Environmental risk factors for oesophageal cancer in Malawi: A case-control study.

AIM: There is a high burden of oesophageal cancer in Malawi with dismal outcomes. It is not known whether environmental factors are associated with oesophageal cancer. Without knowing this critical information, prevention interventions are not possible. The purpose of this analysis was to explore environmental factors associated with oesophageal cancer in the Malawian context. METHODS: A hospital-based case-control study of the association between environmental risk factors and oesophageal cancer was conducted at Kamuzu Central Hospital in Lilongwe, Malawi and Queen Elizabeth Central Hospital in Blantyre, Malawi. Ninety-six persons with squamous cell carcinoma and 180 controls were enrolled and analyzed. These two groups were compared for a range of environmental risk factors, using logistic regression models. Unadjusted and adjusted odds ratios and 95% confidence intervals (CI) were calculated. RESULTS: Firewood cooking, cigarette smoking, and use of white maize flour all had strong associations with squamous cell carcinoma of the oesophagus, with adjusted odds ratios of 12.6 (95% CI: 4.2-37.7), 5.4 (95% CI: 2.0-15.2) and 6.6 (95% CI: 2.3-19.3), respectively. CONCLUSIONS: Several modifiable risk factors were found to be strongly associated with squamous cell carcinoma. Research is needed to confirm these associations and then determine how to intervene on these modifiable risk factors in the Malawian context.

Role of cytokines in Trypanosoma brucei-induced anaemia: A review of the literature.

BACKGROUND: Anaemia is an important complication of trypanosomiasis. The mechanisms through which trypanosomal infection leads to anaemia are poorly defined. A number of studies have implicated inflammatory cytokines, but these data are limited and inconsistent. In this article, we reviewed the published literature on cytokines associated with Trypanosoma brucei infections and their role in the immunopathology leading to anaemia. METHODOLOGY: Articles were searched in PubMed through screening of titles and abstracts with no limitation on date of publishing and study design. Articles in English were searched using keywords "African trypanosomiasis", "sleeping sickness", "Trypanosoma brucei", in all possible combinations with "anaemia" and/or "cytokines". RESULTS: Twelve articles examining cytokines and their role in trypanosomeinduced anaemia were identified out of 1095 originally retrieved from PubMed. None of the articles identified were from human-based studies. A total of eight cytokines were implicated, with four cytokines (IFN-γ, IL-10, TNF-α, IL-12) showing an association with anaemia. These articles reported that mice lacking TNF-α were able to control anaemia, and that IFN-γ was linked to severe anaemia given its capacity to suppress erythropoiesis, while IL-10 was shown to regulate IFN-γ and TNF-α, providing a balance that was associated with severity of anaemia. IFN-γ and TNF-α have also been reported to work in concert with other factors such as nitric oxide and iron in order to induce anaemia. CONCLUSION: IFN-γ, IL-10, and TNF-α were the three major cytokines identified to be heavily involved in anaemia caused by Trypanosoma brucei infection. The anti-inflammatory cytokine, IL-10, was shown to counter the effects of proinflammatory cytokines in order to balance the severity of anaemia. The mechanism of anaemia is multifactorial and therefore requires further, more elaborate research. Data from human subjects would also shed more light.

Presentation of trypanosomiasis in nkhotakota.

In 2002, we identified 28 people in Nkhotakota District who were suffering from Human African Trypanosomiasis (HAT). Sixteen of these were identified when they presented to the District Hospital with a febrile illness. The remaining twelve were identified through a rural cross-sectional survey, in which 500 people were visited in their homes, persons found to be febrile, were examined by blood film microscopy. Of the 28 people, 50% (14) presented within a month of the onset of symptoms. Sixteen (57%) had splenomegaly, and 24 were anaemic ([Hb] <12 g/dl). Four patients died (14%), of which two were in the late stage of the disease. None of the patients recall having a chancre that could be attributed to the bite of tsetse flies. 9 out of 28 (32%) reported illness longer than 90 days. Of the 9 patients 6 (66%) of them remained in the early stage after reporting illness of 180 days. This study reports on the prevalence and clinical features of Trypansoma brucei rhodesiense infection in a endemic district in Malawi.

Anthropometric indices in rural Malawians aged 45-75 years.

