Novel cyclovirus in human cerebrospinal fluid, Malawi, 2010-2011.

To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism.

The College of Medicine in the Republic of Malawi: towards sustainable staff development.

BACKGROUND: Malawi has a critical human resources problem particularly in the health sector. There is a severe shortage of doctors; there are only few medical specialists. The College of Medicine (COM) is the only medical school and was founded in 1991. For senior staff it heavily depends on expatriates. In 2004 the COM started its own postgraduate training programme (Master of Medicine) in the clinical specialties. METHODS: We explore to what extent a brain drain took place among the COM graduates by investigating their professional development and geographical distribution. Using current experience with the postgraduate programme, we estimate at what point all senior academic positions in the clinical departments could be filled by Malawians. We demonstrate the need for expatriate staff for its most senior academic positions in the interim period and how this can be phased out. Lastly we reflect on measures that may influence the retention of Malawian doctors. RESULTS: Since the start of the COM 254 students have graduated with an average of 17 students per year. Most (60%) are working in Malawi. Of those working abroad, 60% are in various postgraduate training programmes. In 2015, adequate numbers of Malawi senior academics should be available to fill most senior positions in the clinical departments, taking into account a 65% increase in staff to cope with increasing numbers of students. CONCLUSION: There seems to be no significant brain drain among graduates of the COM. The postgraduate programme is in place to train graduates to become senior academic staff. In the interim, the COM depends heavily upon expatriate input for its most senior academic positions. This will be necessary at least until 2015 when sufficient numbers of well trained and experienced Malawian specialists may be expected to be available. Improved pay structure and career development perspectives will be essential to consolidate the trend that most doctors will remain in the country.

Prevalence and indicators of HIV and AIDS among adults admitted to medical and surgical wards in Blantyre, Malawi.

Despite high seroprevalence there are few recent studies of the effect of human immunodeficiency virus (HIV) on hospitals in sub-Saharan Africa. We examined 1226 consecutive patients admitted to medical and surgical wards in Blantyre, Malawi during two 2-week periods in October 1999 and January 2000: 70% of medical patients were HIV-positive and 45% had acquired immune deficiency syndrome (AIDS); 36% of surgical patients were HIV-positive and 8% had AIDS. Seroprevalence rose to a peak among 30-40 year olds; 91% of medical, 56% of surgical and 80% of all patients in this age group were HIV-positive. Seropositive women were younger than seropositive men (median age 29 vs. 35 years, P < 0.0001). Symptoms strongly indicative of HIV were history of shingles, chronic diarrhoea or fever or cough, history of tuberculosis (TB), weight loss and persistent itchy rash (adjusted odds ratios [AORs] all > 5). Clinical signs strongly indicative of HIV were oral hairy leukoplakia, shingles scar, Kaposi's sarcoma, oral thrush and hair loss (AORs all > 10). Of surgical patients with 'deep infections' (breast abscess, pyomyositis, osteomyelitis, septic arthritis and multiple abscesses), 52% were HIV-positive (OR compared with other surgical patients = 2.4). Severe bacterial infections, TB and AIDS caused 68% of deaths. HIV dominates adult medicine, is a major part of adult surgery, is the main cause of death in hospital and affects the economically active age group of the population.

Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi.

BACKGROUND: Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis. METHODS: In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, alpha-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting. RESULTS: Body mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 micromol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Wasting, defined as BMI<18.5 was present in 59% of study participants and was independently associated with a higher risk of low carotenoids, and vitamin A and selenium deficiency. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids. CONCLUSIONS: These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition.

Merits and pitfalls of currently used diagnostic tools in mycetoma.

Treatment of mycetoma depends on the causative organism and since many organisms, both actinomycetes (actinomycetoma) and fungi (eumycetoma), are capable of producing mycetoma, an accurate diagnosis is crucial. Currently, multiple diagnostic tools are used to determine the extent of infections and to identify the causative agents of mycetoma. These include various imaging, cytological, histopathological, serological, and culture techniques; phenotypic characterisation; and molecular diagnostics. In this review, we summarize these techniques and identify their merits and pitfalls in the identification of the causative agents of mycetoma and the extent of the disease. We also emphasize the fact that there is no ideal diagnostic tool available to identify the causative agents and that future research should focus on the development of new and reliable diagnostic tools.

A screen-and-treat strategy targeting visceral leishmaniasis in HIV-infected individuals in endemic East African countries: the way forward?

