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.
Despite the great importance of Aureobasidium pullulans in biotechnology, the fungus had emerged as an opportunistic human pathogen, especially among immunocompromised patients. Clinical detection of this rare human fungal pathogen presently relies on morphology diagnosis which may be misleading. Thus, a sensitive and accurate quantitative molecular assay for A. pullulans remains lacking. In this study, we presented the microscopy observations of A. pullulans that reveals the phenotypic plasticity of the fungus. A. pullulans-specific primers and molecular beacon probes were designed based on the fungal 18S ribosomal RNA (rRNA) gene. Comparison of two probes with varied quencher chemistry, namely BHQ-1 and Tamra, revealed high amplification efficiency of 104% and 108%, respectively. The optimized quantitative real-time PCR (qPCR) assays could detect and quantify up to 1 pg concentration of A. pullulans DNA. Both assays displayed satisfactory performance parameters at fast thermal cycling mode. The molecular assay has great potential as a molecular diagnosis tool for early detection of fungal infection caused by A. pullulans, which merits future study in clinical diagnosis.
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.
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.
Ten out of 237 patients who underwent renal transplantation between 1975 and October 1986 developed tuberculosis. Most patients presented with vague symptoms, and typical symptoms commonly associated with tuberculosis were not common. Six had positive urine cultures. One patient had positive sputum and urine cultures and one had positive sputum and cerebrospinal fluid cultures for tuberculosis. In this last patient cryptococcus was also cultured from the sputum and CSF. Nine of the 10 patients responded well to antituberculosis therapy and was cured of the infection. The patient with associated cryptococcal infection died 2 months after presentation. Side effects of antituberculous therapy was minimal and easily resolved on stopping the offending drug.
A 35 year old man with a fatal Campylobacter jejuni infection is described. He had HbE/beta zero thalassaemia and had undergone splenectomy nine months previously for hypersplenism; he also had chronic hepatitis C infection. He presented with high grade fever but no gastrointestinal symptoms and rapidly progressed to septicaemic shock and hepatic encephalopathy despite treatment with penicillin, gentamicin, and, later, chloramphenicol and ceftazidime. Only one case of Campylobacter jejuni septicaemia occurring post-splenectomy has been reported previously, also in an iron overloaded thalassaemia patient. Unusual Gram negative bacilli must be covered by the chosen antibiotic regimen when splenectomised thalassaemic patients present with high grade fever.
OBJECTIVE: To assess the role of fine needle aspiration cytology (FNAC) in lymphadenopathy in human immunodeficiency virus-infected individuals (HIVII).
STUDY DESIGN: Thirty-nine HIVII presenting with lymphadenopathy at University Hospital, Kuala Lumpur, were subjected to FNAC. Cytologic smears were routinely stained with May-Grünwald-Giemsa stain. Special stains and immunostains were used when necessary.
RESULTS: In nine cases, the cytologic appearance was compatible with HIV type A and in one case with HIV type C lymphadenopathy. In 21 cases, acid-fast bacilli (AFB) were demonstrated in the cytologic smears, enabling a diagnosis of mycobacterial lymphadenitis. In one of these cases there was a concomitant infection with Penicillium marneffei that was overlooked on initial cytologic examination. The cause of granulomatous lymphadenitis could not be ascertained in one case, where neither AFB nor any other organisms were demonstrable. Two cases of histoplasma and one of cryptococcal lymphadenitis were diagnosed, as was one high grade non-Hodgkin's lymphoma that could be immunophenotyped on cytologic material. In three cases the aspirates were inadequate for a cytologic diagnosis.
CONCLUSION: Lymph node FNAC is a valuable investigative modality in HIVII. Most opportunistic infections (bacterial and fungal) can be correctly identified, and high grade lymphoma can be diagnosed and phenotyped.
Clostridium septicum infection has been shown to have a strikingly high association with either bowel or blood malignancies. The infection may be fatal if unrecognised. We report a case of C. septicum bacteremia in a man diagnosed with acute myeloid leukaemia.
Between 1987 to 1995, a total of 334 patients infected with HIV were treated at the Hospital Kuala Lumpur. There were 159 Malays, 108 Chinese, 64 Indians, and 3 from other ethnic groups. Three hundred and twenty-one (96.1%) of these individuals were males and 262 (65.9%) were between the ages of 26-45 years. Intravenous drug users made up 77% (256) of the attributable risk behaviour from the group although many of them also had added risk behaviours like heterosexual activity with multiple partners (50 patients), tattoos (7 patients), homosexual practice (4 patients) and previous transfusions (3 patients). The others acquired their infection through heterosexual promiscuity (59 patients), homo/bisexual activity (7 patients), previous transfusion (5 patients) and tattoos (1 patient). Sixty-six patients (all males) had since progressed to full blown AIDS and 10 have died. The two commonest AIDS-defining events were tuberculosis infection and Pneumocystic carinii pneumonia occurring in 37 (56%) and 15 (22.7%) of patients respectively. Forty-one patients with AIDS presented for the first time with their AIDS-defining infections. The mean CD4 count of the patients when they progressed to AIDS was 130/mm3. The mean time for progression from "known" seropositivity to AIDS was 2.42 years. These results suggest that Malaysians infected with HIV are not coming forward for treatment until they are in the advanced stage of the disease.
