Spatial and demographic patterns of Cholera in Ashanti region - Ghana

Background  

Cholera has claimed many lives throughout history and it continues to be a global threat, especially in countries in Africa. The disease is listed as one of three internationally quarantinable diseases by the World Health organization, along with plague and yellow fever. Between 1999 and 2005, Africa alone accounted for about 90% of over 1 million reported cholera cases worldwide. In Ghana, there have been over 27000 reported cases since 1999. In one of the affected regions in Ghana, Ashanti region, massive outbreaks and high incidences of cholera have predominated in urban and overcrowded communities.     

Histopathologic features of Mycobacterium ulcerans infection

Because of the emergence of Buruli ulcer disease, the World Health Organization launched a Global Buruli Ulcer Initiative in 1998. This indolent skin infection is caused by Mycobacterium ulcerans. During a study of risk factors for the disease in Ghana, adequate excisional skin-biopsy specimens were obtained from 124 clinically suspicious lesions. Buruli ulcer disease was diagnosed in 78 lesions since acid-fast bacilli (AFB) were found by histopathologic examination. Lesions with other diagnoses included filariasis (3 cases), zygomycosis (2 cases), ulcerative squamous cell carcinomas (2 cases), keratin cyst (1 case), and lymph node (1 case). Thirty-seven specimens that did not show AFB were considered suspected Buruli ulcer disease cases. Necrosis of subcutaneous tissues and dermal collagen were found more frequently in AFB-positive specimens compared with specimens from suspected case-patients (p<0.001). Defining histologic criteria for a diagnosis of Buruli ulcer disease is of clinical and public health importance since it would allow earlier treatment, leading to less deforming sequelae.     

Risk factors for Mycobacterium ulcerans infection, southeastern Australia

Buruli/Bairnsdale ulcer (BU) is a severe skin and soft tissue disease caused by Mycobacterium ulcerans. To better understand how BU is acquired, we conducted a case-control study during a sustained outbreak in temperate southeastern Australia. We recruited 49 adult patients with BU and 609 control participants from a newly recognized BU-endemic area in southeastern Australia. Participants were asked about their lifestyle and insect exposure. Odds ratios were calculated by using logistic regression and were adjusted for age and location of residence. Odds of having BU were at least halved for those who frequently used insect repellent, wore long trousers outdoors, and immediately washed minor skin wounds; odds were at least doubled for those who received mosquito bites on the lower legs or lower arms. This study provides new circumstantial evidence that implicates mosquitoes in the transmission of M. ulcerans in southeastern Australia.     

Buruli ulcer (Mycobacterium ulcerans infection)

Mycobacterium ulcerans is an emerging infection that causes indolent, necrotizing skin lesions known as Buruli ulcer (BU). Bone lesions may include reactive osteitis or osteomyelitis beneath skin lesions, or metastatic osteomyelitis from lymphohematogenous spread of M. ulcerans. Pathogenesis is related to a necrotizing and immunosuppressive toxin produced by M. ulcerans, called mycolactone. The incidence of BU is highest in children up to 15 years old, and is a major public health problem in endemic countries due to disabling scarring and destruction of bone. Most patients live in West Africa, but the disease has been confirmed in at least 30 countries. Treatment options for BU are antibiotics and surgery. BCG vaccination provides short-term protection against M. ulcerans infection and prevents osteomyelitis. HIV infection may increase risk for BU, and renders BU highly aggressive. Unlike leprosy and tuberculosis, BU is related to environmental factors and is thus considered non-communicable. The most plausible mode of transmission is by skin trauma at sites contaminated by M. ulcerans. The reemergence of BU around 1980 may be attributable to environmental factors such as deforestation, artificial topographic alterations and increased manual agriculture of wetlands. The first cultivation of M. ulcerans from nature was reported in 2008.     

Postulated epidemiology of Mycobacterium ulcerans infection.

