Ebola virus disease in Africa: epidemiology and nosocomial transmission.

The 2014 Ebola outbreak in West Africa, primarily affecting Guinea, Sierra Leone, and Liberia, has exceeded all previous Ebola outbreaks in the number of cases and in international response. There have been 20 significant outbreaks of Ebola virus disease in Sub-Saharan Africa prior to the 2014 outbreak, the largest being that in Uganda in 2000, with 425 cases and a mortality of 53%. Since the first outbreaks in Sudan and Zaire in 1976, transmission within health facilities has been of major concern, affecting healthcare workers and acting as amplifiers of spread into the community. The lack of resources for infection control and personal protective equipment are the main reasons for nosocomial transmission. Local strategies to improve infection control, and a greater understanding of local community views on the disease, have helped to bring outbreaks under control. Recommendations from previous outbreaks include improved disease surveillance to enable more rapid health responses, the wider availability of personal protective equipment, and greater international preparedness.

Outbreak of zoonotic cutaneous leishmaniasis with local dissemination in Balkh, Afghanistan.

OBJECTIVES: In Afghanistan zoonotic cutaneous leishmaniasis (CL) due to Leishmania major has been less widely reported than anthroponotic CL due to L. tropica. However, an outbreak of zoonotic CL occurred amongst a group of British soldiers at a military camp near Mazar-e-Sharif in the Balkh province of northern Afghanistan in 2004. METHODS: A study was performed to assess the epidemiology, clinical features, parasitology results, treatment outcomes and environmental health measures associated with this incident. RESULTS: Twenty (17%) of 120 soldiers developed CL due to L. major and the risk of infection increased with the proximity of their accommodation to an area of recently cleared scrub, where many wild rodents were observed. Most cases had features of local dissemination, including secondary lesions from the pseudo-Koebner phenomenon, sporotrichoid lymphatic spread, lymphadenopathy and satellite papules or milia formation around healing lesions. Several cases responded poorly to fluconazole and low dose (10 mg/kg) sodium stibogluconate, which were considered suitable treatments at the time. Environmental health measures at the military camp were found to be deficient. CONCLUSIONS: Zoonotic CL due to L. major is a significant threat for foreign troops based in Balkh, Afghanistan and may present with unusually severe clinical features and be resistant to previously recommended treatments.

Globalisation, complex humanitarian emergencies and health.

A new political economy of conflict has emerged in the aftermath of colonialism and the Cold War. Complex political emergencies have been simmering in the post-colonial world for more than three decades. Intra-country armed conflict, often combined with natural disasters, at present contributes to the displacement of over 20 million people world-wide. The international community remains profoundly uncomfortable with the complex political emergencies of the new era, torn between the respect for national sovereignty upon which the international political system of the United Nations and other agencies is built, and the growth of concern with human rights and a burgeoning International Humanitarian Law. Globalisation may have brought many benefits to some but there are also many losers. The Word Bank and the International Monetary Fund imposed structural adjustment policies to ensure debt repayment and economic restructuring that have resulted in a net reduction in expenditure on health, education and development. A downward spiral has been created of debt, disease, malnutrition, missed education, economic entrapment, poverty, powerlessness, marginalization, migration and instability. Africa's complex political emergencies are particularly virulent and tenacious. Three examples that are among the most serious humanitarian emergencies to have faced the world in recent times--those in Angola, the Democratic Republic of Congo and Sudan--are reviewed here in detail. The political evolution of these emergencies and their impact on the health of the affected populations are also explored.

Nasopharyngeal carriage of pneumococci in Gambian children and in their families.

