The interrelation of HIV, cervical human papillomavirus, and neoplasia among antenatal clinic attenders in Tanzania.

OBJECTIVES: To determine the prevalence and interrelation of cervical human papillomavirus (HPV) genotypes, squamous intraepithelial lesions (SIL), HIV, and other reproductive tract infections (RTIs) among urban antenatal clinic attenders in Mwanza, Tanzania. METHODS: Genital swabs were collected from 660 pregnant women and tested for a range of RTIs and for cervical cytology. Cervical HPV-DNA was detected by PCR and genotyped. HIV and syphilis serologies were performed. RESULTS: HPV prevalence was 34% (209/612 women). Of the 144 typeable samples, 83% were high risk (HR-HPV) oncogenic strains (56% HPV 16 related types). SIL was detected in 43 women (7%), with high grade SIL in 3%. There was a high prevalence of HIV (15%), and of any RTI (83%). Genital warts were detected in 20 women (3%). HPV infection was associated with some behavioural factors (short duration of relationship, single status, not using condoms) and gonorrhoea. There was no overall association between HPV and HIV (OR=1.02, 95% CI 0.6-1.6), but a non-significant trend towards a stronger association with HR-HPV in women aged 15-19 (OR=2.79, 95% CI 0.8-9.5) and women aged > or =30 (OR=3.20, 95% CI 0.7-15). SIL was associated with HPV (OR=3.66, 95% CI 1.9-7.0), but not significantly with HIV (OR=1.54, 95% CI 0.7-3.4). Prevalence of SIL was higher among women dually positive for HPV/HIV compared to HPV infection only (21% v 12%), although this difference was not statistically significant (p=0.17). CONCLUSIONS: HPV infection was highly prevalent in this young antenatal population. The association of HIV with HR-HPV types in older women may suggest that the principal HIV/HPV interaction in this population is for HIV to upregulate HPV persistence, leading to subsequent development of SIL.

Effectiveness, impact and cost of syndromic management of sexually transmitted diseases in Tanzania.

PIP: HIV infection continues to occur at high levels in sub-Saharan Africa, with adult prevalence often exceeding 20% in some urban areas. Prevalence is lower, but steadily increasing in rural areas where most Africans still live. Managing STDs is an increasingly recommended HIV prevention strategy, since the results of many epidemiological studies suggest that the presence of STDs may enhance the sexual transmission of HIV. However, in many parts of Africa, no resources exist with which to properly diagnose STDs. The World Health Organization has therefore been promoting the syndromic management of STDs, an approach which provides immediate diagnosis and treatment without expensive and time-consuming laboratory tests. Findings are reported from a study conducted to assess the impact of improved STD services at the primary care level upon the incidence of HIV infection in Mwanza Region, northern Tanzania. 6 rural communities received improved STD case management, while 6 other communities received only the usual STD services. Communities were matched in pairs based upon pre-intervention STD attendance rates and location. Over the course of 2 years, 11,632 STD syndromes were treated in the intervention health units. Observed cure rates were high. At baseline, HIV-1 prevalence rates in the intervention and control communities were 3.8% and 4.4%, respectively. HIV-1 seroconversion was 1.2% over 2 years in the intervention communities and 1.9% in the control communities, corresponding to a 42% decreased risk of seroconversion in the intervention communities after adjusting for age, sex, history of travel, baseline STD prevalence, and male circumcision.^ieng

Validation of a WHO algorithm with risk assessment for the clinical management of vaginal discharge in Mwanza, Tanzania.

