Opportunistic Infections As Aids-Defining Conditions: Case Study Of Hiv Infected Persons In Eastern Nigeria
aids defining illnesses, immune suppression, opportunistic infections
U Dibua. Opportunistic Infections As Aids-Defining Conditions: Case Study Of Hiv Infected Persons In Eastern Nigeria. The Internet Journal of Epidemiology. 2009 Volume 8 Number 2.
The prevalence of opportunistic infections as WHO’s AIDS defining illnesses was investigated microbiologically in 2199 HIV positive Nigerians using urine, stool, sputa and nasopharyngeal secretions. ANOVA and the Pearson Chi-Square tests were used for data analysis. Frequently isolated gastrointestinal bacterial pathogens included non-typhoidal
Opportunistic infections in HIV/AIDS are the infections, which become clinically apparent due to the weakened immune system of the patient, otherwise they would be unapparent. These constitute the bulk of the conditions included in the 1993-revised CDC AIDS case-definition, for surveillance among person over 13 years of age (CDC, 1994). In this revised case-definition, a person is suspected to have AIDS either when the CD4+ lymphocyte count drops below 200 cells per cubic millimeter (i.e., below 14% of total lymphocyte count) and there is a laboratory confirmation of HIV infection or a diagnosis is made of one of the clinical conditions. Thus, diagnosis of disease such as candidiasis of the esophagus, Cytomegalovirus retinitis, pulmonary tuberculosis or other Mycobacteriosis, Kaposi’s sarcoma, Pneumocystis carinii pneumonia, Toxoplasmosis of the brain, etc., are regarded as indicative of AIDS. These criteria have been employed in HIV/AIDS surveillance in the United States of America (CDC, 1995a).
Opportunistic infections are so prominent in AIDS that they are often the definitive illnesses in both adult and paediatric AIDS. Thus, most of the major and minor signs of the WHO case definition of the disease reflect underlying opportunistic infections. The CDC case definition relies on the accurate diagnosis of opportunistic infections. They tend to occur concomitantly at unusual sites in the body of the patient, and produce abnormal tissue responses in the host, now with altered immunity. Predominance of certain opportunistic infections in one geographical location and not in others has been explained by variations in prevalence and virulence of strains of some organisms coupled with immune interaction or cross-immunity (Lucas, 1990). Hence there are significant differences between opportunistic infections prevalent in Africa and those prevalent in United States of America and Europe (Butungwanayo et al., 1990; Lucas et al., 1991). Among all HIV/AIDS associated infections or diseases, tuberculosis stands prominent as cutting across geographical boundaries. Reason for this may be obvious; it has a worldwide distribution with endemicity in certain areas and cultures (Murray et al., 1990; De Cock et al., 1992).
The CDC outlined certain opportunistic infections in the United States and categorized them as AIDS related-complex (ARC), a categorization connoting them as indicators of damaged immune system (CDC, 1995a). Apparently, these infections coincide with reduction in CD4+ lymphocyte count of the patient to < 100 cells /mm. Diagnosis of some of these opportunistic infections such as Apthous ulcers and bacillary angiomatosis prove somewhat difficult because of their resemblance to other disease conditions (CDC, 1994; AIDSLINE, 1994). Although opportunistic infections have been associated with apparent reduction in CD4+ counts, the critical level of CD4+ count reduction at which these infections may be expected, i.e., the level of immune damage at which these otherwise non-virulent organisms seize the “opportunity” to enter, is not often well defined. For example, Aspergillosis would occur with complications in people with CD4+ cell count of ≤ 100 per ml of blood but has also occurred in people with higher counts (BALA, 1995). Candidiasis occurs at various CD4+ count levels but those with counts < 200 cells/mm seem to be more severely affected (CDC, 1993). The importance of Coccidioidomycosis due to Coccidioides immitis or Cryptococcus neoformans in AIDS-related meningitis cannot be overlooked; nor can that of Cryptosporidium parvum and Isospora belli in AIDS-related diarrhoea (Hing et al., 1992; CDC, 1993; ATN, 1994;).
