Efficacy of pretomanid-containing regiments for drug-resistant tuberculosis: A systematic review and meta-analysis of clinical trials.

Concerns regarding the rise of drug-resistant tuberculosis (DR-TB) infections and the need for new drugs with shorter treatment time and fewer side effects have been voiced by the World Health Organization (WHO). The WHO revised its guideline to treat multidrug resistant tuberculosis (MDR-TB) with a 6-month course of BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) in 2022. However, a thorough study and meta-analysis of available evidence is required due to the limited confidence of the evidence confirming the effectiveness of pretomanid-containing regiments. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of pretomanid-containing regiments in treating DR-TB patients. Data from six search engines were searched using inclusion criteria based on the PICOS framework. The keywords of pretomanid and tuberculosis or their alternatives were used. Using RoB2 Cochrane risk-of-bias tool for randomized clinical trials, data were independently extracted and the quality of the data was evaluated. Odds ratio (OR) and heterogeneity tests were used and the findings were presented in ORs and forest plots. A total of four studies with 237 patients was included in the final analysis and 204 (86%) patients had favorable outcome (cured) and 33 (14%) was not cured. Pretomanid-containing regimen (OR: 46.73; 95%CI: 11.76-185.7) and BPaLM/BPaL (OR: 41.67; 95%CI: 8.86-196.73) regimens were associated with favorable outcome (cured). This meta-analysis indicates that the pretomanid-containing regimen and the BPaLM/BPaL regimen could increase the chance to have favorable outcome in DR-TB patients.

Prevention and control of blood stream infection using the balanced scorecard approach.

AIM: to obtain formulation of an effective and efficient strategy to overcome blood stream infection (BSI). METHODS: operational research design with qualitative and quantitative approach. The study was divided into two stages. Stage I was an operational research with problem solving approach using qualitative and quantitative method. Stage II was performed using quantitative method, a form of an interventional study on strategy implementation, which was previously established in stage I. The effective and efficient strategy for the prevention and control of infection in neonatal unit Cipto Mangunkusumo (CM) Hospital was established using Balanced Scorecard (BSC) approach, which involved several related processes. RESULTS: the BSC strategy was proven to be effective and efficient in substantially reducing BSI from 52.31°/oo to 1.36°/oo in neonates with birth weight (BW) 1000-1499 g (p=0.025), and from 29.96°/oo to 1.66°/oo in BW 1500-1999 g (p=0.05). Gram-negative bacteria still predominated as the main cause of BSI in CMH Neonatal Unit. So far, the sources of the microorganisms were thought to be from the environment of treatment unit (tap water filter and humidifying water in the incubator). Significant reduction was also found in neonatal mortality rate weighing 1000-1499 g at birth, length of stay, hospitalization costs, and improved customer satisfaction. CONCLUSION: effective and efficient infection prevention and control using BSC approach could significantly reduce the rate of BSI. This approach may be applied for adult patients in intensive care unit with a wide range of adjustment.

Shigella spp. surveillance in Indonesia: the emergence or reemergence of S. dysenteriae.

From June 1998 through November 1999, Shigella spp. were isolated in 5% of samples from 3,848 children and adults with severe diarrheal illness in hospitals throughout Indonesia. S. dysenteriae has reemerged in Bali, Kalimantan, and Batam and was detected in Jakarta after a hiatus of 15 years.

Cholera in Indonesia in 1993-1999.

Cholera-specific surveillance in Indonesia was initiated to identify the introduction of the newly recognized Vibrio cholerae non-O1, O139 serotype. Findings from seven years (1993-1999) of surveillance efforts also yielded regional profiles of the importance of cholera in both epidemic and sporadic diarrheal disease occurrence throughout the archipelago. A two-fold surveillance strategy was pursued involving 1) outbreak investigations, and 2) hospital-based case recognition. Rectal swabs were transported to Jakarta for culture and isolates were characterized by serotypic identification. Outbreak findings showed that V. cholerae O1, Ogawa serotype, was the predominant etiology in all 17 instances of investigated epidemic transmission. Monitoring of eight hospitals representing seven provinces provided 6,882 specimens, of which 9% were culture positive for V. cholerae: 589 (9%) for O1 and 20 (< 1%) for non-O1 strains. Proportional representation of V. cholerae O1 among cases of sporadic diarrheal illness was variable, ranging from 13% in Jakarta to < 1% in Batam. Overall, 98% of V. cholerae O1 cases were the Ogawa serotype. There was no instance of non-O1, O139 serotype introduction in either epidemic or sporadic disease form. Anti-microbial drug susceptibility was consistently demonstrated, both temporally and spatially, except against colistin. Evidence is provided that epidemic and sporadic cholera occurrence in western Indonesia is associated with periods of low rainfall. Conversely, in the more eastern portion of the country, heavy rainfall may have contributed to epidemic cholera transmission.

