Etiology and risk factors of meningitis in patients admitted at a Central Hospital in Harare.

Objective: To determine etiology and risk factors of meningitis in patients admitted a tertiary referral Hospital in Harare. Design: Cross-Sectional Study. Setting: Urban Referral Health Facility. Subjects: Patients suspected of having Meningitis admitted at Parirenyatwa Hospital were consecutively consented and recruited into the study until sample size accrual. Main Outcome Measures: Prevalence of pathogens associated with Meningitis. Risk factors of meningitis. Results: Two Hundred and Ninety Six (296) clinically suspected meningitis patients were recruited into the study, 51.7 %( n=115) were male. Meningitis was confirmed in 20.6% (n=61) cases with the following pathogen proportions, C. neoformans - 45.9 %( n=28), S. pneumoniae ­ 27.9 % (n=17), TBM ­ 4.9 %( n=3), probable viral meningitis ­ 6.6% (n=4 and other bacteria- 14.8% (n=9). Patients from crowded households were also more likely to suffer from meningitis than those from sparsely populated households (p<0.001). Conclusion: The use of Latex agglutination increases the proportion of detected pathogens both fungal and bacterial when used in conjunction with CSF gram stain and culture. Cryptococcus neoformans and S. pneumoniae are the leading causes of meningitis in patients admitted at Parirenyatwa Hospital.

Optimization of the oligonucleotide ligation assay for the detection of nevirapine resistance mutations in Zimbabwean Human Immunodeficiency Virus type-1 subtype C.

An oligonucleotide ligation assay (OLA) designed to detect Human Immunodeficiency Virus type-1 (HIV)-drug-resistance to the nevirapine (NVP) selected mutations K103N, Y181C, V106M and G190A was used to evaluate 200 archived dried blood spots (DBS) from infected infants participating in the Zimbabwean Early Infant Diagnosis (EID) Program. Consensus sequencing of specimens with indeterminate OLA results was performed to identify genetic sequence polymorphisms that appeared to compromise performance of the OLA. When consistent patterns of polymorphisms were observed the probes were redesigned, and DBS specimens with indeterminate OLA results were retested with the new Zimbabwe-specific (ZW) probes. OLA results obtained in Zimbabwe were compared to repeat testing in a US reference laboratory. 188/200 (94%) DBS yielded polymerase chain reaction (PCR) amplification of HIV pol. ZW probes reduced indeterminate OLA results from 5.2% to 2.8% of codons evaluated (p=0.02), with 98.2% concordance between results obtained in the Zimbabwean and US laboratories. Optimization of OLA probes to accommodate polymorphisms in regional HIV variants improved OLA performance, and comparison to the USA results showed successful implementation of the OLA in Zimbabwe for detection of NVP resistance mutations in DBS specimens.

The effects of genital schistosoma haematobium on human papillomavirus and the development of cervical neoplasia after five years in a Zimbabwean population.

BACKGROUND: High-risk human papillomavirus (HPV) is responsible for cervical cancer and genital Schistosoma haematobium infection has been hypothesized to be an additional co-factor or even an independent risk factor for cervical neoplasia. The present study aimed to investigate the impact of schistosomiasis on HPV persistence and development of cell atypia in a group of rural Zimbabwean women with confirmed high-risk HPV. METHODS: A five-year follow-up was done among women previously included in a study on genital schistosomiasis. Women who had high-risk HPV at baseline were invited after 5 years for examination of cell atypia, genital schistosomiasis, and high-risk HPV. Both vaginal lavage samples (low-cost) and cervix brush samples (high-cost) were obtained for further analysis. RESULTS: Thirty-seven women were re-examined. Genital Schistosoma haematobium of a minimum of five years' duration was associated with the development high-grade squamous intraepithelial neoplasia, but not with persistent high-risk HPV. There was a high concordance between the brush and vaginal lavage (96.3% agreement, kappa 0.93); however, the number of beta-globin negative vaginal lavage samples was unacceptably high. CONCLUSIONS: Findings warrant an exploration in a larger longitudinal study where a vaginal swab should be explored.

Human immunodeficiency virus, smoking and self-rated health in Harare, Zimbabwe.