OBJECTIVE: The aim of this cross-sectional study was to assess anthropometric parameters of rural people aged 45-75 years in the Southern Region of Malawi. SUBJECTS: 97 males and 101 females aged 45-75 years were selected from 10 villages in Balaka district using a stratified cluster sampling method. Most responders were small-scale farmers growing maize and vegetables for household consumption. The anthropometric measurements taken were height, weight, triceps skinfold (TSK) and mid-upper arm circumference (MUAC). The derivatives from anthropometric measurements included body mass index (BMI), mid-upper arm muscle area (MUAMA) and mid-upper arm fat area (MUAFA). Weight status of Malawian subjects was estimated using WHO (1995) categories for BMI values, and height, weight, TSK, MUAC, MUAMA and MUAFA were compared with NHANES reference data for black sample. RESULTS: Correlation between age of subjects and the anthropometric indices was weak and insignificant. Males were generally taller and lighter than females. All anthropometric indices of Malawian subjects were considerably lower than NHANES medians. However the mean values of height, weight, MUAC and MUAMA of females were closer to the reference values than those of males. It was found that 9.1% of Malawian subjects had mild thinness (BMI 17.0-18.4 kg m(-2)), 13.6% had moderate thinness (BMI 16.0-16.9 kg m(-2)) and 18.2% exhibited severe thinness (BMI<16.0 kg m(-2)). The proportion of thin persons was higher (chi2 = 9.58, n = 1, p<0.01) among males than females (50.0% versus 35.7%). CONCLUSIONS: This study indicates that undernutrition is a serious problem among rural Malawians aged 45-75 years.

Is handedness related to health status?

Handedness is the most important behavioural asymmetry due to its intimate association with the specialisation of the brain for language. It exists in 3 forms, namely right, left and mixed. Left-handers constitute the biggest minority group in the world and in many aspects they are in a disadvantaged position compared to right-handers. Numerous studies demonstrated association between left-handedness and different health problems ranging from learning disorders to breast cancer and decreased longevity. This paper reviews the relevant literature on the genesis of handedness and connection between handedness and health. Deviations from the "normal" pattern of braininess observed in some left-handers might contribute to developmental, cognitive and some mental disorders. However increased incidence of some of pathological conditions among sinistrals could hardly be explained by the "abnormal" pattern of braininess or by the action of a gene or genes responsible for handedness determination. Review of literature suggests that many of health problems of left-handers develop due to environmental, developmental and other mechanisms related to genesis of handedness.

Anaemia in human African trypanosomiasis caused by Trypanosoma brucei rhodesiense.

OBJECTIVE: To find out if indeed anaemia is a major sign in human trypanosomiasis caused by Trypanosoma brucei rhodensiense. DESIGN: A one year cross-sectional study of all admitted and surveyed Trypanosoma brucei rhodensiense infected patients (June 2001-June 2002) SETTING: Nkhotakota District Hospital-Central Region of Malawi. RESULTS: After survey and investigations, 28 patients (16 males and 12 females) were admitted to Nkhotakota District Hospital with a parasite positive Trypanosoma brucei rhodensiense infection. Twenty four (85.7%) of them were anaemic. Their mean haemoglobin was 8.96 +/- 3.07 g/dl compared to controls that had a mean haemoglobin concentration of 12.17 +/- 1.35 g/dl (p < 0.000001, 95% CI -4.342 to -2.0785) (n = 45). None of the trypanosomiasis infected individuals had schistosomiasis or hookworms. Two patients had malaria. One of them was an 18-year-old pregnant woman with hepatosplenomegaly, who developed ante partum haemorrhage. She was jaundiced and had haemoglobin of 10 g/dl. She died after two weeks following the diagnosis and treatment. The other was a two-year-old girl who had haemoglobin of 8.4 g/dl. She also had hepatosplenomegaly. All the other patients looked well nourished with no other signs of chronic diseases. Hepatosplenomegaly was significantly related to the severity of illness (p = 0.011) but not to anaemia. CONCLUSION: Though basic, this study has shown that anaemia is indeed a complication of human Africa trypanosomiasis caused by Trypanosoma brucei rhodesiense. There is need for further investigation to investigate the type of anaemia that is caused by this disease.

Leprosy in Nkhotakota District Hospital.

