Research Articles (Infectious Diseases)

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Acute and chronic exposure to air pollution in relation with incidence, prevalence, severity and mortality of COVID-19 : a rapid systematic review
(BMC, 2021-04-10) Katoto, Patrick D. M. C.; Brand, Amanda S.; Bakan, Buket; Obadia, Paul M.; Kuhangana, Carsi; Kayembe-Kitenge, Tony; Kitenge, Joseph P.; Nkulu, Celestin B. L.; Vanoirbeek, Jeroen; Nawrot, Tim S.; Hoet, Peter; Nemery, Benoit
Background: Air pollution is one of the world’s leading mortality risk factors contributing to seven million deaths annually. COVID-19 pandemic has claimed about one million deaths in less than a year. However, it is unclear whether exposure to acute and chronic air pollution influences the COVID-19 epidemiologic curve. Methods: We searched for relevant studies listed in six electronic databases between December 2019 and September 2020. We applied no language or publication status limits. Studies presented as original articles, studies that assessed risk, incidence, prevalence, or lethality of COVID-19 in relation with exposure to either short-term or long-term exposure to ambient air pollution were included. All patients regardless of age, sex and location diagnosed as having COVID-19 of any severity were taken into consideration. We synthesised results using harvest plots based on effect direction. Results: Included studies were cross-sectional (n = 10), retrospective cohorts (n = 9), ecological (n = 6 of which two were time-series) and hypothesis (n = 1). Of these studies, 52 and 48% assessed the effect of short-term and longterm pollutant exposure, respectively and one evaluated both. Pollutants mostly studied were PM2.5 (64%), NO2 (50%), PM10 (43%) and O3 (29%) for acute effects and PM2.5 (85%), NO2 (39%) and O3 (23%) then PM10 (15%) for chronic effects. Most assessed COVID-19 outcomes were incidence and mortality rate. Acutely, pollutants independently associated with COVID-19 incidence and mortality were first PM2.5 then PM10, NO2 and O3 (only for incident cases). Chronically, similar relationships were found for PM2.5 and NO2. High overall risk of bias judgments (86 and 39% in short-term and long-term exposure studies, respectively) was predominantly due to a failure to adjust aggregated data for important confounders, and to a lesser extent because of a lack of comparative analysis. Conclusion: The body of evidence indicates that both acute and chronic exposure to air pollution can affect COVID-19 epidemiology. The evidence is unclear for acute exposure due to a higher level of bias in existing studies as compared to moderate evidence with chronic exposure. Public health interventions that help minimize anthropogenic pollutant source and socio-economic injustice/disparities may reduce the planetary threat posed by both COVID-19 and air pollution pandemics.
Afri-Can Forum 2
(Biomed Central, 2016-07-12) Mukudu, Hillary; Martinson, Neil; Sartorius, Benn; Coetzee, Jenny; Dietrich, Janan; Mokgatswana, Kgaugelo; Jewkes, Rachel; Gray, Glenda E.; Dugas, Marylene; Behanzin, Luc; Guedou, Fernand A.; Gagnon, Marie-Pierre; Alary, Michel; Rutakumwa, Rwamahe; Mbonye, Martin; Kiwanuka, Thadeus; Nakamanya, Sarah; Muhumuza, Richard; Nalukenge, Winfred; Seeley, Janet; Atujuna, Millicent; Wallace, Melissa; Brown, Ben; Bekker, Linda G.; Newman, Peter A.; Harryparsad, Rushil; Olivier, Abraham J.; Jaspan, Heather B.; Wilson, Douglas; Dietrich, Janan; Martinson, Neil; Mukudu, Hillary; Mkhize, Nonhlanhla; Morris, Lynn; Cianci, Gianguido; Dinh, Minh; Hope, Thomas; Passmore, Jo-Ann S.; Gray, Clive M.; Henrick, Bethany M.; Yao, Xiao-Dan; Rosenthal, Kenneth L.; Henrick, Bethany M.; Yao, Xiao-Dan; Drannik, Anna G.; Rosenthal, Kenneth