The unique riverine ecology of hepatitis E virus transmission in South-East Asia.

The ecology of hepatitis E virus (HEV) transmission in South-East Asia was assessed from a review of 6 published and 3 unpublished NAMRU-2 reports of hepatitis outbreak investigations, cross-sectional prevalence studies, and hospital-based case-control studies. Findings from Indonesia and Viet Nam show epidemic foci centred in jungle, riverine environments. In contrast, few cases of acute, clinical hepatitis from cities in Indonesia, Viet Nam and Laos could be attributed to HEV. When communities in Indonesia were grouped into areas of low (< 40%), medium (40-60%), and high (> 60%) prevalence of anti-HEV antibodies, uses of river water for drinking and cooking, personal washing, and human excreta disposal were all significantly associated with high prevalence of infection. Conversely, boiling of river drinking water was negatively associated with higher prevalence (P < 0.01). The protective value of boiling river water was also shown in sporadic HEV transmission in Indonesia and in epidemic and sporadic spread in Viet Nam. Evidence from Indonesia indicated that the decreased dilution of HEV in river water due to unusually dry weather contributed to risk of epidemic HEV transmission. But river flooding conditions and contamination added to the risk of HEV infection in Viet Nam. These findings attest to a unique combination of ecological and environmental conditions predisposing to epidemic HEV spread in South-East Asia.

Prevalence of enteric hepatitis A and E viruses in the Mekong River delta region of Vietnam.

A study of antibody prevalence for hepatitis A virus (HAV) and hepatitis E virus (HEV) was carried out in southwestern Vietnam in an area adjacent to a known focus of epidemic HEV transmission. The purpose of this investigation was first to provide a prevalence measure of hepatitis infections, and second to determine the outbreak potential of HEV as a function of the susceptible population. Blood specimens collected from 646 persons in randomly selected village hamlets were examined by an ELISA for anti-HEV IgG and anti-HAV IgG. The prevalences of anti-HEV IgG and anti-HAV IgG were 9% and 97%, respectively. There was a significant increase (P < 0.01) in age-specific anti-HEV IgG. A notable increase in anti-HAV IgG prevalence (P < 0.0001) occurred between child populations 0-4 (64%) and 5-9 (95%) years of age. No evidence of familial clustering of anti-HEV IgG-positive individuals was detected, and household crowding was not associated with the spread of HEV. Boiling of water was found to be of protective value against HEV transmission. A relatively low prevalence of anti-HEV indicates considerable HEV outbreak potential, against a background of 1) poor, water-related hygiene/sanitation, 2) dependence on a (likely human/animal waste)-contaminated Mekong riverine system, and 3) periodic river flooding.

Acute jaundice in Vientiane, Lao People's Democratic Republic.

Analysis of serum samples from patients with acute jaundice by means of enzyme-linked immunosorbent assay and polymerase chain reaction testing provided the first profile of this condition in Vientiane, Lao PDR, in 1995 and 1996. In a case-control, hospital-based study, evidence of acute infections due to hepatitis A and B viruses was found in 14% and 10% of cases, respectively. Hepatitis E virus, however, did not appear to contribute to clinically recognized acute jaundice. Similarly, antibody to hepatitis C virus was recognized in almost equal proportions of cases (8%) and controls (6%), thus representing probable background infections. The detection of hepatitis G virus marks the first report of this virus in Lao PDR. The large proportion (21%) of new leptospiral infections in cases without acute hepatitis A or B was notable. This finding suggests significant regional underreporting of leptospirosis as a cause of acute jaundice. The limited laboratory diagnostic capabilities for confirming a differential diagnosis of leptospirosis contribute to the lack of attention paid to this important health problem.

Impact of epidemic influenza A-like acute respiratory illness in a remote jungle highland population in Irian Jaya, Indonesia.

A suspected epidemic of unknown etiology was investigated in April/May 1996 in the remote jungle highlands of easternmost Indonesia. Trend analysis demonstrates the area-wide occurrence of a major respiratory infection outbreak in November 1995 through February 1996. The monthly mean rate of respiratory infection episodes for the peak outbreak months (2,477 episodes/100,000 persons) was significantly higher (P < .0001) than for the 34 months leading up to the outbreak (109 episodes/100,000 persons). Notable were the high attack rates, particularly among adults: 202 episodes/1,000 persons aged 20-50 years in one community. Excess morbidity attributed to the outbreak was an estimated 4,338 episodes. The overall case-fatality rate was 15.1% of outbreak cases. Laboratory evidence confirmed the circulation of influenza A/Taiwan/1/86-like viruses in the study population, and high hemagglutination inhibition titer responses were indicative of recent infections. Historical documents from neighboring Papua New Guinea highlight the role of influenza A virus in repeated area outbreaks.