SETTING: Twenty-two urban factories in Harare. OBJECTIVE: To determine the relationship between the human immunodeficiency virus (HIV), smoking and self-rated health in a high HIV prevalence urban workforce. DESIGN: Cross-sectional survey. RESULTS: Of 7482 employees, 6111 (82%) consented to interview and anonymous HIV serology; 88% were male; median age was 34 years. HIV prevalence was 19%. Current (median 6 cigarettes per day) and former smoking were reported by 17% and 7%, respectively. Smoking (current or former) was more common among HIV-positive (27%) than -negative participants (17%; P < 0.001). Factors significantly associated with being a smoker on multivariate analysis were being HIV-infected (OR 1.5, 95% CI 1.4-1.7), older age (P < 0.001), non-Christian (OR 1.6, 95% CI 1.2-2.2) and manual job (OR 1.4, 95% CI 1.2-1.6). Women (OR 0.05, 95% CI 0.03-0.11) and the better educated (OR 0.7, 95% CI 0.5-0.9) were significantly less likely to smoke. HIV-positive smokers had the highest risk of reporting poor health (adjusted OR compared to HIV-negative non-smokers 3.4, 95% CI 2.3-5.0). CONCLUSIONS: Smoking was significantly more common among HIV-positive than -negative employees in this predominantly male workforce. There was evidence of a combined effect on self-rated poor health, a variable shown to be a strong independent predictor of mortality in industrialised countries. Interventions to encourage smoking cessation may be an important component of HIV care in Southern Africa.

Asymptomatic bacteriuria among outpatients with diabetes mellitus in an urban black population.

OBJECTIVE: To determine the prevalence of asymptomatic bacteriuria (ASB) in individuals afflicted by Diabetes mellitus; the antibiotic susceptibility of the microbial isolates and the association of host factors with ASB. DESIGN: This was a prospective cross sectional study. SETTING: Attendants of outpatient polyclinics at three main tertiary hospitals; namely, Harare, Chitungwiza and Parirenyatwa Hospitals. SUBJECTS: 176 participants. MAIN OUTCOME MEASURES: Patients attending the polyclinics between 6.30 am and 9.30 am from Monday to Friday were randomly selected. Demographic data was obtained at enrollment using a standardized questionnaire. Fasting venous blood was withdrawn from the participants for glucose analysis. Clean-catch midstream urine samples from all men and women were cultured and the causal organisms were isolated and identified by standard microbiological methods. Antibiotic susceptibility testing was performed using a disc diffusion method. Potential host factors included age, type of diabetes, duration of diabetes, glucosuria and leukocyturia. RESULTS: The prevalence of ASB was 32% in the diabetics and 11% in nondiabetic participants. The commonest bacterial organism isolated in participants afflicted by Diabetes mellitus was Escherichia coli (26%) followed by Staphylococcus aureus (21%), Streptococcus group B (14%), Streptococcus group D and non-lactose fermenting coliforms (7% respectively). Other isolates were Micrococcus and Pseudomonas (5% respectively), Klebsiella and Proteus (2% respectively). Gentamicin, nitrofurantoin, ampicillin and nicene were the most effective antimicrobials in the majority of isolates. Certain isolates exhibited some bacterial resistance to conventional antibiotics. Of the host factors, an association was found between bacteriuria and glucosuria (p < 0.001) and between leukocyturia and bacteriuria (p = 0.005). CONCLUSION: The prevalence of ASB is increased in diabetes and the rather high blood glucose levels exhibited by these individuals may further complicate this condition. As some bacterial species exhibited resistance to some common antimicrobials, these results raise questions regarding future clinical reliability of some conventional antimicrobials when considering therapy for asymptomatic bacteriuria.

The prevalence of Herpes simplex virus type-2 infection in blood donors in Harare, Zimbabwe.