L.; Chanzu, Nadia; Mwanda, Walter; Oyugi, Julius; Anzala, Omu; Mbow, Moustapha; Jallow, Sabelle; Thiam, Moussa; Davis, Alberta; Diouf, Assane; Ndour, Cheikh T.; Seydi, Moussa; Dieye, Tandakha N.; Mboup, Souleymane; Goodier, Martin; Rilley, Eleanor; Jaye, Assan; Yao, Xiao-Dan; Omange, R. W.; Henrick, Bethany M.; Lester, Richard T.; Kimani, Joshua; Ball, T. B.; Plummer, Francis A.; Rosenthal, Kenneth L.; Behanzin, Luc; Guedou, Fernand A.; Geraldo, Nassirou; Mastetse, Ella G.; Sossa, Jerome C.; Zannou, Marcel D.; Alary, Michel; Osawe, Sophia; Okpokoro, Evaezi; Okolo, Felicia; Umaru, Stephen; Abimiku, Rebecca; Audu, Sam; Datong, Pam; Abimiku, Alashle; Nyange, Jacquelyn; Olenja, Joyce; Mutua, Gaudensia; Jaoko, Walter; Omosa-Manyonyi, Gloria; Farah, Bashir; Khaniri, Maureen; Anzala, Omu; Cockcroft, Anne; Tonkin, Kendra; Girish, Indu; Mhati, Puna; Cunningham, Ashley; Andersson, Neil; Farah, Bashir; Indangasi, Jackton; Jaoko, Walter; Mutua, Gaudensia; Khaniri, Maureen; Nyange, Jacquelyn; Anzala, Omu; Diphoko, Thabo; Gaseitsiwe, Simani; Maiswe, Victoria; Iketleng, Thato; Maruapula, Dorcas; Bedi, Keabetswe; Moyo, Sikhulile; Musonda, Rosemary; Wainberg, Mark; Makhema, Joseph; Novitsky, Vladimir; Marlink, Richard; Essex, Max; Okoboi, Stephen; Ssali, Livingstone; Kalibala, Sam; Birungi, Josephine; Egessa, Aggrey; Wangisi, Jonathan; Okullu, Lyavala J.; Bakanda, Celestin; Obare, Francis; Boer, I. M. S.; Semvua, Hadija H.; Van den Boogaard, Jossy; Kiwango, Krisanta W.; Ngowi, Kennedy M.; Nieuwkerk, Pythia T.; Aarnoutse, Rob E.; Kiwelu, Ireen; Muro, Eva; Kibiki, Gibson S.; Datiri, Ruth; Choji, Grace; Osawe, Sophia; Okpokoro, Evaezi; Okolo, Felicia; Umaru, Stephen; Abimiku, Rebecca; Datong, Pam; Abimiku, Alashle; Fomsgaard, A.; Karlsson, I.; Jensen, K. J; Jensen, S. S.; Leo-Hansen, C.; Jespersen, S.; Da Silva Te, D.; Rodrigues, C. M.; Da Silva, Z. J.; Janitzek, C. M.; Gerstoft, J.; Kronborg, G.; Okpokoro, Evaezi; Osawe, Sophia; Daitiri, Ruth; Choji, Grace; Umaru, Stephen; Okolo, Felicia; Datong, Pam; Emily, Nyariki; Joyce, Olenja; Robert, Lorway R.; Anzala, Anzala; Viljoen, Katie; Wendoh, Jerome; Kidzeru, Elvis; Karaoz, Ulas; Brodie, Eoin; Botha, Gerrit; Mulder, Nicola; Gray, Clive; Cameron, William; Stintzi, Alain; Jaspan, Heather; Levett, Paul N.; Alexander, David; Gulzar, Naveed; Grewal, Prabvir S.; Poon, Art F Y.; Brumme, Zabrina; Harrigan, P. R.; Brooks, James I.; Sandstrom, Paul A.; Calvez, Stryker; Sanche, Stephen E.; Scott, Jamie K.; Swartz, Leslie; Kagee, Ashraf; Lesch, Anthea; Kafaar, Zuhayr; De Wet, Anneliese; Okpokoro, Evaezi; Osawe, Sophia; Daitiri, Ruth; Choji, Grace; Umaru, Stephen; Okolo, Felicia; Datong, Pam; Abimiku, Alashle; Dietrich, Janan; Smith, Tricia; Cotton, Laura; Hornschuh, Stefanie; Van der Watt, Martin; Miller, Cari L.; Gray, Glenda; Smit, Jenni; Jaggernath, Manjeetha; Ndungu, Thumbi; Brockman, Mark; Kaida, Angela; Akolo, Maureen; Kimani, Joshua; Gelmon, Larry; Chitwa, Michael; Osero, Justus; Cockcroft, Anne; Marokoane, Nobantu; Kgakole, Leagajang; Maswabi, Boikhutso; Mpofu, Neo; Ansari, Umaira; Andersson, Neil; Nakinobe, Elizabeth; Miiro, George M.; Zalwango, Flavia; Nakiyingi-Miiro, Jessica; Kaleebu, Potiano; Semwanga, John R.; Nyanzi, Emily; Musoke, Saidat N.; Nakinobe, Elizabeth; Miiro, George; Mbidde, Edward K.; Lutalo, Tom; Kaleebu, Pontiano; Handema, Ray; Chianzu, Graham P.; Thiam, Moussa; Diagne-Gueye, Diabou; Ndiaye, Mame K.; Mbow, Moustapha; Ndiaye, Birahim P.; Traore, Ibrahima; Dia, Mamadou C.; Thomas, Gilleh; Tour-Kane, Coumba; Mboup, Souleymane; Jaye, Assan; Nyanzi, Emily; Mbidde, Edward K.; Kaleebu, Pontiano; Mpendo, Juliet; Kimani, Joshua; Birungi, Josephine; Muyindike, Winnie; Kambugu, Andrew; Sebastian, Hachizovu; Ray, Handema; Mike, Chaponda; Bertin, Kabuya J.; Modest, Mulenga; Thiam, Moussa; Janha, Omar; Davis, Alberta; Amambua-Ngwa, Alfred; Nwakanma, Davis