Role of probiotic as adjuvant in treating various infections: a systematic review and meta-analysis.

BACKGROUND: Research on the advantages of probiotics has attracted increasing interest based on the number of publications, products, and public awareness of their benefits. This review evaluated the role of probiotics (single and multiple regimens) as an additional regimen to treat common infectious diseases, including Helicobacter. pylori, diarrheal infections, urinary tract infections (UTIs), upper respiratory tract infections (URTIs), and HIV infections. METHODS: We searched randomized controlled trials from PubMed, Scopus, Embase, and Cochrane and identified 6,950 studies. Duplicates were removed, and titles and abstracts were filtered. Bias was evaluated using the Cochrane Risk of Bias Tool for Randomized Trials (ROB 1.0 and 2.0). The certainty of the evidence was evaluated using GRADE. Data were extracted and meta-analysis was performed using RevMan. RESULTS: A total of 32 studies were included in this study (22 H. pylori studies, 2 diarrheal infection studies, 6 UTI studies, and 2 HIV infection studies). There was no study on URTI. Probiotics, in addition to primary treatment, could improve the eradication of H. pylori versus the control (RR: 1.09; 95% CI:1.04 - 1.13, p value = 0.001) and achieve a cure range of Nugent score in UTI patients (RR 1.38; 95% CI: 1.01 - 1.89, p value = 0.04). For eradicating H. pylori infection, subgroup analysis based on the therapy regimen showed that standard triple therapy was slightly superior compared to quadruple therapy in eradicating H. pylori (RR: 1.14 vs. 1.01, respectively). Single strain probiotics showed a similar effect to multiple strain probiotic regimens (both had an RR of 1.09). The effect estimates of the use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI had a high certainty of evidence. Meta-analysis was not performed for infectious diarrheal because there were only two eligible studies with different probiotic supplementations and outcome parameters. Nonetheless, they showed that the diarrheal incidence was lower and complete remission of diarrheal was higher after the regimen of probiotics. Similarly, a meta-analysis was not performed for HIV infection because the two eligible studies used different designs and comparators with contradicting findings. CONCLUSION: This meta-analysis showed beneficial use of single strain probiotics as adjuvant therapy in eradicating H. pylori and the use of probiotics in UTI. Probiotic supplementation might not be beneficial for patients given a quadruple therapy. Single-strain and multi-strain probiotic regimens had similar effects in increasing the eradication rate of H. pylori. Our study also suggested that the benefits of probiotics as an additional regimen in infectious diarrheal and HIV infections remain unclear; more studies are needed to confirm the benefits.

MPox Skin Lesions.

Mpox is caused by the Monkeypox virus, which belongs to the Orthopoxvirus genus and Poxviridae family. The Monkeypox virus was first identified as a cause of disease in humans in the 1970s in the Democratic Republic of the Congo. Mpox was considered endemic in several African countries. A global outbreak of Mpox was first recognized in Europe in May 2022 and was declared a public health emergency of international concern on July 23, 2022. The first reported Mpox case in Indonesia was in October 2022 which was identified as an imported case, there were no new confirmed Mpox cases until 13 October 2023. Since then there were 72 cases of confirmed Mpox cases in Indonesia by the end of 2023, distributed across 6 provinces, mostly in the Java island.We present two different spectrums of Mpox skin lesions in patients living with HIV, with a positive polymerase chain reaction test for Mpox. The first patient is a 48-year-old male, who developed a maculopapular lesion, that was initially noticed on the face, the lesions were then spread to the back and hand. He identifies as men who have sex with men and living with HIV for the past 18 years. There were no lesions on the genitalia or mucosa. The second patient is a 28-year-old male, the initial symptom was fever, followed by skin lesions after around 1 week of fever. The lesion initially appears as pustules on the face and then spreads throughout the whole body, the lesions also grow larger and become pseudo-pustules and ulcers. There were also mucosal involvements in the mouth, making oral intake difficult. This patient also identified as men who have sex with men with multiple partners, HIV status was not known at the initial presentation. HIV screening was done with positive results.

Association of G6PD status and haemolytic anaemia in patients receiving anti-malarial agents: a systematic review and meta-analysis.