Mycobacterium ulcerans infection occurs in closely defined areas throughout the world, mostly in the tropics. Whenever it occurs there is a relationship with rain forest and this relationship is apparent in Gippsland, Australia which is not tropical but which contains isolated pockets of relict warm temperate rain forest. Human infection follows rain forest disturbance; it is postulated that the mycobacterium is carried into draining lacustrine systems where it multiplies over a period of months or years and is then disseminated in aerosol from to re-infect its ancestral home and incidentally to infect man.     

Mycobacterium ulcerans disease, Peru

Eight adult patients (ages 18-58, 5 women) with Buruli ulcer (BU) confirmed by at least 2 diagnostic methods were seen in a 10-year period. Attempts to culture Mycobacterium ulcerans failed. Five patients came from jungle areas, and 3 from the swampy northern coast of Peru. The patients had 1-5 lesions, most of which were on the lower extremities. One patient had 5 clustered gluteal lesions; another patient had 2 lesions on a finger. Three patients were lost to follow-up. All 5 remaining patients had moderate disease. Diverse treatments (antituberculous drugs, World Health Organization [WHO] recommended antimicrobial drug treatment for BU, and for 3 patients, excision surgery) were successful. Only 1 patient (patient 7) received the specific drug treatment recommended by WHO. BU is endemic in Peru, although apparently infrequent. Education of populations and training of health workers are first needed to evaluate and understand the full extent of BU in Peru.     

Blood pressure patterns in rural,semi-urban and urban children in the Ashanti region of Ghana,West Africa

Background  

High blood pressure, once rare, is rapidly becoming a major public health burden in sub-Saharan/Africa. It is unclear whether this is reflected in children. The main purpose of this study was to assess blood pressure patterns among rural, semi-urban, and urban children and to determine the association of blood pressure with locality and body mass index (BMI) in this sub-Saharan Africa setting.     

Mycobacterium ulcerans disease

Mycobacterium ulcerans disease (Buruli ulcer) is an important health problem in several west African countries. It is prevalent in scattered foci around the world, predominantly in riverine areas with a humid, hot climate. We review the epidemiology, bacteriology, transmission, immunology, pathology, diagnosis and treatment of infections. M. ulcerans is an ubiquitous micro-organism and is harboured by fish, snails, and water insects. The mode of transmission is unknown. Lesions are most common on exposed parts of the body, particularly on the limbs. Spontaneous healing may occur. Many patients in endemic areas present late with advanced, severe lesions. BCG vaccination yields a limited, relatively short-lived, immune protection. Recommended treatment consists of surgical debridement, followed by skin grafting if necessary. Many patients have functional limitations after healing. Better understanding of disease transmission and pathogenesis is needed for improved control and prevention of Buruli ulcer.     

Mycobacterium ulcerans treatment costs, Australia

Mycobacterium ulcerans gives rise to severe skin ulceration that can be associated with considerable illness. The cost of diagnosis, treatment, and lost income has never been assessed in Australia. A survey of 26 confirmed cases of the disease in Victoria was undertaken. Data were collected on demographic details, diagnostic tests, treatment, time off work, and travel to obtain treatment. All costs are reported in Australian dollars in 1997-98 prices. The cost varies considerably with disease severity. For mild cases, the average direct cost is 6,803 Australian dollars, and for severe cases 27,681 Australian dollars. Hospitalization accounts for 61% to 90% of costs, and indirect costs amount to 24% of the total per case. M. ulcerans can be an expensive disease to diagnose and treat. Costs can be reduced by early diagnosis and definitive treatment. Research is needed to find cost-effective therapies for this disease.     

