Exogenous re-infection by a novel Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis in a child from The Gambia

We report a case of an infant who experienced exogenous re-infection of Streptococcus pneumoniae serotype 14 as a cause of recurrent meningitis after apparently successful antibiotic treatment with ceftriaxone. eBURST analysis revealed that isolates from the two episodes of meningitis belonged to hypervirulent ST63 and ST3321 clonal complexes respectively

A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children.

BACKGROUND: A Tuberculin skin test (TST) survey was conducted to assess the prevalence of latent TB Infection (LTBI) and to estimate the annual risk of M. tuberculosis infection (ARTI) in Gambian school children. The results are expected to contribute to understanding of Tuberculosis epidemiology in The Gambia. METHODS: This was a nationwide, multi-cluster survey in children aged 6-11 years. Districts, 20 of 37, were selected by probability proportional to size and schools by simple random sampling. All TST were performed using the Mantoux method. Height and weight measurements were obtained for all participants. We calculated prevalence of LTBI using cut-off points of 10mm, the mirror and mixture modelling methods. RESULTS: TST readings were completed 13,386 children with median age of 9 years (interquartile range [IQR] 8-10 years). Mixture analysis yielded a cut-off point of 12 mm, and LTBI prevalence of 6.9% [95%CI 6.47-7.37] and the ARTI was 0.75% [95%CI 0.60-0.91]. LTBI was associated gender and urban residence (p <0.01). Nutritional status was not associated with non-reactive TST or sizes of TST indurations. ARTI did not differ significantly by age, gender, BCG vaccination or residence. CONCLUSIONS: This estimates for LTBI prevalence and ARTI were low but this survey provides updated data. Malnutrition did not affect estimates of LTBI and ARTI. Given the low ARTI in this survey and the overlapping distribution of indurations with mixture modelling, further surveys may require complementary tests such as interferon gamma release assays or novel diagnostic tools

Disease-specific mortality burdens in a rural Gambian population using verbal autopsy, 1998-2007.

OBJECTIVE: To estimate and evaluate the cause-of-death structure and disease-specific mortality rates in a rural area of The Gambia as determined using the InterVA-4 model. DESIGN: Deaths and person-years of observation were determined by age group for the population of the Farafenni Health and Demographic Surveillance area from January 1998 to December 2007. Causes of death were determined by verbal autopsy (VA) using the InterVA-4 model and ICD-10 disease classification. Assigned causes of death were classified into six broad groups: infectious and parasitic diseases; cancers; other non-communicable diseases; neonatal; maternal; and external causes. Poisson regression was used to estimate age and disease-specific mortality rates, and likelihood ratio tests were used to determine statistical significance. RESULTS: A total of 3,203 deaths were recorded and VA administered for 2,275 (71%). All-age mortality declined from 15 per 1,000 person-years in 1998-2001 to 8 per 1,000 person-years in 2005-2007. Children aged 1-4 years registered the most marked (74%) decline from 27 to 7 per 1,000 person-years. Communicable diseases accounted for half (49.9%) of the deaths in all age groups, dominated by acute respiratory infections (ARI) (13.7%), malaria (12.9%) and pulmonary tuberculosis (10.2%). The leading causes of death among infants were ARI (5.59 per 1,000 person-years [95% CI: 4.38-7.15]) and malaria (4.11 per 1,000 person-years [95% CI: 3.09-5.47]). Mortality rates in children aged 1-4 years were 3.06 per 1,000 person-years (95% CI: 2.58-3.63) for malaria, and 1.05 per 1,000 person-years (95% CI: 0.79-1.41) for ARI. The HIV-related mortality rate in this age group was 1.17 per 1,000 person-years (95% CI: 0.89-1.54). Pulmonary tuberculosis and communicable diseases other than malaria, HIV/AIDS and ARI were the main killers of adults aged 15 years and over. Stroke-related mortality increased to become the leading cause of death among the elderly aged 60 years or more in 2005-2007. CONCLUSIONS: Mortality in the Farafenni HDSS area was dominated by communicable diseases. Malaria and ARI were the leading causes of death in the general population. In addition to these, diarrhoeal disease was a particularly important cause of death among children under 5 years of age, as was pulmonary tuberculosis among adults aged 15 years and above

PCR-based genotyping of Helicobacter pylori of Gambian children and adults directly from biopsy specimens and bacterial cultures