BACKGROUND: Some anti-malarial drugs often cause haemolytic anaemia in glucose-6-phosphate-dehydrogenase deficiency (G6PDd) patients. This study aims to analyse the association of G6PDd and anaemia in malaria patients receiving anti-malarial drugs. METHODS: A literature search was performed in major database portals. All studies searched using keywords with Medical Subject Headings (MeSH) were included, without date or language restriction. Pooled mean difference of haemoglobin and risk ratio of anaemia were analysed using RevMan. RESULTS: Sixteen studies comprising 3474 malaria patients that included 398 (11.5%) with G6PDd were found. Mean difference of haemoglobin in G6PDd/G6PD normal (G6PDn) patients was - 0.16 g/dL (95% CI - 0.48, 0.15; I2 5%, p = 0.39), regardless of the type of malaria and dose of drugs. In particular with primaquine (PQ), mean difference of haemoglobin in G6PDd/G6PDn patients with dose < 0.5 mg/kg/day was - 0.04 (95% CI - 0.35, 0.27; I2 0%, p = 0.69). The risk ratio of developing anaemia in G6PDd patients was 1.02 (95% CI 0.75, 1.38; I2 0%, p = 0.79). CONCLUSION: Single or daily standard doses of PQ (0.25 mg/kg/day) and weekly PQ (0.75 mg/kg/week) did not increase the risk of anaemia in G6PDd patients.

Current Updates on Diagnosis and Management of Cholangiocarcinoma: from Surgery to Targeted Therapy.

Cholangiocarcinoma is commonly described as any malignancy arising from the lining of the bile duct and is recognized as one of the most common biliary malignancies. We conducted a literature review of current available evidences and guidelines.Based on the anatomical location of the origin of the mass, cholangiocarcinoma can be divided into intrahepatic, perihilar, and distal cholangiocarcinoma. Each of these subtypes has their own risk factors, best treatment options, and prognosis. The most common risk factors for cholangiocarcinoma also differs based on geography and population backgrounds. Histopathological biopsy remained the gold standard for cholangiocarcinoma diagnosis, however various advances has been made in diagnostic procedure, including MRCP, EUS, ERCP, EBUS, and cholangioscopy. Surgical resection is still the best treatment modality for cholangiocarcinoma, but it can only be done in few patients considering most patients were diagnosed in the unresectable state. Other treatment options includes conventional chemotherapy, locoregional therapy, systemic targeted therapy, and palliative best supportive care. Cholangiocarcinoma has an abundance of molecular targets and advances in biomolecular technologies bring further hope for future curative treatment options. Treatment options should be chosen individually based on each patient's condition and setting. Cholangiocarcinoma is still a major health problem in hepatobiliary malignancies. Multiple options are available for cholangiocarcinoma treatments.

Recent advances in the diagnosis of intestinal tuberculosis.

BACKGROUND: Intestinal tuberculosis still has a high incidence, especially in developing countries. The biggest challenge of this disease is the establishment of the diagnosis because the clinical features are not typical. Investigations such as culture, acid-fast bacilli (AFB) staining, and histopathology have low sensitivity, so other investigations are needed. Latest molecular-based diagnostic modalities such as GeneXpert, interferon-gamma (IFN-γ) release assays (IGRA), polymerase chain reaction (PCR), multiplex-PCR, and immunological markers are expected to help diagnose intestinal tuberculosis. This article review will examine the latest diagnostic modalities that can be used as a tool in establishing the diagnosis of intestinal tuberculosis. RESULTS: Through a literature search, we were able to review the diagnostic values of various available diagnostic modalities as the appropriate additional test in intestinal tuberculosis. Culture as a gold standard has a sensitivity and specificity value of 9.3% and 100% with the MGIT BACTEC system as the most recommended medium. The sensitivity values of AFB staining, histopathology examination, GeneXpert, IGRA, PCR, multiplex-PCR and, immunological markers were ranged between 17.3 and 31%; 68%; 81-95.7%; 74-88%; 21.6-65%; 75.7-93.1%; and 52-87%, respectively. Meanwhile the specificity values were 100%; 77.1%; 91-100%; 74-87%; 93-100%; 96.4-100%; and 70-95%, respectively. CONCLUSION: The combination of clinical examination, conventional examination, and the latest molecular-based examination is the best choice for establishing the diagnosis of intestinal tuberculosis. Most recent modalities such as multiplex PCR and immunological marker examinations are diagnostic tools that deserve to be used in diagnosing intestinal tuberculosis as their sensitivity and specificity values are quite high and more evidences are expected to support the application of these examinations shortly soon.

