WHO Clinical Case Definition Research Articles

#4473 PREVALENCE OF POST-COVID-19 CONDITION IN PATIENTS WITH CHRONIC KIDNEY DISEASE, ON DIALYSIS AND LIVING WITH A KIDNEY TRANSPLANT

Abstract Background and Aims The prevalence of post-COVID-19 condition (PCC) is estimated to be 13% in healthy individuals. We analyzed the prevalence and disease burden of PCC in patients with chronic kidney disease (CKD) G4/5, dialysis patients and kidney transplant recipients (KTR). Method Patients participated in the RECOVAC study, in which SARS-CoV-2 antibodies were measured in CKD G4/5, dialysis patients and KTR after the second and third COVID-19 vaccination in the Netherlands. A questionnaire was sent to 4868 participants one year after initial vaccination asking for the presence of long-lasting symptoms after diagnosis in COVID-19 positive patients, or since the start of the pandemic in COVID-19 negative patients. PCC was defined according to the WHO clinical case definition. Blood samples at one month after the second and third vaccination were analysed with anti-RBD IgG ELISA. COVID-19 diagnosis was assessed by questionnaire or positive anti-nucleocapsid IgG antibodies. Logistic regression analysis was used to compare the presence of one or more long-lasting symptoms between COVID-19 positive and negative patients. In COVID-19 positive patients, we likewise identified predictors of PCC by backward selection and estimated the association between log-transformed antibody levels and PCC. Results 2747 patients were included, of which 222 patients with CKD G4/5, 390 dialysis patients and 2135 KTR. PCC was present in 25%, 16%, and 21% of CKD G4/5 patients, dialysis patients and KTR with high or very high symptom burden in 57%, 61% and 71%, respectively. In COVID-19 negative patients, long-lasting symptoms were present in 15%, 13% and 18%, respectively. COVID-19 positive patients (n = 1004) were at higher odds of having one or more long-lasting symptoms compared with COVID-19 negative patients (n = 1743) (OR: 1.33 [1.09–1.61], p = .005). Predictors of PCC were chronic lung disease (adjusted OR 2.04 [1.18#x2013;3.50], p = .01) and hospital/ICU admission (adjusted OR 5.03 [3.22-7.86], p < .001). Log anti-RBD IgG antibody level was negatively associated with PCC (adjusted OR: 0.79 [0.66#x2013;0.94], p = .008). Conclusion Patients with CKD G4/5, dialysis patients and KTR are at risk for PCC with a high symptom burden, especially if antibody levels after COVID-19 vaccination are low.

Comparison of Clinical Profile and Outcomes of Japanese Encephalitis and Acute Encephalitis Syndrome among Rural Children.

The study compared the clinical profile and outcomes of Japanese encephalitis (JE) and acute encephalitis syndrome (AES) in children. Fifty-six consecutive children with symptoms fulfilling the WHO clinical case definition of AES from June 2018 to June 2020 were included in the study. All patients who tested positive for either serum or cerebrospinal fluid (CSF) anti-JE-IgM antibodies were JE patients (n = 24) and compared with non-JE AES cases (n = 32). Fever, seizures, and altered sensorium were the most common presenting symptoms. Low GCS, status epilepticus, meningeal irritation, raised CSF protein, and INR > 1.5 of JE children showed significant association with mortality (p value < 0.05), whereas only low GCS showed significant association in non-JE AES cases. The JE-specific mortality rate was 29%, which was less than the mortality rate of non-JE AES children at 41%. Both JE and non-JE AES children had a similar clinical profile, but only the JE children's poor clinical and laboratory parameters were associated with adverse outcomes.

COVID-19 in Malawi: lessons in pandemic preparedness from a tertiary children’s hospital

The COVID-19 pandemic curve in Africa has lagged behind that of Europe. The first case of SARS-CoV-2 in Malawi was confirmed on 2 April.1 Malawi closed schools and airports, but...

