Emilio Letang

Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital

Objectives  To describe the prevalence, aetiology and prognostic implications of coexisting invasive bacterial disease in children admitted with severe malaria in a rural Mozambican Hospital.

A 10 year study of the cause of death in children under 15 years in Manhiça, Mozambique

BackgroundApproximately 46 million of the estimated 60 million deaths that occur in the world each year take place in developing countries. Further, this mortality is highest in Sub-Saharan Africa, although causes of mortality in this region are not well documented. The objective of this study is to describe the most frequent causes of mortality in children under 15 years of age in the demographic surveillance area of the Manhiça Health Research Centre, between 1997 and 2006, using the verbal autopsy tool.MethodsVerbal autopsy interviews for causes of death in children began in 1997. Each questionnaire was reviewed independently by three physicians with experience in tropical paediatrics, who assigned the cause of death according to the International Classification of Diseases (ICD-10). Each medical doctor attributed a minimum of one and a maximum of 2 causes. A final diagnosis is reached when at least two physicians agreed on the cause of death.ResultsFrom January 1997 to December 2006, 568499 person-year at risk (pyrs) and 10037 deaths were recorded in the Manhiça DSS. 3730 deaths with 246658 pyrs were recorded for children under 15 years of age. Verbal autopsy interviews were conducted on 3002 (80.4%) of these deaths. 73.6% of deaths were attributed to communicable diseases, non-communicable diseases accounted for 9.5% of the defined causes of death, and injuries for 3.9% of causes of deaths. Malaria was the single largest cause, accounting for 21.8% of cases. Pneumonia with 9.8% was the second leading cause of death, followed by HIV/AIDS (8.3%) and diarrhoeal diseases with 8%.ConclusionThe results of this study stand out the big challenges that lie ahead in the fight against infectious diseases in the study area. The pattern of childhood mortality in Manhiça area is typical of developing countries where malaria, pneumonia and HIV/AIDS are important causes of death.

Experimental reconstruction of the canine trachea with a free revascularized small bowel graft

Extensive tracheal stenotic lesions caused by tracheomalacia or neoplasms represent a surgical challenge. Segmental tracheal substitution is sometimes required to obtain radical cure. We present an experimental study of 27 dogs undergoing replacement of the cervical trachea using a vascularized small bowel segment as a tubular graft. A silicone stent was placed in the lumen of the intestinal fragment and was removed the second week after operation. Endoscopic and histological examinations were performed between the first week and second month after operation, and rigidity of the graft was assessed in all cases. No evidence of anastomotic stricture or mucous formation was found. Microscopic examination showed the substitution of bowel mucosa by squamous epithelium as well as the development of connective tissue favoring the fixation of the skeletal muscular structures of the neck to the serous layer of the graft, thus avoiding collapse of the new airway.

Predictors of Immune Reconstitution Inflammatory Syndrome-Associated With Kaposi Sarcoma in Mozambique: A Prospective Study

Background:The impact and relevance of immune reconstitution inflammatory syndrome-associated with Kaposi sarcoma (IRIS-KS) has not been assessed in sub-Saharan African countries, where the bulk of HIV-1 and KS-associated herpesvirus (KSHV) coinfection occurs. Understanding the risk factors for developing IRIS-KS would aid in the identification and in the improvement of clinical management for high-risk patients. Methods:Sixty-nine consecutive HIV-1 and KSHV coinfected Mozambican adults initiating cART were prospectively followed for development of IRIS-KS over 10 months as part of a larger prospective observational study. Plasma HIV RNA, CD4+ counts, anti-KSHV lytic antibodies, and plasma KSHV DNA viral load were assessed at the pre-cART visit and at 4 and 10 months after cART initiation. A survival analysis was performed to assess potential risk factors for developing IRIS-KS. Results:During the first 10 months of combined antiretroviral therapy (cART), 8 patients (8/69, 11.6%) experienced IRIS-KS at a median time of 13.8 weeks after cART initiation. Multivariate analysis identified 4 independent IRIS-KS predictors: clinical pretreatment KS [hazard ratio (HR) 91.7], detectable plasma KSHV DNA (HR 24.4), hematocrit <30% (HR 26.5), and plasma HIV-1 RNA viral load (HR 34.6 per log viral load increase). Treatment with either cART alone or with a combination of cART and systemic chemotherapy led to partial or complete clinical response in 62.5% (5/8) of IRIS-KS cases. Conclusions:This study identified 4 independent predictors of IRIS-KS, which may help to develop screening tools aiding in the identification of patients at high risk of IRIS-KS for whom close clinical supervision is warranted.

Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma: higher incidence and mortality in Africa than in the UK.

Objectives:To assess the incidence, predictors, and outcomes of Kaposi sarcoma-associated paradoxical immune reconstitution inflammatory syndrome (KS-IRIS) in antiretroviral therapy (ART)-naive HIV-infected patients with Kaposi sarcoma initiating ART in both well resourced and limited-resourced settings. Design:Pooled analysis of three prospective cohorts of ART-naive HIV-infected patients with Kaposi sarcoma from sub-Saharan Africa (SSA) and one from the UK. Methods:KS-IRIS case definition was standardized across sites. Cox regression and Kaplan–Meier survival analysis were used to identify the incidence and predictors of KS-IRIS and Kaposi sarcoma-associated mortality. Results:Fifty-eight of 417 (13.9%) eligible individuals experienced KS-IRIS with an incidence 2.5 times higher in the African vs. European cohorts (P = 0.001). ART alone as initial Kaposi sarcoma treatment (hazard ratio 2.97, 95% confidence interval (CI) 1.02–8.69); T1 Kaposi sarcoma stage (hazard ratio 2.96, 95% CI 1.26–6.94); and plasma HIV-1 RNA more than 5 log10 copies/ml (hazard ratio 2.14, 95% CI 1.25–3.67) independently predicted KS-IRIS at baseline. Detectable plasma Kaposi sarcoma-associated herpes virus (KSHV) DNA additionally predicted KS-IRIS among the 259 patients with KSHV DNA assessed (hazard ratio 2.98, 95% CI 1.23–7.19). Nineteen KS-IRIS patients died, all in SSA. Kaposi sarcoma mortality was 3.3-fold higher in Africa, and was predicted by KS-IRIS (hazard ratio 19.24, CI 7.62–48.58), lack of chemotherapy (hazard ratio 2.35, 95% CI 1.09–5.05), pre-ART CD4 cell count less than 200 cells/&mgr;l (hazard ratio 2.04, 95% CI 0.99–4.2), and detectable baseline KSHV DNA (hazard ratio 2.12, 95% CI 0.94–4.77). Conclusion:KS-IRIS incidence and mortality are higher in SSA than in the UK. This is largely explained by the more advanced Kaposi sarcoma disease and lower chemotherapy availability. KS-IRIS is a major contributor to Kaposi sarcoma-associated mortality in Africa. Our results support the need to increase awareness on KS-IRIS, encourage earlier presentation, referral and diagnosis of Kaposi sarcoma, and advocate on access to systemic chemotherapy in Africa.

Surveillance of acute bacterial meningitis among children admitted to a district hospital in rural Mozambique.

BACKGROUND Acute bacterial meningitis (ABM) remains an important cause of mortality among African children. Epidemiologic data with regard to ABM infection are necessary for prioritizing public health interventions. METHODS We strengthened hospital-based surveillance of ABM among children admitted to Manhiça District Hospital (Maputo, Mozambique). Cerebrospinal fluid (CSF) samples were collected from children admitted to the hospital who met clinical criteria of ABM. Laboratory determinations were performed. Clinical information and outcome of cases were recorded. RESULTS During the first 12 months of surveillance, which began in January 2006, CSF samples were collected from 642 children <15 years of age with suspected meningitis (18% of all pediatric patients admitted to the hospital during that time). ABM was confirmed in 43 (7%) of the 642 cases. Haemophilus influenzae type b (Hib) (14 cases), pneumococcus (9 cases), and meningococcus (7 cases) represented approximately 70% of confirmed cases. Four of the 9 pneumococci were serotypes covered by the 7-valent pneumococcal conjugate vaccine. The case fatality rate among patients with ABM was 24% (8 of 33 with known outcome); an additional 8 patients left the hospital before discharge. The incidence of ABM was 85 per 100,000 population, which peaked at 2-12 months of age at 1078 cases per 100,000 population. All 9 pneumococci isolates were susceptible to chloramphenicol, and 8 were susceptible to penicillin (the additional 1 had intermediate resistance). For the 10 Hib isolates tested, only 1 was susceptible to chloramphenicol, and 5 were susceptible to ampicillin. CONCLUSION These data reinforce the importance of ABM as a cause of hospital admission and death in rural sub-Saharan Africa. Most observed ABM cases could have been prevented by current pneumococcal and Hib conjugate vaccines.

High prevalence of symptomatic acute HIV infection in an outpatient ward in southern Mozambique: identification and follow-up.