BACKGROUND: Nasopharyngeal carriage of pneumococci is prevalent among children in developing countries but little is known about the relationship of nasopharyngeal carriage to invasive disease or about the way in which pneumococci spread within households. OBJECTIVES: To determine the prevalence of nasopharyngeal carriage in healthy and sick Gambian children and to investigate transmission within households. METHODS: Nasopharyngeal swabs were obtained by the per nasal route and cultured for pneumococci on selective media. Pneumococci were serotyped with the use of latex particles coated with type-specific antisera. RESULTS: Pneumococci were isolated from the nasopharynx of 73 (90.1%) of 81 children with invasive pneumococcal disease, 86 (76.1%) of 113 healthy, age-matched control children and 911 (85.1%) of 1071 sick children. Pneumococci belonging to serotypes 1, 14 and 12 were isolated significantly more frequently from cases than from matched controls. In 43 (76.8%) of 56 children with invasive disease, pneumococci isolated from the nasopharynx and from the blood or other sterile site belonged to the same serotype. Pneumococci of the same serotype as the bacterium responsible for invasive disease in a child were obtained from 72 (8.5%) of 843 family members, most frequently from young siblings of the case patients. CONCLUSION: Nasopharyngeal carriage of pneumococci is more prevalent among young Gambian children than among adults and invasive infections are probably acquired more frequently from siblings than from parents. However, further studies are needed to confirm this hypothesis with more discriminating markers than polysaccharide serotyping.

A study of risk factors for pneumococcal disease among children in a rural area of west Africa.

BACKGROUND: Pneumoccal infection is one of the leading causes of pneumonia, meningitis and septicaemia in developing countries. We have investigated possible risk factors for pneumococcal disease among children living in a rural area of The Gambia. METHODS: A prospective case-control study was conducted in which children with pneumococcal infection were identified from among children attending out-patient and under-fives clinics and matched according to age with healthy children selected randomly from the local community. A questionnaire was used to investigate possible nutritional, medical, socioeconomic and environmental risk factors for pneumococcal disease. RESULTS: An increased risk of pneumococcal disease was associated with poor weight gain, a history of serious illness in the previous 6 months, exposure to cigarette smoke or being carried on mother's back while cooking. The risk of pneumococcal disease was reduced among children whose mothers had a personal source of income. CONCLUSIONS: The incidence of pneumococcal disease could be reduced by improving nutrition and taking steps to identify and rehabilitate those children whose weight is faltering or falling. Encouraging mothers to develop greater financial independence may also be beneficial. Reduced exposure to smoke should be promoted by improving ventilation in kitchens, introducing more efficient and less polluting stoves, keeping children away from smoky environments and discouraging parental smoking.

PIP: Pneumococcal infection is a leading cause of pneumonia, meningitis, and septicemia in developing countries. The authors investigated possible risk factors for pneumococcal disease during 1989-91 among children living in the rural Upper River Division of The Gambia. A prospective case-control study approach was used in which 80 children with pneumococcal infection were matched according to age with 159 healthy children randomly selected from the local community. The subjects were of mean age 14.0-14.2 months. A questionnaire was used to identify possible nutritional, medical, socioeconomic, and environmental risk factors for pneumococcal disease. The study found an increased risk of pneumococcal disease to be associated with poor weight gain, a history of serious illness during the previous 6 months, exposure to cigarette smoke, or being carried upon a mother's back while she cooks. The risk of pneumococcal disease was reduced among children whose mothers had a personal source of income. The authors suggest reducing the incidence of pneumococcal disease by improving nutrition and growth monitoring, encouraging mothers to develop greater financial independence, and reducing children's exposure to smoke.

Immunization with a pneumococcal capsular polysaccharide vaccine during pregnancy.

The feasibility of preventing invasive pneumococcal infections during the first few months of life by immunization during pregnancy has been investigated. One hundred and fifty Gambian women were immunized with either a 23-valent pneumococcal polysaccharide vaccine or a meningococcal polysaccharide vaccine during the last trimester of pregnancy. Pregnant women showed a good antibody response to five of the six pneumococcal polysaccharides tested (types 1, 3, 5, 6, 14 and 19) but not to type 6 polysaccharide. Mean cord blood/maternal blood IgG antibody ratios varied from 24% (type 1) to 49% (type 3) and differed substantially between individual mother/infant pairs. Pneumococcal antibody levels were higher at birth in infants of women immunized with pneumococcal polysaccharide vaccine than in control infants. However, these antibodies disappeared rapidly during the first few months of life and it is uncertain how much clinical protection against pneumococcal infection maternal immunization would have provided.