Clinical spectrum of paediatric HIV infection in a tertiary care centre in South India

Background: The global burden of paediatric HIV and acquired immune deficiency syndrome (AIDS) remains a challenge for healthcare workers around the world, particularly in developing countries. The objective of this study is to describe the spectrum of HIV infection in children including the mode of transmission, clinical manifestations and opportunistic infections associated with HIV infection.Methods: Confirmed HIV seropositive children aged between 18 months to 19 years admitted to paediatric ward of JSS hospital, Mysore during two-year period were enrolled in this prospective observational study. Detailed history, socio-demographic characteristics and clinical manifestations were recorded in the predesigned performa. Nutritional assessment, complete physical, systemic and neurological examination was performed at the time of admission and was supplemented with ancillary investigations. Patients were correlated with modified WHO clinical case definition for AIDS and categorized as per revised CDC NABC classification of pediatric HIV infection.Results: Forty HIV-infected children were enrolled: with mean age of 4.5 years. Vertical transmission was the predominant mode of HIV transmission (97.5%). Most of the children were severely symptomatic belonging to category-C of NABC classification. Common clinical manifestations noted were failure to thrive (45%), recurrent respiratory infections (42%), bacterial skin infection (36%), recurrent otitis (42.5%), papulo-pruritic dermatitis (22%), hepatosplenomegaly (85%), lymphadenopathy (45%) and HIV encephalopathy (52%). The common opportunistic infections observed were pulmonary tuberculosis (45%), recurrent diarrhoea (35%), oral candidiasis (30%). The rare presentations of HIV noted were chronic thrombocytopenia and a case of dilated cardiomyopathy.Conclusions: Vertical transmission was the major route of HIV infection. HIV encephalopathy was more common among severely affected children. Tuberculosis was the commonest opportunistic infection.

Risk factors for Mycobacterium ulcerans infection (Buruli Ulcer) in Togo \u2500 a case-control study in Zio and Yoto districts of the maritime region

BackgroundBuruli ulcer (BU) is a neglected mycobacterial skin infection caused by Mycobacterium ulcerans. This disease mostly affects poor rural populations, especially in areas with low hygiene standards and sanitation coverage. The objective of this study was to identify these risk factors in the districts of Zio and Yoto of the Maritime Region in Togo.MethodsWe conducted a case-control study in Zio and Yoto, two districts proved BU endemic from November 2014 to May 2015. BU cases were diagnosed according to the WHO clinical case definition at the Centre Hospitalier Régional de Tsévié (CHR Tsévié) and confirmed by Ziehl-Neelsen (ZN) microscopy and IS2404 polymerase chain reaction (PCR). For each case, up to two controls matched by sex and place of residence were recruited. Socio-demographic, environmental or behavioral data were collected and conditional logistic regression analysis was used to identify and compare risk factors between BU cases and controls.ResultsA total of 83 cases and 128 controls were enrolled. The median age was 15 years (range 3–65 years). Multivariate conditional logistic regression analysis after adjustment for potential confounders identified age (< 10 years (OR =11.48, 95% CI = 3.72–35.43) and 10–14 years (OR = 3.63, 95% CI = 1.22–10.83)), receiving insect bites near a river (OR = 7.8, 95% CI = 1.48–41.21) and bathing with water from open borehole (OR = 5.77, (1.11–29.27)) as independent predictors of acquiring BU infection.ConclusionsThis study identified age, bathing with water from open borehole and receiving insect bites near a river as potential risk of acquiring BU infection in Zio and Yoto districts of the Maritime Region in south Togo.

An update of the global burden of pertussis in children younger than 5 years: a modelling study

Since the publication in 2003 of a model to estimate the disease burden of pertussis, new evidence of the protective effect of incomplete pertussis vaccination against severe pertussis has been reported. We revised the model to provide new estimates of regional and global pertussis cases and deaths for children younger than 5 years. We developed a revised model with data from 2014 to estimate pertussis cases and deaths. Pertussis cases were defined according to the WHO clinical case definition, as a coughing illness lasting at least 2 weeks with paroxysms of coughing, inspiratory whooping, or post-tussive vomiting. We used UN population estimates and WHO and UNICEF data on national pertussis immunisation coverage. Estimates were made for vaccine effectiveness against pertussis cases and deaths for one, two, and three doses of vaccination, probability of infection in low and high coverage countries, and case fatality ratios in low and high mortality countries in two age groups: infants younger than 1 year and children aged 1-4 years. We did sensitivity analyses with a range of input parameters to assess the effect of uncertainty of the input parameters on the model outputs. We estimated that there were 24·1 million pertussis cases and 160 700 deaths from pertussis in children younger than 5 years in 2014, with the African region contributing the largest proportions (7·8 million [33%] cases and 92 500 [58%] deaths). 5·1 million (21%) estimated pertussis cases and 85 900 (53%) estimated deaths were in infants younger than 1 year. In the sensitivity analyses, the estimated number of cases ranged from 7 million to 40 million and deaths from 38 000 to 670 000. Our estimates suggest that, compared with the 1999 estimates published in 2003 (30·6 million pertussis cases and 390 000 deaths from pertussis in children younger than 5 years), the numbers of cases and deaths of pertussis have fallen substantially. Model sensitivity emphasised the importance of better surveillance to improve country-level decision making and pertussis control. None.

