Risk Factors of Streptococcus suis Infection in Vietnam. A Case-Control Study

Background: Streptococcus suis infection, an emerging zoonosis, is an increasing public health problem across South East Asia and the most common cause of acute bacterial meningitis in adults in Vietnam. Little is known of the risk factors underlying the disease. Methods and Findings: A case-control study with appropriate hospital and matched community controls for each patient was conducted between May 2006 and June 2009. Potential risk factors were assessed using a standardized questionnaire and investigation of throat and rectal S. suis carriage in cases, controls and their pigs, using real-time PCR and culture of swab samples. We recruited 101 cases of S. suis meningitis, 303 hospital controls and 300 community controls. By multivariate analysis, risk factors identified for S. suis infection as compared to either control group included eating "high risk" dishes, including such dishes as undercooked pig blood and pig intestine (OR1 = 2.22; 95% CI = [1.15-4.28] and OR2 = 4.44; 95% CI = [2.15-9.15]), occupations related to pigs (OR1 = 3.84; 95% CI = [1.32-11.11] and OR2 = 5.52; 95% CI = [1.49-20.39]), and exposures to pigs or pork in the presence of skin injuries (OR1 = 7.48; 95% CI = [1.97-28.44] and OR2 = 15.96; 95% CI = [2.97-85.72]). S. suis specific DNA was detected in rectal and throat swabs of 6 patients and was cultured from 2 rectal samples, but was not detected in such samples of 1522 healthy individuals or patients without S. suis infection. Conclusions: This case control study, the largest prospective epidemiological assessment of this disease, has identified the most important risk factors associated with S. suis bacterial meningitis to be eating 'high risk' dishes popular in parts of Asia, occupational exposure to pigs and pig products, and preparation of pork in the presence of skin lesions. These risk factors can be addressed in public health campaigns aimed at preventing S. suis infectio

A Multi-Center Randomized Trial to Assess the Efficacy of Gatifloxacin versus Ciprofloxacin for the Treatment of Shigellosis in Vietnamese Children

The bacterial genus Shigella is the most common cause of dysentery (diarrhea containing blood and/or mucus) and the disease is common in developing countries with limitations in sanitation. Children are most at risk of infection and frequently require hospitalization and antimicrobial therapy. The WHO currently recommends the fluoroquinolone, ciprofloxacin, for the treatment of childhood Shigella infections. In recent years there has been a sharp increase in the number of organisms that exhibit resistance to nalidixic acid (an antimicrobial related to ciprofloxacin), corresponding with reduced susceptibility to ciprofloxacin. We hypothesized that infections with Shigella strains that demonstrate resistance to nalidixic acid may prevent effective treatment with ciprofloxacin. We performed a randomized controlled trial to compare 3 day ciprofloxacin therapy with 3 days of gatifloxacin, a newer generation fluoroquinolone with greater activity than ciprofloxacin. We measured treatment failure and time to the cessation of individual disease symptoms in 249 children with dysentery treated with gatifloxacin and 245 treated with ciprofloxacin. We could identify no significant differences in treatment failure between the two groups or in time to the cessation of individual symptoms. We conclude that, in Vietnam, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute dysentery

Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired

Severe paradoxical reaction in tuberculous meningitis

A 31-year-old female presented with a 3-week history of fever and headache. CSF Ziehl-Neelsen smear microscopy revealed acid-fast bacilli, and CSF GeneXpert MTB/RIF was positive for&nbsp;Mycobacterium tuberculosis&nbsp;with no mutations of rifampicin resistance. Tuberculous meningitis (TBM) was diagnosed. Baseline contrast-enhanced brain magnetic resonance imaging (MRI) was unremarkable. Eight weeks later the patient developed markedly reduced visual acuity and clinical signs consistent with left 3rd and 6th cranial nerve palsies. Repeat contrast-enhanced brain MRI revealed extensive tuberculous exudate filling the basal cisterns of the brain consistent with a severe paradoxical reaction of TBM. High dose intravenous dexamethasone was administered, with visual acuity returning to near-normal over 3&ndash;4 weeks. In TBM paradoxical inflammatory reactions are common yet difficult to predict. When severe, they may result in substantial neurological morbidity and death. Prompt host directed therapies such as corticosteroids may reduce chances of permanent neurological damage.</p

Comparison of artemisinin suppositories with intravenous artesunate and intravenous quinine in the treatment of cerebral malaria.

Seventy-nine comatose cerebral malaria patients given standard supportive treatment were randomized to receive specific antimalarial chemotherapy of intravenous quinine, intravenous artesunate, or artemisinin suppositories. Artesunate and artemisinin reduced peripheral asexual parasitaemia significantly more rapidly than quinine (90% clearance time 16 h, 18.9 h and 34.5 h respectively), but did not significantly reduce the duration of coma or mortality. The rapid lowering of peripheral parasitaemia may not ameliorate complications already present. These results demonstrate that artemisinin suppositories are as effective as artesunate and quinine given intravenously, and have economic and practical advantages for the treatment of severe malaria in areas remote from major medical centres. However, large numbers of patients will need to be studied if differences in mortality between the 3 treatment groups are to be demonstrated

An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria.