The Vascular Access Related Infections: Have We Anticipated Them Adequately?

The number of patients in need of haemodialysis (HD) is increasing from time to time. In 2018, the Indonesian Renal Registry documented more than 130,000 active patients from 651 registered HD centres. Twenty percent are diabetic patients with end-stage renal disease (ESDR) equal to 8,633 patients. Diabetes Mellitus accounts for 2% of all diabetes cases in the age of 15 year-old and above. Hence, the increasing need for HD is inevitable and is parallel with the need for vascular access procedures.One of the major problems that occurs with vascular access is the risk of infection. Among HD patients, mortality and morbidity are predominantly associated with infection; about one-fifth as a cause of hospital admissions, one-fourth of the infection-related admissions are due to infection of vascular access. Susilo et.al, reported around 40% of patients with temporary vascular access had an infection. Data is limited and might be also underestimated.Unfortunately, the available studies examining risk factors for vascular access-associated infection are scarce and mostly collected with substandard methodology. It is to be highlighted that the study of Susilo et al. may represent the population of a  referral hospital for HD, yet as a reader it is worth noting that heterogeneity among centres and populations should be acknowledged. A comprehensive in-depth review and further research of these studies are crucial for a greater level of understanding for the cause of infection and therefore inform effective early detection and prevention strategies to reduce morbidity and mortality among haemodialysis patients, especially at-risk patients.

Extrapulmonary Manifestations COVID-19.

After being declared as a pandemic on March 11, 2020 by the World Health Organization, COVID-19 has affected 497 million people worldwide as of 9 April 2022. COVID-19 is a disease with a plethora of clinical manifestations, which extends to those beyond pulmonary signs and symptoms. Studies that report on the clinical presentation of COVID-19 rarely report specifically on cases with only extrapulmonary manifestations of COVID-19. Extrapulmonary clinical presentations of COVID-19 without pulmonary signs and symptoms is rare, and in such cases, COVID-19 is rarely suspected.We herewith describe four patients with extrapulmonary manifestations of COVID-19, with positive SARS-COV-2 PCR when the test was performed for initial patient screening. The first patient is a 44-year-old female who developed painful ulcer with burning sensation at the lateral side of the tongue along with low grade fever. This symptom appeared after the initial complaints of coughing and nasal congestion subsided.  The second patient is a 37-year-old male, who complained of red eyes  with itchiness and increased tear production for 3 days before seeing an ophthalmologist. The third patient is a 44-year-old female who developed burning sensation and soreness on her throat upon swallowing with fever and chills. These symptoms appear consecutively without any respiratory complaint. The fourth patient is a previously healthy, 30-year-old female, with a normal weight and BMI, and without any comorbidity, cardiovascular risk and neither personal nor family history of cardiovascular disease. In these 4 patients, COVID-19 stomatitis, conjunctivitis, pharyngitis and COVID-19-associated atrial fibrillation was subsequently diagnosed, respectively.In the pandemic stage of COVID-19, COVID-19 screening has often been routinely performed due to the high risk of transmission. However, the decrease in the number of COVID-19 cases may prompt physicians to perform SARS-COV-2 testing based on clinical suspicion. It is imperative to consider the likelihood of COVID-19 and perform SARS-COV-2 PCR in patients with extrapulmonary complaints that have persisting complaints despite treatment.