Epidemiology of primary rubella infection in the Central African Republic: data from measles surveillance, 2007-2014.

BackgroundAlthough rubella is generally considered a benign childhood disease, infection of a pregnant woman can cause foetal congenital rubella syndrome, which results in embryo-foetal disease and malformations. The syndrome is still a public health problem in developing countries where the vaccine has not yet been introduced, such as the Central African Republic (CAR). The aim of the study reported here was to define the epidemiology of primary rubella infection, in order to determine its effect on morbidity rates in the country.MethodsData derived from epidemiological surveillance of measles and rubella were analysed retrospectively between 1 January 2007 and 31 December 2014. The database includes cases of suspected measles, according to the WHO clinical case definition. In this algorithm, samples that are negative or doubtful by ELISA for measles (presence of immunoglobulin M) are tested in another ELISA for detection of rubella-specific IgM. Descriptive analyses were conducted for socio-demographic characteristics, including age, sex and health region, for patients tested for rubella.ResultsOf the sera tested for rubella, 30.2 % (425/1409) were positive, 62.3 % (878/1409) were negative, and 7.5 % (106/1409) were doubtful. Among the 425 positive cases, 213 (50.1 %) were female and 212 (40.9 %) were male with a sex ratio of 1.03. The mean age was 8 years (range, 6–37 years). The highest prevalence (47.3 %; 116/425) was seen in 2007 and the lowest (8.9 %; 11/425) in 2012. Primary infections were always more frequent during the first 3 months of the year, with a peak at the same time, between January and February which is the hottest period of the year in the CAR. In both sexes, rubella IgM was rarely found before the age of 1 year (0.5 %; 2/425). The highest rate (43.5 %; 185/425) was observed at ages 5–9 years; however, at least 8 % (18/213) of girls aged 15 or more had primary infections.ConclusionsSentinel sites for surveillance of congenital rubella syndrome are urgently needed, and introduction of vaccination against rubella in the Expanded Programme of Immunization should be considered, to ensure immunization of girls of reproductive age.

The WHO clinical case definition for suspected cases of Ebola virus disease arriving at Ebola holding units: reason to worry?

The WHO clinical case definition for suspected cases of Ebola virus disease arriving at Ebola holding units: reason to worry?

Risk factors for buruli ulcer in Ghana-a case control study in the Suhum-Kraboa-Coaltar and Akuapem South Districts of the eastern region.

BackgroundBuruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans. Its exact mode of transmission is not known. Previous studies have identified demographic, socio-economic, health and hygiene as well as environment related risk factors. We investigated whether the same factors pertain in Suhum-Kraboa-Coaltar (SKC) and Akuapem South (AS) Districts in Ghana which previously were not endemic for BU.MethodsWe conducted a case control study. A case of BU was defined as any person aged 2 years or more who resided in study area (SKC or AS District) diagnosed according to the WHO clinical case definition for BU and matched with age- (+/−5 years), gender-, and community controls. A structured questionnaire on host, demographic, environmental, and behavioural factors was administered to participants.ResultsA total of 113 cases and 113 community controls were interviewed. Multivariate conditional logistic regression analysis identified presence of wetland in the neighborhood (OR = 3.9, 95% CI = 1.9–8.2), insect bites in water/mud (OR = 5.7, 95% CI = 2.5–13.1), use of adhesive when injured (OR = 2.7, 95% CI = 1.1–6.8), and washing in the Densu river (OR = 2.3, 95% CI = 1.1–4.96) as risk factors associated with BU. Rubbing an injured area with alcohol (OR = 0.21, 95% CI = 0.008–0.57) and wearing long sleeves for farming (OR = 0.29, 95% CI = 0.14–0.62) showed protection against BU.ConclusionThis study identified the presence of wetland, insect bites in water, use of adhesive when injured, and washing in the river as risk factors for BU; and covering limbs during farming as well as use of alcohol after insect bites as protective factors against BU in Ghana. Until paths of transmission are unraveled, control strategies in BU endemic areas should focus on these known risk factors.

