Bacterial co-infection and early mortality among pulmonary tuberculosis patients in Manila, The Philippines.

OBJECTIVE: To investigate the prevalence of bacterial co-infection and its effect on early mortality among hospitalised human immunodeficiency virus (HIV) negative pulmonary tuberculosis (PTB) patients in Manila, the Philippines. DESIGN: A prospective observational study was conducted at a national infectious disease hospital. HIV-negative PTB patients aged 13 years hospitalised from November to December 2011 and from December 2012 to May 2013 were enrolled. Sputum samples were tested for Mycobacterium tuberculosis and six respiratory bacterial pathogens using polymerase chain reaction (PCR). RESULTS: Of 466 patients, 228 (48.9%) were TB-PCR-positive. Overall, bacterial pathogens in purulent sputum were detected in 135 (29.0%) patients: Haemophilus influenzae was the most common bacterium (21.2%), followed by Streptococcus pneumoniae (7.9%). The prevalence of bacterial co-infection did not differ between TB-PCR-positive and -negative patients. A total of 92 (19.7%) patients died within 2 weeks. Bacterial co-infection was significantly associated with an increased risk of 2-week mortality among TB-PCR-positive patients (adjusted risk ratio [aRR] 1.67, 95%CI 1.03-2.72). This association was also observed but did not reach statistical significance among TB-PCR-negative patients (aRR1.7, 95%CI 0.95-3.02). CONCLUSION: Bacterial co-infection is common and contributes to an increased risk of early mortality among HIV-negative PTB patients.

Retrospective seroepidemiological study of chikungunya infection in South Asia, Southeast Asia and the Pacific region.

Chikungunya virus (CHIKV) and Ross River virus (RRV) of the genus Alphavirus, family Togaviridae are mainly transmitted by Aedes mosquitoes and the symptoms they cause in patients are similar to dengue. A chikungunya (CHIK) outbreak re-emerged in several Asian countries during 2005-2006. This study aimed to clarify the prevalence of CHIKV infection in suspected dengue patients in six countries in South Asia and Southeast Asia. Seven hundred forty-eight serum samples were from dengue-suspected patients in South Asia and Southeast Asia, and 52 were from patients in Fiji. The samples were analysed by CHIKV IgM capture ELISA, CHIKV IgG indirect ELISA and focus reduction neutralization test against CHIKV or RRV. CHIK-confirmed cases in South Asia, particularly Myanmar and Sri Lanka, were 4·6%, and 6·1%, respectively; and in Southeast Asia, particularly Indonesia, the Philippines and Vietnam, were 27·4%, 26·8% and 25·0%, respectively. It suggests that CHIK was widely spread in these five countries in Asia. In Fiji, no CHIK cases were confirmed; however, RRV-confirmed cases represented 53·6% of suspected dengue cases. It suggests that RRV is being maintained or occasionally entering from neighbouring countries and should be considered when determining a causative agent for dengue-like illness in Fiji.

Risk factors for death among hospitalised tuberculosis patients in poor urban areas in Manila, The Philippines.

OBJECTIVE: To determine the mortality rate and risk factors for in-hospital death among hospitalised human immunodeficiency virus (HIV) negative tuberculosis (TB) patients in poor urban areas in the Philippines. DESIGN: A cross-sectional study was conducted at a national infectious disease hospital in Manila City. The target population was patients aged ≥ 13 years with all forms of HIV-negative TB admitted from October to December 2009. Demographic and clinical information was collected from medical charts, and risk of in-hospital death was measured. RESULTS: Of 407 HIV-negative TB patients, four were excluded due to missing records, and 403 were included in the analysis. The majority were poor urban residents (90%), and 66% were males. Overall, 37.5% of hospitalised patients died in the hospital (151/403), 30% of whom died before the third day of hospitalisation. Risk factor analysis demonstrated that complications of bacterial pneumonia had the greatest effect on in-hospital death (aOR 4.53, 95%CI 2.65-7.72), followed by anorexia (aOR 3.01, 95%CI 1.55-5.84), anaemia (haemoglobin <10 g/dl, aOR 2.35, 95%CI 1.34-4.13) and older age (aged ≥ 50 years, aOR 1.85, 95%CI 1.08-3.17). The presence of haemoptysis (aOR 0.44, 95%CI 0.25-0.80) was associated with improved survival. CONCLUSION: Mortality among hospitalised HIV-negative TB patients was extremely high in poor urban areas in the Philippines.