What opportunistic infections characterize HIV/AIDS in Africa? Unlike the United States and Europe, Africa has no facilities for a clinical case definition based on laboratory testing. In 1986, the WHO established a clinical case definition not requiring laboratory testing for use in Africa (WHO, 1989). The African case definition requires the existence of two major and one minor signs in the absence of known immunosuppression. This is with the exception of two conditions generally considered in themselves to define AIDS, i.e. generalized Kaposi’s sarcoma and generalized Cryptococcus meningitis (Sonnabend et al., 1983; UNAIDS, 1998). It would be noticed that in this WHO case definition, recurrent herpes zoster, oropharyngeal candidiasis and disseminated herpes simplex were the only opportunistic infections included. Its usefulness was tested in Kinshasa, Zaire and it was found to have a sensitivity of 59%, specificity of 90% and a positive predictive value of 74% for HIV infection among hospitalized patients (CDC, 1995b). Matched with the CDC definition in a different study, its sensitivity was 79%, specificity 91% but a low positive predictive value of 30%, (WHO, 1989; CDC, 1995b; Shah, 2002). The positive predictive value of the African case definition is so low that as a surveillance tool for comparisons with AIDS reporting in the developed world, its usefulness is doubtful. The difficulty in undertaking an effective AIDS surveillance in Africa, and in deed Asia remains the limited availability of HIV testing and/or poor diagnostic facilities. Perhaps more investigations into a wider spectrum of opportunistic infections characterizing AIDS disease and the inclusion of the more prevalent ones such as tuberculosis or Mycobacterium avium complex (MAC), may improve the positive predictive value of the above African AIDS case definition provided by the WHO.
It is against this background that the present study was designed to elucidate the possible aetiologic agents incriminated in immune suppression, and the development of AIDS in a sample African community located in the South Eastern Part of Nigeria.
Materials and Methods
The study was carried out in specific locations in Eastern Nigeria, chosen for their peculiarities, and include the 9th-Mile-Corner (Udi Local Government Area), Eha-Alumona (Nsukka Local Government Area), Orba and Obollo-Afor (Udenu Local Government Area). Enugu and Nsukka urban centres were included as reference points for sample populations with no known risk behaviours while the groups in the major locations were selected because of their known HIV/STD risk behaviours. The study population consisted of 2199 HIV positive persons (929 males and 1290 females) in 6 clinics/health centers in the surveyed area.
Ethical consideration: Consent to carry out the study was obtained prior to the commencement from the Administrators, Proprietors or Directors of all health institutions used. Informed consent (without undue influences) was obtained from participants before their inclusion in the project.
Screening For Sexually Transmitted Diseases (STDs)
The screening of syphilitic exudates for spirochetes was carried out by serological screening using the cardiolipin Antigen Test which consisted of Venereal Diseases Reference Laboratory (VDRL) test, and the Rapid Plasma Reagin (RPR) CARD TEST described by Cruickshank (1980) and (Cheesbrough, 1991). Gonococcal infections were investigated using standard procedures described by Cheesbrough (1991). Specific standard techniques were employed for the investigation of non-gonococcal infections. A smear of the pus expressed from the characteristic
Examination of Stool Samples for Occult Blood and Pathogenic Protozoan Infections
Stool samples were first examined macroscopically for colour, odour, consistency, (formed unformed, watery or mucoid) and for presence of blood and worms, and then microscopically for protozoa, fungi or bacteria. Black stools samples were subjected to occult blood tests using the occult blood tablets. Cysts, larva and eggs of parasites were investigated by examination of stool samples in eosin and iodine preparations and by modified Ziehl Neelsen staining for oval Cryptosporidium oocysts Cheesbrough (1991).
Bacterial Cultivation and Identification
Faecal specimens were analysed for the presence of bacterial pathogens following emulsification on Peptone water (Oxoid, CM9), and subsequently seeding on MacConkey agar and the incubated at 37o C for 24h. Lactose fermenters were sub-cultured on Blood agar and incubated at 37o C for 24h, while non-lactose fermenters were cultivated on Salmonella Shigella agar Brilliant Green agar (Modified) Mannitol Salt Agar, Xyline-Lysine (XLD), Butzler, medium, Desoxycholate agar (DCA) and Thiosulphate Citrate Bile Salt (TCBS) according to the standard methods described by Cheesbrough (1991).
Urine microscopy and Culture
Centrifuged midstream urine samples were examined microscopically under X10 and X40 objective for parasites, pus cells, blood cells, yeast cells, epithelial cells and bacteria. Samples containing bacteria (105 ) per ml, were subsequently seeded on Cystine-Lactose-Electrolyte Deficient (CLED) medium and Blood agar and incubated in a Gallenkamp incubator at 37o C for 18-48h. Isolated pathogens of medical importance were identified and characterized according to the methods of Cruickshank, (1980); Cheesbrough, (1991).