Pneumococcal disease among children in a rural area of west Africa.

BACKGROUND: The pneumococcus is a frequent cause of pneumonia and other serious infections among young children in developing countries. Defining the pattern of pneumococcal infection in these countries is important so that, with the advent of pneumococcal conjugate vaccines, rational vaccination policies can be developed. METHODS: Children younger than 5 years of age who attended clinics in a rural area of The Gambia, West Africa, were screened by assistants during a 2-year period. Children with predefined features suggestive of a diagnosis of pneumonia, meningitis or septicemia were referred to the Medical Research Council Field Station at Basse for investigation. RESULTS: Of 2898 children investigated 103 cases of invasive pneumococcal disease (70 definite and 33 probable) were identified, suggesting that the incidence of this infection in the study community is at least 554/100,000/year in children younger than 1 year of age and 240/100,000/year in those younger than 5 years, rates many times higher than those found in industrialized societies. The mean age of presentation was 15 months; more boys than girls were affected. Cases of pneumonia were encountered 8 times more frequently than those of meningitis. Antibiotic resistance was rarely found and cases of pneumonia, but not meningitis, responded well to treatment. Case-fatality rates in children with pneumonia and meningitis were 1 and 55%, respectively. The most prevalent pneumococcal serotypes were types 6, 14, 19, 1 and 5. CONCLUSION: About 60% of invasive pneumococcal infection in children in this community could potentially be prevented by a nine-valent pneumococcal conjugate vaccine (types 1, 4, 5, 6B, 9, 14, 18, 19F and 23) given at the ages of 2, 3 and 4 months.

Predictors for a positive blood culture in African children with pneumonia.

BACKGROUND: Blood culture isolation rates for children with pneumonia are generally low. Therefore it would be helpful if epidemiologic studies could identify children who have a higher than average chance of yielding a positive culture. METHODS: Simple clinical and laboratory predictors of a positive blood culture were investigated in 1222 children younger than 5 years of age with pneumonia who presented at rural dispensaries in The Gambia, West Africa. RESULTS: A high temperature (chi square for linear trend, 24.1; P < 0.0001), a rapid respiratory rate (chi square for linear trend, 6.33; P = 0.010), dehydration (odds ratio, 2.33; P < 0.001), nasal flaring (odds ratio, 2.06; P = 0.001), grunting (odds ratio, 4.01; P < 0.001), dullness to percussion (odds ratio, 2.31; P < 0.001), bronchial breathing (odds ratio, 2.61; P < 0.001) and diminished breath sounds (odds ratio, 2.07; P < 0.001) were positive predictors for a positive blood culture. Wheezing (odds ratio, 0.16; P < 0.001) and malaria parasitemia (odds ratio, 0.26; P = 0.008) were negative predictors. A combination of these findings were used to assess how the number of cultures taken might be reduced without substantially reducing the yield of positive cultures. For example it was found that exclusion of children with a temperature of < 38.0 degrees C and/or a respiratory rate of < 50/min and/or wheezing would have reduced the number of cultures taken by 55.6% but would have led to a loss of only 31.3% of positive cultures. CONCLUSION: Careful selection of children investigated by blood culture could help to reduce the work required during the preparations for and conduct of pneumococcal vaccine trials.

Meningococcal antibody titres in infants of women immunised with meningococcal polysaccharide vaccine during pregnancy.

Seventy five Gambian women were immunised with a single dose of a group A+group C meningococcal polysaccharide vaccine during the last trimester of pregnancy. IgG antibody titres were measured in mothers and in their infants by an enzyme-linked immunosorbent assay (ELISA). All women had a good response to vaccination and maternal antibodies were high at the time of delivery (23.2 micrograms/ml for group A antibodies and 14.3 micrograms/ml for group C antibodies). However, only a proportion of this antibody crossed the placenta; cord blood:maternal antibody ratios were 30% for group A antibody and 44% for group C antibody, respectively. Considerable variability in cord blood:maternal blood ratios was seen between individuals. This could not be related to age, parity, or ethnic group. Mean group A and group C cord blood:maternal blood ratios were lower in women with serological evidence of syphilis than in seronegative women, and diminished transfer of group A antibody was noted in women with active malarial infection of the placenta. Antibody titres declined rapidly in infants and by the age of 3-4 months these had reached control values. Maternal immunisation may give infants some protection against group A and group C meningococcal disease but only during the first few months of life.