C.; Mboup, Souleymane; Jaye, Assan; Jespersen, Sanne; Hønge, Bo L.; Esbjornsson, Joakim; Medina, Candida; Te, David Da Silva; Correira, Faustino G.; Laursen, Alex L.; Ostergaard, Lars; Andersen, Andreas; Aaby, Peter; Erikstrup, Christian; Wejse, Christian; Dieye, Siry; Sarr, Moussa; Sy, Haby; Mbodj, Helene D.; Ndiaye, Marianne; Ndiaye, Amy; Moussa, Seydi; Jaye, Assan; Mboup, Souleymane; Nyombi, Balthazar M.; Shao, Elichilia R.; Chilumba, Innocent B.; Moyo, Sikhulile; Gaseitsiwe, Simani; Musonda, Rosemary; Datong, Pam; Inyang, Bucky; Osawe, Sophia; Izang, Abel; Cole, Chundung; Okolo, Felicia; Cameron, Bill; Rosenthal, Kenneth; Gray, Clive; Jaspan, Heather; Seraise, Boitumelo; Andrea-Marobela, Kerstin; Moyo, Sikhulile; Musonda, Rosemary; Makhema, Joseph; Essex, Max; Gaseitsiwe, Simani
ENGLISH ABSTRACT: We are pleased to present peer reviewed forum proceedings of the 2nd synchronicity forum of GHRI/CHVIfunded Canadian and African HIV prevention and vaccine teams Forum objectives ∙GHRI-funded capacity building and HIV prevention research teams presented highlights of achievements ∙Teams discussed how to jointly build on achievements for sustainability ∙Provided an opportunity for inter-team collaboration, synchronize best approach to capacity building, mentoring of new researchers and building leadership ∙Provided opportunities for informal discussions and networking among the teams. ∙Teams learnt about recent advances in the area of African regulatory and ethics review process ∙The forum proceedings was a special supplement in an openaccess journal was produced
Balancing the risks to individual and society : a systematic review and synthesis of qualitative research on antibiotic prescribing behaviour in hospitals
(Elsevier, 2019) Krockow, E. M.; Colman, A. M.; Chattoe-Brown, E.; Jenkins, D. R.; Perera, N.; Mehtar, S.; Tarrant, C.
Background: Antimicrobial resistance is a global health threat, partly driven by inappropriate antibiotic prescriptions for acute medical patients in hospitals. Aim: To provide a systematic review of qualitative research on antibiotic prescribing decisions in hospitals worldwide, including broad-spectrum antibiotic use. Methods: A systematic search of qualitative research on antibiotic prescribing for adult hospital patients published between 2007 and 2017 was conducted. Drawing on the Health Belief Model, a framework synthesis was conducted to assess threat perceptions associated with antimicrobial resistance, and perceived benefits and barriers associated with antibiotic stewardship. Findings: The risk of antimicrobial resistance was generally perceived to be serious, but the abstract and long-term nature of its consequences led physicians to doubt personal susceptibility. While prescribers believed in the benefits of optimizing prescribing, the direct link between over-prescribing and antimicrobial resistance was questioned, and prescribers’ behaviour change was frequently considered futile when fighting the complex problem of antimicrobial resistance. The salience of individual patient risks was a key barrier to more conservative prescribing. Physicians perceived broad-spectrum antibiotics to be effective and low risk; prescribing broad-spectrum antibiotics involved low cognitive demand and enabled physicians to manage patient expectations. Antibiotic prescribing decisions in low-income countries were shaped by a context of heightened uncertainty and risk due to poor microbiology and infection control services. Conclusions: When tackling antimicrobial resistance, the tensions between immediate individual risks and long-term collective risks need to be taken into account. Efforts to reduce diagnostic uncertainty and to change risk perceptions will be critical in shifting practice.
