Global health security: the wider lessons from the west African Ebola virus disease epidemic.

The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security--its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing.

Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana.

BACKGROUND: We explored the association between antituberculosis drug pharmacokinetics and treatment outcomes among patients with pulmonary tuberculosis in Botswana. METHODS: Consenting outpatients with tuberculosis had blood samples collected 1, 2, and 6 h after simultaneous isoniazid, rifampin, ethambutol, and pyrazinamide ingestion. Maximum serum concentrations (C(max)) and areas under the serum concentration time curve were determined. Clinical status was monitored throughout treatment. RESULTS: Of the 225 participants, 36 (16%) experienced poor treatment outcome (treatment failure or death); 155 (69%) were infected with human immunodeficiency virus (HIV). Compared with published standards, low isoniazid C(max) occurred in 84 patients (37%), low rifampin C(max) in 188 (84%), low ethambutol C(max) in 87 (39%), and low pyrazinamide C(max) in 11 (5%). Median rifampin and pyrazinamide levels differed significantly by HIV status and CD4 cell count category. Only pyrazinamide pharmacokinetics were significantly associated with treatment outcome; low pyrazinamide C(max) was associated with a higher risk of documented poor treatment outcome, compared with normal C(max) (50% vs. 16%; P < .01). HIV-infected patients with a CD4 cell count <200 cells/microL had a higher risk of poor treatment outcome (27%) than did HIV-uninfected patients (11%) or HIV-infected patients with a CD4 cell count 200 cells/microL (12%; P = .01). After adjustment for HIV infection and CD4 cell count, patients with low pyrazinamide C(max) were 3 times more likely than patients with normal pyrazinamide C(max) to have poor outcomes (adjusted risk ratio, 3.38; 95% confidence interval, 1.84-6.22). CONCLUSIONS: Lower than expected antituberculosis drug C(max) occurred frequently, and low pyrazinamide C(max) was associated with poor treatment outcome. Exploring the global prevalence and significance of these findings may suggest modifications in treatment regimens that could improve tuberculosis cure rates.

Overview, Control Strategies, and Lessons Learned in the CDC Response to the 2014-2016 Ebola Epidemic.

During 2014-2016, CDC, working with U.S. and international partners, mounted a concerted response to end the unprecedented epidemic of Ebola virus disease (Ebola) in West Africa. CDC's response, which was the largest in the agency's history, was directed simultaneously at controlling the epidemic in West Africa and strengthening preparedness for Ebola in the United States. Although experience in responding to approximately 20 Ebola outbreaks since 1976 had provided CDC and other international responders an understanding of the disease and how to stop its spread, the epidemic in West Africa presented new and formidable challenges. The initial response was slow and complicated for several reasons, including wide geographic spread of cases, poor public health and societal infrastructure, sociodemographic factors, local unfamiliarity with Ebola, and distrust of government and health care workers. In the United States, widespread public alarm erupted after Ebola cases were diagnosed in Dallas, Texas, and New York City, New York. CDC, in collaboration with its U.S. and international counterparts, applied proven public health strategies as well as innovative new approaches to help control the Ebola epidemic in West Africa and strengthen public health readiness in the United States. Lessons learned include the recognition that West African and other countries need effective systems to detect and stop infectious disease threats, the need for stronger international surge capacity for times when countries are overwhelmed by an outbreak, and the importance of improving infection prevention and control in health care settings. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana.

BACKGROUND: We conducted a pharmacokinetic study of antimycobacterial drugs involving a cohort of patients with pulmonary tuberculosis (TB) in Gaborone, Botswana, to assess the prevalence of and risk factors for low drug concentrations in serum. METHODS: Adults participated if they had a history of cough > or =2 weeks, had abnormal chest radiograph findings, consented to testing for human immunodeficiency virus (HIV), had sputum cultures positive for Mycobacterium tuberculosis, and were receiving antituberculous therapy for >7 days. Observed maximum serum concentrations were compared with published normal ranges. RESULTS. Of 91 patients enrolled, 89 (98%) were outpatients, and 59 (68%) of 87 patients tested had HIV infection. The following numbers of patients had low serum concentrations of the following drugs: isoniazid, 27 (30%) of 90; rifampin, 71 (78%) of 91; ethambutol, 37 (41%) of 91; and pyrazinamide, 1 (1%) of 91. Low serum concentrations of both isoniazid and rifampin occurred in 23 (26%) of 90 patients. Low serum concentrations of rifampin were found in both HIV-infected and non-HIV-infected patients, and such patients were less likely to have >4 weeks of symptoms, more likely to have lymphadenopathy, and more likely to have low serum albumin levels (P<.05 for all). The associations with noncavitary pulmonary disease (P=.12) and HIV infection (P=.07) did not reach statistical significance. Delayed absorption was most common with ethambutol, followed by rifampin. CONCLUSIONS: These data, predominantly from HIV-infected patients with TB, suggest that low isoniazid, rifampin, and ethambutol concentrations are common in Botswana. In contrast, pyrazinamide usually is well absorbed.