A trial of a group A plus group C meningococcal polysaccharide-protein conjugate vaccine in African infants.

The safety and immunogenicity of a group A plus group C meningococcal polysaccharide-CRM197 conjugate vaccine was evaluated in 304 8- to 10-week-old Gambian infants. Infants were immunized with one, two, or three doses of conjugate vaccine or with two doses of a meningococcal A plus C polysaccharide vaccine. The conjugate vaccine produced few systemic side effects, and local reactions were similar to those produced by the polysaccharide vaccine. Postvaccination group A meningococcal polysaccharide antibody levels, measured by ELISA, increased progressively after one, two, or three doses of conjugate vaccine. However, one dose of conjugate vaccine given at the age of 6 months induced a higher group C meningococcal antibody response than did two doses of conjugate vaccine given at 2 and 6 months. Two doses of conjugate vaccine induced higher levels of antibody than did two doses of polysaccharide vaccine. Thus, this new meningococcal conjugate vaccine proved to be safe and immunogenic.

Importance of enteric bacteria as a cause of pneumonia, meningitis and septicemia among children in a rural community in The Gambia, West Africa.

Two thousand eight hundred ninety-eight children younger than 5 years old were investigated during a 2-year period in a rural area of The Gambia for possible pneumonia, meningitis or septicemia. After clinical examination and appropriate investigations, 1014 children were diagnosed as having pneumonia, 31 as having meningitis and 100 as having septicemia. Nine hundred seven children had a final diagnosis of malaria including 702 who satisfied the World Health Organization criteria for a diagnosis of pneumonia. A bacterial etiology was established in 115 (11%) patients with a final diagnosis of pneumonia, in 25 (81%) with meningitis and in 29 (29%) with suspected septicemia. Overall the pneumococcus was the leading pathogen identified among children with pneumonia and meningitis and ranked third among those with septicemia. However, during the wet season, when malaria transmission was highest, 50% of blood culture isolates obtained from children satisfying the World Health Organization criteria for a diagnosis of pneumonia were Salmonella or coliform species, and the pneumococcus and Haemophilus influenzae type b accounted for only 43% of isolates. Thus enteric bacteria may be as important as those bacteria more usually associated with respiratory disease among children presenting with a clinical picture of pneumonia during the wet season. This finding has important implications for case management and surveillance for antibiotic resistance.

The limitations of verbal autopsy in a malaria-endemic region.

Verbal autopsies are being used widely to describe the causes of mortality and to assess the effect of interventions against specific diseases in developing countries where many deaths occur at home. A verbal autopsy has been in use in the Upper River Division of The Gambia since 1988. In this paper we present the results of a validation study of this technique. One hundred and forty-one verbal autopsies were reviewed on two occasions by the same three physicians. In 38 (27%) of the cases, the first and subsequent diagnoses differed. In 94 children admitted to Basse Health Centre, the results of verbal autopsies were compared with the diagnoses made by a paediatrician--only 44 (47%) matched. The poor sensitivity and specificity of the verbal autopsy in this study may have been due to the confounding effect of malaria, which can be difficult to distinguish from other causes of death in this community.

Overlap in the clinical features of pneumonia and malaria in African children.

Pneumonia and malaria are common causes of childhood morbidity and mortality in many developing countries and simple guidelines have been proposed to facilitate their diagnosis by relatively unskilled health workers. We have studied children in The Gambia attending out-patient and under-five clinics with clinically suspected pneumonia (cough or difficulty in breathing and a raised respiratory rate) during periods of high or low malaria transmission. During a period of high malaria transmission, 33% of these children had radiological evidence of pneumonia (with or without malaria parasitaemia) compared to 38% who had malaria parasitaemia, no radiological evidence of pneumonia and no other obvious cause of fever. Corresponding figures during a period of low malaria transmission were 48% and 6% respectively. The clinical overlap between pneumonia and malaria has important implications for case management strategies and evaluation of disease-specific interventions in regions in which both pneumonia and malaria are prevalent.