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is an important agent of gastroduodenal disease in Africa and throughout the world. We sought to determine an optimum method for genotyping <it>H. pylori </it>strains from children and adults in The Gambia, West Africa.</p> <p>Results</p> <p>Virulence genes were amplified in 127 of 190 cases tested (121 adults and 6 children); each of 60 bacterial cultures, and 116 from DNA extracted directly from biopsies. The proportion of biopsies that were <it>cagA</it>+, the ratio of <it>vacAs1</it>/<it>s2</it>, and <it>vacAm1</it>/<it>m2</it>, and the proportion of mixed strain populations in individual subjects changed with age. Strains lacking virulence <it>cagA </it>and <it>vacA </it>genes and with apparently homogeneous (one predominant strain) infections were more common among infants than adults.</p> <p>Conclusions</p> <p>In order to detect the range of bacterial genotypes harbored by individual patients, direct PCR proved slightly superior to isolation of <it>H. pylori </it>by biopsy culture, but the techniques were complementary, and the combination of both culture and direct PCR produced the most complete picture. The seemingly higher virulence of strains from adult than infant infections in The Gambia merits further analysis.</p

Deciphering the growth behaviour of Mycobacterium africanum.

BACKGROUND: Human tuberculosis (TB) in West Africa is not only caused by M. tuberculosis but also by bacteria of the two lineages of M. africanum. For instance, in The Gambia, 40% of TB is due to infections with M. africanum West African 2. This bacterial lineage is associated with HIV infection, reduced ESAT-6 immunogenicity and slower progression to active disease. Although these characteristics suggest an attenuated phenotype of M. africanum, no underlying mechanism has been described. From the first descriptions of M. africanum in the literature in 1969, the time to a positive culture of M. africanum on solid medium was known to be longer than the time to a positive culture of M. tuberculosis. However, the delayed growth of M. africanum, which may correlate with the less virulent phenotype in the human host, has not previously been studied in detail. METHODOLOGY/PRINCIPAL FINDINGS: We compared the growth rates of M. tuberculosis and M. africanum isolates from The Gambia in two liquid culture systems. M. africanum grows significantly slower than M. tuberculosis, not only when grown directly from sputa, but also in growth experiments under defined laboratory conditions. We also sequenced four M. africanum isolates and compared their whole genomes with the published M. tuberculosis H37Rv genome. M. africanum strains have several non-synonymous SNPs or frameshift mutations in genes that were previously associated with growth-attenuation. M. africanum strains also have a higher mutation frequency in genes crucial for transport of sulphur, ions and lipids/fatty acids across the cell membrane into the bacterial cell. Surprisingly, 5 of 7 operons, recently described as essential for intracellular survival of H37Rv in the host macrophage, showed at least one non-synonymously mutated gene in M. africanum. CONCLUSIONS/SIGNIFICANCE: The altered growth behaviour of M. africanum might indicate a different survival strategy within host cells

Etiology of severe childhood pneumonia in the Gambia, West Africa, determined by conventional and molecular microbiological analyses of lung and pleural aspirate samples.

Molecular analyses of lung aspirates from Gambian children with severe pneumonia detected pathogens more frequently than did culture and showed a predominance of bacteria, principally Streptococcus pneumoniae, >75% being of serotypes covered by current pneumococcal conjugate vaccines. Multiple pathogens were detected frequently, notably Haemophilus influenzae (mostly nontypeable) together with S. pneumoniae

Whole-genome sequencing illuminates the evolution and spread of multidrug-resistant tuberculosis in Southwest Nigeria.

Nigeria has an emerging problem with multidrug-resistant tuberculosis (MDR-TB). Whole-genome sequencing was used to understand the epidemiology of tuberculosis and genetics of multi-drug resistance among patients from two tertiary referral centers in Southwest Nigeria. In line with previous molecular epidemiology studies, most isolates of Mycobacterium tuberculosis from this dataset belonged to the Cameroon clade within the Euro-American lineage. Phylogenetic analysis showed this clade was undergoing clonal expansion in this region, and suggests that it was involved in community transmission of sensitive and multidrug-resistant tuberculosis. Five patients enrolled for retreatment were infected with pre-extensively drug resistant (pre-XDR) due to fluoroquinolone resistance in isolates from the Cameroon clade. In all five cases resistance was conferred through a mutation in the gyrA gene. In some patients, genomic changes occurred in bacterial isolates during the course of treatment that potentially led to decreased drug susceptibility. We conclude that inter-patient transmission of resistant isolates, principally from the Cameroon clade, contributes to the spread of MDR-TB in this setting, underscoring the urgent need to curb the spread of multi-drug resistance in this region

Seasonality and outbreak of a predominant Streptococcus pneumoniae serotype 1 clone from The Gambia: Expansion of ST217 hypervirulent clonal complex in West Africa