OBJECTIVE: To study the profile of leprosy cases at Nkhotakota District Hospital in Central Region of Malawi. DESIGN: Retrospective cross-sectional study of all registered cases of leprosy from records over a nine year period (January 1992 to April 2001) SETTING: Nkhotakota District Hospital-Central Region of Malawi. RESULTS: In total 526 cases of leprosy were identified from the records. The prevalence rates gradually increased from 0.998 per 10,000 cases in 1992 to 3.39 cases per 10,000 in 1995. There was however a gradual decline of prevalence rates from 1997/1998 that had 3.17 cases per 10,000 to 1.3 cases per 10,000 in 2001. 1996 registered 2.34 cases per 10,000. Fifty seven cases (10.8%) were found with children of the age of 14 or below and 469 (89.2%) cases were of adults. Paucibacillary leprosy presented with more cases than multibacillary leprosy (p < 0.0000001). There were 80 (15.2%) cases of multibacillary leprosy compared to 446 (84.8%) cases of paucibacillary leprosy. In addition more males were affected by multibacillary leprosy than females (p < 0.0001) and females were more affected by paucibacillary leprosy (p < 0.01) than males. CONCLUSION: The results show that paucibacillary leprosy though minor in Malawi can become endemic as paucibacillary leprosy is a reflection of leprosy contacts in the population. We therefore recommend continued epidemiological surveys of leprosy. Training in leprosy detection should be encouraged so that this disease can be totally eradicated in Malawi.

Quantitative analysis of gait pattern in hemiparetic patients.

OBJECTIVE: To characterise gait pattern in hemiparetic patients quantitatively using clinical footprint method. DESIGN: A case control study. SUBJECTS: Sixteen hemiparetic patients (12 males and 4 females) aged 16 to 64 years who attended neurological clinic at Queen Elizabeth Central Hospital, Blantyre, Malawi. MAIN OUTCOME MEASURES: Stride length, step width, foot rotation angle measured using footprint method. RESULTS: The difference in mean values of the three variables of gait between affected and unaffected sides in hemiparetic patients was not significant. However, strides were significantly longer in controls than in patients (P<0.001) while patients had significantly broader steps (P<0.02). In the controls, foot was rotated externally in 87.7% of steps and internally in 14.3% of steps. In the hemiparetic patients, intoeing pattern was observed in 41.3% of steps. The difference in variability of stride length and foot angle between affected and non-affected sides of patients was not significant. Stride-to-stride variability in stride length in patients was 1.6 times higher than in controls. Variability of step width and foot progression angle was 1.4 and 1.6 times higher in patients than in controls. CONCLUSION: Footprint method provides fast and inexpensive tool for clinical gait analysis and is suitable for evaluation of hemiparetic patients. Our findings suggest that areas of emphasis for physical therapy of hemiparetic patients should include increasing stride length and decreasing step width and internal rotation of foot, particularly on the affected side.

Captopril inhibits in vitro and in vivo the proliferation of primitive haematopoietic cells induced into cell cycle by cytotoxic drug administration or irradiation but has no effect on myeloid leukaemia cell proliferation.

Angiotensin I-converting enzyme (ACE) has been shown to be involved in the catabolism of the tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP). As AcSDKP is a physiological inhibitor of haematopoietic stem cell proliferation, we investigated the in vitro and in vivo effects of captopril, one of the specific inhibitors of ACE, on the proliferation of primitive haematopoietic cells. Regenerating bone marrow cells obtained from mice given one injection of cytosine arabinoside (100 mg/kg) as well as SA2 myeloid leukaemia cells were incubated in vitro for 24 h with 10-6 M captopril. Captopril significantly reduced the proportion of high proliferative potential colony-forming cells (HPP-CFC-1) in S-phase, whereas it had no effect on the proportion of SA2 leukaemic colony-forming cells in S-phase. When given in vivo to mice 1 h after 2 Gy gamma-irradiation or cytosine arabinoside (AraC) injection, captopril (100 mg/kg) was shown to prevent HPP-CFC-1 entry into S-phase induced by these cytotoxic treatments. The observed effects correlated with a reduction in ACE degradative activity and an increase in the level of endogenous AcSDKP both in the supernatants of captopril-treated bone marrow cells and in plasma of treated animals. The present findings suggest that AcSDKP might mediate the observed in vitro and in vivo inhibitory effects of captopril on primitive haematopoietic cell proliferation.

The incidence of cleft lip, cleft palate, hydrocephalus and spina bifida at Queen Elizabeth Central Hospital, Blantyre, Malawi.