Prehypertension in the Ashanti region of Ghana, West Africa: an opportunity for early prevention of clinical hypertension

OBJECTIVE: To assess prehypertension among Ghanaian adults in the Ashanti region of Ghana, West Africa. DESIGN: Cross-sectional study. PARTICIPANTS: There were 1431 participants aged 18 years or more. Prehypertension was defined as blood pressure of 120-139/80-89 mmHg. MAIN OUTCOME MEASURES: Prehypertension. RESULTS: Overall, 31% of the study population were normotensive, 40% were prehypertensive and 29% were hypertensive. Prehypertension was more common in non-hypertensive males than non-hypertensive females (66% vs 49%, P<0.001). Prehypertension was also more common in those aged 35 years compared with those aged <35 years (P<0.001), and in overweight and obese people compared with people of normal weight (P=0.03). In a multivariate logistic regression model, male sex [odds ratio (OR) 2.36; 95% confidence interval (CI) 1.77-3.15; P<0.001], age 35-49 years (OR 1.56; 95% CI 1.12-2.18; P<0.01) and 50 years (OR 2.13; 95% CI 1.33-3.42; P=0.002)], overweight (OR 1.61; 95% CI 1.09-2.36; P=0.02) and obesity (OR 2.71; 95% CI 1.40-5.24; P=0.003) were independently associated with higher odds of prehypertension, whilst current smoking (OR 0.36; 95% CI 0.16-0.81; P=0.01) was associated with lower odds of prehypertension. CONCLUSION: Prehypertension is very common among non-hypertensive subjects in the Ashanti region of Ghana. As a large proportion of people with prehypertension will progress to clinical hypertension, targeting these people early with lifestyle modifications such as weight reduction may provide important long-term benefits.     

Mycobacterium ulcerans in wild animals

Mycobacterium ulcerans infection, or Buruli ulcer, is the third most frequent mycobacterial disease in humans, often causing serious deformities and disability. The disease is most closely associated with tropical wetlands, especially in west and central Africa. Most investigators believe that the aetiological agent proliferates in mud beneath stagnant waters. Modes of transmission may involve direct contact with the contaminated environment, aerosols from water surfaces, and water-dwelling fauna (e.g. insects). Person-to-person transmission is rare. Trauma at the site of skin contamination by M. ulcerans appears to play an important role in initiating disease. Once introduced into the skin or subcutaneous tissue, M. ulcerans multiplies and produces a toxin that causes necrosis. However, the type of disease induced varies from a localised nodule or ulcer, to widespread ulcerative or non-ulcerative disease and osteomyelitis. Although culture of M. ulcerans from a patient was first reported in 1948, attempts to culture the mycobacterium from many specimens of flora and fauna have been unsuccessful. Failure to cultivate this organism from nature may be attributable to inadequate sampling, conditions of transport, decontamination and culture of this fastidious heat-sensitive organism, and to a long generation time relative to that of other environmental mycobacteria. Nevertheless, recent molecular studies using specific primers have revealed M. ulcerans in water, mud, fish and insects. Although no natural reservoir has been found, the possibility that M. ulcerans may colonise microfauna such as free-living amoebae has not been investigated. The host range of experimental infection by M. ulcerans includes lizards, amphibians, chick embryos, possums, armadillos, rats, mice and cattle. Natural infections have been observed only in Australia, in koalas, ringtail possums and a captive alpaca. The lesions were clinically identical to those observed in humans. Mycobacterium ulcerans infection is a rapidly re-emerging disease in some developing tropical countries. The re-emergence may be related to environmental and socioeconomic factors, for example, deforestation leading to increased flooding, and population expansion without improved agricultural techniques, thus putting more people at risk. Eradication of diseases related to these factors is difficult. Whether wild animals have a role in transmission is an important question that, to date, has been virtually unexplored. To address this question, surveys of wild animals are urgently required in those areas in which Buruli ulcer is endemic.     

An outreach education and treatment project in Ghana for the early stage of Mycobacterium ulcerans disease

Mycobacterium ulcerans disease starts as a painless, subcutaneous nodule, excision of which prevents the development of large Buruli ulcers. An outreach programme was set up in Ghana to promote nodule recognition and excision. The programme was cost-effective and shifted the pattern of disease presentation. This could from a model for other countries.     

