Emile Fox

Endemic malaria in four villages of the Pakistani province of Punjab

The prevalence of malaria in 4 villages 60 km south of Lahore, Punjab, where Anopheles culicifacies is the vector was estimated from blood films made during three mass malaria surveys (MS) and at 204 clinics (CS) held over 18 consecutive months. The highest parasite rate occurred during October 1984 when 43% of the CS population had parasitaemias. Plasmodium vivax predominated early in the major transmission season (23% and 15% vivax parasitaemias in August 1983 and 1984 respectively) whereas P. falciparum was the most common species later in the transmission season (an average falciparum prevalence of 37% in October and November 1984) and following the transmission season through March. Despite the proximity and habitat similarity of the 4 villages, both total and species malaria prevalence rates showed inter-village differences. Asexual stage and gametocyte parasite rates in children were 2 to 5 times higher than in adults. No increased mortality due to malaria was detected among the 4000 study population. Malaria was stable and endemic, albeit seasonally transmitted, in these 4 villages during 1983 and 1984.

CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM: NOW IN PAKISTANI PUNJAB

To investigate the susceptibility of Plasmodium falciparum to chloroquine in Pakistani Punjab, in-vivo and in-vitro drug susceptibility was tested in 3 villages. Of 66 patients followed for up to 14 days after chloroquine treatment, 53 (80%) had parasites sensitive to chloroquine, 10 (15%) had parasites with early RI resistance, and 3 (5%) had parasites with RII resistance. Of 42 falciparum isolates investigated in vitro, 12 were sensitive, 8 intermediate, and 22 resistant to chloroquine. The degree of in-vivo resistance correlated with the degree of in-vitro resistance. It is concluded that chloroquine resistance is common among falciparum parasites in Pakistan and that this chloroquine resistance could explain the recent increase in the prevalence of falciparum malaria in the Punjab. Alternative antimalarials should therefore be investigated for both treatment and chemoprophylaxis against falciparum parasites in Pakistan.

Diagnostic usefulness of five screening assays for HIV in an East African city where prevalence of infection is low.

Five commercial screening assays for HIV-1, evaluated for their usefulness in detecting infection in high-risk groups in the East African country of Djibouti, produced varying degrees of performance when compared to Western blot and immunofluorescence confirmatory assays. In this population with a low prevalence of HIV infection (16/599), two enzyme-linked immunosorbent assays (ELISA; Abbott and Elavia) and two rapid assays (cambridge latex agglutination and Du Ponts HIV-CHEK) exhibited less than optimal sensitivities. However, with the exception of Elavia, these assays displayed excellent specificities. The fifth test (Serodia gelatin agglutination) produced the highest sensitivity (0.938) and negative predictive value but the lowest specificity and positive predictive value of all five tests. False positive reactions, which occurred only with the Elavia and Serodia tests, could not be explained on the basis of early infection in patients or cross-reactions with the related retroviruses HIV-2 and HTLV-I. We conclude that none of the five tests alone is sufficient in this testing situation, but that a combination of tests could satisfy most requirements for identifying HIV-1 reactive and non-reactive sera.

Amodiaquine fails to cure chloroquine resistant Plasmodium falciparum in the Punjab

We evaluated amodiaquine as a replacement drug for treating falciparum malaria in an area of Pakistani Punjab where chloroquine-resistant Plasmodium falciparum has recently emerged. Amodiaquine appeared to be 4 to 8 times more effective than chloroquine when P. falciparum isolates were tested in vitro. However, the recrudescence rate was greater than 50% after oral treatment with 20 mg/kg amodiaquine given over two successive days. This lack of therapeutic response from amodiaquine may have been due to selection of resistant parasites in the villages where the study was performed through extensive use of chloroquine for presumptive malaria treatment during the preceding 18 months. We conclude that amodiaquine is not a suitable replacement for chloroquine for treating falciparum malaria in our study area despite in vitro sensitivity data suggesting that it would be efficacious. Baseline in vitro sensitivity to mefloquine is also reported.

The interrelationship of Plasmodium falciparum and P. vivax in the Punjab

Analysis of data obtained from Giemsa-stained blood films from patients with mixed Plasmodium vivax and P. falciparum parasitaemias seen in outpatient clinics held over 20 consecutive months in 4 villages in the Pakistani Punjab suggest that infections with P. falciparum and P. vivax were independent of each other. There was no evidence to support the hypothesis that P. falciparum suppressed P. vivax. A likely explanation for the seasonal variation in species parasitaemia rates in the Punjab is that P. vivax was predominant early in the transmission season due to late relapses, while P. falciparum was predominant later in the transmission season because of community-wide development of immunity to P. vivax.