Parenteral and Oral Anticoagulant Treatment for Hospitalized and Post-Discharge COVID-19 Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of anticoagulants has been endorsed by different hematological societies as coagulation abnormalities are key features of COVID-19 patients. This systematic review and meta-analysis aims to provide the most recent update on available evidence on the clinical benefits and risk of oral and parenteral anticoagulants, as well agents with anticoagulant properties, in hospitalized and post-discharge COVID-19 patients. METHODS: This systematic review synthesizes data on the outcome of anticoagulation in hospitalized and post-discharge COVID-19 patients. Dichotomous variables from individual studies were pooled by risk ratio (RR) and their 95% confidence interval (95% CI) using the random-effects model. Meta-analyses were performed when feasible. RESULTS: We included 32 studies from 2.815 unique citations, including 7 randomized clinical trials. A total of 33.494 patients were included. Outcomes measured include mortality and survival rates, the requirement for ICU care and mechanical ventilation. A pooled meta-analysis favors anticoagulant compared to no anticoagulant with reduced mortality in hospitalized patients (RR 0,55; 95%CI 0,43-0,66; p<0,001). Higher dose of anticoagulant also showed treatment benefit compared to standard prophylactic dose in selected populations (RR 0,68; 95%CI 0,40-0,96; p<0,001). Regular, pre-hospital anticoagulation prior to hospitalization yielded mixed result. There are currently no data on the benefit of anticoagulation on post-discharge COVID-19 patients. CONCLUSION: Determination of the presence of thrombosis in COVID-19 is important, as therapeutic dosage of anticoagulants, rather than prophylatic dose, would be indicated in such clinical situation. Anticoagulants were found to decrease the mortality of hospitalized COVID-19. The results from this study are important in the tailored treatment of COVID-19 patients. Further studies on the need for oral anticoagulation for outpatients or post-discharge is warranted. This study has been registered in PROSPERO database (CRD42020201418).

Revisiting the Overlooked Infection: Rickettsioses.

The prevalence of human Rickettsioses cases in Indonesia is unknown and could probably be underestimated. The high prevalence of seropositive Rickettsia sp. was reported in small mammals (as vectors) and humans. In Indonesia, a recent study in patients with acute fever revealed that the prevalence of Rickettsioses is 10%. Many cases of Rickettsioses were often misdiagnosed with dengue fever, enteric fever, or leptospirosis due to their overlapping clinical manifestation. The limitation of point of care testing in Indonesia hindered the adequacy of diagnosis confirmation. Appropriate empirical or definitive treatment with macrolide, mainly doxycycline, is preferable compared to other broad-spectrum antibiotics, such as cephalosporin or quinolones. Moreover, when left untreated, Rickettsioses may deteriorate progressively to fatal outcomes, such as meningitis, sepsis, and even death. The awareness of health care practitioners, the availability of confirmatory rapid diagnostic tests and adequate treatment choices are important in eradicating this disease.

Black Fungus Complicated with COVID-19 in a Man with Underlying Non-Hodgkin's Lymphoma.

COVID-19 is a disease reported to suppress cellular immunity. This may lead to the development of opportunistic infections, among others black fungus, or mucormycosis. On the other hand, pre-existing defect in immunity may render patients susceptible to both mucormycosis and COVID-19. Mucormycosis is a relatively rare fungal infection with rapid progression unless diagnosed promptly and treated adequately, and urgent surgical and medical intervention is lifesaving. The manifestation of mucormycosis largely depends on the presence of exposure to the pathogen and the existing risk factor of the host. As black fungus is locally invasive, the majority of cases will involve tissue damage with local destruction and contiguous spread to nearby structure. We here with present a case of black fungus complicated with COVID-19 in a man with underlying non-Hodgkin's lymphoma.

Hospital-acquired Skin and Skin-structure Infection in COVID-19 Infected Patient with Prolonged Hospitalization.

Acute bacterial skin and skin-structure infections (ABSSSI) is defined in 2013 by the US Food and Drug Administration as a bacterial cellulitis/erysipelas, major skin abscesses, and wound infections. The Infectious Diseases Society of America (IDSA) in 2014 classifies skin and soft-tissue infection (SSTI) as either non-purulent (which includes cellulitis, erysipelas, and necrotizing infection) or purulent (including furuncle, carbuncle, and abscess). Among hospitalized patients with SSTI, healthcare-associated infections account for 73.5% of all cases. Notably, skin and skin-structure infections caused by Pseudomonas aeruginosa, a common hospital pathogen, was reported to cause higher total cost and longer hospital length of stay compared to non-P. aeruginosa cases, despite causing only approximately 5.7% of all healthcare-associated SSTIs. Infection with P. aeruginosa should always be considered in non-healing skin infections in patients with prolonged hospitalization and antibiotic exposure. Tissue culture, preferably taken by surgical debridement, should be promptly performed; and when hospital-infection is suspected, appropriate antibiotics should be started along with removal of all devitalized tissue and to promote skin and soft tissue healing. Expedited discharge should be considered when possible, with adequate antibiotic treatment and follow up for definitive wound treatment.