First reported case of Mycobacterium ulcerans infection in a patient from China

Buruli ulcers have not been previously described in China, and only once at higher latitudes on the northern hemisphere. A patient who travelled in the Shan Dong Province in the People's Republic of China developed an ulcer which was proven to be a Buruli ulcer. The clinical picture and histopathological findings from biopsy specimens are characteristic for a Buruli ulcer, and also the growth in culture (Coletsos medium) at a restricted temperature of 30 degrees C. A multiplex polymerase chain reaction (PCR) based on the amplification of the gene encoding for 16S ribosomal RNA and a nested PCR based on the Mycobacterium ulcerans specific repeated sequence 2404 were performed. These PCR investigations identified the bacteria as M. ulcerans, subspecies shinshuense. The patient was initially treated with clarithromycin and rifampicin, which was changed to ciprofloxacin and rifabutin when rifampicin resistance of the first isolate was established. There were no signs of reactivation of the disease 6 months after the end of treatment. M. ulcerans infection occurs above 30 degrees latitude on the northern hemisphere in China and is caused by M. ulcerans, subspecies shinshuense. This case appears to be cured by chemotherapy alone, in contrast to the general experience that surgical treatment is indicated. The granulomatous reaction with only fragments of acid-fast bacteria in the biopsy at the end of treatment many indicate the development of an adequate cell-mediated immune response leading to resistance to the infection.     

Gender and the utilisation of health services in the Ashanti Region, Ghana

The survey seeks to structure a model for gender-based health services utilisation for the Ashanti Region of Ghana, and in addition, recommend intervention measures to ensure gender equity in the utilisation of health services. A sample size of 650 covered over 3108 houses, and the main research instruments were the questionnaire and formal interview. A multiple regression model is used for the analysis of the relationship between the complex independent variables and utilisation by gender. Results show that although females have a greater need for health services than males, they do not utilise health services as much. Secondly, whereas quality of service, health status, service cost and education have greater effect on male utilisation than females, distance and income have higher impact on female utilisation. It is recommended that, to ensure equity in health care utilisation, females be empowered through increased access to formal education and sustainable income opportunities. The introduction of a national health insurance scheme is also recommended to ensure adequate access by both sexes.     

Ongoing genome reduction in Mycobacterium ulcerans

Elucidation of the transmission, epidemiology, and evolution of Mycobacterium ulcerans, the causative agent of Buruli ulcer, is hampered by the striking lack of genetic diversity of this emerging pathogen. However, by using a prototype plasmid-based microarray that covered 10% of the genome, we found multiple genomic DNA deletions among 30 M. ulcerans clinical isolates of diverse geographic origins. Many of the changes appear to have been mediated by insertion sequence (IS) elements IS2404 and IS2606, which have high copy numbers. Classification of the deleted genes according to their biological functions supports the hypothesis that M. ulcerans has recently evolved from the generalist environmental M. marinum to become a niche-adapted specialist. The substantial genomic diversity, along with a prototype microarray that covered a small portion of the genome, suggests that a genome-wide microarray will make available a genetic fingerprinting method with the high resolution required for microepidemiologic studies.     

Protective effect of a dewaxed whole-cell vaccine against Mycobacterium ulcerans infection in mice

Mycobacterium ulcerans causes Buruli ulcer, a chronic and destructive necrotizing ulcer in humans. Effective vaccination should be one of the best methods for the prevention of this ulcer. However, no effective vaccines have been developed against M. ulcerans infection. In an effort to develop such a vaccine, we examined protective immunity against M. ulcerans infection in a mouse footpad-infection model. Prior infection of mice with a virulent strain of M. ulcerans or a mycolactone-deficient strain of M. ulcerans resulted in limited protection against subsequent challenge by a virulent strain of M. ulcerans. Protection was not induced in mice immunized with a formalin-treated killed whole-cell preparation of M. ulcerans. By contrast, a dewaxed whole-cell vaccine, prepared by dewaxing M. ulcerans with organic solvents that removed mycolactones and waxy cell walls from the cells, induced significant protection in mice. Our observations should facilitate development of effective vaccines against Buruli ulcer for control of this disease.