Objectives:To determine the prevalence of acute HIV infection (AHI) within the HIV-seronegative adult population presenting with reported fever in a district hospital in southern Mozambique and evaluate clinical, immunological and virological parameters of AHI. Design:This is a prospective observational study. Methods:Three hundred and forty-six adults presenting with reported fever at an outpatient ward at the Manhiça District Hospital in Mozambique were screened for AHI by HIV rapid serology testing, followed by HIV-RNA testing in HIV-seronegative individuals. Plasma from HIV-seronegative patients was pooled in the ratio of 1: 5 for HIV-RNA testing. Whole blood was used for Plasmodium falciparum rapid test determination at screening visit. Follow-up visits at day 7, 4 and 10 months included clinical examination, HIV serotesting and assessment of HIV-RNA, CD4 cell counts and percentage of activated CD8 T cells. Results:HIV serotesting revealed that 37.8% (95% confidence interval 32.7–43.2) of the adults had previously undiagnosed established HIV infection. Among the HIV-seronegative patients, 3.3% (95% confidence interval 1.3–6.7) were found to have AHI as demonstrated by positive HIV-1 RNA testing. Median HIV-1 RNA levels at diagnosis of AHI were 6.21 log10 copies/ml (interquartile range 5.92–6.41) and significantly higher than median HIV-RNA load at 4 months. At day 7 after screening, patients showed a median CD4 cell count of 384 cells/μl (interquartile range 239–441) and a median percentage of activated CD8 T cells of 68.4% (interquartile range 59.6–87.8). Conclusion:Of patients reporting with fever, 3.3% were shown to be potentially due to AHI. High prevalence of AHI in southern African populations may warrant investigation of tools and target populations for AHI screening as a novel way to address HIV prevention.

Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus Patients in Rural Tanzania: A Preventable Cause of Early Mortality

Cryptococcal antigenemia was prevalent and an independent predictor of mortality/loss-to-follow-up in this Tanzanian cohort of ART-naïve HIV-infected individuals with CD4 <150 cells/μL. Fluconazole decreased mortality/loss-to-follow-up. These findings support the urgent adoption of the CD4-targeted cryptococcal antigen screening recommendations in Tanzania.

Incidence and predictors of immune reconstitution inflammatory syndrome in a rural area of Mozambique.

Background There is limited data on the epidemiology of Immune Reconstitution Inflammatory Syndrome (IRIS) in rural sub-Saharan Africa. A prospective observational cohort study was conducted to assess the incidence, clinical characteristics, outcome and predictors of IRIS in rural Mozambique. Methods One hundred and thirty-six consecutive antiretroviral treatment (ART)-naïve HIV-1-infected patients initiating ART at the Manhiça district hospital were prospectively followed for development of IRIS over 16 months. Survival analysis by Cox regression was performed to identify pre-ART predictors of IRIS development. Results Thirty-six patients developed IRIS [26.5%, incidence rate 3.1 cases/100 persons-month of ART (95% CI 2.2–4.3)]. Median time to IRIS onset was 62 days from ART initiation (IQR 35.5–93.5). Twenty-five cases (69.4%) were “unmasking”, 10 (27.8%) were “paradoxical”, and 1 (2.8%) developed a paradoxical worsening followed by the unmasking of another condition. Systemic OI (OI-IRIS) accounted for 47% (17/36) of IRIS cases, predominantly of KS (8 cases) and TB (6 cases) IRIS. Mucocutaneous IRIS manifestations (MC-IRIS) accounted for 53% (19/36) of IRIS events, mostly tinea (9 cases) and herpes simplex infection (3 cases). Multivariate analysis identified two independent predictors of IRIS development: pre-ART CD4 count <50 cells/µl (HR 2.3, 95% CI 1.19–4.44, p = 0.01) and body mass index (BMI) <18.5 (HR 2.15, 95% CI 1.07–4.3, p = 0.03). The pre-cART proportion of activated T-cells, as well as the immunologic and virologic response to ART were not associated with IRIS development. All patients continued on ART, 7 (19.4%) required hospitalization and there were 3 deaths (8.3%) attributable to IRIS. Conclusions IRIS is common in patients initiating ART in rural Mozambique. Pre-ART CD4 counts and BMI can easily be assessed at ART initiation in rural sub-Saharan Africa to identify patients at high risk of IRIS, for whom close supervision is warranted.

Viral hepatitis and rapid diagnostic test based screening for HBsAg in HIV-infected patients in rural Tanzania

Background Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Methods Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Results Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32–47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97–439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2–13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8–99.6%) and specificity at 100% (95% CI, 98.9–100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0–6.4%) of patients. Conclusion This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.