Tuberculosis serodiagnosis in a predominantly HIV-infected population of hospitalized patients with cough, Botswana, 2002.

A sensitive and accurate tuberculosis (TB) serodiagnostic test would aid in the control of TB, but results of current tests are relatively unreliable for persons infected with human immunodeficiency virus (HIV). We evaluated a new prototype immunochromatographic strip test and 5 commercially available serodiagnostic TB tests in a prospective study comprised of 465 consecutively enrolled patients with suspected TB from 2 hospitals in Botswana. Consenting adults underwent HIV testing, >/=2 sputum smears and cultures, and mycobacterial blood culture. Patients were defined as having TB on the basis of any positive smear or culture. Between January and September 2002, 465 of 498 consecutive patients consented to enrollment. A total of 384 patients (83%) were infected with HIV, and 175 (38%) had TB; the mycobacterial blood culture was the sole source of diagnosis for 26 patients (15%) with TB. Among the tests evaluated, the sensitivity was 0%-63%, the specificity was 39%-99%, the positive predictive value was 0%-39%, and the negative predictive value was 63%-65%. We conclude that the serodiagnostic tests evaluated in this study lacked sufficient sensitivity as sole tests for TB in this population.

Pathology and causes of death in a series of human immunodeficiency virus-positive and -negative pediatric referral hospital admissions in Botswana.

BACKGROUND: Little is known about causes of death among children seriously affected by the AIDS epidemic in southern African countries. METHODS: Autopsies were performed on 47 children 1 month to 13 years of age in Francistown, Botswana, between July 1997 and July 1998. RESULTS: Median age was 10 months; 68% were HIV-positive. The leading cause of death was respiratory infection, accounting for 29 of 35 (83%) deaths among HIV-positive and 8 of 12 (67%) deaths among HIV-negative children. Among HIV-positive children, Pneumocystis carinii pneumonia (PCP) was responsible for 31% of all deaths and for 48% of deaths in infants < or =1 year. Among children < or =2 years with cough and dyspnea, age < or =1 year, interstitial infiltrate and HIV positivity were highly predictive of PCP (sensitivity, 100%; specificity, 63%). CONCLUSION: Respiratory disease accounted for most deaths in HIV-positive children. Children < or =1 year who are known or suspected to be HIV-positive and who have cough, dyspnea and pulmonary infiltrates should be treated presumptively for PCP.

HIV risk factors among patients with tuberculosis--Botswana 1999.

To identify factors associated with HIV in Botswana, a standardized questionnaire was administered to 135 tuberculosis patients with known HIV status. HIV-positive patients were more likely than HIV-negative patients to: be female (45% vs 26% (adjusted prevalence odds ratio (aPOR)=3.8, 95% confidence interval (CI)=1.1-12.7)); be 26-35 years old (50% vs 19% (aPOR=2.7, CI=0.7-10.7)); be unmarried (91% vs 71% (aPOR=13.3, CI=2.5-72.7)); have higher income (24% vs 10% (aPOR=8.2, CI=1.6-42.9)); report separation from spouse/partner for work (63% vs 52% (aPOR=1.8, CI=0.5-6.2)); have 2 sex partners other than their regular partner (82% vs 67% (aPOR=1.8, CI=0.5-7.5)); and state that they or their partner drank alcohol before sex (77% vs 55% (aPOR=6.8, CI=1.9-24.1)). Only 22% of respondents used condoms during all of their past 10 sexual encounters. These data provide information for HIV prevention strategies.

Field expansion of DNA polymerase chain reaction for early infant diagnosis of HIV-1: The Ethiopian experience.

BACKGROUND: Early diagnosis of infants infected with HIV (EID) and early initiation of treatment significantly reduces the rate of disease progression and mortality. One of the challenges to identification of HIV-1-infected infants is availability and/or access to quality molecular laboratory facilities which perform molecular virologic assays suitable for accurate identification of the HIV status of infants. METHOD: We conducted a joint site assessment and designed laboratories for the expansion of DNA polymerase chain reaction (PCR) testing based on dried blood spot (DBS) for EID in six regions of Ethiopia. Training of appropriate laboratory technologists and development of required documentation including standard operating procedures (SOPs) was carried out. The impact of the expansion of EID laboratories was assessed by the number of tests performed as well as the turn-around time. RESULTS: DNA PCR for EID was introduced in 2008 in six regions. From April 2006 to April 2008, a total of 2848 infants had been tested centrally at the Ethiopian Health and Nutrition Research Institute (EHNRI) in Addis Ababa, and which was then the only laboratory with the capability to perform EID; 546 (19.2%) of the samples were positive. By November 2010, EHNRI and the six laboratories had tested an additional 16 985 HIV-exposed infants, of which 1915 (11.3%) were positive. The median turn-around time for test results was 14 days (range 14-21 days). CONCLUSION: Expansion of HIV DNA PCR testing facilities that can provide quality and reliable results is feasible in resource-limited settings. Regular supervision and monitoring for quality assurance of these laboratories is essential to maintain accuracy of testing.