An open paired randomized comparison of intramuscular and intravenous artesunate was conducted in 28 adult patients with severe falciparum malaria. The dose regimen in both groups was 2 mg/kg given immediately followed by 1 mg/kg at 12 and 24 h, and then daily until the patient could swallow. Both routes of administration were well tolerated and there was no evidence of toxicity. One patient in each treatment group died. Clinical and parasitological measures of recovery in survivors were similar in the 2 groups with mean fever clearance times of 37.3 h (standard deviation [SD] = 26.1 h) and 31.5 h (SD = 24.2 h) and mean parasite clearance times of 33.4 h (SD = 13.9 h) and 29.4 h (SD = 12.7 h) in the intravenous and intramuscular groups respectively. Artesunate is equally effective and well tolerated when given by the intravenous or intramuscular routes

The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection.

BACKGROUND: Adrenaline is used increasingly in the management of septic shock, but its efficacy and safety are uncertain. METHODS: In an open, randomised, crossover study we compared the effects of stepped doses of adrenaline 0.1 to 0.5 microgram/kg per min and dopamine 2.5 to 10 micrograms/kg per min on the haemodynamic and acid-base status of 23 patients critically ill with severe sepsis (n = 10) or severe malaria (n = 13). FINDINGS: All patients completed the dopamine study whereas in 16 (84%) patients the adrenaline infusion had to be terminated before reaching, or during, the maximum dose because of lactic acidosis (p &lt; 0.0002). Adrenaline was associated with a mean (95% CI) increase in plasma lactate of 3.2 (2.6 to 3.8) mmol/L, and mean falls in arterial pH of 0.052 (0.035-0.068) pH units and base excess of 3.8 (2.8-4.7) mmol/L. The geometric mean (95% CI) lactate increment per unit adrenaline dose was 8.2 (5.8-10.5) mmol/L per microgram/kg per min. In contrast dopamine was associated with a fall in lactate of 1.0 (0.4-1.5) mmol/L, a rise in base excess of 1.4 (0.7 to 2.0) mmol/L (p &lt; 0.0001 in each case), and no effect on arterial pH. Both drugs induced significant increases in cardiac index and oxygen delivery with smaller increases in oxygen consumption and falls in systemic vascular resistance which were similar in severe malaria and severe sepsis (p &gt; 0.1 in each case) [corrected]. INTERPRETATION: Infusion of inotropic doses of adrenaline in severe infections causes lactic acidosis

The effects of dopamine and adrenaline infusions on acid-base balance and systemic haemodynamics in severe infection.

BACKGROUND: Adrenaline is used increasingly in the management of septic shock, but its efficacy and safety are uncertain. METHODS: In an open, randomised, crossover study we compared the effects of stepped doses of adrenaline 0.1 to 0.5 microgram/kg per min and dopamine 2.5 to 10 micrograms/kg per min on the haemodynamic and acid-base status of 23 patients critically ill with severe sepsis (n = 10) or severe malaria (n = 13). FINDINGS: All patients completed the dopamine study whereas in 16 (84%) patients the adrenaline infusion had to be terminated before reaching, or during, the maximum dose because of lactic acidosis (p 0.1 in each case) [corrected]. INTERPRETATION: Infusion of inotropic doses of adrenaline in severe infections causes lactic acidosis

Comparison of the Mycobacterium tuberculosis molecular bacterial load assay, microscopy and GeneXpert versus liquid culture for viable bacterial load quantification before and after starting pulmonary tuberculosis treatment

Molecular bacterial load assay (MBLA) rapidly quantifies viable Mycobacterium tuberculosis (Mtb) and may be useful for monitoring treatment response and treatment efficacy. We conducted a prospective study in 56 adults with pulmonary tuberculosis from whom 244 sputum samples were collected before and during the first month of treatment. We evaluated MBLA for early monitoring of bacterial burden and investigated bactericidal activities of first-line therapy in patients infected with drug susceptible and resistant isolates. Mtb loads measured by MBLA and culture were correlated after one-week (r&#x202F;=&#x202F;0.56) and one-month (r&#x202F;=&#x202F;0.73) of treatment. Correlations between culture and GeneXpert or microscopy were weaker during treatment. Mtb load by MBLA declined more rapidly than GeneXpert after one-week (2.73 Ct, P&#x202F;&lt;&#x202F;0.001; 0.95 Ct, P&#x202F;=&#x202F;0.297, respectively) and one-month (8.94 Ct, P&#x202F;&lt;&#x202F;0.001; 6.78 Ct, P&#x202F;&lt;&#x202F;0.001). Mtb loads in multidrug resistant (MDR) infections were significantly greater than in both sensitive and poly/mono-resistance after one-week (P&#x202F;&lt;&#x202F;0.02) and one-month treatment (P&#x202F;=&#x202F;0.001). MBLA performed better than GeneXpert and microscopy in comparison to culture for quantifying viable Mtb during treatment. It can be used for monitoring bacterial load during TB treatment, facilitating early detection of treatment failure thus improving outcomes