Malaria and splenomegaly in the Punjab

Splenomegaly and parasitaemia were correlated in 2891 children examined in outpatient clinics during 13 consecutive months in 4 Punjabi villages. The average monthly splenomegaly rate varied from 0.05-0.13 before the monsoon malaria transmission season to 0.18-0.27 during and after this season. Moderate splenic enlargement reached a peak during the malaria transmission season, while the highest proportion of very enlarged spleens occurred towards the end of, and after, the transmission season. Children with splenomegaly were 3 times more likely to have Plasmodium falciparum and 1.5 times more likely to have P. vivax parasitaemias than were children without palpable spleens. The larger the spleen the more likely a P. falciparum infection, whereas P. vivax was more commonly associated with minimal spleen enlargement. Although the probability of a child with splenomegaly having a malaria parasitaemia was highest (0.58-0.72) during and immediately following periods of malaria transmission, the odds ratio of malaria infections among those with splenomegaly to those without was at its lowest (1.41-2.11) during those months. Mean P. falciparum parasitaemias were significantly higher in infected children with moderately enlarged spleens than in infected children with nonpalpable spleens or in those with minimal or extensive splenomegaly. These results are compatible with splenomegaly being a result of both the malaria infection and the immune response. Early in infection many children had parasitaemia without splenomegaly; after the parasitaemia had cleared splenomegaly often persisted.

HHV-6 in Djibouti—an epidemiological survey in young adults

Human herpesvirus type six (HHV-6), previously called human B-cell lymphotropic virus (HBLV), was first isolated in 1986 from patients with various lymphoproliferative disorders, some related to the acquired immunodeficiency syndrome. In order to investigate the epidemiology of HHV-6 in the Horn of Africa, we studied 281 young adults living in the city of Djibouti during June 1988. Of these, 181 belonged to various groups at risk for human immunodeficiency virus (HIV), while 100 represented the normal young adult population. Sera were screened and titrated for antibodies against HHV-6 by an indirect fluorescent antibody assay. The percentage seropositivity for HHV-6 was 71 in the normal population, 75 in the population at risk for HIV, and 93 in the population of subjects with a confirmed positive HIV Western blot. Mean titres of positive sera were similar in all population groups. No correlation existed between HHV-6 seropositivity and age, sex, tribe, habitat, and risk factors for HIV. A positive correlation was noted between HHV-6 and patients complaining of fatigue.

Viral hepatitis markers in Djibouti: An epidemioiogical survey

A serosurvey involving 656 individuals revealed that hepatitis A infection was virtually universal in Djibouti in 1987, and more than half of the people investigated had serum markers of hepatitis B infection. The rate of chronic HBsAg carriers was 7.3% and was higher for males than for females. Both HBsAg and anti-HBs positivity rates were directly related to increasing age. No uniform mechanism could be found to account for transmission of the hepatitis B virus, and no correlation was noted between HBV-marker status and sexual promiscuity or the classic blood exposure risks. However, a significant association existed between the abuse of khat and the chronic HBsAg carrier state.

Reliable assessment of malaria prevalence through village clinics

In 4 villages in the Pakistani Punjab, clinic surveys (CS) provided similar results on total malaria and malaria species prevalence as those from mass surveys (MS)--and at a fraction of the effort. This was true at 3 different levels of malaria transmission. Both methods requiring blood films from all interviewed subjects are believed to be superior to the classical active (ACD) and passive (PCD) case detection methods which sample only patients with a history of recent fever. These latter methods would not detect the large population of oligo- and asymptomatic parasitaemic subjects in the semi-immune population of malaria endemic areas.

Low prevalence of HIV infection in Djibouti-has the AIDS epidemic come to a stop at the Horn of Africa?

To determine if the HIV-epidemic had reached Djibouti by autumn 1987, we investigated 645 subjects belonging to various risk groups; 150 were patients with a disease compatible with acquired immune deficiency or with a mycobacterial infection, 115 were young males having a sexually transmitted disease, 295 were female prostitutes, and 69 were villagers from a rural area; the remaining 16 belonged to other groups. All subjects answered an epidemiological questionnaire and had their serum tested for evidence of HIV antibodies. Eight sera were HIV-antibody positive by both ELISA and Western blot. Of these, 2 were from young men while 6 were from young women who admitted to prostitution. This accounts for an HIV seropositivity rate of 2.0% +/- 1.6% in the prostitute population. Also, one antibody-positive subject was positive for circulating HIV antigen. Seven of the seropositive individuals had no general complaints or abnormal clinical signs. The eighth subject was a 28 year old man in hospital for pneumonia. We conclude that in Djibouti, in late 1987, the prevalence of both AIDS and HIV infection in high risk individuals was much lower than that reported from other East African countries.