Comparison and critical appraisal of dengue clinical guidelines and their use in Asia and Latin America.

The World Health Organization (WHO) dengue classification scheme for dengue fever (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) has been adopted as the standard for diagnosis, clinical management and reporting. In recent years, difficulties in applying the WHO case classification have been reported in several countries. A multicenter study was carried out in Asia and Latin America to analyze the variation and utility of dengue clinical guidelines (DCGs) taking as reference the WHO/PAHO guidelines (1994) and the WHO/SEARO guidelines (1998). A document analysis of 13 dengue guidelines was followed by a questionnaire and Focus Group discussions (FGDs) with 858 health care providers in seven countries. Differences in DCGs of the 13 countries were identified including the concept of warning signs, case classification, use of treatment algorithms and grading into levels of severity. The questionnaires and FGDs revealed (1) inaccessibility of DCGs, (2) lack of training, (3) insufficient number of staff to correctly apply the DCGs at the frontline and (4) the unavailability of diagnostic tests. The differences of the DCGs and the inconsistency in their application suggest a need to re-evaluate and standardise DCGs. This applies especially to case classification and case management.

Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections.

Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue haemorrhagic fever (DHF). To develop a better understanding of the roles of platelet-associated IgG (PAIgG) and IgM (PAIgM) in inducing thrombocytopenia and its severity of disease in patients with secondary dengue virus infection, the relationship between the PAIgG or PAIgM levels and disease severity as well as thrombocytopenia was examined in 78 patients with acute phase secondary infection in a prospective hospital-based study. The decrease in platelet count during the acute phase recovered significantly during the convalescent phase. In contrast, the increased levels of PAIgG or PAIgM that occurred during the acute phase of these patients decreased significantly during the convalescent phase. An inverse correlation between platelet count and PAIgG or PAIgM levels was found in these patients. Anti-dengue virus IgG and IgM activity was found in platelet eluates from 10 patients in an acute phase of secondary infection. Increased levels of PAIgG or PAIgM were significantly higher in DHF than those in dengue fever (DF). An increased level of PAIgM was associated independently with the development of DHF, representing a possible predictor of DHF with a high specificity. Our present data suggest that platelet-associated immunoglobulins involving antidengue virus activity play a pivotal role in the induction of thrombocytopenia and the severity of the disease in secondary dengue virus infections.

A pilot double-blind, randomized, and placebo-controlled study of orally administered IFN-alpha-n1 (Ins) in pediatric patients with measles.

To determine the safety and effectiveness of low-dose oral interferon-alpha (IFN-alpha) against measles, 30 confined pediatric patients were prospectively and randomly assigned to either a placebo or an oral IFN-alpha group and observed daily for 14 days in a double-blind manner. The IFN patients received a daily sublingual dose of 200 IU of human lymphoblastoid IFN-alpha. The IFN-treated group showed shorter average duration of malaise (3.2 vs. 10.7 days, p < 0.0001), anorexia (3.1 vs. 6.7 days, p < 0.0001), and irritability (1.1 vs. 2.2 days, p < 0.01) and shorter duration of macular/maculopapular/papular lesions (4.3 vs. 8.2 days,p < 0.0001) and branny desquamation (4.6 vs. 5.8 days, p > 0.05) and shorter time for rash to become generalized (5.5 vs. 10.3 days, p < 0.0001). No hematologic, renal, or liver toxicities were noted. It, therefore, appears that low-dose oral human lymphoblastoid IFN-alpha used in this pilot study is both safe and effective in children with measles infection.