OBJECTIVE: To determine the prevalence of HSV-2 infections in a population of blood donors. DESIGN: Cross sectional study. SETTING: Harare Blood Transfusion Service (BTS) Centre. SUBJECTS: 314 serum specimens of voluntary blood donors. MAIN OUTCOME MEASURES: HSV-2 sero-prevalence. RESULTS: The median age (Q1, Q3) of the blood donors was 18 (17,27) years and 65% of them were males. HSV-2 infection was detected in 29 (9.7%) of the 299 specimens that were analyzed. There was a strong association between age of blood donors and HSV-2 seropositivity (p < 0.001). Older blood donors tended to be positive while younger donors tended to be negative for HSV-2 antibodies. Though not as strong, there was also an association between HSV-2 and HIV seropositivity (p = 0.048). CONCLUSION: The prevalence of HSV-2 infections in blood donors in Harare is high, considering the nature of the population studied. Therefore, the testing for HSV-2 in the serum of prospective blood donors should be included in the screening profiles used at the BTS centre in Harare, Zimbabwe to improve blood and blood products.

Enzyme immunoassay for urogenital trichomoniasis as a marker of unsafe sexual behaviour.

Enzyme immunoassay (EIA) was used to detect antibodies to Trichomonas vaginalis in sera from Zimbabwe. The EIA showed a sensitivity of 95 and 94% when compared with vaginal swab culture among women attending a family planning clinic (FPC) and female commercial sex workers (CSW) respectively. The specificity was 85 and 77% in the two groups. Culture-negative FPC women were sub-divided into high risk or low risk of exposure to trichomoniasis. The seroprevalence was 10% (6/61) among low risk women, 21% (10/48) among high risk women and 23% (9/39) among culture negative CSW. The EIA was positive in 46% (18/39) men with genital discharge but only 5% (2/37) healthy blood donors. None of 31 sera from prepubescent children was positive. The EIA may be useful for community surveys of trichomoniasis. Because T. vaginalis is a common sexually transmitted disease, the test may indicate behaviour that increases the risk of STD transmission.

Fatal Pneumocystis carinii pneumonia in HIV-seropositive infants in Harare, Zimbabwe.

Lung biopsies taken post mortem from 24 HIV-seropositive children who died of pneumonia in Harare Hospital (Zimbabwe) during 1995 were examined for pathogens using histology, culture, microscopy and polymerase chain reaction (PCR). Pneumocystis carinii was detected in 16 (67%) children, in 5 of whom bacterial pathogens were also detected. There were 2 cases of cytomegalovirus infection. On the basis of histology and PCR, none of the children had tuberculosis. These data add to the evidence that P. carinii pneumonia may be a significant cause of death in HIV-infected children in southern Africa. Policies on treatment for severe pneumonia, and on prophylaxis for children born to HIV-seropositive mothers need to be re-examined.

Relationship of human herpesvirus 8 peripheral blood virus load and Kaposi's sarcoma clinical stage.

OBJECTIVE: To determine the relationship between human herpesvirus 8 (HHV-8 or Kaposi's sarcoma-associated herpesvirus) peripheral blood virus load and Kaposi's sarcoma (KS) clinical stage. DESIGN: Blinded, cross-sectional analysis of peripheral blood HHV-8 DNA levels in persons with AIDS-related KS in Harare, Zimbabwe. METHODS: Subjects were stratified by KS clinical stage. The amount of HHV-8 DNA in plasma and peripheral blood mononuclear cells (PBMC) was determined by quantitative real-time PCR amplification of the HHV-8 open reading frame 26. RESULTS: Thirty-one HIV-1/HHV-8-coinfected persons were studied: 26 subjects had histologically confirmed KS (one stage II, 11 stage III and 14 stage IV) and five subjects had antibodies to HHV-8 but did not have KS. The age, CD4 lymphocyte count and plasma HIV-1 RNA levels were similar in all groups. HHV-8 DNA was detected in the plasma of all HHV-8-infected subjects (range < 2.4 to 5.2 log10 copies/ml), but plasma HHV-8 DNA levels were not associated with KS disease stage. In contrast, the amount of HHV-8 DNA in PBMC (range < 0.7 to 4.5 log10 copies/microg) was strongly associated with KS clinical stage (P = 0.005). Among stage IV KS cases, there was a linear relationship between plasma and PBMC HHV-8 DNA levels (r2 = 0.42; P = 0.01). CONCLUSION: The strong association observed between the extent of KS disease and the levels of HHV-8 DNA in PBMC provides further evidence for a relationship between HHV-8 virus load and KS pathogenesis.

