Juno Thomas

Risk Factors for Severe Outcomes following 2009 Influenza A (H1N1) Infection: A Global Pooled Analysis

This study analyzes data from 19 countries (from April 2009 to Jan 2010), comprising some 70,000 hospitalized patients with severe H1N1 infection, to reveal risk factors for severe pandemic influenza, which include chronic illness, cardiac disease, chronic respiratory disease, and diabetes.

Increased Prevalence of Severe Malaria in HIV-Infected Adults in South Africa

BACKGROUND Conflicting reports exist regarding the impact of human immunodeficiency virus (HIV) infection on the risk of severe malaria. We aimed to assess the effect of HIV infection status, advancing immunosuppression, and antimalarial immunity on the severity of malaria. METHODS A prospective cohort study was conducted. Consecutive hospitalized adult patients with falciparum malaria were tested for HIV antibodies and to determine CD4+ T cell count. Immunity to malaria was assessed by obtaining a history of childhood residence in an area where malaria is endemic. Patients were assessed for features of severe malaria. RESULTS Three hundred thirty-six patients were enrolled in the study, of whom 32 (10%) had severe malaria. The prevalence of HIV infection was 33%, and 111 patients (33%) were nonimmune to malaria. HIV-infected patients complained more frequently about respiratory and abdominal symptoms and less frequently about rigors and headache. Risk factors for severe malaria determined by multivariate analysis included being nonimmune to malaria, having a positive HIV serostatus, having an elevated parasite count, and having an increased white blood cell count. Risk of severe malaria was increased in HIV-infected patients with a CD4+ T cell count of < 200 x 10(6) cells/L (P < or = .001). Nonimmune HIV-infected patients were significantly more likely to have severe malaria (13 [36%] of 36 patients) than were nonimmune non-HIV-infected patients (9 [12%] of 75 patients; odds ratio, 4.15 [95% confidence interval, 1.57-10.97]; P = .003). HIV serostatus did not affect risk of severe malaria in the group from an area with endemicity (5 [7%] of 74 HIV-infected patients had severe malaria, and 5 [3%] of 151 non-HIV-infected patients had malaria; P = .248). CONCLUSIONS HIV-infected nonimmune adults are at increased risk of severe malaria. This risk is associated with a low CD4+ T cell count. This interaction is of great public health importance.

Epidemiologic Investigations into Outbreaks of Rift Valley Fever in Humans, South Africa, 2008-2011

Rift Valley fever continues to pose a notable public health threat to humans.

Severe Acute Respiratory Illness Deaths in Sub-Saharan Africa and the Role of Influenza: A Case Series From 8 Countries

Abstract Background. Data on causes of death due to respiratory illness in Africa are limited. Methods. From January to April 2013, 28 African countries were invited to participate in a review of severe acute respiratory illness (SARI)–associated deaths identified from influenza surveillance during 2009–2012. Results. Twenty-three countries (82%) responded, 11 (48%) collect mortality data, and 8 provided data. Data were collected from 37 714 SARI cases, and 3091 (8.2%; range by country, 5.1%–25.9%) tested positive for influenza virus. There were 1073 deaths (2.8%; range by country, 0.1%–5.3%) reported, among which influenza virus was detected in 57 (5.3%). Case-fatality proportion (CFP) was higher among countries with systematic death reporting than among those with sporadic reporting. The influenza-associated CFP was 1.8% (57 of 3091), compared with 2.9% (1016 of 34 623) for influenza virus–negative cases (P < .001). Among 834 deaths (77.7%) tested for other respiratory pathogens, rhinovirus (107 [12.8%]), adenovirus (64 [6.0%]), respiratory syncytial virus (60 [5.6%]), and Streptococcus pneumoniae (57 [5.3%]) were most commonly identified. Among 1073 deaths, 402 (37.5%) involved people aged 0–4 years, 462 (43.1%) involved people aged 5–49 years, and 209 (19.5%) involved people aged ≥50 years. Conclusions. Few African countries systematically collect data on outcomes of people hospitalized with respiratory illness. Stronger surveillance for deaths due to respiratory illness may identify risk groups for targeted vaccine use and other prevention strategies.

Measles Outbreak in South Africa: Epidemiology of Laboratory-Confirmed Measles Cases and Assessment of Intervention, 2009–2011

Background Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa. Methods Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009–11 April 2010) and seven months post-vaccination campaign (24 May 2010–31 December 2010) periods in seven provinces of South Africa. Results A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented. Conclusion We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.

Guidelines for the management of acute meningitis in children and adults in South Africa

This guideline provides a rational and cost-effective approach to patients with acute meningitis, which causes considerable morbidity and mortality, predominantly in children.There are many aetiologies, but a small number of bacteria and viruses account for the majority of cases. There should be a low threshold for suspecting acute meningitis, which is a medical emergency and antibiotics should not be delayed. Blood culture and cerebrospinal fluid (CSF) analysis are the most important diagnostic tests and should be performed whenever it is safe and practical. Contraindications to lumbar puncture are discussed and an algorithm is given regarding administering empiric antibiotics and antivirals, performing blood cultures, computer tomography brain scanning and cerebrospinal fluid analysis, depending on the clinical features and availability of resources. Administration of steroids is not recommended. Guidelines are provided for definitive therapy whenever a causative organism is identified. When no organism is identified, treatment and further investigation should be guided by laboratory results and clinical response. An approach to this process is outlined in a second algorithm. The epidemiology of resistance to common pathogens is described and advice given regarding special groups, including those with recurrent meningitis or base-of-skull fractures. Advice regarding infection control, post-exposure prophylaxis and vaccination is provided.

Nosocomial Outbreak of New Delhi Metallo-β-Lactamase-1-Producing Gram-Negative Bacteria in South Africa: A Case-Control Study.