In the wake of the HIV epidemic, visceral leishmaniasis (VL), a disseminated protozoan infection caused by the Leishmania donovani complex, has been re-emerging, particularly in North Ethiopia where up to 40% of patients with VL are co-infected with HIV. Management of VL in HIV co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. Tackling L. donovani infection before disease onset would thus be a logical approach. A screen-and-treat approach targeting latent or the early stage of infection has successfully been implemented in other HIV-associated opportunistic infections. While conceptually attractive in the context of VL-HIV, the basic understanding and evidence underpinning such an approach is currently lacking. Prospective cohort studies will have to be conducted to quantify the risk of VL in different risk groups and across CD4 cell count levels. This will allow developing clinical prognostic tools, integrating clinical, HIV and Leishmania infection markers. Interventional studies will be needed to evaluate prophylactic or pre-emptive treatment strategies for those at risk, ideally relying on an oral (combination) regimen. Issues like tolerability, emergence of resistance and drug interactions will require due attention. The need for maintenance therapy will have to be assessed. Based on the risk-benefit data, VL risk cut-offs will have to be identified to target treatment to those most likely to benefit. Such a strategy should be complemented with early initiation of antiretroviral treatment and other strategies to prevent HIV and Leishmania infection.

Madurella mycetomatis is highly susceptible to ravuconazole.

The current treatment of eumycetoma utilizing ketoconazole is unsatisfactory because of high recurrence rates, which often leads to complications and unnecessary amputations, and its comparatively high cost in endemic areas. Hence, an effective and affordable drug is required to improve therapeutic outcome. E1224 is a potent orally available, broad-spectrum triazole currently being developed for the treatment of Chagas disease. E1224 is a prodrug that is rapidly converted to ravuconazole. Plasma levels of E1224 are low and transient, and its therapeutically active moiety, ravuconazole is therapeutically active. In the present study, the in vitro activity of ravuconazole against Madurella mycetomatis, the most common etiologic agent of eumycetoma, was evaluated and compared to that of ketoconazole and itraconazole. Ravuconazole showed excellent activity with MICs ranging between ≤ 0.002 and 0.031 µg/ml, which were significantly lower than the MICs reported for ketoconazole and itraconazole. On the basis of our findings, E1224 with its resultant active moiety, ravuconazole, could be an effective and affordable therapeutic option for the treatment of eumycetoma.

Report of the Post Kala-azar Dermal Leishmaniasis (PKDL) Consortium Meeting, New Delhi, India, 27-29 June 2012.

Post kala-azar dermal leishmaniasis (PKDL) is a neglected complication of visceral leishmaniasis (VL)-a deadly, infectious disease that claims approximately 20,000 to 40,000 lives every year. PKDL is thought to be a reservoir for transmission of VL, thus, adequate control of PKDL plays a key role in the ongoing effort to eliminate VL. Over the past few years, several expert meetings have recommended that a greater focus on PKDL was needed, especially in South Asia. This report summarizes the Post Kala-Azar Dermal Leishmaniasis Consortium Meeting held in New Delhi, India, 27-29 June 2012. The PKDL Consortium is committed to promote and facilitate activities that lead to better understanding of all aspects of PKDL that are needed for improved clinical management and to achieve control of PKDL and VL. Fifty clinicians, scientists, policy makers, and advocates came together to discuss issues relating to PKDL epidemiology, diagnosis, pathogenesis, clinical presentation, treatment, and control. Colleagues who were unable to attend participated during drafting of the consortium meeting report.

Etiology of suspected pneumonia in adults admitted to a high-dependency unit in Blantyre, Malawi.

The microbiologic etiology of severe pneumonia in hospitalized patients is rarely known in sub-Saharan Africa. Through a comprehensive diagnostic work-up, we aimed to identify the causative agent in severely ill patients with a clinical picture of pneumonia admitted to a high-dependency unit. A final diagnosis was made and categorized as confirmed or probable by using predefined criteria. Fifty-one patients were recruited (45% females), with a mean age of 35 years (range = 17-88 years), of whom 11(22%) died. Forty-eight (94%) of the patients were seropositive for human immunodeficiency virus; 14 (29%) of these patients were receiving antiretroviral treatment. Final diagnoses were bacterial pneumonia (29%), Pneumocystis jirovecii pneumonia (27%), pulmonary tuberculosis (22%), and pulmonary Kaposi's sarcoma (16%); 39 (77%) of these cases were confirmed cases. Fifteen (29%) patients had multiple isolates. At least 3 of 11 viral-positive polymerase chain reaction (PCR) results of bronchoalveolar lavage fluid were attributed clinical relevance. No atypical bacterial organisms were found.

Effect of recurrent invasive pneumococcal disease on serum anti-pneumolysin IgG titres in HIV infected adults.

We measured serum anti-pneumolysin IgG concentrations in a prospective cohort of 34 HIV infected adults who developed recurrent pneumococcal bacteraemia, and compared baseline levels with HIV positive and HIV negative control subjects that remained free of pneumococcal disease. Anti-pneumolysin concentrations in HIV positive cases and controls were higher compared to HIV negative controls. There was no significant difference in levels between HIV positive subjects who did and did not subsequently develop pneumococcal bacteraemia (geometric means 849.1 U/ml vs. 564.6 U/ml, p=0.059). Anti-pneumolysin IgG titres before, and after the recurrent episode of pneumococcal bacteraemia did not differ significantly (p=0.95). High levels of anti-pneumolysin IgG do not predict protection from invasive pneumococcal disease or indicate that an effective immune response has occurred in HIV infected patients.

Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi.

BACKGROUND: In Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ) since sulfadoxine-pyrimethamine (SP) replaced CQ as first line treatment for uncomplicated malaria. When used for prophylaxis, Amodiaquine (AQ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa. Here we compare the efficacy, safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria. METHODOLOGY AND FINDINGS: 455 children aged 1-5 years were recruited into a double-blinded randomised trial comparing SP to the three combination therapies. Using intention to treat analysis with missing outcomes treated as successes, and without adjustment to distinguish recrudescence from new infections, the day 28 adequate clinical and parasitological response (ACPR) rate for SP was 25%, inferior to each of the three combination therapies (p<0.001). AQ+SP had an ACPR rate of 97%, higher than CQ+SP (81%) and ART+SP (70%), p<0.001. Nineteen children developed a neutropenia of

Prevalence and indicators of HIV and AIDS among adults admitted to medical and surgical wards in Blantyre, Malawi.

Despite high seroprevalence there are few recent studies of the effect of HIV on hospitals in sub-Saharan Africa. We examined 1226 consecutive patients admitted during two 2-week periods in October 1999 and January 2000. 70% medical patients were HIV positive, and 45% had AIDS. 36% surgical patients were HIV positive and 8% had AIDS. Seroprevalence rose to a peak among 30-40 year olds; 91% medical, 56% surgical and 80% all patients in this age group were HIV positive. Seropositive women were younger than seropositive men (median age 29 v 35, p<0.0001). Symptoms strongly indicative of HIV were history of shingles, chronic diarrhoea or fever or cough, history of tuberculosis, weight loss, and persistent itchy rash (adjusted odds ratios all over 5). Clinical signs strongly indicative of HIV were oral hairy leukoplakia, shingles scar, Kaposi's sarcoma, oral thrush, and hair loss (adjusted odds ratios all over 10). Of surgical patients with 'deep infections' (breast abscess, pyomyositis, osteomyelitis, septic arthritis, and multiple abscesses), 52% were HIV positive (OR compared with other surgical patients 2.4). Severe bacterial infections, tuberculosis, and AIDS caused 68% deaths. HIV dominates adult medicine, is a major part of adult surgery, is the main cause of death in hospital, and affects the economically active age group of the population.

A prospective study of bloodstream infections as cause of fever in Malawi: clinical predictors and implications for management.

OBJECTIVE: To determine the contribution of a blood culture service to the diagnosis of fever in a resource-poor setting and to identify clinical predictors of specific bloodstream infections (BSI). METHODS: In a descriptive, prospective study at the Medical Wards at Queen Elizabeth Central Hospital, Blantyre, Malawi, we tried to identify a specific cause of fever in febrile patients, comparing the use of routinely available diagnostic methods with the same methods plus blood culture. Clinical predictors of specific BSIs were sought. RESULTS: A total of 352 patients admitted with fever (axillary temperature > or =37.4 degrees C) or a history of fever within the last 4 days were enrolled. Tuberculosis (TB) was the diagnosis most commonly suspected initially on clinical grounds (28%), followed by lower respiratory tract infection (16%), malaria (12%) and gastroenteritis (5%). Blood cultures were positive in 128 patients (36%); Mycobacterium tuberculosis was the most commonly isolated organism (57 patients). In most cases the diagnosis of TB had already been made using routinely available diagnostic methods, including chest radiography. In all 16 cases of Streptococcus pneumoniae bacteraemia, infection with this agent was clinically suspected, usually on the basis of pulmonary symptoms and signs. In contrast, in 30 of 65 patients (65%) with non-typhi salmonellae (NTS) bacteraemia, there were no symptoms or signs specifically suggestive of this diagnosis. Fever > or =39 degrees C and splenomegaly predicted NTS bacteraemia with an odds ratio of 8.4 (95% confidence interval 3.4-20.6, P < 0.001). CONCLUSION: BSIs are common among patients admitted with fever. While BSI with mycobacteraemia and S. pneumoniae can usually be predicted on clinical grounds and with routinely available diagnostic methods, NTS bacteraemia often presents as a primary BSI without localizing symptoms and signs. Splenomegaly in this population indicates NTS bacteraemia rather than malaria.

Poor potential coverage for 7-valent pneumococcal conjugate vaccine, Malawi.

Streptococcus pneumoniae infections can be prevented by using new conjugate vaccines, but these vaccines have limited serogroup coverage. We report the first serogrouping data from carried and invasive isolates obtained from children and adults in Malawi. The 7-valent vaccine would cover 41% of invasive isolates from children and 25% from adults. A 9-valent vaccine, including types 1 and 5, would cover 66% of invasive isolates from children and 55% from adults.