OBJECTIVES: (i) To determine the microbial aetiologies of vaginal discharge in STD clinic and antenatal clinic (ANC) attenders; (ii) to evaluate the performance and costs of a new WHO algorithm for the detection of gonococcal and chlamydial infections in women complaining of vaginal discharge and/or genital itching, using a risk assessment. METHODS: Two groups were enrolled: (i) 395 consecutive female patients attending a hospital outpatient clinic complaining of genital discharge or itching; and (ii) 628 consecutive pregnant women reporting at an urban ANC these symptoms. Patients were interviewed by a nurse, who applied the WHO risk score. They were then referred to the study room for interview concerning the same and other risk factors, examined, and sampled for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), and Candida albicans (CA). Sensitivity, specificity, positive predictive value, overtreatment and correct treatment rates, and cost of drugs per true case treated were estimated. RESULTS: The prevalence of NG and/or CT infections was 11.4% and 8% at the STD clinic and the ANC respectively. The most prevalent pathogens were CA (38% at both clinics) and TV (25% at the STD clinic and 34% at the ANC). The sensitivity of the WHO algorithm for NG and/or CT was 62% at the STD clinic and 46% at the ANC, and the specificities were 64% and 84% respectively. The operational feasibility of the method was good. The cost of drugs per true case treated in applying the risk assessment approach was $3.5 among nonpregnant women and $5.0 among pregnant women. This compared favourably with respective costs of $8.8 and $25.0 in applying the syndromic management alone. CONCLUSIONS: The WHO risk assessment algorithm for the diagnosis of NG and/or CT infections among women complaining of genital discharge can considerably reduce overtreatment of NG and/or CT in both pregnant and non-pregnant women, but in this study it failed to identify 38% of non-pregnant and 54% of pregnant women with these infections. The elements of the risk score may need adjustment in different settings.

Risk scores to detect cervical infections in urban antenatal clinic attenders in Mwanza, Tanzania.

BACKGROUND: Detection and management of gonococcal and/or chlamydial infections in women is a challenge, particularly in developing countries where laboratory tests are not always available. The World Health Organisation (WHO) has developed a risk assessment approach to identify cervical infections among women complaining of vaginal discharge. We have evaluated this approach as a screening strategy among women attending an urban antenatal clinic (ANC) in Tanzania. OBJECTIVES: (i) To measure the prevalence of pathogens associated with sexually transmitted diseases (STD) and reproductive tract infections (RTI) in an urban population of ANC attenders in Tanzania; (ii) to examine characteristics of pregnant women associated with cervical infections; and (iii) to evaluate the performance of a WHO risk assessment algorithm and alternative risk scores for the detection of cervical infections in pregnant women. METHODS: A systematic sample of 660 pregnant women reporting for routine antenatal care at an urban clinic was enrolled. Women were interviewed by a nurse, who applied the WHO risk score. They were referred to a study room for interview about sociodemographic and behavioural factors, examination, and sampling for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, and bacterial vaginosis. Sensitivity, specificity, positive predictive value (PPV), and theoretical cost per true case treated were estimated for the diagnosis of cervical infection with N gonorrhoeae and/or C trachomatis for the WHO and other risk scores. RESULTS: The prevalence of any vaginal or cervical infection was 68%. Prevalence rates of various pathogens were: C albicans 39%, T vaginalis 16%, bacterial vaginosis 24%, N gonorrhoeae 2.3%, C trachomatis 5.9%, any cervical infection (N gonorrhoeae and/or C trachomatis) 7.4%. The WHO score identified only five of 49 women with N gonorrhoeae and/or C trachomatis (sensitivity 10.2%). The specificity and the PPV were 92% and 9.8% respectively. The theoretical cost per true case treated on the basis of the WHO score was over $18. Several risk factors were associated with cervical infection on univariate analysis, but only six remained significant at the 10% level after multivariate analysis. These were: never use of contraceptives (OR 3.09), more than one partner in the past 3 months (OR 3.32), partner with symptoms of genital discharge syndrome (GDS) (OR 7.55), frothy vaginal discharge (OR 1.88), 5-19 polymorphonucleocytes per high power field on cervical smear (OR 3.28), or more than 20 polymorphonucleocytes per high power field (OR 16.08), and wet preparation showing evidence of T vaginalis infection (OR 1.96). Scores based on these variables failed to attain high sensitivities or PPVs (all below 40%) although the costs per true case treated were cheaper than for the WHO score. CONCLUSION: Risk assessment for the screening and management of N gonorrhoeae and/or C trachomatis among women presenting at routine antenatal services appears feasible and acceptable, but of limited value in this population because of its low sensitivity. The optimal risk score may vary considerably from one place to another. The quest for simple, cheap, and reliable tests to diagnose N gonorrhoeae and C trachomatis infections still remains a high priority on the international STD technology research agenda.