OBJECTIVES: To determine the incidence of cleft lip, cleft palate, spina bifida and hydrocephalus; and to compare these with those of Asian and European subjects. DESIGN: A retrospective study. SETTING: The Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. SUBJECTS: Delivery and nursery records compiled between January 1998 and December 1999 were studied. MAIN OUTCOME MEASURES: To measure the incidence of cleft lip, cleft palate, spina bifida and hydrocephalus. RESULTS: Of the total 25562 births, 39 (0.2%) had defects; eight boys and 31 girls. Clefts (all types) comprised the largest group, 43.6%, with an incidence of 0.67/1 000; spina bifida, 30.8% with an incidence of 0.47/1000; hydrocephalus, 15.4%, and an incidence of 0.23/1000; and spina bifida with hydrocephalus, 10.3%, with 0.16/1000 incidence. The respective mean (SD) birth weights for clefts (all types), spina bifida, hydrocephalus and spina bifida with hydrocephalus were 2806.47 (569.07) g, 2650.00 (360.55) g 2610.00 (720.97) g and 3362.50 (696.87) g respectively. CONCLUSION: Our findings show a higher incidence of spina bifida in Malawians than in Caucasians and Orientals, but the incidence was lower than Omani subjects. The incidence of clefts and hydrocephalus in black Malawians, however, was lower than previously reported in other population groups, and hydrocephalus probably showed the lowest incidence among blacks in the continent. Furthermore, congenital malformations affected more girls than boys 4:1, but the infants had normal birth weight.

Captopril inhibits the proliferation of hematopoietic stem and progenitor cells in murine long-term bone marrow cultures.

Drugs used mainly for the treatment of hypertension, such as angiotensin I-converting enzyme (ACE) inhibitors, can cause pancytopenia. The underlying cause of this side effect remains unknown. In the present study, long-term bone marrow cultures (LTBMCs) were utilized to evaluate the role of captopril (D-3-mercapto-2-methylpropionyl-L-proline), one of the potent ACE inhibitors, in regulating hematopoietic stem/progenitor cell proliferation. Captopril (10(-6) M final concentration) was added to LTBMCs at the beginning of the culture period and at weekly intervals for six weeks. There was no toxicity to the bone marrow cells as measured by the unchanged cell number in the nonadherent layer during the whole culture period, and there was an increased cellularity of the adherent layer at the end of the six weeks of treatment. However, captopril decreased the proportion of granulocyte-macrophage colony-forming cells (GM-CFCs) in S phase at weeks 2 and 3 as well as that of high proliferative potential colony-forming cells (HPP-CFCs) at week 3 in the nonadherent layer. There was no change in the kinetics of the GM-CFCs and HPP-CFCs present in the adherent layer. These results suggest that captopril causes myelosuppression by inhibiting hematopoietic cell proliferation of progenitor and stem cells rather than depleting cells of the bone marrow microenvironment.

Inhibitory action of the peptide AcSDKP on the proliferative state of hematopoietic stem cells in the presence of captopril but not lisinopril.

The effect of Angiotensin I-converting enzyme (ACE) inhibitors on their own and in combination with the peptide AcSDKP on the proliferation of hematopoietic stem cells has been investigated. Hematopoietic stem cells from murine bone marrow induced into cell cycle following exposure to 2 Gy gamma-irradiation were incubated in vitro for up to 24 h in the presence of medium, captopril/lisinopril, AcSDKP, and AcSDKP with either ACE inhibitor. Hematopoietic stem cells were monitored using the high proliferative potential-colony forming cell-1 (HPP-CFC-1) population cloned in the presence of human IL-1 beta, murine IL-3, and murine M-CSF. No significant inhibitory effect was observed in the presence of AcSDKP on its own and AcSDKP in combination with lisinopril. However, there was a significant inhibition of stem cell cycling when AcSDKP and captopril were combined. This suggests that captopril inhibits AcSDKP breakdown better than lisinopril. The combination of AcSDKP and captopril also had an inhibitory effect on cell recruitment into S phase. The fact that a combination of AcSDKP and captopril switches cycling hematopoietic stem cells out of cycle indicates the importance of the N-active catalytic site of ACE in AcSDKP hydrolysis in vitro. Thus, AcSDKP in combination with appropriate ACE inhibitors may be of use in regulating the proliferation of hematopoietic stem cells in vitro.