Prospective Evaluation of an Australian Pertussis Toxin IgG and IgA Enzyme Immunoassay

Serological diagnosis of recent pertussis infection is an important part of both clinical assessment and epidemiological documentation of this disease. Standardization of serological testing and interpretation remains challenging despite international efforts to improve it. Currently, determining the anti-pertussis toxin (PT) IgG titer is recommended as the most accurate serological test in Europe and the United States, while Australia relies predominantly on measurement of Bordetella pertussis IgA antibody responses. Using B. pertussis PCR and the WHO clinical case definition as reference standards, the diagnostic utility of in-house anti-PT IgG and anti-PT IgA assays was evaluated prospectively in an Australian community-based cohort (n = 327). Patients provided up to four consecutive serum samples to document the kinetics of antibody response and decay. Previously validated cutoffs for positivity were converted to international units by using WHO-approved reference sera. At currently used cutoffs, both anti-PT IgG (>94 IU/ml) and anti-PT IgA (>20 IU/ml) assays had good specificity (80% [95% confidence interval {95% CI}, 68 to 88%] and 87% [95% CI, 77 to 94%]), but anti-PT IgG assay was consistently more sensitive than anti-PT IgA assay across a range of cutoffs (60 to 79% [95% CI, 53 to 84%] versus 41 to 62% [95% CI, 34 to 69%]). The combination of anti-PT IgG and anti-PT IgA assays performed no better than anti-PT IgG assay alone. The anti-PT IgA response in children under 12 years of age was poor. The accuracy of serology was optimal between 2 and 8 weeks after symptom onset. Cutoffs of >94 IU/ml for anti-PT IgG and >20 IU/ml for anti-PT IgA correlated well with recent pertussis infection and were consistent with recent recommendations from the EU Pertstrain group. Anti-PT IgG assay was superior to anti-PT IgA assay as the test of choice for the diagnosis of pertussis from a single sample.

SP5-32 Risk profile for transmission of Mycobacterium ulcerans in Akuapem South and Suhum Kraboa-Coaltar, Ghana

IntroductionBuruli ulcer (BU) disease is a chronic debilitating skin disease caused by Mycobacterium Ulcerans. The ulcer can be so extensive that it affects daily activities of the person affected, ulcers...

Further efforts needed to achieve measles elimination in Germany: results of an outbreak investigation.

To determine morbidity and costs related to a large measles outbreak in Germany and to identify ways to improve the country's national measles elimination strategy. We investigated a large outbreak of measles in the federal state of North Rhine-Westphalia (NRW) that occurred in 2006 after 2 years of low measles incidence (< 1 case per 100,000). WHO's clinical case definition was used, and surveillance data from 2006 and 2001 were compared. All cases notified in Duisburg, the most severely affected city, were contacted and interviewed or sent a questionnaire. Health-care provider costs were calculated using information on complications, hospitalization and physician consultations. In NRW, 1749 cases were notified over a 48-week period. Compared with 2001, the distribution of cases shifted to older age groups (especially the 10-14 year group). Most cases (n = 614) occurred in Duisburg. Of these, 81% were interviewed; 15% were hospitalized and two died. Of the 464 for whom information was available, 80% were reported as unvaccinated. Common reasons for non-vaccination were parents either forgetting (36%) or rejecting (28%) vaccination. The average cost per measles case was estimated at 373 euros. An accumulation of non-immune individuals led to this outbreak. The shift in age distribution has implications for the effectiveness of measles control and the elimination strategy in place. Immediate nationwide school-based catch-up vaccination campaigns targeting older age groups are needed to close critical immunity gaps. Otherwise, the elimination of measles in Germany and thus in Europe by 2010 will not be feasible.

Effect of handwashing on child health: a randomised controlled trial

More than 3.5 million children aged less than 5 years die from diarrhoea and acute lower respiratory-tract infection every year. We undertook a randomised controlled trial to assess the effect of handwashing promotion with soap on the incidence of acute respiratory infection, impetigo, and diarrhoea. In adjoining squatter settlements in Karachi, Pakistan, we randomly assigned 25 neighbourhoods to handwashing promotion; 11 neighbourhoods (306 households) were randomised as controls. In neighbourhoods with handwashing promotion, 300 households each were assigned to antibacterial soap containing 1.2% triclocarban and to plain soap. Fieldworkers visited households weekly for 1 year to encourage handwashing by residents in soap households and to record symptoms in all households. Primary study outcomes were diarrhoea, impetigo, and acute respiratory-tract infections (ie, the number of new episodes of illness per person-weeks at risk). Pneumonia was defined according to the WHO clinical case definition. Analysis was by intention to treat. Children younger than 5 years in households that received plain soap and handwashing promotion had a 50% lower incidence of pneumonia than controls (95% CI (-65% to -34%). Also compared with controls, children younger than 15 years in households with plain soap had a 53% lower incidence of diarrhoea (-65% to -41%) and a 34% lower incidence of impetigo (-52% to -16%). Incidence of disease did not differ significantly between households given plain soap compared with those given antibacterial soap. Handwashing with soap prevents the two clinical syndromes that cause the largest number of childhood deaths globally-namely, diarrhoea and acute lower respiratory infections. Handwashing with daily bathing also prevents impetigo.