Effect of intravaginal practices on the vaginal and cervical mucosa of Zimbabwean women.

OBJECTIVES: Lesions on the vaginal and cervical mucosa may facilitate transmission of HIV and other sexually transmitted diseases (STDs). We evaluated the relationship between intravaginal practices and the presence of colposcopic lesions in Zimbabwean women. METHODS: Users and nonusers of intravaginal practices were seen at enrollment, and at 1 and 6 months. Interviewing, counseling, and pelvic and colposcopic examinations were performed at each study visit. Specimens were collected at enrollment and 6 months. RESULTS: Colposcopic lesions were found at least once in 83% of the participants (n = 162), and in 66% of all exams (n = 430). Most lesions were classified as related to infection with human Papillomavirus (HPV) (58%) or another pathogen (20%), but 11% of lesions could have been caused by intravaginal practices (signal lesions). Intravaginal practices were not associated with an increased incidence in signal lesions (95 and 124 lesions per 100 person-years of follow-up for users and nonusers respectively; p = .290), nor with the presence of signal lesions in multivariate baseline (odds ratio [OR], 1.32; 95% confidence interval [CI], 0.37-4.72; p = .666) and six month transition models (OR, 1.67; 95% CI, 0.59-4.70; p = .333). CONCLUSIONS: No associations between intravaginal practices and colposcopic lesions were found in this study. However, the potential effect of intravaginal practices on the cervical and vaginal mucosa, and on subsequent HIV and STD transmission, warrants further study. The usefulness of colposcopy as a research tool in areas with high prevalences of HIV and HPV is questioned.

Detection of Kaposi's sarcoma-associated herpesvirus in oral and genital secretions of Zimbabwean women.

Kaposi's sarcoma-associated herpesvirus (KSHV) in oral and genital secretions of women may be involved in horizontal and vertical transmission in endemic regions. Nested polymerase chain reaction assays were used to detect KSHV DNA sequences in one-third of oral, vaginal, and cervical specimens and in 42% of peripheral blood mononuclear cell (PBMC) specimens collected from 41 women infected with human immunodeficiency virus type 1 who had Kaposi's sarcoma (KS). KSHV DNA was not detected in specimens from 100 women without KS, 9 of whom were seropositive for KSHV. A positive association was observed between KSHV DNA detection in oral and genital mucosa, neither of which was associated with KSHV DNA detection in PBMC. These data suggest that KSHV replicates in preferred anatomic sites at levels independent of PBMC viremia. Detection of genital-tract KSHV only among relatively immunosuppressed women may provide an explanation for infrequent perinatal transmission of KSHV.

Intravaginal practices, vaginal flora disturbances, and acquisition of sexually transmitted diseases in Zimbabwean women.

One hundred sixty-nine Zimbabwean women were studied to determine whether the use of intravaginal practices (cleaning with the fingers, wiping the vagina, and inserting traditional substances) are associated with disturbances of vaginal flora and acquisition of sexually transmitted diseases (STDs). Subjects were interviewed and received counseling and a pelvic examination at enrollment, 1 month, and 6 months, and vaginal specimens were collected at enrollment and at 6 months. Users were more likely than nonusers to have vaginal flora disturbances but were not more likely to acquire an STD (relative risk [RR], 2.15; P=.188). Certain vaginal flora disturbances were associated with increased STD incidence and HIV prevalence. The absence of lactobacilli from the vaginal flora was associated with being positive for human immunodeficiency virus in baseline (odds ratio [OR], 0.24; P=.001) and 6-month transition multivariate models (OR, 0.39; P=.025). The presence of clue cells at baseline was associated with a higher incidence of STDs (RR, 1. 94; P=.025).

Chlamydia trachomatis in symptomatic and asymptomatic men: detection in urine by enzyme immunoassay.

