Cryptococcosis is a known opportunistic infection in immunosuppressed hosts. We report our experience of all cases presenting to our Department between December 1975 and September 1988. Eight post-renal transplant patients and three systemic lupus erythematosus (SLE) patients were affected. All were receiving treatment with steroids, in association with either azathioprine or cyclosporin. The diagnosis of cryptococcal meningitis was initially based on a positive cerebrospinal fluid (CSF) cryptococcal antigen, by latex agglutination test, and subsequently confirmed by cultures. Common clinical presentations, in descending order of frequency, included headaches, fever, mental confusion, epilepsy and papilloedema. Meningism was not a prominent feature. CT brain scans were obtained in eight patients and one showed a focal lesion and one showed cerebral atrophy. Four patients also had an abnormal chest X-ray (CXR) and one had disseminated cryptococcosis. Amphotericin and 5-fluorocytosine were the mainstay of therapy, although ketoconazole alone was subsequently used in three selected patients with cure. Four early deaths occurred in patients with delayed diagnosis and treatment, usually in association with other severe concurrent infections. We conclude that awareness of cryptococcosis is essential in immunocompromised hosts presenting with headache with, or without, mental confusion or fever.
Scopulariopsis brevicaulis is a soil fungus normally associated with onychomycosis. It causes subcutaneous infection in immunocompromised patients and is rarely isolated from blood. A case of systemic Scopulariopsis brevicaulis infection was reported in a patient with acute myeloid leukemia. The patient developed persistent fever that did not respond to wide spectrum antibiotics and amphotericin B. Scopulariopsis brevicaulis was the only pathogen isolated from blood cultures. The fever subsided with itraconazole and there was no recurrence of fungal infection with prolonged maintenance of oral itraconazole.
The need for an intensive care protocol, sometimes weekly or biweekly, has led to a significant increase in laboratory costs for kidney recipients. In the present study, an inhouse tetraplex nested PCR assay was developed and validated for the specific detection of BKV, JCV, HCMV and EBV in clinical samples. We determined the Limit of Detection (LOD) and analytical specificity. To demonstrate the diagnostic performance of the assay, a total of 102 archival plasma samples were tested and compared with a commercial uniplex real-time PCR kits. The analytical sensitivity of the in-house tetraplex nested PCR assay was 173 copies/ml, when all four viruses were present in the specimens. These values were 79.2, 58.7, 87.6 and 96.1 copies/ml when only, BKV, JCV, HCMV and EBV respectively, were present. The cross-reactivity assays were shown no detectable signal in the tetraplex PCR results. The estimated diagnostic sensitivities were 92.6% for BKV, 92.3% for JCV and 100% for both HCMV and EBV as compared with commercial kits. Regarding the sensitivity and specificity, it seems that the developed Multiplex Nested PCR assay could be used as a reliable virusassociated renal rejection (VRR) panel in post renal transplant surveillance.
Penicilliosis is a systemic fungal infection caused by Penicillium marneffei. The infection is most commonly seen in Southeast Asia, Southern China, Hong Kong, and Taiwan. It is rarely seen among individuals of African descent. Here, we report a case of penicilliosis in an African man from Namibia who was studying in Malaysia. He presented with multiple umbilicated papules associated with cough, fever, loss of appetite, and weight. He also had urethral discharge and admitted to unprotected sexual intercourse with multiple partners. Histopathological examination of a skin papule showed the presence of multiple 2 to 4 microm intracellular yeast cells. Culture of the papule revealed Penicillium marneffei. The serology for human immunodeficiency virus (HIV) was positive. This case illustrates the need to recognize penicilliosis in any individuals staying or travelling to Southeast Asia and the need to look for underlying HIV infection in adults with umbilicated papules.
Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) is a rare but serious infection that usually occurs within a year after solid organ transplantation. PCP may occur after 1 year post transplantation, but the rate is reported to be very low. Studies have shown an association between cytomegalovirus (CMV) infection in solid organ transplant patients and an increased risk of opportunistic infection. This increased risk is thought to be a result of the immunomodulatory effects of the CMV infection. We present a case of PCP infection occurring 13 years after a renal transplantation. This occurred following a recurrent CMV infection while the patient was on low-dose immunosuppressants.
Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide and the main cause of death in correctional facilities in middle- and low-income countries. Due to the closed environment and the concentration of individuals with TB-related risk factors, effective measures are required to control TB in such settings. Isoniazid preventive therapy (IPT) represents an effective and cost-effective measure. Despite international recommendations that IPT be integral to TB control, it is seldom deployed. A systematic review of interventions used to assess IPT initiation and completion in correctional facilities was conducted using published studies from two biomedical databases and relevant keywords. Additional references were reviewed, resulting in 18 eligible studies. Most (72%) studies were conducted in the United States and in jail settings (60%), with the main objective of improving completion rates inside the facility or after release. Studies that provided data about initiation and completion rates showed poor success in correctional facilities. Adverse consequences and treatment interruption ranged from 1% to 55% (median 5%) in reported studies; hepatotoxicity was the most prevalent adverse reaction. Despite its accelerating effect on the development of active TB, information on human immunodeficiency virus (HIV) status was provided in only half of the studies. Among the four studies where IPT effectiveness was assessed, the results mirror those described in community settings. Future studies require thorough assessments of IPT initiation and completion rates and adverse effects, particularly in low- and middle-income countries and where comorbid viral hepatitis may contribute significantly to outcomes, and in settings where TB and HIV are more endemic.
An observational study was carried out to establish the existence of intestinal microsporidiosis among patients with and without gastrointestinal symptoms in Hospital Universiti Kebangsaan Malaysia, Malaysia. A total of 893 faecal specimens from hospitalized patients were examined for microsporidia using a modification of the usual Gram-chromotrope stain technique. One hundred and sixteen (13.0%) patients were positive for microsporidia: 84 (72.4%), 27 (23.3%) and 5 (4.3%) were low, moderate and high excreters of microsporidia spores, respectively. Of the 91 patients with available medical records, microsporidiosis was commonly observed in children aged 0-6 years (26.4%) and adults aged >or=31 years (57.2%). About one-third of this infection was observed in immunocompetent individuals. Among the immunosuppressive group, microsporidia were observed to be more prevalent in patients with haematological malignancy or a combination of malignancy and diabetes mellitus. About 74% of the patients who had microsporidia in their faeces had gastrointestinal symptoms, which could be related to infections or induced by immunosuppressive therapy. The role of microsporidia in causing gastrointestinal symptoms in this population is as yet unclear.
Head and neck cancer is becoming a more recognizable pathology to the general population and dentists. The modes of treatment include surgery and/or radiation therapy. Where possible, pretreatment dental assessment shall be provided for these patients before they undergo radiation therapy. There are occasions, however, whereby head and neck cancer patients are not prepared optimally for radiation therapy. Because of this, they succumb to complicated oral adverse effects after radiation therapy. The last part of this series reviews the opportunistic infections that can occur to the perioral structure. Their management is briefly discussed.
This retrospective study was conducted at the National Tuberculosis Center (NTBC) where 252 HIV-positive patients coexisting with tuberculosis (TB/HIV) were examined. We found that patients with pulmonary (PTB) and extrapulmonary tuberculosis (EPT) had similar mean age. A higher sex ratio between male to female (10.7:1) was observed in patients with PTB. The other characteristics of patients with pulmonary and extrapulmonary tuberculosis were not statistically different from each other. Cough (88%) and hemoptysis were the most common presenting symptoms, significantly related to patients with PTB. Lymphadenopathy (33.5%) was the most common sign in patients with EPT. The majority of patients with pulmonary and extrapulmonary tuberculosis had CD4 cell counts of less than 200 cells/mm3 (range 0-1,179 with a median of 57 cells/mm3). Lung (89%) and miliary (55.6%) forms were the most frequent disease locations in patients with PTB and EPT, respectively. A higher percentage of patients with PTB (42%) were treated successfully with short-course (6 months) therapy, whereas in patients with EPT (43%) needed a longer period (9 months) for successful treatment. Of the patients who defaulted treatment, a higher proportion (87%) had PTB. No MDR-TB or relapse cases were found in this study.
A study conducted at the Tampin Drug Rehabilitation Center in Malaysia established a high prevalence (23%) of asymptomatic carriers of Cryptosporidium among exposed HIV positive intravenous drug users (IVDUs). A majority of them were young adults and among the ethnic groups, the Malay HIV positive inmates had the highest prevalence of Cryptosporidium infection.