Benefit v. risk when using chloroquine in patients with severe COVID-19 disease
(Health & Medical Publishing Group, 2020-04-02) Decloedt, Eric H.; Allwood, Brian W.; Parker, Arifa; Koegelenberg, Coenraad F. N.; Blockman, Marc; Taljaard, Jantjie; Reuter, Helmuth
ENGLISH ABSTRACT: Chloroquine (CQ) is widely advocated as treatment for coronavirus disease 2019 (COVID-19), including the president of the USA publicly supporting the use of hydroxychloroquine (HCQ) as a ‘game-changer’ on the social media platform Twitter. CQ and HCQ are structurally similar, with HCQ having an N-hydroxyl-ethyl side-chain in place of the N-diethyl group.[1] Currently only CQ is being marketed in South Africa. We encourage the development of curative directed therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using appropriate designed trials and regulatory oversight, and caution against the indiscriminate use of CQ or HCQ. Careful patient selection is essential, including assessing prognosis, anticipated benefit and potential harms prior to initiating CQ/HCQ therapy.
Clinical characteristics and outcomes of patients hospitalized for COVID-19 in Africa : early insights from the Democratic Republic of the Congo
(American Society of Tropical Medicine and Hygiene, 2020) Nachega, Jean B.; Ishoso, Daniel Katuashi; Otokoye, John Otshudiema; Hermans, Michel P.; Machekano, Rhoderick Neri; Sam-Agudu, Nadia A.; Nswe, Christian Bongo-Pasi; Mbala-Kingebeni, Placide; Madinga, Joule Ntwan; Mukendi, Stephane; Koli, Marie Claire; Nkwembe, Edith N.; Mbuyi, Gisele M.; Nsio, Justus M.; Tshialala, Didier Mukeba; Pipo, Michel Tshiasuma; Ahuka-Mundeke, Steve; Muyembe-Tamfum, Jean-Jacques; Mofenson, Lynne; Smith, Gerald; Mills, Edward J.; Mellors, John W.; Zumla, Alimuddin; Landu, Don Jethro Mavungu; Kayembe, Jean-Marie
ENGLISH ABSTRACT: Little is known about the clinical features and outcomes of SARS-CoV-2 infection in Africa. We conducted a retrospective cohort study of patients hospitalized for COVID-19 between March 10, 2020 and July 31, 2020 at seven hospitals in Kinshasa, Democratic Republic of the Congo (DRC). Outcomes included clinical improvement within 30 days (primary) and in-hospital mortality (secondary). Of 766 confirmed COVID-19 cases, 500 (65.6%) were male, with a median (interquartile range [IQR]) age of 46 (34–58) years. One hundred ninety-one (25%) patients had severe/critical disease requiring admission in the intensive care unit (ICU). Six hundred twenty patients (80.9%) improved and were discharged within 30 days of admission. Overall in-hospital mortality was 13.2% (95% CI: 10.9–15.8), and almost 50% among those in the ICU. Independent risk factors for death were age < 20 years (adjusted hazard ratio [aHR] = 6.62, 95% CI: 1.85–23.64), 40–59 years (aHR = 4.45, 95% CI: 1.83–10.79), and ³ 60 years (aHR = 13.63, 95% CI: 5.70–32.60) compared with those aged 20–39 years, with obesity (aHR = 2.30, 95% CI: 1.24–4.27), and with chronic kidney disease (aHR = 5.33, 95% CI: 1.85–15.35). In marginal structural model analysis, there was no statistically significant difference in odds of clinical improvement (adjusted odds ratio [aOR] = 1.53, 95% CI: 0.88–2.67, P = 0.132) nor risk of death (aOR = 0.65, 95% CI: 0.35–1.20) when comparing the use of chloroquine/azithromycin versus other treatments. In this DRC study, the high mortality among patients aged < 20 years and with severe/critical disease is of great concern, and requires further research for confirmation and targeted interventions.
The colliding epidemics of COVID-19, Ebola, and measles in the Democratic Republic of the Congo
(Elsevier, 2020) Nachega, Jean B.; Mbala-Kingebeni, Placide; Otshudiema, John; Zumla, Alimuddin; Tam-Fum, Jean-Jacques Muyembe
ENGLISH ABSTRACT: The Democratic Republic of the Congo is facing major public health challenges due to a confluence of major outbreaks of Ebola virus disease, measles, and COVID-19.1–4 The tenth Ebola outbreak in eastern DR Congo began on Aug 1, 2018, and as of May 28, 2020, there have been 3406 Ebola virus disease cases with 2243 deaths. The Ebola virus disease outbreak was well controlled in northeast DR Congo following a multisectoral response, but four new confirmed Ebola cases were detected in northwest DR Congo on June 1, 2020, and an outbreak response is underway.4 Additionally, the DR Congo has been burdened with recurrent measles outbreaks: 13 3802 cases in 2011, 88381 cases in 2013, and 311471 cases in 2019.2 The first confirmed case of COVID-19 in DR Congo was diagnosed on March 10, 2020, and the government declared a state of emergency on March 24, 2020. A national multisectoral response committee instituted lockdown in the capital, Kinshasa, the epicentre of the epidemic in DR Congo, in which daily confirmed cases now average 100. As of June 16, 2020, 4777 COVID-19 cases with 106 deaths have been reported from the DR Congo.