BACKGROUND: Infection with Chlamydia trachomatis is known to be a common cause of urethritis and cervicitis. The standard methods of detection require the collection of intra-urethral and/or cervical swabs, which may be submitted for culture, antigen detection or nucleic acid amplification. The collection of swabs is suitable only within the context of a health care facility. Recent reports have indicated that antigen detection can be used with urine specimens, and because these can be self-collected, this may be particularly useful for the detection of asymptomatic carriage. OBJECTIVE: To determine the sensitivity and specificity of urine antigen assays in the detection of chlamydial infection in men. SETTING: Two groups of men were investigated; men with urethritis attending clinics or private practitioners, and healthy adult men enrolled into either urban or rural HIV prevention projects. METHODS: Urine samples from men in both groups were collected and assayed for the presence of chlamydial antigen using a commercial enzyme immunoassay (EIA) kit. For symptomatic men an intra-urethral swab was also collected and assayed for antigen detection using a commercial EIA. For asymptomatic men, a ligase chain reaction was carried out on the same urine sample. RESULTS: The prevalence of chlamydial antigen in symptomatic men was 15% (39/257), and in asymptomatic men was 4% (15/349). The sensitivity and specificity of urine EIA for symptomatic men was 87% and 83% respectively. For asymptomatic men, the sensitivity of urine EIA was 86%, and the specificity was 100%. CONCLUSION: Urine EIA is a relatively inexpensive method for the detection of chlamydial infections in men. The true specificity in symptomatic men may be higher, as the "gold standard" that we used may give false negative results. Antigen EIA for examination of urine specimens from community surveys of asymptomatic men may be particularly useful because of the low cost of assays, and because urine samples can be self-collected without discomfort to study subjects. The prevalence of C. trachomatis that we describe here is consistent with other studies of chlamydial epidemiology in Zimbabwe.

Antibiotic sensitivity and plasmid profiles of Pseudomonas aeruginosa.

OBJECTIVE: To determine the susceptibility of Pseudomonas aeruginosa to commonly used antibiotics and to study the relationship between antibiotic resistance and the plasmid profiles of the organism. DESIGN: Cross sectional study SETTING: Samples of burns, wound pus, urine, blood, sputum, stool and aspirates were obtained from Harare Hospital (n = 120) and Parirenyatwa Hospital(n = 80). SUBJECTS: Male and female patients either admitted or attending clinics. MAIN OUTCOME MEASURES: P. aeruginosa isolates obtained were resistant to commonly used antibiotics in this environment. The resistance may be plasmid-dependent. RESULTS: P. aeruginosa is prevalent in burns (76.7%) and wounds (67.5%) and in their respective hospital wards. The isolates of P. aeruginosa were resistant to gentamicin (65.5%); carbenicillin (61.9); polymyxinb (53.0%); ciprofloxacin (61.1%) and ceftriazone (70.8%); but showed high sensitivity to tazocin (89.4%) and nalidixic acid (59.3%) and cotrimoxazole (54.9%). All the isolates resistant to the antibiotics tested possessed plasmid DNA. Strains with four plasmids of molecular weight of approximately, 1.5 x 10(6), 1.8 x 10(6), 2.9 x 10(6) and 7.4 x 10(6) Da showed multiple resistance to the drugs that were tested. CONCLUSION: This study reveals an emergence of multiple antibiotic-resistant strains of P. aeruginosa. The traditional drugs gentamicin, carbenicillin, ciproflaxacin, and polymyxin-b used for treatment of P. aeruginosa infections may no longer be reliable. Therefore, a newer drug such as tazocin and other rarely used drugs such as nalidixic acid should be considered for P. aeruginosa antibiotic therapy.

Prevalence and incidence of herpes simplex virus type 2 infection among male Zimbabwean factory workers.

Stored sera from a cohort of 2397 male factory workers in Harare, Zimbabwe, were screened for herpes simplex virus type 2 (HSV-2)-specific antibodies, to estimate the prevalence and incidence of genital herpes infection and to assess the relation between HSV-2 and human immunodeficiency virus (HIV) acquisition. The prevalence of HSV-2 at enrollment was 39.8%. Correlates of HSV-2 seropositivity were HIV seropositivity, marital status, history of sexually transmitted disease (STD), older age, and higher income. The incidence of HSV-2 seroconversion during follow-up was 6.2/100 person-years. Correlates of HSV-2 seroconversion were enrollment while HIV-positive or seroconversion during follow-up, reported genital ulcer, history of STD, and number of sex partners. No evidence was found that HSV-2 infection was more likely to precede HIV or vice versa. HSV-2 and HIV seropositivity are strong markers for high-risk sexual behavior. Improved interventions targeted to populations in which the incidence of either viral infection is high are needed.