The seroprevalence of toxoplasmosis among 505 of human immunodeficiency virus (HIV)/AIDS patients was 226 (44.8%; 95% CI 42.64-51.76): 27 (47.4%) and 199 (44.4%) showed Toxoplasma seropositivity with and without toxoplasmic encephalitis (TE), respectively (P <0.05). The majority of these patients were in the 25-34 age group (44 versus 39%), male (86 versus 76%), and Chinese (49 versus 53%), though no statistical significance was found between the two. Significant differences between these two groups were noted, however, in terms of marital status, occupation, and present address. The heterosexual exhibited the most frequent behavior at risk for HIV infection, and accounted for 51 and 59% of patients with and without TE, respectively. Only 17/260 (6.5%) and 1/137 (0.7%) of them later acquired TE after receiving primary chemoprophylaxis (cotrimoxazole) and antiretroviral therapy including HAART (P <0.05). Fifty-seven (11.3%) out of those 505 patients were diagnosed with AIDS-related TE. The most common clinical manifestation was headache (56%). The computed tomography scan findings showed most lesions to be multiple (96.4%), hypodense (66.7%), and in the parietal region (39.3%). Twenty-seven (47.4%) patients had chronic (latent) Toxoplasma infection as evidenced by seropositivity for anti-Toxoplasma (IgG) antibody. At the time of diagnosis, the range of CD4 cell count was from 0-239 with a median of 25 cells/cumm. We also found that a CD4 count of less than 100 cells/cumm was significantly associated with development of TE (P <0.05). Clinical outcomes showed that among those who survived, 21 (36.8%), 16 (28.1%), and 2 (3.5%) of patients had completed treatment, transferred out, and were lost to follow up, respectively. Unfortunately, 18 (31.6%) of the cases were officially pronounced dead. Overall, 7 (12.3%) patients were detected as recurrent TE in this study.
The serological responses to Cryptococcus neoformans proteins of blood donors and HIV patients with active cryptococcosis from a tropical region were investigated in this study. Exposure to C. neoformans, an organism ubiquitous in the environment, contributes to the antibody responses observed in the blood donors. IgG responses to cryptococcal proteins were stronger than IgM responses in most sera tested in this study. A 53-kDa cryptococcal protein fragment was identified as the most immunoreactive protein on the IgM immunoblots of both blood donors and patients. Overall, there was no obvious difference in IgG responses of patients when compared with blood donors. Some immunogenic protein fragments (27.5, 76, 78 and 91.5 kDa) were detected at least two times more frequently on IgM immunoblots of patients compared with those of blood donors. It is yet to be investigated whether the proteins identified in this study may have any potential to be used as biomarker for cryptococcosis.
Persistent superficial skin infection caused by multiple fungi is rarely reported. Recently, a number of fungi, both opportunistic and persistent in nature were isolated from the foot skin of a 24-year old male in Malaysia. The fungi were identified as Candida parapsilosis, Rhodotorula mucilaginosa, Phoma spp., Debaryomyces hansenii, Acremonium spp., Aureobasidium pullulans and Aspergillus spp., This is the first report on these opportunistic strains were co-isolated from a healthy individual who suffered from persistent foot skin infection which was diagnosed as athlete's foot for more than 12 years. Among the isolated fungi, C. parapsilosis has been an increasingly common cause of skin infections. R. mucilaginosa and D. hansenii were rarely reported in cases of skin infection. A. pullulans, an emerging fungal pathogen was also being isolated in this case. Interestingly, it was noted that C. parapsilosis, R. mucilaginosa, D. hansenii and A. pullulans are among the common halophiles and this suggests the association of halotolerant fungi in causing persistent superficial skin infection. This discovery will shed light on future research to explore on effective treatment for inhibition of pathogenic halophiles as well as to understand the interaction of multiple fungi in the progress of skin infection.