The Validation of Drug Resistance in Pneumonia (DRIP) Score in Predicting Infections due to Drug-Resistant Pathogens in Community-acquired Pneumonia at Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

BACKGROUND: The emergence of drug-resistant pathogens (DRP) in recent years possibly contributes to the common problems associated with community-acquired pneumonia. However, to predict the risk of the ailment, the DRIP score is mainly applied, although no validation study has been reported in Indonesia. Therefore, the score prediction accuracy in the population, patient characteristics and germ patterns appears indefinite, particularly for Cipto Mangunkusumo Hospital, Jakarta. The purpose of this study is to determine the DRIP performance as an instrument in predicting infections due to drug-resistant pathogens (DRP) in community-acquired pneumonia at Cipto Mangunkusumo Hospital. METHODS: This research employed a cross-sectional design, where the subjects were community-acquired pneumonia patients treated between January 2019 and June 2020. In addition, adequate medical records of the participants were obtained. The condition is defined as DRP when the sputum culture results show resistance to non-pseudomonal ß-lactam antibiotics, macrolides, and respiratory fluoroquinolones. Furthermore, the score performance was analyzed by determining the calibration and discrimination values, using the Hosmer-Lemeshow test and AUROC, respectively. RESULTS: A total of 254 subjects were known to have satisfied the selection criteria. These participants were categorized into DRP and non-DRP groups, with 103 (40.6%) and 151 (59.4%) patients, correspondingly. The DRIP calibration analysis using the Hosmer-Lemeshow test obtained p-value = 0.001 (p <0.05), while an AUC value of 0.759 (CI 95%, 0.702-0.810) was derived from the ROC curve. However, at a score of ≥ 4, the DRIP showed sensitivity, specificity, positive and negative predictive values of 70.9, 92.7, 86.9, and 82.3%, respectively. CONCLUSION: The DRIP score demonstrated a significant performance in predicting infections due to DRP in community-acquired pneumonia.

The Comparison of Point Prevalence Survey (PPS) and Gyssens Flowchart Approach on Antimicrobial Use Surveillance in Indonesian National Referral Hospital.

The antimicrobial resistance (AMR) rate in Indonesia is steadily rising, despite the existing national action plan in 2014. In line with the Global Action Plan on AMR, proper surveillance on antimicrobial usage and resistance are needed. At present, antimicrobial surveillance (AMS) data in Indonesia is heterogeneous, fragmented, and localized. The common method of antimicrobial surveillance (AMS) in referral hospitals is by implementing Gyssens flowchart during Antimicrobial Resistance Control Program Committee clinical rounds. However, the recent method of AMS with Point Prevalence Survey (PPS) offers many advantages include its concise and simple protocol, large data collection, shorter required time, comprehensive data outcomes, real-time data, and standardized parameters. In low-middle income countries such as Indonesia with its restricted resources in AMS, PPS is superior compared to the 'traditional' hospital clinical round in generating representative and homogenous outcomes that can be compared to data from other centers worldwide.

Clinical Evaluation of HIV/AIDS Patients on Antiretroviral Therapy using HIV Symptoms Index: A reliability and Applicability Evaluation using Indonesian Language.