Comparison of antiretroviral therapy adherence among HIV-infected older adults with younger adults in Africa : systematic review and meta-analysis
(Springer, 2019) Soomro, Najeebullah; Fitzgerald, Grace; Seeley, Janet; Schatz, Enid; Nachega, Jean B.; Negin, Joel
ENGLISH ABSTRACT: As access to antiretroviral treatment in low- and middle-income countries improves, the number of older adults (aged ≥ 50 years) living with HIV is increasing. This study compares the adherence to antiretroviral treatment among older adults to that of younger adults living in Africa. We searched PubMed, Medline, Cochrane CENTRAL, CINAHL, Google Scholar and EMBASE for keywords (HIV, ART, compliance, adherence, age, Africa) on publications from 1st Jan 2000 to 1st March 2016. Eligible studies were pooled for meta-analysis using a random-effects model, with the odds ratio as the primary outcome. Twenty studies were included, among them were five randomised trials and five cohort studies. Overall, we pooled data for 148,819 individuals in two groups (older and younger adults) and found no significant difference in adherence between them [odds ratio (OR) 1.01; 95% CI 0.94–1.09]. Subgroup analyses of studies using medication possession ratio and clinician counts to measure adherence revealed higher proportions of older adults were adherent to medication regimens compared with younger adults (OR 1.06; 95% CI 1.02–1.11). Antiretroviral treatment adherence levels among older and younger adults in Africa are comparable. Further research is required to identify specific barriers to adherence in the aging HIV affected population in Africa which will help in development of interventions to improve their clinical outcomes and quality of life.
A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment
(International AIDS Society, 2015-12-16) Johnson, Leigh F.; Dorrington, Rob E.; Laubscher, Ria; Hoffmann, Christopher J.; Wood, Robin; Fox, Matthew P.; Cornell, Morna; Schomaker, Michael; Prozesky, Hans; Tanser, Frank; Davies, Mary-Ann; Boulle, Andrew
Introduction: There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Methods: Completeness of death recording was estimated using a capture recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. Results: After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3 94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2 35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004 2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). Conclusions: South Africa’s civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.
COVID-19 response in low- and middle-income countries : don’t overlook the role of mobile phone communication
(Elsevier, 2020-07-26) Verhagen, Lilly M.; de Groot, R.; Lawrence, C. A.; Taljaard, J.; Cotton, M. F.; Rabie, H.
Estimates of health capacities in the context of the coronavirus disease 2019 (COVID-19) pandemic indicate that most low- and middle-income countries (LMICs) are not operationally ready to manage this health emergency. Motivated by worldwide successes in other infectious disease epidemics and our experience in Sub-Saharan Africa, we support mobile phone communication to improve data collection and reporting, communication between healthcare workers, public health institutions, and patients, and the implementation of disease tracking and subsequent risk-stratified isolation measures. Programmatic action is needed for centrally coordinated reporting and communication systems facilitating mobile phones in crisis management plans for addressing the COVID-19 pandemic in LMICs. We summarize examples of worldwide mobile phone technology initiatives that have enhanced patient care and public health outcomes in previous epidemics and the current COVID-19 pandemic. In addition, we provide an overview of baseline conditions, including transparency about privacy guarantees, necessary for the successful use of mobile phones in assisting in the fight against COVID-19 spread.
COVID-19 travel restrictions and the International Health Regulations : call for an open debate on easing of travel restrictions
(Elsevier, 2020) Petersen, E.; McCloskey, B.; Hui, D. S.; Kock, R. A.; Ntoumi, F.; Memish, Z. A.; Kapata, N.; Azhar, E. I.; Pollack, M.; Madoff, L. C.; Hamer, D. H.; Nachega, Jean B.; Pshenichnaya, N.; Zumla, A.
ENGLISH ABSTRACT: The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) has caused national governments worldwide to mandate several generic infection control measures such as physical distancing, self-isolation, and closure of non-essential shops, restaurants schools, among others. Some models suggest physical distancing would have to persist for 3 months to mitigate the peak effects on health systems and could be required on an intermittent basis for 12 to 18 months (Flaxman et al., 2020).