HIV-associated adult mortality in a rural Tanzanian population.

OBJECTIVE: To measure HIV-associated adult mortality in a rural population in Tanzania. To record the signs and symptoms associated with deaths of HIV-positive adults. DESIGN: Prospective cohort study conducted in the context of a randomized controlled trial to evaluate the impact of a sexually transmitted disease treatment programme. METHODS: A cohort consisting of a random sample of 12501 adults aged 15-54 years was recruited from 12 rural communities in Mwanza region, Tanzania in 1991/1992. Baseline HIV prevalence was 4.0%. The cohort was followed up after 2 years to record mortality according to baseline HIV status. A verbal autopsy questionnaire was administered for each of the deaths reported. RESULTS: A total of 196 deaths were recorded, of which 73 (37%) occurred in HIV-positive individuals. Mortality rates per 1000 person-years were 6.0 in HIV-negatives and 93.5 in HIV-positives. The age-adjusted mortality rate ratio was 15.68 (95% confidence interval, 11.18-21.03). The proportion of adult deaths attributed to HIV infection was 35% overall and 53% in those aged 20-29 years. Verbal autopsies showed that HIV-positive deaths were significantly associated with fever, rash, weight loss, anaemia, cough, chest pain, abdominal pain and headache, but the specificity of individual symptoms was low. The World Health Organization clinical case definition of AIDS was satisfied for only 13 deaths, of which seven were HIV-positive at baseline. Only seven respondents reported that the death was associated with HIV or AIDS. CONCLUSIONS: This study confirms the strong association of HIV infection and mortality in rural Africa, with an annual death rate in adult seropositives of over 9%. In this rural population with a relatively low HIV prevalence of 4%, HIV has increased overall adult mortality by more than 50%. Signs and symptoms associated with HIV deaths were non-specific, and the population seemed largely unaware of the contribution of HIV to mortality, an important obstacle to prevention efforts.

PIP: A cohort of 12,501 adults aged 15-54 years was randomly selected from 12 rural communities in Mwanza region, Tanzania, in 1991-92 and followed for 2 years to assess the contribution of HIV/AIDS to mortality in the region. HIV seroprevalence in the sample was 4% at baseline. 73 of the 196 deaths recorded over the period occurred among HIV-positive individuals. Mortality rates per 1000 person-years were 6.0 among the HIV-seronegative and 93.5 among the HIV-seropositive. The age-adjusted mortality rate ratio was 15.68 overall. 35% of overall mortality was attributed to HIV infection, 53% among those age 20-29 years. Verbal autopsies administered for each death reported showed that HIV-positive deaths were significantly associated with fever, rash, weight loss, anemia, cough, chest pain, abdominal pain, and headache. The specificity of individual symptoms, however, was low. The World Health Organization clinical case definition of AIDS was satisfied for only 13 deaths, of which seven were HIV-positive at baseline. HIV/AIDS was mentioned during the verbal autopsy interview by only seven respondents as being associated with a given death.

Sexual transmission of hepatitis B in Mwanza, Tanzania.