A retrospective study of 144 adults with HIV infection was conducted to investigate the prevalence of upper and lower respiratory tract infections (URTIs and LRTIs). The patients were divided into two groups: those with acquired HIV through intravenous drug abuse (IVDA), and those who had acquired HIV through 'other' risk behaviours. LRTIs were more prevalent than URTIs overall, and LRTIs were significantly more common (p < 0.001) in IVDAs than in the other-risk group. Tuberculosis (40%) and bacterial pneumonias (33%) comprised the majority of LRTIs among IVDAs, while Pneumocystis carinii pneumonia (40%) was the commonest LRTI in the other-risk group. Analysis of CD4 T-lymphocyte counts indicated that HIV-seropositive IVDAs are at greater risk of developing chest infections at higher CD4 counts than other-risk patients. The IVDAs were also found to have a much higher rate of co-infection with hepatitis C and B, which may be a factor accelerating the progression from HIV infection to AIDS. The mean time averaged for the two groups from known seroconversion to development of respiratory tract infection is only 1.37 years, which suggests HIV-infected patients are presenting late for treatment in Malaysia.
Nocardiosis is an increasingly recognised opportunistic infection in immunologically incompetent hosts but diagnosis is often delayed. Between December 1975 to October 1988, our two Nephrology Units have encountered five cases of nocardiosis occurring in two post-renal transplant patients, two patients with systemic lupus erythematous (SLE) and one patient with mesangiocapillary glomerulo--nephritis. All were on immunosuppressants at the time. The first three patients presented with predominant pulmonary disease and were cured by combined trimethoprim-sulphamethoxazole (cotrimoxazole) and doxycycline therapy. The patient with limited skin involvement responded to cotrimoxazole alone. However, the last patient with lymphocutaneous disease initially responded to cotrimoxazole (+ chloramphenicol) but developed acute-on-chronic renal failure and relapsed with dose reduction of cotrimoxazole. Alternative treatment with amikacin and doxycycline was instituted with good response. We shall review potential clues that may suggest the diagnosis of nocardiosis and discuss other effective antimicrobial agents.
At the University Hospital, Kuala Lumpur, Malaysia, nine patients with systemic lupus erythematosus (SLE) were treated for Pneumocystis carinii pneumonia (PCP) between January 1987 and December 1988. When they developed PCP all the patients' SLE disease course was active and eight of them were on prednisolone. Four of these eight patients were also receiving cyclophosphamide. Patients who were on more intensive immunosuppressive therapy were found to develop more severe PCP. All the patients except one were treated with high-dose cotrimoxazole. Four patients responded to antipneumocystis treatment and survived, while PCP was responsible for the death of the five non-survivors.
Pneumocystis pneumonia (PCP) and pulmonary tuberculosis infection (PTB) are important opportunistic infections in HIV-infected patients. The diagnosis remains challenging since Pneumocystis jirovecii cannot be cultured, and expectorated-sputum is frequently difficult to obtain. The monoclonal-antibody detection for P. jirovecii from induced sputum is promising in diagnosing PCP. This study determined the percentage of PCP in HIV-infected patients with pulmonary infiltrates at three government hospitals in Jakarta. The concurrent infection of PTB was carefully documented as well. This cross-sectional study was carried out by documenting the clinical symptoms, laboratory findings, chest X-ray, while clinical outcomes were evaluated during hospitalization. The sputum induction was conducted for P. jirovecii with monoclonal antibody detection at the laboratory of Parasitology Department, Faculty of Medicine Universitas Indonesia, as well as Ziehl-Nielsen staining for PTB. The results indicated that of 55 HIV-infected patients with pulmonary infiltrates, the positive monoclonal antibody for P. jirovecii was detected in eight patients (14.6%). Weight loss, fever, shortness of breath, and crackles were found in all PCP patients; while dry cough in five patients. Moreover, PTB cases with positive acid-fast bacilli (AFB) was detected in five patients (9.1%), the PTB cases with negative AFB was 43.6% (24 out of 55 patients), and the rest 26 patients (47.3%) were not proven to have PTB. The concurrent infections of PCP and PTB were documented in three out of five positive AFB patients. The clinical outcome of eight PCP patients showed improvement in five patients, but the other three patients died. Laboratory findings play an important role in the diagnosis of PCP and PTB, along with clinical characteristics and radiological features. Low CD4+ cell count was considered a possible risk factor for PCP and poor clinical outcomes.
Penicillium marneffei is a dimorphic fungus which commonly causes a life threatening systemic fungal infection in an immunocompromised host. It has been recognized as an AIDS defining illness in Malaysia since the beginning of the HIV pandemic. The presence of various non specific clinical presentations, especially the characteristic umbilicated papular rashes with central necrosis which lead to significant ill health in immunocompromised patients should alarm clinicians to the possibility of Penicillium marneffei infection and prompt investigations accordingly. Simple investigations like blood culture and fungal staining of the skin scrapping can confirm the diagnosis in the majority of cases. Early treatment with appropriate systemic antifungal for a definite duration will significantly decrease the mortality rate from penicilliosis.
Aureobasidium pullulans AY4 is an opportunistic pathogen that was isolated from the skin of an immunocompromised patient. We present here the draft genome of strain AY4, which reveals an abundance of genes relevant to bioindustrial applications, including biocontrol and biodegradation. Putative genes responsible for the pathogenicity of strain AY4 were also identified.
A 7-year-old boy, referred with lymphoma, presented with prolonged fever and intra-abdominal lymphadenopathy demonstrated on computed tomography (CT) of the abdomen. Blood culture isolated Penicillium marneffei. The patient was subsequently proven serologically to be positive for human immunodeficiency virus (HIV). Treatment with amphotericin B followed by itraconazole was successful. A high level of clinical suspicion and awareness is necessary for early diagnosis of penicilliosis, especially in an era of an increasing prevalence of HIV in this region.