COVID-19 travel restrictions and the International Health Regulations – Call for an open debate on easing of travel restrictions
(Elsevier, 2020-05) Petersen, Eskild; McCloskey, Brian; Hui, David S.; Kock, Richard; Ntoumi, Francine; Memish, Ziad A.; Kapata, Nathan; Azhar, Esam I.; Pollack, Marjorie; Madoff, Larry C.; Hamer, Davidson H.; Nachega, Jean B.; Pshenichnaya, N.; Zumla, Alimuddin
The COVID-19 pandemic caused by the novel coronavirus (SARS-CoV-2) has made national governments worldwide to mandate several generic infection control measures such as physical distancing, self-isolation, and closure of non-essential shops, restaurants schools, among others. Some models suggest physical distancing would have to persist for 3 months to mitigate the peak effects on health systems and could be required on an intermittent basis for 12 to 18 months ( Flaxman et al., 2020 ). Apart from these control measures travel restrictions during the early phase of the China outbreak were useful to confine it to Wuhan, the major source of the outbreak ( Kraemer et al., 2020 ) although ultimately these measures did not prevent the spread of COVID-19 to other regions of China. The global spread of the SARS-CoV-2 has clearly been associated with regional and international travel which has contributed to the pandemic ( Candido et al., 2020 ). To limit cross-border spread, both regionally and globally, many countries have swiftly adopted sweeping measures, including full lockdowns of shops, companies, shutting down airports, imposing travel restrictions and completely sealing their borders, to contain transmission ( Gostin and Wiley, 2020 ). The grounding of international travel as part of the global response to prevent spread has caused profound disruption of travel and trade and has threatened the survival of many airlines, travel companies, and associated businesses.
Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings
(Oxford University Press, 2020-10) Wallis, Carole L.; Hughes, Michael D.; Ritz, Justin; Viana, Raquel; de Jesus, Carlos Silva; Saravanan, Shanmugam; van Schalkwyk, Marije; Mngqibisa, Rosie; Salata, Robert; Mugyenyi, Peter; Hogg, Evelyn; Hovind, Laura; Wieclaw, Linda; Gross, Robert; Godfrey, Catherine; Collier, Ann C.; Grinsztejn, Beatriz; Mellors, John W.
Background: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). Methods: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. Results: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. Conclusions: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.
Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa
(Centers for Disease Control and Prevention, 2013-03) Klopper, Marisa; Warren, Robin Mark; Hayes, Cindy; Gey van Pittius, Nicolaas Claudius; Streicher, Elizabeth M.; Muller, Borna; Sirgel, Frederick Adriaan; Chabula-Nxiweni, Mamisa; Hoosain, Ebrahim; Coetzee, Gerrit; Van Helden, Paul David; Victor, Thomas Calldo; Trollip, Andre Phillip
ENGLISH ABSTRACT: Factors driving the increase in drug-resistant tuberculosis (TB) in the Eastern Cape Province, South Africa, are not understood. A convenience sample of 309 drug-susceptible and 342 multidrug-resistant (MDR) TB isolates, collected July 2008–July 2009, were characterized by spoligotyping, DNA fingerprinting, insertion site mapping, and targeted DNA sequencing. Analysis of molecular-based data showed diverse genetic backgrounds among drug-sensitive and MDR TB sensu stricto isolates in contrast to restricted genetic backgrounds among pre–extensively drug-resistant (pre-XDR) TB and XDR TB isolates. Second-line drug resistance was significantly associated with the atypical Beijing genotype. DNA fingerprinting and sequencing demonstrated that the pre-XDR and XDR atypical Beijing isolates evolved from a common progenitor; 85% and 92%, respectively, were clustered, indicating transmission. Ninety-three percent of atypical XDR Beijing isolates had mutations that confer resistance to 10 anti-TB drugs, and some isolates also were resistant to para-aminosalicylic acid. These findings suggest the emergence of totally drug-resistant TB.
Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis
(Massachusetts Medical Society, 2019-12-19) Tait, D. R.; Hatherill, M.; Van Der Meeren, O.; Ginsberg, A. M.; Van Brakel, E.; Salaun, B.; Scriba, T. J.; Akite, E. J.; Ayles, H. M.; Bollaerts, A.; Demoitie, M. -A.; Diacon, A.; Evans, T. G.; Gillard, P.; Hellstrom, E.; Innes, J. C.; Lempicki, M.; Malahleha, M.; Martinson, N.; Vela, D. Mesia; Muyoyeta, M.; Nduba, V.; Pascal, T. G.; Tameris, M.; Thienemann, F.; Wilkinson, R. J.; Roman, F.