BACKGROUND: HIV/AIDS is a chronic, lifelong disease with a wide clinical spectrum which could decrease the quality of life. Objective symptoms measurement is important because it is correlated to treatment adherence and progressivity of the disease. Currently, there is no clinical tool available to evaluate symptoms of HIV infection and the treatment's side effect for the outpatient setting. This study aimed is to assess the reliability of the Indonesian version of HIV Symptom Index for measuring symptoms of HIV/AIDS patients, and use it for assessment of their symptom profile. METHODS: this is a cross sectional study in outpatient HIV/AIDS subjects (n=87) recruited in Cipto Mangunkusumo Hospital's HIV clinic from September-November 2018. The HIV Symptom Index consisted of 20 items evaluating somatic, psychologic, and the combination of both symptoms, and its' language adaptation to Indonesian was done with Beaton and Guillemin method. Reliability of the Indonesian version of HIV Symptom Index was tested by alpha cronbach's a coefficient analysis, and the internal validity was tested with multitrait scaling analysis before being used to profile the symptom pattern of HIV/AIDS patients. RESULTS: Indonesian version of HIV Symptom Index is reliable (cronbach alpha 0.76) and valid (multitrait correlation >0.4) for measuring symptoms of HIV/AIDS patients. The most common symptom is fatigue (55.7%), followed by insomnia (43.3%), dizziness and lightheadedness (42.3%), skin problems (42.3%), and pain, numbness, or tingling in the hands or feet (39.2%). CONCLUSION: Indonesian version of HIV symptom Index is reliable and valid to measure symptoms of HIV/AIDS patiens objectively.

The Threat of Emerging and Re-emerging Infections in Indonesia.

Human immunodeficiency virus (HIV) is one example of an emerging infection with total of 386 district of all province in Indonesia reported having such infection; with cumulative number of HIV infected patient from the year 1987 to 2014 is 150,296 while AIDS is 55,799 patients. The access to care only available for 153,887 patients among all HIV/AIDS patients of whom 70% are eligible for anti-retroviral (ARV) treatment and of these only half adhered to ARV treatment. In addition to that, there is an increased risk of other emerging diseases such as Zika virus, Monkey pox or Hanta pulmonary syndrome since a sporadic cases were reported around the region.Beside new diseases, tuberculosis, dengue virus, malaria and diphteria are continuously reported in Indonesia and classified as re-emerging illnesses. On this edition data on diphteria epidemiology in Indonesia will be shown by Karyanti et al.6 A recent outbreak of diphteria in Indonesia which involved almost all province in the country has led to a response named ORI (outbreak response of Immunization). Regardless of immunization, proper treatment including the distribution of anti-toxin and antibiotics are needed to stop the spread of this particular bacteria, further decreasing the mortality rate. In conclusion, the author of this paper mentioned that immunization gap needs to be handle systematically. Immunization data released on 2017 showed that complete immunization was given only to 20% of targeted group, while almost 75% were either unvaccinated or unknown. During the outbreak of diphteria in Indonesia, the WHO also reported several countries with similar problem such as Bangladesh, Haiti and Yamen. It was shown that a coordination between doctors in clinic/hospital with public health officer to conduct an epidemiological investigation, in conjunction with giving prophylaxis and assuring the logistics of anti-diphteria toxin and antibiotics were accessible were  the key of success in eliminating diphteria like it was in Bangladesh.Adherence to treatment are multifactorial for all illnesses. First, is the duration of treatment and the potential adverse event due to the medication. The Ministry of Health of the Republic of Indonesia has support the early diagnosis of HIV and delivering treatment as soon as possible, in order to avoid transmission of the disease. Second, looking at another side of the story for HIV infected patients, receiving ARV treatment as a long life treatment could possibly cause an adverse event somewhere along the line. Budiman et.al reported factors that might contribute to liver injury. His study shows that measuring baseline liver function test AST routinely might minimize the toxicity of ARV to patients particularly with a low body mass index. Last, despite the adherence to treatment and procedures in minimizing the risk of adverse event to medication, we are now facing the primary resistance virus that transmitted in the community as mentioned by Megasari et al.8 on her report regarding the transmission of drug resistance HIV virus to naïve patients in Bali.The Indonesian government through the Indonesian Ministry of Health has established a collaboration and one health approaches to tackle the threat of diseases in the country, particularly in infectious diseases.

Diphtheria Epidemiology in Indonesia during 2010-2017.