Validation of a New Clinical Case Definition for Paediatric HIV Infection, Bloemfontein, South Africa

In 2003 a study was published evaluating the WHO clinical case definition for paediatric HIV infection in Bloemfontein South Africa. It was found that the WHO case definition could only detect 14.5 per cent of children who were in fact symptomatic and HIV positive on age-appropriate serology testing. Following logistic regression analysis a new case definition was proposed namely that HIV is suspected in a child who has at least two of the following four signs: marasmus hepatosplenomegaly oropharyngeal candidiasis and generalized lymphadenopathy. This new case definition had a sensitivity of 63.2 per cent and a specificity of 96.0 per cent. (excerpt)

Paediatric HIV/AIDS in Abakaliki

Background: The increasing prevalence of HIV infection in Nigeria makes it desirable to document the clinical features of the disease in environments where there are often limited financial resources for HIV testing. Objectives: The study was aimed at determining the mode of transmission, clinical presentation, and outcome of HIV infection in children admitted with clinical manifestations suspicious of HIV infection. It was also to examine whether the WHO clinical case definition for paediatric AIDS in Africa could help predict the infection in the local community. Method: A retrospective review of 342 patients aged between one month and 15 years, who were admitted and screened for suspected HIV infection between January 2000 and September 2001, was carried out. Results: Forty-six (13.7 percent) of the 342 patients were confirmed positive. However, adequate clinical data was obtained in only 31 patients. Vertical transmission was a significant source of infection in these children (p Conclusion: The WHO clinical case definition for paediatric AIDS in Africa was poorly sensitive and poorly specific in this study. In view of this, HIV screening is of vital importance in the diagnosis of AIDS. Prevention of vertical transmission through the prophylactic use of anti-retroviral therapy in pregnancy may be the most powerful tool against HIV infection in the community. Key Words: HIV/AIDS, paediatric age group Nigerian Journal of Paediatrics Vol.30(4) 2003: 128-134

Assessment of clinical case-definition for HIV/AIDS in Tanzania

To evaluate the usefulness of World Health Organisation (WHO's) clinical case-definition (CCD) for AIDS in a private hospital. A prospective study. Shree Hindu Mandal Hospital, Dar es Salaam, Tanzania. A total of 601 patients (> 14 years) were studied from January 1995 to December 1997. Using HIV test results as a reference standard, sensitivity, specificity, positive predictive values (PPV) and negative predictive values of signs and symptoms were calculated. Multiple logistic regression was used to determine a set of predictive symptoms and signs. Stepwise logistic regression modelling was used to choose the final model. The frequently occurring signs and symptoms among the 473 sero-positive patients were fever (226), oral candidiasis (167), weight loss (161), chronic cough (157), diarrhoea (100) and pulmonary tuberculosis in 69 cases. The presence of anorectal lesions and the rarity of pneumocystis carinii pneumonia in this study are important findings. Seven clinical characteristics predicted HIV infection. These included pulmonary tuberculosis (p=0.009), lymphadenopathy (p=0.007), diarrhoea (p=0.000), chronic cough (p=0.001), dermatitis (p=0.003), herpes zoster (p=0.01) and oral candidiasis (p=0.000). A greater number of HIV positive patients presented with signs and symptoms different from those proposed by WHO's CCD were observed in this study. With environmental pathogens varying from one geographical region to another and new ones appearing, opportunistic disease cannot be constant in AIDS patients. Therefore, AIDS diagnosis based on clinical case definition alone without at least one positive HIV antibody test is inaccurate and no longer justified.

Evaluation of the WHO clinical case definition for pediatric HIV infection in Bloemfontein, South Africa.

