Clinics In Harare Research Articles

Evaluation of “Cyscope”, a novel fluorescence-based microscopy technique for the detection of malaria

This study was designed to compare the detection of malaria parasites in peripheral blood smears using the Cyscope malaria rapid fluorescent microscopic technique and light microscopy of Giemsa-stained smears. A total of 295 blood smears were collected from patients of all age groups presenting with clinical signs and symptoms of malaria to 10 City Health Clinics in Harare. For each patient two blood films were prepared. Microscopic examination was done independently in two laboratories, with one performing the Giemsa stain and the other the Cyscope method. After the tests were completed, the results were then matched and recorded without any alterations. An equal number of men and women were malaria positive and their ages ranged from five to 66 years. Concordance in the detection of parasites (positive or negative) was 98.6% (291/295). In all four cases of discordance, malaria parasites were detected using the Cyscope but not with conventional microscopy. The Cyscope gave a 100% sensitivity and a specificity of 98.6%. The Cyscope may be a valuable addition to diagnostics of malaria in resource-limited settings such as Zimbabwe.

Neurodevelopmental impairment among infants born to mothers infected with human immunodeficiency virus and uninfected mothers from three peri-urban primary care clinics in Harare, Zimbabwe

The aim of this article is to document the risk of neurodevelopmental impairment (NDI) among infants enrolled in a programme for the prevention of mother-to-child transmission of HIV (human immunodeficiency virus) in Zimbabwe using the Bayley Infant Neurodevelopmental Screener (BINS). We prospectively followed up infants at three primary care clinics in Harare, Zimbabwe. Neurodevelopmental assessments using the BINS were conducted during the first 12 months of life. NDI risk category and associated risk factors were examined. Of the 598 infants assessed, 305 (51%) were female and 293 (49%) were male. Sixty-five infants (11%) were infected with HIV, 188 (31%) were exposed but uninfected, 287 (48%) were unexposed, and 58 (10%) were of unknown status. The prevalence of a high risk of NDI was 9.4% (95% confidence interval [CI] 7.1-11.1%): 9.2% in males and 9.6% in females. Of the 598 infants, 549 (92%) had ever been breastfed, 49% of whom had mothers infected with HIV. The risk of NDI was higher among infants infected early with HIV, i.e. by 3 months of age (p value <0.001). The NDI high-risk category included twice as many infants infected with HIV as uninfected infants (odds ratio [OR] 2.1; 95% CI 1.0-4.3). After adjusting for other factors, head circumference and family financial subsistence remained risk factors for NDI with an OR of 2.22 (1.04-4.82) and 2.55 (1.02-6.36) respectively. The background prevalence of high-risk NDI category of 9.4% across groups seems high but is similar to that reported previously in developing countries. Integration of an early infant neurodevelopmental screening programme into child HIV management protocols will assist in the early referral of children exposed to HIV.

A primary care level algorithm for identifying HIV‐infected adolescents in populations at high risk through mother‐to‐child transmission

ObjectiveTo present an algorithm for primary-care health workers for identifying HIV-infected adolescents in populations at high risk through mother-to-child transmission.MethodsFive hundred and six adolescent (10–18 years) attendees to two primary care clinics in Harare, Zimbabwe, were recruited. A randomly extracted ‘training’ data set (n = 251) was used to generate an algorithm using variables identified as associated with HIV through multivariable logistic regression. Performance characteristics of the algorithm were evaluated in the remaining (‘test’) records (n = 255) at different HIV prevalence rates.ResultsHIV prevalence was 17%, and infection was independently associated with client-reported orphanhood, past hospitalization, skin problems, presenting with sexually transmitted infection and poor functional ability. Classifying adolescents as requiring HIV testing if they reported >1 of these five criteria had 74% sensitivity and 80% specificity for HIV, with the algorithm correctly predicting the HIV status of 79% of participants. In low-HIV-prevalence settings (<2%), the algorithm would have a high negative predictive value (≥99.5%) and result in an estimated 60% decrease in the number of people needing to test to identify one HIV-infected individual, compared with universal testing.ConclusionsOur simple algorithm can identify which individuals are likely to be HIV infected with sufficient accuracy to provide a screening tool for use in settings not already implementing universal testing policies among this age-group, for example immigrants to low-HIV-prevalence countries.

Ferroportin ( SLC40A1) Q248H mutation is associated with lower circulating plasma tumor necrosis factor-α and macrophage migration inhibitory factor concentrations in African children

Background Iron deficiency and the Q248H mutation in the gene, SLC40A1, that encodes for the cellular iron exporter, ferroportin, are both common in African children. The iron status of macrophages influences the pro-inflammatory response of these cells. We hypothesized that Q248H mutation may modify the inflammatory response by influencing iron levels within macrophages. Methods The Q248H mutation and circulating concentrations of ferritin, C-reactive protein and selected pro-inflammatory cytokines (interleukin-12, interferon-γ, TNF-α, and macrophage migration inhibitory factor) and anti-inflammatory cytokines (interleukin-4 and interleukin-10) were measured in 69 pre-school children recruited from well-child clinics in Harare, Zimbabwe. Results In multivariate analysis, both ferroportin Q248H and ferritin < 10 ug/L were associated with significantly lower circulating concentrations of tumor necrosis factor-α. Ferroportin Q248H but not low iron stores was associated with lower circulating macrophage migration inhibitory factor as well. Anti-inflammatory cytokine levels were not significantly associated with either ferroportin Q248H or iron status. Conclusions Ferroportin Q248H and low iron stores are both associated with lower circulating tumor necrosis factor-α, while only ferroportin Q248H is associated with lower circulating macrophage migration inhibitory factor. Whether the reduced production of tumor necrosis factor-α observed in ferroportin Q248H heterozygotes may be of significance in anemia of chronic disease is yet to be determined.

High prevalence of the CYP2B6 516G→T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe

The study sought to investigate the relationship between efavirenz exposure and the CYP2B6 516G-->T(*6) genotype in HIV/AIDS outpatients, using pharmacokinetic modelling and simulation. Blood samples where obtained from 74 outpatients treated with a combination regimen including 600 mg efavirenz daily for a duration of at least 3 weeks at clinics in Harare, Zimbabwe. The subjects were genotyped for the major CYP2B6 variant, CYP2B6*6, associated with reduced enzyme activity, using a PCR-RFLP method. Efavirenz plasma concentrations were determined by HPLC-UV. Population pharmacokinetic modelling and simulation of the data were performed in NONMEM VI. A high allele frequency of the CYP2B6*6 allele of 49% was observed. Efavirenz plasma concentrations were above 4 mg/L in 50% of the patients. Genotype and sex were identified as predictive covariates of efavirenz disposition. Pharmacokinetic parameter estimates indicate that a dose reduction to 400 mg efavirenz per day is possible in patients homozygous for the CYP2B6*6 genotype without compromising therapeutic efficacy. The CYP2B6*6 allele occurs at a high frequency in people of African origin and is associated with high efavirenz concentrations. Simulations indicate that an a priori 35% dose reduction in homozygous CYP2B6*6 patients would maintain drug exposure within the therapeutic range in this group of patients. Our preliminary results suggest the conduct of a prospective clinical dose optimization study to evaluate the utility of genotype-driven dose adjustment in this population.

Altered Immune Response in Severe Malaria Anemia in Children.

We prospectively assessed immune markers in children <6 years with severe malarial anemia (hemoglobin <5.0 g/dL; n = 72) and uncomplicated malaria (n = 69) who presented to Macha Mission Hospital in Zambia's Southern Province. We also studied 70 children <6 years who presented to well child clinics in Harare, Zimbabwe as controls. Compared to controls, children with uncomplicated malaria had significantly higher temperatures and parasite counts, lower hemoglobin and platelet concentrations, higher plasma levels of interferon-gamma, tumor necrosis factor alpha, and interleukin 10 and lower levels of monocyte inhibitory factor (MIF). Compared to uncomplicated malaria, severe malaria anemia was associated with younger age, longer duration of fever and lower temperature on admission. Reticulocyte index and serum concentrations of bilirubin and LDH did not differ between the malaria groups, suggesting that unusually severe extra- or intra-medullary hemolysis did not explain the severe anemia. Higher white blood cell and platelet counts in the severe malaria group suggested that pan-suppression of the marrow was also not the primary cause. Of originally selected measures of inflammation, plasma levels of TNF-alpha and MIF did not differ between the malaria groups, but concentrations of both interferon-gamma and interleukin-10 were significantly lower in the severe anemia group (P <0.006). Additional testing revealed levels of interleukin-1alpha, interleukin-6, and IP-10 to be lower and levels of sFAS to be higher in the children with severe anemia versus uncomplicated malaria (P <0.0005). In a logistic regression model, severe malarial anemia was associated with younger age (P = 0.010), prior treatment with sulfadoxine/pyrimethamine or traditional medicine (P <0.32), lower levels of Interleukin-10 (P = 0.025) and higher levels of sFAS (P = 0.003) and TNFa (P = 0.013). Our results are consistent with a multifactorial cause of severe malarial anemia, possibly including infection with resistant plasmodia, over-expression of TNF-alpha in conjunction with under-expression of IL-10, and increased apoptosis.

Introducing Diaphragms into the Mix: What Happens to Male Condom Use Patterns?

The objective of this analysis was to assess the effect of introducing the diaphragm on condom use patterns. Participants included one hundred eighty-nine women attending family planning clinics in Harare, Zimbabwe who reported less than 100% condom use. The proportion of acts where at least one method was used significantly increased over using follow-up; male condom use remained stable. A diaphragm was used with 50% to 54% of acts; male condoms were also used about 50% of the time. The proportion of acts where a female condom was used decreased. Women who used both male and female condoms were more likely to use diaphragms than those who reported not using female condoms. Introducing the diaphragm increased the overall proportion of protected acts. The proportion of acts where a male condom was used did not change. Female condoms use declined because concurrent use with the diaphragm is not possible.

Chronic Cough in Primary Health Care Attendees, Harare, Zimbabwe: Diagnosis and Impact of HIV Infection

Cough lasting for > or = 3 weeks (i.e., chronic cough) indicates that a patient has suspected tuberculosis (TB). At the primary health care level, the spectrum of disease that causes chronic cough has not been previously investigated in a setting with a high prevalence of human immunodeficiency virus (HIV) infection. A total of 544 adults with chronic cough were recruited systematically from 2 primary health care clinics, and they were evaluated using preset first- and second-line investigations and diagnostic case definitions. The overall prevalence of HIV infection among the study cohort was 83%. TB was the most common diagnosis, with 207 HIV-positive patients (46%) and 27 HIV-negative patients (30%) having confirmed or probable TB. Of these, 145 HIV-positive patients with TB (70%) and 20 HIV-negative patients with TB (74%) had smear-positive cases of TB. Only 17 HIV-positive and 2 HIV-negative patients had smear-negative but culture-positive cases of TB. Lower respiratory tract infections (n = 178; HIV prevalence, 79%) and pneumonia (n = 87; HIV prevalence, 89%) were the next most common diagnoses. Asthma (n = 26; HIV prevalence, 46%), posttuberculous disease and other fibrotic lung disease (n = 34; HIV prevalence, 88%), and cardiac disease (n = 15; HIV prevalence, 93%) were more common than were Pneumocystis jiroveci pneumonia and cryptococcosis (n = 8 and n = 5, respectively; HIV prevalence, 100%), and we found no cases of nocardiosis or histoplasmosis. TB was diagnosed for 43% of patients who presented with chronic cough to primary health care clinics in Harare, with 71% having smear-positive disease. The findings of TB culture added relatively little to the findings of fluorescent microscopy of concentrated sputum specimens. The prevalence of HIV infection was high across a range of diagnoses, suggesting that an HIV test should be recommended in the initial investigation of chronic cough.

Association of cervical SIL and HIV-1 infection among Zimbabwean women in an HIV/STI prevention study.

A cross-sectional study was conducted on women attending family planning clinics in Harare, Zimbabwe to determine the prevalence of cervical neoplasia among HIV-1 positive women relative to an HIV-1 negative control group. Five hundred and fifty four women were recruited and the prevalence of HIV-1 was 36.8%. Cervical cytology was abnormal in 25.6% of HIV-infected women compared to only 6.7% HIV-1 seronegative women. Cervical neoplasia was significantly associated with HIV infection (chi(2)=42.4, P<0.001). Cellular changes typical of HPV infection (koilocytocis) were recorded in 6.4% of HIV infected women compared with 1.7% of HIV-1-uninfected women (chi(2)=8.43, P=0.004). HIV-1-positive women had twice the risk of having abnormal cervical cells than HIV-negative women (relative risk 2.47, odds ratio 10.14, P<0.001). Therefore the introduction of national cervical screening programme in HIV-1 endemic countries like Zimbabwe where the highest burden of pre-malignant lesions is among HIV-1-infected women needs careful planning because these women have other competing health needs including high rates of opportunistic infections.

Determinants of reproductive tract infections among asymptomatic women in Harare, Zimbabwe.

To determine the prevalence of and risk factors for reproductive tract infections (RTI) among asymptomatic women attending primary health care clinics in Harare, Zimbabwe. A cross sectional study. Prevalent RTI, HIV and socio-demographic data. Two primary health care clinics in Harare. 393 consecutive, consenting women aged 15 to 49 years, presenting at the clinics for antenatal care, family planning, or bringing their children to attend preventive care clinics. More than half of the women had at least one ongoing RTI. Voluntary reporting of symptoms was almost non-existent. Prevalence of HIV was 29.3% and that of classical STIs was 15.4% Trichomoniasis vaginalis, 3.9% syphilis, 3.9% Chlamydia trachomatis and 1.8% Neisseria gonorrhoea. Bacteria vaginosis was diagnosed in 30.3% of the women and candidiasis in 25.4%. Presence of any RTI was significantly associated with lower level of education, sexual debut < 20 years, a non-monogamous partner, and use of a condom during the last sexual encounter. Independent factors associated with cervical infections were young age (< 20 years), being unmarried, current dysuria, warts, clinical signs of purulent or yellowish discharge, lower abdominal pain and cervical friability. Vaginitis was associated with sexual debut or marriage < 20 years, a partner who was a frequent traveller, history of STI, and presence of abnormal vaginal discharge. In view of the high prevalence of RTI and HIV and the low reporting of symptoms by infected women, it is recommended that strategies that improve women's awareness of urogenital symptoms be adopted, along with pro-active inquiry of genital symptoms by the health care workers, and treatment of RTIs, in order to reduce the unnecessary burden of RTIs.

Adjunctive testing for cervical cancer in low resource settings with visual inspection, HPV, and the Pap smear

Objective: To test whether the performance of visual inspection using acetic acid (VIA) could be improved through adjunctive testing and to determine whether the combination of visual inspection of the cervix and HPV testing could prove useful for identifying those at highest risk of cervical precancer. Methods: Between October 1995 and August 1997, 2199 women willing to be screened for cervical cancer in peri-urban clinics in Harare, Zimbabwe received VIA, Pap smear and HPV as screening tests. The presence or absence of (pre)cancer was confirmed via colposcopy with biopsy as indicated for >97% of all women. Computerized simulations of sequential testing scenarios provided estimates of the joint (net) test qualities of different paired combinations of the three tests and allowed for comparisons with the individual test qualities. Results: Using HGSIL/CIN II-III as the reference threshold of disease, the net sensitivity and specificity of VIA and HPV when used sequentially were 63.6 and 81.9%, respectively, compared to 43.3 and 91%, respectively, when Pap smears were followed by HPV testing. VIA followed by the Pap smear yielded a net sensitivity of 37.5% and net specificity of 94.3%. Conclusions: For programs with limited resources but with the capacity for HPV testing, sequential testing involving the use of VIA followed by HPV could yield fewer false positives than the use of VIA alone at a cost of relatively few additional false negatives.

Outcome of common mental disorders in Harare, Zimbabwe.

Little is known about the outcome of common mental disorders (CMD) in primary care attenders in low income countries. Two and 12 month (T1 and T2) follow-up of a cohort of cases of CMD (n = 199) recruited from primary health, traditional medical practitioner, and general practitioner clinics in Harare, Zimbabwe. The Shona Symptom Questionnaire (SSQ) was the measure of caseness. The persistence of case level morbidity was recorded in 41% of subjects at 12 months. Of the 134 subjects interviewed at both follow-up points, 49% had recovered by T1 and remained well at T2 while 28% were persistent cases at both T1 and T2. Higher SSQ scores, a psychological illness model, bereavement and disability predicted a poor outcome at both times. Poorer outcome at T1 only was associated with a causal model of witch-craft and an unhappy childhood. Caseness at follow-up was associated with disability and economic deprivation. A quarter of cases of CMD were likely to be ill throughout the 12 month follow-up period. Targeting risk groups for poor outcome for interventions and policy interventions to reduce the impact of economic deprivation may provide a way of tackling CMD in primary care in low income countries.

Urethral trichomoniasis in men.

Three hundred twenty-five men with confirmed urethral trichomoniasis were seen at sexually transmitted diseases clinics in Harare, Zimbabwe, in 1983-1984. The mean age of these patients was 30.4 years. The most common symptoms were urethral discharge and urethral irritation. Symptoms in 252 patients (78%) had been present for more than four weeks. Only 1.5% of 5548 patients with nontrichomonal nongonococcal urethritis had had symptoms for this length of time. In most patients with trichomoniasis (99.4%), the discharge was milky white and fluid in nature; when a smear of the discharge was made on a glass slide, small clumps of material were noted. Microscopic examination of the gram-stained smear showed relatively few polymorphonuclear leukocytes but many epithelial cells. Although Trichomonas vaginalis was readily demonstrated by microscopy of both urethral secretions and centrifuged deposits of urine, the organism was cultured only from urethral exudates. Concomitant infection with T. vaginalis was uncommon in patients with proved gonococcal urethritis. Treatment of trichomoniasis in men with a single 2-g dose of metronidazole was unsuccessful in 42.9% of cases. However, treatment with 400 mg of metronidazole thrice daily for five days gave a cure rate of 100%.