Screening of Sputum, Naso-pharyngeal Secretions
Each specimen was examined for appearance: purulent, muco-purulent, cheesy, mucoid or muco-salivary, white coloured, yellow or bloody or bloodstained and then Giemsa stained for sporozoites, trophozoites or cysts of
Screening for Bacterial and Fungal Pathogens of the respiratory tract
Digested sputa and nasopharyngeal secretions were cultivated on MacConkey, Blood, and Chocolate agar to which optochin discs (ethylhydrocuprein hydrochloride) were incorporated, and incubated in a carbon dioxide enriched atmosphere (10% CO2) at 37o C, for 48h, and examined for growth after overnight incubation (Cheesbrough, 1991). Isolates were identified by biochemical tests described by Cheesbrough, (1991). Fungal pathogens of the respiratory tract were screened following digestion of sputa, naso-pharyngeal secretions and high vaginal swabs (HVS) in 5ml of 10% potassium hydroxide solution and subsequent examination on physiological saline and Lactophenol cotton blue for fungal budding cells, hyphae and pseudohyphae. Samples were further Giemsa stained and examined for intracellular yeasts of
Fungal Cultivation and Identification
Sputa, nasopharyngeal secretions and HVS were first inoculated onto Sabouraud Dextrose Agar (SDA) incorporated with chloramphenicol and incubated at both ambient temperature (25-30o C), and at 37o C for 2-7days. Rapidly growing colonies on SDA were examined with a hand lens and further on drops of Lactophenol cotton blue for grayish-green, velvety powdery textured and V-shaped septate hyphal colonies of
Prevalence of Other Opportunistic Infections in HIV Positive Subjects
Gastrointestinal Tract (GIT) Pathogens
Some frequently occurring bacterial pathogens of the GIT were isolated during the study: Non-typhoidal
Protozoan pathogens implicated in chronic diarrheal conditions included
Respiratory Tract Infections
Bacterial Infections of the respiratory tract
The most important respiratory tract bacterial pathogens encountered outside the Acid Fast Bacilli were
Bacterial Pathogens of the Urinary Tract
The bacterial pathogens isolated from the urinary tract specimens included
Prevalence of other opportunistic infections was also observed during the study. These infections occurred possibly as a result of compromised immunity of the subjects. Gastrointestinal disorders resulting from opportunistic infections of the gastrointestinal tract (GIT) were established. Bacterial opportunistic pathogens incriminated in diarrheal diseases among the HIV positive subjects included non-typhoidal
The association of non-tuberculosis
The identified parasitic protozoa outlined in the result include
Among the respiratory tract bacterial organisms isolated during the study included
Evaluation of the opportunistic organisms of the urinary tract (by both urinalysis and urine culture) was aimed at establishing the etiology and pathogenicity of the organism. This was indicated by abnormalities in electrolyte and renal function as well as the effect on HIV progression to AIDS. Urine analysis (Urinalysis), carried out with the Urilastic (Combi 9), served as a major identification parameter in establishing the etiology of urinary tract infection (UTI), as abnormalities in HIV disease were identified. However, it was considered unnecessary during the study to culture normal urine with microbial count less than (104) per ml of urine because these produced no growth after more than 2-3 days of incubation. This was based on the consideration that under normal physiological conditions, the kidneys, urethra and urinary bladder of man remain sterile; hence, the sterility of urine produced as a result of the low pH, the presence of urea, and other metabolites such as uric acid, fatty acids, mucin; enzymes, indican, etc., which are cidal to a wide range of bacteria. In addition, the hypertonic nature of the medulla cannot support many microorganisms. Potential pathogens are equally flushed with urine and mucus about 4-10 times daily, thus ensuring further sterility of the area. However, isolated organisms included
Infection of the urinary tract with
Taken together, this study has demonstrated the involvement of various opportunistic organisms as aetiologic agents in the progression to AIDS in people living with HIV/AIDS in South Eastern Nigeria. In the light of these findings, we strongly proffer that such opportunistic infections should be strongly considered in the development of case definition of HIV/AIDS in Africa.
The author expresses sincere appreciations to all the hospitals and clinics where this Ph. D research was carried out. Sincere thanks also to those individuals whose encouragement and kind suggestions were of immense help in the execution of the research.