BACKGROUND: Hepatitis B virus (HBV) is endemic and poses a grave public health problem in Africa where it is mainly transmitted from mother to baby or during childhood. Sexual transmission has also been suggested to play a role in East Africa, but this has never been properly demonstrated. Additional preventive strategies may be proposed if sexual transmission of HBV occurred in this region where HIV and other STDs are highly prevalent. GOALS: To determine the prevalence of markers for hepatitis B virus (HBV)and other sexually transmitted diseases (STD) in routine blood samples taken from three populations in Mwanza, Tanzania, and to use the data collected to look at the association between hepatitis B and other STDs, including human immunodeficiency virus (HIV). STUDY DESIGN: Routine blood samples were collected from 1,025 patients attending a clinic for STDs, 253 voluntary blood donors from secondary schools, and 952 blood donors who gave blood in a hospital specifically for a relative who needed a blood transfusion. All samples were tested for HIV by double enzyme-linked immunosorbent assay (ELISA), and for syphilis using the Treponema pallidum hemagglutination (TPHA) and rapid plasma reagin (RPR) tests. Two markers for HBV were examined by the double ELISA method, the presence of the anti-hepatitis B core antigen (anti-HBc) and the hepatitis B surface antigen (HBsAg). RESULTS: There were high prevalences of HBV, syphilis, and HIV in relative donors and STD patients. Although HBV markers were more prevalent in men of increasing ages, syphilis and HIV markers were more prevalent in young women. Evidence of past infection with HBV (presence of anti-HBc) was associated with serologic markers of recent treponemal infection (both TPHA and RPR positive) in both sexes (men odds ratio [OR] = 1.91, P < 0.011; women OR = 2.34, P < 0.02) and with HIV in men (OR = 1.93, P < 0.003). Current infection with HBV (presence of HBsAg) was associated with recent syphilis in men (OR = 2.13, P < 0.006). In STD patients, current infection with HBV was associated with Trichomonas vaginalis in women (OR = 3.57, P < 0.002) and recent syphilis in men (OR = 3.46, P < 0.001). There was no further association between HBV markers and any other STD pathogen or any particular STD syndrome, nor was there any association between current HBV infection and HIV in both sexes. The population attributable fraction for sexual acquisition of hepatitis B is estimated at 7.2% in men and 3.0% in women, based on the association between hepatitis B and syphilis. CONCLUSIONS: These findings suggest that sexual acquisition of hepatitis B occurs at low levels in Mwanza, and that HBV can be prevented through enhancement of the current HIV/STD control activities, in addition to improved vaccination strategies.

PIP: To investigate the role of sexual transmission of hepatitis B virus (HBV) in East Africa, a cross-sectional serosurvey was conducted in 3 populations with potentially divergent exposure to sexually acquired pathogens. Included were 253 voluntary blood donors (predominantly secondary school students), 952 relative blood donors, and 1025 patients with sexually transmitted diseases (STDs) from Mwanza, Tanzania. The overall prevalence of hepatitis B surface antigen (HBsAg)--a measure of current infection--was 9.9% in voluntary donors, 11.2% in relative donors, and 8.1% in STD patients, with a 2.2:1 carrier ratio of men to women. The prevalences of human immunodeficiency virus (HIV), anti-hepatitis B core antigen (anti-HBc), and past or recent syphilis were significantly lower among voluntary donors than in the other 2 groups. Evidence of past infection with HBV (anti-HBc) was associated with recent syphilis in both men and women (odds ratios (ORs), 1.91 and 2.34, respectively) and with HIV in men (OR, 1.93). Current infection with HBV (HBsAg) was associated with recent syphilis in men (OR, 2.13). In STD patients, current HBV was associated with Trichomonas vaginalis in women (OR, 3.57) and recent syphilis in men (OR, 3.46). There was no significant association between HBV and gonorrhea. Based on the association between syphilis and HBV, the population attributable fraction for sexual acquisition of HBV is estimated at 7.2% in men and 3.0% in women. Overall, these findings suggest that the sexual acquisition of HBV occurs at low levels in Mwanza. Improved vaccination strategies, early detection and treatment of syphilis, and programs aimed at reducing HIV transmission should enhance the control of HBV.

Sexual behaviour patterns and other risk factors for HIV infection in rural Tanzania: a case-control study.