Objective New Delhi metallo-β-lactamase (NDM)-producing Gram-negative bacteria have spread globally and pose a significant public health threat. There is a need to better define risk factors and outcomes of NDM-1 clinical infection. We assessed risk factors for nosocomial infection with NDM-1-producers and associated in-hospital mortality. Methods A matched case-control study was conducted during a nosocomial outbreak of NDM-1-producers in an adult intensive care unit (ICU) in South Africa. All patients from whom NDM-1-producers were identified were considered (n=105). Cases included patients admitted during the study period in whom NDM-1 producing Gram-negative bacteria were isolated from clinical specimens collected ≥48 hours after admission, and where surveillance definitions for healthcare-associated infections were met. Controls were matched for age, sex, date of hospital admission and intensive-care admission. Conditional logistic regression was used to identify risk factors for NDM-1 clinical infection and associated in-hospital mortality. Findings 38 cases and 68 controls were included. Klebsiella pneumoniae was the most common NDM-1-producer (28/38, 74%). Cases had longer mean hospital stays (44.0 vs. 13.3 days; P < 0.001) and ICU stays (32.5 vs. 8.3 days; P < 0.001). Adjusting for co-morbid disease, the in-hospital mortality of cases was significantly higher than controls (55.3% vs. 14.7%; AOR, 11.29; P < 0.001). Higher Charlson co-morbidity index score (5.2 vs. 4.1; AOR, 1.59; P = 0.005), mechanical ventilation days (7.47 vs. 0.94 days; AOR, 1.32; P = 0.003) and piperacillin/tazobactam exposure (11.03 vs. 1.05 doses; AOR, 1.08; P = 0.013) were identified as risk factors on multivariate analysis. Cases had a significantly higher likelihood of in-hospital mortality when the NDM-1-producer was Klebsiella pneumoniae (AOR, 16.57; P = 0.007), or when they had a bloodstream infection (AOR, 8.84; P = 0.041). Conclusion NDM-1 infection is associated with significant in-hospital mortality. Risk factors for hospital-associated infection include the presence of co-morbid disease, mechanical ventilation and piperacillin/tazobactam exposure.

Invasive Neisseria meningitidis with decreased susceptibility to fluoroquinolones in South Africa, 2009

A. pleuropneumoniae. We tested this by electrotransformation of A. pleuropneumoniae 4074 with pHN61 as described above. In this transformant, the MICs of lincomycin and clindamycin increased from 16 to 128 mg/L and 4 to 64 mg/L respectively, whereas the MIC of erythromycin was unchanged (1 mg/L). The presence of pHN61 was verified by plasmid extraction and Southern blot hybridization. These results indicate the possibility of pHN61 circulating between strains of H. parasuis and A. pleuropneumoniae. In conclusion, this is the first report describing the presence of the lincosamide-inactivating gene lnu(C) in Gram-negative bacteria, and, specifically, its location on a plasmid rather than the chromosome. The presence of the lnu(C) gene on a plasmid could facilitate the spread of lincosamide resistance between and across Gram-negative bacterial species.

Human Cases of Wesselsbron Disease, South Africa 2010–2011

Wesselsbron disease is a neglected, mosquito-borne zoonotic infection reported from Africa. The disease primarily affects sheep and other ruminants with incidental spillover to humans. As for other arboviral diseases in Africa, little or no active surveillance is conducted, and the public and veterinary health burden of this disease remains unclear. We report on the clinical histories of 2 human cases of Wesselsbron disease that were laboratory confirmed during the 2010-2011 Rift Valley fever outbreak investigation in South Africa. This report describes the first confirmed human cases of Wesselsbron disease since 1996. Molecular sequencing and analysis of the partial NS5 gene of the Wesselsbron genome was used to identify 2 circulating clades of the virus in southern Africa. Clade I included isolates collected from South Africa and Zimbabwe, whereas clade II only included isolates from the KwaZulu Natal Province of South Africa.

Serum levels of inflammatory cytokines in Rift Valley fever patients are indicative of severe disease

BackgroundRift Valley fever (RVF) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants, camels and humans. Outbreaks of RVF are characterized by a sudden onset of abortions and high mortality amongst domestic ruminants. Humans develop disease ranging from a mild flu-like illness to more severe complications including hemorrhagic syndrome, ocular and neurological lesions and death. During the RVF outbreak in South Africa in 2010/11, a total of 278 human cases were laboratory confirmed, including 25 deaths. The role of the host inflammatory response to RVF pathogenesis is not completely understood.MethodsVirus load in serum from human fatal and non-fatal cases was determined by standard tissue culture infective dose 50 (TCID50) titration on Vero cells. Patient serum concentration of chemokines and cytokines involved in inflammatory responses (IL-8, RANTES, CXCL9, MCP-1, IP-10, IL-1β, IL-6, IL-10, TNF and IL-12p70) was determined using cytometric bead assays and flow cytometry.ResultsFatal cases had a 1-log10 higher TCID50/ml serum concentration of RVF virus (RVFV) than survivors (p < 0.05). There were no significant sequence differences between isolates recovered from fatal and non-fatal cases. Chemokines and pro- and anti-inflammatory cytokines were detected at significantly increased (IL-8, CXCL9, MCP-1, IP-10, IL-10) or decreased (RANTES) levels when comparing fatal cases to infected survivors and uninfected controls, or when comparing combined infected patients to uninfected controls.ConclusionsThe results suggest that regulation of the host inflammatory responses plays an important role in the outcome of RVFV infection in humans. Dysregulation of the inflammatory response contributes to a fatal outcome. The cytokines and chemokines identified in this study that correlate with fatal outcomes warrant further investigation as markers for disease severity.