative first-line options, but more data are needed on their use in pregnant women and people with TB co-infection. The use of new formulations of tenofovir is currently too preliminary to justify immediate adoption and scale-up across HIV programmes in low- and middle-income countries. The evidence supporting use of two-drug combinations is not considered strong enough to justify changed recommendations from use of standard triple drug combinations. Cobicistat does not offer significant safety advantages over ritonavir as a pharmacokinetic booster. CONCLUSIONS: For continued scale-up of antiretroviral treatment in low- and middle-income countries, use of first-line triple combinations including efavirenz 600 mg once daily is supported by the largest evidence base. Additional studies are underway to evaluate new treatments in key populations, and these results may justify changes to these recommendations.

Providing surgical care in Somalia: A model of task shifting.

BACKGROUND: Somalia is one of the most political unstable countries in the world. Ongoing insecurity has forced an inconsistent medical response by the international community, with little data collection. This paper describes the "remote" model of surgical care by Medecins Sans Frontieres, in Guri-El, Somalia. The challenges of providing the necessary prerequisites for safe surgery are discussed as well as the successes and limitations of task shifting in this resource-limited context. METHODS: In January 2006, MSF opened a project in Guri-El located between Mogadishu and Galcayo. The objectives were to reduce mortality due to complications of pregnancy and childbirth and from violent and non-violent trauma. At the start of the program, expatriate surgeons and anesthesiologists established safe surgical practices and performed surgical procedures. After January 2008, expatriates were evacuated due to insecurity and surgical care has been provided by local Somalian doctors and nurses with periodic supervisory visits from expatriate staff. RESULTS: Between October 2006 and December 2009, 2086 operations were performed on 1602 patients. The majority (1049, 65%) were male and the median age was 22 (interquartile range, 17-30). 1460 (70%) of interventions were emergent. Trauma accounted for 76% (1585) of all surgical pathology; gunshot wounds accounted for 89% (584) of violent injuries. Operative mortality (0.5% of all surgical interventions) was not higher when Somalian staff provided care compared to when expatriate surgeons and anesthesiologists. CONCLUSIONS: The delivery of surgical care in any conflict-settings is difficult, but in situations where international support is limited, the challenges are more extreme. In this model, task shifting, or the provision of services by less trained cadres, was utilized and peri-operative mortality remained low demonstrating that safe surgical practices can be accomplished even without the presence of fully trained surgeon and anesthesiologists. If security improves in Somalia, on-site training by expatriate surgeons and anesthesiologists will be re-established. Until then, the best way MSF has found to support surgical care in Somalia is continue to support in a "remote" manner.

Quality of care in humanitarian surgery.

Humanitarian surgical programs are set up de novo, within days or hours in emergency or disaster settings. In such circumstances, insuring quality of care is extremely challenging. Basic structural inputs such as a safe structure, electricity, clean water, a blood bank, sterilization equipment, a post-anesthesia recovery unit, appropriate medications should be established. Currently, no specific credentials are needed for surgeons to operate in a humanitarian setting; the training of more humanitarian surgeons is desperately needed. Standard perioperative protocols for the humanitarian setting after common procedures such as Cesarean section, burn care, open fractures, and amputations and antibiotic prophylaxis, and post-operative pain management must be developed. Outcome data, especially long-term outcomes, are difficult to collect as patients often do not return for follow-up and may be difficult to trace; standard databases for post-operative infections and mortality rates should be established. Checklists have recently received significant attention as an instrument to support the improvement of surgical quality; knowing which items are most applicable to humanitarian settings remains unknown. In conclusion, the quality of surgical services in humanitarian settings must be regulated. Many other core medical activities of humanitarian organizations such as therapeutic feeding, mass vaccination, and the treatment of infectious diseases, such as tuberculosis and human immunodeficiency virus, are subject to rigorous reporting of quality indicators. There is no reason why surgery should be exempted from quality oversight. The surgical humanitarian community should pull together before the next disaster strikes.

Responding to major burn disasters in resource-limited settings: lessons learned from an oil tanker explosion in Nakuru, Kenya.

BACKGROUND: On January 31, 2009, a fuel tanker exploded in rural Kenya, killing and injuring hundreds of people. This article describes the care of >80 burn victims at a rural hospital in Kenya, Nakuru Provincial General Hospital, and provides lessons for care of a large number of burned patients in a resource-limited setting. METHODS: Data were obtained from retrospective review from hospital registers and patient files. RESULTS: Treatment was provided for 89 victims. Eighty-six (97%) were men; median age was 25 years (interquartile range [IQR], 19-32). Half of the patients (45) died, the majority (31, 69%) within the first week. The median total body surface area burned for those who died was 80% (IQR, 60-90%) compared with 28% (IQR, 15-43%) for those who survived (p < 0.001). Twenty patients were transfused a total of 73 units of blood including one patient who received 9 units. Eighty surgical interventions were performed on 31 patients and included 39 split-thickness skin grafts, 21 debridements, 7 escharotomies, 6 dressing changes, 4 contracture releases, and 3 finger amputations. Of the 44 survivors, 39 (89%) were discharged within 4 months of the event. CONCLUSIONS: Mortality after mass burn disasters is high in Africa. In areas where referral to tertiary centers is not possible, district hospitals should have mass disaster plans that involve collaboration with other organizations to augment medical and psychologic services. Even for patients who do not survive, compassionate care with analgesics can be given.

AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa.

BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality. Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential.