Knowledge, attitudes, and preventative practices regarding ischemic heart disease among emergency department patients in northern Tanzania.

OBJECTIVES: The objective of this study is to increase understanding of knowledge, attitudes, and preventative practices regarding ischemic heart disease (IHD) in sub-Saharan Africa in order to develop patient-centered interventions to improve care and outcomes. STUDY DESIGN: This is a prospective observational study. METHODS: Adult patients presenting with chest pain or shortness of breath to an emergency department in northern Tanzania were enrolled. A questionnaire was adapted from existing knowledge attitude and practice surveys regarding cardiovascular disease and the WHO STEPS instrument. Individual five-year risk of cardiovascular event was determined by validated models based on age, sex, systolic blood pressure, body mass index, diabetes, and smoking status. An IHD knowledge score was calculated by giving one point for each correct response to the knowledge-related items, with a maximum score of 10. Associations between IHD knowledge and patient characteristics were assessed by Welch's t-test. RESULTS: A total of 349 patients were enrolled, with median interquartile range (IQR) age 60 (45, 72) years. Of participants, 259 (74.2%) had hypertension, and 228 (65.3%) had greater than 10% five-year risk of cardiovascular event. The mean (SD) knowledge score was 4.8 (3.3). The majority of respondents (224, 64.2%) recognized obesity as a risk factor for heart attack, while a minority (34, 9.7%) knew that a daily aspirin could reduce the risk of cardiovascular event. Greater IHD knowledge was associated with younger age (P = 0.045) and higher levels of education (P < 0.001) but not higher risk of cardiovascular disease (P = 0.123). Most respondents expressed a willingness to diet to improve their health (322, 92.3%) and a preference for treatment from a physician rather than a traditional healer for a heart attack (321, 92.0%). A minority of patients reported exercising regularly (88, 25.2%) or seeing a doctor routinely for checkups (100, 28.7%). CONCLUSIONS: High-risk emergency department patients in northern Tanzania have moderate knowledge regarding IHD but do not consistently engage in healthy preventive practices. Patient-centered interventions are needed to improve IHD knowledge and practices in high-risk populations.

Low sensitivity of T-cell based detection of tuberculosis among HIV co-infected Tanzanian in-patients.

OBJECTIVE: To evaluate the performance of QuantiFERON-TB GOLD (QFTG) in a resource-poor setting among patients with and without HIV infection. DESIGN: Cross-sectional study. SETTING: Two hospitals in Northern Tanzania. SUBJECTS: Eighty three adult male and female inpatients. INTERVENTION: All patients were screened for HIV infection and underwent tuberculin skin test (TST) and QFTG. RESULTS: Eighty-three subjects were enrolled, and 29 (35%) of 83 were HIV-infected. QFTG yielded indeterminate results in 12 (22%; 95% CI 12%-34%) of 54 HIV-uninfected and 13 (45%; 95% CI 26%-64%) of 29 HIV-infected subjects (p = 0.0323). Among those with smear-positive pulmonary tuberculosis, TST was positive in 40 (100%; 95% CI 91%-100%) of 40 HIV-uninfected subjects compared with seven (54%; 95% CI 25%-81%) of 13 HIV-infected subjects (p < 0.0001), and QFTG was positive in 28 (70%; 95% CI 53%-83%) of 40 HIV-uninfected subjects compared with three (23%; 95% CI 5%-54%) of 13 HIV-infected subjects (p = 0.0029). Among medical inpatients at risk for latent tuberculosis infection, TST was positive in seven (50%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p = 0.0701) and QFTG was positive among two (14%) of 14 HIV-uninfected patients and three (19%) of 16 HIV-infected patients (p = 0.7437). CONCLUSIONS: The presence of HIV co-infection was associated with a significant reduction in sensitivity of both the TST (p < 0.0001) and QFTG (p = 0.0029) for the diagnosis of active M. tuberculosis infection. The high proportion of indeterminate QFTG and lack of sensitivity, particularly among HIV-infected patients, may limit its applicability in settings like Tanzania. Larger studies in resource-poor settings are required.

Role of platelet-activating factor in Chinese hamster ovary cell responses to cholera toxin.

Cholera toxin (CT)-induced intestinal secretion and Chinese hamster ovary cell (CHO) elongation involves cyclic adenosine monophosphate and protein synthesis-dependent prostaglandin formation. We previously reported inhibition of CT-induced intestinal secretion and CHO elongation by platelet-activating factor (PAF) receptor antagonists and secretion of PAF by human intestinal epithelial cells exposed to CT. Herein, we show that PAF is involved after cAMP and that PAF, like CT, mediates prostaglandin E2 synthesis in CHO cells. CT-induced CHO elongation was blocked by specific PAF receptor antagonists, BN52021 and SR27417. SR27417 blocked dibutyryl cAMP-induced CHO elongation, but did not alter CHO elongation caused by PGE2. Neither CT-stimulated cAMP accumulation nor PGE2 production was inhibited by SR27417. Both PGE2 and PAF caused significant CHO elongation, but the latter did not stimulate significant cAMP production. In addition, PAF, like CT and dibutyryl cAMP, stimulated significant PGE2 production. Finally, the protein synthesis inhibitor cycloheximide, which completely blocks the effect of CT on prostaglandin synthesis, also blocked that of PAF, suggesting that PAF also mediates protein synthesis-dependent prostaglandin formation. We conclude that PAF is involved in CHO cytoskeletal responses to CT after the accumulation of cAMP and, like CT, PAF stimulates protein synthesis-dependent prostaglandin accumulation.

Hookworm infection of the duodenum associated with dyspepsia and diagnosed by oesophagoduodenoscopy: case report.

Hookworm infection and peptic ulcer disease are common in subtropical and tropical countries. While hookworm infection is endemic where sanitary conditions are poor, peptic ulcer disease is associated with a high prevalence of Helicobacter pylori infection. Dyspepsia and epigastric pain are common presenting symptoms of patients with either hookworm infection or peptic ulcer disease. Consequently it is common practice at our healthcare facility to examine stool for ova or parasites before considering empirical gastric acid suppressive therapy or Helicobacter pylori eradication therapy. We describe a patient who presented with dyspepsia and epigastric pain whose stool examination showed no ova or parasites. The patient's symptoms did not improve with proton pump inhibitor therapy. Endoscopy revealed hookworms in the first part of the duodenum. We review published reports of hookworms at this location. In hookworm endemic areas, when empirical treatment for dyspepsia and upper abdominal pain with acid suppressive agents does not offer remedy, antihelminthic agents should be considered even when stool for ova or parasites is negative.

Sociodemographic and clinical characteristics of clients presenting for HIV voluntary counselling and testing in Moshi, Tanzania.

HIV voluntary counselling and testing (VCT) reduces high-risk sexual behaviour. Factors associated with HIV infection in VCT clients have not been well characterized in northern Tanzania. We prospectively surveyed 813 VCT clients in Moshi, Tanzania. Clients were administered a questionnaire on sociodemographic characteristics, sexual behaviour, and health status. Blood was taken for rapid HIV antibody testing. Factors associated with HIV seropositivity were identified using multivariate logistic regression analysis. Of 813 clients, the seroprevalence was 16.7%. The strongest associations with seropositivity were reporting diarrhoea (odds ratio [OR] 10.4, 95% confidence interval [CI] 3.6-29.9), an ill sexual partner (OR 6.3, 95% CI 3.0-12.9), or being a woman (OR 3.5, 95% CI 2.0-6.3). In a separate regression, the number of symptoms also predicted HIV infection (OR 2.1, 95% CI 1.6-2.6). VCT clients who tested positive had more HIV-related symptoms suggesting presentation at a later stage of HIV infection.

Gender (in) differences in prevalence and incidence of traumatic experiences among orphaned and separated children living in five low- and middle-income countries.

BACKGROUND: Approximately 153 million children worldwide are orphaned and vulnerable to potentially traumatic events (PTEs). Gender differences in PTEs in low- and middle-income countries (LMIC) are not well-understood, although support services and prevention programs often primarily involve girls. METHODS: The Positive Outcomes for Orphans study used a two-stage, cluster-randomized sampling design to identify 2837 orphaned and separated children (OSC) in five LMIC in sub-Saharan Africa and Asia. We examined self-reported prevalence and incidence of several PTE types, including physical and sexual abuse, among 2235 children who were ≥10 years at baseline or follow-up, with a focus on gender comparisons. RESULTS: Lifetime prevalence by age 13 of any PTE other than loss of a parent was similar in both boys [91.7% (95% confidence interval (CI) (85.0-95.5)] and girls [90.3% CI (84.2-94.1)] in institutional-based care, and boys [92.0% (CI 89.0-94.2)] and girls [92.9% CI (89.8-95.1)] in family-based care; annual incidence was similarly comparable between institution dwelling boys [23.6% CI (19.1, -29.3)] and girls [23.6% CI (18.6, -30.0)], as well as between family-dwelling boys [30.7% CI (28.0, -33.6)] and girls [29.3% CI (26.8,-32.0)]. Physical and sexual abuse had the highest overall annual incidence of any trauma type for institution-based OSC [12.9% CI (9.6-17.4)] and family-based OSC [19.4% CI (14.5-26.1)], although estimates in each setting were no different between genders. CONCLUSION: Prevalence and annual incidence of PTEs were high among OSC in general, but gender-specific estimates were comparable. Although support services and prevention programs are essential for female OSC, programs for male OSC are equally important.

Persistent diarrhea in the returned traveler.

In conclusion, the causes of chronic diarrhea in the returned traveler are protean. Careful evaluation requires an understanding of where the traveler has been, when they were there, the type of diarrheal illness, medications taken, and knowledge of the patients' other medical problems. Protozoa, particularly G. lamblia, C. parvum, and C. cayatenensis, are among the more commonly identified agents. If the patient is immunocompromised, microsporidia and Isospora become more likely, and a prior history of antimicrobial use raises the possibility of C. difficile colitis. Occasionally helminths, which establish intimate contact with the intestinal mucosa, may also cause prolonged diarrhea. If these and other gastrointestinal insults, such as tropical sprue, small bowel overgrowth, lactose intolerance, and processes unrelated to travel are excluded by more invasive studies or clinical history, the patient can be reassured that idiopathic chronic diarrhea is usually self-limited.

Emergence of resistance to clarithromycin during treatment of disseminated cutaneous Mycobacterium chelonae infection: case report and literature review.

Results of in vitro susceptibility studies and one clinical trial have led to recommendations of clarithromycin monotherapy for the treatment of disseminated cutaneous Mycobacterium chelonae infections. We describe the case of a 65-year-old woman, immunocompromised by the use of chronic steroid therapy, who developed disseminated cutaneous infection with M. chelonae and failed clarithromycin monotherapy due to the development of drug resistance. In the relapse isolate we document the presence of a single point mutation at position 2058 in the gene coding for 23S rRNA peptidyltransferase regions, a mutation previously implicated in the development of resistance to clarithromycin. Two susceptible control isolates lacked the mutation. Three additional reports in the literature of patients developing recurrent skin lesions with clarithromycin-resistant M. chelonae following initial response to monotherapy are summarized. We demonstrate that clarithromycin monotherapy in patients with disseminated cutaneous infections can lead to clarithromycin resistance and therapeutic failure associated with a single point mutation at position 2058 of 23S rRNA.

Morbidity and mortality among a cohort of HIV-infected adults in a programme for community home-based care, in the Kilimanjaro Region of Tanzania (2003-2005).

Community home-based care (CHBC) plays an integral role in the care of HIV-infected patients living in resource-limited regions. A longitudinal cohort study has recently been conducted, in the Kilimanjaro Region of northern Tanzania, in order to identify the components of an effective CHBC programme. Structured questionnaires were administered to clients over two census rounds, one in October 2003-February 2004 and the other in January 2005-October 2005. In the second round, follow-up interviews were completed for 226 (87.9%) of the 257 clients included in the first round. The clients included in the first round had a median (range) age of 38 (20-66) years and 182 (75.2%) of them were female. Although only 27 (12.9%) of them were using antiretroviral therapy (ART) when first interviewed, 108 (44.6%) were taking trimethoprim-sulfamethoxazole (SXT) prophylaxis. By the time of the follow-up interviews, 102 (45.1%) of the clients included in the first round had died, giving a mortality of 51/100 person-years of observation. The primary cause of death for 87 (85.3%) of the clients who had died was respiratory and/or gastro-intestinal infection, and the most common contributory causes of death were malnutrition (81.4%) and anaemia (42.2%). On bivariable analysis, the following first-round conditions were found to be significantly associated with death by the second census round: weakness for >1 month [odds ratio (OR)=2.64; P=0.008]; oral thrush (OR=2.31; P=0.015); painful swallowing (OR=2.02; P=0.036); staying in bed for part of the day over most of the previous month (OR=1.94; P=0.017); fever for >1 month (OR=1.95; P=0.016); and severe bacterial infections (OR=1.80; P=0.036). The high mortality was associated with advanced, symptomatic HIV disease for which antiretroviral therapy was indicated. Clients who were in the advanced stages of HIV disease (as defined by the World Health Organization's criteria) in the first census round were significantly more likely to have died by the time of the second round than the other clients investigated (log-rank chi(2)=8.115; P=0.044). The high level of morbidity observed in this study, and the causes of mortality that were identified, emphasise the need for CHBC programmes to provide HIV-infected patients with improved access to basic resources such as SXT and isoniazid prophylaxis, clean water, oral rehydration therapy, and micronutrient supplementation, in addition to increased access to ART.

Missed opportunities for diagnosis of tuberculosis and human immunodeficiency virus co-infection in Moshi, Tanzania.

SETTING: A community-based voluntary counseling and testing (VCT) center in Moshi, Tanzania. OBJECTIVE: To compare rates of prior human immunodeficiency virus (HIV) testing among clients with and without previous tuberculosis (TB) treatment, and HIV seropositivity among those with and without current TB symptoms. DESIGN: Cross-sectional study of consecutive clients presenting for initial testing; sociodemographic and clinical data were collected via a structured questionnaire. HIV status was compared among clients with or without three or more TB-related symptoms: weight loss, fever, cough, hemoptysis or night sweats. RESULTS: Overall, 225 (3%) of 6583 VCT clients who responded to questions on previous TB treatment reported a history of TB, but only 34 (15%) reported previous HIV testing. This rate of HIV testing was not different from the rate among those clients without a history of TB (OR 0.77, P = 0.175). One hundred thirty-five (61%) clients with a history of TB were HIV-infected at VCT, compared with 17% of all clients. Of the total 6592 first-time testers who responded, 372 (6%) had at least three symptoms suggestive of TB at VCT. These symptoms were strongly associated with HIV seropositivity (OR 16.30, P < 0.001). CONCLUSION: Missed opportunities for HIV diagnosis at the time of TB treatment appear frequent in this population, underscoring the need for integration of TB and HIV diagnostic services.

Childhood abuse and initial presentation for HIV care: an opportunity for early intervention.

An alarmingly high prevalence of childhood sexual and physical abuse has been observed in HIV-infected men and women, with rates several times higher than observed in the general population. Childhood abuse history has been associated with worse antiretroviral adherence and negative health behaviours in HIV-infected patients. This study evaluates the relationship between childhood abuse and the timing of presentation for HIV care. Participants in a multi-center prospective cohort study, who established initial HIV care after January 1996 and had a CD4 count available within six months of initial presentation, were included in this analysis. Bivariate contingency tables and multivariate logistic regression were used to evaluate the association of childhood abuse with early presentation for HIV care (initial CD4 count > or =200/mm3). Among the 186 subjects included in this analysis, 33% had childhood abuse histories and 58% had an initial CD4 count > or =200/mm3. Participants with a history of childhood abuse were more likely to present early for HIV care (AOR=2.12; p=0.03), perhaps because survivors of abuse tend to have higher utilization of health services. Because HIV-infected patients with childhood abuse histories have worse antiretroviral medication adherence and are more likely to engage in high-risk sexual and injection drug use behaviours, early presentation affords clinicians the opportunity for timely institution of interventions that may improve patient outcomes and prevent secondary HIV infections.

Protozoal agents: what are the dangers for the public water supply?

Safe and efficient treatment of drinking water has been one of the major public health advances of the twentieth century. People in developed countries generally take for granted that their water is safe to drink, a luxury the majority of the world's population does not have. The leading cause of infant mortality in the developing world is infectious diarrhea, and the prevalence of diarrheal pathogens is largely influenced by the quality and quantity of clean water available for drinking and washing. Until recently, modern water treatment had all but eliminated these concerns in developed nations. Over the past two decades, however, the safety of our water supply has been threatened by the emergence of Cryptosporidium parvum, a protozoal pathogen. The hearty oocysts of this organism survive chlorination and filtration to cause a diarrheal illness that, while unpleasant enough in healthy people, is devastating in immunocompromised individuals. The 1993 Milwaukee outbreak, in which 403,000 people developed diarrhea from drinking water that met all the updated federal safety standards, demonstrated the tremendous public health importance of this organism. While earlier attention had focused on Giardia and amebic infections, the other "emerging" protozoan besides Cryptosporidium is Cyclospora. This review discusses the protozoal pathogens, including Cryptosporidium parvum, Giardia lamblia, Entamoeba histolytica, and Cyclospora cayetanensis, that cause waterborne diarrheal outbreaks and the threats they pose to the public.

Role of platelet activating factor in the intestinal epithelial secretory and Chinese hamster ovary cell cytoskeletal responses to cholera toxin.

With the recent heightened concern about cholera around the world come new questions about the mechanism by which cholera toxin causes diarrhea. Peterson and Ochoa have suggested that prostaglandin synthesis is key to both the intestinal epithelial secretory and the CHO cell responses to cholera toxin [Peterson, J. W. and Ochoa, G. (1989) Science 245, 857-859]. Because platelet activating factor (PAF) can be a potent stimulus for prostaglandin synthesis, we examined its role in the intestinal and tissue culture effects of cholera toxin. We report that the specific PAF receptor antagonists BN 52021 and SR 27417 inhibit the effects of cholera toxin on intestinal secretion in rabbit ileal loops in vivo and on the cytoskeleton of Chinese hamster ovary cells in vitro. We also show that PAF itself can cause net fluid secretion in the rabbit model and that PAF potentiates the effects of cholera toxin on intestinal secretion. Finally, we demonstrate that cholera toxin stimulates significant PAF production (2.6-fold) in isolated T-84 intestinal epithelial cells. We conclude that cholera toxin stimulates PAF production and that PAF is involved in both the secretory and cytoskeletal responses to cholera toxin. These findings further support the involvement of additional mediators of cholera toxin effects other than mucosal cell cyclic AMP and help explain the effects of cholera toxin on prostaglandin synthesis.

Role of platelet activating factor in the inflammatory and secretory effects of Clostridium difficile toxin A.

Clostridium difficile is a major recognized cause of antibiotic-associated diarrhea, an effect mediated through its toxin A. Toxin A has been reported to disrupt epithelial tight junctions, attract neutrophils, and cause striking intestinal inflammation and secretion. Having demonstrated that phospholipase A2 inhibitors block the secretory effects of toxin A, we next wished to examine whether platelet activating factor (PAF) was involved in either the direct epithelial or secretory effects of toxin A. The effects of toxin A on net secretion in ligated rabbit ileal segments were significantly inhibited by the PAF antagonists 10(-4)-10(-5) M BN 52021, 10(-5) M WEB 2170, or 10(-5) M SR 27417 by 59-102%. SR 27417 also inhibited secretion induced by toxin A in loops adjacent to the drug (by 58%). Furthermore, the striking inflammation and epithelial disruption seen at 6 h and ligated ileal segments with toxin A was largely prevented by simultaneous treatment with the PAF antagonist SR 27417. In addition, we noted a significant synergistic effect of 10(-8) M PAF with 10 micrograms/ml toxin A in the ligated rabbit ileal segments. To examine direct effects of PAF antagonists on toxin A in T-84 epithelial cell monolayers, rhodamine-labeled phalloidin stained F-actin demonstrated significant disruption of F-actin by toxin A that was reduced by the PAF antagonist BN 52021 or WEB 2170. However, the PAF antagonists (10(-4) M WEB, 10(-5) M BN or 10(-4) M SR) failed to alter the disruption of T-84 cell tissue resistance by C. difficile toxin A (0.03 micrograms/ml). We conclude that PAF may be involved in the secretory effects of C. difficile toxin A, and that PAF antagonists deserve further study in C. difficile diarrhea.

Diagnosis and screening of HIV/AIDS using clinical criteria in Tanzanian adults.

The clinical utility of the World Health Organization (WHO) clinical case definition (CCD) of acquired immune deficiency syndrome (AIDS) in Africa, several proposed modifications of the WHO CCD, and two proposed screening algorithms for human immunodeficiency virus (HIV) infection were examined in adult medical inpatients in Dar es Salaam, Tanzania. Sensitivity, specificity, and positive and negative predictive values were determined for the CCDs and screening algorithms. Multivariable analysis identified factors with high accuracy for HIV infection. Of 223 patients enrolled in the study, 95 were seropositive for HIV infection. The WHO CCD and the modified CCDs had low sensitivities (14.7-32.6%) but high specificities (95.3-99.2%) and positive predictive values (83.8-94.7%). The screening algorithms had moderate sensitivities (66.3-77.9%) and poor specificities (46.1-79.7%). Multivariable analysis consistently identified oral candidiasis and lymphadenopathy as the best predictors of HIV infection. Although patients with asymptomatic or early HIV infection may be missed by clinical criteria, in a high prevalence population, AIDS may be diagnosed accurately clinically because of the effect of prevalence on the positive predictive values of the CCDs. Furthermore, selection of patients for HIV serologic testing may be guided by simple combinations of clinical features.

Delayed-type hypersensitivity testing in Tanzanian adults with HIV infection.

Delayed-type hypersensitivity (DTH) testing and total lymphocyte counts as measures of cell-mediated immune function were assessed for medical patients in Dar es Salaam, Tanzania. DTH testing was performed with the Multitest CMI device which simultaneously administers seven antigens. Of 201 patients completing DTH testing, 90 were HIV seropositive. Anergy occurred more frequently among HIV-seropositive patients (39 of 90) as compared with HIV-seronegative patients (17 of 111). DTH skin test reactivity, measured by anergy, the number of positive antigens, and the combined DTH response induration, was significantly related to the clinical stage of HIV disease. Median total lymphocyte counts were significantly lower in HIV-seropositive patients than in HIV-seronegative patients (1,130 vs. 1,680 lymphocytes x 10(6)/L). Total lymphocyte counts decreased with increasing severity of HIV disease. In multivariable analysis, the number of positive antigens in DTH testing and lymphopenia significantly predicted HIV infection. The findings suggest that DTH testing and total lymphocyte counts may be useful, inexpensive tests of immune function in African patients with HIV disease.

HIV-associated morbidity, mortality and diagnostic testing opportunities among inpatients at a referral hospital in northern Tanzania.

Hospitalized patients with HIV infection are among the most likely to benefit from the expanding availability of anti-retroviral therapy in sub-Saharan Africa. Between 1990 and 2000, 3667 people known to be HIV-infected were admitted to Kilimanjaro Christian Medical Centre (KCMC) in Moshi, northen Tanzania. The level of inpatient mortality among these patients varied from 15%-21%, and the proportion of the HIV-infected patients admitted who were female increased significantly, from 45% at the start of the study period to 52% at the end (P <0.001). When the medical records for 1683 of the HIV-infected patients who had been admitted between 1996 and 2001 were reviewed, the most prevalent diagnoses on admission were found to be pulmonary tuberculosis (21%), malaria (14%) and gastro-enteritis/diarrhoea (12%) among the adults, and non-tubercular pulmonary infection (21%), pulmonary tuberculosis (19%) and gastro-enteritis/diarrhoea (12%) among the children. The crude odds ratios (OR) for inpatient death were greatest for adults presenting with meningitis [OR=3.7; 95% confidence interval (CI)=2.1-6.7], septicaemia (OR=2.9; CI=1.2-7.3) or renal disease (OR=2.6; CI=1.2-5.7), and mortality was higher for men than for women (OR=1.4; CI=1.1-1.8). A single-day, point-prevalence survey in September 2001, among the KCMC's inpatients, identified HIV infection in 21% of those surveyed, many (44%) of the patients found positive being previously unaware of their infection. HIV infection remains a major cause of hospitalization and mortality in Moshi. A policy of routine testing would increase the number of HIV infections detected, allowing improvements in case management and in the prevention of infection.