Epidemic and sporadic hepatitis E virus transmission in West Kalimantan (Borneo), Indonesia.

A cross-sectional survey was conducted in West Kalimantan (Borneo), Indonesia to geographically profile hepatitis E virus (HEV) prevalence in the riverine areas recognized as the foci of epidemic HEV transmission in 1987. Additionally, a contiguous, although distinct, population with no identifiable historical exposure to epidemic HEV was surveyed downstream for comparative purposes. Eight hundred eighty-five sera were assayed by enzyme immunoabsorbent assay for anti-HEV IgG and anti-hepatitis A virus (HAV) IgG markers. A very high percent (90%) of both the outbreak and comparison populations was anti-HAV IgG positive by the age of nine years. In contrast, the prevalence of anti-HEV IgG in the outbreak area (50%) was significantly higher than in the comparison area (23%) (P < 0.0001). In both the outbreak and comparison areas, anti-HEV IgG prevalence increased with age ( < 0.0001), except for the group > or = 50 years of age. The prevalence (53%) of antibody to HEV in the population > or = seven years of age from the outbreak area (alive during the actual 1987 outbreak) was significantly (P < 0.0001) greater than among the children < seven years of age (born after the outbreak) (15%). However, anti-HEV IgG prevalence among the population from the comparison area did not differ significantly between the > or = seven- (23%) and < seven- (20%) year-old age groups. The percentage of anti-HEV IgG-positive individuals among males (47%) from the outbreak area was lower (P < 0.05) compared with females (55%). While overall usage of river water for drinking purposes was not universal, dependence on river water as a primary source was significantly higher (P < 0.001) in households from the outbreak area (60%) compared with the comparison area (30%). This study indicates persistence of an anti-HEV IgG response in a large percentage of the population seven years after an epidemic of HEV infections. Also, the relatively high prevalence (15%) of anti-HEV in children < seven years of age from the outbreak area reflects continuing, sporadic infections.

Seroepidemiologic evidence for murine and scrub typhus in Malang, Indonesia.

Indonesian military personnel stationed in Malang, East Java were among troops deployed to central Cambodia as part of the United Nations' Transition Authority Cambodia peace-keeping operation in 1992. Predeployment blood samples obtained from a cohort of Indonesian soldiers indicated a high prevalence of antibodies to antigens of Rickettsia typhi or Orientia (formerly Rickettsia) tsutsugamushi, the etiologic agents for murine and scrub typhus, respectively. To evaluate the potential risk of these rickettsial diseases in the Malang area, a subsequent seroepidemiologic survey was conducted. This study involved civilian personnel residing within one of three Malang kelurahans (neighborhoods) representing urban, suburban, and rural communities. The heads-of-households from 197 homes completed a detailed epidemiologic survey. In addition, blood samples were collected from 464 individuals residing within the households surveyed. Examination of civilian blood samples disclosed that 34.7% and 1.3% of the study participants were seroreactive to R. typhi and O. tsutsugamushi, respectively. These results were similar to those obtained earlier from the military samples. In addition, assessment of 78 blood samples obtained from peridomestic rodents trapped from within or near the households surveyed showed that 28 were reactive to R. typhi antigens and four were reactive to O. tsutsugamushi antigens. These data indicate that military and civilian personnel living in the Malang area of East Java are at risk of infection with rickettsiae that are antigenically indistinguishable from those that cause murine and scrub typhus.

A waterborne outbreak of hepatitis E virus transmission in southwestern Vietnam.

A hepatitis outbreak affecting primarily adults occurred in southwestern Vietnam, along the Hau river bordering Cambodia, in June and July 1994. One month after the outbreak, sera and epidemiologic information were collected from 150 subjects: 50 patient cases, 50 matched, healthy community controls, and 50 geographic controls living 50 km upriver. The prevalence of immunoglobulin G (IgG) to hepatitis E virus (HEV) was significantly (P < 0.001) higher (76%) among cases than among the matched (38%) and geographic (38%) control populations. Immunoglobulin M to HEV was detected by enzyme-linked immunosorbent assay and Western blot in 16% of sera collected from patients one month after the outbreak. Hepatitis E virus RNA was detected with the polymerase chain reaction in 6% of sera from patients; RNA was not detected in either control group. These results indicate that HEV was the etiologic agent responsible for the outbreak. Children were under-represented among clinical cases. River water served as the principal source for drinking and bathing among most (96%) of the case and control study populations. Boiling of drinking water was negatively associated (P < 0.05) with IgG anti-HEV seropositivity. Unusually heavy rainfall likely contributed to conditions that favored the outbreak. This is the first recognized outbreak of epidemic HEV transmission in Indo-China.