The WHO clinical case definition for pediatric HIV infection has been designed to be used in countries where diagnostic laboratory resources are limited. We evaluated the WHO case definition to determine whether it is a useful instrument to discriminate between HIV-positive and HIV-negative children. In addition, clinical features not included in this case definition were recorded. We recorded clinical data from 300 consecutively admitted children in a state hospital in Bloemfontein, South Africa, and tested these children for HIV infection. A total of 222 children were included in the study; 69 children (31.1 per cent) were HIV positive. The sensitivity of the WHO case definition in this study was 14.5 per cent, the specificity was 98.6 per cent. Apart from weight loss and generalized dermatitis, the signs of the WHO case definition were significantly more often seen in HIV-positive than in HIV-negative children. Of the clinical signs not included in the WHO case definition, marasmus and hepatosplenomegaly especially occurred more frequently in HIV-positive children. Based on these findings we composed a new case definition consisting of four signs: marasmus, hepatosplenomegaly, oropharyngeal candidiasis, and generalized lymphadenopathy. HIV infection is suspected in a child presenting with at least two of these four signs. The sensitivity of this case definition was 63.2 per cent, the specificity was 96.0 per cent. We conclude that in this study the WHO case definition was not a useful instrument to discriminate between HIV-positive and HIV-negative children, mainly because its sensitivity was strikingly low. The simplified case definition we propose, proved to be more sensitive than the WHO case definition (63.2 vs. 14.5 per cent), whilst its specificity remained high.

Blood transfusion related paediatric HIV/AIDS in Ile-Ife, Nigeria

This prospective study was aimed at determining the contribution of blood transfusion to paediatric HIV infection in Ile-Ife, Nigeria. It involved HIV screening of consecutive children presenting at the Obafemi Awolowo University Teaching Hospital (OAUTH), Ile-Ife, between March 1996 and March 2001, with any of the signs in the WHO clinical case definition for paediatric AIDS. The HIV serostatus of blood donors at the OAUTH was also extracted from the blood bank records. Of the 263 children who met the criteria for HIV screening, 35 (13.3%) were HIV-positive. Eighteen of the 263 children screened had a history of blood transfusion and 12 (66.7%) of the 18 were HIV-positive. Eleven (91.7%) of the 12 HIV-positive patients were transfused in private hospitals with blood collected from private laboratories. The blood with which the HIV-positive children were transfused was unscreened in three, screened in two and the HIV status unknown in the others. The sole voluntary donor was an HIV-positive father whose child received his unscreened blood. Only two (16.7%) of the mothers of the previously transfused HIV-positive children were also HIV-positive. 'Paid' donors accounted for 94.3% of total donors in OAUTH blood bank records and cumulative HIV-positivity was statistically significantly higher in 'paid' donors than in voluntary donors (p=0.005). We conclude that transfusion with unsafe blood is an important route for HIV infection in symptomatic children and that HIV-positivity is higher among paid donors. We recommend the establishment of a national blood transfusion service, which is presently non-existent in Nigeria, and the enforcement of laws guiding blood transfusion. Voluntary blood donation should be encouraged and health workers in the private sectors educated on the link between blood transfusion and HIV infection.

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of human immunodeficiency virus infection in Ugandan infants

IgA antibodies to human immunodeficiency virus in serum, saliva and urine for early diagnosis of human immunodeficiency virus infection in Ugandan infants

Causes of death in a rural, population-based human immunodeficiency virus type 1 (HIV-1) natural history cohort in Uganda.

While human immunodeficiency virus (HIV)-related causes of death have been well documented in developed countries, in Africa data are scanty and mainly based on autopsy studies from city hospitals which are highly selective and may not represent causes of HIV-associated deaths in the general population. This study, from a rural population, describes the causes of death in HIV-positive people and their HIV-negative controls. A natural history cohort comprising HIV-1 infected participants and HIV-negative controls was established in rural Uganda in 1990. Causes of death were determined by reviewing the premorbid clinical and laboratory findings and from information obtained from relatives. Blindness to the deceased's HIV serostatus was maintained throughout. In all, 78 deaths occurred over a 6-year period: 63 deaths occurred in the HIV-positive cases (53 prevalent and 10 incident cases) and 15 deaths in the HIV-negative controls. Of the prevalent cases, 56%, and 9% the incident cases enrolled died, compared with 7% of the HIV-negative controls. Of the 55 HIV-positive cases with sufficient data to establish cause of death, 52 (95%) were assessed as having HIV-associated deaths and 48 (87%) died in WHO stage 4 (AIDS). The main causes of death were wasting syndrome (31%), chronic diarrhoea (22%), cryptococcal meningitis (13%) and chest infection (11%). Our results represent an unbiased selection of deaths in a rural area. The HIV-positive cases have high death rates and die of HIV-related pathologies. The main causes of death reflect the WHO clinical case definition of AIDS. Cryptococcal meningitis is also a common cause of death in this population.