OBJECTIVE: To examine the association between HIV infection and patterns of sexual behaviour and other risk factors in a rural Tanzanian population in a case-control study, nested within a randomized trial of improved sexually transmitted disease treatment. METHODS: All HIV-positive patients from the baseline survey of the randomized trial were eligible as cases. Cases (n = 338) and controls (a random sample of one in eight HIV-negative persons; n = 1078) were interviewed about risk factors for HIV infection using a structured questionnaire. RESULTS: A significantly higher HIV prevalence was found among men and women not currently employed in farming [men: odds ratio (OR), 2.08; women: OR, 3.65], women who had travelled (OR, 3.27), educated women (OR, 4.51), and widowed/ divorced people compared with those currently married (men: OR, 3.10; women: OR, 3.54). Two spouse-related factors were significantly associated with HIV, even after adjustment for the sexual behaviour of the index case: HIV was more prevalent in men with younger spouses (P = 0.020 for trend) and in women married to men currently employed in manual work, office work or business (OR, 2.20). In women only, blood transfusions were associated with a higher HIV prevalence (OR, 2.40), but only a small population attributable fraction (4%). There was an increased HIV prevalence associated with increasing numbers of injections. Reported number of lifetime sexual partners was significantly associated with HIV infection (women: OR, 7.33 if > or = 10 lifetime partners compared with < or = 1; men: OR, 4.35 for > or = 50 compared with < or = 1). After adjustment for confounders, male circumcision was associated with a lower HIV prevalence (OR, 0.65; P = 0.11). CONCLUSIONS: In these rural communities, many HIV infections occur through sexual transmission. Some people are at high risk of HIV infection through large numbers of sex partners, whereas some are at risk through their spouse or regular partner. The role of circumcision in HIV transmission is unclear. Commercial sex seems to play a negligible role in HIV transmission in these communities. Our results confirm marked heterogeneity in HIV risk, indicating the scope for risk reduction strategies.

PIP: In a baseline survey a cohort of 12,537 adults was enrolled, interviewed, and examined between November 1991 and December 1992 in the Mwanza Region of Tanzania using random cluster sampling. The study itself took place in May and June of 1993, and it consisted of 338 cases (149 men and 189 women) and 1078 controls (504 men and 574 women). The remainder of the analysis of men was restricted to the 149 cases and 394 controls 20-54 years old. The blood samples from consenting adults were tested for HIV antibodies by enzyme-linked immunosorbent assay (ELISA). A significantly higher HIV prevalence was found among men and women not currently employed in farming (men: odds ratio [OR] 2.08; women: OR 3.65), women who had traveled (OR 3.27), educated women (OR 4.51), and widowed/divorced people compared with those currently married (men: OR 3.10; women: OR 3.54). Two spouse-related factors were significantly associated with HIV even after adjustment for the sexual behavior of the index case: HIV was more prevalent in men with younger spouses (p = 0.020 for trend) and in women married to men currently employed in manual work, office work, or business (OR 2.20). In women only blood transfusions were associated with a 2-fold increased prevalence of HIV (OR 2.40), but only a small population-attributable fraction (4%). There was an increased HIV prevalence associated with increasing numbers of injections, even after adjustment for confounders. The reported number of lifetime sexual partners was significantly associated with HIV infection (women: OR 7.33 if or= 10 lifetime partners compared with or= 1; men: OR 4.35 for or= 50 compared with or= 1). After adjustment for confounders, male circumcision was associated with a lower HIV prevalence (OR 0.65; p = 0.11). Most HIV infections occurred through sexual transmission, although some were attributable to nonsterile injections. Since the large number of sexual partners was a major risk factor, intervention strategies should promote the reduction of partners and the use of condoms.

Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.

A randomised trial was done to evaluate the impact of improved sexually transmitted disease (STD) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania. HIV incidence was compared in six intervention communities and six pair-matched comparison communities. A random cohort of about 1000 adults aged 15-54 years from each community was surveyed at baseline and at follow-up 2 years later. Intervention consisted of establishment of an STD reference clinic, staff training, regular supply of drugs, regular supervisory visits to health facilities, and health education about STDs. 12,537 individuals were recruited. Baseline HIV prevalences were 3.8% and 4.4% in the intervention and comparison communities, respectively. At follow-up, 8845 (71%) of the cohort were seen. Of those initially seronegative, the proportions seroconverting over 2 years were 48 of 4149 (1.2%) in the intervention communities and 82 of 4400 (1.9%) in the comparison communities. HIV incidence was consistently lower in the intervention communities in all six matched pairs. Allowing for the community-randomised design and the effects of confounding factors, the estimated risk ratio was 0.58 (95% CI 0.42-0.79, p = 0.007). No change in reported sexual behaviour was observed in either group. We conclude that improved STD treatment reduced HIV incidence by about 40% in this rural population. This is the first randomised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population.