BACKGROUND: in recent years, diphtheria has reemerged in several countries including Venezuela, Yemen, Bangladesh, and Haiti. Similarly, Indonesia also showed an increased number of diphtheria cases in 2010-2017 despite the Diphteria, Tetanus, Pertussis (DTP) immunization program applied in Indonesia for children. This study aimed to evaluate the epidemiology of diphtheria cases which occurred in Indonesia during 2010-2017. METHODS: this was a retrospective study of diphtheria cases in Indonesia. The following source of data about diphtheria disease burden and vaccine coverage was obtained from Ministry of Health Republic of Indonesia, Indonesian Pediatric Society and World Health Organization South East Asia Regional Office. RESULTS: the number of diphtheria cases in Indonesia were distributed across 30 provinces with a total of 811 cases in 2011; 1,192 cases in 2012; 296 cases in 2014; and 939 cases in 2017. Based on age group, the highest number of case fatality rate were in age group of 5-9 years old. Diphtheria immunization coverage in Indonesia among children was fluctuated, reported as 67.7 % in 2007, 61.9 % in 2010, 75.6% in 2013 and 61.3% in 2018. In addition to that, the organization of internal medicine has recommend booster of DPT immunization every 10 years for those children that had received complete DPT vaccination during childhood, however this was not applied. As the countermeasure towards this trend, the Ministry of Health implemented three rounds of Outbreak Response Immunization (ORI) targeted for the age group of 0-1-6 months old and 1-18 years old in 2017 and tailor approached for adults that had exposed to cases. Banten, DKI Jakarta and West Java were the first three provinces to implement this program considering their condensed population and high risk of disease transmission. CONCLUSION: in Indonesia, there was dramatic increase of diphtheria case in 2010-2017, where immunization in children should be reinforced by increasing coverage more than 95% and adult boosted vaccination approaches should be initiated to prevent the spread of these fatal diphtheria diseases in Indonesia.

Early Detection of Plasma Leakage in Dengue Hemorrhagic Fever.

Dengue viral infection remains a major public health problem. As many as 400 million people are infected yearly. Even though the vaccine is available, the use of dengue vaccine is still limited due to some concerns. Among patient infected with dengue viral infection, early recognition of the virus and prompt supportive treatment are important to avoid complication and mortality.The clinical spectrum of dengue viral infection is diverse ranging from undifferentiated fever to dengue shock syndrome characterized by plasma leak and hemoconcentration. No specific antiviral therapy is available. Therefore, anticipation of complication should be performed adequately.The most dangerous complication of dengue infection is shock syndrome. Hypothetically the occurrence of shock is a result of secondary viral infection. The manifestation of increased vascular permeability and low intravascular volume lead to the development of shock. In addition to that, another complex mechanism underlies the occurrence of shock such as endothelial dysfunction that could happened abruptly. No specific method exists to identify this condition as early as possible.During dengue infection, fever can be last between 2 and 7 days. The localized plasma leakage could happen and manifested as a pleural effusion fluid accumulation in abdominal cavity or hemoconcentration. This will only last for 48 hours and will be resolved later spontaneously. Severity of leakage varies among patients and the unanticipated of leakage due to failure to recognize and treat this manifestation related to mortality.Most of the fatal cases of dengue are related to late detection of the illness as shown by massive hemorrhage and severe intravascular volume depletion. The role of dendritic cells is as the initiator of immune response that facilitate virus uptake. On the other hand, the non-neutralize cross reactive antibodies will increase virus uptake and resulted in more viral replication. Some studies showed higher NS1 protein were found in patients with more severe disease. In addition to that antibody to NS1 could bind to the endothelial cells and lead to apoptosis of these cells. Both host and viral factors contribute to the severity of the illness.One of the important factors for dengue viral infection is the capacity of clinicians to identify the risk factors for shock. Studies reported that female, infants, elderly, patients with concomitant diseases are prone to have more severe infection. Virus serotype and genetic susceptibility may also contribute but the evidence is still limited. So, those are not sensitive enough be used in clinical setting.Besides those, after the diagnosis of with dengue infection based on WHO criteria and confirmation by serology detection or viral material in the blood, no specific sign and symptoms are available to determine any potential severity. There were studies performed to monitor the plasma leakage using mean arterial blood pressure (MAP) instead of hematocrit values. Rapid intervention can be administered by monitoring MAP to avoid deleterious consequences.The classification of WHO 1997 or 2009 were not able to detect the plasma leakage earlier. Nainggolan et al presented the resulted of their observation among early dengue infection which was the occurrence of gallbladder wall thickening as a manifestation of plasma leakage. Ultrasonographic measurement is valuable and applicable to detect plasma leakage in earlier phase with positive likelihood ratio 2.14 (95% CI 1.12 - 4.12). Similar report from Indonesia also showed the role of ultrasonography in dengue.