BACKGROUND: Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity. METHODS: From August 2014 through November 2015, we enrolled adults 18 to 50 years of age with M. tuberculosis infection (defined by positive results on interferon-γ release assay) without evidence of active tuberculosis disease at centers in Kenya, South Africa, and Zambia. Participants were randomly assigned in a 1:1 ratio to receive two doses of either M72/AS01E or placebo, administered 1 month apart. The primary objective was to evaluate the efficacy of M72/AS01E to prevent active pulmonary tuberculosis disease according to the first case definition (bacteriologically confirmed pulmonary tuberculosis not associated with human immunodeficiency virus infection). Participants were followed for 3 years after the second dose. Participants with clinical suspicion of tuberculosis provided sputum samples for polymerase-chain-reaction assay, mycobacterial culture, or both. Humoral and cell-mediated immune responses were evaluated until month 36 in a subgroup of 300 participants. Safety was assessed in all participants who received at least one dose of M72/AS01E or placebo. RESULTS: A total of 3575 participants underwent randomization, of whom 3573 received at least one dose of M72/AS01E or placebo, and 3330 received both planned doses. Among the 3289 participants in the according-to-protocol efficacy cohort, 13 of the 1626 participants in the M72/AS01E group, as compared with 26 of the 1663 participants in the placebo group, had cases of tuberculosis that met the first case definition (incidence, 0.3 vs. 0.6 cases per 100 person-years). The vaccine efficacy at month 36 was 49.7% (90% confidence interval [CI], 12.1 to 71.2; 95% CI, 2.1 to 74.2). Among participants in the M72/AS01E group, the concentrations of M72-specific antibodies and the frequencies of M72-specific CD4+ T cells increased after the first dose and were sustained throughout the follow-up period. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups. CONCLUSIONS: Among adults infected with M. tuberculosis, vaccination with M72/AS01E elicited an immune response and provided protection against progression to pulmonary tuberculosis disease for at least 3 years. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598. opens in new tab.)
From easing lockdowns to scaling up community-based coronavirus disease 2019 screening, testing, and contact tracing in Africa-shared approaches, innovations, and challenges to minimize morbidity and mortality
(Oxford University Press, 2020-05) Nachega, Jean B.; Grimwood, Ashraf; Mahomed, Hassan; Fatti, Geoffrey; Preiser, Wolfgang; Kallay, Oscar; Mbala, Placide K.; Muyembe, Jean-Jacques T.; Rwagasore, Edson; Nsanzimana, Sabin; Ngamije, Daniel; Condo, Jeanine; Sidat, Mohsin; Noormahomed, Emilia V.; Reid, Michael; Lukeni, Beatrice; Suleman, Fatima; Mteta, Alfred; Zumla, Alimuddin
The arrival of coronavirus disease 2019 (COVID-19) on the African continent resulted in a range of lockdown measures that curtailed the spread of the infection but caused economic hardship. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Pandemic control will require efficient community screening, testing, and contact tracing; behavioral change interventions; adequate resources; and well-supported, community-based teams of trained, protected personnel. We discuss COVID-19 control approaches in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality. This crisis presents a unique opportunity to align COVID-19 services with those already in place for human immunodeficiency virus, tuberculosis, malaria, and non communicable diseases through mobilization of Africa's interprofessional healthcare workforce. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.
Gender differences in survival among adult patients starting antiretroviral therapy in South Africa : a multicentre cohort study
(Public Library of Science, 2012-09-04) Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J.; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F.; Egger, Matthias; Boulle, Andrew; Myer, Landon
Background: Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART. Methods and Findings: Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/μl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population. Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/μl, p <0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p <0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p < 0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located. Conclusions: HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic.
Global infection prevention gaps, needs, and utilization of educational resources: A cross-sectional assessment by the International Society for Infectious Diseases
(Elsevier, 2019) Desai, Angel N.; Ramatowski, John W.; Lassmann, Britta; Holmesa, Alison; Mehtar, Shaheen; Bearman, Gonzalo
Objective: The Guide to Infection Control in the Hospital (Guide) is an open access resource produced by the International Society for Infectious Diseases (ISID) to assist in the prevention of infection acquisition and transmission worldwide. A survey was distributed to 8055 current Guide users to understand their needs. Methods: The survey consisted of 48-questions regarding infection prevention and control (IPC) availability and needs. Dichotomous questions, Likert scale-type questions, and open-and closed-ended questions were used. Results: Respondents (n = 1121) from 194 countries and six WHO regions participated in the survey. 43% (488) identified as physicians. Personal protective equipment (PPE) availability, training, and antimicrobial susceptibility testing varied between regions. Only 11% of respondents from low-income countries reported consistent access to respiratory equipment, 12% to isolation gowns, 4% to negative pressure rooms or personnel trained in IPC, and 20% to antimicrobial resistance testing. This differed significantly to high and upper middle-income resource settings (p < 0.05). 80% of all respondents used smartphones or tablets at the workplace. Conclusions: This survey demonstrates varied access to IPC equipment and training between high and low- income settings worldwide. Our results demonstrated many respondents across all regions utilize mobile technology, providing opportunities for rapid distribution of resource specific, up-to-date IPC content.