Screening for a raised rectal temperature in Africa.

The main purpose of this study was to compare rectal and axillary temperature measurements in African children. Altogether 573 sick children were seen in an outpatient setting in rural West Africa. Rectal and axillary temperatures were measured and the parent or guardian was asked if they thought that the child had a raised body temperature. Normal ranges were defined from an age matched population of 203 healthy children. A raised axillary temperature predicted a raised rectal temperature with a sensitivity of 98% and a specificity of 88%. The parents' impression that their child had a fever was a less sensitive (89%) and less specific (59%) indicator of raised rectal temperature. A raised axillary temperature is a good screening test for a raised rectal temperature in African children.

The effect of temperature reduction on respiratory rate in febrile illnesses.

A raised respiratory rate is a useful sign in the diagnosis of pneumonia in children. It was observed that children with malaria and other febrile illnesses may also present with a raised respiratory rate. To determine the extent to which increased body temperature contributes to the raised respiratory rate observed in these children the effect of change in body temperature on respiratory rate was measured in 186 sick Gambian children with a raised respiratory rate, including those with pneumonia or malaria. A temperature dependent effect on respiratory rate of 3.7 breaths per minute per degree centigrade was demonstrated for the whole study cohort, with no significant difference between children with pneumonia or malaria. Twenty three per cent of children with pneumonia whose temperature fell had a final respiratory rate below that currently recommended by the World Health Organisation for the diagnosis of pneumonia. It is concluded that respiratory rate is to some extent dependent on body temperature in children with febrile illnesses such as pneumonia and malaria, but that this does not alone account for the raised respiratory rate seen in these children. The effect of reduction in body temperature on respiratory rate does not help to distinguish children with pneumonia from those with malaria. A history of recent use of an antipyretic or other measures to control fever is important when evaluating children for possible pneumonia.

Sensitivity of Plasmodium falciparum in The Gambia to co-trimoxazole.

In The Gambia co-trimoxazole is used widely to treat children with an acute respiratory infection (ARI). Because malaria may sometimes be mistaken for ARI, some children with malaria are treated with co-trimoxazole. Therefore, we investigated the sensitivity of Gambian isolates of Plasmodium falciparum to this drug. Six days after the start of treatment with co-trimoxazole 3.3% of blood films of 65 asymptomatic subjects were positive, and 7.7% were positive after 21 d. One of 10 patients with ARI and malaria treated with co-trimoxazole had a positive blood film 3 d after the start of treatment but was negative thereafter. All 10 patients recovered satisfactorily. Thirty 'wild' isolates of P. falciparum were tested in vitro against co-trimoxazole at a ration of 5 parts sulphamethoxazole (SMZ) to 1 part trimethoprim (TMP). The mean EC50s, using a 36 h assay, were 1.2 x 10(-7) and 2.5 x 10(-8) M for SMZ and TMP respectively. When a [3H]hypoxanthine incorporation assay was employed, values of 5.7 x 10(-7) M for SMZ and 1.2 x 10(-7) M for TMP were obtained. These values are well below the peak plasma concentration. Our findings suggest that co-trimoxazole is effective against falciparum malaria in The Gambia. However, if it were to be used widely, the parasite would be likely to develop resistance to this and other dihydrofolate reductase inhibitor antimalarials.

Coincidence of malaria parasitaemia and abnormal chest X-ray findings in young Gambian children.

Weekly surveillance of Gambian children aged less than 5 years for both acute lower respiratory infections (ALRI) and clinical malaria showed a high rate of coincidence between abnormal chest X-ray findings and high levels of malaria parasitaemia. Generalized interstitial X-ray changes were particularly associated with these cases of malaria parasitaemia. It is suggested that such ALRIs in these children may be attributable to malaria.