Antifungal Susceptibility Testing in HIV/AIDS Patients: a Comparison Between Automated Machine and Manual Method.

AIM: to evaluate the performance of Vitek2 compact machine (Biomerieux Inc. ver 04.02, France) in reference to manual methods for susceptibility test for Candida resistance among HIV/AIDS patients. METHODS: a comparison study to evaluate Vitek2 compact machine (Biomerieux Inc. ver 04.02, France) in reference to manual methods for susceptibility test for Candida resistance among HIV/AIDS patient was done. Categorical agreement between manual disc diffusion and Vitek2 machine was calculated using predefined criteria. Time to susceptibility result for automated and manual methods were measured. RESULTS: there were 137 Candida isolates comprising eight Candida species with C.albicans and C. glabrata as the first (56.2%) and second (15.3%) most common species, respectively. For fluconazole drug, among the C. albicans, 2.6% was found resistant on manual disc diffusion methods and no resistant was determined by Vitek2 machine; whereas 100% C. krusei was identified as resistant on both methods. Resistant patterns for C. glabrata to fluconazole, voriconazole and amphotericin B were 52.4%, 23.8%, 23.8% vs. 9.5%, 9.5%, 4.8% respectively between manual diffusion disc methods and Vitek2 machine. Time to susceptibility result for automated methods compared to Vitex2 machine was shorter for all Candida species. CONCLUSION: there is a good categorical agreement between manual disc diffusion and Vitek2 machine, except for C. glabrata for measuring the antifungal resistant. Time to susceptibility result for automated methods is shorter for all Candida species.

Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia.

BACKGROUND: Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure. We assessed primaquine (PQ) as hypnozoitocide when administered with dihydroartemisinin-piperaquine (Eurartesim®, DHA-PP) or artesunate-pyronaridine (Pyramax®, AS-PYR) to affirm its good tolerability and efficacy. A third arm, artesunate followed by primaquine, was not intended as therapy for practice, but addressed a hypothesis concerning primaquine efficacy without co-administration of blood schizontocide. METHODS: During March to July 2013, an open-label, randomized trial enrolled Indonesian soldiers with vivax malaria at Sragen, Central Java, after six months duty in malarious Papua, Indonesia. No malaria transmission occurred at the study site and P. vivax recurrences in the 12 months following therapy were classified as relapses. A historic relapse control derived from a cohort of soldiers who served in the same area of Papua was applied to estimate risk of relapse among randomized treatment groups. Those were: 1) AS followed 2d later by PQ (0.5 mg/kg daily for 14d); 2) co-formulated AS-PYR concurrent with the same regimen of PQ; or 3) co-formulated DHA-PP concurrent with the same regimen of PQ. RESULTS: Among 532 soldiers, 219 had vivax malaria during the four months following repatriation to Java; 180 of these were otherwise healthy and G6PD-normal and enrolled in the trial. Subjects in all treatment groups tolerated the therapies well without untoward events and cleared parasitemia within three days. First relapse appeared at day 39 post-enrollment, and the last at day 270. Therapeutic efficacy of PQ against relapse by incidence density analysis was 92 % (95 %CI = 83-97 %), 94 %(95 %CI = 86-97 %), and 95 %(95 %CI = 88-98 %) when combined with AS, AS-PYR, or DHA-PP, respectively. CONCLUSIONS: This trial offers evidence of good tolerability and efficacy of PQ against P. vivax relapse when administered concurrently with DHA-PP or AS-PYR. These offer alternative partner drugs for radical cure with primaquine. The AS arm demonstrated efficacy with a total dose of 7 mg/kg PQ without concurrently administered blood schizontocide, another option when primaquine therapy is removed in time from the treatment of the acute malaria or applied presumptively without an attack. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82366390, assigned 20 March 2013.