HIV viral load as an independent risk factor for tuberculosis in South Africa : collaborative analysis of cohort studies
(Wiley Open Access, 2017) Fenner, Lukas; Atkinson, Andrew; Boulle, Andrew; Fox, Matthew P.; Prozesky, Hans; Zurcher, Kathrin; Ballif, Marie; Furrer, Hansjakob; Zwahlen, Marcel; Davies, Mary-Ann; Egger, Matthias
Introduction: Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART). Methods: We included all HIV-positive adult patients ( 16 years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV-RNA viral loads at ART start (baseline) and during follow-up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV-RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time-updated CD4 and HIV-RNA values, adjusting for age and sex. Results: We included 44,260 patients with a median follow-up time of 2.7 years (interquartile range [IQR] 1.0–5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28–41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/μL (IQR 79–229) and the median HIV-RNA viral load 58,000 copies/mL (IQR 6,000–240,000). Overall TB incidence was 26.2/1,000 person-years (95% confidence interval [CI] 25.3–27.0). Compared to the lowest viral load category (0–999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15–1.75, p < 0.001) in the highest group (>10,000 copies/mL). Time-updated analyses for CD4/HIV-RNA confirmed the association of viral load with the risk for TB. Conclusions: Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART.
The impact of revised PMTCT guidelines : a view from a public sector ARV clinic in Cape Town, South Africa
(Lippincott Williams & Wilkins, 2013-06) Van Schalkwyk, Marije; Andersson, Monique Ingrid; Zeier, Michele Desire; La Grange, Marina; Taljaard, Johannes Jakobus; Theron, Gerhard Barnard
Background: In April 2010, revised Prevention of Mother-to-Child Transmission guidelines were implemented in South Africa, advising fast-tracked lifelong highly active antiretroviral therapy (HAART) initiation at a higher CD4 count (≤350 cells per microliter). This study describes the impact of these changes on the management of pregnant women who initiated HAART at Tygerberg Hospital, Cape Town. Methods: We conducted a retrospective review of all women who initiated HAART in pregnancy at the Tygerberg Hospital between January 2008 and December 2010. Year cohorts were compared. Results: Two hundred and fifty HIV-infected women were included in the study and stratified by HAART initiation year: 2008:N = 82, 2009:N = 71, 2010:N = 97. There were no differences between the groups in age or parity. Median booking CD4 count was 155 cells per microliter [interquartile range (IQR) 107–187], 157 cells per microliter (IQR 104–206) and 208 cells per microliter (IQR 138–270), respectively (P < 0.001). Median gestation at HAART initiation was 31 weeks (IQR 27–35), 30 weeks (IQR 26–34), and 25 weeks (IQR 21–31; P < 0.001). HIV transmission rates were 3/65 (4.6%), 4/57 (7.0%), and 0/90 (0.0%; P = 0.021). Women <8 weeks on HAART before delivery were more likely to transmit than women ≥8 weeks [odds ratio 9.69; 95% confidence interval 1.66 to 56.58; P = 0.017]. Ninety-four (37.6%) women were lost to follow-up, 18.4% within 28 days of delivery. Conclusions: The positive impact of the new Prevention of Mother-to-Child Transmission program is evident. A longer duration of HAART before delivery was associated with less transmission. However, the lost to follow-up rates remain concerning. Further research is needed to better understand the reasons for nonadherence and mechanisms to improve support for these women.
Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda : a prospective cohort analysis
(BioMed Central, 2013-07-13) Chu, Rong; Mills, Edward J.; Beyene, Joseph; Pullenayegum, Eleanor; Bakanda, Celestin; Nachega, Jean B.; Devereaux, P. J.; Thabane, Lehana
Background: Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood. Methods: Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed. Results: A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p < 0.001). The percentages of death during follow-up were 10.47% and 6.38% for patients with and without TB, respectively. The hazard ratio (HR) for mortality comparing TB to non-TB patients using 1,686 PS-matched pairs was 1.37 (95% confidence interval [CI]: 1.08 – 1.75), less marked than the crude estimate (HR = 1.74, 95% CI: 1.49 – 2.04). The other PS-based methods and not PS-based multivariable Cox model produced similar results. Conclusions: After controlling for important confounding variables, HIV patients who had TB at the initiation of ART in Uganda had an approximate 37% increased hazard of overall mortality relative to non-TB patients.

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