Kodamaea ohmeri is a rare opportunistic pathogen belonging to Saccharomycetes family. This yeast was also formerly known as Yamadazyma ohmeri or Pichia ohmeri . This opportunistic pathogen causes illness that typically affects people with impaired immune system. In this report, we discuss a fatal case involving a woman in her late 30s who was admitted to the hospital on the sixth day of her sickness after being given a COVID-19 Category 5A diagnosis. For COVID-19, she received subcutaneous heparin, cefuroxime, and intravenous corticosteroids. She was diagnosed with secondary bacterial and fungal infections in the ICU. Multiple antibiotics and antifungal were given to treat bacterial and fungal infections. An unusual fungus, Kodamaea ohmeri , was isolated from the clinical sample. On day 36, she succumbed to her infection in the ICU. The cause of death was multidrug-resistant sepsis with multiple organ failures due to COVID-19 infection, worsened by an embolism and trachea damage during a tracheostomy. To effectively manage K. ohmeri , clinicians and microbiologists must identify and be aware of this emerging human opportunistic pathogen, which can co-infect debilitated patients such as COVID-19 patients, for effective management.
Two hundred fifty seven articles related to HIV/AIDS were found in a search through a database dedicated to indexing all original data relevant to medicine published in Malaysia between the years 2000-2013. One hundred seventy one articles were selected and reviewed on the basis of clinical relevance and future research implications. This review of literature has been divided into six sections, namely, epidemiology, risk behaviour, clinical features and opportunistic infections, management, diagnosis and discussion. Wherever possible, the reviewed articles have been presented in a chronological order to provide a historical perspective to the reader as many of the results of earlier publications, which are common knowledge now, were relatively unknown then. Since the early days of the HIV epidemic in Malaysia, there have been rapid advances in the understanding and the management of the epidemic in Malaysia based on the insights derived from the results of these research. These insights are invaluable tools for policy makers, advocators, healthcare providers, researchers and everyone and anyone who are involved in the care of individuals with HIV/AIDS. Attempts have been made to identify gaps in certain research areas with the hope of providing directions for future research in HIV/AIDS in Malaysia.
Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.
The HIV-positive population, due to their immuno-compromised nature, is considered more susceptible to parasitic infections than other populations. However despite the reports of other opportunistic pathogens such as Cryptosporidium and tuberculosis reported in vulnerable communities, microsporidia have not been highlighted in the local HIV-positive population in Malaysia. This study aimed to provide preliminary information on the prevalence of microsporidia in the local HIV-population. Microsporidia were detected in 21/247 (8.5%) stool samples from the HIV-infected individuals, a significantly higher (P-value <0.05) prevalence than in the control group, in which 5/173 (2.9%) were positive. HIV patients were 3x more at risk for acquiring microspordium (OR: 3.12; 95% CI 1.15-8.44). Spores were ellipsoid in shape with outlines that stained dark pink with the interior a lighter shade. Approximately 21% of the positive specimens were from individuals in the 40-49 years age group. Ten individuals who were positive for microsporidia were also positive for other enteric parasites such as Blastocystis hominis and Giardia lamblia. We detected Encephalitozoon intestinalis DNA following nested PCR from three of 10 samples analysed, as demonstrated by an amplicon of 370bp. From the findings reported, it appears that microsporidial infection in humans may actually be more common than reported. We strongly advocate greater emphasis on personal hygiene through public education on personal hygiene and the consumption of boiled or filtered water.
Southeast Asia is a region where the number of people infected with HIV/AIDS is one of the fastest growing in the world. Tuberculosis (TB) has grown along with the HIV epidemic. TB is not only the most common AIDS-defining illness but is also the leading cause of morbidity and mortality in AIDS patients. Cryptococcosis (meningitis or disseminated) is one of the most common opportunistic infections in AIDS patients. Cryptococcal meningitis is the first in the differential diagnosis considered with meningeal irritation. Penicillosis, a unique systemic mycosis, is an important emerging public health problem and has been classified as an AIDS defining illness in endemic areas like Thailand. Pneumocystis carinii (jiroveci) pneumonia has been one of the most important opportunistic infections in AIDS patients. Among parasitic infections, cryptosporidiosis is the most common intestinal protozoan infection relating to diarrhea in AIDS patients and toxoplasmosis is the only parasitic infection of the nervous system with a substantial incidence, up to 14.8%. Cytomegalovirus (CMV) retinitis has a lower prevalence compared to other opportunistic infections. In the era of highly active antiretroviral therapy (HAART), the incidence of opportunistic infections has significantly reduced in the past few years. Subsequently, the phenomena of immune restoration inflammatory syndrome (IRIS) in AIDS patients has been reported in this region as a result of HAART.