Antimicrobial susceptibility, auxotype and plasmid content of Neisseria gonorrhoeae in northern Tanzania: emergence of high level plasmid mediated tetracycline resistance.

OBJECTIVE: To study the antimicrobial susceptibility, plasmid content, auxotype and serogroup of strains of Neisseria gonorrhoeae isolated from an urban population of STD clinic attenders in Northern Tanzania. METHODS: The minimum inhibitory concentrations of nine common antimicrobial agents were measured by the agar dilution method against 130 strains of Neisseria gonorrhoeae isolated in a free government STD clinic in Mwanza town. The auxotype, plasmid content and serogroup of these strains were also determined by conventional techniques. RESULTS: 65 strains (50%) were penicillinase producers (PPNG), and 34 (26%) exhibited chromosomally mediated resistance to penicillin. Seven (5%) were sensitive to tetracycline; 78 (60%) showed intermediate levels of resistance, and 45 (35%) had high level plasmid mediated resistance (TRNG), all of which carried a 25.2 MDa plasmid. 79 strains (61%) showed decreased sensitivity to trimethoprim-sulphamethoxazole, and five (4%) were resistant to this agent. All isolates were fully sensitive to spectinomycin, azithromycin, cefotaxime, cefuroxime, norfloxacin and ciprofloxacin. One hundred and one strains (78%) were of type W11/111, 22 type W1, and seven cross reacting strains. The W1 strains were significantly more likely to be carrying plasmid mediated resistance to both penicillin and tetracycline. Six different auxotypes were present, the major type requiring proline. Plasmid profiles showed the presence of both the 3.2 MDa and the 4.4 MDa beta-lactamase encoding plasmids. CONCLUSION: a high proportion of gonococcal isolates remain resistant to penicillin in this region, and most isolates are now also resistant to tetracycline, with the emergence of plasmic mediated tetracycline resistance. Trimethoprim-sulphonamide sensitivity is also decreasing. The population of strains is heterogeneous, and both African and Asian beta-lactamase encoding plasmids are present.

The value of urine specimens in screening for male urethritis and its microbial aetiologies in Tanzania.

OBJECTIVE: To evaluate the first void urine (FVU) specimen in screening for urethritis and its microbial aetiologies in a male African population in which urinary schistosomiasis is also prevalent. PATIENTS AND METHODS: Two hundred and forty eight males aged 15-54 years provided FVU specimens: 55 patients from a clinic for sexually transmitted diseases (STD), 151 patients from a medical outpatient clinic and 42 villagers from an area of high endemicity for S haematobium. Specimens were tested for leucocyte esterase (LE) using a dipstick (Nephur-Test+Leuco, Boehringer-Mannheim France SA). Ova of S haematobium were sought in terminal urine samples from all subjects. For all STD patients, and all medical outpatients with a positive LE test, urine and urethral swabs were tested for Chlamydia trachomatis antigen, and urethral swabs were tested for Neisseria gonorrhoeae by gram stain and isolation. RESULTS: The prevalence of LE positivity was 38/41 in STD patients with urethral signs or symptoms (93%), 5/14 among other STD patients (36%), 21/151 among medical outpatients (15%) and 13/42 among villagers (31%). As a screening test for urethral infection (detection of gonorrhoea or chlamydia and/or > or = 5 polymorphs per high power field on gram stain) the LE test had a sensitivity of 94% and a specificity of 53% among STD patients. Of 24 STD patients with gonococcal or chlamydial infection, 23 had a positive LE test (96%). Among general medical outpatients, 12 of 22 with a positive LE test had either conventionally defined urethritis or gonococcal or chlamydial infection, giving a positive predictive value of 55% for the LE test in this group. Of 18 subjects in all groups with urinary schistosomiasis nine had a positive LE test (50%), although three of these also had gonorrhoea. Chlamydial antigen was detected in the FVU specimen of all six subjects in whom it was detected in a urethral swab, and in an additional three subjects in the outpatient group. CONCLUSIONS: The FVU, which is an easily collected and non-invasive specimen, can provide valuable information on the prevalence of urethritis and on its microbial aetiology among the general male population in African countries.