Risk factors for gonococcal and chlamydial cervical infection in pregnant and non-pregnant women in Zimbabwe.

OBJECTIVE: To identify demographic, behavioural and clinical characteristics of symptomatic and asymptomatic women with gonococcal and/or chlamydial cervicitis a study was conducted among women attending antenatal clinics and primary care clinics in Harare, Zimbabwe. DESIGN: Cross sectional study. SETTING: Primary care clinics and antenatal clinics in Harare. SUBJECTS: 467 women with vaginal discharge and 1,189 asymptomatic pregnant women. MAIN OUTCOME MEASURES: Behavioural and clinical correlates of gonococcal and chlamydial cervical infection. RESULTS: The mean age of symptomatic women was 26.11 +/- 6.84 years (range: 15 to 52 years) and that of asymptomatic pregnant women was 24.67 +/- 5.43 years (range: 15 to 45 years). Gonococcal and/or chlamydial cervical infection was found in 69 of 1,189 (5.8%) pregnant women and in 77 of 467 (16.5%) non-pregnant women. Logistic regression analysis identified the following predictors of gonococcal or chlamydial infection in women with vaginal discharge: being separated from the partner for a month or more (p = 0.002), having had sex with a new partner in the last three months (p = 0.002), current use of condoms (p = 0.011), and the finding on examination of a purulent vaginal discharge (p = 0.004). Amongst these women an increasing educational level was inversely associated with cervical infection (p = 0.007). Amongst asymptomatic pregnant women the following were identified as predictors of cervical infection: the patient admitting to having a vaginal discharge on direct questioning (p = 0.004), and the finding of a purulent vaginal discharge on examination (p = 0.001). CONCLUSIONS: Amongst symptomatic and asymptomatic women certain behavioural factors and some clinical findings are associated with cervical gonococcal or chlamydial infection. Women with multiple partners and with partners who are currently using condoms with them and those women with a purulent vaginal discharge are likely to be infected. The age and marital status of subjects was not associated with cervical infection. These findings are useful in providing appropriate care for women with overt or minimal symptoms.

Syphilis serology and HIV infection in Harare, Zimbabwe.

OBJECTIVE: To determine the reliability of serological tests in detecting syphilis in a factory worker cohort and examine the impact of concurrent HIV infection on serological tests for syphilis. METHOD: Reactions to non-treponemal and treponemal antigens were tested using sera from a cohort of 3401 factory workers in Harare, Zimbabwe. The participants consented to regular testing for syphilis, by VDRL, and HIV using two ELISAs. All sera from men who were VDRL positive, and a random sample of VDRL negative sera, were tested by RPR, TPHA, and where appropriate FTA-Abs. From the results, men were defined as having no syphilis, active syphilis, incident syphilis, historic syphilis, or giving biological false positive reactions. RESULTS: 709 sera were examined from 580 men. There were 78 cases of active syphilis in the cohort, giving a prevalence of 2.3%, and the seroincidence was 0.25 per 100 person years of follow up. The prevalence of HIV in the cohort was 19.8%. There was a strong association between syphilis, whether active, incident or historic, and HIV seropositivity. With both HIV positive and negative sera the negative predictive values of VDRL and RPR were > 99.9% while the positive predictive value for VDRL (30%) was lower than for RPR (39%). Biological false positive reactions were detected in 0.5% of the cohort, with in most cases a transient rise in VDRL titres up to < 1/16. Higher false positive titres occurred in five men, each of whom was HIV positive. CONCLUSIONS: The VDRL is reliable in detecting possible cases of syphilis even in a community with a high prevalence of heterosexually transmitted HIV. There is need, however, for confirmatory tests. The prevalence of syphilis in this cohort is very low in comparison with other countries in southern Africa, but is consistent with recent data from Harare. Despite a strong association between syphilis and HIV it was clear that syphilis could not be counted as a major factor fueling the HIV epidemic in Zimbabwe.