BACKGROUND: Streptococcus pneumoniae serotype 1 causes > 20% of invasive disease, among all age groups combined, in The Gambia. In contrast, it is rarely detected in carriage studies. This study compares the molecular epidemiology of S. pneumoniae serotype 1 causing invasive disease in The Gambia between 1996 and 2005 to those carried in the nasopharynx between 2004 and 2006. RESULTS: A total of 127 invasive and 36 nasopharyngeal carriage serotype 1 isolates were recovered from individuals of all age groups and were analyzed by serotyping, antibiotic susceptibility testing and MLST. MLST analysis revealed 23 different sequence types (STs), 18 of which were novel. The most prevalent clone among the 163 isolates was ST618 (70.5%), followed by ST3575 (7.4%), ST2084 (2.5%) and ST612 (2.5%). A single ST (ST618), previously shown to belong to the ST217 hypervirulent clonal complex, was frequent among carriage (61.1%) and invasive (72.7%) serotype 1 isolates. ST618 causing both paediatric and adult disease peaked annually in the hot dry season and caused outbreak in 1997 and 2002. CONCLUSION: For over a decade, isolates of ST618 have been the dominant lineage among serotype 1 carriage and disease isolates circulating in the Gambia. This lineage shows similar epidemiological features to those of the meningococcus in the African meningitis belt being able to cause outbreaks of disease

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial.

BACKGROUND: The benefit of zinc as an adjunct therapy for severe pneumonia is not established. We assessed the benefit of adjunct zinc therapy for severe pneumonia in children and determined whether the study children were zinc deficient. METHODS: This was a randomized, parallel group, double-blind, placebo-controlled trial with an allocation ratio of 1:1 conducted in children with severe pneumonia to evaluate the efficacy of daily zinc as an adjunct treatment in preventing 'treatment failure' (presence of any sign of severe pneumonia) on day-5 and day-10 and in reducing the time to resolution of signs of severe pneumonia. Six hundred and four children 2-59 months of age presenting with severe pneumonia at six urban and rural health care facilities in The Gambia were individually randomised to receive placebo (n = 301) or zinc (n = 303) for seven days. To determine if the study children were zinc deficient, supplementation was continued in a randomly selected subgroup of 121 children from each arm for six months post-enrolment, and height-gain, nutritional status, plasma zinc concentrations, and immune competence were compared. RESULTS: Percentage of treatment failure were similar in placebo and zinc arms both on day 5 (14.0% vs 14.1%) and day 10 (5.2% vs 5.9%). The time to recovery from lower chest wall indrawing and sternal retraction was longer in the placebo compared to zinc arm (24.4 vs 23.0 hours; P = 0.011 and 18.7 vs 11.0 hours; P = 0.006 respectively). The time to resolution for all respiratory symptoms of severity was not significantly different between placebo and zinc arms (42.3 vs 30.9 hours respectively; P = 0.242). In the six months follow-up sub-group, there was no significant difference in height gain, height-for-age and weight-for-height Z-scores, mid upper arm circumference, plasma zinc concentrations, and anergy at six months post-enrolment. CONCLUSIONS: In this population, zinc given as an adjunct treatment for severe pneumonia showed no benefit in treatment failure rates, or clinically important benefit in time to recovery from respiratory symptoms and showed marginal benefit in rapidity of resolution of some signs of severity. This finding does not support routine use of zinc as an adjunct treatment in severe pneumonia in generally zinc replete children. TRIAL REGISTRATION: ISRCTN33548493

The effectiveness of conjugate Haemophilus influenzae type B vaccine in The Gambia 14 years after introduction.

BACKGROUND: The Gambia was the first country in Africa to introduce conjugate Haemophilus influenzae type b (Hib) vaccine, which, as in other developing countries but unlike industrialized countries, is delivered as a 3-dose primary series with no booster. This study assessed its effectiveness 14 years after introduction. METHODS: Using methods standardized during >20 years in the study site, clinical and microbiological surveillance for invasive Hib disease (primarily meningitis) in the Western Region of The Gambia from 2007 to 2010 was complemented with studies of Hib carriage in children aged 1 to 99% of those surveyed, albeit with lower titers in older children; and coverage of conjugate Hib vaccination was high (91% having 3 doses at 1-2 years of age) using a schedule that was delivered at median ages of 2.6 months, 4.3 months, and 6 months for the first, second, and third doses, respectively. CONCLUSIONS: Conjugate Hib vaccine was delivered on time in a 3-dose primary series without booster to a high proportion of eligible children and this was associated with effective disease control up to 14 years after introduction. It is important that surveillance continues in this first African country to introduce the vaccine to determine if effective control persists or if a booster dose becomes necessary as has been the case in industrialized countries